Quantitative approaches for assessment of white matter hyperintensities in elderly populations

Psychiatry Res. 2011 Aug 30;193(2):101-6. doi: 10.1016/j.pscychresns.2011.03.007. Epub 2011 Jun 16.


White matter hyperintensities (WMH) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI), including fluid attenuated inverse recovery sequences. Total and regional WMH burden (i.e., volume or severity) has been associated with myriad cognitive, neurological, and psychiatric conditions among older adults. In the current report, we illustrate two approaches to quantify periventricular, deep, and total WMH and examine their reliability and criterion validity among 28 elderly patients enrolled in a depression treatment trial. The first approach, an operator-driven quantitative approach, involves visual inspection of individual MRI scans and manual labeling using a three-step series of procedures. The second approach, a fully automated quantitative approach, uses a processing stream that involves image segmentation, voxel intensity thresholding, and seed growing to label WMH and calculate their volume automatically. There was good agreement in WMH quantification between the two approaches (Cronbach's alpha values from 0.835 to 0.968). Further, severity of WMH was significantly associated with worse depression and increased age, and these associations did not differ significantly between the two quantification approaches. We provide evidence for good reliability and criterion validity for two approaches for WMH volume determination. The operator-driven approach may be better suited for smaller studies with highly trained raters, whereas the fully automated quantitative approach may be more appropriate for larger, high-throughput studies.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / drug effects
  • Aging / pathology*
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Brain / drug effects
  • Brain / pathology*
  • Brain Mapping*
  • Depression / drug therapy
  • Depression / pathology
  • Double-Blind Method
  • Electronic Data Processing
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / pathology*
  • Nortriptyline / pharmacology
  • Nortriptyline / therapeutic use
  • Psychiatric Status Rating Scales
  • Sertraline / pharmacology
  • Sertraline / therapeutic use


  • Antidepressive Agents
  • Nortriptyline
  • Sertraline