Non-abstinent recovery in alcohol use disorder is associated with greater regional cortical volumes than heavy drinking.

BACKGROUND: Harm-reduction (i.e., non-abstinent recovery) approaches to substance use treatment have garnered increasing attention. Reduced levels of alcohol consumption post-treatment have been associated with better psychosocial functioning and physical health, yet less is known regarding differences in brain structures associated with varying levels of alcohol consumption. This study investigated regional cortical volumes after alcohol use disorder (AUD) treatment among individuals who achieved complete abstinence and those who returned to lower and higher levels of consumption. METHODS: Data were collected from individuals with AUD (n = 68) approximately 8 months after the initiation of treatment. Using risk drinking levels defined by the World Health Organization, participants were classified as abstaining (AB) or relapsing with low (RL) or higher (RH) levels. Data were also obtained from 34 age-matched light/non-drinking controls (LN). All participants completed a 1.5 T magnetic resonance imaging session and volumes for 34 bilateral cortical regions of interest were quantitated with FreeSurfer. Generalized linear models were used to examine group differences in cortical volume. All group findings are significant at an FDR-corrected value of 0.018. RESULTS: Adjusting for age and intracranial volume, significant group differences were found in 13/34 cortical regions. AB showed greater volumes than RL in 2/13 regions and RH in 6/13 regions. RH demonstrated significantly smaller volumes than LN in 12/13 ROIs, whereas RL differed from LN in 9/13 regions. RH and RL differed in only two cortical regions. CONCLUSIONS: Individuals who consumed low-risk levels of alcohol post-treatment exhibited regional cortical volumes more similar to abstainers than individuals who returned to higher-risk levels. This suggests that low-risk levels of alcohol consumption are associated with brain integrity that is comparable to that seen with complete abstinence. Given the previously demonstrated improvement in psychosocial and physical health with reduced levels of alcohol consumption post-treatment, harm reduction may be a beneficial and more attainable goal for some individuals with AUD who are seeking treatment.

Brain-derived neurotrophic factor genotype is associated with brain gray and white matter tissue volumes recovery in abstinent alcohol-dependent individuals.

Neuroimaging studies have linked the methionine (Met) allele of the brain-derived neurotrophic factor (BDNF) gene to abnormal regional brain volumes in several psychiatric and neurodegenerative diseases. However, no neuroimaging studies assessed the effects of this allele on brain morphology in alcohol use disorders and its demonstrated change during abstinence from alcohol. Here we assessed the effects of the BDNF Val66Met (rs6265) polymorphism on regional brain tissue volumes and their recovery during short-term abstinence in treatment-seeking alcohol-dependent individuals. 3D T1 weighted magnetic resonance images from 62 individuals were acquired at 1.5 T at one week of abstinence from alcohol; 41 of the participants were rescanned at 5 weeks of abstinence. The images were segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid and parcellated into regional volumes. The BDNF genotype was determined from blood samples using the TaqMan technique. Alcohol-dependent Val (Valine)/Met heterozygotes and Val homozygotes had similar regional brain volumes at either time point. However, Val homozygotes had significant GM volume increases, while Val/Met heterozygotes increased predominantly in WM volumes over the scan interval. Longitudinal increases in GM but not WM volumes were related to improvements in neurocognitive measures during abstinence. The findings suggest that functionally significant brain tissue volume recovery during abstinence from alcohol is influenced by BDNF genotype.

Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy.

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV + ) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV- controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P<.05) greater rates of white matter volume loss than HIV- control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

A detailed analysis of localized J-difference GABA editing: theoretical and experimental study at 4 T.

