High-resolution magnetic resonance microscopy and diffusion tensor imaging to assess brain structural abnormalities

Manoj Kumar1, Ilya M Nasrallah, Sungheon Kim

  • 1From the Departments of Radiology (MK, IMN, RI, SP, HP), Neurology (JL), and Pediatrics (JHW), Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania (MKP, JHW); Department of Radiology, New York University School of Medicine, New York, New York (SK); and Research Institute of the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (MKP, JHW).

Insights

High-resolution microscopic magnetic resonance imaging (μMRI) and diffusion tensor imaging (DTI) reveal brain abnormalities in mucopolysaccharidosis type VII (MPS VII) mice. These advanced imaging techniques offer quantitative assessment of brain pathology in disease models.

Area of Science:

  • Neuroimaging
  • Biomedical Engineering
  • Genetics

Background:

  • Mucopolysaccharidosis type VII (MPS VII) is a rare genetic disorder causing lysosomal enzyme deficiency.
  • Brain structural abnormalities are a known complication of MPS VII, impacting neurological function.
  • Accurate characterization of these abnormalities is crucial for understanding disease progression and developing therapies.

Purpose of the Study:

  • To utilize high-resolution microscopic magnetic resonance imaging (μMRI) and diffusion tensor imaging (DTI) to characterize brain structural changes in a mouse model of MPS VII.
  • To quantitatively assess white matter and gray matter integrity using advanced neuroimaging techniques.
  • To correlate imaging findings with histological evidence of neuropathology.

Main Methods:

  • High-resolution microscopic magnetic resonance imaging (μMRI) was performed on MPS VII and wild-type mice.
  • Diffusion tensor imaging (DTI) was conducted both in vivo and ex vivo to analyze diffusion indices in brain tissues.
  • Histological analyses including hematoxylin and eosin, Luxol fast blue, toluidine blue staining, and electron microscopy were used for morphological and myelin assessment.

Main Results:

  • μMRI revealed decreased anterior commissure and corpus callosum volumes and increased hippocampal volume in MPS VII mice.
  • DTI demonstrated significantly reduced fractional anisotropy in multiple brain regions, including the anterior commissure, corpus callosum, external capsule, and hippocampus.
  • Histology confirmed myelin abnormalities and corresponding morphologic differences in MPS VII mouse brains.

Conclusions:

  • High-resolution μMRI and DTI are effective tools for quantitatively assessing brain structural abnormalities in MPS VII mouse models.
  • These imaging modalities can detect white matter and gray matter pathology, providing insights into the neuropathology of MPS VII.
  • The findings highlight the potential of advanced neuroimaging for evaluating brain diseases in preclinical research.

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