Rohit Mahar¹, Huadong Zeng², Anthony Giacalone³, Mukundan Ragavan³, Thomas H. Mareci³, and Matthew E. Merritt^3
1Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States, ²Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility, University of Florida, Gainesville, FL, United States, ³Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States

In this study, we demonstrate the application of deuterium MRS(I) for in vivo rat brain imaging. Administration of [²H₇]glucose via the tail vein produced deuterated lactate and glx analogous to earlier reports, but here we show for the first time that HDO generated from metabolism can be imaged in the rodent brain. By using HDO evolution as a metric of glucose utilization, we introduce a biomarker of cerebral glycolysis and oxidative flux that is imaged with superior sensitivity and resolution.

Natasha N Knier^1,2 and Paula J Foster^1,2
1University of Western Ontario, London, ON, Canada, ²Robarts Research Institute, London, ON, Canada

Magnetic particle imaging (MPI) is an emerging modality that may overcome challenges associated with quantification of iron-based MRI cell tracking. The magnetic properties of an SPION tracer heavily influences the sensitivity and resolution in MPI. Synomag-D™ has been explored as a sensitive tracer for MPI. Currently, no studies exist using this tracer to track cancer cells. Here, we utilize Synomag-D with MPI to detect and quantify iron-labeled breast cancer cells in the mouse brain and compare to MRI. Employing MPI for experimental cancer cell tracking will allow for quantification of the arrest, clearance, and retention of cancer cells in vivo.

Chengchuan Wu¹, Yasmin Blunck¹, and Leigh A. Johnston^1
1Department of Biomedical Engineering, The University of Melbourne, Parkville, Australia

This work presents a mathematical framework that enables the simulation for the dynamics of the spin-3/2 ²³Na density operator. The simulator is featured with easy implementation for ²³Na in biological environment. This work demonstrates the simulator in two ²³Na pulse sequences.

Julian Mevenkamp¹, Yvonne M.H. Bruls^1,2, Robin A. de Graaf³, Joachim E. Wildberger¹, Matthijs K.C. Hesselink², Lucas Lindeboom^1,2, and Vera B. Schrauwen-Hinderling^1,2
1Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²Department of Nutrition & Movement Sciences, Maastricht University, Maastricht, Netherlands, ³Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States

NAD⁺ and NADH play important roles in metabolism and metabolic health. Therefore, a non-invasive ³¹P MRS for the quantification of those metabolites on clinical 3T scanners was developed. This sequence suppresses α-ATP resonances based on homonuclear Bilinear Rotation Decoupling (BIRD). With reduced α-ATP intensity, neighbouring NAD⁺/H resonances appear as a separate peak. Results in eight young, lean and healthy volunteers show that the sequence succeeded in considerable α-ATP suppression. However, a clear separation of NADH and NAD⁺ resonances remains challenging due to remaining α-ATP signal.

Lucas Narciso^1,2, Tracy Ssali^1,2, Linshan Liu¹, Heather Biernaski¹, John Butler¹, Laura Morrison¹, Jennifer Hadway¹, Jeffrey Corsaut¹, Justin W. Hicks¹, Michael C. Langham³, Felix W. Wehrli³, Hidehiro Iida⁴, and Keith St Lawrence^1,2
1Lawson Health Research Institute, London, ON, Canada, ²Department of Medical Biophysics, Western University, London, ON, Canada, ³University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States, ⁴University of Turku and Turku PET Centre, Turku, Finland

OxFlow is a non-invasive MRI method for measuring whole-brain oxidative metabolism. This study presents its validation in an animal model by comparing to a PET-only method, as well as its sensitivity to alterations in cerebral metabolism. Strong correlations were observed between measurements from the MRI and PET techniques, with no significant differences. Furthermore, OxFlow proved sensitive to changes in metabolism induced by an increase in anesthetics.

Byeong-Yeul Lee¹, Jeffrey M. Solomon², Marcelo Castro¹, Dong-Yun Kim³, Joseph Laux¹, Matthew G. Lackemeyer¹, Jordan K. Bohannon⁴, Anna N. Hanko⁵, Dima Hammoud^6,7, and Ji Hyun Lee^1
1Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, United States, ²Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, United States, ³Office of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, MD, United States, ⁴National Biodefense Analysis and Countermeasures Center, Frederick, MD, United States, ⁵Microbiology, Boston University School of Medicine, Boston, MA, United States, ⁶Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, United States, ⁷Center for Infectious Disease Imaging, National Institutes of Health, Bethesda, MD, United States

We performed a quantitative neuroimaging study to determine central nervous system involvement following exposure with Ebola virus (EBOV) variant Makona via the aerosolized route in a rhesus monkey model. Using MR relaxometry, we found increases in T1 and R2* values in multiple brain regions. Notably, R2* changes corresponding to the deep cerebral venous system highly correlated with viral loads in CSF. These results provide in vivo evidence of brain involvement with EBOV and emphasize the potential of advanced imaging techniques to better understand the pathophysiology of organ involvement in various infectious diseases, including the brain.

