Abstract
Magnetic resonance diffusion tensor imaging (DTI) has revealed the disruption of brain white matter microstructure in normal aging and alcoholism undetectable with conventional structural MR imaging. The metrics of DTI can be useful in establishing the nature of the observed microstructural aberrations. Abnormally low fractional anisotropy (FA), a measure of diffusion orientation and coherence, may result from increased intracellular or extracellular fluid, which would be reflected in complementary high apparent diffusion coefficients (bulk mean diffusivity) and low FA, or from disorganization of fiber structure, which would be reflected in low FA but with a lack of the inverse FA and diffusivity relationship. To test these competing possibilities, we examined 15 alcoholic men and 31 control men with DTI to quantify diffusivity in the genu and splenium of the corpus callosum and centrum semiovale. In addition to the previously observed FA deficits in all the three brain regions, the alcoholics had abnormally high white matter diffusivity values in the genu and centrum. Further, inverse correlations between FA and diffusivity were significant in the genu (r=−0.52, p<0.05) and centrum (r=−0.92, p=0.0001). Multiple regression analyses examining diffusivity and age as predictors of FA identified diffusivity as a significant unique contributor to FA in both regions. These results suggest that decreased orientational coherence of brain white matter in alcoholism is attributable, at least in part, to the accumulation of intracellular and extracellular fluid in excess of that occurring in aging, and that the differential influence of these fluid compartments can vary across brain regions.
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References
Agartz I, Brag S, Franck J, Hammarberg A, Okugawa G, Svinhufvud K et al (2003). MR volumetry during acute alcohol withdrawal and abstinence: a descriptive study. Alcohol Alcoholism 38: 71–78.
Alexander A, Hasan K, Kindlmann G, Parker D, Tsuruda J (2000). A geometric analysis of diffusion tensor measurements of the human brain. Magn Reson Med 44: 283–291.
Alling C, Bostrom K (1980). Demyelination of the mamillary bodies in alcoholism. A combined morphological and biochemical study. Acta Neuropathol (Berl) 50: 77–80.
Badsberg-Jensen G, Pakkenberg B (1993). Do alcoholics drink their neurons away? Lancet 342: 1201–1204.
Basser PJ, Jones DK (2002). Diffusion-tensor MRI: theory, experimental design and data analysis—a technical review. NMR Biomed 15: 456–467.
Bykowski JL, Latour LL, Warach S (2004). More accurate identification of reversible ischemic injury in human stroke by cerebrospinal fluid suppressed diffusion-weighted imaging. Stroke 35: 1100–1106.
de Crespigny A, Moseley M (1998). Eddy current induced image warping in diffusion weighted EPI (abs). Proceedings of the ISMRM, Sydney, NSW, Australia. p 661.
De la Monte SM (1988). Disproportionate atrophy of cerebral white matter in chronic alcoholics. Arch Neurol 45: 990–992.
De Rosa E, Desmond JE, Anderson AK, Pfefferbaum A, Sullivan EV (2004). The human basal forebrain integrates the new and the old. Neuron 41: 825–837.
Estruch R, Nicolas JM, Salamero M, Aragon C, Sacanella E, Fernandez-Sola J et al (1997). Atrophy of the corpus callosum in chronic alcoholism. J Neurol Sci 146: 145–151.
Fein G, Bachman L, Fisher S, Davenport L (1990). Cognitive impairments in abstinent alcoholics. Western J Med 152: 531–537.
Gass A, Birtsch G, Olster M, Schwartz A, Hennerici MG (1998). Marchiafava–Bignami disease: reversibility of neuroimaging abnormality. J Comput Assist Tomogr 22: 503–504.
Harper C, Kril J (1991). If you drink your brain will shrink. Neuropathological considerations. Alcohol Alcoholism 1 (Suppl 1): 375–380.
Harper CG, Kril JJ, Daly JM (1987). Are we drinking our neurones away? Br Med J 294: 534–536.
