Carri Glide-Hurst, PhD, DABR, FAAPM

Associate Professor

Department of Human Oncology

Carri Glide-Hurst, PhD, DABR, FAAPM is a tenured Associate Professor in the Department of Human Oncology and member of the UW Carbone Cancer Center.  She serves as the Director of Radiation Oncology Physics and Bhudatt Paliwal Endowed Professor at the University of Wisconsin. Dr. Glide-Hurst obtained a PhD in Medical Physics from Wayne State University with an emphasis on evaluating breast density, a known risk factor for breast cancer, using ultrasound tomography. In 2007, Dr. Glide-Hurst completed an NIH-funded postdoctoral appointment at William Beaumont Hospital focusing on motion management and adaptive radiation therapy in lung cancer.  In 2009, Dr. Glide-Hurst joined the staff at Henry Ford Health System where she rose in the ranks from a senior associate physicist to the Director of Imaging and Translational Research in the Department of Radiation Oncology.  In 2016, Dr. Glide-Hurst was awarded an NIH R01 grant on the “Development of Anatomical Patient Models to Facilitate MR-only Treatment Planning.”

Over the last decade, Dr. Glide-Hurst’s primary areas of research and clinical expertise include magnetic resonance simulation (MR-SIM) and MR-guided radiation therapy.  She has spearheaded efforts for establishing national and international guidelines for safe integration into clinical practice including serving as the Co-chair of AAPM Task Group 284 on the implementation of MR-SIM in Radiation Oncology, AAPM Task Group 352 on the quality assurance of MRI-Linear Accelerators, and as the Vice-Chair of ICRU Report Committee 35 on “Image-Guided Radiation Therapy Using MRI-Linear Accelerators.” As a nationally renowned board-certified medical physicist with over 12 years of clinical experience, Dr. Glide-Hurst is known for multi-disciplinary collaborations and building bridges between clinical, academic, and industry partners.  Above all else, Dr. Glide-Hurst is most passionate about mentoring trainees as they begin their medical physics careers.

Education

PhD, Wayne State University, Detroit, MI, Medical Physics (2007)

B.S.E., University of Michigan, Ann Arbor, MI, Nuclear Engineering and Radiological Sciences (2001)

Academic Appointments

Director of Radiation Oncology Physics, Tenured Associate Professor, Human Oncology (2020-present)

Director of Radiation Oncology Physics Visiting Professor , Human Oncology (2020)

Director of Translational Research, Department of Radiation Oncology, Henry Ford Health System Detroit (2016-2020)

Adjunct Professor, Medical Physics, Oakland University Rochester, MI (2015-2020)

Associate Professor (Clinician Educator) Full-Time Affiliate, Wayne State University School of Medicine, Detroit, MI (2014-present)

Senior Associate Physicist, Department of Radiation Oncology, Henry Ford Health System Detroit, MI (2009-2011)

Senior Staff Physicist, Department of Radiation Oncology, Henry Ford Health System Detroit, MI (2011-2020)

Postdoctoral Training, Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (2007-2009)

Selected Honors and Awards

Bhudatt Paliwal Endowed Professor (2020 - present)

Michael D. Mills Editor in Chief Award of Excellence for Outstanding General Medical Physics (2019)

3rd Place Nationally, Young Investigator Symposium, AAPM Meeting (2019)

Best in Physics Abstract, AAPM Meeting (2019)

Fellow, American Association of Physicists in Medicine (2018)

Outstanding Reviewer of 2014 International Journal of Radiation Oncology*Biology*Physics

Boards, Advisory Committees and Professional Organizations

National Institutes of Health, Ad Hoc Reviewer, Imaging Technology and Development Study Section, Small Business Innovation Research (SBIR) program (2019-2020)

American Radium Society, Membership & Credentials Committee (2019-2022)

American Society for Radiation Oncology, Research Grants and Evaluation Subcommittee (2019-pres.)

Nominating Committee, Academic Therapy Representative (2019-pres.)

American Association of Physicists in Medicine, AAPM Annual Meeting Scientific Work Group, Vice-Chair (2019-pres.)

American Association of Physicists in Medicine, AAPM Annual Meeting Subcommittee (2019-pres.)

American Association of Physicists in Medicine, Ad Hoc Committee on External Communications and Social Media (2019-pres.)

American Association of Physicists in Medicine, Working Group on Student and Trainee Research (2019-pres.)

American Association of Physicists in Medicine, Conference of Radiation Control Program Directors Subcommittee (2019-pres.)

American Association of Physicists in Medicine, Women's Professional Subcommittee (2019-pres.)

American Association of Physicists in Medicine, Task Group 334 Member, “A Guidance document to using Radiotherapy Immobilization Devices and Accessories in an MR Environment” (2019-pres.)

International Commission on Radiation Units & Measurements, Vice-Chair of Report Committee 35 on Image Guided Radiation Therapy Using MRI-Linear Accelerators (MRGRT) (2019-pres.)

American Association of Physicists in Medicine, Research Committee (2018-pres.)

American Association of Physicists in Medicine, Unit No. 50 - Social Media (2018-pres.)

American Association of Physicists in Medicine, Working Group 2 Improving the reader experience by enhancing accessibility and readability, and marketing impact of Journal (2018-pres.)

NRG Oncology, Working Group Lead, Adaptive Radiation Therapy in Clinical Trials (2017-pres.)

American Board of Radiology, Medical Physics Part 3 Therapy oral examiner (2017-pres.)

American Association of Physicists in Medicine, Task Group 284 Co-Chair, “Magnetic Resonance Imaging Simulation in Radiotherapy: Considerations for Clinical Implementation, Optimization, and Quality Assurance” (2016-pres.)

American Society for Radiation Oncology, Annual Meetings Abstract Reviewer and Session Moderator (2014-pres.)

American Association of Physicists in Medicine, Joint Working Group for Research Seed Funding Initiative (2014-pres.)

American Society for Radiation Oncology, Science Education and Program Development Committee, Annual Meeting Track (2013-pres.)

  • Cardiac MRI and blood biomarkers for evaluation of radiation-induced cardiotoxicity in breast cancer patients: results of a phase II clinical trial International journal of radiation oncology, biology, physics
    Speers C, Murthy VL, Walker EM, Glide-Hurst CK, Marsh R, Tang M, Morris EL, Schipper MJ, Weinberg RL, Gits HC, Hayman J, Feng M, Balter J, Moran J, Jagsi R, Pierce LJ
    2021 Sep 9:S0360-3016(21)02732-2. doi: 10.1016/j.ijrobp.2021.08.039. Online ahead of print.
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      PURPOSE: Radiotherapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events following RT for left-sided disease.

      METHODS: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 IRB-approved protocols at 2 institutions. MRI was conducted pretreatment (within one week of starting radiation), at the end of treatment (last day of treatment +/- 1 week), and 3 months post-last day of treatment (+/- 2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (N=28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated.

      RESULTS: Among 51 women enrolled, mean heart dose ranged from 0.80-4.7 Gy and mean left ventricular (LV) dose from 1.1-8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (p=0.059) and mean MHD was not associated with perfusion changes. Significant correlation between baseline IL6 and MHD at the end of RT (ρ 0.44, p=0.007) and and a strong trend between Troponin I and MHD at 3-months post-treatment (ρ 0.33, p=0.07) were observed. No other significant correlations were identified.

      CONCLUSIONS: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation.

      PMID:34509552 | DOI:10.1016/j.ijrobp.2021.08.039


      View details for PubMedID 34509552
  • Toward magnetic resonance fingerprinting for low-field MR-guided radiation therapy Medical physics
    Mickevicius NJ, Kim JP, Zhao J, Morris ZS, Hurst NJ, Glide-Hurst CK
    2021 Sep 6. doi: 10.1002/mp.15202. Online ahead of print.
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      PURPOSE: The acquisition of multiparametric quantitative magnetic resonance imaging (qMRI) is becoming increasingly important for functional characterization of cancer prior to- and throughout the course of radiation therapy. The feasibility of a qMRI method known as magnetic resonance fingerprinting (MRF) for rapid T1 and T2 mapping was assessed on a low-field MR-linac system.

      METHODS: A three-dimensional MRF sequence was implemented on a 0.35T MR-guided radiotherapy system. MRF-derived measurements of T1 and T2 were compared to those obtained with gold standard single spin echo methods, and the impacts of the radiofrequency field homogeneity and scan times ranging between 6 and 48 min were analyzed by acquiring between 1 and 8 spokes per time point in a standard quantitative system phantom. The short-term repeatability of MRF was assessed over three measurements taken over a 10-h period. To evaluate transferability, MRF measurements were acquired on two additional MR-guided radiotherapy systems. Preliminary human volunteer studies were performed.

      RESULTS: The phantom benchmarking studies showed that MRF is capable of mapping T1 and T2 values within 8% and 10% of gold standard measures, respectively, at 0.35T. The coefficient of variation of T1 and T2 estimates over three repeated scans was < 5% over a broad range of relaxation times. The T1 and T2 times derived using a single-spoke MRF acquisition across three scanners were near unity and mean percent errors in T1 and T2 estimates using the same phantom were < 3%. The mean percent differences in T1 and T2 as a result of truncating the scan time to 6 min over the large range of relaxation times in the system phantom were 0.65% and 4.05%, respectively.

      CONCLUSIONS: The technical feasibility and accuracy of MRF on a low-field MR-guided radiation therapy device has been demonstrated. MRF can be used to measure accurate T1 and T2 maps in three dimensions from a brief 6-min scan, offering strong potential for efficient and reproducible qMRI for future clinical trials in functional plan adaptation and tumor/normal tissue response assessment.

      PMID:34487357 | DOI:10.1002/mp.15202


      View details for PubMedID 34487357
  • Quantifying inter-fraction cardiac substructure displacement during radiotherapy via magnetic resonance imaging guidance Physics and imaging in radiation oncology
    Morris ED, Ghanem AI, Zhu S, Dong M, Pantelic MV, Glide-Hurst CK
    2021 Apr 16;18:34-40. doi: 10.1016/j.phro.2021.03.005. eCollection 2021 Apr.
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      PURPOSE: Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI).

      METHODS: Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17-25 s breath-hold (resolution 1.5 × 1.5 × 3 mm3). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated.

      RESULTS: Across substructures, inter-fraction displacements for 14% in the left-right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were > 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted > 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left-right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (> 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left-right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins.

      CONCLUSIONS: This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials.

      PMID:34258405 | PMC:PMC8254195 | DOI:10.1016/j.phro.2021.03.005


      View details for PubMedID 34258405
  • Findings of the AAPM Ad Hoc committee on magnetic resonance imaging in radiation therapy: Unmet needs, opportunities, and recommendations Medical physics
    McGee KP, Tyagi N, Bayouth JE, Cao M, Fallone BG, Glide-Hurst CK, Goerner FL, Green OL, Kim T, Paulson ES, Yanasak NE, Jackson EF, Goodwin JH, Dieterich S, Jordan DW, Hugo GD, Bernstein MA, Balter JM, Kanal KM, Hazle JD, Pelc NJ
    2021 Aug;48(8):4523-4531. doi: 10.1002/mp.14996. Epub 2021 Jul 6.
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      The past decade has seen the increasing integration of magnetic resonance (MR) imaging into radiation therapy (RT). This growth can be contributed to multiple factors, including hardware and software advances that have allowed the acquisition of high-resolution volumetric data of RT patients in their treatment position (also known as MR simulation) and the development of methods to image and quantify tissue function and response to therapy. More recently, the advent of MR-guided radiation therapy (MRgRT) - achieved through the integration of MR imaging systems and linear accelerators - has further accelerated this trend. As MR imaging in RT techniques and technologies, such as MRgRT, gain regulatory approval worldwide, these systems will begin to propagate beyond tertiary care academic medical centers and into more community-based health systems and hospitals, creating new opportunities to provide advanced treatment options to a broader patient population. Accompanying these opportunities are unique challenges related to their adaptation, adoption, and use including modification of hardware and software to meet the unique and distinct demands of MR imaging in RT, the need for standardization of imaging techniques and protocols, education of the broader RT community (particularly in regards to MR safety) as well as the need to continue and support research, and development in this space. In response to this, an ad hoc committee of the American Association of Physicists in Medicine (AAPM) was formed to identify the unmet needs, roadblocks, and opportunities within this space. The purpose of this document is to report on the major findings and recommendations identified. Importantly, the provided recommendations represent the consensus opinions of the committee's membership, which were submitted in the committee's report to the AAPM Board of Directors. In addition, AAPM ad hoc committee reports differ from AAPM task group reports in that ad hoc committee reports are neither reviewed nor ultimately approved by the committee's parent groups, including at the council and executive committee level. Thus, the recommendations given in this summary should not be construed as being endorsed by or official recommendations from the AAPM.

      PMID:34231224 | DOI:10.1002/mp.14996


      View details for PubMedID 34231224
  • Attention-Guided Generative Adversarial Network to Address Atypical Anatomy in Synthetic CT Generation 2020 IEEE 21st International Conference on Information Reuse and Integration for Data Science : IRI 2020 : proceedings : virtual conference, 11-13 August 2020. IEEE International Conference on Information Reuse and Integration (21st : 2...
    Emami H, Dong M, Glide-Hurst CK
    2020 IEEE 21st Int Conf Inf Reuse Integr Data Sci (2020). 2020 Aug;2020:188-193. doi: 10.1109/iri49571.2020.00034. Epub 2020 Sep 10.
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      Recently, interest in MR-only treatment planning using synthetic CTs (synCTs) has grown rapidly in radiation therapy. However, developing class solutions for medical images that contain atypical anatomy remains a major limitation. In this paper, we propose a novel spatial attention-guided generative adversarial network (attention-GAN) model to generate accurate synCTs using T1-weighted MRI images as the input to address atypical anatomy. Experimental results on fifteen brain cancer patients show that attention-GAN outperformed existing synCT models and achieved an average MAE of 85.223±12.08, 232.41±60.86, 246.38±42.67 Hounsfield units between synCT and CT-SIM across the entire head, bone and air regions, respectively. Qualitative analysis shows that attention-GAN has the ability to use spatially focused areas to better handle outliers, areas with complex anatomy or post-surgical regions, and thus offer strong potential for supporting near real-time MR-only treatment planning.

      PMID:34094039 | PMC:PMC8174818 | DOI:10.1109/iri49571.2020.00034


      View details for PubMedID 34094039
  • Adaptive Radiation Therapy (ART) Strategies and Technical Considerations: A State of the ART Review From NRG Oncology International journal of radiation oncology, biology, physics
    Glide-Hurst CK, Lee P, Yock AD, Olsen JR, Cao M, Siddiqui F, Parker W, Doemer A, Rong Y, Kishan AU, Benedict SH, Li XA, Erickson BA, Sohn JW, Xiao Y, Wuthrick E
    2021 Mar 15;109(4):1054-1075. doi: 10.1016/j.ijrobp.2020.10.021. Epub 2020 Oct 24.
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      The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided.

      PMID:33470210 | PMC:PMC8290862 | DOI:10.1016/j.ijrobp.2020.10.021


      View details for PubMedID 33470210
  • Task group 284 report: magnetic resonance imaging simulation in radiotherapy: considerations for clinical implementation, optimization, and quality assurance Medical physics
    Glide-Hurst CK, Paulson ES, McGee K, Tyagi N, Hu Y, Balter J, Bayouth J
    2021 Jul;48(7):e636-e670. doi: 10.1002/mp.14695.
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      The use of dedicated magnetic resonance simulation (MR-SIM) platforms in Radiation Oncology has expanded rapidly, introducing new equipment and functionality with the overall goal of improving the accuracy of radiation treatment planning. However, this emerging technology presents a new set of challenges that need to be addressed for safe and effective MR-SIM implementation. The major objectives of this report are to provide recommendations for commercially available MR simulators, including initial equipment selection, siting, acceptance testing, quality assurance, optimization of dedicated radiation therapy specific MR-SIM workflows, patient-specific considerations, safety, and staffing. Major contributions include guidance on motion and distortion management as well as MRI coil configurations to accommodate patients immobilized in the treatment position. Examples of optimized protocols and checklists for QA programs are provided. While the recommendations provided here are minimum requirements, emerging areas and unmet needs are also highlighted for future development.