Vladimir Grouza^1,2, Zhe Wu^1,3, Marius Tuznik^1,2, Hooman Bagheri⁴, Dan Wu⁵, Alan C Peterson^2,4,6, and David Rudko^1,2,7
1McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, Montreal, QC, Canada, ²Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada, ³Techna Institute, University Health Network, Toronto, ON, Canada, ⁴Department of Human Genetics, McGill University, Montreal, QC, Canada, ⁵Russell H. Morgan Department of Radiology & Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ⁶Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada, ⁷Department of Biomedical Engineering, McGill University, Montreal, QC, Canada

We investigated a novel mouse model of CNS hypomyelination using T₂* weighted mGRE and diffusion weighted imaging. By integrating a recently developed method for MWF estimation from mGRE data (BSS-rPCA), we observed strong correlations between Mbp/Golli mRNA expression levels and MVF in select WM tracts in the brain. In addition, WM tract g-ratio values computed from BSS-rPCA MVF combined with NODDI-derived parameters were consistent with those found in the literature computed using differing methods. These results support integrating BSS-rPCA MWF estimates into quantitative microstructure evaluation workflows.

Duen-Pang Kuo^1,2, Yi-Tien Li^1,3, Chen-Yin Ou¹, Yung-Chieh Chen^1,2, and Cheng-Yu Chen^1,2
1Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ²Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, ³Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan

Thalamocortical dysrhythmia (TCD) has been implicated in the neuropsychiatric disorders in patients following mild traumatic brain injury (mTBI). We investigated the time-course diffusion tensor changes in the rodent brain up to 35 days using a controlled closed head injury model. Significant and persistent elevation of fractional anisotropy (FA) and reduced radial and mean diffusivities were found at the boundary of bilateral thalami where high shear stress was expected, suggesting that disinhibition of inhibitory circuits from the thalamic reticular nucleus (TRN) may play a role in TCD.

Aditya Bade¹, Howard Gendelman¹, and Yutong Liu^2
1Pharmacology and Exp Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States, ²Radiology, University of Nebraska Medical Center, Omaha, NE, United States

HIV theranostics that enables the in vivo imaging of antiretroviral drugs is a powerful tool for the development of antiretrovirals (ARVs) targeting HIV reservoirs, and the development of long-acting ARVs that affect drug adherence and as such reduce viral transmission, prevent new infections, and limit the emergence of viral drug resistance. We tested the possibility to develop HIV theranostics based on the intrinsic CEST contrasts of ARVs. Herein, we measured the CEST effects of first-line ARVs including 3TC (lamivudine) and FTC (emtricitabine) and developed CEST MRI methods for in vivo detection of ARVs in the central nervous system (CNS).

Yuemeng Li¹, Hee Kwon Song¹, Miguel Romanello Giroud Joaquim¹, Stephen Pickup¹, Rong Zhou¹, and Yong Fan^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States

Respiratory motion and high magnetic fields pose challenges for quantitative diffusion weighted MRI (DWI) of mouse abdomen on preclinical MRI systems. EPI-based DWI method yields inadequate suppression of motion and magnetic susceptibility artifacts. Diffusion-weighted radial spin-echo (Rad-SE-DW) produces artifact-free images but require substantially longer acquisition times.  Here, we demonstrate a new deep learning concept for accelerating acquisition of RAD-SE-DW. Fully sampled Rad-SE-DW images are used to train a convolution neural network for directly extracting apparent diffusion coefficient (ADC) maps from highly under-sampled Rad-SE-DW data. Comparisons with standard ADC extraction and acceleration methods are made to support this concept.

shuangshuang xie¹, caixin qiu¹, yajie sun¹, jinxia zhu², Robert Grimm³, and wen shen^1
1Tianjin First Central Hospital, Tianjin, China, ²MR Collaboration, Siemens Healthcare Ltd., Beijing, China, ³MR Application Development, Siemens Healthcare GmbH, Erlangen, Germany

