Christoph Meyer^1,2,3, Damian Hertig^1,2, Christian Urzi^1,2,3, Janine Arnold², Jean-Marc Nuoffer^2,4, and Peter Vermathen^1
1Magnetic Resonance Methodology, Institute of Diagnostic and Interventional Neuroradiology, University Bern, Bern, Switzerland, ²Institute of Clinical Chemistry, University Hospital Bern, Bern, Switzerland, ³Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland, ⁴Department of Pediatric Endocrinology, Diabetology and Metabolism, University Children’s Hospital of Bern, Bern, Switzerland

Mitochondrial respiratory chain defects present as highly heterogeneous disorders which cannot be unambiguously diagnosed using standard laboratory methods. In this study we observed the biochemical consequences of complex I and complex V deficient human skin fibroblasts when cultivated under galactose stress condition compared to glucose based cell culture condition. We investigated extracellular flux using Seahorse XFe96 cell analyzer and assessed the metabolome fingerprints using High Resolution Magic Angle Spinning NMR. The selective culture method reveals CI and CV defect-specific changes in metabolites associated with the TCA cycle, malate aspartate shuttle and choline metabolism.

Xiaoling Gong¹, Xiaoxiao Zhang², Xiaoyong Zhang², and Bing Wu^1
1Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Chengdu, China, ²Philips Healthcare, Beijing, China

CEST MRI is a novel molecular imaging technique in which the contrast is generated by the dynamic exchange between the exchangeable proton and water. Self-assembled G4·K+ Hydrogel can be fully characterized by its intrinsically endowed CEST contrast.

Xiaoxiao Zhang¹, Zhigang Wu¹, Peng Sun¹, Zhiwei Shen¹, Liangjie Lin¹, Geli Hu¹, Haoyu Huang¹, and Jiazheng Wang^1
1Philips Healthcare, Wuhan, China

CEST MRI is an novel molecular imaging technique in which the contrast is generated by the dynamic exchange between the exchangeable proton and water. Porphyrin and its analogues are a promising class of highly sensitive, diamagnetic CEST agents with highly upfield shifted protons. We synthesized a water-soluble polymeric CEST MRI agent grafted with protoporphyrin IX(PpIX). The PpIX polymeric agent resonated at -13.5 ppm from water and showed excellent CEST MRI properties.

Xiaoling Gong¹, Xiaoxiao Zhang², Xiaoyong Zhang³, Kai Ai⁴, and Bing Wu^5
1Departments of Radiology, West China Hospital, Sichuan University, Cheng du, China, ²Department of Clinical, Philips Healthcare, China, Wuhan, China, ³Department of Clinical, Philips Healthcare, China, Chengdu, China, ⁴Department of Clinical, Philips Healthcare, China, Xian, China, ⁵Departments of Radiology, West China Hospital, Sichuan University, Chengdu, China

Contrast agents play a significant role in clinical MRI and are administered to detect pathology in over a third of clinical scans. Gadolinium (Gd)-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. Although GBCAs have shown efficacy and are safe to use with most patients, some GBCAs have a small risk of adverse effects, such as nephrogenic systemic fibrosis (NSF) and gadolinium deposition in the human brain. Therefore, developing novel Gd-free MRI contrast agents are in great demand. Herein, we developed a new type of MRI contrast agent using naturally derived hemin to shorten the T1 relaxation time of water.

 

Steffen Houe Sejersen¹, Camilla Rasmussen¹, Nikolaj Bøgh¹, Esben Hansen¹, Rolf Schulte², and Christoffer Laustsen^1
1MR Centeret, Klinisk Institut, AU, Århus C, Denmark, ²GE Healthcare, Munich, Germany

Hyperpolarized [1-13C]pyruvate MRI is an exciting emerging clinical tool for metabolic imaging. It has the potential for absolute quantitative metabolic imaging. However, in contrast to the most abundant metabolic imaging techniques, the signal itself is less quantitative by nature and, thus the most abundant analyses are relative or semiquantitative. Here, we propose a simple normalization to the whole body metabolic oxidative metabolism to overcome this limitation.

