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Yaewon Kim¹, Hsin-Yu Chen¹, Tanner Nickles¹, Jeremy Gordon¹, Peder Larson¹, Xiaoxi Liu¹, Louise Magat¹, Philip Lee¹, Daniel Gebrezgiabhier¹, Cornelius von Morze², Dan Vigneron^1,3, and Michael Ohliger^1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, ²Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States, ³Department of Neurological Surgery, University of California, San Francisco, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Perfusion

[¹³C,¹⁵N₂]urea and [1-¹³C]pyruvate were polarized together using dynamic nuclear polarization and simultaneously injected into healthy volunteers for simultaneous imaging of metabolism and perfusion in the abdomen. Whole-abdomen images were successfully obtained and the distribution of urea was compared to pyruvate and its metabolites. While the relative intensity in various organs were similar between urea and pyruvate, the temporal courses were different. This represents the first use of co-polarized pyruvate and urea in the human abdomen, and will be a powerful potential tool for simultaneous imaging of perfusion and metabolism in tumors and metabolic diseases.

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Jasmine Hu¹, Sana Vaziri¹, Nikolaj Bøgh², Yaewon Kim¹, Adam Autry¹, Robert Bok¹, Yan Li¹, Christoffer Laustsen², Peder Larson¹, Duan Xu¹, Daniel Vigneron¹, and Jeremy Gordon^1
1UC San Francisco, San Francisco, CA, United States, ²MR Research Center, Clinical Medicine, Aarhus University, Aarhus, Denmark

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

Bias correction of hyperpolarized [1-¹³C]pyruvate brain MRI allows for improved quantification of cerebral perfusion. In the healthy volunteers studied, bias corrected pyruvate and ASL rCBF exhibited higher correlation than uncorrected pyruvate and ASL rCBF. We hypothesize that N4ITK bias correction can be used to remove low frequency inhomogeneities from hyperpolarized MRI before single-metabolite analyses.

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Sule Sahin^1,2, Xiaoxi Liu¹, Nicholas Dwork³, Shuyu Tang⁴, Zhen Jane Wang¹, and Peder E.Z. Larson^1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, ²UC Berkeley - UCSF Graduate Program in Bioengineering, Berkeley, CA, United States, ³Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, United States, ⁴HeartVista, Los Altos, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Modelling, Kidney, Tumor

Lactate T2 values were fit in vivo for animal and human hyperpolarized carbon-13 pyruvate MR datasets. A pharmacokinetic model was used to leverage T2 weighting of a bSSFP acquisition. For healthy rat kidneys lactate T2 values were 0.929 ± 0.111s, for TRAMP tumor 1.663 ± 0.485s, for human RCC tumor 1.119 ± 0.168s and for human RCC normal-appearing region 1.089 ± 0.375s. Lactate T2 maps showed heterogeneity across the kidney of RCC patients but median T2 values were consistent across patients. This work demonstrates a method of using bSSFP hyperpolarized data to fit T2 values. 

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Jack J. Miller^1,2, Justin Y C Lau³, Andrew Lewis⁴, and Christoffer Laustsen^1
1The MR Research Centre, Aarhus University, Aarhus, Denmark, ²OCMR, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom, ³GE Healthcare, Schenectady, NY, United States, ⁴OCMR, University of Oxford, Oxford, United Kingdom

Keywords: Hyperpolarized MR (Non-Gas), Cardiovascular

Fractional-order derivatives represent the smooth analytic continuation of differentiation by a non-integer order. Their use for total-variation spatial regularisation has been proposed as they effectively smoothly interpolate data from the entirety of the image domain, and are reported to avoid ``blocky'' artefacts and better capture edges. Here, we show that their use permits the rapid and parsimonious optimisation of a piecewise metabolic model in the human heart, able to reconstruct terms representing perfusion delay and apparent metabolic rate constants of interconversion. 

