Intern, University of Wisconsin - Madison, (2021)
MD, Ohio State University College of Medicine, (2020)
PhD, Southern Illinois University, Applied Physics (2016)
BS, Drake University, Physics (2011)
Selected Honors and Awards
Sigma-Pi-Sigma: Physics Honor Society Member (2014-2021)
American Society for Therapeutic Radiation and Oncology (ASTRO): Student Membership (2021)
XeUS: A second-generation automated open-source batch-mode clinical-scale hyperpolarizer Journal of magnetic resonance (San Diego, Calif. : 1997)
Birchall JR, Irwin RK, Nikolaou P, Coffey AM, Kidd BE, Murphy M, Molway M, Bales LB, Ranta K, Barlow MJ, Goodson BM, Rosen MS, Chekmenev EY
2020 Oct;319:106813. doi: 10.1016/j.jmr.2020.106813. Epub 2020 Sep 1.
We present a second-generation open-source automated batch-mode 129Xe hyperpolarizer (XeUS GEN-2), designed for clinical-scale hyperpolarized (HP) 129Xe production via spin-exchange optical pumping (SEOP) in the regimes of high Xe density (0.66-2.5 atm partial pressure) and resonant photon flux (~170 W, Δλ = 0.154 nm FWHM), without the need for cryo-collection typically employed by continuous-flow hyperpolarizers. An Arduino micro-controller was used for hyperpolarizer operation. Processing open-source software was employed to program a custom graphical user interface (GUI), capable of remote automation. The Arduino Integrated Development Environment (IDE) was used to design a variety of customized automation sequences such as temperature ramping, NMR signal acquisition, and SEOP cell refilling for increased reliability. A polycarbonate 3D-printed oven equipped with a thermo-electric cooler/heater provides thermal stability for SEOP for both binary (Xe/N2) and ternary (4He-containing) SEOP cell gas mixtures. Quantitative studies of the 129Xe hyperpolarization process demonstrate that near-unity polarization can be achieved in a 0.5 L SEOP cell. For example, %PXe of 93.2 ± 2.9% is achieved at 0.66 atm Xe pressure with polarization build-up rate constant γSEOP = 0.040 ± 0.005 min-1, giving a max dose equivalent ≈ 0.11 L/h 100% hyperpolarized, 100% enriched 129Xe; %PXe of 72.6 ± 1.4% is achieved at 1.75 atm Xe pressure with γSEOP of 0.041 ± 0.001 min-1, yielding a corresponding max dose equivalent of 0.27 L/h. Quality assurance studies on this device have demonstrated the potential to refill SEOP cells hundreds of times without significant losses in performance, with average %PXe = 71.7%, (standard deviation σP = 1.52%) and mean polarization lifetime T1 = 90.5 min, (standard deviation σT = 10.3 min) over the first ~200 gas mixture refills, with sufficient performance maintained across a further ~700 refills. These findings highlight numerous technological developments and have significant translational relevance for efficient production of gaseous HP 129Xe contrast agents for use in clinical imaging and bio-sensing techniques.
PMID:32932118 | DOI:10.1016/j.jmr.2020.106813
View details for PubMedID 32932118
Helium-rich mixtures for improved batch-mode clinical-scale spin-exchange optical pumping of Xenon-129 Journal of magnetic resonance (San Diego, Calif. : 1997)
Birchall JR, Nikolaou P, Irwin RK, Barlow MJ, Ranta K, Coffey AM, Goodson BM, Pokochueva EV, Kovtunov KV, Koptyug IV, Chekmenev EY
