Hanwei Chen^1,2, Yuguo Li^1,3, Anna Jablonska¹, Shuixing Zhang⁴, Jeff W Bulte^1,3, Peter C.M. Van Zijl^1,3, Mirek Janowski^1,5, Piotr Walczak¹, and Guanshu Liu^1,3
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Radiology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁴Department of Radiology, Guangdong General Hospital, Guangzhou, Guangdong, China, ⁵NeuroRepair Department, MMRC PAS, Warsaw, Poland

Cytidine-5’-diphosphocholine (citicoline or CDP-choline) is a highly safe supplement with well-documented neuroprotective effects, and has been approved for the treatment of head trauma, stroke, and neurodegenerative disease. In the present study, we aimed to explore the possibility to use citicholine as an imaging agent detected by CEST MRI. Our results demonstrated that citicholine has a desirable CEST MRI contrast at 2 ppm, which enables the direct imaging of drug delivery of citicholine-loaded liposomes in the brain after stroke, indicating such a system can be used as not only a therapeutics but also a diagnostics of brain damage.

Alexia Daoust¹, Stephen Dodd¹, and Alan Koretsky^1
1NINDS, LFMI, NIH, Bethesda, MD, United States

MEMRI can be used for different applications such as tracing neuronal connections. However, the detailed mechanisms responsible for Mn transport and synaptic transmission are still unclear. To study these mechanisms, a hippocampal slice culture was developed that enables high resolution MEMRI. Excellent MRI contrast of hippocampal structures could be obtained after incubating slices with 10 uM for 24 hours. Mn microinjection into CA3 led to tract tracing into CA1/2 and then in the Schaffer collaterals. This hippocampal slice culture should be useful to study mechanisms of Mn transport in neurons and across synapses.

Jessica AM Bastiaansen^1,2, Hikari AI Yoshihara^3,4, Andrea Capozzi³, Juerg Schwitter⁴, Matthew E Merritt⁵, and Arnaud Comment^3
1Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland, ²Center for Biomedical Imaging (CIBM), Lausanne, Switzerland, ³Institute of Physics of Biological Systems, EPFL, Lausanne, Switzerland, ⁴Division of Cardiology and Cardiac MR Center, University Hospital Lausanne (CHUV), Lausanne, Switzerland, ⁵Advanced Imaging Research Center,Department of Radiology,Molecular Biophysics,Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, Texas, United States

The combination of hyperpolarized 13C technology and co-administration of separate imaging agents enables simultaneous monitoring of separate metabolic pathways in vivo in a single experiment. However, for clinical applications, it is currently necessary to use 13C preparations containing persistent radicals which require a time consuming filtration process before the injection, resulting in polarization losses. Here we present a radical-free, additive-free method, to co-hyperpolarize mixtures of 13C-labeled metabolites and respective in vivo detection in the heart. This study illustrates a method for measuring substrate competition that could be generalized to humans.

Yunkou Wu¹, Shanrong Zhang¹, Todd C Soesbe¹, and A. Dean Sherry^1,2
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ²Department of Chemistry, The University of Texas at Dallas, Richardson, TX, United States

This study is to explore the feasibility of using a frequency-dependent paraCEST agent for in vivo pH imaging of mouse kidneys. CEST signals were acquired with a steady state gradient echo pulse sequence. The B0 magnetic field inhomogeneities were corrected using WASSR method. Kidney pH maps were derived by following the resonance frequencies of the paraCEST agent signals. The pH maps show the expected pH gradient across the renal cortex, medulla and pelvis in healthy mice. This studies provide a direct measure of Kidney pH maps without the prior knowledge of the paraCEST contrast agent concentration in vivo.