Harper CG, Kril JJ (1993). Neuropathological changes in alcoholics. In: Hunt WA and Nixon SJ (eds). Alcohol Induced Brain Damage: NIAAA Research Monograph No. 22. National Institute of Health: Rockville, MD, USA. pp 39–69.
Hommer D, Momenan R, Rawlings R, Ragan P, Williams W, Rio D et al (1996). Decreased corpus callosum size among alcoholic women. Arch Neurol 53: 359–363.
Hommer DW, Momenan R, Kaiser E, Rawlings RR (2001). Evidence for a gender-related effect of alcoholism on brain volumes. Am J Psychiatry 158: 198–204.
Jernigan TL, Archibald SL, Berhow MT, Sowell ER, Foster DS, Hesselink JR (1991). Cerebral structure on MRI.1. Localization of age-related changes. Biol Psychiatry 29: 55–67.
Kittler J, Illingworth J (1986). Minimum error thresholding. Pattern Recogn 19: 41–47.
Kubicki M, Westin C-F, Maier SE, Mamata H, Frumin M, Ersner-Hershfield H et al (2002). Diffusion tensor imaging and its application to neuropsychiatric disorders. Harvard Rev Psychiatry 10: 324–336.
Lancaster FE (1993). Ethanol and white matter damage in the brain. In: Hunt WA and Nixon SJ (eds). Alcohol-Induced Brain Damage: NIAAA Research Monograph No. 22. National Institute of Health: Rockville, MD, USA. pp 387–399.
Langlais PJ, Zhang SX (1997). Cortical and subcortical white matter damage without Wernicke's encephalopathy after recovery from thiamine deficiency in the rat. Alcohol Clin Exp Res 21: 434–443.
Lewohl J, Wang L, Miles M, Zhang L, Dodd P, Harris R (2000). Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcoholism Clin Exp Res 24: 1873–1882.
Lim KO, Helpern JA (2002). Neuropsychiatric applications of DTI—a review. NMR Biomed 15: 587–593.
Lim KO, Pfefferbaum A (1989). Segmentation of MR brain images into cerebrospinal fluid spaces, white and gray matter. J Comput Assist Tomogr 13: 588–593.
Moseley ME, Cohen Y, Kucharczyk J, Mintorovitch J, Asgari HS, Wendland MF et al (1990). Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology 176: 439–445.
Moselhy HF, Georgiou G, Kahn A (2001). Frontal lobe changes in alcoholism: a review of the literature. Alcohol Alcoholism 36: 357–368.
Nelson HE (1982). The National Adult Reading Test (NART). Nelson Publishing Company: Windsor, Canada.
Nixon SJ, Tivis R, Parsons OA (1995). Behavioral dysfunction and cognitive efficiency in male and female alcoholics. Alcoholism Clin Exp Res 19: 577–581.
Nixon SJ (1993). Application of theoretical models to the study of alcohol-induced brain damage. In: Hunt W and Nixon SJ (eds). Alcohol Induced Brain Damage, NIAAA Monograph. National Institute of Health: Rockville, MD, USA. pp 213–228.
Norris DG, Niendorf T, Leibfritz D (1994). Healthy and infarcted brain tissues studied at short diffusion times: the origins of apparent restriction and the reudction in apparent diffusion coefficient. NMR Biomed 7: 304–310.
O'Neill J, Cardenas VA, Meyerhoff DJ (2001). Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse. Alcoholism Clin Exp Res 25: 1673–1682.
Oscar-Berman M (2000). Neuropsychological vulnerabilities in chronic alcoholism. In: Noronha A, Eckardt M and Warren K (eds). Review of NIAAA's Neuroscience and Behavioral Research Portfolio. NIAAA Research Monograph No. 34. Bethesda, MD, USA. pp 437–472.
Otsu N (1979). A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybernet 9: 63–66.
Paula-Barbosa MM, Tavares MA (1985). Long term alcohol consumption induces microtubular changes in the adult rat cerebellar cortex. Brain Res 339: 195–199.
