Margaret Caroline Stapleton ¹, John Richard Chaillet ², Eric Goetzman³, Devin R. E. Cortes⁴, Kristina Elsa Schwab¹, Amanda Sferruzzi-Perri ⁵, Michal Neeman⁶, Anthony Christodoulou ⁷, and Yijen L Wu^1
1Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States, ²Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States, ³Pediatrics, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Biomedical Engineering, University of Pittsburgh, Pittsburgh, PA, United States, ⁵Physiology, University of Cambridge, Cambridge, United Kingdom, ⁶Biological Regulation, Weizmann Institute, Rehovot, Israel, ⁷Cedars Sinai Medical Center, Los Angeles, CA, United States

Peri-conceptional alcohol (PCA) exposure leading to fetal alcohol spectrum disorder continues to a significant public health concern because alcohol use ceases only after recognition of pregnancy weeks after conception, but the teratogenic damages have already occurred. Our study showed that PCA exposure in mice resulted in compromised placental perfusion and placental capability to adapt to acute hypoxia challenges. Placental abnormalities due to PCA may further exacerbate fetal neurodevelopmental deficits.

Fatimah Al Darwish¹, Bram Coolen¹, Fieke Terstappen², Caren van Kammen², Lindy Alles¹, Raymond Schiffelers², Titia lely², and Gustav Strijkers^1
1Biomedical engineering and physics, Amsterdam University Medical Center, Amsterdam, Netherlands, ²University Medical Center Utrecht, Utrech, Netherlands

Developing preclinical imaging techniques in the field of preeclampsia is essential to test the effectiveness of new therapeutic approaches. We applied T2* weighted and three-dimensional dynamic contrast-enhanced MRI in a pregnant rat model of reduced uterine perfusion pressure (RUPP) to test their feasibility and ability to detect differences in placental oxygenation and perfusion in RUPP rats compared to control. These techniques produced high-quality data that enabled the assessment of oxygenation and perfusion parameters. Oxygenation was decreased in RUPP placenta; however, perfusion parameters did not reveal differences, which requires further investigations.

Natalie Serkova¹, Julia E Slack², Jenna L Steiner³, Anna De Schutter³, Aaya AlKassi³, Jamie Henry⁴, and Mark S Brown^3
1Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States, ²Emory University, Atlanta, GA, United States, ³University of Colorado Anschutz Medical Campus, Aurora, CO, United States, ⁴Colorado State University, Fort Collins, CO, United States

We report on a multi-modal quantitative MRI/ CT imaging protocol for characterizing the comprehensive body composition and bone health in a genetically modified mouse model. Follicle stimulating hormone (FSH) is directly involved in the regulation of estrogen production, osteoclasto-genesis, and adiposity. In this study we show that the deletion of FSH gene (-/-) in the mouse results in increased adiposity and decreased tibia density in male and female mice as they age. Multi-parametric imaging provides a unique opportunity to quantify visceral adiposity levels, muscle mass, and bone density in mutant animals, non-invasively and in real time.

Xiaodong Zhang¹ and Chun-Xia Li^1
1Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States

Therapeutic hypothermia can improve neurological recovery and reduce mortality in acute stroke. Pharmacologically-induced hypothermia (PIH) has been investigated in preclinical and clinical studies. Usually the core temperature (rectal or esophageal) is measured to monitor the temperature changes of the subject during the treatment. However, it remains unknown how the brain temperature is affected by PIH as the brain temperature can be different from the core temperature and affected by the anesthesia. In the present study, the brain temperature changes of adult rhesus monkeys maintained under isoflurane for over 3 hours were examined and evaluated using diffusion MRI. 

Viktoria Ehret¹, Usevalad Ustsinau², Joachim Friske³, Thomas Scherer¹, Clemens Fürnsinn¹, Thomas Helbich³, Cécile Philippe², and Martin Krššák^1
1Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna, Vienna, Austria, ²Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria, ³Division of Molecular and Structural Preclinical Imaging, Department of Biomedical Imaging and Image-Guided Therapy, Medical University Vienna, Vienna, Austria

Deuterium Metabolic Imaging (DMI) is a novel method to assess metabolism in vivo using ²H MR Spectroscopic Imaging (MRSI) combined with the administration of deuterated substrates. In this pilot study, we applied 2D DMI following an intravenous injection of deuterated glucose and palmitic acid to evaluate the differences in liver metabolism of rats on standard and high fat diet at 9.4T. The spectra show a lower uptake of glucose and a higher uptake of palmitic acid after injection in high fat diet rats, indicating that liver metabolism is slowed down in rats with fatty livers.

