Biranavan Uthayakumar^1,2, Casey Y Lee^1,2, Nadia Bragagnolo^1,2, Hany Soliman³, Albert P Chen⁴, Ruby Endre⁵, William J Perks², Chris Heyn⁶, Sandra E Black², and Charles Cunningham^7
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Radiation oncolocy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁴GE Healthcare, Toronto, ON, Canada, ⁵Physical sciences, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁶Radiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁷Medical Biophysics, Sunnybrook research institute, Toronto, ON, Canada

In this study, hyperpolarized ¹³C MRI was used to investigate age-related changes to lactate and bicarbonate production in the brain in a healthy aging population. A whole-brain parcellation method was used to investigate regional changes. A global reduction in the production of both ¹³C-lactate and ¹³C-bicarbonate was observed vs. age, with certain regions showing increased rates of change in comparison to the rest of the brain. Our results suggest an age-related change in the underlying metabolic processes, and paves the way for future analysis of pathological aging as seen in disorders like Alzheimer's disease.

Caroline Guglielmetti^1,2, Huihui Li³, Lydia M. Le Page^1,2, Lauren Y. Shields³, Jeffrey C. Rathmell⁴, Ken Nakamura³, and Myriam M. Chaumeil^1,2
1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Sciences, University of California San Francisco, San Francisco, CA, United States, ³Gladstone Institute of Neurological Disease, San Francisco, CA, United States, ⁴Vanderbilt Center for Immunobiology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States

We used hyperpolarized ¹³C magnetic resonance spectroscopic imaging (HP ¹³C MRSI), fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) imaging and T₂-weighted MRI to detect brain glucose metabolism in mice harboring deletion of the glucose transporter 3 (GLUT3) in CA1 hippocampal neurons. GLUT3 deletion induced memory impairment in males and females, highlighting the importance of glucose uptake by neurons. HP [1-¹³C]lactate-to-pyruvate ratios and brain volumes were decreased in female GLUT3 deficient mice, but not in males, indicating sex-specific vulnerability. No changes were detected using ¹⁸F-FDG PET imaging, highlighting the potential of HP [1-¹³C]pyruvate to detect downstream alterations in brain glucose metabolism.

Frits H.A. van Heijster¹, Jason G. Skinner¹, Tim Wartewig², Christian Hundshammer¹, Martin Grashei¹, Geoffrey J. Topping¹, Erik Hameister², Jürgen Ruland², and Franz Schilling^1
1Technical University Munich, Nuclear Medicine, Klinikum rechts der Isar, München, Germany, ²Technical University Munich, TranslaTUM, Center for Translational Cancer Research, München, Germany

High- and low- glycolytic phenotypes of murine T-cell lymphoma are characterized using hyperpolarized MR spectroscopy/imaging and [¹⁸F]FDG-PET. Differences in pyruvate-to-lactate conversion are found within tumor groups, where PET imaging did not show this distinction. Using tumor metabolic volumes derived from PET imaging on the other hand, it’s possible to distinguish between low- and high-grade tumors. The complementary information of the two modalities gives a more complete view of the characteristics of the glycolytic phenotypes in T-cell lymphoma.

Jun Chen¹, Junjie Ma¹, Crystal E Harrison¹, James Ratnakar¹, Zungho Zun², Jeff Liticker¹, Galen D Reed³, Avneesh Chhabra⁴, Thomas Jue⁵, Craig R Malloy^1,3,6, and Jae Mo Park^1,4,7
1AIRC, UT Southwestern Medical Center, Dallas, TX, United States, ²The Developing Brain Institute, Children’s National Hospital, Washington, DC, United States, ³GE, Chicago, IL, United States, ⁴Radiology, UT Southwestern Medical Center, Dallas, TX, United States, ⁵Biochemistry and Molecular Medicine, UC Davis, Davis, CA, United States, ⁶Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States, ⁷Electrical and Computer Engineering, University of Texas at Dallas, Richardson, TX, United States

Pyruvate dehydrogenase (PDH) and lactate dehydrogenase (LDH) are essential for ATP production in skeletal muscle. However, directly PDH flux in exercising human muscle has been challenging and never assessed. This study was to demonstrate the feasibility of assessing PDH activation and changes in pyruvate metabolism in human skeletal muscle after the onset of exercise using hyperpolarized [1-13C]pyruvate. During moderate flexion-extension exercise, total HP 13C signals (tC), [1-13C]lactate/tC, and [13C]bicarbonate/tC increased significantly compared to resting state. This study demonstrates that PDH flux in skeletal muscle increases rapidly after the onset of exercise and decreases during recovery. 

Georgios Batsios¹, Celine Taglang¹, Anne Marie Gillespie¹, Peder Larson¹, Sabrina M Ronen¹, and Pavithra Viswanath^1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States

Glucose metabolism via the pentose phosphate pathway (PPP) is typically upregulated in tumors, including gliomas. We previously showed that hyperpolarized δ-[1-¹³C]gluconolactone metabolism via the PPP to 6-phospho-[1-¹³C]gluconate (6PG) differentiates tumor from contralateral normal brain in preclinical glioma models. Here, we examined the ability of hyperpolarized δ-[1-¹³C]gluconolactone to probe response to temozolomide, which is a key chemotherapeutic drug for glioma patients. Our studies in live cells and rats bearing orthotopic gliomas indicate that 6PG production from hyperpolarized δ-[1-¹³C]gluconolactone serves as an early biomarker of response to temozolomide, a finding that has the potential to improve treatment response monitoring for glioma patients.