Jennifer Lewis¹, Adam Gaunt¹, Irene Marco-Rius¹, and Arnaud Comment^1,2
1Cambridge University, Cambridge, United Kingdom, ²General Electric Healthcare, Chalfont St Giles, United Kingdom

The use of the endogenous molecule alpha-ketoglutarate (α-KG) as a non-persistent radical is examined to hyperpolarise ¹³C-glucose. A radical build-up curve was obtained and the maximum radical concentration was calculated to be 29 ± 3 mM. The microwave irradiation frequency was then examined to optimise the polarisation transfer between the electron on α-KG and glucose. A dissolution was successfully carried out and a hyperpolarised ¹³C spectrum of ¹³C-glucose was obtained.

Nathan H. Williamson^1,2, Rea Ravin¹, Teddy X. Cai^1,3, Melanie Falgairolle⁴, Michael J. O'Donovan⁴, and Peter J. Basser^1
1National Institute of Child Health and Human Development, Potomac, MD, United States, ²National Institute of General Medical Sciences, Potomac, MD, United States, ³Department of Clinical Neurosciences, Wellcome Centre for Integrative Neuroimaging, FMRIB, University of Oxford, Oxford, United Kingdom, ⁴National Institute of Neurological Disorders and Stroke, Potomac, MD, United States

Currently, no MRI method exists to non-invasively and absolutely measure cellular activity. One approach is to quantify steady-state transmembrane water exchange rates. Diffusion Exchange Spectroscopy (DEXSY) non-invasively and directly encodes for exchange of endogenous components. Using DEXSY-based methods implemented on a low-field, high-gradient MR system, we show in viable ex vivo neonatal mouse spinal cord samples that the rate at which water exchanges across cell membranes decreases drastically after perturbation known to induce persistent membrane depolarization. We also show that the exchange rate recovers to normal values after perturbations known to restore membrane potential.

Drew Parker¹, Victoria E. Johnson², H. Isaac Chen^2,3, John A. Wolf^2,3, and Ragini Verma^1
1DiCIPHR (Diffusion and Connectomics in Precision Healthcare Research) Lab, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ³Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, United States

The way brain injury can evolve has different manifestations on imaging in multiple MRI modalities, pointing to different pathological etiologies. The true picture can be seen only by correcting for free water, as it biases all the diffusion measurements, especially the longitudinal outcome. While this has been observed in humans, it is for the first time free water analysis has been carried out in a gyrencephalic pig model of TBI. In the future, co-registration with histopathological outcomes will be undertaken to verify the specificity of the diffusion measurements, which will lay the foundation for interpretation of unbiased diffusion measurements.

Leo Cheng¹, Aidan Pavao², Brintha Girinathan², Johann Peltier³, Pamela Altamirano Silva⁴, Bruno Dupuy⁵, Isabella Muti¹, Craig Malloy⁶, and Lynn Bry^2
1Radiology and Pathology, Massachusetts General HospitalMassachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States, ²Massachusetts Host-Microbiome Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States, ³Institut Pasteur, Université de Paris, Paris, France, ⁴Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica, San Jose, Costa Rica, ⁵Laboratory of the Pathogenesis of Bacterial Anaerobes, Institut Pasteur, Université de Paris, Paris, France, ⁶Radiology, The University of Texas Southwestern Medical Center, Dallas, TX, United States

Anaerobic microbial metabolism drives critical functions within global ecosystems, host-microbiota interactions, and industrial applications, yet remains ill-defined. We resolved dynamic metabolism in living cells of the anaerobic pathogen Clostridioides difficile using High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy to inform genome-scale predictions of cellular metabolism. Analyses leveraged the sensitivity of ¹³C NMR spectroscopy to simultaneously track cellular carbon and nitrogen flow from fermentable ¹³C and ¹⁵N-labeled substrates. We illustrate a versatile approach to elaborate complex anaerobic metabolism for clinical, scientific, and industrial applications. 