Sudath Hapuarachchige¹, Yoshinori Kato^1,2, Wenlian Zhu¹, Joseph M Backer³, Marina V Backer³, Susanta K Sarkar⁴, and Dmitri Artemov^1,5
1Department of Radiology & Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Life Science Tokyo Advanced Research Center, Hoshi University, Japan, ³SibTec, Inc., Brookfield, CT, United States, ⁴Sanofi Oncology, Cambridge, MA, United States, ⁵Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Noninvasive tracking of drug-loaded nanocarriers adds significant value to cancer chemotherapy by allowing prediction of thetherapy outcome, which will eventually benefit cancer patients. Superparamagnetic iron oxide nanoparticles (SPIONs) are highly sensitive MRI contrast agents. However, rapid clearance of SPIONs by the reticuloendothelial system, presents significant problems for their use as an image-guided drug delivery platform. This study was intended to investigate if tumor delivery of SPIONs can be enhanced by encapsulating them in liposomes for either “passive” delivery via the enhanced permeability and retention effect (EPR) or “active” delivery via the receptors for vascular endothelial growth factor (VEGF).

Dung Minh Hoang¹, Matthew J Gounis², Youssef Zaim Wadghiri¹, Peter Caravan³, and Alexei A Bogdanov Jr.^2
1Radiology, Bernard and Irene Schwartz Center for Biomedical Imaging, New York University, New York, NY, United States, ²Radiology, University of Massachusetts Medical School, Worcester, MA, United States, ³Radiology, A.Martinos' Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

We aimed to investigate the feasibility of imaging myeloperoxidase (MPO) activity, i.e a marker of vessel wall inflammation and instability with novel paramagnetic (DOTAGA(Gd)-5-hydroxytryptamide) and fluorescent (Cy3-5-hydroxytryptamide) substrates in surgically excised specimens of human ruptured and unruptured intracranial aneurysms using fluorescence and micro-MR imaging. Fluorescent MPO substrate resulted in localized staining of several areas in the adventitia of the ruptured aneurysm as well as perivascular areas within the lumen of the unruptured samples. The highly detailed MR images (57-µm in-plane resolution) acquired revealed the presence of high focal T1w-enhancement corresponding to the blood vessel wall and atherosclerotic plaque.

Gary V. Martinez¹, Parastou Foroutan², Valerie E. Moberg¹, Suryakiran Navath³, Roha Afzal¹, Robert J. Gillies¹, Eugene A. Mash³, and David L. Morse^1
1Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States, ²Bruker Biospin, Billerica, Massachusetts, United States, ³Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, United States

Colorectal cancer (CRC) has a high incidence as it is the third most common cancer in both males and females, and the second leading cause of death from cancer in the United States. Despite these statistics, it is known that early detection can mitigate the risk and improve outcome dramatically, if detected early. In this work, we present an approach that may potentially mitigate all of the drawbacks of currently existing methods by using a Gd sucrose scaffold that has a high relaxivity, is robust and resilient to the GI tract, and may be administered orally with minimal bowel preparation.

Patrick Waxmann¹, Ralf Mekle¹, Florian Schubert¹, Andre Kuehne², Tomasz Dawid Lindel¹, Frank Seifert¹, Oliver Speck³, and Bernd Ittermann^1
1Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Berlin, Germany, ²Medical University of Vienna, Vienna, Austria, ³Otto-von-Guericke-University, Magdeburg, Germany

Spatially selective excitation (SSE) with parallel transmission was applied as a means to acquire signal from anatomy adapted voxels for in vivo 1H MR spectroscopy. A novel method to select spectroscopy voxels with two-dimensional arbitrary shapes was investigated. An on/off scheme with an adiabatic slice selective inversion pulse preceding a 2D-SSE pulse enabled rapid free induction decay acquisitions. High spatial fidelity of the SSE profiles on and off resonance was achieved. Metabolite concentrations in human brain determined with SHAVE were reliably quantified with LCModel (CRLB < 20 %) and did not deviate systematically from results acquired with a conventional SPECIAL sequence.

Charlie Yi Wang¹, Yuchi Liu¹, Mark Alan Griswold^1,2, and Xin Yu^1,2
1Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, ²Radiology, Case Western Reserve University, Cleveland, Ohio, United States

ATP synthesis through ATP synthase rate measurement by conventional ³¹P saturation transfer (ST) methods requires long experiment times. A novel ³¹P magnetization transfer spectroscopic magnetic resonance fingerprinting (MT-MRF) pulse sequence was designed to encode magnetization transfer of ATP metabolites. The flexibility in sequence design was utilized to improve encoding of magnetization transfer through ATP synthase. Measurement using ³¹P MT-MRF method was shown in vivo rat hind-limb to agree with conventional ST method for ATP synthesis rate measurement. ³¹P MT-MRF exhibited improved measurement precision over ST for rate measurement of ATP synthesis through ATP synthase, suggesting decreased required imaging time.