2020 Jun;315:106739. doi: 10.1016/j.jmr.2020.106739. Epub 2020 Apr 30.
We present studies of spin-exchange optical pumping (SEOP) using ternary xenon-nitrogen-helium gas mixtures at high xenon partial pressures (up to 1330 Torr partial pressure at loading, out of 2660 Torr total pressure) in a 500-mL volume SEOP cell, using two automated batch-mode clinical-scale 129Xe hyperpolarizers operating under continuous high-power (~170 W) pump laser irradiation. In this pilot study, we explore SEOP in gas mixtures with up to 45% 4He content under a wide range of experimental conditions. When an aluminum jacket cooling/heating design was employed (GEN-3 hyperpolarizer), 129Xe polarization (%PXe) of 55.9 ± 0.9% was observed with mono-exponential build-up rate γSEOP of 0.049 ± 0.001 min-1 for the 4He-rich mixture (1000 Torr Xe/900 Torr He, 100 Torr N2), compared to %PXe of 49.3 ± 3.3% at γSEOP of 0.035 ± 0.004 min-1 for the N2-rich gas mixture (1000 Torr Xe/100 Torr He, 900 Torr N2). When forced-air cooling/heating was used (GEN-2 hyperpolarizer), %PXe of 83.9 ± 2.7% was observed at γSEOP of 0.045 ± 0.005 min-1 for the 4He-rich mixture (1000 Torr Xe/900 Torr He, 100 Torr N2), compared to %PXe of 73.5 ± 1.3% at γSEOP of 0.028 ± 0.001 min-1 for the N2-rich gas mixture (1000 Torr Xe and 1000 Torr N2). Additionally, %PXe of 72.6 ± 1.4% was observed at a build-up rate γSEOP of 0.041 ± 0.003 min-1 for a super-high-density 4He-rich mixture (1330 Torr Xe/1200 Torr 4He/130 Torr N2), compared to %PXe = 56.6 ± 1.3% at a build-up rate of γSEOP of 0.034 ± 0.002 min-1 for an N2-rich mixture (1330 Torr Xe/1330 Torr N2) using forced air cooling/heating. The observed SEOP hyperpolarization performance under these conditions corresponds to %PXe improvement by a factor of 1.14 ± 0.04 at 1000 Torr Xe density and by up to a factor of 1.28 ± 0.04 at 1330 Torr Xe density at improved SEOP build-up rates by factors of 1.61 ± 0.18 and 1.21 ± 0.11 respectively. Record %PXe levels have been obtained here: 83.9 ± 2.7% at 1000 Torr Xe partial pressure and 72.6 ± 1.4% at 1330 Torr Xe partial pressure. In addition to improved thermal stability for SEOP, the use of 4He-rich gas mixtures also reduces the overall density of produced inhalable HP contrast agents; this property may be desirable for HP 129Xe inhalation by human subjects in clinical settings-especially in populations with heavily impaired lung function. The described approach should enjoy ready application in the production of inhalable 129Xe contrast agent with near-unity 129Xe nuclear spin polarization.
PMID:32408239 | DOI:10.1016/j.jmr.2020.106739
View details for PubMedID 32408239
High Xe density, high photon flux, stopped-flow spin-exchange optical pumping: Simulations versus experiments Journal of magnetic resonance (San Diego, Calif. : 1997)
Skinner JG, Ranta K, Whiting N, Coffey AM, Nikolaou P, Rosen MS, Chekmenev EY, Morris PG, Barlow MJ, Goodson BM
2020 Mar;312:106686. doi: 10.1016/j.jmr.2020.106686. Epub 2020 Jan 16.
Spin-exchange optical pumping (SEOP) can enhance the NMR sensitivity of noble gases by up to five orders of magnitude at Tesla-strength magnetic fields. SEOP-generated hyperpolarised (HP) 129Xe is a promising contrast agent for lung imaging but an ongoing barrier to widespread clinical usage has been economical production of sufficient quantities with high 129Xe polarisation. Here, the 'standard model' of SEOP, which was previously used in the optimisation of continuous-flow 129Xe polarisers, is modified for validation against two Xe-rich stopped-flow SEOP datasets. We use this model to examine ways to increase HP Xe production efficiency in stopped-flow 129Xe polarisers and provide further insight into the underlying physics of Xe-rich stopped-flow SEOP at high laser fluxes.
PMID:32006793 | PMC:PMC7436892 | DOI:10.1016/j.jmr.2020.106686
View details for PubMedID 32006793
XeNA: an automated 'open-source' (129)Xe hyperpolarizer for clinical use Magnetic resonance imaging
Nikolaou P, Coffey AM, Walkup LL, Gust BM, Whiting N, Newton H, Muradyan I, Dabaghyan M, Ranta K, Moroz GD, Rosen MS, Patz S, Barlow MJ, Chekmenev EY, Goodson BM
2014 Jun;32(5):541-50. doi: 10.1016/j.mri.2014.02.002. Epub 2014 Feb 10.
Here we provide a full report on the construction, components, and capabilities of our consortium's "open-source" large-scale (~1L/h) (129)Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The 'hyperpolarizer' is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800Torr Xe in 0.5L) in either stopped-flow or single-batch mode-making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell (129)Xe nuclear spin polarization values of ~30%-90% have been measured for Xe loadings of ~300-1600Torr. Typical (129)Xe polarization build-up and T1 relaxation time constants were ~8.5min and ~1.9h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~200W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long (129)Xe relaxation times (up to nearly 6h) were observed in Tedlar bags following transport to a clinical 3T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine.
PMID:24631715 | PMC:PMC4011489 | DOI:10.1016/j.mri.2014.02.002
View details for PubMedID 24631715