Akira Sumiyoshi¹, Keigo Hikishima², and Ichio Aoki^1
1National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan, ²Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan

We report here in vivo 50-micron cerebral blood volume (CBV) mapping of the mouse brain using intraperitoneal injection protocol of gadolinium-based contrast agent. Based on k-means clustering we identified different vascular clusters that separately range from macro- to micro-vasculature. The CBV map demonstrated layer-dependent macro- and micro-vascular densities in the cortex where different cortical regions exhibited different vascular patterns. The CBV map also identified different vascular densities and patterns in the hippocampus. These results suggest that CBV map would be a useful and alternative tool that assesses brain function and metabolism at extremely high spatial resolution.

Tanzil Mahmud Arefin¹, Choong Heon Lee¹, Zifei Liang¹, and Jiangyang Zhang^1
1Radiology, NYU School of Medicine, New York, NY, United States

In this work, we used our previously reported high-resolution dMRI-based mouse brain atlas⁸ to trace node-to-node thalamo-cortical structural connectivity in the mouse brain. Taking advantage of the rich viral tracer data from the Allen Mouse Brain Connectivity Atlas (AMBCA)⁴, the tractography results were examined using the tracer data as ground truth. Our findings pinpoint the potentiality of mapping reliable structural connectivity in gray matter structures using tractography and at the same time, highlight the necessity of further investigation on determining the imaging and tractography parameters for accurate estimation of such connectivity.

Aurea B. Martins Bach¹, Lily Qiu¹, Jacob Ellegood², Nick Wang², Brian J. Nieman², John G. Sled², Remya R. Nair³, Elizabeth M. C. Fisher^3,4, Thomas J. Cunningham³, Jason Lerch¹, and Karla L. Miller^1
1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada, ³Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire, United Kingdom, ⁴Department of Neuromuscular Diseases, Institute of Neurology, University College London, London, United Kingdom

This study assesses changes in brain anatomy with MRI in the homozygous humanized FUSDelta14 mouse model of amyotrophic lateral sclerosis (ALS). Post-mortem brain T2w-images were acquired at 7T, with 40μm isotropic resolution. After registration, the deformation fields were compared between mutant and wild-type mice. Homozygous FUSDelta14 mice exhibited atrophy in multiple grey and white matter structures. These results are in agreement with observations such as cortical thinning and alterations in white matter microstructure in ALS patients. Homozygous humanized FUSDelta14 mice show an early brain phenotype and are therefore a promising model for the study of ALS pathogenic mechanisms.

Steven Jillings¹, Jan Morez², Nicholas Vidas-Guscic³, Johan Van Audekerke³, Floris Wuyts¹, Marleen Verhoye³, Jan Sijbers², and Ben Jeurissen^2
1Lab for Equilibrium Investigations and Aerospace, Dept. of Physics, University of Antwerp, Antwerp, Belgium, ²imec-Vision Lab, Dept. of Physics, University of Antwerp, Antwerp, Belgium, ³Bio Imaging Lab, Dept. of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

Multi-tissue constrained spherical deconvolution (MT-CSD) leverages the unique b-value dependency of each brain tissue type to estimate the full white matter (WM) fiber orientation density function (fODF) as well as the apparent densities of gray matter (GM) and cerebrospinal fluid (CSF), directly from multi-shell diffusion MRI (dMRI) data. Currently, its adoption is focussed almost entirely on imaging of the human brain. In this work, we demonstrate that the sequence, the pipeline and the advantages that are now well established for human brains, can be transferred to murine brains, bringing the technique into the preclinical realm.

Charlie Wang¹, Yuning Gu², Rasim Boyacioglu², Charlie Androjna³, Mark Alan Griswold², and Xin Yu^2
1Metrohealth Hospital, Cleveland, OH, United States, ²Case Western Reserve University, Cleveland, OH, United States, ³Cleveland Clinic, Cleveland, OH, United States

Magnetic Resonance Fingerprinting with Quadratic Phase (qRF-MRF) was previously validated in 2D clinical imaging for simultaneous off-resonance, T1, T2, and T2* mapping.  Translation of qRF-MRF to high-field preclinical systems for small animal imaging is challenging due to the higher field inhomogeneity and the higher spatial resolution required.  Here, a 3D qRF-MRF method was explored to address these challenges.  High-resolution simultaneous mapping of off-resonance, T1, T2, and T2* on in vivo mouse brain at 7T was demonstrated.   Computational limitations for large dictionary parameter space and reconstruction times were addressed using randomized SVD time compression and quadratic fitting methods. 

Liesbeth Vanherp¹, Kristof Govaerts¹, Amy Hillen², Jennifer Poelmans³, Katrien Lagrou⁴, Greetje Vande Velde¹, and Uwe Himmelreich^1
1Biomedical MRI, University of Leuven, Leuven, Belgium, ²Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden, ³Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium, ⁴Laboratory of Clinical Bacteriology and Mycology, University of Leuven, Leuven, Belgium

Multi-parametric MRI was correlated with in vivo Fibred Confocal Fluorescence Microscopy and histology in two preclinical models of cryptococcosis. Increased ADCs and T2 relaxation times were linked to differences in capsule size and associated fungal density in brain lesions caused by the two pathogenic fungi Cryptococcus neoformans and C. gattii. This provides not only a non-invasive means to assess one of the most important virulence factors of Cryptococci in preclinical research but may also affect patient management by providing a method for differential diagnosis. 