Keshav Datta¹, Arif Wibowo², Stephen R. Lynch², and Daniel Spielman^3
1Dept. of Electrical Engineering, Stanford University, Stanford, CA, United States, ²Dept. of Chemistry, Stanford University, CA, United States, ³Dept. of Radiology, Stanford University, Stanford, CA, United States

We propose an improved Proton Observed Carbon Edited (POCE) method, PROCEED, that eliminates splitting due to short-range ¹³C-¹H J-coupling. Although the overall SNR for the PROCEED method is √2 less than that achieved using a decoupled POCE acquisition, spectral simplification and reduced metabolite peak overlap is achieved without SAR-intensive decoupling. The elimination of decoupling makes in vivo ¹³C MRS of neuroenergetics and neurotransmitter cycling potentially viable for studies throughout the human brain.

Ming Lu¹, Wei Chen¹, and Xiao-Hong Zhu^1
1Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, United States

NAD⁺ and NADH play key roles in cellular respiration. Intracellular redox state defined by the NAD⁺/NADH ratio (RX) reflects the cellular metabolic and physiopathological status. By taking the advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo ³¹P MRS based NAD assay for noninvasive measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T, respectively. To explore its potential for clinical translation, in this study, we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a relatively lower field of 4 T by incorporating ¹H-decoupling technique with the ³¹P NAD assay. The use of ¹H-decoupling significantly narrowed the linewidths of NAD and -ATP resonances, resulting in higher sensitivity and better-resolved resonance signals as compare to the ¹H-coupled spectrum. These improvements made it possible for reliably quantifying cerebral RX and NAD concentrations, which are consistent with previously reported results obtained at 7 T in similar aged human subjects. In summary, this work demonstrates the capability and utility of the ¹H-decoupled ³¹P MRS-based NAD assay at lower field strength, which indicates potential opportunities for studying NAD metabolism and redox state in human brain at clinical setting.

Francesca Branzoli^1,2, Daniel Garcia-Lorenzo^1,2, Romain Valabrègue^1,2, and Stephane Lehéricy^1,2
1Institut du Cerveau et de la Moelle épinière – ICM, Centre de Neuroimagerie de Recherche – CENIR, Paris, France, ²Sorbonnes Université, Université Pierre et Marie Curie and Inserm UMR-S1127; CNRS, UMR 7225, Paris, France

Diffusion-weighted MR Spectroscopy (DW-MRS) allows to measure the diffusion properties of intra-cellular metabolites in-vivo, and in recent years it has been proved a powerful tool to investigate brain tissue microstructure and function in both healthy and disease. However, due to the low concentration of brain metabolites, the applicability of DW-MRS in clinical protocols may be prevented by the long acquisition times often required by this technique. In this study, we simulated the variability of the apparent diffusion coefficients (ADCs) of total n-acetylaspartate (tNAA), total creatine (tCr) and choline compounds (tCho) associated with different acquisition schemes of different durations, and propose a short and efficient acquisition protocol to be used in clinical application.

Stéphanie Battini¹, Alessio Imperiale^1,2, David Taieb³, Karim Elbayed¹, Frédéric Sebag⁴, Laurent Brunaud⁵, and Izzie-Jacques Namer^1,6
1ICube laboratory UMR 7357, University of Strasbourg/CNRS and FMTS, Strasbourg, France, ²University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Hautepierre, Strasbourg, France, ³La Timone University Hospital, European Center for Research in Medical Imaging, Aix-Marseille University, Marseille, France, ⁴Department of Endocrine Surgery, La Timone University Hospital, Aix-Marseille University, Marseille, France, ⁵Department of Digestive, Hepato-Biliary and Endocrine Surgery, Brabois University Hospital, Nancy, France, ⁶University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Hautepierre Hospital, Strasbourg, France

Context: Primary hyperparathyroidism (pHPT) may be related to a single gland (SGD) or multiglandular disease (MGD) and is probably related to defects in a set of specific genes that control parathyroid cell growth. By contrast, in patients on long-standing dialysis, parathyroid develop a diffuse hyperplasia and with time progressively shift to monoclonal growth. The aim of the present study was to characterize the metabolomic profiles of parathyroid disorders of different origin by High Resolution Magic Angle Spinning (HR-MAS) Nuclear Magnetic Resonance (NMR).

