Jörn Kaufmann

Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral Sclerosis

BackgroundWidespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS) has been described in neuropathological studies. The presence of cortical atrophy in conventional and scientific neuroimaging has been a matter of debate. In studies using computertomography, positron emission tomography, proton magnetic resonance spectroscopy and conventional T2-weighted and proton-weighted images, results have been variable. Recent morphometric studies by magnetic resonance imaging have produced conflicting results regarding the extent of grey and white matter involvement in ALS patients.MethodsThe authors used optimized voxel-based morphometry as an unbiased whole brain approach to detect differences between regional grey and white matter volumes. Seventeen patients with a diagnosis of ALS according to El-Escorial criteria and seventeen age-matched controls received a high resolution anatomical T1 scan.ResultsIn ALS patients regional grey matter volume (GMV) reductions were found in the pre- and postcentral gyrus bilaterally which extended to premotor, parietal and frontal regions bilaterally compared with controls (p < 0.05, corrected for the entire volume). The revised ALS functional rating scale showed a positive correlation with GMV reduction of the right medial frontal gyrus corresponding to the dorsolateral prefrontal cortex. No significant differences were found for white matter volumes or when grey and white matter density images were investigated. There were no further correlations with clinical variables found.ConclusionIn ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent feature of the disease. Supporting the concept of ALS being a multisytem disorder, our study provides further evidence for extramotor involvement which is widespread. The lack of correlation with common clinical variables probably reflects the fact that heterogeneous disease processes underlie ALS. The discrepancy within all published morphometric studies in ALS so far may be related to differences in patient cohorts and several methodological factors of the data analysis process. Longitudinal studies are required to further clarify the time course and distribution of grey and white matter pathology during the course of ALS.

Experience-dependent plasticity of white-matter microstructure extends into old age

Experience-dependent alterations in the human brains white-matter microstructure occur in early adulthood, but it is unknown whether such plasticity extends throughout life. We used cognitive training, diffusion-tensor imaging (DTI), and structural MRI to investigate plasticity of the white-matter tracts that connect the left and right hemisphere of the frontal lobes. Over a period of about 180 days, 20 younger adults and 12 older adults trained for a total of one hundred and one 1-h sessions on a set of three working memory, three episodic memory, and six perceptual speed tasks. Control groups were assessed at pre- and post-test. Training affected several DTI metrics and increased the area of the anterior part of the corpus callosum. These alterations were of similar magnitude in younger and older adults. The findings indicate that experience-dependent plasticity of white-matter microstructure extends into old age and that disruptions of structural interhemispheric connectivity in old age, which are pronounced in aging, are modifiable by experience and amenable to treatment.

Eddy current correction in diffusion-weighted imaging using pairs of images acquired with opposite diffusion gradient polarity.

In echo‐planar‐based diffusion‐weighted imaging (DWI) and diffusion tensor imaging (DTI), the evaluation of diffusion parameters such as apparent diffusion coefficients and anisotropy indices is affected by image distortions that arise from residual eddy currents produced by the diffusion‐sensitizing gradients. Correction methods that coregister diffusion‐weighted and non‐diffusion‐weighted images suffer from the different contrast properties inherent in these image types. Here, a postprocessing correction scheme is introduced that makes use of the inverse characteristics of distortions generated by gradients with reversed polarity. In this approach, only diffusion‐weighted images with identical contrast are included for correction. That is, non‐diffusion‐weighted images are not needed as a reference for registration. Furthermore, the acquisition of an additional dataset with moderate diffusion‐weighting as suggested by Haselgrove and Moore (Magn Reson Med 1996;36:960–964) is not required. With phantom data it is shown that the theoretically expected symmetry of distortions is preserved in the images to a very high degree, demonstrating the practicality of the new method. Results from human brain images are also presented. Magn Reson Med 51:188–193, 2004.

Quantitation of simulated short echo time 1H human brain spectra by LCModel and AMARES.

