Kadharbatcha S Saleem¹, Alexandru V Avram¹, Daniel Glen², Michal Komlosh¹, and Peter J Basser^3
1Neuroscience, Center for Neuroscience and Regenerative Medicine (CNRM), Henry M. Jackson Foundation (HJF) for the Advancement of Military Medicine, Bethesda, MD 20817; Section on Quantitative Imaging and Tissue Sciences (SQITS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, Bethesda, MD, United States, ²Scientific and Statistical Computing Core, Scientific and Statistical Computing Core, National Institute of Mental Health (NIMH), Bethesda, MD 20892, Bethesda, MD, United States, ³Section on Quantitative Imaging and Tissue Sciences (SQITS), Center for Neuroscience and Regenerative Medicine (CNRM), Henry M. Jackson Foundation (HJF) for the Advancement of Military Medicine, Bethesda, MD 20817; Section on Quantitative Imaging and Tissue Sciences (SQITS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892, Bethesda, MD, United States

Despite its essential use as a model for neurological disorders in humans, the rhesus macaque lacks a comprehensive MRI-histology-based segmentation of subcortical regions. Here, we mapped the subcortical regions in the macaque monkey using MAP-MRI, and postmortem histology of the same brain. Our results demonstrate that, at high spatial resolution, MAP-MRI can distinguish a large number of gray and white matter structures in deep brain areas. The ability to delineate and validate these in a given subject is useful for neurosurgical planning and navigation of implantable devices to potential targets for deep brain stimulation in the macaque model of neurological or psychiatric disorders.

Eugene Kim¹, Eilidh MacNicol¹, Jemeen Sreedharan², and Diana Cash^1
1Neuroimaging, King's College London, London, United Kingdom, ²Basic & Clinical Neuroscience, King's College London, London, United Kingdom

The most popular mouse brain templates are created from ex vivo scans while in vivo templates are not widely available. We have released openly accessible in vivo multi-contrast mouse brain templates and associated tissue probability maps for analyses of in vivo mouse neuroimaging data. Deformation-based morphometry was performed on a test dataset using a study-specific template, our new “MouseIn” template, or the ex vivo DSURQE template. The results using the MouseIn template better matched those using the “gold-standard” study-specific template compared to those using the ex vivo template.

Reggie Taylor^1
1Institute of Mental Health Research, The Royal Ottawa Mental Health Centre, Ottawa, ON, Canada

A TE-Averaged sequence was created on a Siemens Biograph mMR 3 Tesla scanner for the purpose of detecting glycine at a clinical field strength in a healthy population. The sequence demonstrated that it can detect glycine and glutamate with moderate reproducibility, potentially providing a method to indirectly measure the health of the NMDA receptor

Ravi Prakash Reddy Nanga¹, Mark Elliott², Neil Wilson², Sophia Swago³, Walter Witschey², and Ravinder Reddy^2
1Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, Center for Advance Metabolic Imaging in Precision Medicine, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, United States, ³Bioengineering, University of Pennsylvania, Philadelphia, PA, United States

In this study, we investigated the optimal acquisition parameters in terms of voxel size, SNR and total scan time to obtain high quality NAD^+ 1H downfield (>4.7 ppm) spectra from human brain at 7 Tesla. Using a spectrally selective excitation spatially selective localization pulse sequence and without water suppression, large voxel size and shorter TR, we were able to acquire NAD⁺ spectra with an SNR of ~30 in about 5 min.  Preliminary results of high SNR and resolution enhanced NAD⁺ spectra from human brain of healthy volunteers are presented.  

Rajakumar Nagarajan¹, Anant Shinde^2,3, Muhammed Enes Gunduz⁴, and Gottfried Schlaug^1,2,3
1Human Magnetic Resonance Center, Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, MA, United States, ²Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, United States, ³University of Massachusetts Medical School - Baystate Medical Center, Springfield, MA, United States, ⁴University of Massachusetts Medical School, Worcester, MA, United States

Up- or downregulation of neurotransmitter/receptor concentration have been seen when transcranial direct current stimulation (tDCS) and proton Magnetic Resonance Spectroscopy (MRS) were combined in concurrent experiments; however, results have been mixed and not reliable across studies. In this study, we investigated dose and polarity effects of tDCS in an MRS voxel centered over the anterior cingulate/prefrontal region using three dose levels of tDCS with stimulation electrode placed over left a supraorbital area and return electrode over right mastoid bone. Dose and polarity dependent modulation of GABA and Glx was observed in a single subject study. 