      PMID:33386620 | DOI:10.1002/mp.14695


      View details for PubMedID 33386620
  • Introduction to special issue on datasets hosted in The Cancer Imaging Archive (TCIA) Medical physics
    Kirby J, Prior F, Petrick N, Hadjiski L, Farahani K, Drukker K, Kalpathy-Cramer J, Glide-Hurst C, Naqa IE
    2020 Dec;47(12):6026-6028. doi: 10.1002/mp.14595.
  • Incorporating sensitive cardiac substructure sparing into radiation therapy planning Journal of applied clinical medical physics
    Morris ED, Aldridge K, Ghanem AI, Zhu S, Glide-Hurst CK
    2020 Nov;21(11):195-204. doi: 10.1002/acm2.13037. Epub 2020 Oct 18.
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      PURPOSE: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs.

      METHODS: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches.

      RESULTS: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA0.03cc (0.0-63.9% and 0.0 to 17.3 Gy, respectively). LV0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D0.03cc . One patient exhibited >10 Gy reduction in D0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions.

      CONCLUSIONS: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities.

      PMID:33073454 | PMC:PMC7701109 | DOI:10.1002/acm2.13037


      View details for PubMedID 33073454
  • Rapid multicontrast brain imaging on a 0.35T MR-linac Medical physics
    Nejad-Davarani SP, Zakariaei N, Chen Y, Haacke EM, Hurst NJ, Siddiqui MS, Schultz LR, Snyder JM, Walbert T, Glide-Hurst CK
    2020 Sep;47(9):4064-4076. doi: 10.1002/mp.14251. Epub 2020 Jul 6.
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      PURPOSE: Magnetic resonance-guided radiation therapy (MRgRT) has shown great promise for localization and real-time tumor monitoring. However, to date, quantitative imaging has been limited for low field MRgRT. This work benchmarks quantitative T1, R2*, and Proton Density (PD)mapping in a phantom on a 0.35 T MR-linac and implements a novel acquisition method, STrategically Acquired Gradient Echo (STAGE). To further validate STAGE in a clinical setting, a pilot study was undertaken in a cohort of brain tumor patients to elucidate opportunities for longitudinal functional imaging with an MR-linac in the brain.

      METHODS: STAGE (two triple-echo gradient echo (GRE) acquisitions) was optimized for a 0.35T low-field MR-linac. Simulations were performed to choose two flip angles to optimize signal-to-noise ratio (SNR) and T1-mapping precision. Tradeoffs between SNR, scan time, and spatial resolution for whole-brain coverage were evaluated in healthy volunteers. Data were inputted into a STAGE processing pipeline to yield four qualitative images (T1-weighted, enhanced T1-weighted, proton-density (PD) weighted, and simulated FLuid-Attenuated Inversion Recovery (sFLAIR)), and three quantitative datasets (T1, PD, and R2*). A benchmarking ISMRM/NIST phantom consisting of vials with variable NiCl2 and MnCl2 concentrations was scanned using variable flip angles (VFA) (2-60 degrees) and inversion recovery (IR) methods at 0.35 T. STAGE and VFA T1 values of vials were compared to IR T1 values. As measures of agreement with reference values and repeatability, relative error (RE) and coefficient of variability (CV) were calculated, respectively, for quantitative MR values within the phantom vials (spheres). To demonstrate feasibility, longitudinal STAGE data (pretreatment, weekly, and ~ 2 months post-treatment) were acquired in an IRB-approved pilot study of brain tumor cases via the generation of temporal and differential quantitative MRI maps.

      RESULTS: In the phantom, RE of measured VFA T1 and STAGE relative to IR reference values were 7.0 ± 2.5% and 9.5 ± 2.2% respectively. RE for the PD vials was 8.1 ± 6.8% and CV for phantom R2* measurements was 10.1 ± 9.9%. Simulations and volunteer experiments yielded final STAGE parameters of FA = 50°/10°, 1 × 1 × 3 mm3 resolution, TR = 40 ms, TE = 5/20/34 ms in 10 min (64 slices). In the pilot study of brain tumor patients, differential maps for R2* and T1 maps were sensitive to local tumor changes and appeared similar to 3 T follow-up MRI datasets.

      CONCLUSION: Quantitative T1, R2*, and PD mapping are promising at 0.35 T agreeing well with reference data. STAGE phantom data offer quantitative representations comparable to traditional methods in a fraction of the acquisition time. Initial feasibility of implementing STAGE at 0.35 T in a patient brain tumor cohort suggests that detectable changes can be observed over time. With confirmation in a larger cohort, results may be implemented to identify areas of recurrence and facilitate adaptive radiation therapy.

      PMID:32434276 | PMC:PMC7677202 | DOI:10.1002/mp.14251


      View details for PubMedID 32434276
  • Cardiac substructure segmentation with deep learning for improved cardiac sparing Medical physics
    Morris ED, Ghanem AI, Dong M, Pantelic MV, Walker EM, Glide-Hurst CK
    2020 Feb;47(2):576-586. doi: 10.1002/mp.13940. Epub 2019 Dec 29.
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      PURPOSE: Radiation dose to cardiac substructures is related to radiation-induced heart disease. However, substructures are not considered in radiation therapy planning (RTP) due to poor visualization on CT. Therefore, we developed a novel deep learning (DL) pipeline leveraging MRI's soft tissue contrast coupled with CT for state-of-the-art cardiac substructure segmentation requiring a single, non-contrast CT input.

      MATERIALS/METHODS: Thirty-two left-sided whole-breast cancer patients underwent cardiac T2 MRI and CT-simulation. A rigid cardiac-confined MR/CT registration enabled ground truth delineations of 12 substructures (chambers, great vessels (GVs), coronary arteries (CAs), etc.). Paired MRI/CT data (25 patients) were placed into separate image channels to train a three-dimensional (3D) neural network using the entire 3D image. Deep supervision and a Dice-weighted multi-class loss function were applied. Results were assessed pre/post augmentation and post-processing (3D conditional random field (CRF)). Results for 11 test CTs (seven unique patients) were compared to ground truth and a multi-atlas method (MA) via Dice similarity coefficient (DSC), mean distance to agreement (MDA), and Wilcoxon signed-ranks tests. Three physicians evaluated clinical acceptance via consensus scoring (5-point scale).

      RESULTS: The model stabilized in ~19 h (200 epochs, training error <0.001). Augmentation and CRF increased DSC 5.0 ± 7.9% and 1.2 ± 2.5%, across substructures, respectively. DL provided accurate segmentations for chambers (DSC = 0.88 ± 0.03), GVs (DSC = 0.85 ± 0.03), and pulmonary veins (DSC = 0.77 ± 0.04). Combined DSC for CAs was 0.50 ± 0.14. MDA across substructures was <2.0 mm (GV MDA = 1.24 ± 0.31 mm). No substructures had statistical volume differences (P > 0.05) to ground truth. In four cases, DL yielded left main CA contours, whereas MA segmentation failed, and provided improved consensus scores in 44/60 comparisons to MA. DL provided clinically acceptable segmentations for all graded patients for 3/4 chambers. DL contour generation took ~14 s per patient.

      CONCLUSIONS: These promising results suggest DL poses major efficiency and accuracy gains for cardiac substructure segmentation offering high potential for rapid implementation into RTP for improved cardiac sparing.

      PMID:31794054 | PMC:PMC7282198 | DOI:10.1002/mp.13940


      View details for PubMedID 31794054
  • Real-time Magnetic Resonance-guided Liver Stereotactic Body Radiation Therapy: An Institutional Report Using a Magnetic Resonance-Linac System Cureus
    Feldman AM, Modh A, Glide-Hurst C, Chetty IJ, Movsas B
    2019 Sep 26;11(9):e5774. doi: 10.7759/cureus.5774.
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      Background Stereotactic body radiation therapy (SBRT) is a proven and effective modality for treatment of hepatic primary and metastatic tumors. However, these lesions are challenging for planning and treatment execution due to natural anatomic changes associated with respiration. Magnetic resonance imaging (MRI) offers superior soft tissue contrast resolution and the ability for real-time image-guided treatment delivery and lesion tracking. Objective To evaluate the plan quality, treatment delivery, and tumor response of a set of liver SBRT cancer treatments delivered with magnetic resonance (MR)-guided radiotherapy on a MR-linear accelerator (MR-linac). Methods Treatment data from 29 consecutive patients treated with SBRT were reviewed. All treatments were performed using a step and shoot technique to one or more liver lesions on an MR-linac platform. Patients received 45 to 50 Gy prescribed to at least 95% of the planning target volume (PTV) in five fractions except for two patients who received 27-30 Gy in three fractions. Computed tomography and MRI simulation were performed in the supine position prior to treatment in the free-breathing, end exhalation, and end inhalation breath-hold positions to determine patient tolerability and potential dosimetric advantages of each technique. Immobilization consisted of using anterior and posterior torso MRI receive coils embedded in a medium-sized vacuum cushion. Gating was performed using sagittal cine images acquired at 4 frames/second. Gating boundaries were defined in the three major axes to be 0.3 to 0.5 cm. An overlapping region of interest, defined as the percentage volume allowed outside the boundary for beam-on to occur, was set between 1 and 10%. The contoured target was assigned a 5-mm PTV expansion. Organs at risk constraints adopted by the American Association of Physicists in Medicine Task Group 101 were used during optimization. Results Twenty-nine patients, with a total of 34 lesions, successfully completed the prescribed treatment with minimal treatment breaks or delays. Twenty-one patients were treated at end-exhale, and six were treated at end-inhale. Two patients were treated using a free-breathing technique due to poor compliance with breath-hold instructions. The reported mean liver dose was 5.56 Gy (1.39 - 10.43; STD 2.85) and the reported mean liver volume receiving the prescribed threshold dose was 103.1 cm3 (2.9 - 236.6; STD 75.2). Follow-up imaging at one to 12 months post treatment confirmed either stable or decreased size of treated lesions in all but one patient. Toxicities were mild and included nausea/vomiting, abdominal pain and one case of bloody diarrhea. Four patients died due to complications from liver cirrhosis unrelated to radiation effect. Conclusion SBRT treatment using a gated technique on an MR-linac has been successfully demonstrated. Potential benefits of this modality include decreased liver dose leading to decreased toxicities. Further studies to identify the benefits and risks associated with MR-guided SBRT are necessary.

      PMID:31723533 | PMC:PMC6825488 | DOI:10.7759/cureus.5774


      View details for PubMedID 31723533
  • Impact of CT reconstruction algorithm on auto-segmentation performance Journal of applied clinical medical physics
    Miller C, Mittelstaedt D, Black N, Klahr P, Nejad-Davarani S, Schulz H, Goshen L, Han X, Ghanem AI, Morris ED, Glide-Hurst C
    2019 Sep;20(9):95-103. doi: 10.1002/acm2.12710.
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      Model-based iterative reconstruction (MBIR) reduces CT imaging dose while maintaining image quality. However, MBIR reduces noise while preserving edges which may impact intensity-based tasks such as auto-segmentation. This work evaluates the sensitivity of an auto-contouring prostate atlas across multiple MBIR reconstruction protocols and benchmarks the results against filtered back projection (FBP). Images were created from raw projection data for 11 prostate cancer cases using FBP and nine different MBIR reconstructions (3 protocols/3 noise reduction levels) yielding 10 reconstructions/patient. Five bony structures, bladder, rectum, prostate, and seminal vesicles (SVs) were segmented using an auto-segmentation pipeline that renders 3D binary masks for analysis. Performance was evaluated for volume percent difference (VPD) and Dice similarity coefficient (DSC), using FBP as the gold standard. Nonparametric Friedman tests plus post hoc all pairwise comparisons were employed to test for significant differences (P < 0.05) for soft tissue organs and protocol/level combinations. A physician performed qualitative grading of 396 MBIR contours across the prostate, bladder, SVs, and rectum in comparison to FBP using a six-point scale. MBIR contours agreed with FBP for bony anatomy (DSC ≥ 0.98), bladder (DSC ≥ 0.94, VPD < 8.5%), and prostate (DSC = 0.94 ± 0.03, VPD = 4.50 ± 4.77% (range: 0.07-26.39%). Increased variability was observed for rectum (VPD = 7.50 ± 7.56% and DSC = 0.90 ± 0.08) and SVs (VPD and DSC of 8.23 ± 9.86% range (0.00-35.80%) and 0.87 ± 0.11, respectively). Over the all protocol/level comparisons, a significant difference was observed for the prostate VPD between BSPL1 and BSTL2 (adjusted P-value = 0.039). Nevertheless, 300 of 396 (75.8%) of the four soft tissue structures using MBIR were graded as equivalent or better than FBP, suggesting that MBIR offered potential improvements in auto-segmentation performance when compared to FBP. Future work may involve tuning organ-specific MBIR parameters to further improve auto-segmentation performance. Running title: Impact of CT Reconstruction Algorithm on Auto-segmentation Performance.

      PMID:31538718 | PMC:PMC6753741 | DOI:10.1002/acm2.12710


      View details for PubMedID 31538718
  • A novel and rapid approach to estimate patient-specific distortions based on mDIXON MRI Physics in medicine and biology
    Weiss S, Nejad-Davarani S, Eggers H, Orasanu E, Renisch S, Glide-Hurst C
    2019 Aug 1;64(15):155002. doi: 10.1088/1361-6560/ab2b0a.
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      While MRI-only radiation treatment planning (RTP) is becoming more widespread, a robust clinical solution for patient-specific distortion corrections is not available. This work explores B 0 mapping based on mDIXON imaging, often performed for MR-only RTP, as an alternative to separate dual-acquisition gradient-recalled echo imaging, with the overarching goal of developing an efficient and robust approach for patient-specific distortion correction. Initial benchmarking was conducted by scanning a phantom and generating B 0 field maps with two approaches: (1) conventional B 0 mapping and (2) experimental mDIXON imaging. Distortion maps were derived from the field maps and compared. The head and neck regions, including brain, of ten healthy volunteers were then evaluated at 1.5 T and 3 T. Distortion maps were again compared between approaches, using difference maps and histogram analysis. Overall, conventional B 0 mapping was well approximated by mDIXON imaging: The distortions of 95% of the voxels in the phantom estimated by mDIXON and conventional B 0 mapping differed by <0.02 mm (1.5 T) and <0.04 mm (3 T), while the 95-percentiles of the distortions estimated by conventional B 0 mapping were <0.06 mm (1.5 T) and <0.12 mm (3 T). In head and neck the distortions of 99% of the voxels were within ±0.2 mm at 1.5 T for both approaches and within ±0.4 mm and ±0.5 mm at 3 T for mDIXON imaging and conventional B 0 mapping, respectively. The majority of differences in vivo were confined to regions with high spatial variation of the B 0 field, mostly around internal air cavities. For 1.5 T, the mDIXON imaging-based correction alone reduced the 95-percentile of distortions from 0.15 mm to 0.03 mm and within the brain from 0.06 mm to 0.02 mm. Slightly lower reductions were observed at 3 T. In conclusion, mDIXON imaging closely approximated conventional B 0 mapping for patient-specific distortion assessment. Estimates in the brain were in good agreement, and slight differences were observed near air/tissue interfaces in the head and neck. Overall, mDIXON imaging-based B 0 field maps may be advantageous for rapid patient-specific distortion correction without additional imaging.