Puneet Bagga¹, Laurie J Rich¹, Neil E Wilson¹, Mark Elliott¹, Mitch D Schnall¹, Mohammad Haris^2,3, John A Detre⁴, and Ravinder Reddy^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Sidra Medicine, Doha, Qatar, ³LARC, Qatar University, Doha, Qatar, ⁴Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States

Energy metabolism and neurotransmission are two crucial processes affecting almost all aspects of cerebral function and ¹H MRS allows the non-invasive detection and quantification of neurochemicals. In this study, we performed ¹H MRS in conjuction with the administration of [6,6′-²H₂]glucose to measure turnover kinetics of glutamate, glutamine and GABA in rat brain. As ²H is invisible on ¹H MRS, the turnover of metabolites leads to a corresponding drop in their ¹H MR signal visualized by subtraction of the Post-[6,6′-²H₂]glucose administration from the Pre-administration ¹H MR spectra. The fractional enrichment data can be fitted to evaluate the rates of cerebral energetics.

Xiongqi Han¹, Jianpan Huang¹, and Kannie Wai Yan Chan^1,2
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, ²Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD, United States

Self-healing hydrogels can adapt to the dynamic and mechanically demanding environment in the brain when compare to conventional brittle hydrogels. Herein, we developed a series of self-healing chitosan-dextran based hydrogels (CDgels) which were mechanically soft and its composition could be detected via CEST-MRI. Once crosslinked, CEST-MRI contrast at 1.2 ppm decreased when the crosslinking density increased. Interestingly, this phenomenon was observed when we further incorporated barbituric acid (BA) into CDgels to form part of the Schiff-base interaction. The resultant BA-loaded CDgels showed both CEST contrast at 3T, demonstrating a robust approach for imaging-guided hydrogel-based therapy in brain.

Mohammed Salman Shazeeb^1,2, Robert King^1,2, Josephine Kolstad¹, Christopher Raskett¹, Natacha Le Moan³, Jonathan A. Winger³, Lauren Kelly³, Ana Krtolica³, Nils Henninger¹, and Matthew Gounis^1
1University of Massachusetts Medical School, Worcester, MA, United States, ²Worcester Polytechnic Institute, Worcester, MA, United States, ³Omniox Inc., San Carlos, CA, United States

The dog large vessel occlusion (LVO) model mimics the clinical trend observed in patients where the brain infarct follows either a slow or fast progression. The dog LVO model can be used in the design of new therapeutics to improve clinical outcome in patients. This study examined the effect of an oxygen carrier in its ability to slow infarct growth in the dog LVO model. In fast evolvers, the oxygen carrier therapy prolonged infarct progression and reduced the final normalized infarct volume. Delaying infarct progression can potentially extend the time-window for thrombectomy enabling more patients to receive this critical treatment.

Dimitra Flouri^1,2, Jack RT Darby³, Stacey L Holman³, Sunthara R Perumal⁴, Anna L David^5,6, Janna L Morrison³, and Andrew Melbourne^1,2
1School of Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom, ²Department of Medical Physics & Biomedical Engineering, University College London, London, United Kingdom, ³Early Origins of Adult Health Research Group, University of South Australia, Adelaide, Australia, ⁴Preclinical Imaging and Research Laboratories, South Australian Health and Medical Research Institute, Adelaide, Australia, ⁵Institute for Women's Health, University College London, London, United Kingdom, ⁶NIHR University College London Hospitals Biomedical Research Center, London, United Kingdom

Abnormalities of placental development and function result in fetal growth restriction. There is growing interest in understanding placenta structure and function throughout pregnancy to gain better understanding of placenta dysfunction. Advances in technology enables derivation of quantitative indices that reflect tissue microcapillary perfusion and tissue diffusivity from MRI.  Despite recent progress, in-vivo diffusion-weighted MRI remains challenging due to long scan times, respiratory motion and low signal-to-noise ratio. Sheep provide a relevant large-scale model for invasive validation studies for MRI measurements. We aimed to improve parameter mapping using Bayesian inference. Bayesian analysis yields improved parameter maps relative to conventional least-squares fitting.

Qingjia Bao¹, Ricardo Martinho ¹, and Lucio Frydman^1
1Weizmann Institute of Science, Rehovot, Israel

   A challenge in functional, diffusivity and spectroscopic MRI studies of mouse body regions is B0 inhomogeneity, especially at ultrahigh fields. To map and correct these DB0s, phase difference images are usually acquired using gradient echo sequences. These, however, are hard to obtain with good quality in abdominal studies due to motion artifacts. In this study we report a fully automated 3D map-based shimming method based on an ultrafast sequence that can overcome these artifacts, delivering optimal B0 homogeneity over the targeted ROIs. This technique is exemplified with mice studies at 15.2T, where its usefulness and reproducibility is demonstrated.

xiaoyu jiang¹, junzhong xu¹, sean p. devan¹, and john c. gore^1
1Vanderbilt University Institute of Imaging Science, nashville, TN, United States

The diffusion time (t_diff) dependence of diffusion MRI signals provides a means to characterize tissue microstructure at cellular levels. Several studies have reported the diffusion time dependence of diffusion signals from rodent brains in health and disease, as well as human brains. Here, we apply IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion), a temporal diffusion spectroscopy-based method that we have described previously, to map the mean restriction size for water diffusion in gray matter of the rat brain in vivo by fitting the t_diff dependence of diffusion signals to a simple biophysical model.