The problem of low signal-to-noise ratio for gamma-aminobutyric acid (GABA) in vivo is exacerbated by inefficient detection schemes and non-optimal experimental parameters. To analyze the mechanisms for GABA signal loss of a MEGA-PRESS J-difference sequence at 4 T, numerical simulations were performed ranging from ideal to realistic experimental implementation, including volume selection and experimental radio frequency (RF) pulse shapes with a macromolecular minimization scheme. The simulations were found to be in good agreement with phantom and in vivo data from human brain. The overall GABA signal intensity for the simulations with realistic conditions for the MEGA-PRESS difference spectrum was calculated to be almost half of the signal simulated under ideal conditions (~43% signal loss). In contrast, creatine was reduced significantly less then GABA (~19% signal loss). The 'four-compartment' distribution due to J-coupling in the PRESS-based localization was one of the most significant sources of GABA signal loss, in addition to imperfect RF profiles for volume selection and editing. An alternative strategy that reduces signal loss due to the four-compartment distribution is suggested. In summary, a detailed analysis of J-difference editing is provided with estimates of the relative amounts of GABA signal losses due to various mechanisms. The numerical simulations presented in this study should facilitate both implementation of the more efficient acquisition and quantification process of J-coupled systems.

Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes.

BACKGROUND: Recent in vivo research using magnetic resonance spectroscopy demonstrated that chronic cigarette smoking exacerbates regional chronic alcohol-induced brain injury. Other studies associated cigarette smoking with gray matter volume reductions in healthy adults, with greater brain atrophy in aging, and with poorer neurocognition. Although cigarette smoking is common among alcohol-dependent individuals, previous research did not account for the potential effects of chronic smoking on regional brain volumes in alcoholism. METHODS: High-resolution T1-weighted magnetic resonance images from one-week-abstinent, alcohol-dependent individuals and light drinkers were automatically segmented into gray matter, white matter, and cerebral spinal fluid of lobes and subcortical structures. A brief neuropsychological test battery was used to assess cognition in alcohol-dependent individuals. The alcoholic and nondrinking groups were retrospectively divided into chronic smokers and nonsmokers, and the volumetric data were analyzed as a function of alcohol and smoking status. RESULTS: Chronic alcohol dependence was associated with smaller volumes of frontal and parietal white matter, parietal and temporal gray matter, and thalami, accompanied by widespread sulcal but not ventricular enlargements. Chronic cigarette smoking was associated with less parietal and temporal gray matter and with more temporal white matter. Among alcoholics, better visuospatial learning and memory and greater visuomotor scanning speed were correlated with larger lobar white matter volumes in the nonsmoking alcohol-dependent group only. CONCLUSIONS: These data provide preliminary evidence that comorbid chronic cigarette smoking accounts for some of the variance associated with cortical gray matter loss and appears to alter relationships between brain structure and cognitive functions in alcohol-dependent individuals.

Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites.

BACKGROUND: The main goals are to investigate the effects of chronic active heavy drinking on N-acetylaspartate (NAA) and other metabolites throughout the brain and to determine whether they are affected by family history (FH) of alcoholism and long-term drinking pattern. METHODS: Forty-six chronic heavy drinkers (HD) and 52 light drinkers (LD) were recruited from the community and compared on measures of regional brain structure using magnetic resonance imaging and measures of common brain metabolites in gray matter (GM) and white matter (WM) of the major lobes, subcortical nuclei, brainstem, and cerebellum using short-echo time magnetic resonance spectroscopic imaging. Regional atrophy-corrected levels of NAA, myoinositol (mI), creatine, and choline-containing metabolites were compared as a function of group, FH of alcoholism, and bingeing. RESULTS: Frontal WM NAA was lower in FH-negative HD than FH-positive HD and tended to be lower in women than men. Creatine-containing metabolites in parietal GM were higher in HD than LD. FH-negative compared with FH-positive HD also had more mI in the brainstem and tended to have lower NAA and more mI in frontal GM. Although parietal GM NAA was not significantly lower in HD than LD, it was lower in non-binge drinkers than bingers. Frontal WM NAA was lower in HD than LD, with the difference driven by a small number of women, FH-negative HD, and older age. Lower frontal WM NAA in HD was associated with lower executive and working memory functions and with lower P3b amplitudes at frontal electrodes. CONCLUSIONS: Community-dwelling HD who are not in alcoholism treatment have brain metabolite changes that are associated with lower brain function and are likely of behavioral significance. Age, FH, and binge drinking modulate brain metabolite abnormalities. Metabolite changes in active HD are less pronounced and present with a different spatial and metabolite pattern than reported in abstinent alcoholics.