      PMID:31216529 | PMC:PMC7259737 | DOI:10.1088/1361-6560/ab2b0a


      View details for PubMedID 31216529
  • Organ-At-Risk Segmentation in Brain MRI using Model-Based Segmentation: Benefits of Deep Learning-Based Boundary Detectors Shape in medical imaging : International Workshop, ShapeMI 2018, held in conjunction with MICCAI 2018, Granada, Spain, September 20, 2018 : proceedings. ShapeMI (Workshop) (2018 : Granada, Spain)
    Orasanu E, Brosch T, Glide-Hurst C, Renisch S
    2018). 2018 Sep;11167:291-299. doi: 10.1007/978-3-030-04747-4_27. Epub 2018 Nov 23.
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      Organ-at-risk (OAR) segmentation is a key step for radiotherapy treatment planning. Model-based segmentation (MBS) has been successfully used for the fully automatic segmentation of anatomical structures and it has proven to be robust to noise due to its incorporated shape prior knowledge. In this work, we investigate the advantages of combining neural networks with the prior anatomical shape knowledge of the model-based segmentation of organs-at-risk for brain radiotherapy (RT) on Magnetic Resonance Imaging (MRI). We train our boundary detectors using two different approaches: classic strong gradients as described in [4] and as a locally adaptive regression task, where for each triangle a convolutional neural network (CNN) was trained to estimate the distances between the mesh triangles and organ boundary, which were then combined into a single network, as described by [1]. We evaluate both methods using a 5-fold cross- validation on both T1w and T2w brain MRI data from sixteen primary and metastatic brain cancer patients (some post-surgical). Using CNN-based boundary detectors improved the results for all structures in both T1w and T2w data. The improvements were statistically significant (p < 0.05) for all segmented structures in the T1w images and only for the auditory system in the T2w images.

      PMID:31093609 | PMC:PMC6511992 | DOI:10.1007/978-3-030-04747-4_27


      View details for PubMedID 31093609
  • Large field of view distortion assessment in a low-field MR-linac Medical physics
    Nejad-Davarani SP, Kim JP, Du D, Glide-Hurst C
    2019 May;46(5):2347-2355. doi: 10.1002/mp.13467. Epub 2019 Mar 23.
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      PURPOSE: MR-guided radiation therapy (RT) offers unparalleled soft tissue contrast for localization and target tracking. However, MRI distortions may be detrimental to high precision RT. This work characterizes the gradient nonlinearity (GNL) and total distortions over the first year of clinical operation of a 0.35T MR-linac.

      METHODS: For GNL characterization, an in-house large field of view (FOV) phantom (60 × 42.5 × 55 cm3 , >6000 spherical landmarks) was configured and scanned at four timepoints with forward/reverse read polarities (Gradient Echo sequence, FA/TR/TE = 28°/30 ms/6 ms). GNL was measured in Anterior-Posterior (AP), Left-Right (LR), and Superior-Inferior (SI) frequency-encoding directions based on deviation of the auto-segmented landmark centroids between rigidly registered MR and CT images and assessed based on radial distance from magnet isocenter. Total distortion was assessed using a 30 × 30 cm2 grid phantom oriented along the cardinal axes over >1 year of operation.

      RESULTS: The scanner's spatial integrity within the first ~10 months was stable (maximum total distortion variation = 10/6/8%, maximum distortion = 1.41/0.99/1.56 mm in Axial/Coronal/Sagittal planes, respectively). GNL distortions measured during this time period <10 cm from isocenter were (-0.74, 0.45), (-0.67, 0.53), and (-0.86, 0.70) mm in AP/LR/SI directions. In the 10-20 cm range, <1.5% of the distortions exceeded 2 mm in the AP and LR axes while <4% of the distortions exceeded 2 mm for SI. After major repairs and magnet re-shim, detectable changes were observed in total and GNL distortions (20% reduction in AP and 36% increase in SI direction in the 20-25 cm range). Across all timepoints and axes, 38-53% of landmarks in the 20-25 cm range were displaced by >1 mm.

      CONCLUSIONS: GNL distortions were negligible within a 10 cm radius from isocenter. However, in the periphery, non-negligible distortions of up to ~7 mm were observed, which may necessitate GNL corrections for MR-IGRT for treatment sites distant from magnet isocenter.

      PMID:30838680 | PMC:PMC6510606 | DOI:10.1002/mp.13467


      View details for PubMedID 30838680
  • Geometric and dosimetric impact of anatomical changes for MR-only radiation therapy for the prostate Journal of applied clinical medical physics
    Nejad-Davarani SP, Sevak P, Moncion M, Garbarino K, Weiss S, Kim J, Schultz L, Elshaikh MA, Renisch S, Glide-Hurst C
    2019 Apr;20(4):10-17. doi: 10.1002/acm2.12551. Epub 2019 Mar 1.
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      PURPOSE: With the move towards magnetic resonance imaging (MRI) as a primary treatment planning modality option for men with prostate cancer, it becomes critical to quantify the potential uncertainties introduced for MR-only planning. This work characterized geometric and dosimetric intra-fractional changes between the prostate, seminal vesicles (SVs), and organs at risk (OARs) in response to bladder filling conditions.

      MATERIALS AND METHODS: T2-weighted and mDixon sequences (3-4 time points/subject, at 1, 1.5 and 3.0 T with totally 34 evaluable time points) were acquired in nine subjects using a fixed bladder filling protocol (bladder void, 20 oz water consumed pre-imaging, 10 oz mid-session). Using mDixon images, Magnetic Resonance for Calculating Attenuation (MR-CAT) synthetic computed tomography (CT) images were generated by classifying voxels as muscle, adipose, spongy, and compact bone and by assignment of bulk Hounsfield Unit values. Organs including the prostate, SVs, bladder, and rectum were delineated on the T2 images at each time point by one physician. The displacement of the prostate and SVs was assessed based on the shift of the center of mass of the delineated organs from the reference state (fullest bladder). Changes in dose plans at different bladder states were assessed based on volumetric modulated arc radiotherapy (VMAT) plans generated for the reference state.

      RESULTS: Bladder volume reduction of 70 ± 14% from the final to initial time point (relative to the final volume) was observed in the subject population. In the empty bladder condition, the dose delivered to 95% of the planning target volume (PTV) (D95%) reduced significantly for all cases (11.53 ± 6.00%) likely due to anterior shifts of prostate/SVs relative to full bladder conditions. D15% to the bladder increased consistently in all subjects (42.27 ± 40.52%). Changes in D15% to the rectum were patient-specific, ranging from -23.93% to 22.28% (-0.76 ± 15.30%).

      CONCLUSIONS: Variations in the bladder and rectal volume can significantly dislocate the prostate and OARs, which can negatively impact the dose delivered to these organs. This warrants proper preparation of patients during treatment and imaging sessions, especially when imaging required longer scan times such as MR protocols.

      PMID:30821881 | PMC:PMC6448347 | DOI:10.1002/acm2.12551


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  • FMEA of MR-Only Treatment Planning in the Pelvis Advances in radiation oncology
    Kim J, Miller B, Siddiqui MS, Movsas B, Glide-Hurst C
    2018 Sep 7;4(1):168-176. doi: 10.1016/j.adro.2018.08.024. eCollection 2019 Jan-Mar.
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      PURPOSE: To evaluate the implementation of a magnetic resonance (MR)-only workflow (ie, implementing MR simulation as the primary planning modality) using failure mode and effects analysis (FMEA) in comparison with a conventional multimodality (MR simulation in conjunction with computed tomography simulation) workflow for pelvis external beam planning.

      METHODS AND MATERIALS: To perform the FMEA, a multidisciplinary 9-member team was assembled and developed process maps, identified potential failure modes (FMs), and assigned numerical values to the severity (S), frequency of occurrence (O), and detectability (D) of those FMs. Risk priority numbers (RPNs) were calculated via the product of S, O, and D as a metric for evaluating relative patient risk. An alternative 3-digit composite number (SOD) was computed to emphasize high-severity FMs. Fault tree analysis identified the causality chain leading to the highest-severity FM.

      RESULTS: Seven processes were identified, 3 of which were shared between workflows. Image fusion and target delineation subprocesses using the conventional workflow added 9 and 10 FMs, respectively, with 6 RPNs >100. By contrast, synthetic computed tomography generation introduced 3 major subprocesses and propagated 46 unique FMs, 15 with RPNs >100. For the conventional workflow, the largest RPN scores were introduced by image fusion (RPN range, 120-192). For the MR-only workflow, the highest RPN scores were from inaccuracies in target delineation resulting from misinterpretation of MR images (RPN = 240) and insufficient management of patient- and system-level distortions (RPN = 210 and 168, respectively). Underestimation (RPN = 140) or overestimation (RPN = 192) of bone volume produced higher RPN scores. The highest SODs for both workflows were related to changes in target location because of internal anatomy changes (conventional = 961, MR-only = 822).

      CONCLUSIONS: FMEA identified areas for mitigating risk in MR-only pelvis RTP, and SODs identified high-severity process modes. Efforts to develop a quality management program to mitigate high FMs are underway.

      PMID:30706025 | PMC:PMC6349599 | DOI:10.1016/j.adro.2018.08.024


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  • Cardiac Substructure Segmentation and Dosimetry Using a Novel Hybrid Magnetic Resonance and Computed Tomography Cardiac Atlas International journal of radiation oncology, biology, physics
    Morris ED, Ghanem AI, Pantelic MV, Walker EM, Han X, Glide-Hurst CK
    2019 Mar 15;103(4):985-993. doi: 10.1016/j.ijrobp.2018.11.025. Epub 2018 Nov 22.
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      PURPOSE: Radiation dose to the heart and cardiac substructures has been linked to cardiotoxicities. Because cardiac substructures are poorly visualized on treatment-planning computed tomography (CT) scans, we used the superior soft-tissue contrast of magnetic resonance (MR) imaging to optimize a hybrid MR/CT atlas for substructure dose assessment using CT.

      METHODS AND MATERIALS: Thirty-one patients with left-sided breast cancer underwent a T2-weighted MR imaging scan and noncontrast simulation CT scans. A radiation oncologist delineated 13 substructures (chambers, great vessels, coronary arteries, etc) using MR/CT information via cardiac-confined rigid registration. Ground-truth contours for 20 patients were inputted into an intensity-based deformable registration atlas and applied to 11 validation patients. Automatic segmentations involved using majority vote and Simultaneous Truth and Performance Level Estimation (STAPLE) strategies with 1 to 15 atlas matches. Performance was evaluated via Dice similarity coefficient (DSC), mean distance to agreement, and centroid displacement. Three physicians evaluated segmentation performance via consensus scoring by using a 5-point scale. Dosimetric assessment included measurements of mean heart dose, left ventricular volume receiving 5 Gy, and left anterior descending artery mean and maximum doses.

      RESULTS: Atlas approaches performed similarly well, with 7 of 13 substructures (heart, chambers, ascending aorta, and pulmonary artery) having DSC >0.75 when averaged over 11 validation patients. Coronary artery segmentations were not successful with the atlas-based approach (mean DSC <0.3). The STAPLE method with 10 matches yielded the highest DSC and the lowest mean distance to agreement for all high-performing substructures (omitting coronary arteries). For the STAPLE method with 10 matches, >50% of all validation contours had centroid displacements <3.0 mm, with the largest shifts in the coronary arteries. Atlas-generated contours had no statistical difference from ground truth for left anterior descending artery maximum dose, mean heart dose, and left ventricular volume receiving 5 Gy (P > .05). Qualitative contour grading showed that 8 substructures required minor modifications.

      CONCLUSIONS: The hybrid MR/CT atlas provided reliable segmentations of chambers, heart, and great vessels for patients undergoing noncontrast CT, suggesting potential widespread applicability for routine treatment planning.

      PMID:30468849 | PMC:PMC6476733 | DOI:10.1016/j.ijrobp.2018.11.025


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  • Development and evaluation of a novel MR-compatible pelvic end-to-end phantom Journal of applied clinical medical physics
    Cunningham JM, Barberi EA, Miller J, Kim JP, Glide-Hurst CK
    2019 Jan;20(1):265-275. doi: 10.1002/acm2.12455. Epub 2018 Nov 8.
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      MR-only treatment planning and MR-IGRT leverage MRI's powerful soft tissue contrast for high-precision radiation therapy. However, anthropomorphic MR-compatible phantoms are currently limited. This work describes the development and evaluation of a custom-designed, modular, pelvic end-to-end (PETE) MR-compatible phantom to benchmark MR-only and MR-IGRT workflows. For construction considerations, subject data were assessed for phantom/skeletal geometry and internal organ kinematics to simulate average male pelvis anatomy. Various materials for the bone, bladder, and rectum were evaluated for utility within the phantom. Once constructed, PETE underwent CT-SIM, MR-Linac, and MR-SIM imaging to qualitatively assess organ visibility. Scans were acquired with various bladder and rectal volumes to assess component interactions, filling capabilities, and filling reproducibility via volume and centroid differences. PETE simulates average male pelvis anatomy and comprises an acrylic body oval (height/width = 23.0/38.1 cm) and a cast-mold urethane skeleton, with silicone balloons simulating bladder and rectum, a silicone sponge prostate, and hydrophilic poly(vinyl alcohol) foam to simulate fat/tissue separation between organs. Access ports enable retrofitting the phantom with other inserts including point/film-based dosimetry options. Acceptable contrast was achievable in CT-SIM and MR-Linac images. However, the bladder was challenging to distinguish from background in CT-SIM. The desired contrast for T1-weighted and T2-weighted MR-SIM (dark and bright bladders, respectively) was achieved. Rectum and bone exhibited no MR signal. Inputted volumes differed by <5 and <10 mL from delineated rectum (CT-SIM) and bladder (MR-SIM) volumes. Increasing bladder and rectal volumes induced organ displacements and shape variations. Reproduced volumes differed by <4.5 mL, with centroid displacements <1.4 mm. A point dose measurement with an MR-compatible ion chamber in an MR-Linac was within 1.5% of expected. A novel, modular phantom was developed with suitable materials and properties that accurately and reproducibly simulate status changes with multiple dosimetry options. Future work includes integrating more realistic organ models to further expand phantom options.

      PMID:30411477 | PMC:PMC6333127 | DOI:10.1002/acm2.12455


      View details for PubMedID 30411477
  • Impact of a novel exponential weighted 4DCT reconstruction algorithm Journal of applied clinical medical physics
    Morris ED, Kim JP, Klahr P, Glide-Hurst CK
    2018 Nov;19(6):217-225. doi: 10.1002/acm2.12423. Epub 2018 Sep 11.
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      PURPOSE: This work characterizes a novel exponential 4DCT reconstruction algorithm (EXPO), in phantom and patient, to determine its impact on image quality as compared to the standard cosine-squared weighted 4DCT reconstruction.

      METHODS: A motion platform translated objects in the superior-inferior (S-I) direction at varied breathing rates (8-20 bpm) and couch pitches (0.06-0.1) to evaluate interplay between parameters. Ten-phase 4DCTs were acquired and data were reconstructed with cosine squared and EXPO weighting. To quantify the magnitude of image blur, objects were translated in the anterior-posterior (A-P) and S-I directions for full-width half maximum (FWHM) analysis between both 4DCT algorithms and a static case. 4DCT sinogram data for 10 patients were retrospectively reconstructed using both weighting factors. Image subtractions elucidated intensity and boundary differences. Subjective image quality grading (presence of image artifacts, noise, spatial resolution (i.e., lung/liver boundary sharpness), and overall image quality) was conducted yielding 200 evaluations.

      RESULTS: After taking static object size into account, the FWHM of EXPO reconstructions in the A-P direction was 3.3 ± 1.7 mm (range: 0-4.9) as compared to cosine squared 9.8 ± 4.0 mm (range: 2.6-14.4). The FWHM of objects translated in the S-I direction reconstructed with EXPO agreed better with the static FWHM than the cosine-squared reconstructions. Slower breathing periods, faster couch pitches, and intermediate 4DCT phases had the largest reductions of blurring with EXPO. 18 of 60 comparisons of artifacts were improved with EXPO reconstruction, whereas no appreciable changes were observed in image quality scores. In 18 of 20 cases, EXPO provided sharper images although the reduced projections also increased baseline noise.

      CONCLUSION: Exponential weighted 4DCT offers potential for reducing image blur (i.e., improving image sharpness) in 4DCT with a tendency to reduce artifacts. Future work will involve evaluating the impact on treatment planning including delineation ability and dose calculation.

