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Nicole I.C. Cappelletto¹, Hany Soliman², Casey Y. Lee¹, Nadia D. Bragagnolo³, Biranavan Uthayakumar¹, Arjun Sahgal², Albert P. Chen⁴, Ruby Endre³, Nathan Ma⁵, William J. Perks⁵, Jay S. Detsky², Chris Heyn⁶, and Charles H. Cunningham^1,3
1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ⁴GE Healthcare, Toronto, ON, Canada, ⁵Pharmacy, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁶Radiology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Keywords: Hyperpolarized MR (Non-Gas), Cancer, Treatment Response Prediction, Radiotherapy, Brain Metastases, Metabolism

Brain metastases are increasingly being treated with stereotactic radiosurgery; however, 20-30% of treated tumors locally recure post treatment. Hyperpolarized [1-¹³C]pyruvate magnetic resonance imaging (HP ¹³C MRI) is an emerging metabolic imaging modality that measures key metabolic phenotypes indicative of aggressive tumor phenotypes. Here we show that the pre-treatment tumor ¹³C-lactate to ¹³C-bicarbonate ratio – a marker of glycolysis and (indirectly) oxidative phosphorylation – measured via HP [1-¹³C]pyruvate MRI is a robust predictor of local recurrence (AUC_ROC=0.95, p=0.0008; AUC_PRC=0.92) and can inform treatment decisions should the model predict  a non-response to SRS.

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Jack J. Miller^1,2, Nikolaj Bøgh¹, Andrew Tyler³, Justin Y C Lau⁴, Esben Søvsø Szocska Hansen¹, Michael Væggemose^1,5, Oliver Rider⁶, Damian Tyler⁶, and Christoffer Laustsen^1
1The MR Research Centre, Aarhus University, Aarhus, Denmark, ²OCMR, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom, ³King's College London, London, United Kingdom, ⁴GE Healthcare, Schenectady, NY, United States, ⁵GE Healthcare, Brøndby, Denmark, ⁶OCMR, RDM, University of Oxford, Oxford, United Kingdom

Keywords: Hyperpolarized MR (Non-Gas), Data Analysis

Hyperpolarized metabolic imaging is translating into clinical practice. However, the desire to obtain chemical, spatial and temporal information combined with the finite and non-renewable exogenous magnetisation provided by hyperpolarized techniques often results  in imaging sequences with a poor point-spread function. Here we compare multiple deconvolution algorithms to improve apparent reconstructed resolution, as is commonly performed in PET imaging. We show that deconvolution can significantly improve the reconstructed resolution of hyperpolarized images. 

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Georgios Batsios¹, Celine Taglang¹, Anne Marie Gillespie¹, and Pavithra Viswanath^1
1University of California, San Francisco, San Francisco, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Cancer, animals, preclinical, brain, metabolism

TERT expression is essential for telomere maintenance and uncontrolled tumor proliferation in oligodendrogliomas. TERT is an attractive therapeutic target and the drug 6-thio-2’-deoxyguanosine that disrupts telomere maintenance is in clinical trials for cancer. We previously showed that TERT expression is associated with upregulation of the pentose phosphate pathway in oligodendrogliomas. Here, we have established the ability of hyperpolarized δ-[1-¹³C]-gluconolactone, a probe of the pentose phosphate pathway, to assess TERT expression and response to 6-thio-2’-deoxyguanosine in oligodendrogliomas in vivo. Our findings provide a non-invasive method of imaging a hallmark of cancer and have the potential to improve management of oligodendroglioma patients.

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Martin Grashei¹, Pascal Wodtke¹, Jason G Skinner¹, Sandra Sühnel¹, Nadine Setzer¹, Christian Hundshammer¹, and Franz Schilling^1
1TUM School of Medicine, Department of Nuclear Medicine, Technical University of Munich, Munich, Germany

Keywords: Hyperpolarized MR (Non-Gas), Non-Proton, Z-OMPD, Urea, Kidney

Fast and accurate assessment of kidney function is crucial for monitoring and detection of kidney disease and failure in various oncological scenarios. Current techniques rely on non‑spatially resolved blood or urine biomarkers and possess time- or safety-related constraints when using MRI or CT. Here, we demonstrate fast 3D bSSFP imaging and slice spectroscopy protocols using hyperpolarized [1,5-¹³C₂]Z-OMPD for assessment of renal perfusion and filtration in comparison with ¹³C-urea as an established perfusion agent. Measured renal blood flow and glomerular filtration rates agree with literature and between agents and methods, thereby rendering Z-OMPD a versatile agent for assessment of kidney functionality.