Petr Bulanov¹, Petr Menshchikov², Andrei Manzhurtsev³, Alexey Yakovlev³, Tolib Akhadov³, Richard Edden⁴, and Natalia Semenova^3,5
1Lomonosov Moscow State Univesity, Moscow, Russian Federation, ²Emanuel Institute of Biochemical Physics of RAS, Moscow, Russian Federation, ³Clinical and Research Institute of Emergency Pediatric Surgery and Traumatology, Moscow, Russian Federation, ⁴Johns Hopkins University, Baltimore, MD, United States, ⁵Semenov Institute of Chemical Physics of the Russian Academy of Sciences, Moscow, Russian Federation

Changes in Aspartate (Asp) concentrations are a potential biomarker of malate-aspartate shuttle dysfunction, as well as disturbances in the synthesis of NAA. J-difference editing allows the detection of a resolved Asp signal at δAsp ≈ 2.71ppm. This resonance has a complex shape and therefore approximation of the Asp signal is a challenging task. In our study we compare the performance of six Asp-approximation models applied to data from three brain regions (anterior cingulate gyrus (ACC), dorsolateral pre-frontal area (DLPFA) and visual cortex (VC)). A model consisting of four Gauss signals shows the best performance for all brain regions studied.           

Balbino Yagüe¹, Irene Guadilla¹, Sebastián Cerdán¹, Blanca Lizarbe¹, and Pilar López^1
1Instituto de Investigaciones Biomédicas Alberto Sols, Madrid, Spain

Aquaporin-4 (AQP4) is a transmembrane water channel highly expressed in central nervous system, regulating fluid exchange by water transport between two sides of plasmatic membrane, and depending on concentration gradients of solutes, like glucose. On these grounds, we studied AQP4’s role in glucose uptake. AQP4 inhibitor TGN-020 was administrated in adult mice before vehicle and glucose stimulus. Diffusion and T2* images were acquired and apparent diffusion coefficient and T2* were measured. Ex vivo ¹H high-resolution magic angle spinning spectra were acquired. Results showed that TGN avoid physiological cerebral response linked to glucose uptake, noting the AQP4 involvement in the process.

Jonghyun Bae^1,2,3, Jin Zhang³, Mihaela Stavarache³, Ayesha Das³, Sawwal Qayyum³, Karl Kiser³, and Sungheon Gene Kim^3
1Vilcek Institute of Biomedical Science, New York University School of Medicine, New York, NY, United States, ²Radiology, Center for Advanced Imaging Innovation and Research, New York, NY, United States, ³Radiology, Weill Cornell Medical College, New York, NY, United States

This study explores two different approachs of measuring subtle BBB disruption. To induce different levels of BBB disruption, we used a focused ultrasound (FUS) sonication with intravenously injected microbubbles with an animal model. Each animal underwent FUS procedure with different acoustic power levels. We compared the changes measured using DCE-MRI with Gadolinium-based contrast agent for volume transfer rate constant and Ferumoxytol-based ACE-MRI to measure transendotheliel water exchange rate. Our results suggest that both the water exchange rate and the contrast exchange rate show sensitive detection of subtle BBB disruption, which could shed light on understanding different permeability changes in BBB.

Christian Stald Skoven¹, Mariam Andersson¹, Marco Pizzolato^1,2,3, Bente Pakkenberg^4,5, Hartwig Roman Siebner^1,5,6, and Tim Bjørn Dyrby^1,3
1Danish Research Centre for Magnetic Resonance (DRCMR), Copenhagen Universital Hospital Amager and Hvidovre, Copenhagen, Hvidovre, Denmark, ²Signal Processing Lab (LTS5), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Department of Applied Mathematics and Computer Science, Technical University of Denmark (DTU), Kgs. Lyngby, Denmark, ⁴Research Laboratory for Stereology and Neuroscience, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark, ⁵Department of Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark, ⁶Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark

The structure-function relationship of axons within the intact brain proves challenging to delineate. We recorded transcallosal conduction time in the rat brain with optogenetics and electrophysiology, estimated pathway length with tractography, - and axon diameters (AD) with dw-MRI and transmission electron microscopy. The modalities exhibit different sensitivity profiles. Recorded latencies correspond only to smaller axons below the mode of the distribution of ADs from histology. dw-MRI is only sensitive to larger axons, not accounted for by electrophysiology and only sparsely with histology. Future correlative studies should choose modalities with a sufficient sensitivity profile for the structural or functional metric of interest.