Cortical gray matter loss in treatment-naïve alcohol dependent individuals.

BACKGROUND: Most studies of the impact of alcohol dependence on the brain have examined individuals in treatment. Such samples represent a small proportion of alcoholics in the general population. Such samples may embody a bias (Berkson's fallacy) if the association between variables (for example, alcoholism and cortical gray matter loss) differs between the population of alcoholics in treatment and alcoholics in the general population. Our objective was to determine if treatment-naïve alcoholics show structural brain changes versus controls and to compare our findings with reports evaluating alcoholic samples drawn from treatment populations. METHODS: Structural MRI was used to assess whole brain and regional volumes of cortical gray matter and white matter in 24 young to middle-aged treatment-naïve alcohol-dependent males versus 17 controls. RESULTS: Cortical gray matter volumes in alcohol-dependent individuals were negatively associated with age and lifetime duration of alcohol use (which were highly confounded). These subjects showed reduced whole brain (p < 0.05), prefrontal (p < 0.01), and parietal (p < 0.05) cortical gray matter compared with controls. White matter and temporal cortex, tissues that usually show volume reductions in samples drawn from treatment, did not differ between treatment-naïve alcoholics and controls (all p > 0.40). CONCLUSIONS: Our findings are consistent with the hypothesis that structural brain changes in treatment-naïve alcoholics are less severe than those reported in clinical samples of alcoholics, perhaps due to less concomitant psychopathology and a reduced severity of alcoholism in treatment-naïve alcoholics. However, caution must be taken when comparing our findings with results from clinical samples, as we did not directly compare treatment-naïve alcoholics with treated alcoholics and our treatment-naïve sample tended to be younger than the (clinical) samples reported in the literature. Nevertheless, we suggest that most of the reports of the central nervous system consequences of alcoholism may not accurately describe the majority of alcoholic-dependent individuals.

Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse.

BACKGROUND: Structural brain damage, especially to white matter, is well documented in chronic alcohol abuse. There is also evidence for brain metabolic abnormalities in this condition. It is unknown, however, to what extent these structural and metabolic changes are present in treated alcohol abusers who achieve long-term abstinence versus treatment-naïve, heavily drinking individuals. METHODS: This study compared 12 recovering alcoholics with 8 actively heavily drinking subjects. Participants underwent magnetic resonance (MR) imaging and proton MR spectroscopic imaging of the brain. Semiautomated image segmentation techniques yielded volumes for gray matter, white matter, white matter lesions, and cerebral spinal fluid in multiple brain regions defined by Talairach stereotaxic coordinates. Automated spectral processing methods yielded gray and white matter concentrations of the metabolites N-acetylaspartate, creatine, and choline for the same regions. RESULTS: Recovering alcoholics had greater volumes of frontal white matter, but the opposite was true for white matter in a "remainder" region encompassing the basal frontal and temporal lobes, the cerebellum, and the brainstem. Recovering alcoholics also had smaller volumes of white matter lesions in whole brain, in occipital and mesial parietal regions, and in the remainder region. Recovering alcoholics had greater gray matter volumes in the orbital frontal pole and postcentral gyrus, but smaller gray matter volumes in the anterior cingulate. Whole-brain and regional metabolite concentrations did not differ significantly between the two groups. CONCLUSIONS: White and gray matter volumes in different regions of the brain were greater or smaller in recovering, treated alcoholics. The findings suggest region-specific structural recovery from chronic alcohol-induced brain injury, but also region-specific long-term structural damage in abstinent alcoholics. White matter lesions were widespread in active drinkers and may partly resolve during long-term abstinence. Proton MR spectroscopic measures, as applied in this cross-sectional study, were largely ineffective in revealing metabolic effects of abstinence on the alcohol-damaged brain.

