Periannan Kuppusamy¹, Benjamin B Williams², Eunice Y Chen³, Maciej M Kmiec⁴, and Philip E Schaner^2
1Radiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States, ²Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States, ³Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States, ⁴Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States

We report a first-in-humans clinical study of EPR oximetry using the OxyChip to establish its feasibility and utility for clinically useful tumor oxygen measurements in cancer patients. Repeated measurements from a cohort of 11 cancer patients in 33 sessions over a long period of time revealed variable levels of clinically significant hypoxia as well as variable responses to a hypoxia-mitigation intervention. Overall, in light of this variability, this study further underscores the need to provide individualized repeatable assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.

Maciej M Kmiec¹, Kendra A Hebert¹, Dan Tse¹, Sassan Hodge¹, Benjamin B Williams², Philip E Schaner², and Periannan Kuppusamy^3
1Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States, ²Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States, ³Radiology, Geisel School of Medicine at Dartmouth College, Lebanon, NH, United States

EPR oximetry using the OxyChip can provide direct and repeated measurement of tissue oxygen; however, a significant limitation is its inability to identify the location of the probe in the tissue. We report the development of an OxyChip embedded with gold nanoparticles to visualize the implant using clinical ultrasound or CT. In vitro characterization, imaging, and histopathology of the probe using tissue phantoms, excised tissues, and in vivo animal models demonstrated a substantial enhancement of CT contrast with OxyChip-GNP without compromising its oxygen-sensing properties or biocompatibility. The OxyChip-GNP can facilitate precisely localized in vivo oxygen measurements in the clinical setting.

Nallathamby Devasahayam¹, Shun Kishimoto¹, Gadisetti Chandramouli², Yasunori C Otowa¹, Kota Yamashita¹, Kazutoshi Yamamoto¹, Jeffrey R Brender¹, and Murali C Krishna^1
1NCI, Bethesda, MD, United States, ²GenEpria Consulting, Inc, Columbia, MD, United States

In this work, we present our first 3D in vivo EPR oximetry study using Ox071 spin probe in comparison with Ox063 oximetry.  The R2* change with [Ox071] and pO₂ was calibrated using standard solutions. In vivo EPR imaging of a mouse tumor was performed on successive days by using either Ox071 or Ox063.  The zero gradient signal level of Ox071 was about twice stronger and lasted almost twice longer compared to Ox063. The spin density, and pO₂ maps and pO₂ histograms of tumor regions marked by co-registration with MRI were similar between Ox063 and Ox071.

Graham Norquay¹, Guilhem J. Collier¹, Rolf F. Schulte², and Jim M. Wild^1
1Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom, ²GE Healthcare, Munich, Germany

3D density-weighted MRSI was used to regionally measure the ¹²⁹Xe chemical shift from xenon in the lung airspaces (G), lung tissue/plasma (TP) and pulmonary red blood cells (RBC) at three lung inflation states. The ¹²⁹Xe-RBC and ¹²⁹Xe-G chemical shifts were both found to increase with increasing lung inflation (increase in alveolar pO2) while the ¹²⁹Xe-TP shift was observed to be lung-inflation independent. The RBC chemical shift maps presented here may be used in patient populations to detect areas of low blood oxygenation in diseases presenting regional hypoxia in the lungs and other well-perfused organs such as the brain and kidneys.

Junlan Lu¹, Jesse Zhang², Suphachart Leewiwatwong³, Isabelle Dummer⁴, David Mummy⁵, and Bastiaan Driehuys^3
1Medical Physics, Duke University, Durham, NC, United States, ²Mathematics, Duke University, Durham, NC, United States, ³Biomedical Engineering, Duke University, Durham, NC, United States, ⁴Biomedical Engineering, McGill University, Montreal, QC, Canada, ⁵Radiology, Duke University, Durham, NC, United States

Quantitative analysis of hyperpolarized ¹²⁹Xe MRI, segmentation of the thoracic cavity, a crucial step that is often the bottleneck in an otherwise fully automated pipeline. This problem is attractive to solve using deep learning methods, but they are limited by their large appetite for manually segmented training data. To this end, we propose a method to automatically synthesize both ¹²⁹Xe ventilation MR images and their corresponding thoracic cavity masks using general adversarial networks. This data augmentation technique can accelerate the training of deep learning segmentation models.