Noam Shemesh¹, Andrada Ianus¹, and Sune N Jespersen^2,3
1Champalimaud Centre for the Unknown, Lisbon, Portugal, ²Center for Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, ³Department of Physics and Astronomy, Aarhus University, Aarhus, Denmark

The sensitivity of diffusion MRI (dMRI) towards microstructural features is quite high, but its specificity is low due to the ubiquity of water in biological tissues. Here, we harness a strongly filtered diffusion kurtosis imaging (DKI) approach to (i) suppress fast diffusion spins typically associated with extracellular space and (ii) measure the time dependencies of the full filtered diffusion and kurtosis tensors in an ex-vivo mouse brain at 16.4T. Following the application of a very strong filter of b₁=15ms/µm² perpendicular to axon fibers, we find signatures for restricted diffusion that are tentatively associated with intracellular space.

Dariya I. Malyarenko¹, Thomas L Chenevert¹, Shigeto Ono², Ted Lynch², and Scott D. Swanson^1
1Radiology, University of Michigan, Ann Arbor, MI, United States, ²CIRS, Inc, Norfolk, VA, United States

Recently developed quantitative phantom based on lamellar-vesicles provides the range of tissue relevant diffusion kurtosis parameters for accurate evaluation of advanced multi-b DWI protocols and parametric diffusion models.  This work studies temperature dependence of phantom diffusion kurtosis parameters to supply accurate nominal parameter values for typical scan room temperature range.

Mirsad Mahmutovic¹, Manisha Shrestha¹, Matthäus Poniatowski¹, Jarmila Jedelská², Udo Bakowsky³, Alexander M. König^2,4, Andreas H. Mahnken^2,4, and Boris Keil^1
1Institute of Medical Physics and Radiation Protection, TH Mittelhessen University of Applied Sciences, Giessen, Germany, ²Center for Tumor Biology and Immunology, Core Facility for Small Animal MRI, Marburg, Germany, ³Department of Pharmaceutics and Biopharmaceutics, Philipps-University of Marburg, Marburg, Germany, ⁴Department of Diagnostic and Interventional Radiology, Philipps-University of Marburg, Marburg, Germany

The chorioallantoic membrane (CAM) model is a simple and low-cost model that allows screening of a large number of pharmacological samples. It is used in preclinical research as an intermediate step between in vitro and in vivo experiments and does not require approval by the animal experiment ethics committee. Latest studies show that MRI is a suitable imaging modality for evaluating drug delivering systems with the CAM-model. However, appropriate hardware for high-resolution MR imaging of the CAM model is still missing. To fill this gap, we designed, constructed, and evaluated a transceiver solenoid coil for in ovo imaging at 7T.

Jacob Patrick Berardinelli¹, Julia Kofler¹, Noah Schweitzer¹, Nadim Farhat¹, Tales Santini¹, Andrea Sajewski¹, Joseph Mettenburg¹, Milos Ikonomovic¹, Howard J. Aizenstein¹, and Tamer S. Ibrahim^1
1University of Pittsburgh, Pittsburgh, PA, United States

A 3D printed re-usable box enclosure and two-piece cutting guide were developed to produce high quality 7T MR images that can be easily registered to gross anatomy and histology. Cuts can be made parallel or at multiple angles at 5mm intervals in both the axial and coronal orientations.

Sydney Sherman¹ and Michael Cima^2
1HST, MIT, Cambridge, MA, United States, ²DMSC, MIT, Cambridge, MA, United States

A low-field portable MR-based sensor was fabricated for the acquisition of clinical T2 relaxometry measurements in skeletal muscle. We have previously reported methods for designing low-field permanent magnet array configurations with varying sensitive region profiles. The newly constructed array has a sensitive region 15-20mm from the surface of the magnet; field maps from the constructed magnet show good alignment with simulated fields. The exclusion of subcutaneous fat tissue in the sensitive region will improve sensitivity to fluid shifts within the skeletal muscle.