IN VIVO DIFFUSION AND SPECTROSCOPIC BRAIN IMAGING IN ALCOHOLISM

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aims: Use DTI and conventional MRI to examine the brain of chronic alcoholics through abstinence and/or relapse. Methods: We studied 57 alcoholics (40 m, 17 w) and 74 controls (32 m, 42 w) 3 months post-treatment. 19 alcoholics and 37 controls returned 2 years later. Of the alcoholics, 12 had maintained sobriety for at least one year prior to follow-up and 7 had resumed drinking. A single shot spin-echo echo-planar coronal DTI sequence, combined with fast spin-echo (FSE), SPoiled Gradient Recalled Echo (SPGR), and Fluid Attenuated Inversion Recovery (FLAIR) structural sequences at 1.5T assessed the interaction of aging and alcoholism on microscopic white matter and macroscopic changes. We segmented SPGR data to assess global volumes of cortical and subcortical gray matter, white matter and CSF and measured area of corpus callosum on a midsagittal slice. From the DTI we computed FA and from geometrically defined regions of corpus callosum as well as manually identified fully-volumed, focal 5 mm3 samples. Results: Control men and women both exhibited age-related increases in CSF and decreases in tissue volumes, especially for gray matter. Volumes for controls and alcoholics were statistically adjusted for the variance associated with ICV and age measured in the controls. Alcoholic men and women had gray and white matter volume tissue deficits and CSF enlargement compared with sex-matched controls. Alcoholic men and women showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. This shrinkage was accompanied by abnormalities in FA and more prominent in the genu than the splenium. Older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities. On follow-up, there was a significant increase in for relapsers compared to abstainers in the genu, but not the splenium. Using a nonrigid registration algorithm to compare entry and follow-up scans, we observed modest ventricular expansion in controls, more prominent ventricular and fissure expansion in the relapsers. Abstainers showed either conrol-like ventricular expansion (women) or modest evidence for contraction (men). Conclusions: At baseline after three months abstinence, alcoholism interacted with age to exerted a compounded untoward effect on callosal macrostructure and microstructure with frontal distribution and functional ramifications. Sobriety at follow-up was associated with modest improvements in the condition of white matter microstructure and macrostructure.