Oliver Speck

Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study.

Objective: To determine whether proton MRS (1H MRS) can detect long-term metabolite abnormalities in abstinent methamphetamine users. Background: Methamphetamine is toxic to dopaminergic and serotonergic neurons in rodents; however, little data are available on the toxic effects of methamphetamine on the human brain. Methods: 1H MRS was performed in 26 abstinent methamphetamine abusers with a history of methamphetamine dependence (median total cumulative lifetime exposure, 3,640 g; median recency of last methamphetamine use, 4.25 months) and 24 healthy subjects without a history of drug abuse. Cerebral metabolite concentrations on 1H MRS were measured in the frontal cortex, frontal white matter, and basal ganglia. Results: The concentration of N-acetylaspartate ([NA]), a neuronal marker, was reduced significantly (−5 to −6%) in the basal ganglia and frontal white matter of methamphetamine users compared with control subjects. The frontal white matter [NA] correlated inversely with the logarithm of the lifetime methamphetamine use. The methamphetamine users also showed significantly reduced total creatine in the basal ganglia (−8%), and increased choline-containing compounds ([CHO], +13%) and myo-inositol ([MI], +11%) in the frontal grey matter. Conclusions: The reduced [NA] on 1H MRS provides evidence for long-term neuronal damage in abstinent methamphetamine users.

Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia

Objective: To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART). Background: Patients with HIV–cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia. Methods: Sixteen patients with HIV-CMC were evaluated before and after HAART, and compared with 15 HIV-negative healthy volunteers. Cerebral metabolite ratios and concentrations in the frontal lobe and basal ganglia were measured using proton MRS (1H MRS). Results: In 14 of 16 patients who tolerated HAART, CD4 count increased by 133 ± 101 cells/mm3 (p = 0.0003), HIV Dementia Scale score increased by 1.8 ± 2.4 points (p = 0.02), and AIDS dementia complex (ADC) stage decreased by 0.54 ± 0.54 points (p = 0.003). The initially increased choline/creatine (CHO/CR) reversed in the midfrontal cortex (−8.0%; p = 0.02) and in the basal ganglia (−14.7%; p = 0.01). The initially elevated myoinositol (MI)/CR and myoinositol concentration [MI] in the basal ganglia also decreased ( MI/CR: −14.1%; p = 0.005; [MI]: 11.8%; p = 0.02), along with normalization of [MI] in the frontal white matter (11.4%; p = 0.05). Furthermore, the change in [MI] in the frontal white matter correlated with the change in CD4 count (r = −0.67, p = 0.03) and with the change in ADC stage (p = 0.04). Conclusions: HAART improves HIV-CMC in addition to systemic measures of HIV infection. 1H MRS detects improvement of brain injury measured by cerebral metabolites, particularly the glial marker [MI], in patients with early HIV-CMC after HAART. In addition, the degree of improvement in clinical severity of HIV-CMC is related to the degree of recovery with [MI].

Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users

This study aims to determine possible persistent abnormalities in regional cerebral blood flow (relative rCBF) and cognitive function in abstinent methamphetamine (METH) users. Twenty METH-dependent subjects (abstinent for 8+/-2 months) and 20 age- and gender-matched controls were evaluated with perfusion magnetic resonance imaging (pMRI) and neuropsychological tests. METH users showed decreased relative rCBF bilaterally in putamen/insular cortices (right: -12%; left: -10%) and the right lateral parietal brain region (-11%), but increased relative rCBF bilaterally in the left temporoparietal white matter (+13%), the left occipital brain region: (+10%) and the right posterior parietal region (+24%). Interaction effects were observed between METH and gender in the right occipital cortex and a midline brain region; female METH users showed increased relative rCBF (+15% both regions) whereas the male METH users had decreased relative rCBF (-10% and -18%, respectively). METH users performed within normal ranges on standard neuropsychological tests; however, they were slower on several tasks on the California Computerized Assessment Package (CalCAP), especially tasks that required working memory. These findings suggest that METH abuse is associated with persistent physiologic changes in the brain, and these changes are accompanied by slower reaction times on computerized measures of cognitive function.

