Jürgen Ruhlmann

Language mapping in less than 15 minutes: Real-time functional MRI during routine clinical investigation

Neurosurgical interventions often require the presurgical determination of language dominance or mapping of language areas. Results obtained by fMRI are closely correlated with invasive procedures such as electrical stimulation mapping or the intracarotid amobarbital test. However, language fMRI is not used routinely, because postprocessing is time-consuming. We utilized a real-time analysis software installed directly on the MR console computer and SPM99 as reference postprocessing software. We assessed the reliability of the immediate determination of language dominance based on individual activation maps by comparing the results of the visual analysis of images derived from conventional postprocessing with those produced by the real-time tool. All images were rated independently by six senior neurologists blinded to other data. We validated the robustness of the real-time method statistically by comparing global and regional lateralization indices derived from real-time and postprocessing analysis. Functional MRI was performed with a standard 1.5-T whole-body scanner. Brain activity was contrasted between an alternating semantic judgment and letter matching task. Twelve right-handed, healthy control subjects and 12 consecutive patients with drug-resistant, localization-related epilepsy were investigated. The semantic condition induced almost invariably left hemispheric activations in Brocas area, the premotor cortex, the dorsolateral prefrontal cortex, and the temporoparietal region. Although real-time analysis reduced noise less effectively than SPM99, visual ratings and lateralization indices produced highly concordant results with both methods. In conclusion, real-time fMRI, as used here, allowed reliable language lateralization and mapping in less than 15 min during routine clinical MRI investigation with no need for postprocessing.

Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters.

Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P) are distinguished. We used voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA-C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and several cortical regions including insular cortex. Gray matter loss in the cerebellum and insular cortex was correlated with disease duration and severity. There was white matter loss in the brainstem, which was correlated with disease duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2 in cerebellum, pontine brainstem and cortical regions including insular cortex. In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina, and several cortical regions including insular cortex. A correlation with disease duration and severity was detected only for some small cortical areas. Direct comparison of MSA-C and MSA-P showed differences only in infratentorial brain regions where structural abnormalities were more pronounced in MSA-C than in MSA-P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem.

Standardized uptake values of fluorine-18 fluorodeoxyglucose: the value of different normalization orocedures

While the evident advantages of absolute metabolic rate determinations cannot be equalled by static image analysis of fluorine-18 fluorodeoxyglucose positron emission tomographic (FDG PET) studies, various algorithms for the normalization of static FDG uptake values have been proposed. This study was performed to compare different normalization procedures in terms of dependency on individual patient characteristics. Standardized FDG uptake values (SUVs) were calculated for liver and lung tissue in 126 patients studied with wholebody FDG PET. Uptake values were normalized for total body weight, lean body mass and body surface area. Ranges, means, medians, standard deviations and variation coefficients of these SUV parameters were calculated and their interdependency with total body weight, lean body mass, body surface area, patient height and blood sugar levels was calculated by means of regression analysis. Standardized FDG uptake values normalized for body surface area were clearly superior to SUV parameters normalized. for total body weight or lean body mass. Variation and correlation coefficients of body surface area-normalized uptake values were minimal when compared with SUV parameters derived from the other normalization procedures. Normalization for total body weight resulted in uptake values still dependent on body weight and blood sugar levels, while normalization for lean body mass did not eliminate the positive correlation with lean body mass and patient height. It is concluded that normalization of FDG uptake values for body surface area is less dependent on the individual patient characteristics than are FDG uptake values normalized for other parameters, and therefore appears to be preferable for FDG PET studies in oncology.

Presurgical language fMRI in patients with drug-resistant epilepsy: effects of task performance.

Summary:  Purpose: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels.

