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Gino G. Rincon^1,2, Philip S. Boyd¹, Vanessa L. Franke^1,2, Cornelius J. Bauer^1,2, Mark E. Ladd^1,2,3, Peter Bachert^1,2, and Andreas Korzowski^1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, ³Faculty of Medicine, University of Heidelberg, Heidelberg, Germany

Keywords: Non-Proton, Spectroscopy, Phosphorous MRSI

Compressed sensing (CS) techniques suggest the feasibility of reducing the measurement duration of high‑resolution ³¹P‑MRSI at 7T to a clinically reasonable time (20 minutes) while preserving data quality. The proposed Compressed Adaptive SenSing Algorithm with Variable k‑space Averaging (CASSAVA) reconstructs ³¹P‑MRSI data with an undersampling factor of $$$R=3.8$$$ while simultaneously maintaining spectral peak accuracy and a high spatial resolution. This was demonstrated in the conducted simulation, retrospective, and prospective studies by evaluating the reconstructed spectra and intracellular pH maps of healthy and tumor tissues as a benchmark test. As a result, clinical research on larger patient cohorts becomes feasible.

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Qingping Chen^1,2, Wieland A. Worthoff¹, and N. Jon Shah^1,3,4,5
1Institute of Neuroscience and Medicine 4, Forschungszentrum Jülich GmbH, Jülich, Germany, ²Faculty of Medicine, RWTH Aachen University, Aachen, Germany, ³Institute of Neuroscience and Medicine 11, Forschungszentrum Jülich GmbH, Jülich, Germany, ⁴JARA–BRAIN–Translational Medicine, Aachen, Germany, ⁵Department of Neurology, RWTH Aachen University, Aachen, Germany

Keywords: Non-Proton, Pulse Sequence Design, Multiple-quantum filtering; Sodium MRI

Enhanced simultaneous single-quantum and triple-quantum-filtered imaging of ²³Na (SISTINA) enables images to be weighted towards restricted sodium, a promising biomarker for clinical practice, but suffers from long acquisition times and low image quality. However, this can be alleviated by applying compressed sensing (CS). This work establishes a novel enhanced SISTINA sequence using FLORET sampling at 7T and demonstrates that CS can accelerate SISTINA acquisitions with less noise and better structure preservation than non-uniform fast Fourier transform while maintaining proper weightings towards total, non-restricted, and restricted sodium. The reduced acquisition time facilitates the clinical transition of enhanced SISTINA.

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Simon Reichert¹, Victor Schepkin², Dennis Kleimaier¹, and Lothar Schad^1
1Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, ²National High Magnetic Field Laboratory, Tallahassee, FL, United States

Keywords: Non-Proton, Non-Proton, Sodium, X-Nuclei, Triple-Quantum, TQ, new contrast mechanism

This study demonstrates a method to estimate the biological relevant sodium TQ signal with a single-pulse sequence. Comparison of this method with theory and experiments using TQTPPI sequence showed a close agreement of the TQ signal. Therefore, the TQ signal can be  estimated on the time scale of sodium SQ signal acquisition using the proposed sequence.

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Natalia Ziolkowska^1,2, Katerina Sulkova¹, Lucie Kracikova³, Martin Vit¹, Richard Laga³, and Daniel Jirak^1
1Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²First Faculty of Medicine, Institute of Biophysics and Informatics, Charles University, Prague, Czech Republic, ³Department of Polymer and Colloid Immunotherapeutics, Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic

Keywords: Non-Proton, Tumor

Presented novel phosphorus- and fluorine-containing polymer possess high sensitivity at ³¹P/¹⁹F-MR and a large chemical shift from biological phosphorus signal (∆δ=60 ppm) due to phosphorothioate P=S group in its structure. The probe represents a conceptually new approach for phosphorus MR, as it undergoes oxidation-induced structural changes in the presence of ROS, represented in greater amounts in cancer tissue. The additional ¹⁹F-MR signal serve as an on-site information on the polymer distribution in the organism.

