Ivan Tkac¹, Raghavendra Rao², and Megan Paulsen^2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States

Wild-type and transgenic mice derived from the C57BL/6J mouse strain are widely used in animal models of different human diseases. However, this mouse strain suffers from random appearances of sporadic congenital portosystemic shunts resulting in extremely high glutamine levels in the brain. In our recent study aimed at effects of maternal obesity on their offspring we found that in 9 out of 31 studied C57BL/6J mice had high levels of brain Gln. The purpose of this abstract is to highlight the awareness of this persisting problem in animal models based on C57BL/6J background strain.

Diana Rotaru¹, Steve Sawiak^2,3, Camilla Simmons^1,4, Eugene Kim^1,4, Maria Elisa Serrano Navacerrada^1,4, Davide Di Censo^1,4, Adrien Le Guennec⁵, Richard Edden^6,7, David Lythgoe¹, and Diana Cash^1,4
1Neuroimaging, King's College London, London, United Kingdom, ²Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom, ³Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom, ⁴BRAIN Centre (Biomarker Research And Imaging for Neuroscience), King's College London, London, United Kingdom, ⁵NMR Facility, Wolfson CARD, Guy's Campus, King's College London, London, United Kingdom, ⁶Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Baltimore, MD, United States, ⁷F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

In vivo GABA measurements with conventional (PRESS) and spectral editing methods (MEGAPRESS and HERMES) were investigated in healthy mice at 9.4 T. Animals were divided in two groups, control mice injected with saline and mice injected with Aminooxyacetic acid to intentionally elevate GABA concentration levels (n=7 per group). Our results show all three methods successfully discriminate GABA from overlapping metabolites with stronger signals. The precision of concentration estimates is more reliable for spectral editing methods given their specificity to GABA. These outcomes suggest spectral editing methods are less susceptible to systematic biases.

Aditya Jhajharia¹, Riccardo Serra², Muznabanu Bachani², Jemima Olu-Owotade², Minjie Zhu¹, Joshua Rogers¹, Alexander Ksendzovsky², and Dirk Mayer^1
1Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, ²Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States

In this study, we investigated hyperpolarized (HP) magnetic resonance spectroscopy (MRS) as a means to identify differential lactate release in an in vitro model of epilepsy. When neurons are chronically activated, they increase LDHA expression and upregulate glycolysis as a means of cellular energy metabolism, thus increasing the production of lactate. Using MRS of HP [1-¹³C]pyruvate, we showed conversion to lactate in a chronic model of epilepsy. These results indicate that metabolic imaging of HP [1-¹³C]pyruvate can potentially be used as a tool to identify lactate elevations and thus the epileptic focus in epilepsy patients.

Jeff Brender¹, Shun Kishimoto¹, Jeeva Munasinghe², Helmutt Merkle², Kota Yamashita¹, Yasunori Otowa¹, Kazutoshi Yamamoto¹, and Murali Cherukuri Krishna^1
1Radiation Biology Branch, NCI, Bethesda, MD, United States, ²NINDS, Bethesda, MD, United States

Glycogen synthase kinase 3 (GSK3) has been tied as a critical factor in the development of multiple major diseases from cancer to Alzheimer’s, but drug development has been stymied by a lack of options to detect GSK3 activity in vivo. We show here that GSK3 activity can be measured accurately in vivo by following the production of glycogen from a single bolus of unlabeled glucose on a standard 3T preclinical imaging system. Imaging of glycogen synthesis was possible at 9.4T by CSI, where it was found in mice to be centered on the olfactory bulb, as expected from post-mortem analysis 

Zoona Javed^1,2, Gary Martinez³, AnaPaula Candiota^1,4,5, Miquel Cabanas^2,4, and Silvia Lope^2,4
1Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Bellaterra, Spain, ²Servei de Ressonància Magnètica Nuclear, Universitat Autonoma de Barcelona, Bellaterra, Spain, ³Department of Imaging Physics, University of Texas, Houston, TX, United States, ⁴Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN),, Universitat Autonoma de Barcelona, Bellaterra, Spain, ⁵Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autonoma de Barcelona, Bellaterra, Spain

This work describes an improved multi-voxel Chemical shift imaging (CSI) pulse sequence that uses the semi-LASER localization approach. Bruker CSI sequence containing PRESS localization block (CSI-PRESS) was modified by replacing the aforementioned PRESS block with a semi-LASER one resulting in a CSI-semi-LASER sequence. This work was developed on a 7T Bruker BioSpec 70/30 USR spectrometer running ParaVision 5.1 which does not contain neither built-in blocks for semi-LASER sequence nor adiabatic pulses. The sequence was tested in wt C57/BL6 mouse brain and compared with the stock CSI-PRESS sequence. The results show improved homogeneity and reduction in chemical shift displacement error (CSDE).