Jessica Archibald¹, Erin L. MacMillan^2,3, Niklaus Zölch⁴, and John L.K. Kramer^5
1Experimental Medicine, University of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Comulbia, Vancouver, BC, Canada, ³Philips, Vancouver, BC, Canada, ⁴Wissenschaftlicher Mitarbeiter Forensische Medizin und Bildgebung, Universität Zürich, Zürich, Switzerland, ⁵Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada

¹H-MRS provides a window into brain chemistry without the need to directly sample tissue. The growing prevalence of neurological conditions highlight the need for evidence based treatments. Specifically, preclinical and clinical evidence suggest a link between glutamate and pain. This study shows spatial neurochemical differences from  different voxels across the cingulate cortex using sLASER at 3 T. A significant correlation between pain ratings and the anterior cingulate cortex is seen. As MRS moves towards becoming a standardized clinical technique, understanding the spatial distributions and variability will provide an important basis for the understanding of the healthy human brain’s biochemical environment.

Colleen Pletcher¹, Lauren Heinrich¹, Marissa DiPiero^1,2, Andrew Alexander^1,3,4, Steven Kecskemeti ¹, Elizabeth Planalp¹, and Douglas Dean III^1,3,5
1Waisman Center, University of Wisconsin-Madison, Madison, WI, United States, ²Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, United States, ³Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States, ⁴Department of Psychiatry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States, ⁵Department of Pediatrics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States

The emergence of executive function (EF) in children is an important developmental process that impacts later cognitive and behavioral outcomes; however, much remains unknown about the neural processes underlying the development of EF. In this study, we quantified volumetric measures from structural MRI to investigate associations between EF and brain structure in children aged 3 to 10 years old. Results indicated that there were correlations between EF and structures in subcortical brain regions and regions of the frontal and parietal lobes. 

Matthias Weigel^1,2,3, Riccardo Galbusera^1,2, Peter Dechent⁴, Erik Bahn⁵, Govind Nair⁶, Ludwig Kappos^1,2, Wolfgang Brück⁵, Christine Stadelmann⁵, and Cristina Granziera^1,2
1Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Basel, Switzerland, ²Neurological Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, ³Dept. of Radiology, Division of Radiological Physics, University Hospital Basel, Basel, Switzerland, ⁴Department of Cognitive Neurology, MR-Research in Neurology and Psychiatry, University Medical Center Göttingen, Göttingen, Germany, ⁵Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany, ⁶Translational Neuroradiology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States

MRI of the fixed human brain is highly interesting, since it basically allows very long scan times for unprecedented MRI resolutions on clinical scanners. Recent work utilized T2* weighted RF spoiled gradient echo sequences to achieve isotropic resolutions up to 160-microns at 3T. This work establishes a T1 weighted MR imaging protocol based on RF spoiled gradient echo sequences that currently enables isotropic resolutions of 240-microns at 3T and depicts the complex fine structure of the fixed cerebellum very well.

Mark David Platt¹, Antonius Plagge², and Harish Poptani^1
1Centre for Preclinical Imaging, University of Liverpool, Liverpool, United Kingdom, ²Cellular and Molecular Physiology, University of Liverpool, Liverpool, United Kingdom

Microcephaly and intellectual disability is associated with mutation of the TRAPPC9 gene. A knockout mouse model of TRAPPC9-associated intellectual disability and microcephaly was characterised using high resolution T1 and T2 weighted Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) alongside behavioural assays. Behavioural differences suggested learning impairment in the model, MRI elucidated the developmental timeline of the disorder and highlighted several brain regions with reduced volume. DTI revealed reduced structural integrity in the corpus callosum.