Alessio Imperiale^1,2, Stéphanie Battini¹, Philippe Roche³, François-Marie Moussallieh¹, Ercument A Cicek⁴, Frédéric Sebag⁵, Laurent Brunaud⁶, Anne Barlier⁷, Karim Elbayed¹, Anderson Loundou⁸, Philippe Bachellier⁹, Bernard Goichot¹⁰, Constantine A Stratakis^11,12, Karel Pacak^13,14, David Taieb¹⁵, and Izzie-Jacques Namer^1,2
1ICube laboratory UMR 7357, University of Strasbourg/CNRS and FMTS, Strasbourg, France, ²University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Hautepierre Hospital, Strasbourg, France, ³Integrative Structural & Chemical Biology (iSCB) & INT-3D Molecular Modeling Platform, Cancer Resear, CNRS UMR7258; INSERM U1068; Institut Paoli Calmettes; Aix-Marseille University UM105, Marseille, France, ⁴Lane Center for Computational Biology, School of Computer Science, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15222, United States, ⁵Department of Endocrine Surgery, La Timone University Hospital, Aix-Marseille University, Marseille, France, ⁶Department of Digestive, Hepato-Biliary and Endocrine Surgery, Brabois University Hospital, Nancy, France, ⁷Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Aix-Marseille, University, Marseille, France, ⁸Department of Public Health, Aix-Marseille University, Marseille, France, ⁹Department of Visceral Surgery and Transplantation, Hautepierre Hospital, University Hospitals of Strasbourg, Strasbourg, France, ¹⁰Department of Internal Medicine, Diabetes and Metabolic Disorders, Hautepierre Hospital, University Hospitals of Strasbourg, Strasbourg, France, ¹¹Section on Genetics and Endocrinology (SEGEN), Program on Developmental Endocrinology and Genetics (PDEGEN), Bethesda, United States, ¹²Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States,¹³Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, United States, ¹⁴National Institutes of Health, Bethesda, United States, ¹⁵La Timone University Hospital, European Center for Research in Medical Imaging, Marseille, France

Pheochromocytomas/paragangliomas (PHEOs/PGLs) are characterized by high genetic heterogeneity. Mutations in succinate dehydrogenase genes (SDHx) increase susceptibility to develop PHEOs/PGLs. The SDHx genes encode the SDH enzyme that catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid cycle (TCA) and the respiratory chain. The aim of the present study was to investigate the HRMAS NMR-based metabolomic profiling of PHEOs/PGLs in order to: (a) define the global metabolomic profile of the SDH-related PHEOs/PGLs in comparison to sporadic tumors and (b) identify metabolites that could be used as clinical predictors of SDH deficiency

Karim Snoussi^1,2, Joseph S. Gillen^1,2, Michael Schär^1,2, Richard A.E. Edden^1,2, Andrew A. Maudsley³, and Peter B. Barker^1,2
1Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medidine, Baltimore, Maryland, United States,²Kennedy Krieger Institute, Johns Hopkins University, Baltimore, Maryland, United States, ³Miller School of Medicine, University of Miami, Miami, Florida, United States

MR spectroscopy at high field is expected to benefit from improved signal-to-noise ratios and spectral resolution, due to increased chemical shift dispersion and reduced strong coupling effects. This study describes the development of a volumetric proton echo-planar spectroscopic imaging (EPSI) sequence for 7T. It is demonstrated in vivo that the spin-echo 7T EPSI sequence can be used to record high quality spectroscopic imaging data with extended 3D coverage and low RF power deposition.