Effects of abstinence from alcohol on the broad phospholipid signal in human brain: an in vivo 31P magnetic resonance spectroscopy study.

BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a magnetic field strength of 1.5 T allows measurement of fairly mobile membrane phospholipids in the human brain. We previously showed that subjects who are heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2) of white matter phospholipids than light drinkers, which suggested lower concentrations and molecular mobility of phospholipids in heavy drinkers. The purpose of the present study was to measure if such chronic alcohol-induced white matter tissue changes are persistent in long-term abstinent alcoholics. METHODS: Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were studied by localized 31P MRS in the centrum semiovale and were compared with 13 male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17 men, 6 women) of similar age. Methods for measurements of the broad membrane phospholipid signal and its relaxation time were described previously. RESULTS: Phospholipid concentrations and relaxation times in alcoholics abstinent for an average of 31 months were not significantly different from those measured in light drinkers. The contribution of fast and slowly relaxing signal components to the broad phospholipid signal, however, was still different in abstinent alcoholics compared with light drinkers. No effects of sex or of family history of alcoholism were noted on any of our spectroscopic measures within the light-drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least partial recovery of chronic alcohol-induced white matter phospholipid damage with long-term abstinence. They offer myelination changes and/or dendritic rearborization as a possible mechanism for the commonly observed white matter volume gain with prolonged abstinence. But the results also suggest a persistent abnormality in the nature and/or physical properties of white matter phospholipids in long-term abstinent alcoholics.

Effects of chronic alcohol consumption on the broad phospholipid signal in human brain: an in vivo 31P MRS study.

BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the measurement of phospholipids and their breakdown products in the human brain. Fairly mobile membrane phospholipids give rise to a broad signal that co-resonates with metabolic phosphodiesters. Chronic alcohol exposure increases the rigidity of isolated brain membranes and, thus, may affect the amount and transverse relaxation times (T2) of MRS-detectable phospholipids. We tested the hypothesis that subjects who were heavy drinkers have stiffer membranes than controls who were light drinkers, as reflected in a smaller broad signal component and a shorter T2 of the broad signal in 31P MR spectra of the brain. METHODS: Thirteen alcohol-dependent heavy drinkers (mean age 44 years) were studied by localized 31P MRS in the centrum semiovale and compared with 17 nondependent light drinkers of similar age. The broad component signal was separated from the metabolite signal by convolution difference, which is based on the large difference in line widths of these two signals. Longitudinal and T2 relaxation times were measured using standard methods. RESULTS: The broad component integral was 13% lower in the brain of heavy drinkers compared with light drinkers (p < 0.001) and remained significantly smaller after corrections for both longitudinal and transverse relaxations (p < 0.01). The T2 distribution of the broad component consistently showed two resolvable components in both groups. The fast relaxing component had the same T2 in both groups (T2 = 1.9 msec). The slower relaxing component T2 was 0.6 msec shorter in heavy drinkers compared with light drinkers (p = 0.08). CONCLUSIONS: These results, observed in the absence of white matter volume loss, are consistent with biochemical alterations and higher rigidity of white matter phospholipids associated with long-term chronic alcohol abuse. The observed smaller broad signal component in these relatively young heavy drinkers is a sensitive measure of white matter phospholipid damage.

Effects of alcohol and HIV infection on the central nervous system.

