Evidence of white matter tract disruption in MRI hyperintensities
Introduction
Hyperintensities are common findings on T2-weighted magnetic resonance imaging (MRI) of the brain. White matter hyperintensities (WMH) are more common in elderly depressed patients than in nondepressed control subjects Coffey et al 1988, Coffey et al 1989, Coffey et al 1990, Coffey et al 1993, Krishnan et al 1988, Salloway et al 1996, and WMH severity predicts poorer responses to antidepressant therapy (Hickie et al 1995). White matter hyperintensities are also associated with increased age (Awad et al 1986b) and vascular risk factors, including cardiac disease, carotid artery disease, hypertension, and diabetes (Fazekas et al 1988). Pathologic studies support the vascular origin of WMH Awad et al 1986a, Awad et al 1986b, but WMH may have other etiologies, including demyelinating diseases.
Diffusion tensor imaging (DTI) is a novel MRI technique that may be useful in the analysis of hyperintensities. DTI uses diffusion-weighted pulse sequences sensitive to microscopic random water motion. It quantifies isotropic diffusion, characterized by unrestrained diffusion properties in all directions, as the apparent diffusion coefficient (ADC). It also quantifies anisotropic diffusion, a directional measurement (Basser et al 1996); as diffusion is constrained by barriers such as cell membranes or fiber tracts, anisotropy measures tissue structure and integrity (Peled et al 1998). Diffusion-weighted imaging is sensitive to ischemic changes (Lansberg et al 2000) and can demonstrate age-related changes in normal tissue (Engelter et al 2000). Lim et al (1999) provide a more thorough review of DTI in an article examining DTI differences in schizophrenia.
We used DTI to compare hyperintensities with normal brain tissue. We hypothesized that if hyperintensities are caused by ischemic changes, they would damage the tissue’s natural structure and exhibit trends similar to ischemic cerebrovascular disease. If hyperintensities do indicate damage to tissue structure, this would result in an increased isotropic diffusion (increased ADC) and decreased constrained diffusion (decreased anisotropy).
Our second hypothesis examined DTI differences of hyperintensities between depressed subjects and nondepressed control subjects. Hyperintensities are common in both groups, and research suggests that their location is the critical factor for the pathogenesis of depression. No evidence suggests a qualitative difference in the hyperintensities themselves. Given this background, we hypothesized there would be no significant difference in the DTI measurements of hyperintensities between the groups.
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Subjects
The subjects were from the Mental Health Clinical Research Center (MHCRC) study at Duke University Medical Center. We studied 14 (8 female) subjects who met DSM-IV criteria for major depression and 19 (10 female) healthy control subjects. The mean age for both groups was 69 years (SD = 1.66 for subjects, 1.43 for control subjects). Control subjects were community volunteers with no evidence of depression or neuropsychiatric illness; they were not initially screened for neuroradiologic
Results
Table 1 shows differences in ADC values. The apparent diffusion coefficient was uniformly higher in hyperintensities than normal tissue (resulting in a negative mean difference) and was most significant in the pooled, posterior parietal, and periventricular WM. Similar trends were also seen in the frontal and anterior parietal hyperintensities, but fewer subjects exhibited WMH in these regions.
Table 2 shows anisotropy differences. Hyperintensities consistently exhibited lower anisotropy than
Discussion
We hypothesized that hyperintensities damage tissue structure and compromise normal barriers to diffusion, leading to increased isotropic diffusion (increased ADC) and decreased directional diffusion (decreased anisotropy). This was demonstrated by the pooled WM data and the regions with larger numbers of subjects exhibiting hyperintensities (the periventricular and posterior parietal WM regions); they exhibited a significantly increased ADC and decreased anisotropy. Similar trends were present
Acknowledgements
This research was supported by NIMH grants P 30 MH40159 and R01 MH54846.
The authors would like to acknowledge the contributions of Ms. Jean Smith, MS, of the Duke University Medical Center Department of Radiology for writing the diffusion tensor eigenvalue program modifications, and Dr. Maj Hedehus of Stanford University for providing the diffusion tensor pulse sequence.
Results presented in part at the 2001 Annual Meeting of the American Association for Geriatric Psychiatry in San Francisco,
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