Neural correlates of attention and working memory deficits in HIV patients

Objectives: To evaluate the neural correlates of attention and working memory deficits in patients with HIV-1. Method: fMRI was used to evaluate brain activity in 11 patients with HIV and 11 age-, sex-, education-, and handedness-matched seronegative subjects, while performing a battery of tasks that required different levels of attention for working memory. Results: Patients with HIV showed greater brain activation (blood oxygenation level dependent signal changes) in some regions compared with control subjects while performing the same tasks. For the simpler tasks, patients with HIV showed greater activation in the parietal regions. However, with more difficult tasks, patients with HIV showed greater activation additionally in the frontal lobes. Reaction times during these tasks were slower but accuracy was similar in the patients with HIV compared with control subjects. Conclusion: Injury to the neural substrate caused by HIV infection may necessitate greater attentional modulation of the neural circuits, hence a greater use of the brain reserve; additional activation of the frontal lobes is required to perform the more complex tasks. The task-dependent increased frontal activation in patients with HIV suggests that the neural correlate of attentional deficits may be excessive attentional modulation as a result of frontostriatal brain injury.

Perfusion MRI of the human brain with dynamic susceptibility contrast: Gradient-echo versus spin-echo techniques†

In this study, spin‐echo and gradient‐echo‐based perfusion magnetic resonance imaging (MRI) techniques are systematically compared with respect to their application in the human brain. Six healthy subjects were evaluated with both techniques consecutively and injected twice with a gadolinium‐based contrast agent. In accordance with theoretical predictions and with previous animal experiments, the spin‐echo‐based technique shows a markedly reduced appearance of large vessels. The intersubject standard deviations of the two methods are similar but smaller for the spin‐echo technique in small regions adjacent to large vessels. Therefore, the sensitivity of the two acquisition methods for evaluating pathologic abnormalities may be similar despite the higher contrast‐to‐noise ratio of the gradient‐echo‐based technique. The gray‐to‐white matter ratio of the regional cerebral blood flow of the spin‐echo method is closer to previous nuclear medicine measurements than that of the gradient‐echo method. Our measurements indicate that spin‐echo‐based perfusion MRI is more representative of capillary perfusion than gradient‐echo measurements. J. Magn. Reson. Imaging 2000;12:381–387.

Cerebral perfusion abnormalities in abstinent cocaine abusers: a perfusion MRI and SPECT study.

Nuclear medicine studies found decreased regional cerebral blood flow (rCBF) in the cortex and deep gray matter of cocaine users. Perfusion magnetic resonance imaging (MRI), a non-radioactive technique, has not been applied to evaluate persistent rCBF abnormalities. Twenty-five abstinent cocaine users and 15 healthy subjects without a history of drug use were examined with perfusion MRI, using dynamic bolus-tracking, and single photon emission computed tomography (SPECT), using 133Xe-calibrated 99mTc-HMPAO. After coregistration of SPECT with MRI, the relative rCBF (from perfusion MRI and SPECT) and absolute rCBF (from SPECT) were determined in 10 brain regions in each hemisphere. There was a statistically significant interaction between drug use and brain region on SPECT alone (relative and absolute rCBF), and on SPECT and perfusion MRI combined, but not on perfusion MRI alone. There also was a significant interaction among gender, drug use, and brain region. Compared to the control subjects, cocaine users showed increased rCBF in the frontal white matter (+8.6%, P=0.02) and in the globus pallidus (+6.3%, P=0.05), and decreased rCBF in the putamen (-3.9%, P=0.04) and the temporal cortex (-2.4%, P=0.02). SPECT and perfusion MRI detect a regional pattern of rCBF abnormalities in cocaine users that is consistent across the two methods. The hypoperfusion in the cortex and deep gray matter of the cocaine users is consistent with previous results. The increased rCBF in the white matter of cocaine users may be due to the presence of reactive glia.

Correlation of regional cerebral blood flow from perfusion MRI and spect in normal subjects.