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Ernesto Diaz¹, Renuka Sriram¹, Jeremey W. Gordon¹, Avantika Sinha¹, Xiaoxi Liu¹, Jenna Bernard¹, Daniel B. Vigneron¹, Zhen Jane Wang¹, Duan Xu¹, and Peder E.Z. Larson^1
1Radiology & Biomedical Images, University of California,San Francisco, San Francisco, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Contrast Mechanisms, Data,DICOM

Hyperpolarized (HP) ¹³C MRI has shown promise as a valuable modality for in vivo measurements of metabolism, and is currently in human trials at over 15 human research sites worldwide. It is important to adopt standardized data storage practices as it will allow sites to meaningfully compare data. We propose using specific Attributes in DICOM format, including “Contrast Agents”, and provide a Python based implementation to add these values for individual studies. Moreover, we propose best practices for HP ¹³C MRI data storage that will support future multi-site trials and research studies and technical developments of this imaging technique.

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William Dominguez-Viqueira¹, Veronica C Estrella², Epifanio Ruiz¹, Gary V Martinez³, and Jung W Choi^4
1Small Animal Imaging Lab, Moffitt Cancer Center, Tampa, FL, United States, ²Moffitt Cancer Center, Tampa, FL, United States, ³MD Anderson Cancer Center, Houston, TX, United States, ⁴Radiology Department, Moffitt Cancer Center, Tampa, FL, United States

Keywords: Hyperpolarized MR (Non-Gas), Cancer

Elevated concentrations of choline and phosphocholine are known to be a metabolic hallmark for tumor hypoxia in prostate cancer. An inhibition of hyperpolarized ¹⁵N choline to phosphocholine conversion is shown in this work in hypoxic PC-3 cells in-vitro as seen by other methods in the literature. In-vivo tumor volumes and hyperpolarized ¹⁵N phosphocholine to choline ratios were measured in twelve NSG mice with subcutaneous flank xenograft PC-3 tumors, showing a moderate correlation. The findings in this work support the hypothesis that hyperpolarized ¹⁵N-Choline may be useful as a marker of malignancy.

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Jun Chen¹, Tamara Kaur Singh², Sarah Al Nemri¹, Kelvin L Billingsley ³, and Jae Mo Park^1,4
1Advanced Imaging Research Center, UT Southwestern Medical Center at Dallas, Dallas, TX, United States, ²Chemistry, California State University, Fullerton, Fullerton, CA, United States, ³Chemistry and Biochemistry, Loyola University Chicago, Chicago, IL, United States, ⁴Department of Radiology, UT Southwestern Medical Center at Dallas, Dallas, TX, United States

Keywords: Hyperpolarized MR (Non-Gas), Metabolism

Hyperpolarized [1-13C]acetyl-L-carnitine was developed as a probe to investigate cardiac TCA cycle activity in vivo. [5-13C]Glutamate, which is produced via TCA cycle intermediate a-ketoglutarate, was successfully observed in rat heart under both fasting and fed conditions. Importantly, although pyruvate dehydrogenase activity is decreased in the fasted state, [5-13C]glutamate remained observable at appreciable levels, suggesting that [1-13C]acetyl-L-carnitine provides complementary information relative to standard assessments of pyruvate oxidation with hyperpolarized [1-13C]pyruvate. In turn, this novel probe may facilitate comprehensive metabolic analyses of acetyl-CoA uptake by the TCA cycle for various cardiac applications.

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Keilian Macculloch¹, Austin Browning¹, Patrick TomHon¹, Soren Lehmkuhl¹, Eduard Y Checkmenev^2,3,4, and Thomas Theis^1,5
1Chemistry, North Carolina State University, Raleigh, NC, United States, ²Wayne State University, Detroit, MI, United States, ³Karmanos Cancer Institute, Detroit, MI, United States, ⁴Russian Academy of Science, Moscow, Russian Federation, ⁵University of North Carolina, Chapel Hill, NC, United States

Keywords: Hyperpolarized MR (Non-Gas), Cancer

Signal Amplification By Reversible Exchange in Shields Enable Alignment Transfer to Heteronuclei (SABRE-SHEATH) was employed to boost ¹⁵N magnetic resonance sensitivity on common anti-cancer agents. The SABRE-SHEATH hyperpolarization dynamics of letrozole and anastrozole were independently optimized with respect to solution temperature and polarization transfer field. These studies enabled single scan ¹⁵N detection of the drugs at natural isotopic abundance working with mM concentrations for over 30 minutes, paving the way for more sensitive drug development.