Stephen Sawiak^1,2, Shaun Quah¹, and Angela C Roberts^1
1Translational Neuroimaging Laboratory, PDN, University of Cambridge, Cambridge, United Kingdom, ²Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom

We created high-resolution paediatric templates of the marmoset brain from infancy to puberty, producing maps of anatomical variability at different ages. We show that greatest variability is present in juveniles and corresponds well with regions in a recently described transmodal apex network of higher order association areas in the marmoset (and human) brain. We hypothesise this time-period of high variability may indicate a period of heightened vulnerability to environmental stressors which may be a causal factor in the development of mental health disorders.

Antoine Cherix¹, Mohamed Tachrount¹, and Jason Lerch^1,2
1Wellcome Centre for Integrative Neuroimaging, WIN-FMRIB, NDCN, University of Oxford, Oxford, United Kingdom, ²Mouse Imaging Centre (MICe), Hospital for Sick Children, Toronto, ON, Canada

³¹P-MRS is challenging in small samples as it suffers from long T1s, short T2s and low nucleus sensitivity (γ). Thus, ultra-high field has been generally preferred for investigating the mouse brain. Less is known about its feasibility at lower field strength with more readily available scanners. Here, we assess the applicability of ³¹P-MRS in mouse at 7T to study neuroenergetics by comparing 3D-ISIS, PRESS and sLASER. Then, by performing a test-retest analysis and power calculations we assessed the relevance of our method for potential preclinical studies application.

Fuminori Hyodo¹, Hinako Eto², Tatsuya Naganuma³, Abdelazim Elsayed ELHELALY¹, Masaharu Murata², Yoshifumi Noda¹, Hiroki Kato¹, and Masayuki Matsuo^1
1Gifu University, Gifu, Japan, ²Kyushu University, Fukuoka, Japan, ³Japan REDOX Limited, Fukuoka, Japan

To use the current methods in clinical practice, the development of a prototype in vivo DNP-MRI system for preclinical examinations of large animals is indispensable for clarifying the problems peculiar to the increase in size of the DNP-MRI device. Therefore, we developed a in vivo DNP-MRI (Overhauser MRI) system with a sample bore size of 20 cm and a 16-mT magnetic field using a U-shaped permanent magnet. The in vivo DNP-MRI system developed was used to non-invasively image the redox reaction of a carbamoyl-PROXYL probe in the livers of large rats weighing 800 g and hepatitis-model rats.  

Florian Schmid¹, Georgios Koukos¹, Matt Sooknah¹, Sanam Assili¹, and Johannes Riegler^1
1Calico Life Sciences, South San Francisco, CA, United States

We present an improved MRI acquisition and data processing pipeline to assess disease progression in mouse models of polycystic kidney disease. High-resolution anatomical T₂ weighted images as well as T₂ mapping are used to track changes in kidney volume, cyst burden and tissue composition. We established versatile deep-learning automatic kidney segmentation, trained on a range of kidney disease stages, animal models and image resolutions.

Zhongmiao Wang¹, Yang Ruan¹, Qichan Gao¹, Hongxia Lei¹, Renkuan Zhai¹, Yao Xing¹, Zhongqi Zhang², Jian Xu², and Qi Liu^2
1Wuhan United Imaging Life Science Instrument Co., Ltd., Wuhan, China, ²UIH America, Inc., Houston, TX, United States

The feasibility of cardiac T1 mapping in mouse is demonstrated at 9.4T using Multitasking, an ECG-free and free-breathing technique. High spatial- and temporal-resolution T1 maps of healthy mouse hearts without either respiratory or cardiac triggering were obtained. This technique simplifies experimental setup and opens possibilities of investigating numerous heart disease/transgenic mouse models.