Aryil Liam Bechtel¹, Elianna Bier², Junlan Lu³, Alexander Church⁴, Jennifer Korzekwinski⁴, David Mummy⁵, and Bastiaan Driehuys^5
1Physics, Duke University, Durham, NC, United States, ²Biomedical Engineering, Duke University, Durham, NC, United States, ³Radiation Oncology, Clinical Science, Duke University, Durham, NC, United States, ⁴Duke University, Durham, NC, United States, ⁵Radiology, Clinical Science, Duke University, Durham, NC, United States

Hyperpolarized ¹²⁹Xe gas MRI provides a spatially resolved method of monitoring gas exchange function in the lungs via 3D reconstruction of RBC/gas and barrier/gas signals. However, the strength of these signals is affected by patient hemoglobin concentration (Hgb). Thus, correcting for Hgb is important for establishing normative healthy reference distributions and accurately assessing the degree of gas exchange impairment. Here, we use a 1D physical diffusion model to establish Hgb-dependent correction factors to standardize gas exchange MRI relative to a fixed Hgb value. This correction can result in substantial changes in the visualization and quantification of gas exchange MRI.

Kolja Them¹ and Jan Hövener^1
1Section Biomedical Imaging, Molecular Imaging North Competence Center (MOIN CC), Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein and Kiel University, Kiel, Germany

Parahydrogen-induced polarization relayed via proton exchange (PHIP-X) is a new method to hyperpolarize a variety of molecules that participate in suitable fast proton exchange with allyl alcohol. The combination of the wide applicability of polarization-transfer via proton exchange and the strong polarization obtained using hydrogenative of PHIP opens up new avenues to hyperpolarize biological molecules such as glucose, lactate and pyruvate. Hence, PHIP-X provides a promisingnew platform for potential applications in metabolic MRI.

Emma Linnea Wiström¹, Andrea Capozzi¹, Thanh Phong Lê¹, Rolf Gruetter¹, and Jean-Noël Hyacinthe^2
1LIFMET, École polytechnique fédérale de Lausanne, Lausanne, Switzerland, ²Geneva School of Health Sciences (HES-SO), University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland

Dissolution DNP (dDNP) is an alternative for hyperpolarizing ¹²⁹Xe to the well acknowledged method spin exchange optical pumping (SEOP). As opposed to SEOP, DNP takes place in the solid state at very low temperatures. Therefore, it can potentially produce a large volume of hyperpolarized gas after dissolution. In this study, by implementing a new way of preparing the sample, we ease the overall process and establish a superior incorporation of the gas atoms into the solvent. Additionally, due to a surprisingly short radical electron T₁, we show that a higher polarization was achieved by applying microwave frequency modulation. 

Marrissa J McIntosh^1,2, Maksym Sharma^1,2, Alexander M Matheson^1,2, Harkiran K Kooner^1,2, Rachel L Eddy³, Christopher Licskai⁴, David G McCormack⁴, Michael Nicholson⁴, Cory Yamashita⁴, and Grace Parraga^1,2,4,5
1Department of Medical Biophysics, Western University, London, ON, Canada, ²Robarts Research Institute, London, ON, Canada, ³Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada, ⁴Division of Respirology, Department of Medicine, Western University, London, ON, Canada, ⁵School of Biomedical Engineering, Western University, London, ON, Canada

¹²⁹Xe MRI ventilation images consist of embedded texture features that may help explain ventilation heterogeneity. We previously showed that ¹²⁹Xe MRI ventilation features predicted response to biologic therapy in asthma and thus, we postulated that texture features may help explain central and peripheral airways resistance. We employed machine-learning techniques to identify specific ¹²⁹Xe MRI features that were related to airway resistance. Ventilation texture analysis yielded four unique and two common features that independently explained central and peripheral airways resistance, respectively. These promising results suggest that ¹²⁹Xe ventilation texture analysis may reveal hidden anatomic-physiologic measurements that lead to ventilation heterogeneity. 