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Keshav Datta¹, Shie-Chau Liu¹, Usman Rehman², James Graham³, Ralph Hurd¹, Daniel Spielman¹, and Thomas Jue^2
1Radiology, Stanford University, Stanford, CA, United States, ²Biochemistry and Molecular Medicine, University of California, Davis, CA, United States, ³Nutrition, University of California, Davis, CA, United States

Keywords: Hyperpolarized MR (Non-Gas), Alzheimer's Disease, Neurodegenerative Metabolism Diabetes MRI MRS

Epidemiology studies have detected type 2 diabetes (T2D) increasing the risk of Alzheimer’s disease (AD). How insulin insensitivity in T2D influences AD onset/progression poses a puzzling question. In this study using dynamic nuclear polarization (DNP) magnetic resonance (MR) experiments, we interrogated the metabolic alteration by following the conversion of [1-¹³C]Pyr in the brain of control (CRL), T2D with no AD (T2D-AD -/-), and T2D with AD (T2D-AD +/-) rats. Pyruvate dehydrogenase (PDH) activity decreases in T2D and decreases further in T2D with AD.
 

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David O. Guarin Bedoya^1,2, Sameer M. Joshi³, Anna Samoilenko³, Mohammad S. H. Kabir³, Atsushi M. Takahashi⁴, Jan Henrik Ardenkjaer-Larsen^2,5, Eduard Y. Chekmenev^3,6, and Yi-Fen Yen^1
1Radiology Department, Athinoula A. Martinos Center for Biomedical Imaging, MGH, Charlestown, MA, United States, ²Polarize ApS, Frederiksberg, Denmark, ³Department of Chemistry, Wayne State University, Detroit, MI, United States, ⁴Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States, ⁵Department of Health Technology, Technical University of Denmark, Lyngby, Denmark, ⁶Russian Academy of Sciences, Moscow, Russian Federation

Keywords: Hyperpolarized MR (Non-Gas), Contrast Agent, Contrast Mechanism

In this work, we studied the dynamic nuclear polarization (DNP) process of [¹⁵N₃]metronidazole (MNZ), an FDA-approved antibiotic that achieved good polarization (~6%) with very short polarization build-up time constants (~12min). We used Electron Paramagnetic Resonance (EPR) spectroscopy to show that a sample of [¹⁵N₃]MNZ + trityl AH111501 had narrower EPR linewidth and larger magnitude than AH111501 alone, indicating an efficient polarization transfer from the radical electrons to ¹⁵N and supporting our observations of fast DNP buildup. We also demonstrated that an addition of gadolinium-based compound to the [¹⁵N₃]MNZ +AH111501 sample broadened the EPR spectrum and prolonged DNP buildup as observed.

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Mary McLean¹, Ashley Grimmer¹, Elizabeth Latimer¹, Alixander Khan¹, Pascal Wodtke¹, Joshua Kaggie¹, James Grist², Fulvio Zaccagna¹, Martin Graves¹, and Ferdia Gallagher^1
1Radiology, University of Cambridge, Cambridge, United Kingdom, ²Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom

Keywords: Hyperpolarized MR (Non-Gas), Brain

Human brain metabolite SNR in studies with hyperpolarized [1-¹³C]pyruvate was found to best correlate with percentage polarization in the liquid state and with the polarization adjusted for pyruvate concentration and the delay between dissolution and injection (‘injectable signal’). It did not depend on the volume of pyruvate injected, suggesting that the current dose (which is adjusted by body weight) is adequate. It may be worth further exploring whether the SNR of bicarbonate could be enhanced by a longer delay between injection and the start of acquisition. Liquid and solid-state polarizations did not correlate, highlighting the importance of liquid state measurement.