      PMID:30207053 | PMC:PMC6236850 | DOI:10.1002/acm2.12423


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  • Per-organ assessment of subject-induced susceptibility distortion for MR-only male pelvis treatment planning Radiation oncology (London, England)
    Glide-Hurst C, Nejad-Davarani S, Weiss S, Zheng W, Chetty IJ, Renisch S
    2018 Aug 15;13(1):149. doi: 10.1186/s13014-018-1090-2.
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      BACKGROUND: Patient-specific distortions, particularly near tissue/air interfaces, require assessment for magnetic resonance (MR) only radiation treatment planning (RTP). However, patients are dynamic due to changes in physiological status during imaging sessions. This work investigated changes in subject-induced susceptibility distortions to pelvic organs at different bladder states to support pelvis MR-only RTP.

      METHODS: Pelvises of 9 healthy male volunteers were imaged at 1.0 Tesla (T), 1.5 T, and 3.0 T. Subject-induced susceptibility distortion field maps were generated using a dual-echo gradient-recalled echo (GRE) sequence with B0 field maps obtained from the phase difference between the two echoes acquired at several bladder volume states (3-4/subject, 32 overall). T2 turbo spin echo images were also acquired at each bladder state for organ delineation. Magnet central frequency was tracked over time. Distortion map differences and boxplots were computed to characterize changes within the clinical target volume (CTV), bladder, seminal vesicles, and prostate volumes.

      RESULTS: The time between the initial and final B0 maps was 42.6 ± 13.9 (range: 13.2-62.1) minutes with minimal change in magnet central frequency (0.02 ± 0.05 mm (range: - 0.06 - 0.12 mm)). Subject-induced susceptibility distortion across all bladder states, field strengths, and subjects was relatively small (1.4-1.9% of all voxels in the prostate and seminal vesicles were distorted > 0.5 mm). In the bladder, no voxels exhibited distortions > 1 mm. An extreme case acquired at 3.0 T with a large volume of rectal air yielded 27.4-34.6% of voxels within the CTVs had susceptibility-induced distortions > 0.5 mm across all time points.

      CONCLUSIONS: Our work suggests that subject-induced susceptibility distortions caused by bladder/rectal conditions are generally small and subject-dependent. Local changes may be non-negligible within the CTV, thus proper management of filling status is warranted. Future work evaluating the impact of multiple models to accommodate for extreme status changes may be advantageous.

      PMID:30111376 | PMC:PMC6094890 | DOI:10.1186/s13014-018-1090-2


      View details for PubMedID 30111376
  • Generating synthetic CTs from magnetic resonance images using generative adversarial networks Medical physics
    Emami H, Dong M, Nejad-Davarani SP, Glide-Hurst CK
    2018 Jun 14:10.1002/mp.13047. doi: 10.1002/mp.13047. Online ahead of print.
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      PURPOSE: While MR-only treatment planning using synthetic CTs (synCTs) offers potential for streamlining clinical workflow, a need exists for an efficient and automated synCT generation in the brain to facilitate near real-time MR-only planning. This work describes a novel method for generating brain synCTs based on generative adversarial networks (GANs), a deep learning model that trains two competing networks simultaneously, and compares it to a deep convolutional neural network (CNN).

      METHODS: Post-Gadolinium T1-Weighted and CT-SIM images from fifteen brain cancer patients were retrospectively analyzed. The GAN model was developed to generate synCTs using T1-weighted MRI images as the input using a residual network (ResNet) as the generator. The discriminator is a CNN with five convolutional layers that classified the input image as real or synthetic. Fivefold cross-validation was performed to validate our model. GAN performance was compared to CNN based on mean absolute error (MAE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR) metrics between the synCT and CT images.

      RESULTS: GAN training took ~11 h with a new case testing time of 5.7 ± 0.6 s. For GAN, MAEs between synCT and CT-SIM were 89.3 ± 10.3 Hounsfield units (HU) and 41.9 ± 8.6 HU across the entire FOV and tissues, respectively. However, MAE in the bone and air was, on average, ~240-255 HU. By comparison, the CNN model had an average full FOV MAE of 102.4 ± 11.1 HU. For GAN, the mean PSNR was 26.6 ± 1.2 and SSIM was 0.83 ± 0.03. GAN synCTs preserved details better than CNN, and regions of abnormal anatomy were well represented on GAN synCTs.

      CONCLUSIONS: We developed and validated a GAN model using a single T1-weighted MR image as the input that generates robust, high quality synCTs in seconds. Our method offers strong potential for supporting near real-time MR-only treatment planning in the brain.

      PMID:29901223 | PMC:PMC6294710 | DOI:10.1002/mp.13047


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  • Retroperitoneal Metastasis Abutting Small Bowel: A Novel Magnetic Resonance-Guided Radiation Approach Cureus
    Ghanem AI, Glide-Hurst C, Siddiqui MS, Chetty IJ, Movsas B
    2018 Apr 2;10(4):e2412. doi: 10.7759/cureus.2412.
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      Stereotactic body radiation therapy (SBRT) is an option for selected patients with metastatic disease. However, sometimes these lesions are located in such close proximity to critical normal structures that the use of safe tumoricidal SBRT doses is not achievable. Here we present a case in which real-time imaging and tracking with a magnetic resonance linear accelerator (MR-LINAC) provided a novel treatment approach and enabled safe treatment of the tumor using SBRT. Our case is a 69-year-old female who presented with localized recurrent small cell lung cancer with a retroperitoneal (FDG-avid) soft tissue lesion measuring 2.4 x 4.1 cm that was causing pain and right hydronephrosis. A Food and Drug Administration (FDA)-approved MR-LINAC system was utilized for planning and the delivery of 21 Gy in three fractions to the retroperitoneal lesion planning target volume (PTV), limited by the neighboring small bowel tolerance. The gross tumor volume (GTV) itself received 27 Gy (9 Gy per fraction). Simulation was performed using a volumetric MR imaging study in treatment position co-registered to a 4D-computed tomography (CT) image set for contouring of the target and organs at risk (OAR). Treatment planning was performed using the primary CT dataset. We developed a reasonable SBRT treatment plan to deliver the prescribed dose without exceeding tolerance doses to the right kidney, the small bowel and all other OAR's. Real-time MR imaging and tracking during treatment delivery enabled assessment of respiratory-induced target movement in relation to the small bowel and kidney. Gating was performed to halt treatment when PTV movement exceeded the 2-mm range as specified by the treating physician. The treatment course was concluded successfully. The patient denied any acute gastrointestinal or genitourinary toxicity. The pain was significantly improved within a short time following treatment. Follow-up CT showed a near complete response of the mass with total restoration of renal functions, allowing the ureteric stent to be removed. This response has been maintained for five months till the last follow-up. In conclusion, MR-guided planning and delivery using real-time MR imaging and tracking facilitated the treatment of the retroperitoneal mass accurately and efficiently with excellent clinical and radiological response and minimal to no toxicity. We would not discern it safe to treat this mass utilizing SBRT without this ability to accurately visualize the tumor boundary using magnetic resonance imaging (MRI), and offer tracking of the target within the millimeter of surrounding critical OAR's.

      PMID:29872593 | PMC:PMC5984256 | DOI:10.7759/cureus.2412


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  • Using synthetic CT for partial brain radiation therapy: Impact on image guidance Practical radiation oncology
    Morris ED, Price RG, Kim J, Schultz L, Siddiqui MS, Chetty I, Glide-Hurst C
    2018 Sep-Oct;8(5):342-350. doi: 10.1016/j.prro.2018.04.001. Epub 2018 Apr 6.
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      PURPOSE: Recent advancements in synthetic computed tomography (synCT) from magnetic resonance (MR) imaging data have made MRI-only treatment planning feasible in the brain, although synCT performance for image guided radiation therapy (IGRT) is not well understood. This work compares geometric equivalence of digitally reconstructed radiographs (DRRs) from CTs and synCTs for brain cancer patients and quantifies performance for partial brain IGRT.

      METHODS AND MATERIALS: Ten brain cancer patients (12 lesions, 7 postsurgical) underwent MR-SIM and CT-SIM. SynCTs were generated by combining ultra-short echo time, T1, T2, and fluid attenuation inversion recovery datasets using voxel-based weighted summation. SynCT and CT DRRs were compared using patient-specific thresholding and assessed via overlap index, Dice similarity coefficient, and Jaccard index. Planar IGRT images for 22 fractions were evaluated to quantify differences between CT-generated DRRs and synCT-generated DRRs in 6 quadrants. Previously validated software was implemented to perform 2-dimensional (2D)-2D rigid registrations using normalized mutual information. Absolute (planar image/DRR registration) and relative (differences between synCT and CT DRR registrations) shifts were calculated for each axis and 3-dimensional vector difference. A total of 1490 rigid registrations were assessed.

      RESULTS: DRR agreements in anteroposterior and lateral views for overlap index, Dice similarity coefficient, and Jaccard index were >0.95. Normalized mutual information results were equivalent in 75% of quadrants. Rotational registration results were negligible (<0.07°). Statistically significant differences between CT and synCT registrations were observed in 9/18 matched quadrants/axes (P < .05). The population average absolute shifts were 0.77 ± 0.58 and 0.76 ± 0.59 mm for CT and synCT, respectively, for all axes/quadrants. Three-dimensional vectors were <2 mm in 77.7 ± 10.8% and 76.5 ± 7.2% of CT and synCT registrations, respectively. SynCT DRRs were sensitive in postsurgical cases (vector displacements >2 mm in affected quadrants).

      CONCLUSIONS: DRR synCT geometry was robust. Although statistically significant differences were observed between CT and synCT registrations, results were not clinically significant. Future work will address synCT generation in postsurgical settings.

      PMID:29861348 | PMC:PMC6123249 | DOI:10.1016/j.prro.2018.04.001


      View details for PubMedID 29861348
  • Evaluation of a magnetic resonance guided linear accelerator for stereotactic radiosurgery treatment Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
    Wen N, Kim J, Doemer A, Glide-Hurst C, Chetty IJ, Liu C, Laugeman E, Xhaferllari I, Kumarasiri A, Victoria J, Bellon M, Kalkanis S, Siddiqui MS, Movsas B
    2018 Jun;127(3):460-466. doi: 10.1016/j.radonc.2018.04.034. Epub 2018 May 25.
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      INTRODUCTION: The purpose of this study was to investigate the systematic localization accuracy, treatment planning capability, and delivery accuracy of an integrated magnetic resonance imaging guided Linear Accelerator (MR-Linac) platform for stereotactic radiosurgery.

      MATERIALS AND METHODS: The phantom for the end-to-end test comprises three different compartments: a rectangular MR/CT target phantom, a Winston-Lutz cube, and a rectangular MR/CT isocenter phantom. Hidden target tests were performed at gantry angles of 0, 90, 180, and 270 degrees to quantify the systematic accuracy. Five patient plans with a total of eleven lesions were used to evaluate the dosimetric accuracy. Single-isocenter IMRT treatment plans using 10-15 coplanar beams were generated to treat the multiple metastases.

      RESULTS: The end-to-end localization accuracy of the system was 1.0 ± 0.1 mm. The conformity index, homogeneity index and gradient index of the plans were 1.26 ± 0.22, 1.22 ± 0.10, and 5.38 ± 1.44, respectively. The average absolute point dose difference between measured and calculated dose was 1.64 ± 1.90%, and the mean percentage of points passing the 3%/1 mm gamma criteria was 96.87%.

      CONCLUSIONS: Our experience demonstrates that excellent plan quality and delivery accuracy was achievable on the MR-Linac for treating multiple brain metastases with a single isocenter.

      PMID:29807837 | PMC:PMC6223121 | DOI:10.1016/j.radonc.2018.04.034


      View details for PubMedID 29807837
  • MRI-only treatment planning: benefits and challenges Physics in medicine and biology
    Owrangi AM, Greer PB, Glide-Hurst CK
    2018 Feb 26;63(5):05TR01. doi: 10.1088/1361-6560/aaaca4.
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      Over the past decade, the application of magnetic resonance imaging (MRI) has increased, and there is growing evidence to suggest that improvements in the accuracy of target delineation in MRI-guided radiation therapy may improve clinical outcomes in a variety of cancer types. However, some considerations should be recognized including patient motion during image acquisition and geometric accuracy of images. Moreover, MR-compatible immobilization devices need to be used when acquiring images in the treatment position while minimizing patient motion during the scan time. Finally, synthetic CT images (i.e. electron density maps) and digitally reconstructed radiograph images should be generated from MRI images for dose calculation and image guidance prior to treatment. A short review of the concepts and techniques that have been developed for implementation of MRI-only workflows in radiation therapy is provided in this document.

      PMID:29393071 | PMC:PMC5886006 | DOI:10.1088/1361-6560/aaaca4


      View details for PubMedID 29393071
  • Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model Sleep & breathing = Schlaf & Atmung
    Xi J, Wang Z, Talaat K, Glide-Hurst C, Dong H
    2018 May;22(2):463-479. doi: 10.1007/s11325-017-1588-0. Epub 2017 Nov 3.
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      BACKGROUND: Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation.

      METHODS: Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose.

      RESULTS: Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20-2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100-500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz.

      CONCLUSION: Results show that a severely narrowing glottis during inhalation, as well as flow fluctuations in the downstream trachea, can generate audible sound levels.

      PMID:29101633 | PMC:PMC5962264 | DOI:10.1007/s11325-017-1588-0


      View details for PubMedID 29101633
  • The AAPM should significantly revise its current governance structure Medical physics
    Glide-Hurst CK, Gibbons JP, Orton CG
    2017 Nov;44(11):5541-5543. doi: 10.1002/mp.12456. Epub 2017 Aug 12.
  • Optimization of a novel large field of view distortion phantom for MR-only treatment planning Journal of applied clinical medical physics
    Price RG, Knight RA, Hwang K, Bayram E, Nejad-Davarani SP, Glide-Hurst CK
    2017 Jul;18(4):51-61. doi: 10.1002/acm2.12090. Epub 2017 May 12.
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      PURPOSE: MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution.

      METHOD AND MATERIALS: To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3D Slicer application platform.

      RESULTS: All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000 psi, density ~20 lb/ft3 ) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55 × 55 × 37.5 cm3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 × 55 × 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3D Slicer's plugin framework and results agreed with the literature.

      CONCLUSION: The design and implementation of a modular, extendable distortion phantom was optimized for several bore configurations. The phantom and analysis software will be available for multi-institutional collaborations and cross-validation trials to support MR-only planning.

      PMID:28497476 | PMC:PMC5539340 | DOI:10.1002/acm2.12090


      View details for PubMedID 28497476
  • MRI geometric distortion: Impact on tangential whole-breast IMRT Journal of applied clinical medical physics
    Walker A, Metcalfe P, Liney G, Batumalai V, Dundas K, Glide-Hurst C, Delaney GP, Boxer M, Yap ML, Dowling J, Rivest-Henault D, Pogson E, Holloway L
    2016 Sep;17(5):7-19. doi: 10.1120/jacmp.v17i5.6242.
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      The purpose of this study was to determine the impact of magnetic resonance imaging (MRI) geometric distortions when using MRI for target delineation and planning for whole-breast, intensity-modulated radiotherapy (IMRT). Residual system distortions and combined systematic and patient-induced distortions are considered. This retrospective study investigated 18 patients who underwent whole-breast external beam radiotherapy, where both CT and MRIs were acquired for treatment planning. Distortion phantoms were imaged on two MRI systems, dedicated to radiotherapy planning (a wide, closed-bore 3T and an open-bore 1T). Patient scans were acquired on the 3T system. To simulate MRI-based planning, distortion maps representing residual system distortions were generated via deformable registration between phantom CT and MRIs. Patient CT images and structures were altered to match the residual system distortion measured by the phantoms on each scanner. The patient CTs were also registered to the corresponding patient MRI scans, to assess patient and residual system effects. Tangential IMRT plans were generated and optimized on each resulting CT dataset, then propagated to the original patient CT space. The resulting dose distributions were then evaluated with respect to the standard clinically acceptable DVH and visual assessment criteria. Maximum residual systematic distortion was measured to be 7.9 mm (95%<4.7mm) and 11.9 mm (95%<4.6mm) for the 3T and 1T scanners, respectively, which did not result in clinically unacceptable plans. Eight of the plans accounting for patient and systematic distortions were deemed clinically unacceptable when assessed on the original CT. For these plans, the mean difference in PTV V95 (volume receiving 95% prescription dose) was 0.13±2.51% and -0.73±1.93% for right- and left-sided patients, respectively. Residual system distortions alone had minimal impact on the dosimetry for the two scanners investigated. The combination of MRI systematic and patient-related distortions can result in unacceptable dosimetry for whole-breast IMRT, a potential issue when considering MRI-only radiotherapy treatment planning. PACS number(s): 87.61.-c, 87.57.cp, 87.57.nj, 87.55.D.