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Yaewon Kim¹, Duy Dang¹, James Slater¹, Andrew Riselli¹, Jeremy Gordon¹, Susan Chang², Yan Li¹, Evelyn Escobar¹, Hsin-Yu Chen¹, Chou T Tan³, Chris Suszczynski³, Robert Bok¹, and Dan Vigneron^1,2
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, ²Department of Neurological Surgery, University of California, San Francisco, CA, United States, ³ISOTEC Stable Isotope Division, MilliporeSigma, Miamisburg, OH, United States

Keywords: Hyperpolarized MR (Non-Gas), Non-Proton

Hyperpolarized [1-¹³C]alpha-ketoglutarate (aKG) is a metabolic probe that can provide direct access to the metabolic pathway for glutamate production or 2-HG production in altered alpha-ketoglutarate metabolism via IDH mutations. With its potential to serve as a biomarker of IDH1 mutational status in glioma and a measure of aKG metabolism in normal healthy subjects, we developed a new chemistry preparation and standard operating procedure (SOP) for on-site production of hyperpolarized GMP [1-¹³C]alpha-ketoglutarate and characterized the probe to investigate the feasibility of this probe in clinical setting. Following process qualification trials with HP [1-¹³C]aKG, an FDA IND application was prepared and submitted.

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Jun Chen¹, Edward Hackett¹, Laura Ingle², Sarah Al Nemri¹, Erik J Plautz², Brenda L Bartnik-Olson³, and Jae Mo Park^4,5
1Advanced Imaging Research Center, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ²Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ³Radiology, Loma Linda University, Loma Linda, CA, United States, ⁴Advanced Imaging Research Center,, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ⁵Department of Radiology, UT Southwestern Medical Center at Dallas, Dallas, TX, United States

Keywords: Hyperpolarized MR (Non-Gas), Brain

Due to the rapid and complex progression of metabolic alteration after traumatic brain injury (TBI), prompt assessment of cerebral metabolism is critical in preventing the subsequent injury processes and developing proper therapeutic strategies. In this study, we assessed longitudinal changes in bicarbonate production from hyperpolarized [1-13C]pyruvate in a rat TBI model. In addition to elevated lactate production, we observed significantly reduced bicarbonate production in the injured site. The contrast of bicarbonate signals between the injured region and the contralateral brain peaked at one day post-injury. A subset of TBI rats demonstrated markedly increased bicarbonate in contralateral brain regions post-injury.

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Kazutoshi Yamamoto¹, Yutaro Saito², Hiroyuki Yatabe², Norikazu Koyasu¹, Iori Tamura², Yohei Kondo², Ryo Ishida¹, Tomohiro Seki¹, Akihiro Eguchi², Yoichi Takakusagi¹, Nobu Oshima¹, Murali C. Krishna¹, and Shinsuke Sando^2
1National Cancer Institute, National Institutes of Health, Bethesda, MD, United States, ²The University of Tokyo, Bunkyo-ku, Japan

Keywords: Hyperpolarized MR (Non-Gas), Molecular Imaging

Profiling the metabolic phenotypes of tumors by molecular imaging is a promising approach in treatment planning and response monitoring.  Here, dissolution Dynamic Nuclear Polarization (dDNP) is an emerging technique to detect site-specific enzymatic activities noninvasively. While drastic dDNP sensitivity enhancements are advantageous for real-time measurements, the limited number of applicable probes with longer T₁ relaxation times continues to be a major drawback particularly for in vivo use. In this presentation, we will demonstrate a framework to design novel dDNP probes, detecting APN enzymatic activities which is a cancer therapeutic target, and its applications to in vivo pancreatic cancer.

