Cell specificity of Manganese-enhanced MRI signal in the cerebellum
Harikrishna Rallapalli,
N. Sumru Bayin,
Hannah Goldman,
Dragan Maric,
Brian J. Nieman,
Alan P. Koretsky,
Alexandra L. Joyner,
Daniel H. Turnbull
Affiliations
Harikrishna Rallapalli
Department of Radiology, NYU Langone Radiology - Center for Biomedical Imaging, New York University School of Medicine, 660 First Avenue, New York, NY 10016, United States; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
N. Sumru Bayin
Developmental Biology Program, Sloan Kettering Institute, New York, NY, United States; Gurdon Institute, University of Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, UK
Hannah Goldman
Department of Radiology, NYU Langone Radiology - Center for Biomedical Imaging, New York University School of Medicine, 660 First Avenue, New York, NY 10016, United States
Dragan Maric
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
Brian J. Nieman
Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Canada; Translational Medicine, The Hospital for Sick Children, Toronto, Canada; Medical Biophysics, University of Toronto, Toronto, Canada; Ontario Institute for Cancer Research, Toronto, Canada
Alan P. Koretsky
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
Alexandra L. Joyner
Developmental Biology Program, Sloan Kettering Institute, New York, NY, United States
Daniel H. Turnbull
Department of Radiology, NYU Langone Radiology - Center for Biomedical Imaging, New York University School of Medicine, 660 First Avenue, New York, NY 10016, United States; Corresponding author.
Magnetic Resonance Imaging (MRI) resolution continues to improve, making it important to understand the cellular basis for different MRI contrast mechanisms. Manganese-enhanced MRI (MEMRI) produces layer-specific contrast throughout the brain enabling in vivo visualization of cellular cytoarchitecture, particularly in the cerebellum. Due to the unique geometry of the cerebellum, especially near the midline, 2D MEMRI images can be acquired from a relatively thick slice by averaging through areas of uniform morphology and cytoarchitecture to produce very high-resolution visualization of sagittal planes. In such images, MEMRI hyperintensity is uniform in thickness throughout the anterior-posterior axis of sagittal sections and is centrally located in the cerebellar cortex. These signal features suggested that the Purkinje cell layer, which houses the cell bodies of the Purkinje cells and the Bergmann glia, is the source of hyperintensity. Despite this circumstantial evidence, the cellular source of MRI contrast has been difficult to define. In this study, we quantified the effects of selective ablation of Purkinje cells or Bergmann glia on cerebellar MEMRI signal to determine whether signal could be assigned to one cell type. We found that the Purkinje cells, not the Bergmann glia, are the primary of source of the enhancement in the Purkinje cell layer. This cell-ablation strategy should be useful for determining the cell specificity of other MRI contrast mechanisms.