Pentney RJ (1991). Remodeling of neuronal dendritic networks with aging and alcohol. Alcohol Alcoholism 1 (Suppl 1): 393–397.
Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO (1999a). In vivo spectroscopic quantification of the N-acetyl moiety, creatine and choline from large volumes of gray and white matter: effects of normal aging. Magn Reson Med 41: 276–284.
Pfefferbaum A, Lim KO, Desmond J, Sullivan EV (1996). Thinning of the corpus callosum in older alcoholic men: a magnetic resonance imaging study. Alcoholism Clin Exp Res 20: 752–757.
Pfefferbaum A, Lim KO, Zipursky RB, Mathalon DH, Lane B, Ha CN et al (1992). Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. Alcoholism Clin Exp Res 16: 1078–1089.
Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO (1994). A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 51: 874–887.
Pfefferbaum A, Sullivan EV, Adalsteinsson E, Garrick T, Harper C (2004). Postmortem MR imaging of formalin-fixed human brain. NeuroImage 21: 1585–1595.
Pfefferbaum A, Sullivan EV, Hedehus M, Adalsteinsson E, Lim KO, Moseley M (2000a). In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism. Alcoholism Clin Exp Res 24: 1214–1221.
Pfefferbaum A, Sullivan EV, Hedehus M, Lim KO, Adalsteinsson E, Moseley M (2000b). Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magn Reson Med 44: 259–268.
Pfefferbaum A, Sullivan EV, Hedehus M, Moseley M, Lim KO (1999b). Brain gray and white matter transverse relaxation time in schizophrenia. Schizophr Res Neuroimaging Sect 91: 93–100.
Pfefferbaum A, Sullivan EV, Mathalon DH, Shear PK, Rosenbloom MJ, Lim KO (1995). Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcoholism Clin Exp Res 19: 1177–1191.
Pfefferbaum A, Sullivan EV (2003). Increased brain white matter diffusivity in normal adult aging: relationship to anisotropy and partial voluming. Magn Reson Med 49: 953–961.
Pfefferbaum A, Sullivan EV (2002). Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism. Neuroimage 15: 708–718.
Pierpaoli C, Barnett A, Pajevic S, Chen R, Penix L, Virta A et al (2001). Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. NeuroImage 13: 1174–1185.
Pratt OE, Rooprai HK, Shaw GK, Thomson AD (1990). The genesis of alcoholic brain tissue injury. Alcohol Alcoholism 25: 217–230.
Putzke J, De Beun R, Schreiber R, De Vry J, Tolle T, Zieglgansberger W et al (1998). Long-term alcohol self-administration and alcohol withdrawal differentially modulate microtubule-associated protein 2 (MAP2) gene expression in the rat brain. Brain Res Mol Brain Res 62: 196–205.
Rickert CH, Karger B, Varchmin-Schultheiss K, Brinkmann B, Paulus W (2001). Neglect-associated fatal Marchiafava–Bignami disease in a non-alcoholic woman. Int J Legal Med 115: 90–93.
Ringer TM, Neumann-Haefelin T, Sobel RA, Moseley ME, Yenari MA (2001). Reversal of early diffusion-weighted magnetic resonance imaging abnormalities does not necessarily reflect tissue salvage in experimental cerebral ischemia. Stroke 32: 2362–2369.
Rosenbloom MJ, Sullivan EV, Pfefferbaum A (2003). Use of MRI to determine brain damage in alcoholics. Alcohol Res Health 27: 146–152.
Rumpel H, Ferrini B, Martin E (1998). Lasting cytotoxic edema as an indicator of irreversible brain damage: a case of neonatal stroke. Am J Neuroradiol 19: 1636–1638.
Sehy JV, Ackerman JJ, Neil JJ (2002). Evidence that both fast and slow water ADC components arise from intracellular space. Magn Reson Med 48: 765–770.