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Alixander S Khan^1,2, Joshua Kaggie^1,2, Ines Horvat-Menih^1,2, Tomasz Matys¹, Rolf F Schulte³, Matthew Locke^1,2, Ashley Grimmer^1,2, Elizabeth Latimer^1,2, Amy Frary^1,2, Martin Graves¹, Mary McLean^1,2, and Ferdia Gallagher^1,2
1Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ²Cancer Research UK Cambridge Institute, Cambridge, United Kingdom, ³GE Healthcare, GE Healthcare, Munich, Germany

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas)

Hyperpolarized ¹³C MRS was used to measure human brain pH for the first time following ¹³C imaging through measurements of ¹³CO₂ and bicarbonate. Aspartate concentration was also found offering insight into amino acid metabolism.  Global brain pH was measured in the brain to be 6.98 ± 0.06. Non-invasive measurements of cerebral pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid-base balance. Aspartate was measured in 4 of 9 volunteers with no age-related trends seen. Pyruvate carboxylase flux was found to be 6% of pyruvate dehydrogenase flux.

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Prasanta Dutta¹, Deanna Glassman², Mark Kim², Meredith L Spradlin³, Emine Bayraktar², Elaine Stur², Selanere Mangala², Katherine Foster², Sanghoon Lee², Timothy A Yap⁴, Shannon Westin², Livia Eberlin⁵, Anil K Sood², and Pratip Bhattacharya^1
1Cancer Systems Imaging, UT-MD Anderson Cancer Center, Houston, TX, United States, ²Gynecologic Oncology and Reproductive Medicine, UT-MD Anderson Cancer Center, Houston, TX, United States, ³Chemistry, UT- Austin, Austin, TX, United States, ⁴Investigational Cancer Therapeutics, UT-MD Anderson Cancer Center, Houston, TX, United States, ⁵Surgery, Baylor College of Medicine, Houston, TX, United States

Keywords: Hyperpolarized MR (Non-Gas), Metabolism, Metabolic Imaging

The metabolic vulnerability of anti-VEGF antibody (AVA) resistant ovarian cancer with glutaminase inhibitor (GLSi) therapy was assessed by hyperpolarized ¹³C-pyruvate magnetic resonance spectroscopy (HP-MRS) in vivo and by desorption electrospray ionization spectroscopic (DESI-MS) imaging ex vivo. The lactate-to-pyruvate ratio was used as the treatment response imaging biomarker.

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Anna Bennett¹, Xioaxi Liu¹, Avantika Sinha¹, Sule Sahin¹, Peder E. Z. Larson¹, and Charlie Wang^1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

Keywords: MR Fingerprinting/Synthetic MR, RF Pulse Design & Fields, variable flip angle

A pyruvate-specific bSSFP protocol was defined, based on prior work, demonstrating increased signal efficiency over GRE sequences.   Monte Carlo simulations evaluated signal efficiency and kinetic performance of potential flip angle schemes.  A sigmoid-based flip scheme, varying from 5 to 80 degrees, showed greatest performance of kPL estimation compared to simulated GRE and constant flip angle bSSFP. Small animal studies validated the expected signal increase and kPL estimation, with resulting kinetic parameter maps showing consistency among methods and qualitative noise reduction.

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Christopher M Walker¹, Renjie He², Zhan Xu¹, Keith Michel¹, Gary Martinez¹, Collin J. Harlan¹, Abdallah S. R. Mohamed², Clifton D. Fuller ², Stephen Y. Lai³, and James A Bankson^1
1Imaging Physics, MD Anderson Cancer Center, Houston, TX, United States, ²Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, United States, ³Head and Neck Surgery, MD Anderson Cancer Center, Houston, TX, United States

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas)

Dynamic contrast enhanced MRI was used to derive perfusion terms which were incorporated into the fitting of hyperpolarized pyruvate to lactate apparent conversion rates. Incorporation of the DCE data reduced the fit metabolic conversion rates across the data set but more so for the post therapy data resulting in a significant decrease in kpl after therapy. These results suggest that more effort is needed to disentangle perfusion from metabolic effects when analyzing HP MRI data.