      PMID:28297426 | PMC:PMC5495026 | DOI:10.1120/jacmp.v17i5.6242


      View details for PubMedID 28297426
  • Development of a deformable dosimetric phantom to verify dose accumulation algorithms for adaptive radiotherapy Journal of medical physics
    Zhong H, Adams J, Glide-Hurst C, Zhang H, Li H, Chetty IJ
    2016 Apr-Jun;41(2):106-14. doi: 10.4103/0971-6203.181641.
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      Adaptive radiotherapy may improve treatment outcomes for lung cancer patients. Because of the lack of an effective tool for quality assurance, this therapeutic modality is not yet accepted in clinic. The purpose of this study is to develop a deformable physical phantom for validation of dose accumulation algorithms in regions with heterogeneous mass. A three-dimensional (3D) deformable phantom was developed containing a tissue-equivalent tumor and heterogeneous sponge inserts. Thermoluminescent dosimeters (TLDs) were placed at multiple locations in the phantom each time before dose measurement. Doses were measured with the phantom in both the static and deformed cases. The deformation of the phantom was actuated by a motor driven piston. 4D computed tomography images were acquired to calculate 3D doses at each phase using Pinnacle and EGSnrc/DOSXYZnrc. These images were registered using two registration software packages: VelocityAI and Elastix. With the resultant displacement vector fields (DVFs), the calculated 3D doses were accumulated using a mass-and energy congruent mapping method and compared to those measured by the TLDs at four typical locations. In the static case, TLD measurements agreed with all the algorithms by 1.8% at the center of the tumor volume and by 4.0% in the penumbra. In the deformable case, the phantom's deformation was reproduced within 1.1 mm. For the 3D dose calculated by Pinnacle, the total dose accumulated with the Elastix DVF agreed well to the TLD measurements with their differences <2.5% at four measured locations. When the VelocityAI DVF was used, their difference increased up to 11.8%. For the 3D dose calculated by EGSnrc/DOSXYZnrc, the total doses accumulated with the two DVFs were within 5.7% of the TLD measurements which are slightly over the rate of 5% for clinical acceptance. The detector-embedded deformable phantom allows radiation dose to be measured in a dynamic environment, similar to deforming lung tissues, supporting the validation of dose mapping and accumulation operations in regions with heterogeneous mass, and dose distributions.

      PMID:27217622 | PMC:PMC4870999 | DOI:10.4103/0971-6203.181641


      View details for PubMedID 27217622
  • Image Guided Radiation Therapy Using Synthetic Computed Tomography Images in Brain Cancer International journal of radiation oncology, biology, physics
    Price RG, Kim JP, Zheng W, Chetty IJ, Glide-Hurst C
    2016 Jul 15;95(4):1281-9. doi: 10.1016/j.ijrobp.2016.03.002. Epub 2016 Mar 10.
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      PURPOSE: The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT).

      METHODS AND MATERIALS: Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism.

      RESULTS: Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, -0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, -0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, -0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, -0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, -0.3 to 1.2 mm), and 0.2 ± 0.3 mm (range, -0.2 to 1.2 mm) for the S-I, L-R, and A-P axes, respectively. The CT-SIM and synCT derived margins were <0.3 mm different.

      CONCLUSION: DRRs generated by synCT were in close agreement with CT-SIM. Planar and volumetric image registrations to synCT-derived targets were comparable with CT for phantom and patients. This validation is the next step toward MR-only planning for the brain.

      PMID:27209500 | PMC:PMC5450663 | DOI:10.1016/j.ijrobp.2016.03.002


      View details for PubMedID 27209500
  • Impact of incorporating visual biofeedback in 4D MRI Journal of applied clinical medical physics
    To DT, Kim JP, Price RG, Chetty IJ, Glide-Hurst CK
    2016 May 8;17(3):128-137. doi: 10.1120/jacmp.v17i3.6017.
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      Precise radiation therapy (RT) for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast in 4D CT. 4D MRI offers improved con-trast although long scan times and irregular breathing patterns can be limiting. To address this, visual biofeedback (VBF) was introduced into 4D MRI. Ten volunteers were consented to an IRB-approved protocol. Prospective respiratory-triggered, T2-weighted, coronal 4D MRIs were acquired on an open 1.0T MR-SIM. VBF was integrated using an MR-compatible interactive breath-hold control system. Subjects visually monitored their breathing patterns to stay within predetermined tolerances. 4D MRIs were acquired with and without VBF for 2- and 8-phase acquisitions. Normalized respiratory waveforms were evaluated for scan time, duty cycle (programmed/acquisition time), breathing period, and breathing regularity (end-inhale coefficient of variation, EI-COV). Three reviewers performed image quality assessment to compare artifacts with and without VBF. Respiration-induced liver motion was calculated via centroid difference analysis of end-exhale (EE) and EI liver contours. Incorporating VBF reduced 2-phase acquisition time (4.7 ± 1.0 and 5.4 ± 1.5 min with and without VBF, respectively) while reducing EI-COV by 43.8% ± 16.6%. For 8-phase acquisitions, VBF reduced acquisition time by 1.9 ± 1.6 min and EI-COVs by 38.8% ± 25.7% despite breathing rate remaining similar (11.1 ± 3.8 breaths/min with vs. 10.5 ± 2.9 without). Using VBF yielded higher duty cycles than unguided free breathing (34.4% ± 5.8% vs. 28.1% ± 6.6%, respectively). Image grading showed that out of 40 paired evaluations, 20 cases had equivalent and 17 had improved image quality scores with VBF, particularly for mid-exhale and EI. Increased liver excursion was observed with VBF, where superior-inferior, anterior-posterior, and left-right EE-EI displacements were 14.1± 5.8, 4.9 ± 2.1, and 1.5 ± 1.0 mm, respectively, with VBF compared to 11.9 ± 4.5, 3.7 ± 2.1, and 1.2 ± 1.4 mm without. Incorporating VBF into 4D MRI substantially reduced acquisition time, breathing irregularity, and image artifacts. However, differences in excursion were observed, thus implementation will be required throughout the RT workflow.

      PMID:27167270 | PMC:PMC5690930 | DOI:10.1120/jacmp.v17i3.6017


      View details for PubMedID 27167270
  • Dosimetric evaluation of synthetic CT relative to bulk density assignment-based magnetic resonance-only approaches for prostate radiotherapy Radiation oncology (London, England)
    Kim J, Garbarino K, Schultz L, Levin K, Movsas B, Siddiqui MS, Chetty IJ, Glide-Hurst C
    2015 Nov 24;10:239. doi: 10.1186/s13014-015-0549-7.
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      BACKGROUND: Magnetic resonance imaging (MRI) has been incorporated as an adjunct to CT to take advantage of its excellent soft tissue contrast for contouring. MR-only treatment planning approaches have been developed to avoid errors introduced during the MR-CT registration process. The purpose of this study is to evaluate calculated dose distributions after incorporating a novel synthetic CT (synCT) derived from magnetic resonance simulation images into prostate cancer treatment planning and to compare dose distributions calculated using three previously published MR-only treatment planning methodologies.

      METHODS: An IRB-approved retrospective study evaluated 15 prostate cancer patients that underwent IMRT (n = 11) or arc therapy (n = 4) to a total dose of 70.2-79.2 Gy. Original treatment plans were derived from CT simulation images (CT-SIM). T1-weighted, T2-weighted, and balanced turbo field echo images were acquired on a 1.0 T high field open MR simulator with patients immobilized in treatment position. Four MR-derived images were studied: bulk density assignment (10 HU) to water (MRW), bulk density assignments to water and bone with pelvic bone values derived either from literature (491 HU, MRW+B491) or from CT-SIM population average bone values (300 HU, MRW+B300), and synCTs. Plans were recalculated using fixed monitor units, plan dosimetry was evaluated, and local dose differences were characterized using gamma analysis (1 %/1 mm dose difference/distance to agreement).

      RESULTS: While synCT provided closest agreement to CT-SIM for D95, D99, and mean dose (<0.7 Gy (1 %)) compared to MRW, MRW+B491, and MRW+B300, pairwise comparisons showed differences were not significant (p < 0.05). Significant improvements were observed for synCT in the bladder, but not for rectum or penile bulb. SynCT gamma analysis pass rates (97.2 %) evaluated at 1 %/1 mm exceeded those from MRW (94.7 %), MRW+B300 (94.0 %), or MRW+B491 (90.4 %). One subject's synCT gamma (1 %/1 mm) results (89.9 %) were lower than MRW (98.7 %) and MRW+B300 (96.7 %) due to increased rectal gas during MR-simulation that did not affect bulk density assignment-based calculations but was reflected in higher rectal doses for synCT.

      CONCLUSIONS: SynCT values provided closest dosimetric and gamma analysis agreement to CT-SIM compared to bulk density assignment-based CT surrogates. SynCTs may provide additional clinical value in treatment sites with greater air-to-soft tissue ratio.

      PMID:26597251 | PMC:PMC4657299 | DOI:10.1186/s13014-015-0549-7


      View details for PubMedID 26597251
  • Magnetic Resonance-Based Automatic Air Segmentation for Generation of Synthetic Computed Tomography Scans in the Head Region International journal of radiation oncology, biology, physics
    Zheng W, Kim JP, Kadbi M, Movsas B, Chetty IJ, Glide-Hurst CK
    2015 Nov 1;93(3):497-506. doi: 10.1016/j.ijrobp.2015.07.001. Epub 2015 Jul 9.
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      PURPOSE: To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first step toward MR-only radiation therapy treatment planning for brain cancer.

      METHODS AND MATERIALS: Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis.

      RESULTS: On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone-air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort.

      CONCLUSIONS: A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain.

      PMID:26460991 | DOI:10.1016/j.ijrobp.2015.07.001


      View details for PubMedID 26460991
  • Technical Note: Characterization and correction of gradient nonlinearity induced distortion on a 1.0 T open bore MR-SIM Medical physics
    Price RG, Kadbi M, Kim J, Balter J, Chetty IJ, Glide-Hurst CK
    2015 Oct;42(10):5955-60. doi: 10.1118/1.4930245.
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      PURPOSE: Distortions in magnetic resonance imaging (MRI) compromise spatial fidelity, potentially impacting delineation and dose calculation. We characterized 2D and 3D large field of view (FOV), sequence-independent distortion at various positions in a 1.0 T high-field open MR simulator (MR-SIM) to implement correction maps for MRI treatment planning.

      METHODS: A 36 × 43 × 2 cm(3) phantom with 255 known landmarks (∼1 mm(3)) was scanned using 1.0 T high-field open MR-SIM at isocenter in the transverse, sagittal, and coronal axes, and a 465 × 350 × 168 mm(3) 3D phantom was scanned by stepping in the superior-inferior direction in three overlapping positions to achieve a total 465 × 350 × 400 mm(3) sampled FOV yielding >13 800 landmarks (3D Gradient-Echo, TE/TR/α = 5.54 ms/30 ms/28°, voxel size = 1 × 1 × 2 mm(3)). A binary template (reference) was generated from a phantom schematic. An automated program converted MR images to binary via masking, thresholding, and testing for connectivity to identify landmarks. Distortion maps were generated by centroid mapping. Images were corrected via warping with inverse distortion maps, and temporal stability was assessed.

      RESULTS: Over the sampled FOV, non-negligible residual gradient distortions existed as close as 9.5 cm from isocenter, with a maximum distortion of 7.4 mm as close as 23 cm from isocenter. Over six months, average gradient distortions were -0.07 ± 1.10 mm and 0.10 ± 1.10 mm in the x and y directions for the transverse plane, 0.03 ± 0.64 and -0.09 ± 0.70 mm in the sagittal plane, and 0.4 ± 1.16 and 0.04 ± 0.40 mm in the coronal plane. After implementing 3D correction maps, distortions were reduced to <1 pixel width (1 mm) for all voxels up to 25 cm from magnet isocenter.

      CONCLUSIONS: Inherent distortion due to gradient nonlinearity was found to be non-negligible even with vendor corrections applied, and further corrections are required to obtain 1 mm accuracy for large FOVs. Statistical analysis of temporal stability shows that sequence independent distortion maps are consistent within six months of characterization.

      PMID:26429270 | PMC:PMC4583515 | DOI:10.1118/1.4930245


      View details for PubMedID 26429270
  • Four dimensional magnetic resonance imaging optimization and implementation for magnetic resonance imaging simulation Practical radiation oncology
    Glide-Hurst CK, Kim JP, To D, Hu Y, Kadbi M, Nielsen T, Chetty IJ
    2015 Nov-Dec;5(6):433-42. doi: 10.1016/j.prro.2015.06.006. Epub 2015 Jun 19.
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      PURPOSE: Precise radiation therapy for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast from 4-dimensional (4D) computed tomography, whereas 4D magnetic resonance imaging MRI (4DMRI) provides superior tissue discrimination. This work evaluates a novel 4DMRI algorithm for motion management in radiation therapy.

      METHODS AND MATERIALS: Respiratory-triggered, T2-weighted, single-shot 4DMRI was evaluated for an open 1.0T magnetic resonance simulation platform. An in-house programmable platform was devised that translated objects for a variety of breathing patterns. Coronal 4DMRIs were acquired to evaluate the impact of number of phases on excursion and scan time. The impact of breathing period and regularity on scan time was assessed. A novel clinical 4D prototype phantom was scanned to characterize excursion and absolute volume differences between phase acquisitions. Optimized parameters were applied to abdominal 4DMRIs of 5 volunteers and 2 abdominal cancer patients on an institutional review board-approved protocol. Duty cycle, scan time, and waveform analysis were evaluated. Maximum intensity projection datasets were analyzed.

      RESULTS: Two- to 5-fold acquisition time increase was measured for 10-phase versus 2-phase phantom experiments. Regular breathing patterns yielded higher duty cycles than irregular (48.5% and 35.9%, respectively, P < .001), whereas faster breathing rates yielded shorter 4DMRI acquisition times. Volumes of a hypodense target were underestimated 4% to 5% for 2 and 4 phases compared with 10 phases. Better agreement was obtained for 6- and 8-phase acquisitions (~3% different from 10 phase). Internal target volume centroids on minimum and maximum images across all phases were <2 mm different across all 10 phases, although slight target excursion variations (up to 4 mm) were observed. In humans, a strong negative association between breathing rate and acquisition time (Pearson's r = -0.68, P < .05) was observed. Eight-phase acquisition times ranged from 7 to 15 minutes, depending on the patient.

      CONCLUSION: 4DMRI has been optimized and implemented. Irregular breathing patterns and slow breathing rate adversely impacted 4DMRI efficiency; thus, interventions such as biofeedback may be desirable.