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Alex Ensworth^1,2, Cariad-Arianna Knight¹, Piotr Kozlowski^1,2,3,4, Cornelia Laule^1,2,3,5, Alex L. MacKay^1,3,4, and Carl A. Michal^1
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada, ³Radiology, University of British Columbia, Vancouver, BC, Canada, ⁴UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, ⁵Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Keywords: Non-Proton, White Matter, myelin, phosphorus, hydrogen, spinal cord tissue, cross polarization, NMR, microstructure

Tools to better characterize myelin health are urgently needed. We demonstrate the use of the solid-state NMR techniques cross polarization (CP) and WIdeline Separation (WISE) to directly probe the phosphorous (³¹P) of phospholipid myelin bilayers and characterize protons (¹H) involved in CP. This work demonstrates the feasibility of unconventional CP from ³¹P→¹H in porcine spinal cord and investigates the contributing ¹H. The results of this work provide crucial insight into the characteristics exploitable by CP in myelin and reinforce the potential of a two-step transfer of semi-solid ³¹P signals into aqueous ¹H, providing a more direct and myelin-specific MRI signal.

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Claudius Sebastian Mathy^1,2, Armin Michael Nagel^1,3, Matthias Türk^4,5, Michael Uder¹, Rafael Heiß¹, Marc-André Weber⁶, and Lena Vanessa Gast^1
1Institute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ²Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University, New Haven, CT, United States, ³Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁵Centre for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁶Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, University Medical Center Rostock, Rostock, Germany

Keywords: Non-Proton, Muscle, Potassium

Combined ³⁹K/²³Na MRI at 7T has become feasible recently after technical advances of ³⁹K MRI. Here we assessed ion homeostasis alterations, especially tissue potassium and sodium concentrations (TPC/TSC) in a small pilot cohort of patients of hypokalemic periodic paralysis (HypoPP). Depending on the severity of fatty involvement of muscles, TSC was elevated in slightly to moderately involved muscles and TPC showed a tendency to decrease in an inverse correlated fashion. Almost entirely fatty infiltrated muscle showed a decrease of TSC and TPC. Therefore, combined ³⁹K/²³Na MRI could help to examine the pathophysiological processes in HypoPP and other muscular channelopathies.

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Lieke van den Wildenberg¹, Bobby Runderkamp², Leonard Seelen¹, Hanneke van Laarhoven^3,4, Mark Gosselink¹, Wybe van der Kemp¹, Nadia Haj Mohammad⁵, Dennis Klomp¹, and Jeanine Prompers^1
1Center for Image Sciences, University Medical Center Utrecht, Utrecht, Netherlands, ²Department of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands, ³Department of Medical Oncology, Amsterdam UMC, Amsterdam, Netherlands, ⁴Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, Netherlands, ⁵Department of Medical Oncology, Utrecht Medical Center Utrecht, Utrecht, Netherlands

Keywords: Non-Proton, Cancer

Methods for early treatment response evaluation to systemic therapy of liver metastases are lacking. Tumor tissue is characterized by an increased PME/PDE ratio. However, with commonly used ³¹P surface coils for liver ³¹P MRS, the liver is not fully covered. Using an integrated ³¹P whole-body transmit coil in combination with a 16-channel body receive array at 7T, we were able to spatially map ³¹P metabolite levels throughout the whole liver in a patient with liver metastases. We found highly elevated levels of both PE/ATP and PC/ATP in liver metastases in comparison with healthy liver tissue.

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Dayna L. Richter^1,2, Samuel Holder^1,2, and Samuel Colles Grant^1,2
1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, ²Chemical & Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, United States

Keywords: Non-Proton, Neuro, Migraine, Extreme field

Migraine disproportionately affects women in part due to menstrual migraine, linked to 17β-estradiol deprivation. This study implements 23Na MRI at 21.1 T in female Sprague-Dawley rats to evaluate the impact of estradiol deprivation on widespread sodium increases previously reported in the male model. Ovariectomy was implemented, and animals dosed with controlled estradiol to mimic the natural estrus cycle. It was found that females at physiological estradiol concentrations are resilient to sodium increases in the brainstem and CSF, while estradiol deprivation removes this resiliency. This interaction may play a role in menstrual migraine, and the clinical migraine gap between sexes.

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Christian Licht¹, Stanislas Rapacchi², and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²CRMBM, Aix-Marseille Université, Marseille, France

Keywords: Non-Proton, Multi-Contrast, Sodium

Sodium (²³Na) MRI has received increased attention as a potential biomarker for disease states thanks to the advent of ultra-high field MRI. One interesting asset from ²³Na MRI is the distinction between single and triple quantum signal to further characterize tissues. However, 3D ²³Na multi-quantum coherences (MQC) imaging requires multiple radiofrequency phase-cycling, which is inherently time-consuming and therefore difficult to include in protocols. In this work, we propose to accelerate ²³Na MQC MRI by leveraging multi-dimensional under-sampling coupled with a dedicated Low-Rank matrix completion image reconstruction.