Many people at risk for or infected with the human immunodeficiency virus (HIV) are heavy drinkers. Both HIV infection and heavy alcohol use adversely affect the immune system and central nervous system (CNS) function. However, little research has addressed the effects of heavy alcohol use on the severity and progression of HIV disease, including the development of HIV-associated CNS disease. Animal and in-vitro studies suggest that alcohol impairs various aspects of the immune system and increases the susceptibility to HIV infection, but may not accelerate progression of HIV disease. However, heavy alcohol use may interfere with the patient's adherence to antiretroviral treatment regimens. Neuropathological and neuropsychological studies have indicated that certain brain areas are affected by both HIV-infection and chronic alcohol abuse. Magnetic resonance spectroscopy studies of both HIV-positive and HIV-negative people who were either heavy or light drinkers found that chronic alcohol abuse exacerbates some metabolic injury in the brains of HIV-infected people, although this effect may be less pronounced in patients receiving effective antiretroviral therapy.

Separate and interactive effects of cocaine and alcohol dependence on brain structures and metabolites: quantitative MRI and proton MR spectroscopic imaging.

The effects of chronic cocaine and alcohol abuse on human brain structure and metabolites are not fully known. We studied controls (n = 13) and abstinent subjects dependent on cocaine (8), alcohol (12), and cocaine and alcohol (17) using quantitative MRI and proton MR spectroscopic imaging. Talairach-based techniques yielded tissue and CSF volumes and gray- and white-matter concentrations of N-acetylaspartate (NAA), creatine and choline metabolites in multiple brain regions. Alcohol dependents had lower gray-matter NAA concentrations and more sulcal CSF than non-alcohol dependents throughout the brain. They also had less subcortical gray matter and (regionally) less white matter. Cocaine dependents compared with non-cocaine dependents had higher posterior parietal white-matter creatine concentration. They also had less gray and white matter in the prefrontal lobes and in a region encompassing the temporal lobes and cerebellum. Structural white-matter deficits in cocaine dependents were greater with longer duration of cocaine use. Subjects with concurrent cocaine and alcohol dependence had less prefrontal white matter, especially in the anterior cingulate, than subjects dependent on only one substance. Chronically abused cocaine and alcohol each leave multiple metabolic and structural brain defects after long-term abstinence. Concurrent dependence on both substances may aggravate white-matter structural defects, primarily in frontal brain.

Short TE in vivo (1)H MR spectroscopic imaging at 1.5 T: acquisition and automated spectral analysis.

Spectral analysis of short TE in vivo proton magnetic resonance spectroscopic imaging (MRSI) data are complicated by the presence of spectral overlap, low signal to noise and uncharacterized signal contributions. In this study, it is shown that an automated data analysis method can be used to generate metabolite images from MRSI data obtained from human brain at TE = 25 ms and 1.5 T when optimized pulse sequences and a priori metabolite knowledge are used. The analysis approach made use of computer simulation methods to obtain a priori spectral information of the metabolites of interest and utilized a combination of parametric spectral modeling and non-parametric signal characterization for baseline fitting. This approach was applied to data from optimized PRESS-SI and multi-slice spin-echo SI acquisitions, for which sample spectra and metabolite images are shown.

Ethanol in human brain by magnetic resonance spectroscopy: correlation with blood and breath levels, relaxation, and magnetization transfer.