      PMID:26419444 | DOI:10.1016/j.prro.2015.06.006


      View details for PubMedID 26419444
  • Initial clinical experience with a radiation oncology dedicated open 1.0T MR-simulation Journal of applied clinical medical physics
    Glide-Hurst CK, Wen N, Hearshen D, Kim J, Pantelic M, Zhao B, Mancell T, Levin K, Movsas B, Chetty IJ, Siddiqui MS
    2015 Mar 8;16(2):5201. doi: 10.1120/jacmp.v16i2.5201.
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      The purpose of this study was to describe our experience with 1.0T MR-SIM including characterization, quality assurance (QA) program, and features necessary for treatment planning. Staffing, safety, and patient screening procedures were developed. Utilization of an external laser positioning system (ELPS) and MR-compatible couchtop were illustrated. Spatial and volumetric analyses were conducted between CT-SIM and MR-SIM using a stereotactic QA phantom with known landmarks and volumes. Magnetic field inhomogeneity was determined using phase difference analysis. System-related, in-plane distortion was evaluated and temporal changes were assessed. 3D distortion was characterized for regions of interest (ROIs) 5-20 cm away from isocenter. American College of Radiology (ACR) recommended tests and impact of ELPS on image quality were analyzed. Combined ultrashort echotime Dixon (UTE/Dixon) sequence was evaluated. Amplitude-triggered 4D MRI was implemented using a motion phantom (2-10 phases, ~ 2 cm excursion, 3-5 s periods) and a liver cancer patient. Duty cycle, acquisition time, and excursion were evaluated between maximum intensity projection (MIP) datasets. Less than 2% difference from expected was obtained between CT-SIM and MR-SIM volumes, with a mean distance of &lt; 0.2 mm between landmarks. Magnetic field inhomogeneity was &lt; 2 ppm. 2D distortion was &lt; 2 mm over 28.6-33.6 mm of isocenter. Within 5 cm radius of isocenter, mean 3D geometric distortion was 0.59 ± 0.32 mm (maximum = 1.65 mm) and increased 10-15 cm from isocenter (mean = 1.57 ± 1.06 mm, maximum = 6.26 mm). ELPS interference was within the operating frequency of the scanner and was characterized by line patterns and a reduction in signal-to-noise ratio (4.6-12.6% for TE = 50-150 ms). Image quality checks were within ACR recommendations. UTE/Dixon sequences yielded detectability between bone and air. For 4D MRI, faster breathing periods had higher duty cycles than slow (50.4% (3 s) and 39.4% (5 s), p &lt; 0.001) and ~fourfold acquisition time increase was measured for ten-phase versus two-phase. Superior-inferior object extent was underestimated 8% (6 mm) for two-phase as compared to ten-phase MIPs, although &lt; 2% difference was obtained for ≥ 4 phases. 4D MRI for a patient demonstrated acceptable image quality in ~ 7 min. MR-SIM was integrated into our workflow and QA procedures were developed. Clinical applicability was demonstrated for 4D MRI and UTE imaging to support MR-SIM for single modality treatment planning.

      PMID:26103190 | PMC:PMC5690096 | DOI:10.1120/jacmp.v16i2.5201


      View details for PubMedID 26103190
  • Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients Radiation oncology (London, England)
    Doemer A, Chetty IJ, Glide-Hurst C, Nurushev T, Hearshen D, Pantelic M, Traughber M, Kim J, Levin K, Elshaikh MA, Walker E, Movsas B
    2015 Feb 11;10:37. doi: 10.1186/s13014-014-0309-0.
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      BACKGROUND: This study describes initial testing and evaluation of a vertical-field open Magnetic Resonance Imaging (MRI) scanner for the purpose of simulation in radiation therapy for prostate cancer. We have evaluated the clinical workflow of using open MRI as a sole modality for simulation and planning. Relevant results related to MRI alignment (vs. CT) reference dataset with Cone-Beam CT (CBCT) for daily localization are presented.

      METHODS: Ten patients participated in an IRB approved study utilizing MRI along with CT simulation with the intent of evaluating the MRI-simulation process. Differences in prostate gland volume, seminal vesicles, and penile bulb were assessed with MRI and compared to CT. To evaluate dose calculation accuracy, bulk-density-assignments were mapped onto respective MRI datasets and treated IMRT plans were re-calculated. For image localization purposes, 400 CBCTs were re-evaluated with MRI as the reference dataset and daily shifts compared against CBCT-to-CT registration. Planning margins based on MRI/CBCT shifts were computed using the van Herk formalism.

      RESULTS: Significant organ contour differences were noted between MRI and CT. Prostate volumes were on average 39.7% (p = 0.002) larger on CT than MRI. No significant difference was found in seminal vesicle volumes (p = 0.454). Penile bulb volumes were 61.1% higher on CT, without statistical significance (p = 0.074). MRI-based dose calculations with assigned bulk densities produced agreement within 1% with heterogeneity corrected CT calculations. The differences in shift positions for the cohort between CBCT-to-CT registration and CBCT-to-MRI registration are -0.15 ± 0.25 cm (anterior-posterior), 0.05 ± 0.19 cm (superior-inferior), and -0.01 ± 0.14 cm (left-right).

      CONCLUSIONS: This study confirms the potential of using an open-field MRI scanner as primary imaging modality for prostate cancer treatment planning simulation, dose calculations and daily image localization.

      PMID:25889107 | PMC:PMC4340286 | DOI:10.1186/s13014-014-0309-0


      View details for PubMedID 25889107
  • High-quality t2-weighted 4-dimensional magnetic resonance imaging for radiation therapy applications International journal of radiation oncology, biology, physics
    Du D, Caruthers SD, Glide-Hurst C, Low DA, Li HH, Mutic S, Hu Y
    2015 Jun 1;92(2):430-7. doi: 10.1016/j.ijrobp.2015.01.035. Epub 2015 Mar 30.
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      PURPOSE: The purpose of this study was to improve triggering efficiency of the prospective respiratory amplitude-triggered 4-dimensional magnetic resonance imaging (4DMRI) method and to develop a 4DMRI imaging protocol that could offer T2 weighting for better tumor visualization, good spatial coverage and spatial resolution, and respiratory motion sampling within a reasonable amount of time for radiation therapy applications.

      METHODS AND MATERIALS: The respiratory state splitting (RSS) and multi-shot acquisition (MSA) methods were analytically compared and validated in a simulation study by using the respiratory signals from 10 healthy human subjects. The RSS method was more effective in improving triggering efficiency. It was implemented in prospective respiratory amplitude-triggered 4DMRI. 4DMRI image datasets were acquired from 5 healthy human subjects. Liver motion was estimated using the acquired 4DMRI image datasets.

      RESULTS: The simulation study showed the RSS method was more effective for improving triggering efficiency than the MSA method. The average reductions in 4DMRI acquisition times were 36% and 10% for the RSS and MSA methods, respectively. The human subject study showed that T2-weighted 4DMRI with 10 respiratory states, 60 slices at a spatial resolution of 1.5 × 1.5 × 3.0 mm(3) could be acquired in 9 to 18 minutes, depending on the individual's breath pattern. Based on the acquired 4DMRI image datasets, the ranges of peak-to-peak liver displacements among 5 human subjects were 9.0 to 12.9 mm, 2.5 to 3.9 mm, and 0.5 to 2.3 mm in superior-inferior, anterior-posterior, and left-right directions, respectively.

      CONCLUSIONS: We demonstrated that with the RSS method, it was feasible to acquire high-quality T2-weighted 4DMRI within a reasonable amount of time for radiation therapy applications.

      PMID:25838186 | PMC:PMC4431950 | DOI:10.1016/j.ijrobp.2015.01.035


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  • Intrafraction variability and deformation quantification in the breast International journal of radiation oncology, biology, physics
    Glide-Hurst CK, Shah MM, Price RG, Liu C, Kim J, Mahan M, Fraser C, Chetty IJ, Aref I, Movsas B, Walker EM
    2015 Mar 1;91(3):604-11. doi: 10.1016/j.ijrobp.2014.11.003. Epub 2015 Jan 30.
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      PURPOSE: To evaluate intrafraction variability and deformation of the lumpectomy cavity (LC), breast, and nearby organs.

      METHODS AND MATERIALS: Sixteen left-sided postlumpectomy and 1 bilateral breast cancer cases underwent free-breathing CT (FBCT) and 10-phase 4-dimensional CT (4DCT). Deformable image registration was used for deformation analysis and contour propagation of breast, heart, lungs, and LC between end-exhale and end-inhale 4DCT phases. Respiration-induced motion was calculated via centroid analysis. Two planning target volumes (PTVs) were compared: PTV(FBCT) from the FBCT volume with an isotropic 10 mm expansion (5 mm excursion and 5 mm setup error) and PTV(4DCT) generated from the union of 4DCT contours with isotropic 5 mm margin for setup error. Volume and geometry were evaluated via percent difference and bounding box analysis, respectively. Deformation correlations between breast/cavity, breast/lung, and breast/heart were evaluated. Associations were tested between cavity deformation and proximity to chest wall and breast surface.

      RESULTS: Population-based 3-dimensional vector excursions were 2.5 ± 1.0 mm (range, 0.8-3.8 mm) for the cavity and 2.0 ± 0.8 mm (range, 0.7-3.0 mm) for the ipsilateral breast. Cavity excursion was predominantly in the anterior and superior directions (1.0 ± 0.8 mm and -1.8 ± 1.2 mm, respectively). Similarly, for all cases, LCs and ipsilateral breasts yielded median deformation values in the superior direction. For 14 of 17 patients, the LCs and breast interquartile ranges tended toward the anterior direction. The PTV(FBCT) was 51.5% ± 10.8% larger (P<.01) than PTV(4DCT). Bounding box analysis revealed that PTV(FBCT) was 9.8 ± 1.2 (lateral), 9.0 ± 2.2 (anterior-posterior), and 3.9 ± 1.8 (superior-inferior) mm larger than PTV(4DCT). Significant associations between breast and cavity deformation were found for 6 of 9 axes. No dependency was found between cavity deformation and proximity to chest wall or breast surface.

      CONCLUSIONS: Lumpectomy cavity and breast deformation and motion demonstrated large variability. A PTV(4DCT) approach showed value in patient-specific margins, particularly if robust interfraction setup analysis can be performed.

      PMID:25680602 | DOI:10.1016/j.ijrobp.2014.11.003


      View details for PubMedID 25680602
  • Implementation of a novel algorithm for generating synthetic CT images from magnetic resonance imaging data sets for prostate cancer radiation therapy International journal of radiation oncology, biology, physics
    Kim J, Glide-Hurst C, Doemer A, Wen N, Movsas B, Chetty IJ
    2015 Jan 1;91(1):39-47. doi: 10.1016/j.ijrobp.2014.09.015. Epub 2014 Nov 7.
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      PURPOSE: To describe and evaluate a method for generating synthetic computed tomography (synCT) images from magnetic resonance simulation (MR-SIM) data for accurate digitally reconstructed radiograph (DRR) generation and dose calculations in prostate cancer radiation therapy.

      METHODS AND MATERIALS: A retrospective evaluation was performed in 9 prostate cancer patients who had undergone MR-SIM in addition to CT simulation (CT-SIM). MR-SIM data were used to generate synCT images by using a novel, voxel-based weighted summation approach. A subset of patients was used for weight optimization, and the number of patients to use during optimization was determined. Hounsfield unit (HU) differences between CT-SIM and synCT images were analyzed via mean absolute error (MAE). Original, CT-based treatment plans were mapped onto synCTs. DRRs were generated, and agreement between CT and synCT-generated DRRs was evaluated via Dice similarity coefficient (DSC). Dose was recalculated, and dose-volume metrics and gamma analysis were used to evaluate resulting treatment plans.

      RESULTS: Full field-of-view synCT MAE across all patients was 74.3 ± 10.9 HU with differences from CTs of 2.0 ± 8.1 HU and 11.9 ± 46.7 HU for soft tissue structures (prostate, bladder, and rectum) and femoral bones, respectively. Calculated DSCs for anterior-posterior and lateral DRRs were 0.90 ± 0.04 and 0.92 ± 0.05, respectively. Differences in D99%, mean dose, and maximum dose to the clinical target volume from CT-SIM dose calculations were 0.75% ± 0.35%, 0.63% ± 0.34%, and 0.54% ± 0.33%, respectively, for synCT-generated plans. Gamma analysis (2%/2 mm dose difference/distance to agreement) revealed pass rates of 99.9% ± 0.1% (range, 99.7%-100%).

      CONCLUSION: Generated synCTs enabled accurate DRR generation and dose computation for prostate MR-only simulation. Dose recalculated on synCTs agreed well with original planning distributions. Further validation using a larger patient cohort is warranted.

      PMID:25442341 | DOI:10.1016/j.ijrobp.2014.09.015


      View details for PubMedID 25442341
  • Point/Counterpoint. MRI/CT is the future of radiotherapy treatment planning Medical physics
    Glide-Hurst CK, Low DA, Orton CG
    2014 Nov;41(11):110601. doi: 10.1118/1.4894495.
  • IMRT and RapidArc commissioning of a TrueBeam linear accelerator using TG-119 protocol cases Journal of applied clinical medical physics
    Wen N, Zhao B, Kim J, Chin-Snyder K, Bellon M, Glide-Hurst C, Barton K, Chen D, Chetty IJ
    2014 Sep 8;15(5):4843. doi: 10.1120/jacmp.v15i5.4843.
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      The purpose of this study is to evaluate the overall accuracy of intensity-modulated radiation therapy (IMRT) and RapidArc delivery using both flattening filter (FF) and flattening filter-free (FFF) modalities based on test cases developed by AAPM Task Group 119. Institutional confidence limits (CLs) were established as the baseline for patient specific treatment plan quality assurance (QA). The effects of gantry range, gantry speed, leaf speed, dose rate, as well as the capability to capture intentional errors, were evaluated by measuring a series of Picket Fence (PF) tests using the electronic portal imaging device (EPID) and EBT3 films. Both IMRT and RapidArc plans were created in a Solid Water phantom (30 × 30 × 15 cm3) for the TG-119 test cases representative of normal clinical treatment sites for all five photon energies (6X, 10X, 15X, 6X-FFF, 10X-FFF) and the Exact IGRT couch was included in the dose calculation. One high-dose point in the PTV and one low-dose point in the avoidance structure were measured with an ion chamber in each case for each energy. Similarly, two GAFCHROMIC EBT3 films were placed in the coronal planes to measure planar dose distributions in both high- and low-dose regions. The confidence limit was set to have 95% of the measured data fall within the tolerance. The mean of the absolute dose deviation for variable dose rate and gantry speed during RapidArc delivery was within 0.5% for all energies. The corresponding results for leaf speed tests were all within 0.4%. The combinations of dynamic leaf gap (DLG) and MLC transmission factor were optimized based on the ion chamber measurement results of RapidArc delivery for each energy. The average 95% CLs for the high-dose point in the PTV were 0.030 ± 0.007 (range, 0.022-0.038) for the IMRT plans and 0.029 ± 0.011 (range, 0.016-0.043) for the RapidArc plans. For low-point dose in the avoidance structures, the CLs were 0.029 ± 0.006 (range, 0.024-0.039) for the IMRT plans and 0.027 ± 0.013 (range, 0.017-0.047) for the RapidArc plans. The average 95% CLs using 3%/3 mm gamma criteria in the high-dose region were 5.9 ± 2.7 (range, 1.4-8.6) and 3.9 ± 2.9 (range, 1.5-8.8) for IMRT and RapidArc plans, respectively. The average 95% CLs in the low-dose region were 5.3 ± 2.6 (range, 1.2-7.4) and 3.7 ± 2.8 (range, 1.8-8.3) for IMRT and RapidArc plans, respectively. Based on ion chamber, as well as film measurements, we have established CLs values to ensure the high precision of IMRT and RapidArc delivery for both FF and FFF modalities.

      PMID:25207569 | PMC:PMC5711094 | DOI:10.1120/jacmp.v15i5.4843


      View details for PubMedID 25207569
  • Characterization of a commercial hybrid iterative and model-based reconstruction algorithm in radiation oncology Medical physics
    Price RG, Vance S, Cattaneo R, Schultz L, Elshaikh MA, Chetty IJ, Glide-Hurst CK
    2014 Aug;41(8):081907. doi: 10.1118/1.4885976.
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      PURPOSE: Iterative reconstruction (IR) reduces noise, thereby allowing dose reduction in computed tomography (CT) while maintaining comparable image quality to filtered back-projection (FBP). This study sought to characterize image quality metrics, delineation, dosimetric assessment, and other aspects necessary to integrate IR into treatment planning.