Maximilian Fuetterer¹, Julia Traechtler¹, Andreas Dounas¹, Tobias Hoh¹, Mohammed Albannay¹, and Sebastian Kozerke^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zürich ETH-Zentrum, Switzerland

Motivated by the fact that the hyperpolarized MRI signal does not quadratically scale with field strength as for conventional MRI at thermal equilibrium, the achievable SNR at reduced field strengths is explored. It is demonstrated that for larger coil diameters, sample noise dominates electrical noise at 1.5T and achievable SNR becomes comparable to 3T. By adaptively reducing acquisition bandwidth to the reduced spectral span and given longer T2* decay, effective SNR at 1.5T exceeds 3T. Feasibility is demonstrated with the first in-vivo data acquired on a clinical 1.5T system using hyperpolarized ¹³C pyruvate.

Gigin Lin¹, Ying-Chieh Lai¹, Kuan-Ying Lu¹, Albert P Chen², and Ching-Yi Hsieh^3
1Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taiwan, ²GE Healthcare, Toronto, ON, Canada, ³Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan

Successful cancer therapy depends on an optimal immune response, but noninvasive tools are lacking to monitor this dynamic process. In this proof-of-concept human study, we demonstrated hyperpolarized [1-13C]pyruvate MRI of the spleen monitoring the immune activation for cancer patients at the early time point following radiotherapy, by measuring the pyruvate-to-lactate conversion rate. The ADC-based cellularity of the spleen, however, did not detect remarkable changes.

Viivi Hyppönen¹, Jessica Rosa¹, and Mikko Kettunen^1
1A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland

fMRI is widely used to study cerebral metabolism to stimulus through combination of BOLD and hemodynamic changes. Hyperpolarized carbon can also be used to study cerebral metabolism, but it is currently poorly understood. Here we performed simultaneous ¹H fMRI and ¹³C MRS experiments to compare their response to nicotine stimulus. Cortical BOLD signal increase was accompanied by increased bicarbonate labelling. Combined ¹H fMRI and ¹³C MRS may therefore offer complementary information on brain response to stimulus.

Emily Buchanan^1,2,3, James Ratnakar¹, Eul Hyun Suh¹, Jun Chen¹, Ivan Dimitrov^1,4, Jae Mo Park¹, A. Dean Sherry^1,2, and Zoltan Kovacs^1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ²Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX, United States, ³Physical Measurement Laboratory, National Institute of Standards and Technology, Boulder, CO, United States, ⁴Phillips Medical Systems, Cleveland, OH, United States

In this study, we prepared a ¹⁵N-enriched analog of NAD⁺ (N-methyl nicotinamide = MNA⁺) and demonstrated that it undergoes reduction by sodium dithionate to form MNAH. The ¹⁵N chemical shifts of the oxidized and reduced forms differ by 124.2ppm. DNP of MNA⁺ followed by dissolution and ¹⁵N NMR showed a favorable T₁ relaxation time of 130s at 1T and 50s at 3T. Deuteration of the methyl protons only increased the T₁ of ¹⁵N by ~10s. The long T₁ of ¹⁵N in these NAD⁺/NADH mimetics and the large chemical shift difference offer the exciting potential for their use as redox sensors.

Josh Peters¹, Arne Brahms², Vivian Janicaud^1,3, Mariia Anikeeva¹, Eva Peschke¹, Frowin Ellermann¹, Arianna Ferrari¹, Konrad Aden⁴, Stefan Schreiber⁴, Rainer Herges², Jan-Bernd Hövener¹, and Andrey N. Pravdivtsev^1
1SBMI, MOIN CC, UKSH, Kiel University, Kiel, Germany, ²Otto Diels Institute for Organic Chemistry, Kiel University, Kiel, Germany, ³Universität zu Lübeck, Lübeck, Germany, ⁴Institute of Clinical Molecular Biology, UKSH, Kiel University, Kiel, Germany

We synthesized 1-¹⁵N nicotinamide (NA) and built a saddle-shaped mouse body linear coil for ¹⁵N imaging. We found a way to polarize 1-¹⁵N-NA by dissolution dynamic nuclear polarization to 9.1±4.4% and measured the effect of the radical load. The lifetime of hyperpolarized NA was field-dependent: 100 s at 1 T, 60 s at 7 T, and 30 s at 9.4 T. An effect of the pH on liquid-state polarization was found.  N FLASH MRI of hyperpolarized NA was acquired in less than 1 s.