Henning Schroeder¹, Theresa Hune¹, Salvatore Mamone¹, Anil Jagtap¹, Sonja Sternkopf¹, Gabriele Stevanato¹, Sergey Korchak¹, Claudia Fokken², Christoph Müller^3,4, Dorothea Becker², Andreas Schmidt^3,4,5, and Stefan Glöggler^1
1NMR Signal Enhancement, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany, ²Department of NMR-based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany, ³Division of Medical Physics, Department of Radiology, Medical Center, University of Freiburg, Freiburg, Germany, ⁴German Cancer Consortium (DKTK), partner site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁵Intergrative Biosciences (Ibio), Department of Chemistry, Karmanos Cancer Institute (KCI), Wayne State University, Detroit, MI, United States

Keywords: Hyperpolarized MR (Non-Gas), Cancer

Using a Parahydrogen-induced polarization (PHIP) based approach, we enhanced the signal of pyruvate, one of the key metabolites for energy production in the body. By injecting this metabolite into a mouse carrying a human melanoma tumor, we could perform real time spectroscopy and visualization of the tumors metabolism using a NMR machine. This offers a fast and powerful tool for metabolic imaging without using radio tracers. 

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Tyler Blazey¹ and Cornelius von Morze^1
1Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United States

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

HP ¹³C MR imaging in humans has largely been restricted to GE scanners. To facilitate a human HP ¹³C imaging program at our institution and expand the translational potential of HP ¹³C MRI in general, we have developed a 3D symmetric EPI sequence for imaging HP ¹³C agents on Siemens scanners. Sequence development was performed using Pulseq, a flexible open-source tool for prototyping platform-agnostic pulse sequences. Metabolites were selectively excited using spectral-spatial RF pulses. Optional acceleration was achieved using partial Fourier undersampling in the slice direction. The sequence was tested using a thermally polarized phantom and a HP [1-¹³C]pyruvate phantom.

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Collin J. Harlan^1,2, Yunyun Chen³, Gary V. Martinez², Vlad C. Sandulache⁴, Stephen Y. Lai^3,5,6, and James A. Bankson^1,2
1The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, United States, ²Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ³Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁴Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, United States, ⁵Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ⁶Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

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

Metabolic imaging of hyperpolarized pyruvate can provide new insight into tumor progression and response to therapy. Pharmacokinetic modeling can be used to determine k_PL, the apparent rate constant for conversion of hyperpolarized pyruvate into lactate. In this work, we sought to characterize the effect of hyperpolarized pyruvate concentration on intracellular k_PL in ATC cell suspensions using a two-compartment pharmacokinetic model for k_PL quantification. Improved understanding of the effects of concentration on intracellular chemical conversion rates could lead to more accurate quantification of in vivo and clinical hyperpolarized MRI imaging biomarkers of metabolism.  

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Francesca Reineri¹, Silvio Aime¹, Carla Carrera^1,2, Eleonora Cavallari¹, Erika Cerutti¹, and Ginevra Di Matteo^1
1Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy, ²National Research Council, Torino, Italy

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

Hyperpolarized [1-¹³C]pyruvate can be obtained by means of ParaHydrogen Induced Polarization-Side Arm Hydrogenation, a hyperpolarization technique that is significantly more cost effective and faster than the gold-standard method d-DNP. The hyperpolarization level that we reported previously, for the fully biocompatible aqueous solution of this HP metabolite, was sufficient to carry out metabolic studies, but still low. In this work we show that the use of a lower catalyst concentration, together with a co-catalyst, and an improved magnetic field cycle profile for spin order transfer can double the HP level on this metabolite.