      METHODS: CT images (Brilliance Big Bore v3.6, Philips Healthcare) were acquired of several phantoms using 120 kVp and 25-800 mAs. IR was applied at levels corresponding to noise reduction of 0.89-0.55 with respect to FBP. Noise power spectrum (NPS) analysis was used to characterize noise magnitude and texture. CT to electron density (CT-ED) curves were generated over all IR levels. Uniformity as well as spatial and low contrast resolution were quantified using a CATPHAN phantom. Task specific modulation transfer functions (MTF task) were developed to characterize spatial frequency across objects of varied contrast. A prospective dose reduction study was conducted for 14 patients undergoing interfraction CT scans for high-dose rate brachytherapy. Three physicians performed image quality assessment using a six-point grading scale between the normal-dose FBP (reference), low-dose FBP, and low-dose IR scans for the following metrics: image noise, detectability of the vaginal cuff/bladder interface, spatial resolution, texture, segmentation confidence, and overall image quality. Contouring differences between FBP and IR were quantified for the bladder and rectum via overlap indices (OI) and Dice similarity coefficients (DSC). Line profile and region of interest analyses quantified noise and boundary changes. For two subjects, the impact of IR on external beam dose calculation was assessed via gamma analysis and changes in digitally reconstructed radiographs (DRRs) were quantified.

      RESULTS: NPS showed large reduction in noise magnitude (50%), and a slight spatial frequency shift (∼ 0.1 mm(-1)) with application of IR at L6. No appreciable changes were observed for CT-ED curves between FBP and IR levels [maximum difference ∼ 13 HU for bone (∼ 1% difference)]. For uniformity, differences were ∼ 1 HU between FBP and IR. Spatial resolution was well conserved; the largest MTFtask decrease between FBP and IR levels was 0.08 A.U. No notable changes in low-contrast detectability were observed and CNR increased substantially with IR. For the patient study, qualitative image grading showed low-dose IR was equivalent to or slightly worse than normal dose FBP, and is superior to low-dose FBP (p < 0.001 for noise), although these did not translate to differences in CT number, contouring ability, or dose calculation. The largest CT number discrepancy from FBP occurred at a bone/tissue interface using the most aggressive IR level [-1.2 ± 4.9 HU (range: -17.6-12.5 HU)]. No clinically significant contour differences were found between IR and FBP, with OIs and DSCs ranging from 0.85 to 0.95. Negligible changes in dose calculation were observed. DRRs preserved anatomical detail with <2% difference in intensity from FBP combined with aggressive IRL6.

      CONCLUSIONS: These results support integrating IR into treatment planning. While slight degradation in edges and shift in texture were observed in phantom, patient results show qualitative image grading, contouring ability, and dosimetric parameters were not adversely affected.

      PMID:25086538 | DOI:10.1118/1.4885976


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  • Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies Journal of thoracic disease
    Glide-Hurst CK, Chetty IJ
    2014 Apr;6(4):303-18. doi: 10.3978/j.issn.2072-1439.2013.11.10.
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      In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation.

      PMID:24688775 | PMC:PMC3968554 | DOI:10.3978/j.issn.2072-1439.2013.11.10


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  • Direct dose mapping versus energy/mass transfer mapping for 4D dose accumulation: fundamental differences and dosimetric consequences Physics in medicine and biology
    Li HS, Zhong H, Kim J, Glide-Hurst C, Gulam M, Nurushev TS, Chetty IJ
    2014 Jan 6;59(1):173-88. doi: 10.1088/0031-9155/59/1/173. Epub 2013 Dec 13.
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      The direct dose mapping (DDM) and energy/mass transfer (EMT) mapping are two essential algorithms for accumulating the dose from different anatomic phases to the reference phase when there is organ motion or tumor/tissue deformation during the delivery of radiation therapy. DDM is based on interpolation of the dose values from one dose grid to another and thus lacks rigor in defining the dose when there are multiple dose values mapped to one dose voxel in the reference phase due to tissue/tumor deformation. On the other hand, EMT counts the total energy and mass transferred to each voxel in the reference phase and calculates the dose by dividing the energy by mass. Therefore it is based on fundamentally sound physics principles. In this study, we implemented the two algorithms and integrated them within the Eclipse treatment planning system. We then compared the clinical dosimetric difference between the two algorithms for ten lung cancer patients receiving stereotactic radiosurgery treatment, by accumulating the delivered dose to the end-of-exhale (EE) phase. Specifically, the respiratory period was divided into ten phases and the dose to each phase was calculated and mapped to the EE phase and then accumulated. The displacement vector field generated by Demons-based registration of the source and reference images was used to transfer the dose and energy. The DDM and EMT algorithms produced noticeably different cumulative dose in the regions with sharp mass density variations and/or high dose gradients. For the planning target volume (PTV) and internal target volume (ITV) minimum dose, the difference was up to 11% and 4% respectively. This suggests that DDM might not be adequate for obtaining an accurate dose distribution of the cumulative plan, instead, EMT should be considered.

      PMID:24334328 | PMC:PMC3980482 | DOI:10.1088/0031-9155/59/1/173


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  • Using patient-specific phantoms to evaluate deformable image registration algorithms for adaptive radiation therapy Journal of applied clinical medical physics
    Stanley N, Glide-Hurst C, Kim J, Adams J, Li S, Wen N, Chetty IJ, Zhong H
    2013 Nov 4;14(6):4363. doi: 10.1120/jacmp.v14i6.4363.
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      The quality of adaptive treatment planning depends on the accuracy of its underlying deformable image registration (DIR). The purpose of this study is to evaluate the performance of two DIR algorithms, B-spline-based deformable multipass (DMP) and deformable demons (Demons), implemented in a commercial software package. Evaluations were conducted using both computational and physical deformable phantoms. Based on a finite element method (FEM), a total of 11 computational models were developed from a set of CT images acquired from four lung and one prostate cancer patients. FEM generated displacement vector fields (DVF) were used to construct the lung and prostate image phantoms. Based on a fast-Fourier transform technique, image noise power spectrum was incorporated into the prostate image phantoms to create simulated CBCT images. The FEM-DVF served as a gold standard for verification of the two registration algorithms performed on these phantoms. The registration algorithms were also evaluated at the homologous points quantified in the CT images of a physical lung phantom. The results indicated that the mean errors of the DMP algorithm were in the range of 1.0 ~ 3.1 mm for the computational phantoms and 1.9 mm for the physical lung phantom. For the computational prostate phantoms, the corresponding mean error was 1.0-1.9 mm in the prostate, 1.9-2.4mm in the rectum, and 1.8-2.1 mm over the entire patient body. Sinusoidal errors induced by B-spline interpolations were observed in all the displacement profiles of the DMP registrations. Regions of large displacements were observed to have more registration errors. Patient-specific FEM models have been developed to evaluate the DIR algorithms implemented in the commercial software package. It has been found that the accuracy of these algorithms is patient dependent and related to various factors including tissue deformation magnitudes and image intensity gradients across the regions of interest. This may suggest that DIR algorithms need to be verified for each registration instance when implementing adaptive radiation therapy.

      PMID:24257278 | PMC:PMC4041490 | DOI:10.1120/jacmp.v14i6.4363


      View details for PubMedID 24257278
  • Evaluation of two synchronized external surrogates for 4D CT sorting Journal of applied clinical medical physics
    Glide-Hurst CK, Smith MS, Ajlouni M, Chetty IJ
    2013 Nov 4;14(6):4301. doi: 10.1120/jacmp.v14i6.4301.
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      The purpose of this study was to quantify the performance and agreement between two different external surrogate acquisition systems: Varian's Real-Time Position Management (RPM) and Philips Medical Systems' pneumatic bellows, in the context of waveform and 4D CT image analysis. Eight patient displacement curves derived from RPM data were inputted into a motion platform with varying amplitudes (0.5 to 3 cm) and patterns. Simultaneous 4D CT acquisition, with synchronized X-ray on detection, was performed with the bellows and RPM block placed on the platform. Bellows data were used for online retrospective phase-based sorting, while RPM data were used for off-line reconstruction of raw 4D CT data. RPM and bellows breathing curves were resampled, normalized, and analyzed to determine associations between different external surrogates, relative amplitude differences, and system latency. Maximum intensity projection (MIP) images were generated, phantom targets were delineated, and volume differences, overlap index, and Dice similarity coefficient differences were evaluated. A prospective patient study of ten patients was performed and waveforms were evaluated for latency (i.e., absolute time differences) and overall agreement. 4D CT sorting quality and subtraction images were assessed. Near perfect associations between the RPM and bellows-acquired breathing traces were found (Pearson's r = 0.987-0.999). Target volumes were 200.4 ± 12 cc and 199.8 ± 12.6 cc for RPM and bellows targets, respectively, which was not significantly different (U = 33, p &gt; 0.05). Negligible centroid variations were observed between bellows and RPM-contoured MIP targets (largest discrepancy = -0.24 ± 0.31 mm in superior-inferior direction). The maximum volume difference was observed for an RPM target 2.5 cc (1%) less than bellows, yielding the largest difference in centroid displacement (0.9 mm). Strong correlations in bellows and RPM waveforms were observed for all patients (0.947 ± 0.037). Latency between external surrogates was &lt; 100 ms for phantom and patient data. Negligible differences were observed between MIP, end-exhale, and end-inhale phase images for all cases, with delineated RPM and bellows lung volumes demonstrating a mean difference of -0.3 ± 0.51%. Dice similarity coefficients and overlap indices were near unity for phantom target volumes and patient lung volumes. Slight differences were observed in waveform and latency analysis between Philips bellows and Varian's RPM, although these did not translate to differences in image quality or impact delineations. Therefore, the two systems were found to be equivalent external surrogates in the context of 4D CT for treatment planning purposes.

      PMID:24257273 | PMC:PMC5714627 | DOI:10.1120/jacmp.v14i6.4301


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  • An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy Physics in medicine and biology
    Wen N, Kumarasiri A, Nurushev T, Burmeister J, Xing L, Liu D, Glide-Hurst C, Kim J, Zhong H, Movsas B, Chetty IJ
    2013 Nov 7;58(21):7733-44. doi: 10.1088/0031-9155/58/21/7733. Epub 2013 Oct 18.
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      The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7-9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIM-CT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation based on biological models, might yield higher quality treatments.

      PMID:24140847 | PMC:PMC4073000 | DOI:10.1088/0031-9155/58/21/7733


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  • Voxel-based statistical analysis of uncertainties associated with deformable image registration Physics in medicine and biology
    Li S, Glide-Hurst C, Lu M, Kim J, Wen N, Adams JN, Gordon J, Chetty IJ, Zhong H
    2013 Sep 21;58(18):6481-94. doi: 10.1088/0031-9155/58/18/6481. Epub 2013 Sep 3.
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      Deformable image registration (DIR) algorithms have inherent uncertainties in their displacement vector fields (DVFs).The purpose of this study is to develop an optimal metric to estimate DIR uncertainties. Six computational phantoms have been developed from the CT images of lung cancer patients using a finite element method (FEM). The FEM generated DVFs were used as a standard for registrations performed on each of these phantoms. A mechanics-based metric, unbalanced energy (UE), was developed to evaluate these registration DVFs. The potential correlation between UE and DIR errors was explored using multivariate analysis, and the results were validated by landmark approach and compared with two other error metrics: DVF inverse consistency (IC) and image intensity difference (ID). Landmark-based validation was performed using the POPI-model. The results show that the Pearson correlation coefficient between UE and DIR error is rUE-error = 0.50. This is higher than rIC-error = 0.29 for IC and DIR error and rID-error = 0.37 for ID and DIR error. The Pearson correlation coefficient between UE and the product of the DIR displacements and errors is rUE-error × DVF = 0.62 for the six patients and rUE-error × DVF = 0.73 for the POPI-model data. It has been demonstrated that UE has a strong correlation with DIR errors, and the UE metric outperforms the IC and ID metrics in estimating DIR uncertainties. The quantified UE metric can be a useful tool for adaptive treatment strategies, including probability-based adaptive treatment planning.

      PMID:24002435 | PMC:PMC4068011 | DOI:10.1088/0031-9155/58/18/6481


      View details for PubMedID 24002435
  • Evaluation of the deformation and corresponding dosimetric implications in prostate cancer treatment Physics in medicine and biology
    Wen N, Glide-Hurst C, Nurushev T, Xing L, Kim J, Zhong H, Liu D, Liu M, Burmeister J, Movsas B, Chetty IJ
    2012 Sep 7;57(17):5361-79. doi: 10.1088/0031-9155/57/17/5361. Epub 2012 Aug 3.
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      The cone-beam computed tomography (CBCT) imaging modality is an integral component of image-guided adaptive radiation therapy (IGART), which uses patient-specific dynamic/temporal information for potential treatment plan modification. In this study, an offline process for the integral component IGART framework has been implemented that consists of deformable image registration (DIR) and its validation, dose reconstruction, dose accumulation and dose verification. This study compares the differences between planned and estimated delivered doses under an IGART framework of five patients undergoing prostate cancer radiation therapy. The dose calculation accuracy on CBCT was verified by measurements made in a Rando pelvic phantom. The accuracy of DIR on patient image sets was evaluated in three ways: landmark matching with fiducial markers, visual image evaluation and unbalanced energy (UE); UE has been previously demonstrated to be a feasible method for the validation of DIR accuracy at a voxel level. The dose calculated on each CBCT image set was reconstructed and accumulated over all fractions to reflect the 'actual dose' delivered to the patient. The deformably accumulated (delivered) plans were then compared to the original (static) plans to evaluate tumor and normal tissue dose discrepancies. The results support the utility of adaptive planning, which can be used to fully elucidate the dosimetric impact based on the simulated delivered dose to achieve the desired tumor control and normal tissue sparing, which may be of particular importance in the context of hypofractionated radiotherapy regimens.

      PMID:22863976 | PMC:PMC3652266 | DOI:10.1088/0031-9155/57/17/5361


      View details for PubMedID 22863976
  • Coupling surface cameras with on-board fluoroscopy: a feasibility study Medical physics
    Glide-Hurst CK, Ionascu D, Berbeco R, Yan D
    2011 Jun;38(6):2937-47. doi: 10.1118/1.3581057.
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      PURPOSE: To investigate the feasibility of using three-dimensional surface imaging cameras as an external surrogate of tumor motion through a temporal synchronization with kV imaging.

      METHODS: To obtain an "x-ray on" signal from the on-board kV fluoroscopy system (XVI, Elekta), a hardware controller (Gate Controller) was interfaced between the kV fluoroscopy and Gate CT (VisionRT Ltd., London) computers. First, phantom experiments were performed using a programmable respiratory motion platform (sinusoidal motion, period = 3-5 s). The platform included a chest-wall component (A-P amplitude = 1 cm) tracked with the surface camera, while tumorlike objects translated in the superior-inferior direction were tracked using kV fluoroscopy (300 frames, frequency 5.5 fps). Accuracy of tracking the chest-wall platform was assessed, and the latency of the system was characterized by performing linear regression between the peak times obtained from Gate CT and fluoroscopy. Increasing the complexity of experiments, tumor displacement curves from three patients were simulated using synchronous tumor-abdomen data (RTRT). Our approach was further validated by imaging four free-breathing lung cancer patients with simultaneous Gate CT and kV fluoroscopy for approximately 55 s. Consideration was also given to varied sizes and locations of the tracked region of interest on the patient surface.

      RESULTS: For simple sinusoidal curves, measured amplitude (peak-to-peak) was 1.005 +/- 0.003 cm, 1.013 +/- 0.003 cm, and 1.003 +/- 0.005 cm for periods of 5, 4, and 3.3 s, respectively, demonstrating an excellent agreement with the actual chest platform amplitude of 1.0 cm. Period measurements were within 0.2% of actual using the surface cameras and within 0.9% of actual value using fluoroscopy. For the sinusoidal motion, the system latency was 0.64 +/- 0.02 s. This was further validated for the simulated tumor motion from three patients (latency = 0.65 +/- 0.03 s). Five of the nine patient fractions studied showed the associations between the abdomen and tumor were equivalent or better (Pearson r = 0.93-0.98) than those observed between the diaphragm and tumor (Pearson r = 0.89-0.95). A repeat analysis of five different tracked surfaces on the same patient further demonstrated strong agreement with the diaphragm and tumor, although no improvement in association strength was observed with increased size of region of interest.

      CONCLUSIONS: The feasibility of using surface imaging cameras to track the patient's abdomen as an external surrogate, while using kV imaging to track internal anatomy in synchrony, has been demonstrated. With further validation through additional patient studies to confirm these findings, gated radiation therapy treatments using surface imaging cameras as the external surrogate can be facilitated.

