Brain Tissue Pulsatility is Increased in Midlife Depression: a Comparative Study Using Ultrasound Tissue Pulsatility Imaging

Abstract

Cerebrovascular disease (CVD) is consistently associated with late-life depression but poorly documented in midlife depression. It can be hypothesized that the relatively low sensitivity of conventional neuroimaging techniques does not allow the detection of subtle CVD in midlife depression. We used tissue pulsatility imaging (TPI), a novel ultrasound (US) neuroimaging technique that has demonstrated good sensitivity to detect changes in the pulsatility of small brain volumes, to identify early and subtle changes in brain vascular function in midlife depression. We compared the maximum and mean brain tissue pulsatility (MaxBTP and MeanBTP), as identified by TPI, between three groups of middle-aged females matched for age: patients with depression (n=25), patients with remitted depression (n=24) and community controls (n=25). MRI arterial spin labeling, white matter hyperintensities (WMHs) and transcranial doppler (TCD) were used as control conventional markers for CVD. We found no difference in the MRI and TCD measures among the three groups. In contrast, depressive patients showed an increased BTP related to the mean global brain pulsatility (MeanBTP) and no change related to large vessels (MaxBTP) in comparison with the remitted and control groups. US neuroimaging is a highly accurate method to detect brain pulsatility changes related to cerebrovascular functioning, and TPI identified an increased BTP in midlife depressed patients, suggesting early and subtle vascular impairments in this population at risk for CVD such as stroke or WMHs. Because high pulsatility could represent prodromal cerebrovascular changes that damage the brain over time, this paper provides a potential target for blocking the progression of CVD.

Figure 1

Comparisons of the TPI measures of MaxBTP (in red—top left: Peak-to-Peak, top right: RMS) and MeanBTP (in blue—bottom left: Peak-to-Peak, bottom right: RMS) among the three groups.

Figure 2

Brain tissue pulsatility (BTP) color maps from three representative subjects of each group and picture of the ultrasound beam of the TPI overlaid on a MRI axial image. We filtered BTP matrixes with a threshold equal to 50% of the MaxBTP of the depressed subject to distinguish between high- and low-amplitude BTP, shown, respectively, at the top and bottom of the figure. We also applied the Horn—Schunck method to estimate the optical flow and displacement speed of each volume in the region of acquisition, the color maps of which show maximum values. Depressed subjects (left) exhibit more distributed high BTP compared with remitted (center) and control (right) subjects, who, in contrast, exhibit very localized high BTP, probably around the main large arteries of the circle of Willis. Low BTP appears to be similarly distributed in each of the three subjects in various small regions, possibly corresponding to small vessels. These maps suggest that high brain pulsatility, normally limited to large vessels in remitted and control subjects, affects the whole brain in depressed patients, consistently with our result of a higher MeanBTP in depressed patients. As shown on the bottom figure, the ultrasound beam of the TPI overlays parts of the temporal lobes (including parts of the hippocampus), the orbitofrontal cortex and the brainstem (midbrain). Hip: hippocampus; MB: midbrain; MCA: middle cerebral artery; OFC: orbitofrontal cortex; TL: temporal lobe.