This study investigated the feasibility of multiparametric magnetic resonance imaging (MRI) (IVIM, DKI, BOLD) to evaluate the liver regeneration process after 70% hepatectomy in rats. MRI examination and pathologic samples were performed at multiple time-points. The results showed that D, D*, FP, MD, MK, and T2* can be used to monitor the microstructural changes after surgery, and D* and MK were significantly correlated with proliferative indexes of Ki - 67 and hepatocyte size. This suggests that multiparametric MRI can aid in noninvasive radiologic monitoring of liver regeneration and intrinsic microstructure evaluation

Martina Vermathen¹, Hendrik von Tengg-Kobligk^2,3, Martin Nils Hungerbühler^2,3, Christoph Kempf^2,3, Peter Vermathen^2,3, and Nico Ruprecht^2,3
1Department of Chemistry and Biochemistry, University Bern, Bern, Switzerland, ²University Institute of Diagnostic, Interventional and Pediatric Radiology, University Bern, Bern, Switzerland, ³Department of BioMedical Research, University Bern, Bern, Switzerland

Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. However, drug resistance is a major problem. Here, a high resolution magic angle spinning (HR-MAS) NMR study is presented determining the metabolic profile of lung cancer cells (A24) and metabolic adaptations in different levels of induced cisPt-resistance as well as in their de-induced counterparts. More than 40 metabolites were identified. Metabolic adaptations were determined, which increased with higher cisPt-resistance. Importantly, de-induced cell lines demonstrated similar metabolic adaptations. Metabolites predominantly changed in cisPt resistant cells and their de-induced counterparts include glutathione or taurine.

Dounia El Hamrani^1,2, Julie Magat^1,2, Jérôme Naulin^1,2, Frédéric Perros³, Marilyne Campagnac², David Benoist^1,2, Christelle Guibert², and Bruno Quesson^1,2
1IHU LIRYC, Bordeaux, France, ²INSERM U1045, CRCTB, Bordeaux, France, ³INSERM UMR_S 999, Université Paris–Saclay, Le Kremlin Bicêtre, France

The transgenic rat line studied has a monoallelic mutation of Bmpr2 which is a model of heritable pulmonary arterial hypertension. The purpose of this study is to evaluate cardiac differences between wild type and asymptomatic mutated rats by cardiac MRI and ³¹P MRS. Transgenic rats showed a decrease in end-diastolic and end-systolic volumes of ventricles leading to a reduced stroke volume. These results indicate a significant decrease in cardiac output but without ventricular hypertrophy (constant wall thickness) and no significant variation of ejection fraction. The cardiac energy balance (phosphocreatine/ATPβ) remained unaltered in Bmpr2 rats at rest and post-injection of dobutamine.

Xueru Liu^1,2, Huilin Hong³, Zhentao Zuo^1,2,4, Hui Zhao³, Rui Tian³, Yongqing Zhang^2,3,4, and Yan Zhuo^1,2,4
1State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, BeiJing, China, ²University of Chinese Academy of Sciences, Beijing, China, ³State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China, ⁴CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Beijing, China

Social interactions, like sleep, is the basic needs for humans and animals, its neural mechanism is not fully understood. Domestic dog has similar emotional and social processing with humans, it would be a promising animal model for social interaction. In this study, 3 beagles were social deprived (SD) 4-week, and performed resting-state fMRI and diffusion MRI. The functional connectivity and diffusion metrics were compared between SD and wild type dogs. We found the functional connectivity strengthened within prefrontal cortex and weakened between prefrontal cortex with visual and auditory cortex in SD. Demyelination observed in frontal, temporal, and insula regions.

Cristiana Tisca¹, Mohamed Tachrount ¹, Frederik Lange¹, Chaoyue Wang¹, Lily Qiu¹, Javier Barallobre-Barreiro², Marika Fava², Manuel Mayr², Jason Lerch^1,3,4, Aurea Martins-Bach¹, and Karla Miller^1
1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom, ³Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, ⁴Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Recent genome-wide association studies using UK Biobank datasets have shown associations between diffusion-weighted MRI (dMRI) phenotypes and genetic loci associated with the human VCAN gene, spanning most white matter tracts. To understand the biological cause of this association, we acquired ex vivo structural and dMRI data in a Vcan mouse model and evaluated whether it displays similar changes in white matter microstructure. We show that male Vcan mice display related dMRI phenotypes to those associated with mutations in VCAN in humans. This gives us the ability to investigate the biological interpretations of human GWAS results using histology. 