LCModel and AMARES, two widely used quantitation tools for magnetic resonance spectroscopy (MRS) data, were employed to analyze simulated spectra similar to those typically obtained at short echo times (TEs) in the human brain at 1.5 T. The study focused mainly on the influence of signal‐to‐noise ratios (SNRs) and different linewidths on the accuracy and precision of the quantification results, and their effectiveness in accounting for the broad signal contribution of macromolecules and lipids (often called the baseline in in vivo MRS). When applied in their standard configuration (i.e., fitting a spline as a baseline for LCModel, and weighting the first data points for AMARES), both methods performed comparably but with their own characteristics. LCModel and AMARES quantitation benefited considerably from the incorporation of baseline information into the prior knowledge. However, the more accurate quantitation of the sum of glutamate and glutamine (Glx) favored the use of LCModel. Metabolite‐to‐creatine ratios estimated by LCModel with extended prior knowledge are more accurate than absolute concentrations, and are nearly independent of SNR and line broadening. Magn Reson Med 51:904–912, 2004.

Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging

BackgroundPathophysiological evidence suggests an involvement of fronto-striatal circuits in Tourette syndrome (TS). To identify TS related abnormalities in gray and white matter we used optimized voxel-based morphometry (VBM) and magnetization transfer imaging (MTI) which are more sensitive to tissue alterations than conventional MRI and provide a quantitative measure of macrostructural integrity.MethodsVolumetric high-resolution anatomical T1-weighted MRI and MTI were acquired in 19 adult, unmedicated male TS patients without co-morbidities and 20 age- and sex-matched controls on a 1.5 Tesla neuro-optimized GE scanner. Images were pre-processed and analyzed using an optimized version of VBM in SPM2.ResultsUsing VBM, TS patients showed significant decreases in gray matter volumes in prefrontal areas, the anterior cingulate gyrus, sensorimotor areas, left caudate nucleus and left postcentral gyrus. Decreases in white matter volumes were detected in the right inferior frontal gyrus, the left superior frontal gyrus and the anterior corpus callosum. Increases were found in the left middle frontal gyrus and left sensorimotor areas. In MTI, white matter reductions were seen in the right medial frontal gyrus, the inferior frontal gyrus bilaterally and the right cingulate gyrus. Tic severity was negatively correlated with orbitofrontal structures, the right cingulate gyrus and parts of the parietal-temporal-occipital association cortex bilaterally.ConclusionOur MRI in vivo neuropathological findings using two sensitive and unbiased techniques support the hypothesis that alterations in frontostriatal circuitries underlie TS pathology. We suggest that anomalous frontal lobe association and projection fiber bundles cause disinhibition of the cingulate gyrus and abnormal basal ganglia function.

Contemporary ultrasound systems allow high-resolution transcranial imaging of small echogenic deep intracranial structures similarly as MRI: a phantom study.

Transcranial sonography (TCS) of small deep brain structures, such as substantia nigra and brainstem raphe, is increasingly used for assessment of neurodegenerative disorders. Still, there are reservations against TCS because of the smallness of evaluated structures and constraints on image resolution that is discussed to be lower compared to magnetic resonance imaging (MRI). To evaluate two different-generation TCS systems in visualizing fine intracranial structures, we studied image resolution on a phantom consisting of 0.80 mm x 1.05 mm regular meshwork of nylon threads embedded in a wet, gel-filled ex vivo human skull. Imaging was performed with a former-generation and a present-day clinical ultrasound system and for comparison with MRI. In axial direction of insonation both TCS systems resolved 0.80-mm and 1.05-mm thread-to-thread distance at depths between 55 and 120 mm using transmission frequencies > or =2.5 MHz. The meshwork, however, was recognizable as such only with the contemporary TCS system at depths between 60 and 85 mm due to its higher lateral resolution. MRI resolved the meshwork if image resolution was chosen sufficiently high but not if realistic clinical conditions were applied with its trade-offs between image SNR, resolution, total scan time, and unavoidable head motion during the latter. Hence, if the requirements for optimal TCS image resolution are fulfilled, i.e. sufficient acoustic bone window, increased echogenicity of target structure and its localization in a distance of maximum +/-15 mm from midsagittal plane, findings suggest that contemporary TCS systems achieve higher image resolution of intracranial structures in comparison not only to former-generation systems, but also to MRI under clinical conditions.

