Lin Chen^1,2, Peter C.M. van Zijl^1,2, Zhiliang Wei^1,2, Hanzhang Lu^1,2, Wenzhen Duan³, Philip C. Wang^4,5, Tong Li^4,5, and Jiadi Xu^1,2
1Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States, ⁴Department of Pathology, Johns Hopkins University, Baltimore, MD, United States, ⁵Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United States

We demonstrate the feasibility of creatine chemical exchange saturation transfer (CrCEST) MRI in detecting altered pH in Alzheimer’s disease (AD) mouse brain. In two early-stage AD models, namely Tau and APP mice, CrCEST contrast in the brain was significantly reduced compared to that of WT mice at 6-7 months (P<0.007). From MRS experiments, the brain creatine concentration between WT and AD mice was the same within error, which indicates that the reduced CrCEST contrast in the AD brain can be contributed mainly to pH reduction. Immunohistochemical analysis showed neuroinflammation in the APP mice, a potential factor for causing pH reduction. 

Jean-Baptiste Perot¹, Marina Célestine¹, Marc Dhenain¹, Sandrine Humbert², Emmanuel Brouillet¹, and Julien Flament^1
1Université Paris-Saclay, Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Molecular Imaging Research Center (MIRCen), Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France, ²Université Grenoble-Alpes, Grenoble Institute of Neurosciences (GIN), INSERM U1216, Grenoble, France

Huntington’s Disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats on the exon 1 of the HTT gene. Although genetic origin of HD is well-established, early and predictive biomarkers of disease onset and progression are still lacking. In the present study, we performed a multiparametric longitudinal MRI study on a mouse model of HD. Our results in gluCEST, Magnetization Transfer, morphometry and Diffusion Tensor Imaging revealed early modifications of white matter followed by progressive functional and anatomical changes in HD mice. Such network seems to point out the central role of white matter in HD pathogenesis.  

Abdullah Althobity^1,2, Nemat Khan³, Trent Woodruff³, Gary Cowin^1,4, Ian Brereton^1,4, and Nyoman Kurniawan^1
1Centre for Advanced imaging, University of Queensland, Brisbane, Australia, ²Ministry of Education, Riyadh, Saudi Arabia, ³Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, Australia, ⁴National Imaging Facility, Brisbane, Australia

Multiple sclerosis (MS) is an autoimmune disease with uncertain aetiology. In this work, we used two genetically modified mice, each derived by gene ablation to complement protein C5aR1 and C5L2 receptors, designed to investigate their roles in mediating the disease model experimental autoimmune encephalomyelitis (EAE). MR spectroscopy and DTI were measured using a 9.4T MRI with cryoprobe at the level of lumbar spinal cord. Changes in metabolites and DTI parameters indicate that the ablation of C5L2, to a greater extent than the ablation of C5aR1, made these mice less susceptible to EAE induced neuronal damage compared to wild-type mice.
 

Seong-Eun Kim¹, J Scott McNally¹, Matthew Alexander¹, Dennis L Parker¹, Matthew S Zabriskie ¹, and Ronald Day^2
1UCAIR, Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT, United States, ²Department of Pediatrics, University of Utah, Salt Lake City, UT, United States

After intravenous injection, gadolinium(GBCA), commonly used for MR contrast, distributes from intravascular to the extravascular space and rapidly cleaned by renal excretion. This pharmacologic behavior makes GBCA unfavorable as in blood pool agent. One potential alternative agent is endogenous intracellular methemoglobin (MetHb), a paramagnetic molecule in our blood cells. Intracellular levels of MetHb can be increased by exposing blood to sodium nitrite. We evaluated change of T1 of blood according to a transient increase in intracellular MetHb in in vivo animal model. Our results demonstrated that MetHb modulation resulted T1 shortening of blood and soft tissue enhancement.

Xiongqi Han¹, Jianpan Huang¹, and Kannie Wai Yan Chan^1,2,3
1Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, ²Biomedical Engineering, Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China, ³Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Glioblastoma (GBM) is the most malignant brain tumor with notorious heterogeneous, infiltrative and chemoresistance. Here, we developed a hydrogel-based drug delivery system for sequential and sustainable local drug delivery with rheological properties that favor applications to the brain. We designed methotrexate (MTX) to release prior to gemcitabine (Gem). Using CEST, the multicomponent of hydrogel matrix could be detected at 3 T, including the contrast of loaded drugs (5.4%) at 2.2-2.4 ppm and liposomal hydrogel matrix at -3.6 ppm in vitro. Furthermore, it showed combined cytotoxicity on U87 cells, demonstrating its potential on CEST MRI guided local treatment.