Shear PK, Jernigan TL, Butters N (1994). Volumetric magnetic resonance imaging quantification of longitudinal brain changes in abstinent alcoholics. Alcoholism Clin Exp Res 18: 172–176.
Silva MD, Omae T, Helme rKG, Li F, Fisher M, Sotak CH (2002). Separating changes in the intra- and extracellular water apparent diffusion coefficient following focal cerebral ischemia in the rat brain. Magn Reson Med 48: 826–837.
Skinner HA, Sheu WJ (1982). Reliability of alcohol use indices: the lifetime drinking history and the MAST. J Studies Alcohol 43: 1157–1170.
Skinner HA (1982). Development and Validation of a Lifetime Alcohol Consumption Assessment Procedure. Addiction Research Foundation: Toronto, Canada.
Sullivan EV, Adalsteinsson E, Hedehus M, Ju C, Moseley M, Lim KO et al (2001). Equivalent disruption of regional white matter microstructure in aging healthy men and women. Neuroreport 12: 99–104.
Sullivan EV, Pfefferbaum A (2003). Diffusion tensor imaging in normal aging and neuropsychiatric disorders. Eur J Radiol 45: 244–255.
Sullivan EV, Shear PK, Zipursky RB, Sagar HJ, Pfefferbaum A (1994). A deficit profile of executive, memory, and motor functions in schizophrenia. Biol Psychiatry 36: 641–653.
Sullivan EV (2003). Compromised pontocerebellar and cerebellothalamocortical systems: speculations on their contributions to cognitive and motor impairment in nonamnesic alcoholism. Alcoholism Clin Exp Res 27: 1409–1419.
Sullivan EV (2000). Human brain vulnerability to alcoholism: evidence from neuroimaging studies. In: Noronha A, Eckardt M and Warren K (eds). Review of NIAAA's Neuroscience and Behavioral Research Portfolio, NIAAA Research Monograph No. 34. National Institutes of Health: Bethesda, MD, USA. pp 473–508.
Symonds LL, Archibald SL, Grant I, Zisook S, Jernigan TL (1999). Does an increase in sulcal or ventricular fluid predict where brain tissue is lost? J Neuroimaging 9: 201–209.
Tarnowska-Dziduszko E, Bertrand E, Szpak G (1995). Morphological changes in the corpus callosum in chronic alcoholism. Folia Neuropathol 33: 25–29.
Victor M, Adams RD, Collins GH (1989). The Wernicke–Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition, 2nd ed. F.A. Davis Co.: Philadelphia.
Wechsler D (1987). Wechsler Memory Scale—Revised. The Psychological Corporation: San Antonio, TX.
Westin CF, Maier SE, Mamata H, Nabavi A, Jolesz FA, Kikinis R (2002). Procesing and visualization for diffusion tensor MRI. Med Image Anal 6: 93–108.
Woods R, Grafton S, Holmes C, Cherry S, Mazziotta J (1998). Automated image registration: I. General methods and intrasubject, intramodality validation. J Comput Assist Tomogr 22: 139–152.
Woods RP, Cherry SR, Mazziotta JC (1992). Rapid automated algorithm for aligning and reslicing PET images. J Comput Assist Tomogr 16: 620–633.
Acknowledgements
A partial report of these data was presented at the Research Society on Alcoholism, Fort Lauderdale, FL, 19–26 June 2003. We would like to thank Elfar Adalsteinsson, PhD for assistance with the three phase analysis, Barton Lane, MD for clinical readings of structural MRI, Anjali Deshmukh, MD and Anne O'Reilly, PhD for subject clinical evaluation, and Catherine Ju, BA, for subject scheduling and scanning. This research was supported by AA12388, AA05965, AA10723, and AA12999.
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Pfefferbaum, A., Sullivan, E. Disruption of Brain White Matter Microstructure by Excessive Intracellular and Extracellular Fluid in Alcoholism: Evidence from Diffusion Tensor Imaging. Neuropsychopharmacol 30, 423–432 (2005). https://doi.org/10.1038/sj.npp.1300623
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