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Yupeng Zhao¹, Rie Beck Olin¹, Lars G. Hanson^1,2, Esben Søvsø Szocska Hansen³, Christoffer Laustsen³, and Jan Henrik Ardenkjær-Larsen^1
1Technical University of denmark, Kongens Lyngby, Denmark, ²Danish Research Centre for Magnetic Resonance, Hvidovre, Denmark, ³MR Research Centre, Aarhus University, Aarhus, Denmark

Keywords: Hyperpolarized MR (Non-Gas), Perfusion

We propose a 3D gradient echo sequence with hyperpolarized HP001 as contrast agent for whole heart myocardial perfusion quantification. The estimated perfusion values are correlated with the perfusion values estimated from dynamic contrast enhanced (DCE)-MRI. 

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Wolfgang Gottwald¹, Irina Heid², Luca Nagel¹, Martin Grashei¹, Sebastian Bauer¹, Mariia Semina², Nadine Setzer¹, Sandra Suehnel¹, Geoffrey J. Topping¹, Rickmer Braren^2,3, and Franz Schilling^1
1TUM School of Medicine, Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany, ²TUM School of Medicine, Institute of Diagnostic and Interventional Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany, ³German Cancer Consortium (DKTK, partner Site Munich), Munich, Germany

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas)

A newly developed multi-voxel point resolved spectroscopy (MV-PRESS) sequence was evaluated for the study of murine pancreatic ductal adenocarcinoma (PDAC) using hyperpolarized (HP) ¹³C-labelled molecules. First, the sequence was compared to standard 2D free-induction decay chemical shift imaging (2D FID-CSI) in vivo using HP [1-¹³C]pyruvate (PA). Then, multiple ROIs in mice with endogenous PDAC were selected based on anatomical ¹H imaging. From those voxels, high resolution spectra using the MV-PRESS sequence were acquired to evaluate differences in pyruvate-to-lactate conversion. Finally, the sequence was used to determine the extracellular pH of tumor lesions and kidneys in the same animal model.

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Marc Azagra¹, Jose Yeste Lozano¹, Maria Alejandra Ortega ¹, Alejandro Ernesto Portela¹, Gergö Matajsz¹, Alba Herrero Gómez¹, Kim Yaewon², Renuka Sriram², John Kurhanewicz², Daniel Vigneron², and Irene Marco Rius^1
1MIPMED, IBEC, Barcelona, Spain, ²UCSF, San Francisco, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), New Devices, dissolution DNP, MRSI, microfluidics, multisample measurement

High throughput dissolution Dynamic Nuclear Polarization (dDNP) magnetic resonance spectroscopic imaging (MRSI) was achieved by developing a multiwell microfluidic platform. This platform allows for multiple experiments to be performed with a single injection of a dDNP substrate, enabling faster and more reproducible data gathering, reducing experimental costs and time by a factor of 8. Here, we present a proof of concept of the methodology with an oxidation reaction combining [1-13C]pyruvic acid with hydrogen peroxide, testing 2 different conditions with 3 replicates each.

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Thomas Theis¹, Austin Browning¹, Keilian MacCulloch¹, Patrick TomHon², Carlos Dedesma², Boyd M. Goodson³, Matthew Rosen⁴, Eduard Chekmenev⁵, David Orestes Guarin-Bedoya⁴, and Yi-Fen Yen^4
1Chemistry, North Carolina State University, Raleigh, NC, United States, ²Vizma Life Sciences, Raleigh, NC, United States, ³Chemistry, Southern Illinois University, Carbondale, IL, United States, ⁴A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ⁵Chemistry, Wayne State University, Detroit, MI, United States

Keywords: Hybrid & Novel Systems Technology, Hyperpolarized MR (Non-Gas)

We present the first in vivo hyperpolarized MR using Signal Amplification By Reversible Exchange.