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Amelie Tourais¹, Cameron Hery¹, Martine Guillermier¹, Julien Valette¹, and Celine Baligand^1
1Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France

Keywords: Non-Proton, Metabolism

CMRO₂ is an important metric for the evaluation of neurovascular and neurometabolic coupling. However, the degree of coupling between brain activity and CMRO₂ remains a matter of debate. In this work, we used ¹⁷O-ZTE-MRI at 11.7 T to measure CMRO₂ during neuronal activation in the rat primary somatosensory cortex. To improve measurements sensitivity, we acquired data over two consecutive cycles of ¹⁷O₂ inhalation-washout. We show that a significant functional increase in CMRO₂ (+7±5%, p=0.016), and in the rates of metabolized water gain and loss K_G (+19±11%, p=0.18) and K_L (10±6%, p=0.014) can be detected with good spatial resolution after summation.

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Jingxuan Zhu¹, Christian Beaulieu¹, Karim Damji¹, and Rob Stobbe^1
1Biomedical Engineering, University of Alberta, Edmonton, AB, Canada

Keywords: Non-Proton, Body

Non-proton (²³Na) MRI studies have measured greater body tissue (skin) sodium concentration in disorders such as hypertension, diabetes, and chronic kidney disease, but literature values of ~15 mM are well below the 77 mM from atomic absorption spectroscopy. Previous studies have used gradient-echo imaging with long TE=2 ms, knee volume-coils, and large 3×3×30=270 mm³ voxels. Here, short TE=0.1 ms twisted projection imaging is used, and signal loss is progressively lowered with surface coil imaging, reshaped 0.4x4x4 = 6.4 mm³ voxels, and lower 60^o flip-angle excitation, ultimately yielding 42 mM calf skin measurement in 10 young adults. 

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Wieland A. Worthoff¹, Qingping Chen^1,2, and N. Jon Shah^1,3,4,5
1Institute of Neuroscience and Medicine - 4, Forschungszentrum Jülich GmbH, Jülich, Germany, ²Faculty of Medicine, RWTH Aachen University, Jülich, Germany, ³Institute of Neuroscience and Medicine - 11, Forschungszentrum Jülich GmbH, Jülich, Germany, ⁴Faculty of Medicine, RWTH Aachen University, Aachen, Germany, ⁵JARA-BRAIN - Translational Medicine, Jülich-Aachen Research Alliance, Aachen, Germany

Keywords: Non-Proton, Relaxometry, Sodium, Multiple Qunatum Filtering

 Sodium relaxometry has great potential value for research and clinical practice. Enhanced Simultaneously Acquired Single and Triple Quantum Filtered Imaging of  Sodium (eSISTINA) can yield information on both fast and slow transversal relaxation times. The eSISTINA sequence is optimised by adding an early echo in the multiple-quantum-filtered readout train using FLORET k-space trajectories. The optimised sequence is compared and verified against a conventional, Cartesian multi-echo gradient echo based enhanced eSISTINA sequence on a group of four healthy volunteers. The experimental results show that the optimised sequence has better in vivo relaxometry performance than the conventional sequence.

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Georgios Batsios¹, Celine Taglang¹, Meryssa Tran¹, Anne Marie Gillespie¹, and Pavithra Viswanath^1
1University of California, San Francisco, San Francisco, CA, United States

Keywords: Non-Proton, Metabolism, preclinical, animals, brain, spectroscopy, deuterium

Diffuse midline gliomas (DMGs) are lethal pediatric brain tumors. DMG patients are typically treated with radiation in combination with an experimental agent in clinical trials. ONC206 is a novel drug with promising efficacy in preclinical models. Successful clinical translation and deployment of ONC206 requires the identification of companion biomarkers of treatment response. Therefore, the goal of this study was to identify magnetic resonance spectroscopy (MRS)-detectable biomarkers of response to ONC206 in preclinical DMG models. Our studies identify a combination of ¹H- and ²H-MRS-detectable biomarkers that serve as imaging biomarkers of early response to ONC206 in mice bearing intracranial DMG xenografts.