Hippocampal CA1 deformity is related to symptom severity and antipsychotic dosage in schizophrenia

Abnormalities of the hippocampus are intricately involved in the pathophysiology of schizophrenia. Hippocampal volume decrease is present at disease onset and has mainly been observed in the anterior and posterior part of the hippocampus. Nevertheless, an association between regionally specific hippocampal shape deformities putatively affecting a pathophysiologically crucial region, i.e. cornu ammonis field 1 (CA1), and symptomatology as well as required maintenance medication has not been observed. The aim of this study was to characterize the relationship between CA1-specific hippocampal surface deformations and symptom severity. Furthermore, we aimed to explore whether such specific morphological hippocampus abnormalities statistically predict the maintenance dosage of antipsychotic medication. Hippocampal shape and volume were determined by manual segmentation of high resolution, whole brain, three-dimensional structural magnetic resonance imaging scans. Associations between hippocampal volume, specific shape deformities in CA1, and positive and negative symptoms were assessed in 32 patients with schizophrenia and compared with 34 healthy control subjects. In addition to volume reductions of the left hippocampus, patients with schizophrenia displayed specific shape deformities in the left anterior and posterior CA1 subfield. Overall, the severity of positive symptoms was closely associated to these morphological deformities, specifically delusions and hallucinations. In addition, CA1 deformity was linked to the required antipsychotic dosage. Findings were replicated in a second, independent sample. Hippocampal CA1 deformity, possibly reflecting shrinkage, might result from a specific hyperactivity, leading to a circumscribed volume loss. Owing to its physiological function, deficits in CA1 may be directly involved in the pathogenesis of hallucinations and delusions, core symptoms in schizophrenia.

Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy.

Purpose: In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N‐acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy (1H‐MRS) reflects the epilepsy‐associated loss of hippocampal pyramidal neurons or metabolic dysfunction.

Quantitative MR analyses of the hippocampus: Unspecific metabolic changes in aging

The age-related structural changes of the human hippocampus are not entirely understood. The goal of the present investigation was to understand better the nature of age-related hippocampal changes by a comparative MR-analysis of four complementary aspects of hippocampal integrity: total volume, metabolite concentration, neuron to glial cell ratio and amount of extracellular diffusion space for water. To that end, we applied MR-based methods of manual and computerized (voxel-based morphometry) volumetry, diffusion-weighted imaging and 1H MR spectroscopy to characterize specific age-related hippocampal effects in a group of 22 healthy old adults in comparison with a group of 13 healthy younger adults. Age-related reductions of the hippocampal N-acetyl aspartate to creatine/choline ratio together with only marginal age-related reductions in hippocampal volumes and increases in diffusion parameters suggest that the process of aging affects mainly the metabolic status of the hippocampus with little equivalent age-related changes in hippocampal cell density. The metabolic changes are unspecific as they are not restricted to the hippocampus but equally occur in measures obtained from extrahippocampal temporal lobe regions.

Hippocampal Atrophy in Temporal Lobe Epilepsy Is Correlated with Limbic Systems Atrophy

AbstractHippocampal sclerosis in temporal lobe epilepsy (TLE) is often associated with hippocampal atrophy. This study assessed whether such atrophy is correlated with loss of gray matter volume in other brain regions. In 16 patients with TLE and clear magnetic resonance imaging–based evidence of hippocampal sclerosis, hippocampal volumes were determined manually and the local gray matter (LGM) amount was estimated throughout the entire brain using voxel–based morphometry. Voxelwise correlations between the volume of the sclerotic hippocampus and LGM were computed. The pattern of voxels whose LGM correlated with hippocampal volume outlined remarkably well the anatomy of the extended limbic system and included the parahippocampal region, cingulate gyrus throughout its extent, basal forebrain, thalamic nuclei, medial orbitofrontal areas and the insula. These correlations emerged mainly on the side ipsilateral to the affected hippocampus but were also found contralaterally. No such correlations were found in a group of 16 healthy controls. The present data show that hippocampal volume loss in TLE is associated with a widespread limbic systems atrophy. These findings are helpful to better understand the functional deficit and reorganization often found in temporal lobe epilepsy and will also provide a basis to assess neural plasticity in the limbic system for those patients who will undergo curative temporal lobe surgery.