Marked relationship between matrix metalloproteinase 7 and brain atrophy in HIV infection

Abstract

Circulating levels of matrix metalloproteinases (MMP-1 and 7) have been found to correlate with the severity of brain injury in HIV-infected subjects. This study used high-resolution neuroanatomic imaging and automated segmentation algorithms to clarify this relationship. Both metalloproteinases were significantly correlated with increased cerebrospinal fluid volume fraction. Comprehensive brain volumetric analysis revealed a more marked relationship with atrophy for MMP-7, which was significantly correlated with neural injury in multiple brain regions and nearly all ventricular measurements. MMP-7 was also correlated with measures of virologic and cognitive status.

Figure 1

Parenchyma (white) is segmented from CSF (blue) to generate the brain parenchyma volume measure, as shown in a single axial slice. A partial 3D image of the brain is shown to illustrate that the voume is determined across the entire brain.

Figure 2

Proton density and T2 images in original gray scale (left) with segmentation of each tissue class (right) shown in red. Volume fractions are calculated across all slice levels.

Figure 3

A representative FA map shown at the level of the interventricular foramen (left). FA is calculated for each voxel containing brain tissue. Thresholding and manual editing are used to remove voxels containing primarily CSF and skull. For each subject, a histogram of the resulting FA values is generated (right) and summarized as the histogram mean. The same approach was used to generate whole brain MD values.