Jiyo S Athertya¹, Alecio F Lombardi², Jonathan Wong², Hyungseok Jang¹, Saeed Jerban¹, Jiang Du¹, Koichi Masuda³, Eric Y Chang^1,2, and Ya-Jun Ma^1
1Radiology, University of California San Diego, San Diego, CA, United States, ²Radiology Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, United States, ³Orthopedic Surgery, University of California San Diego, San Diego, CA, United States

Quantitative MR imaging is a powerful tool for assessing biochemical changes in tissue. In this study, we propose to measure the transverse magnetization relaxation time, diffusivity, and magnetization transfer ratio for a whole intervertebral disc (IVD), including the annulus fibrosis, cartilaginous endplate (CEP), and nucleus pulposus, on a 3T pre-clinical scanner. The sequence parameters were optimized for high resolution and high signal-to-noise ratio imaging and mapping, utilizing the high-performance gradient system on the pre-clinical scanner, and the echo times were sufficiently minimized to capture the fast-decaying CEP signals for all the quantitative imaging sequences.

Zakia Gironda¹, Mihály Vöröslakos², Youssef Wadghiri³, Omid Yaghmazadeh⁴, and Leeor Alon^3
1Radiology, NYU School of Medicine, NEW YORK, NY, United States, ²Neuroscience Institute, NYU School of Medicine, New york, NY, United States, ³NYU School of Medicine, New York, NY, United States, ⁴Neuroscience Institute, NYU School of Medicine, NEW YORK, NY, United States

Despite their costly nature, the inexactitude of design in off-the-shelf MRI animal holders translates to a fastidious setup, iso-center misalignment, and incorrect animal body positioning. Our open-source 3D-print design provides precise iso-center alignment and minimizes motion artifact using its various head fixing mechanisms. It ensures comfortable positioning for rats and mice during in-vivo anesthetized and awake animal scan acquisition. The modular holder parts enable the same design to be used with other imaging modalities with minimal intervention. The design is low cost, ensures reproducibility and time efficiency of setup.

Noémie Hamilton¹, Claire Allen², and Steven Reynolds^3
1Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom, ²The Bateson Centre, University of Sheffield, Sheffield, United Kingdom, ³Medical School, University of Sheffield, Sheffield, United Kingdom

Zebrafish have become a ubiquitous animal model for studying a range of diseases and conditions. Typically, these studies are conducted in transparent juvenal fish where optical imaging techniques can be used. However, this is more difficult in adult zebrafish, restricting their use in longitudinal studies. Brain pathology in adult zebrafish can be imaged by preclinical MRI. Administering gadolinium based contrast agents (GBCA), which can also reduce scanning time, can highlight brain abnormalities such as lesions. T1/T2 values have been reported for gadolinium treated fixed/sacrificed zebrafish, however, this has not been reported for live zebrafish.

Chungseok Oh¹, Yu Gyeong Kim^2,3, Jeongheon Park⁴, Youngkyu Song⁴, Chang-Yeop Jeon², Kyung Seob Lim⁵, Jincheol Seo², Jung Bae Seong², Jee-Hyun Cho⁴, Youngjeon Lee², Jongho Lee¹, and Hyeong-Geol Shin^1
1Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of, ²National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Korea, Republic of, ³Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Korea, Republic of, ⁴Center for Research Equipment, Korea Basic Science Institute, Cheongju, Korea, Republic of, ⁵Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Korea, Republic of

Due to the small size of the cynomolgus brain, imaging the fine structures in the brain is a challenging task. In this study, a sample preparation method is suggested for imaging the ex-vivo cynomolgus monkey brain with sub-millimeter resolution in 7T MRI. Using the proposed method, we acquired 150 um isotropic resolution MR images for whole brain, and the fine structures in the cynomolgus monkey brain was observed. 