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Anna K. Scheipers^1,2, Armin M. Nagel^1,3, Laurent Ruck³, Lena V. Gast³, Mark E. Ladd^1,2,4, and Tanja Platt^1
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Faculty of Physics and Astronomy, Heidelberg University, Heidelberg, Germany, ³University Hospital Erlangen, Institute of Radiology, Friedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU), Erlangen, Germany, ⁴Faculty of Medicine, Heidelberg University, Heidelberg, Germany

Keywords: Non-Proton, High-Field MRI, Kidney, Quantitative Imaging

²³Na-MRI is a non-invasive tool for the in-vivo quantification of the tissue sodium concentration (TSC); however, it suffers from low in-vivo signals and short relaxation times. High magnetic field strengths, dedicated hardware and pulse sequences as well as various correction methods contribute to obtaining reliable TSCs. In the presented work we employ a custom-built coil and reference vial setup and perform T₁, B₁⁺ and B₁^- corrections that were validated in phantom measurements. We use a sliding window reconstruction for the quantitative ²³Na-images to investigate the changes in the TSC before, during and after a water load in two healthy volunteers.

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Simon Reichert¹, Victor Schepkin², Dennis Kleimaier¹, and Lothar Schad^1
1Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, ²National High Magnetic Field Laboratory, Tallahassee, FL, United States

Keywords: Non-Proton, Non-Proton, Sodium, X-Nuclei, Very-High B-Field

This study investigates a model of ion motion that is compatible with ²³Na T₁­ and T₂ mechanism of relaxation and even works with quasi mono-exponential T₁. We compare this model with the commonly used Debye model using agar as a tissue model system at 9.4T and 21.1T.

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Ben Prestwich¹ and Susan Francis^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom

Keywords: Non-Proton, Non-Proton, sodium MRI, T1 mapping, muscle, tissue sodium concentration

Sodium (²³Na) MRI measures of tissue are SNR limited. Here, we compare a 3D gradient recalled echo (GRE) ²³Na scans with a short TR and fully recovered TR for estimation of tissue sodium concentration (TSC) in the calf. We validate measures by collecting ²³Na T₁ measures of the calf and reference bottles. A short TR scan is shown to provide increased image SNR, resulting in higher measures of TSC, along with improved depiction of the skin. Using the short TR GRE scan, older subjects and haemodialysis patients are shown to have higher calf TSC than younger subjects.

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Ferenc E Mózes¹, William T Clarke², and Ladislav Valkovič^1,3
1Oxford Centre for Clinical MR Research (OCMR), RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom, ²Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ³Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

Keywords: Non-Proton, Heart, phosphorus

Cardiac 31P-MRS provides insight into metabolism of the failing heart. The commonly employed 3D-MRSI acquisitions are rather slow, even at 7T. Fast readout trajectories, such as concentric ring (CRT) have been recently suggested to substitute the slow Cartesian sampling (CSI), however their repeatability is yet unknown. Our preliminary data suggest comparable intra-session repeatability, but somewhat lower inter-session repeatability for mid septal voxels using 2.5 min CRT in comparison to 6.5 min CSI. Similar trends were observed for higher resolution CRT.

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Justyna Platek^1,2, Florian Kroh^1,2, Vanessa L. Franke^1,2, Philip S. Boyd¹, Nina Weckesser³, Heinz-Peter Schlemmer^3,4, Daniel Paech^3,5, Mark E. Ladd^1,2,4, Peter Bachert^1,2, and Andreas Korzowski^1
1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidleberg, Germany, ²Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, ³Division of Radiology, German Cancer Research Center (DKFZ), Heidleberg, Germany, ⁴Faculty of Medicine, University of Heidelberg, Heidelberg, Germany, ⁵Division of Neuroradiology, University Hospital Bonn, Bonn, Germany

Keywords: Non-Proton, Spectroscopy, Phosphorus, pH, cancer

In this study, we analyzed pH values obtained via high-resolution ³¹P MRSI at 7T in different subjects and different regions of the human brain, and identified a trend towards lower pH values in the frontal region compared to other brain regions. The potential regional variation should be taken into account in cases, where only small pH changes between different tissues are expected and partial volume effects might dominate.