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Kolja Them¹, Jule Kuhn¹, and Jan-Bernd Hövener^1
1Radiology and Neuroradiology, MOIN CC and SBMI, UKSH, Kiel, Germany

Keywords: Hybrid & Novel Systems Technology, Hyperpolarized MR (Non-Gas), Hyperpolarized Lactate, Parahydrogen, Proton Exchange

Hyperpolarization of biological molecules^1,2,3 is a promising approach for metabolic MR imaging. Hyperpolarization methods based on parahydrogen and proton exchange^4,5 promise almost universal polarization of many molecules, but current polarization yields are relatively low. Here, we present a new variant of Parahydrogen-Induced Polarization relayed via proton exchange (PHIP-X), which we demonstrate using the important biomolecule lactate. Polarization transfer between labile and covalent bound protons at different fields, combined with an RF pulse sequence, enables significantly enhanced ¹³C polarization of lactate. We believe that this approach may be used as a general strategy for the polarization of various biomolecules.

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Enya E. Hachem¹, Sung-Han Li², Mai Huynh², Junjie Ma³, and Jae Mo Park^1,2,4
1Electrical Engineering, UT Dallas, Richardson, TX, United States, ²Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ³GE Healthcare, New York, NY, United States, ⁴Department of Radiology, UT Southwestern Medical Center, Dallas, TX, United States

Keywords: Image Reconstruction, Phantoms

In this study, we introduced the parallel imaging technique GRAPPA to the flyback EPI with controlled aliasing in order to accelerate the acquisition time while simultaneously reducing artifacts. The GRAPPA-accelerated flyback EPI was characterized using MR phantoms with varying SNR and acceleration factor (R) and the feasibility of simultaneous bicarbonate and lactate imaging with the proposed scheme was also demonstrated. The proposed acquisition method has potential advantages for in vivo studies with hyperpolarized substrates by shortening acquisition time, improving spatial resolution, and increasing effective flip angles.  

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Minjie Zhu¹, Dirk Mayer¹, Aditya Jhajharia¹, and Joshua Rogers^1
1University of Maryland, Baltimore, Baltimore, MD, United States

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

Improve the accuracy of under-sampled dynamic images for lower intensity metabolites with low rank and local sparsity reconstruction

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Henri de Maissin^1,2, Obaid Mohiuddin¹, Marvin Herzog¹, Eduard Y. Chekmenev^3,4, Sergey Korchak^5,6, Stefan Glöggler^5,6, Jan-Bernd Hövener⁷, Maxim Zaitsev¹, Dominik v. Elverfeldt¹, and Andreas B. Schmidt^1,3,8
1Division of Medical Physics, University Medical Center Freiburg, Freiburg im Breisgau, Germany, ²German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany, ³Integrative biosciences (Ibio), department of Chemistry, Wayne state university, Detroit, MI, United States, ⁴Russian Academy of Sciences (RAS), Moscow, Russian Federation, ⁵NMR Signal Enhancement Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany, ⁶Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany, ⁷Section Biomedical Imaging, Molecular Imaging North Competence Center, Kiel, Germany, ⁸German Cancer Consortium (DKTK), Heidelberg, Germany

Keywords: High-Field MRI, Hyperpolarized MR (Non-Gas), parahydrogen cancer spectroscopy

Parahydrogen-induced Polarization (PHIP) by Synthesis Amid the Magnet Bore Allows Dramatically Enhanced Nuclear Alignment (SAMBADENA) of agents in situ within the MRI magnet and requires very little hardware in addition to the MRI system. However, side-arm hydrogenation (PHIP-SAH), fast side-arm cleavage and purification have not been attempted yet.
Here, we present a SAMBADENA setup made from commercially-available components for future preclinical applications. Using this setup, we demonstrate high ¹³C polarizations of 17% for 25mM ethyl-[1-¹³C]-acetate. In addition, for ethyl-pyruvate, fast side-arm cleavage and removal of 96% of the organic solvent within 10s to obtain pyruvate in neat water is demonstrated.