"A new imaging modality to non-invasively assess multiple sclerosis pathology"

Abstract

We describe a novel imaging method to assess central nervous system pathology called "Diffusion Basis Spectrum Imaging" (DBSI). Diffusion tensor imaging (DTI) has been widely used to estimate axonpathology and demyelination. However, in the settings of acute inflammation and chronic tissue loss asare common in multiple sclerosis, DTI signals can lead to false interpretations. DBSI is a computationallynovel method that separates isotropic from anisotropic components in imaging voxels. Isotropicdiffusion is believed to reflect inflammatory components (cells, edema), as well as intrinsic cells andextracellular space. DBSI enables the measurement of axial and radial diffusivities within the anisotropiccomponents of imaging voxels, which reflect the integrity of axon fibers and myelin, respectively.

Keywords: Diffusion tensor imaging; Inflammation; Multiple sclerosis.

Copyright © 2016 Elsevier B.V. All rights reserved.

Figures

Figure 1. Isotropic and Anisotropic diffusion depicted graphically

A) Free and restricted isotropic diffusion. B) Anisotropic diffusion.

Figure 1. Isotropic and Anisotropic diffusion depicted graphically

A) Free and restricted isotropic diffusion. B) Anisotropic diffusion.

Figure 2. Conceptual comparison between DTI and DBSI

DTI (figuratively depicted at left) is a single averaged tensor, whereas DBSI (depicted at right) uses multiple tensors to describe structural integrity and underlying pathologies in tissues.

Figure 3. DBSI can discern and measure cells of different diameters

A phantom was prepared with mouse lymphocytes (diameter 7μm) and High Five insect cells (diameter 13.5μm) in 2% agarose gel. The cell types were distinguishable based on the smaller cells having lower ADC (left) vs. the larger insect cells with higher ADC (middle). DBSI correctly quantified the proportions of the two cell types. The largest peak in all three panels is the water signal of 2% agarose. ADC on the x-axis has unit of μm2/ms.

Figure 4. DBSI performed on living EAE-affected mice correlates with axon content, myelination and cell count within mouse spinal cords

Representative in vivo DBSI derived (A) axial and (B) radial diffusivity, and (C) cell fraction maps co-registered with immunohistochemical staining for (D) phosphorylated axons using SMI-31, (E) myelin using anti-myelin basic protein antibody, and (F) cell content using DAPI stain with identical ROI co-localized. Modeling of DBSI used in these studies was for white matter, and thus seven regions of interest within white matter were analyzed at four different time points during the course of EAE. The correlation between (G) axial diffusivity and SMI-31 positive axon counts (R=0.87, p<.05 radial diffusivity and mbp positive axon counts p cell fraction dapi of spinal cord l2 level from eae-affected c57bl mice at baseline onset peak chronic states were determined. scale bar="300">2/ms.