Martina Vermathen¹, Tobias Emmanuel Kämpfer^1,2, and Peter Vermathen^2
1Department of Chemistry and Biochemistry, University Bern, Bern, Switzerland, ²Departments of BioMedical Research and Radiology, University Bern, Bern, Switzerland

Porphyrinic photosensitizers (PSs) like chlorin e4 (Ce4) are applied with polymer-based carriers for photodynamic therapy of cancer. However, the impact of PSs and their carriers on the metabolic state of cells in the dark-interval before light treatment are not clear. Here, HR-MAS NMR metabolomics was applied to cancer cells treated with Ce4 alone or combined with polyvinylpyrrolidone (PVP) or block-copolymer micelles (BCMs). A Ce4-concentration dependent metabolic response was observed that was clearly attenuated by BCMs and more pronounced by PVP indicating the beneficial role of the carriers. Direct interaction of Ce4 with glycero-phosphocholine was observed suggesting intracellular membrane localization.

Jabrane Karkouri¹, Stanislav Frištyk², Lucian AB Purvis³, Christopher T. Rodgers*¹, and Ladislav Valkovic*^3
1Wolfson Brain Imaging Center, University of Cambridge, Cambridge, United Kingdom, ²Department of Electromagnetic and Biomedical Engineering, University of Žilina, Zilina, Slovakia, ³Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom

Phosphorus magnetic resonance spectroscopy (31P-MRS) delivers unique information to aid our understanding of cardiac metabolism. To quantify “absolute” concentrations of phosphorus metabolites (i.e. in recognised units such as mmol / kg wet weight), sensitivity calibration and transmit field correction are required. Ultrahigh field (>7 T) magnets and the use of multichannel RF coils make this even more challenging. In this study, we investigate the feasibility of absolute concentration of phosphorus metabolites in the human heart at 7T, compare our findings to literature values and evaluate reproducibility with different coils and different MR systems.

Andrey N. Pravdivtsev¹, Arne Brahms², Jens Gröbner³, Rosa Rojas⁴, Eva Peschke¹, Anna-Sophia Buschhoff⁴, Frowin Ellermann¹, Rainer Herges², Jan-Bernd Hövener¹, and Peer Wulff^4
1Section Biomedical Imaging, MOIN CC, Kiel University, Kiel, Germany, ²Otto Diels Institute for Organic Chemistry, Kiel University, Kiel, Germany, ³Fachhochschule Südwestfalen, Fachbereich Elektrotechnik und Informationstechnik, Lüdenscheid, Germany, ⁴Institute of Physiology, Kiel University, Kiel, Germany

The mechanisms of action of many common antiepileptics are currently not fully understood. These drugs have a narrow therapeutic window with some severe side effects. Here, we are setting up a pipeline to study the distribution of CNS-targeting drugs non-invasively with MRI, using deuterium (²H) labelling and deuterium magnetic resonance spectroscopy.

Stephanie J Blocker¹, James Cook¹, Yvonne M Mowery², Jeffrey I Everitt³, Yi Qi¹, Kathryn Hornburg¹, Gary P Cofer¹, Fernando Zapata¹, Alex M Bassil², Cristian T Badea¹, David G Kirsch², and G. Allan Johnson^1
1Radiology, Duke University, Durham, NC, United States, ²Radiation Oncology, Duke University, Durham, NC, United States, ³Pathology, Duke University, Durham, NC, United States

Identification of MR imaging biomarkers for solid tumors requires a reliable means of correlating multiparametric MR and pathological data.  We have constructed a platform for registration of multi-scale preclinical imaging libraries that utilizes MR histology and cytometric feature mapping for correlative studies.  With this platform we have identified a selection of cytometric features in murine sarcomas which demonstrate correlative trends with ex vivo and in vivo MR, including ADC and T2*.

Catherine Foss¹, Desmond Jacob¹, Flonné Wildes¹, and Marie-France Penet^1
1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Major limitations of radiological evaluation of ovarian cancer arise from the inability to consistently detect small lesions. Here, we combine the anatomic imaging capabilities of MRI with the highly sensitive molecular imaging capabilities of PET in an orthotopic syngeneic model of ovarian cancer. [124I]iodo-DPA-713, a macrophage-specific imaging agent, is used to detect and stage ovarian cancer. Specific uptake of the radiotracer was observed within and proximal to the primary tumor at early stages, and in the peritoneal ascitic fluid and within metastases at later stage. These studies will provide insights into ovarian cancer progression that will complement emerging host-directed therapeutics.