      PMID:21815367 | DOI:10.1118/1.3581057


      View details for PubMedID 21815367
  • Comparison of IGRT registration strategies for optimal coverage of primary lung tumors and involved nodes based on multiple four-dimensional CT scans obtained throughout the radiotherapy course International journal of radiation oncology, biology, physics
    Mohammed N, Kestin L, Grills I, Shah C, Glide-Hurst C, Yan D, Ionascu D
    2012 Mar 15;82(4):1541-8. doi: 10.1016/j.ijrobp.2011.04.025. Epub 2011 Jun 12.
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      PURPOSE: To investigate the impact of primary tumor and involved lymph node (LN) geometry (centroid, shape, volume) on internal target volume (ITV) throughout treatment for locally advanced non-small cell lung cancer using weekly four-dimensional computed tomography (4DCT).

      METHODS AND MATERIALS: Eleven patients with advanced non-small cell lung cancer were treated using image-guided radiotherapy with acquisition of weekly 10-Phase 4DCTs (n = 51). Initial ITV was based on planning 4DCT. Master-ITV incorporated target geometry across the entire treatment (all 4DCTs). Geographic miss was defined as the % Master-ITV positioned outside of the initial planning ITV after registration is complete. Registration strategies considered were bony (B), primary tumor soft tissue alone (T), and registration based on primary tumor and involved LNs (T_LN).

      RESULTS: The % geographic miss for the primary tumor, mediastinal, and hilar lymph nodes based on each registration strategy were (1) B: 30%, 30%, 30%; (2) T: 21%, 40%, 36%; and (3) T_LN: 26%, 26%, 27%. Mean geographic expansions to encompass 100% of the primary tumor and involved LNs were 1.2 ± 0.7 cm and 0.8 ± 0.3 cm, respectively, for B and T_LN. Primary and involved LN expansions were 0.7 ± 0.5 cm and 1.1 ± 0.5 cm for T.

      CONCLUSION: T is best for solitary targets. When treatments include primary tumor and LNs, B and T_LN provide more comprehensive geographic coverage. We have identified high % geographic miss when considering multiple registration strategies. The dosimetric implications are the subject of future study.

      PMID:21664070 | DOI:10.1016/j.ijrobp.2011.04.025


      View details for PubMedID 21664070
  • Advances in treatment techniques: arc-based and other intensity modulated therapies Cancer journal (Sudbury, Mass.)
    Jin J, Wen N, Ren L, Glide-Hurst C, Chetty IJ
    2011 May-Jun;17(3):166-76. doi: 10.1097/PPO.0b013e31821f8318.
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      Treatment planning and radiation delivery techniques have advanced significantly during the past 2 decades. The development of the multileaf collimator has changed the scope of radiotherapy. The dynamic conformal arc technique emerged from traditional cone-based conformal arc therapies, which aim to improve target dose uniformity and reduce normal tissue doses. With dynamic conformal arc, the multileaf collimator aperture is shaped dynamically to conform to the target. With the advent of intensity-modulated radiotherapy (IMRT), the concept of arc therapy in combination with IMRT has enabled better-quality dose distributions and more efficient delivery. Helical tomotherapy has been developed to treat targets sequentially by modulating the beam intensity in each "slice" of the patient. Helical tomotherapy offers improved dose distributions for complicated treatments, such as whole-body radiation. Intensity-modulated arc therapy has been studied to modulate fluences in a cone beam rather than fan beam geometry to improve delivery efficiency. This article reviews arc-based IMRT, intensity-modulated arc therapy, and helical tomotherapy techniques. We compare the dosimetric results reported in the literature for each technique in various treatment sites. We also review the application of these techniques in specialized clinical procedures including total marrow irradiation, simultaneous treatment of multiple brain metastases, dose painting, simultaneous integrated boost, and stereotactic radiosurgery.

      PMID:21610470 | DOI:10.1097/PPO.0b013e31821f8318


      View details for PubMedID 21610470
  • Point/counterpoint. Ultrasonography is soon likely to become a viable alternative to x-ray mammography for breast cancer screening Medical physics
    Glide-Hurst CK, Maidment DA, Orton CG
    2010 Sep;37(9):4526-9. doi: 10.1118/1.3459019.
  • Anatomic and pathologic variability during radiotherapy for a hybrid active breath-hold gating technique International journal of radiation oncology, biology, physics
    Glide-Hurst CK, Gopan E, Hugo GD
    2010 Jul 1;77(3):910-7. doi: 10.1016/j.ijrobp.2009.09.080.
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      PURPOSE: To evaluate intra- and interfraction variability of tumor and lung volume and position using a hybrid active breath-hold gating technique.

      METHODS AND MATERIALS: A total of 159 repeat normal inspiration active breath-hold CTs were acquired weekly during radiotherapy for 9 lung cancer patients (12-21 scans per patient). A physician delineated the gross tumor volume (GTV), lungs, and spinal cord on the first breath-hold CT, and contours were propagated semiautomatically. Intra- and interfraction variability of tumor and lung position and volume were evaluated. Tumor centroid and border variability were quantified.

      RESULTS: On average, intrafraction variability of lung and GTV centroid position was <2.0 mm. Interfraction population variability was 3.6-6.7 mm (systematic) and 3.1-3.9 mm (random) for the GTV centroid and 1.0-3.3 mm (systematic) and 1.5-2.6 mm (random) for the lungs. Tumor volume regressed 44.6% +/- 23.2%. Gross tumor volume border variability was patient specific and demonstrated anisotropic shape change in some subjects. Interfraction GTV positional variability was associated with tumor volume regression and contralateral lung volume (p < 0.05). Inter-breath-hold reproducibility was unaffected by time point in the treatment course (p > 0.1). Increases in free-breathing tidal volume were associated with increases in breath-hold ipsilateral lung volume (p < 0.05).

      CONCLUSIONS: The breath-hold technique was reproducible within 2 mm during each fraction. Interfraction variability of GTV position and shape was substantial because of tumor volume and breath-hold lung volume change during therapy. These results support the feasibility of a hybrid breath-hold gating technique and suggest that online image guidance would be beneficial.

      PMID:20510201 | PMC:PMC2956181 | DOI:10.1016/j.ijrobp.2009.09.080


      View details for PubMedID 20510201
  • A simplified method of four-dimensional dose accumulation using the mean patient density representation Medical physics
    Glide-Hurst CK, Hugo GD, Liang J, Yan D
    2008 Dec;35(12):5269-77. doi: 10.1118/1.3002304.
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      The purpose of this work was to demonstrate, both in phantom and patient, the feasibility of using an average 4DCT image set (AVG-CT) for 4D cumulative dose estimation. A series of 4DCT numerical phantoms and corresponding AVG-CTs were generated. For full 4D dose summation, static dose was calculated on each phase and cumulative dose was determined by combining each phase's static dose distribution with known tumor displacement. The AVG-CT cumulative dose was calculated similarly, although the same AVG-CT static dose distribution was used for all phases (i.e., tumor displacements). Four lung cancer cases were also evaluated for stereotactic body radiotherapy and conformal treatments; however, deformable image registration of the 4DCTs was used to generate the displacement vector fields (DVFs) describing patient-specific motion. Dose discrepancy between full 4D summation and AVG-CT approach was calculated and compared. For all phantoms, AVG-CT approximation yielded slightly higher cumulative doses compared to full 4D summation, with dose discrepancy increasing with increased tumor excursion. In vivo, using the AVG-CT coupled with deformable registration yielded clinically insignificant differences for all GTV parameters including the minimum, mean, maximum, dose to 99% of target, and dose to 1% of target. Furthermore, analysis of the spinal cord, esophagus, and heart revealed negligible differences in major dosimetric indices and dose coverage between the two dose calculation techniques. Simplifying 4D dose accumulation via the AVG-CT, while fully accounting for tumor deformation due to respiratory motion, has been validated, thereby, introducing the potential to streamline the use of 4D dose calculations in clinical practice, particularly for adaptive planning purposes.

      PMID:19175086 | PMC:PMC2673609 | DOI:10.1118/1.3002304


      View details for PubMedID 19175086
  • Volumetric breast density evaluation from ultrasound tomography images Medical physics
    Glide-Hurst CK, Duric N, Littrup P
    2008 Sep;35(9):3988-97. doi: 10.1118/1.2964092.
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      Previous ultrasound tomography work conducted by our group showed a direct correlation between measured sound speed and physical density in vitro, and increased in vivo sound speed with increasing mammographic density, a known risk factor for breast cancer. Building on these empirical results, the purpose of this work was to explore a metric to quantify breast density using our ultrasound tomography sound speed images in a manner analogous to computer-assisted mammogram segmentation for breast density analysis. Therefore, volumetric ultrasound percent density (USPD) is determined by segmenting high sound speed areas from each tomogram using a k-means clustering routine, integrating these results over the entire volume of the breast, and dividing by whole-breast volume. First, a breast phantom comprised of fat inclusions embedded in fibroglandular tissue was scanned four times with both our ultrasound tomography clinical prototype (with 4 mm spatial resolution) and CT. The coronal transmission tomograms and CT images were analyzed using semiautomatic segmentation routines, and the integrated areas of the phantom's fat inclusions were compared between the four repeated scans. The average variability for inclusion segmentation was approximately 7% and approximately2%, respectively, and a close correlation was observed in the integrated areas between the two modalities. Next, a cohort of 93 patients was imaged, yielding volumetric coverage of the breast (45-75 sound speed tomograms/patient). The association of USPD with mammographic percent density (MPD) was evaluated using two measures: (1) qualitative, as determined by a radiologist's visual assessment using BI-RADS Criteria and (2) quantitative, via digitization and semiautomatic segmentation of craniocaudal and mediolateral oblique mammograms. A strong positive association between BI-RADS category and USPD was demonstrated [Spearman rho = 0.69 (p < 0.001)], with significant differences between all BI-RADS categories as assessed by one-way ANOVA and Scheffé posthoc analysis. Furthermore, comparing USPD to calculated mammographic density yielded moderate to strong positive associations for CC and MLO views (r2 = 0.75 and 0.59, respectively). These results support the hypothesis that utilizing USPD as an analogue to mammographic breast density is feasible, providing a nonionizing, whole-breast analysis.

      PMID:18841850 | DOI:10.1118/1.2964092


      View details for PubMedID 18841850
  • A new method for quantitative analysis of mammographic density Medical physics
    Glide-Hurst CK, Duric N, Littrup P
    2007 Nov;34(11):4491-8. doi: 10.1118/1.2789407.
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      Women with mammographic percent density >50% have a approximately three-fold increased risk of developing breast cancer, potentially making them screening candidates for breast MRI scanning. The purpose of this work is to introduce a new method to quantify mammographic percent density (MPD), and to compare the results with the current standard of care for breast density assessment. Craniocaudal (CC) and mediolateral oblique (MLO) mammograms for 104 patients were digitized and analyzed using an interactive computer-assisted segmentation routine implemented for two purposes: (1) to segment the breast area from background and radiographic markers, and (2) to segment dense from fatty portions of the breast. Our technique was evaluated by comparing the results to qualitative estimates determined by a certified breast radiologist using the BI-RADS Categorical Assessment (1 (fatty) to 4 (dense) scale). Statistically significant correlations (two-tailed, p < 0.01) were observed between calculated MPD and BI-RADS for both CC (Spearman rho = 0.67) and MLO views (Spearman rho = 0.71). For the CC view, statistically significant differences were revealed between the mean MPD for each BI-RADS category except between fatty (BI-RADS 1) and scattered (BI-RADS 2). Finally, for the MLO views, statistically significant differences in the mean MPD between all BI-RADS categories were observed. Comparing the CC and MLO views revealed a strong positive correlation (Pearson r = 0.8) in calculated MPD. In addition, an evaluation of the reproducibility of our segmentation demonstrated the average standard deviation of MPD for a subsample of eight patients, measured five times, was 1.9% (range: 0.03%-9.9%). Eliminating one misassignment reduced the average standard deviation to 0.75% (range: 0.03%-3.16%). Further analysis of approximately 10% of the patient sample revealed strong agreement (ICC = 0.80-0.85) in the reliability of MPD estimates for both mammographic views. Overall, these results demonstrate the feasibility of utilizing our approach for quantitative breast density segmentation, which may be useful for detecting small changes in MPD introduced through chemoprevention, diet, or other interventions.

      PMID:18072514 | DOI:10.1118/1.2789407


      View details for PubMedID 18072514
  • Detection of breast cancer with ultrasound tomography: first results with the Computed Ultrasound Risk Evaluation (CURE) prototype Medical physics
    Duric N, Littrup P, Poulo L, Babkin A, Pevzner R, Holsapple E, Rama O, Glide C
    2007 Feb;34(2):773-85. doi: 10.1118/1.2432161.
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      Although mammography is the gold standard for breast imaging, its limitations result in a high rate of biopsies of benign lesions and a significant false negative rate for women with dense breasts. In response to this imaging performance gap we have been developing a clinical breast imaging methodology based on the principles of ultrasound tomography. The Computed Ultrasound Risk Evaluation (CURE) system has been designed with the clinical goals of whole breast, operator-independent imaging, and differentiation of breast masses. This paper describes the first clinical prototype, summarizes our initial image reconstruction techniques, and presents phantom and preliminary in vivo results. In an initial assessment of its in vivo performance, we have examined 50 women with the CURE prototype and obtained the following results. (1) Tomographic imaging of breast architecture is demonstrated in both CURE modes of reflection and transmission imaging. (2) In-plane spatial resolution of 0.5 mm in reflection and 4 mm in transmission is achieved. (3) Masses > 15 mm in size are routinely detected. (4) Reflection, sound speed, and attenuation imaging of breast masses are demonstrated. These initial results indicate that operator-independent, whole-breast imaging and the detection of breast masses are feasible. Future studies will focus on improved detection and differentiation of masses in support of our long-term goal of increasing the specificity of breast exams, thereby reducing the number of biopsies of benign masses.

      PMID:17388195 | DOI:10.1118/1.2432161


      View details for PubMedID 17388195
  • Novel approach to evaluating breast density utilizing ultrasound tomography Medical physics
    Glide C, Duric N, Littrup P
    2007 Feb;34(2):744-53. doi: 10.1118/1.2428408.
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      Women with high mammographic breast density have a four- to fivefold increased risk of developing breast cancer compared to women with fatty breasts. Many preventative strategies have attempted to correlate changes in breast density with response to interventions including drugs and diet. The purpose of this work is to investigate the feasibility of assessing breast density with acoustic velocity measurements with ultrasound tomography, and to compare the results with existing measures of mammographic breast density. An anthropomorphic breast tissue phantom was first imaged with our computed ultrasound tomography clinical prototype. Strong positive correlations were observed between sound speed and material density, and sound speed and computed tomography number (Pearson correlation coefficients= 0.87 and 0.91, respectively). A cohort of 48 women was then imaged. Whole breast acoustic velocity was determined by creating image stacks and evaluating the sound speed frequency distribution. The acoustic measures of breast density were evaluated by comparing these results to two mammographic density measures: (1) qualitative estimates determined by a certified radiologist using the BI-RADS Categorical Assessment based on a 1 (fatty) to 4 (dense) scale, and (2) quantitative measurements via digitization and computerized analysis of archival mammograms. A one-way analysis of variance showed that a significant difference existed between the mean values of sound speed according to BI-RADS category, while post hoc analyses using the Scheffé criterion for significance indicated that BI-RADS 4 (dense) patients had a significantly higher sound speed than BI-RADS 1, 2, and 3 at an alpha level of 0.05. Using quantitative measures of breast density, a direct correlation between the mean acoustic velocity and calculated mammographic percent breast density was demonstrated with correlation coefficients ranging from 0.75 to 0.89. The results presented here support the hypothesis that sound speed can be used as an indicator of breast tissue density. Noninvasive, nonionizing monitoring of dietary and chemoprevention interventions that affect breast density are now possible.

      PMID:17388192 | DOI:10.1118/1.2428408


      View details for PubMedID 17388192

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