The objective of this study was to determine the relationship in regional cerebral blood flow (rCBF) as measured with perfusion magnetic resonance imaging (pMRI) and single photon emission computer tomography (SPECT). rCBF was determined in 26 healthy subjects with pMRI and SPECT. After co-registration of pMRI with SPECT, rCBF was determined in 10 brain regions relative to the whole slice value. pMRI was evaluated with and without elimination of large vessels. rCBF from pMRI correlates significantly with rCBF from SPECT (r = 0.69 with and r = 0.59 without elimination of large vessels; p < 0.0001 for both). Elimination of large vessels reduced the interindividual variance of the pMRI measurements in most regions. rCBF from pMRI shows good correlation with rCBF from SPECT. Because pMRI is sensitive to flow in large vessels while SPECT is not, elimination of large vessels in pMRI reduces the interindividual variability of pMRI and improves the-correlation between the two methods. pMRI is a reliable noninvasive method for rCBF measurements.

Simultaneous correction for interscan patient motion and geometric distortions in echoplanar imaging.

A method is presented for simultaneous correction of linear geometric distortions and interscan patient motion in echoplanar imaging (EPI). The technique does not require the acquisition of specialized scans other than high‐resolution magnetic resonance images. The method is based on a generalized surface‐based coregistration algorithm, which accounts for a complete 3‐dimensional affine transformation, i.e., rotations, translations, scaling, and shearing, between two volumetric image data sets. Any minimally distorted high‐resolution scan may serve as a reference data set, to which the EPI data set is matched. The algorithmic accuracy was assessed using simulated data sets with known affine distortions. The deviation of the parameters determined by the coregistration program from the true values typically was 1% or less. Precise alignment of functional and anatomic information will be important for many future clinical applications. Magn Reson Med 42:201–205, 1999.

Biexponential modeling of multigradient-echo MRI data of the brain.

Functional MRI (fMRI) using fast multigradient‐echo acquisition methods allows the quantitative determination of the relevant parameter T u2009*2 . Previously, the TE‐dependent signal decay has been modeled with a monoexponential function despite the complex composition of the brain. In this study, biexponential modeling was used to evaluate the relaxation of brain parenchyma and blood separate from that of cerebrospinal fluid. Single‐shot multigradient‐echo data acquired with spiral or EPI techniques were analyzed. In phantom experiments the biexponential method proved to be accurate. Compared to the biexponential procedure, the monoexponential model overestimated T u2009*2 (72.2 msec vs. 65.3 msec) and underestimated ΔT u2009*2 (2.96 msec vs. 3.19 msec) during visual stimulation. The biexponential method may allow intrinsic correction for partial volume effects due to cerebrospinal fluid. The activation‐induced parameter changes are detected with a sensitivity equal to that of a monoexponential method. The resulting T u2009*2 and ΔT u2009*2 values describe the experimental data more accurately. Magn Reson Med 45:1116–1121, 2001.

Comparison of static and dynamic MRI techniques for the measurement of regional cerebral blood volume.

Two different acquisition and processing strategies to determine the regional cerebral blood volume (rCBV) with magnetic resonance imaging (MRI) are compared. The first method is based on the acquisition of the signal time course during a bolus administration of a contrast agent (dynamic method). The second method evaluates signal changes before and after the contrast agent injection (static method), assuming the contrast agent remains primarily intravascular in the brain after the first pass. Both methods were applied to the same data sets, acquired with either echoplanar imaging (EPI, n = 18) or fast low‐angle shot (FLASH, n = 28) techniques. A voxel‐by‐voxel correlation between the static and dynamic method yielded a correlation coefficient of 0.76 ± 0.06 for the EPI and 0.71 ± 0.10 for the FLASH measurements. The static method was less sensitive and showed higher standard deviations for rCBV than the dynamic method. With the development of truly intravascular contrast agents, the static perfusion MRI method, which can be performed with higher signal‐to‐noise ratio and higher spatial resolution, may become an alternative to ultra‐fast MRI for measuring rCBV. Magn Reson Med 41:1264–1268, 1999.