Cristiana Tisca¹, Mohamed Tachrount¹, Frederik J Lange¹, Amy FD Howard¹, Chaoyue Wang¹, Lily R Qiu¹, Benjamin C Tendler¹, Jason P Lerch^1,2,3, Aurea B Martins-Bach¹, 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, Hospital for Sick Children, Toronto, ON, Canada, ³Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Recent genome-wide association studies using UK Biobank brain imaging datasets showed associations between microstructural MRI measures in white matter and genetic loci of BCAN, a gene encoding a protein implicated in neurodegeneration and synaptic transmission. To investigate these associations, we acquired ex vivo MRI data in a Bcan knockout mouse model. Our results show significant differences in FA and T2* for some tracts in wild-type males compared to homozygous males, with consistent trends of higher FA and MD across WM tracts. Future histology work in the same brains will reveal the biological changes underpinning these differences.

Hedok Lee¹, Burhan Ozturk¹, Michael Stringer², Bradley MacIntosh³, Douglas Rothman⁴, and Helene Benveniste^1
1Anesthesiology, Yale School of Medicine, New Haven, CT, United States, ²Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, ³Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁴Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, United States

In this study choroid plexus tissue perfusion and blood to CSF barrier function in rats were studied using long and short TE continuous arterial spin labeling technique. Non-mono exponential perfusion weighted signal decay in the CP was modelled by a two-compartment perfusion model and we report that partial volume effect is significant and must be considered to derive accurate choroid plexus tissue perfusion measurements.

Naman Jain¹, Saskia Bollmann¹, Jonathan R. Polimeni^2,3,4, Kai-Hsiang Chuang^1,5, and Markus Barth^1,6,7
1Centre for Advanced Imaging, St. Lucia, Australia, ²Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ³Department of Radiology, Harvard Medical School, Boston, MA, United States, ⁴Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States, ⁵Queensland Brain Institute, The University of Queensland, St. Lucia, Australia, ⁶School of Information Technology and Electrical Engineering, St. Lucia, Australia, ⁷ARC Centre for Innovation in Biomedical Imaging and Technology, The University of Queensland, St. lucia, Australia

CBV-based fMRI has been demonstrated to have better spatial specificity than BOLD. CBV estimates based on iron-oxide contrast agents (CA) reflect this microvascular sensitivity, however because of strong extravascular dephasing CBV changes within large vessels are more difficult to detect. Here, we measured functional CBV changes after injecting CA with UTE-MRI and found positive signal changes (+0.5%) predominantly localized at large vessels at a TE of 0.164ms, and negative signal changes (-2%) at a TE of 4ms localized within the tissue. This indicates sensitivity to different vascular compartments at different TEs reflecting the respective T1 and T2* effects of CA.

Shabnam khorasani gerdekoohi¹, Pankaj Sah¹, and Kai-Hsiang Chuang^1
1Queensland Brain Institute, The University of Queensland, Brisbane, Australia

· Evoked BOLD and calcium signals were recorded in the visual pathway using standard (TR=1s) and ultrafast (TR=0.3s) EPI of two TEs.

· Hemodynamic response function was estimated based on neuronal calcium activity. HRF estimated from ultrafast fMRI shows faster kinetics in the lateral geniculate nucleus than the visual cortex.

· BOLD signal was predicted from calcium signal convoluted by HRF. Using ultrafast fMRI significantly improved the accuracy of the predicted BOLD.

Alesa Hughson Netzley¹, Andrew Badachhape², Lauren Wade-Kleyn³, Jie Huang⁴, Kirk Munoz⁵, Aimee Colbath⁵, Avner Meoded², and Galit Pelled^1
1Biomedical Engineering, Michigan State University, East Lansing, MI, United States, ²Radiology, Baylor College of Medicine, Houston, TX, United States, ³Neuroscience, Michigan State University, East Lansing, MI, United States, ⁴Radiology, Michigan State University, East Lansing, MI, United States, ⁵Veterinary Medicine, Michigan State University, East Lansing, MI, United States

The goal of this work is to identify MRI biomarkers of mild traumatic brain injury (mTBI) using a pig model of pediatric concussion. We have found changes in the brain using DTI and fMRI in the days and weeks immediately following injury. We also collected data from a battery of cognitive, emotional, and motor assessments. Together, we anticipate these data will help us to identify biomarkers of injury that will improve diagnostics of children to decrease the risk of post-injury complications.