18FDG PET and acetazolamide-enhanced99mTc-HMPAO SPET in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. Measurements of cerebral blood flow and metabolism by means of positron emission tomography (PET) and single-photon emission tomography (SPET) can contribute to the diagnostic assessment of the involvement of the central nervous system (CNS) in SLE. Functional imaging has been proven to be more sensitive than morphological imaging (magnetic resonance imaging and computed tomography). In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and a PET scan with fluorine-18 deoxyglucose (18FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that “preclinical” CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE.

18F-fluorodeoxyglucose-PET and99mTc-bicisate-SPECT in Creutzfeldt-Jakob disease

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with99mTc-bicisate showed a “coupled” decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

Association between scalp hair-whorl direction and hemispheric language dominance

Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language dominance.

Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2

Myotonic dystrophy type 2 (DM2) is an autosomal dominantly inherited multisystemic disorder and a common cause of muscular dystrophy in adults. Although neuromuscular symptoms predominate, there is clinical and imaging evidence of cerebral involvement. We used voxel-based morphometry (VBM) based on T1-weighted magnetic resonance images to investigate brain morphology in 13 DM2 patients in comparison to 13 sex- and age-matched controls. Further, we employed novel computational surface-based methods that specifically assess callosal thickness. We found grey and white matter loss along cerebral midline structures in our patient group. Grey matter reductions were present in brainstem and adjacent hypothalamic and thalamic regions, while white matter was mainly reduced in corpus callosum. The reduced callosal size was highly significant and independently confirmed by different methods. Our data provide first evidence for grey and white matter loss along brain midline structures in DM2 patients. The reduced size of the corpus callosum further extends the spectrum of white matter changes in DM2 and may represent the morphological substrate of neuropsychological abnormalities previously described in this disorder.

Callosal tissue loss in multiple system atrophy—A one‐year follow‐up study

Multiple system atrophy (MSA) is a neurodegenerative disease not only affecting the basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord but also the cerebral cortex. Clinically, cerebellar (MSA‐C) and parkinsonian variants of MSA (MSA‐P) are distinguished. We investigated 14 MSA patients (10 MSA‐C, 4 MSA‐P, men: 7, women: 7; age: 61.1 ± 3.3 years) and 14 matched controls (men: 7, women: 7; age: 58.6 ± 5.1 years) with voxel‐based morphometry (VBM) to analyze gray and white matter differences both at baseline and at follow‐up, 1 year later. Baseline comparisons between patients and controls confirmed significantly less gray matter in MSA in the cerebellum and cerebral cortex, and significantly less white matter in the cerebellar peduncles and brainstem. Comparisons of tissue‐loss profiles (i.e., baseline versus follow‐up) between patients and controls, revealed white matter reduction in MSA along the middle cerebellar peduncles, reflecting degeneration of the ponto‐cerebellar tract as a particularly prominent and progressive morphological alteration in MSA. Comparisons between baseline and follow‐up, separately performed in patients and controls, revealed additional white matter reduction in MSA along the corpus callosum at follow‐up. This was replicated through additional shape‐based analyses indicating a reduced callosal thickness in the anterior and posterior midbody, extending posteriorly into the isthmus. Callosal atrophy may possibly reflect a disease‐specific pattern of neurodegeneration and cortical atrophy, fitting well with the predominant impairment of motor functions in the MSA patients.

In vivo voxel-based relaxometry in amyotrophic lateral sclerosis.

We applied voxel-based relaxometry (VBR) in 12 ALS patients and 12 matched healthy controls and compared the results with those of voxel-based morphometry (VBM). VBR revealed a reduced relaxation rate in the right precentral gyrus and ventral pons. Individual region of interest (ROI)-based analysis of R2 maps confirmed our VBR results. VBM depicted a reduction of white matter in the paracentral lobules and in the right middle cerebellar peduncle. Our data suggests that VBR and ROI analysis of R2 maps may have a higher sensitivity in detecting local tissue atrophy in the motor cortex and along the corticospinal tract than VBM. Larger prospective studies are necessary to evaluate the usefulness and relevance of VBR and ROI-based analysis of R2 maps in clinical practice.