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Obaid Mohiuddin¹, Henri de Maissin^1,2, Marvin Herzog^1,2, Andrey Pravdivtsev³, Arne Brahms⁴, Eduard Y. Chekmenev^5,6, Rainer Herges⁴, Jan-Bernd Hövener³, Maxim Zaitsev¹, Dominik von Elverfeldt¹, and Andreas Benjamin Schmidt^1,2,5
1Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Frieburg, Freiburg, Germany, ²German Cancer Research Center (DKFZ), Heidelberg, Germany, ³Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein and Kiel University, Kiel, Germany, ⁴Otto Diels Institute for Organic Chemistry, Kiel University, Kiel, Germany, ⁵Chemistry, Wayne State Univeristy, Detroit, MI, United States, ⁶Russian Academy of Sciences (RAS), Moscow, Russian Federation

Keywords: High-Field MRI, Hyperpolarized MR (Non-Gas), Parahydrogen

Parahydrogen is a cost-efficient source of spin order for high-throughput production of hyperpolarized contrast agents. The parahydrogen approach SAMBADENA has shown great potential for biomedical applications: agents are polarized in situ in the MRI system at low cost with little additional hardware, repeatedly every 15s, and administration in vivo has been demonstrated. Here we present a new setup and high ¹³C polarization of 28% or 19% for ethyl-[1-¹³C]-acetate-d₆ and ethyl-[1-¹³C]-pyruvate-d₆, respectively, at concentrations of up to 80mM. We envision SAMBADENA to become a versatile method for the widespread application of hyperpolarized MRI and high throughput metabolic ¹³C MRI studies.

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Joseph W Plummer^1,2, Abdullah S Bdaiwi^1,2, Stephanie A Soderlund¹, Matthew M Willmering¹, Jason C Woods^1,3,4,5, Zackary I Cleveland^1,2,4,5, and Laura L Walkup^1,2,4,5
1Center for Pulmonary Imaging Research, Department of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ²Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States, ³Department of Physics, University of Cincinnati, Cincinnati, OH, United States, ⁴Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States, ⁵Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

Keywords: Hyperpolarized MR (Gas), Image Reconstruction

Hyperpolarized ¹²⁹Xe MRI is a powerful pulmonary imaging modality to assess regional ventilation, gas exchange, and lung microstructure. However, non-equilibrium magnetization decay and relatively long breath-hold durations remain major limitations to routine clinical dissemination. While non-Cartesian sampling methods can improve sampling efficiency, these methods are yet to be combined with non-linear reconstruction methods like compressed sensing to further increase speed and reduce image noise. Here, we implement compressed-sense reconstructions across a range of non-Cartesian ¹²⁹Xe MRI techniques and show that SNR and image quality can all be improved while reducing scan time.

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Anna Costelle¹, Junlan Lu¹, Aryil Bechtel², Elianna Bier², Sakib Kabir³, Joseph Mammarrappallil³, Haoran Dai¹, David Mummy³, and Bastiaan Driehuys^1,2,3
1Medical Physics, Duke University, Durham, NC, United States, ²Biomedical Engineering, Duke University, Durham, NC, United States, ³Radiology, Duke University, Durham, NC, United States

Keywords: Hyperpolarized MR (Gas), Spectroscopy

Hyperpolarized ¹²⁹Xe gas exchange MR spectra exhibit cardiogenic oscillations that have been found to distinguish between groups of cardiopulmonary diseases. Specifically, oscillations in the amplitude of the ¹²⁹Xe red blood cell (RBC) resonance can differentiate pre-capillary and post-capillary pulmonary hypertension. Before diagnostic relevance can be established, these oscillations must be robustly quantified and definitive reference values must be determined. Here, we compare oscillation quantification using a constrained peak-finding algorithm against results from conventional sine fitting. We then employ a well-curated healthy cohort to establish reference values for cardiogenic oscillations in ¹²⁹Xe RBC spectral parameters, using both methods.

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Faraz Amzajerdian¹, Hooman Hamedani¹, Ryan Baron¹, Mostafa Ismail¹, Luis Loza¹, Kai Ruppert¹, Stephen Kadlecek¹, and Rahim Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

Keywords: Hyperpolarized MR (Gas), Lung

While hyperpolarized ¹²⁹Xe (HXe) MRI is capable of quantifying gas exchange, these measurements are heavily dependent on both cardiac and pulmonary activity. Since traditional HXe approaches are performed during extended breath-holds at fixed lung inflation levels, the measured gas exchange can differ greatly based on the chosen inflation position, and may thus not be representative of steady-state behavior. To explore the sensitivity of HXe to cardiac pulsations and the different phases of respiration, we acquired spectra continuously over approximately 40 breaths of low-dose HXe before retrospectively gating the signals based on both cardiac and respiratory cycles.