Helen Marshall¹, Grace T Mussell¹, Laurie J Smith¹, Alberto M Biancardi¹, Paul JC Hughes¹, Andrew J Swift¹, Smitha Rajaram¹, Alison M Condliffe¹, Guilhem J Collier¹, Chris S Johns¹, Nick D Weatherley¹, Ian Sabroe², and Jim M Wild^1
1University of Sheffield, Sheffield, United Kingdom, ²Sheffield Teaching Hospitals, Sheffield, United Kingdom

The ability of hyperpolarised gas MRI to translate into real-world clinical practice is unknown.  ¹²⁹Xe ventilation images were acquired as part of routine care in patients referred from a difficult asthma service, and evaluated by a multi-disciplinary team.  Evidence of airways obstruction on MRI can support the use of further treatment, for example in those with normal spirometry and high symptom burden.  Well preserved ventilation on MRI alongside poor spirometry and/or symptom control may suggest coexisting breathing control issues or laryngeal disorders.  ¹²⁹Xe MRI can provide additional unique and valuable information in the evaluation of clinical presentations of asthma. 

Elianna Ada Bier¹, Fawaz Alenezi², Junlan Lu³, Joseph G Mammarappallil⁴, Bastiaan Driehuys⁴, and Sudarshan Rajagopal^2
1Biomedical Engineering, Duke University, Durham, NC, United States, ²Division of Cardiology, Department of Medicine, Duke Univeristy, Durham, NC, United States, ³Medical Physics Graduate Program, Duke University, Durham, NC, United States, ⁴Radiology, Duke University, Durham, NC, United States

¹²⁹Xe dynamic spectroscopy combined with ¹²⁹Xe gas exchange MRI can detect both pre- and postcapillary pulmonary hypertension (PH). However, reliance on whole lung spectroscopy limits this technique’s ability to detect spatially heterogeneous impacts of PH. For example, the algorithm cannot identify combined pre- and postcapillary PH (CpcPH) and does not currently account for out-of-proportion PH in patients with parenchymal disease.  Here we use the recently introduced method of imaging signal oscillations from ¹²⁹Xe in red blood cells to gain additional insights into 26 subjects who have also undergone right heart catheterization to determine PH status within 2 months of imaging. 

Agilo Luitger Kern^1,2, Marcel Gutberlet^1,2, Frank Wacker^1,2, Jens Hohlfeld^2,3,4, and Jens Vogel-Claussen^1,2
1Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany, ²Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany, ³Department of Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, ⁴Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany

A pulse sequence for hyperpolarized ¹²⁹Xe NMR based on accumulated stimulated echoes has been implemented. Pairs of 90° pulses are repeatedly irradiated at the frequency of ¹²⁹Xe in tissue-plasma and the decaying signal transferred to the gas phase is subsequently acquired. A study with healthy volunteers and patients of chronic obstructive pulmonary disease (COPD) has been performed to assess the method’s sensitivity for disease. A significant reduction of initial stimulated echo signal and trend for faster decay are observed in COPD. The proposed method has been demonstrated to be highly sensitive for emphysema and hyperinflation and shows promising diagnostic potential.

Harkiran K Kooner¹, Marrissa J McIntosh¹, Maksym Sharma¹, Alexander M Matheson¹, Yasal Rajapaksa¹, Inderdeep Dhaliwal², Michael Nicholson², and Grace Parraga^1
1Robarts Research Institute, Western University, London, ON, Canada, ²Department of Medicine, Western University, London, ON, Canada

Persistent, long-term COVID-19 symptoms and pulmonary function abnormalities, beyond the acute infectious pulmonary disease phase, is now recognized in certain patients and referred to as long-haul or long COVID. We used hyperpolarized ¹²⁹Xe MRI ventilation defect percent (VDP) and texture analysis to evaluate and characterize second-order ¹²⁹Xe MRI ventilation texture features in a pilot study of participants with long-haul COVID-19. We observed statistically significant differences in ¹²⁹Xe MRI VDP and ventilation texture features between COVID-19 survivors and volunteers who were not infected. Second-order ¹²⁹Xe MRI ventilation texture features dichotomized long-haul COVID-19 and volunteers in the absence of qualitative VDP differences.

Brice J Albert¹, Peter J Niedbalski¹, and Zackary I Cleveland^1,2,3,4
1Center for Pulmonary Imaging Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ³Department of Pediatrics, University of Cincinnati Medical Center, Cincinnati, OH, United States, ⁴Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States

Center-out trajectories are often used in preclinical HP gas MRI to reduce the impact of physiological motion and magnetization decay on image quality. Recently, implementation of 3D spiral (FLORET) imaging for human ¹²⁹Xe ventilation imaging demonstrated higher accuracy in detecting ventilation abnormalities than traditional sequences. Here we show FLORET sequences provide superior SNR, consume less xenon, and reduce scan time by more than five times when used to image ventilation in mice.