BACKGROUND: Proton magnetic resonance spectroscopy (1H MRS) allows measurement of alcohol in the human brain after alcohol consumption. However, the quantity of alcohol that can be detected in the brain by 1H MRS pulse sequences has been controversial, with values ranging from about 24% to 94% of the temporally concordant blood alcohol concentrations. The quantitation of brain alcohol is critically affected by the kinetics of alcohol uptake and elimination, by the relaxation times of the protons that give rise to the brain alcohol signal, and by the specifics of both pulse sequence timing and radio frequency pulse applications. METHODS: We investigated these factors in 20 light-drinking subjects after oral administration of approximately 0.85 g/kg body weight of alcohol by localized 1H MRS and measurements of blood and breath alcohol concentrations obtained at the same time. Specifically, we measured transverse and longitudinal relaxation times of brain alcohol and its signal saturation on application of on- or off-resonance radio frequency pulses. All 1H MRS measurements were performed at a time after brain and blood alcohol concentrations had equilibrated. RESULTS: 1H MRS measures of brain alcohol were correlated highly with both breath and blood alcohol concentrations after equilibration in brain tissue. The measured 1H MRS relaxation times of brain alcohol were shorter than given in previous reports that were limited by smaller subject numbers, improper use of 1H MRS methods, and estimates rather than measurements. The brain alcohol signal decreased by about 30% on application of on- or off-resonance saturation pulses. CONCLUSIONS: 1H MRS allows direct measurement of brain alcohol, formerly only possible indirectly through inferences from breath alcohol levels. Quantitation of brain alcohol levels need to take into account measured relaxation times and alcohol signal attenuation due to presence and timing of standard radio frequency MRS pulses. Saturation experiments give evidence for the existence of more than one compartment of brain alcohol characterized by different molecular environments. They suggest that a fraction of brain alcohol is invisible to 1H MRS.

Proton magnetization transfer of metabolites in human brain.

Off-resonance or pulsed on-resonance saturation pulses were used together with localized proton magnetic resonance spectroscopy in three brain regions of 20 healthy individuals. Statistically significant signal attenuations were observed for creatine-containing metabolites in posterior-parietal brain (12%), basal ganglia (18%), and cerebellum (15%). N-acetyl- and choline-containing metabolites were not significantly attenuated upon application of saturation pulses in either brain region. The findings are interpreted to reflect possible magnetization transfer between pools of creatine-containing metabolites with different molecular mobility. Magn Reson Med 42:417-420, 1999.

Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients.

OBJECTIVE: To determine whether the concentrations of the neuronal marker N-acetylaspartate (NAA) and the choline-containing metabolites (Cho) are altered in the subcortical brain of HIV+ patients who are cognitively normal and clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. BACKGROUND: Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with involvement of subcortical and frontostriatal brain systems in HIV disease. Noninvasive proton magnetic resonance spectroscopy (1H MRS) suggests neuronal preservation and macrophage infiltration in the subcortical brain of clinically symptomatic and cognitively impaired HIV+ individuals. Improved 1H MRS methods may allow the early detection of metabolite alterations in the subcortical brain of asymptomatic HIV+ individuals. METHODS: Two-dimensional 1H MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ patients with varying severities of systemic disease and neuropsychological impairments, but without cerebral opportunistic infections. RESULTS: Subcortical Cho was elevated in HIV+ patients compared with control subjects regardless of the presence or absence of cognitive impairment or clinical symptoms. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts. CONCLUSIONS: 1H MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative 1H MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.

Cortical metabolite alterations in abstinent cocaine and cocaine/alcohol-dependent subjects: proton magnetic resonance spectroscopic imaging.

Chronic abuse of cocaine or alcohol is associated with structural, neuropathological and cognitive impairments that have been documented extensively. Little is known, however, about neurobiochemical changes in chronic substance abusers.We performed MRI and multi-slice brain proton magnetic resonance spectroscopic imaging (MRSI) to assess neuronal viability (via N-acetylaspartate (NAA)) and white matter metabolite status in 22 4-months-abstinent individuals dependent on crack cocaine only and on both crack cocaine and alcohol. Compared to 11 non-dependent controls we found (1) significantly lower NAA measures in the dorsolateral prefrontal cortex of the combined cocaine-dependent groups; (2) comparable spatial distribution and magnitude of these NAA effects for both cocaine-dependent groups; (3) higher choline-containing metabolites in frontal white matter of individuals dependent on both cocaine and alcohol; (4) absence of brain atrophy in both abstinent cocaine-dependent samples; and (5) partial recovery from prefrontal cortical NAA loss, primarily with abstinence from alcohol. The MRSI findings suggest preferential neuronal damage to the frontal cortex of both cocaine-dependent samples and gliosis in frontal white matter of individuals dependent on both alcohol and cocaine, conditions that persist for more than 4 months of abstinence.

Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal brain.

PURPOSE: To replicate previous hydrogen-1 magnetic resonance (MR) spectroscopic imaging findings of metabolic abnormalities in patients with Alzheimer disease (AD), to verify that metabolic abnormalities are not an artifact of structural variations measured at MR imaging, to determine whether metabolic changes correlate with dementia severity, and to test whether MR imaging and MR spectroscopic imaging findings together improve ability to differentiate AD. MATERIALS AND METHODS: MR spectroscopic imaging and MR imaging were performed in 28 patients with AD and 22 healthy elderly subjects. Spectroscopic imaging data were coregistered with MR imaging segmentation data to obtain volume-corrected metabolite concentrations. RESULTS: Consistent with previous results, N-acetyl aspartate (NAA) levels were statistically significantly reduced in frontal and posterior mesial cortex of AD patients, presumably due to neuronal loss. NAA level reductions were independent of structural variations measured at MR imaging and, in parietal mesial cortex, were correlated mildly with dementia severity. Spectroscopic imaging findings of NAA level combined with MR imaging measures did not improve discrimination power for AD relative to that of MR imaging alone. CONCLUSION: Reduced NAA levels in frontoparietal brain are of limited use for diagnosis of AD. However, they are not an artifact of structural variations and thus may provide useful information for the understanding of the pathologic processes underlying AD.

1H MRSI of normal appearing white matter in multiple sclerosis.

The primary goal of this study was to determine if differences in proton magnetic resonance spectroscopy signals exist between normal appearing white matter (NAWM) of multiple sclerosis (MS) patients and white matter of control subjects. Water suppressed proton magnetic resonance spectroscopic imaging was used to determine the signal intensities of N-acetylated moieties (NA, predominantly N-acetylaspartate (NAA) the putative neuronal marker), creatine and phosphocreatine (Cr), and cholines (Ch) in 19 MS patients (15 relapsing-remitting and four secondary progressive) and 19 age matched control subjects. NA/Cr was significantly reduced (P < 0.001) in MS NAWM (1.8 +/- 0.2; x +/- s.d.) distant from MRI detected lesion areas compared to white matter of control subjects (2.1 +/- 0.2). This reduction was due to an increase in Cr from 0.39 +/- 0.04 (arbitrary units) in controls to 0.45 +/- 0.05 in MS patients. There was no significant change in NA or Ch in MS NAWM compared to controls. NA/Cr, distant from MRI lesion, was negatively correlated with total brain lesion volume as measured from T2-weighted MRI. We interpret the reduced NA/Cr in MS NAWM to indicate diffuse microscopic disease.

Brain atrophy in HIV infection is more strongly associated with CDC clinical stage than with cognitive impairment.

HIV infection often results in MRI-detectable brain atrophy and white matter signal hyperintensities (WMSHs). Magnetic resonance images were obtained from 31 HIV+ male patients and 10 high-risk controls. Variation within the HIV+ group on neuropsychological (NP) impairment and stage of systemic disease were relatively independent, allowing examination of the relative association of MRI measures with NP impairment versus with systemic stage of disease. HIV+ patients compared to high-risk controls evidenced global atrophy, reduced caudate nuclei volume, and a trend to gray matter volume loss but no difference in white matter volume or in WMSHs. These effects were progressive with CDC clinical stage such that patients at CDC stage A had values very close to those of controls, while patients at CDC stage C had the most abnormal values. In contrast, the relationship between these MRI variables and severity of NP impairment was much less dramatic, with the mildly to moderately impaired HIV+ subjects showing MRI volume effects greater than or equal to those of the severely impaired HIV+ subjects. These results suggest that MRI-detectable brain atrophy secondary to HIV infection is not the primary substrate underlying the progressive NP impairment in HIV disease.