Katrien Vandoorne^1,2, I-Hsiu Lee¹, Jana Grune¹, Shuang Zhang¹, Cameron S. McAlpine¹, Maximilian J. Schloss¹, Ribhu Nayar¹, Gabriel Courties¹, Vanessa Frodermann¹, Gregory Wojtkiewicz¹, Lisa Honold¹, Qi Chen³, Yoshiko Iwamoto¹, Yuan Sun¹, Sebastian Cremer¹, Oriol Iborra-Egea⁴, Christian Munoz-Guijosa⁴, Fei Ji⁵, Bin Zhou⁶, Ralf H. Adams³, Joshua D. Wythe⁷, Juan Hidalgo⁸, Hideto Watanabe⁹, Yookyung Jung¹⁰, Anja van der Laan¹¹, Jan J. Piek¹¹, Youmna Kfoury^12,13, Pauline A. Désogère¹⁴, Claudio Vinegoni¹, Partha Dutta¹⁵, Ruslan I. Sadreyev^5,16, Peter Caravan¹⁴, Antoni Bayes-Genis⁴, Peter Libby¹⁷, David T. Scadden^12,13, Charles P. Lin^1,9, Kamila Naxerova¹, Filip K Swirski¹, Matthias Nahrendorf¹, and David Rohde^1,18
1Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ²Biomedical Engineering, Technion, Israel Institute of Technology, Haifa, Israel, ³Max Planck Institute for Molecular Biomedicine, Muenster, Germany, ⁴Institut del Cor Germans Trias i Pujol, Barcelona, Spain, ⁵Genetics, Harvard Medical School, Boston, MA, United States, ⁶State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academic of Sciences, Shanghai, China, ⁷Cardiovascular Research Institute, Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States, ⁸Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain, ⁹Institute for Molecular Science of Medicine, Aichi Medical University, Aichi, Japan, ¹⁰Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ¹¹Heart Center, Department of Cardiology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Amsterdam, Netherlands, ¹²Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA, United States, ¹³Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, United States, ¹⁴Martinos Center for Biomedical Imaging, Department of Radiolog, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, ¹⁵Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States, ¹⁶Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ¹⁷Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States, ¹⁸Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany

Hematopoietic stem cells at the bone marrow (BM) niche generates excess inflammatory leukocytes harming the heart after a myocardial infarction (MI). Whether MI affects the hematopoietic organ’s microvasculature is unknown. Here intravital microscopy shows that MI triggers endothelial dysfunction, leakage, and angiogenesis in the BM, leading to systemic leukocytosis. These novel findings were imaged by noninvasive PET imaging of integrin αVβ3 activation concomitant with measuring leakiness using dynamic contrast enhanced MRI. Endothelial deletion of Vegf receptor 2 (Vegfr2) curbed emergency hematopoiesis after MI. Our findings establish that MI remodels the vascular BM niche, stimulating hematopoiesis and production of inflammatory leukocytes.

Megdouda BENAMARA^1,2, Asma Bakkali², tania-del-socorro Vergara Gomez^2,3, Camille Raynard², Christophe Vilmen³, Pierre Jomin², Amira Trabelsi^2,3, Djamel Berrahou¹, Marc Dubois¹, Yann Le Fur³, Frank Kober³, David Bendahan³, Emmanuel Bergeret⁴, Matthieu Egels⁴, Stefan Enoch², and Redha Abdeddaim^2
1Multiwave Imaging, Marseille, France, ²Aix Marseille Univ, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France, ³Aix Marseille Univ, CNRS, CRMBM, Marseille, France, ⁴IM2NP - UMR 7334 CNRS, Aix-Marseille University, Marseille, France, Marseille, France

The energy harvesting system was developed for preclinical 4.7 T MRI scanners. The system is composed of a commercial birdcage coil tuned and matched at 200.1 MHz, a harvesting coil and an RF-DC rectifier. The collected energy was used to power a respiratory pressure sensor. The efficiency of the harvesting system was optimized as function of the angular positioning of the harvesting coil in the birdcage. The experiments were carried out with a water phantom and a mouse in vivo. A peak voltage of 1.5V was harvested for 45V input voltage and delivered to a load of 350 Ω.

Laura Maugeri¹, Charles Nicaise², Maria Guidi³, Aleksandar Jankovski⁴, Emil Malucelli⁵, Alejandra Sierra⁶, Ali Abdollahzadeh⁶, Raimo A. Salo⁶, Irene Egidi³, Giuseppe Gigli⁷, Federico Giove³, Alessia Cedola⁸, and Michela Fratini^8
1CNR -Institute of Nanotechnology, Lecce Unit & Roma Unit, LECCE, Italy, ²URPhyM – NARILIS, Université de Namur, Namur, Belgium, ³Museo Storico della Fisica e Centro Studi e Ricerche Enrico Fermi, Rome, Italy, ⁴NEUR division, Université catholique de Louvain (UCLouvain), Institute of NeuroScience (IoNS), Brussels, Belgium, ⁵Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy, ⁶A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ⁷CNR -Institute of Nanotechnology, Lecce Unit, LECCE, Italy, ⁸CNR -Institute of Nanotechnology, Roma Unit, Rome, Italy

Many serious pathologies of the central nervous system (CNS) are related to anomalous development or damages to the vascular and neuronal networks. Here, we show our approach based on MRI/XPCT, XPCT/ HISTOLOGY combination in order to study neuronal and vascular alterations following a damage in mouse models.