Paul Begovatz¹, Lawrence Lechuga¹, Monica Cho², Mallery Olsen², Rachel McMahon³, David Vail^3,4, and Sean Fain^1,5,6
1Medical Physics, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ²Pediatrics, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ³Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States, ⁴Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, United States, ⁵Radiology, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States, ⁶Biomedical Engineering, Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States

Fluorine magnetic resonance imaging (19F-MRI) has been demonstrated as a non-invasive method to track and quantify immune cells in vivo. However due to the low ¹⁹F spin density of immune cell labeling, these studies have been mostly conducted on ultra-high field MRI systems, or with small sensitive surface coils at clinical field strengths. This feasibility study found that concentrations of perfluoropolyether (PFPE), and phantoms consisting of fewer than one million PFPE labeled NK cells were reliably detected through ¹⁹F-MRI with the combination of a cartesian 3D fast spin echo imaging sequence, and a dual tuned 1H/19F torso coil at 3T.

Nivin N Nyström¹, Hanlin Liu², Francisco Martínez-Santiesteban¹, Xiao-an Zhang², Timothy J Scholl¹, and John A Ronald^1
1Robarts Research Institute, London, ON, Canada, ²University of Toronto, Toronto, ON, Canada

We have developed a manganese(III) porphyrin probe for targeted imaging of cells expressing organic-anion transporting polypeptides. OATP1 targeting and relaxation characteristics were evaluated in vitro in engineered cells, and in vivo and ex vivo in different organs in mice.

Dimitra Flouri^1,2, Jack RT Darby³, Stacey L Holman³, Sunthara R Perumal⁴, Anna L David^5,6, Janna L Morrison³, and Andrew Melbourne^2,7
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, ⁵Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, United Kingdom, ⁶NIHR Biomedical Research Centre, University College London Hospitals, London, United Kingdom, ⁷School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom

MRI techniques are considered to give additional placental information in vivo to support clinical decision-making. Preclinical models such as in pregnant sheep provide an invasive method to validate MRI measurements, as they allow for controlled experiments and analysis during pregnancy. Here we characterised diffusion and perfusion properties of normal sheep placenta such as apparent diffusion coefficient, T2 measurements and fractional anisotropy analysis.  We also presented the first application of multi-compartment MRI model to normal sheep placenta. 

Enrica Wilken¹, Felix Freppon¹, Max Masthoff¹, and Cornelius Faber^1
1Translational Research Imaging Center, Clinic of Radiology, University Hospital Muenster, Muenster, Germany

Repetitive T2*-weighted image acquisition in vivo and contrast simulations were used to show that single iron oxide nanoparticle labeled cells can be resolved and tracked non-invasively by time-lapse MRI. Calculation of the velocity of intravascular moving immune cells in mice brain and velocity-dependent blurring of time-lapse contrast in simulations indicate that cell dynamics slower than 1 µm/s are detectable. Therefore, time-lapse MRI is able to reveal patrolling immune cells as hypointense spots and can be a suitable tool to study inflammatory diseases and the progression of cancer metastasis.

Lydia M. Le Page¹, Jayson Ball², Linda Watkins², and Myriam Chaumeil^1
1Physical Therapy and Rehabilitation Science, Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ²Department of Psychology & Neuroscience & the Center for Neuroscience, University of Colorado, Boulder, CO, United States

Microglia are an essential part of the brain’s immune system. In 2006, Frank et al. described a rapid isolation technique to obtain high-purity quiescent microglia from the rat brain, enabling study of their role in health and disease. Metabolomics via NMR is a robust, data-rich strategy for understanding cell metabolism. Given the central role of microglial metabolic reprogramming in numerous diseases, we investigated whether ultra-high-field ¹H NMR could detect key metabolites in freshly isolated adult microglia. We optimized the isolation and extraction protocols and showed that several key microglia metabolites can be reliably quantified using high-resolution ¹H NMR at 18.8Tesla.