PubMed Health⌕ Search

Biomedical subjects

Bernd J Krause

Publications and source records attributed to Bernd J Krause.

10 recordsLinked to original sources

Molecular imaging of proliferation in malignant lymphoma.

We have determined the ability of positron emission tomography (PET) with the thymidine analogue 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) to detect manifestation sites of malignant lymphoma, to assess proliferative activity, and to differentiate aggressive from indolent tumors. In this prospective study, FLT-PET was done additionally to routine staging procedures in 34 patients with malignant lymphoma. Sixty minutes after i.v. injection of approximately 330 MBq FLT, emission and transmission scanning was done. Tracer uptake in lymphoma was evaluated semiquantitatively by calculation of standardized uptake values (SUV) and correlated to tumor grading and proliferation fraction as determined by Ki-67 immunohistochemistry. FLT-PET detected a total of 490 lesions compared with 420 lesions revealed by routine staging. In 11 patients with indolent lymphoma, mean FLT-SUV in biopsied lesions was 2.3 (range, 1.2-4.5). In 21 patients with aggressive lymphoma, a significantly higher FLT uptake was observed (mean FLT-SUV, 5.9; range, 3.2-9.2; P < 0.0001) and a cutoff value of SUV = 3 accurately discriminated between indolent and aggressive lymphoma. Linear regression analysis indicated significant correlation of FLT uptake in biopsied lesions and proliferation fraction (r = 0.84; P < 0.0001). In this clinical study, FLT-PET was suitable for imaging malignant lymphoma and noninvasive assessment of tumor grading. Due to specific imaging of proliferation, FLT may be a superior PET tracer for detection of malignant lymphoma in organs with high physiologic fluorodeoxyglucose uptake and early detection of progression to a more aggressive histology or potential transformation.

Adult↗

11C-methionine PET improves the target volume delineation of meningiomas treated with stereotactic fractionated radiotherapy.

PURPOSE: To evaluate the role of 11C-methionine positron emission tomography (MET-PET) in target volume delineation for meningiomas and to determine the interobserver variability. METHODS AND MATERIALS: Two independent observers performed treatment planning in 10 patients according to a prospective written protocol. In the first step, they used coregistered computed tomography (CT) and magnetic resonance imaging (MRI). In the second step, MET-PET was added to CT/MRI (image fusion based on mutual information). RESULTS: The correlation between gross tumor volume (GTVs) delineated by the two observers based on CT/MRI was r=0.855 (Spearman's correlation coefficient, p=0.002) and r=0.988 (p=0.000) when MET-PET/CT/MRI were used. The number of patients with agreement in more then 80% of the outlined volume increased with the availability of MET-PET from 1 in 10 to 5 in 10. The median volume of intersection between the regions delineated by two observers increased significantly from 69% (from the composite volume) to 79%, by the addition of MET-PET (p=0.005). The information of MET-PET was useful to delineate GTV in the area of cavernous sinus, orbit, and base of the skull. CONCLUSIONS: The hypothesis-generating findings of potential normal tissue sparing and reduced interobserver variability provide arguments for invasive studies of the correlation between MET-PET images and histologic tumor extension and for prospective trials of target volume delineation with CT/MRI/MET-PET image fusion.

Aged↗

Learning related interactions among neuronal systems involved in memory processes.

Functional neuroimaging techniques using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have provided new insights in our understanding of brain function from the molecular to the systems level. While subtraction strategy based data analyses have revealed the involvement of distributed brain regions in memory processes, covariance analysis based data analysis strategies allow functional interactions between brain regions of a neuronal network to be assessed. The focus of this chapter is to (1) establish the functional topography of episodic and working memory processes in young and old normal volunteers, (2) to assess functional interactions between modules of networks of brain regions by means of covariance based analyses and systems level modelling and (3) to relate neuroimaging data to the underpinning neural networks. Male normal young and old volunteers without neurological or psychiatric illness participated in neuroimaging studies (PET, fMRI) on working and episodic memory. Distributed brain areas are involved in memory processes (episodic and working memory) in young volunteers and show much of an overlap with respect to the network components. Systems level modelling analyses support the hypothesis of bihemispheric, asymmetric networks subserving memory processes and revealed both similarities in general and differences in the interactions between brain regions during episodic encoding and retrieval as well as working memory. Changes in memory function with ageing are evident from studies in old volunteers activating more brain regions compared to young volunteers and revealing more and stronger influences of prefrontal regions. We finally discuss the way in which the systems level models based on PET and fMRI results have implications for the understanding of the underlying neural network functioning of the brain.

Animals↗

Systems level modeling of a neuronal network subserving intrinsic alertness.

Cognitive control of alertness in unwarned situations (intrinsic alertness) relies on a predominantly right hemisphere cortical and subcortical network. In a previous functional activation study, we have demonstrated that this network comprises the anterior cingulate gyrus, the dorsolateral and polar frontal as well as the inferior parietal cortex, the thalamus and ponto-mesencephalic parts of the brain stem. The aim of this study was to study effective connectivity of this network by employing structural equation modeling. Fifteen right-handed male subjects participated in the PET study. The functional network showed stronger connectivity in the right hemisphere. Furthermore, there were strong effective connections between thalamus and brainstem on the one hand and between thalamus and anterior cingulate on the other. Our results suggest that the anterior cingulate functions as the central coordinating structure for the right hemispheric neural network of intrinsic alertness and that the anterior cingulate gyrus is modulated mainly by prefrontal and parietal cortex.

Adult↗

Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD.

A heterozygous R1101K mutation of the p150 subunit of dynactin (DCTN1) is reported in a family with amyotrophic lateral sclerosis (ALS) and co-occurrence of frontotemporal dementia (FTD). Two members of our kindred were affected with motor neuron disease and two with dementia in an autosomal dominant pattern of inheritance. We excluded the involvement of the ALS and FTD-linked genes for copper/zinc superoxide dismutase (SOD1) and tau. The R1101K sequence alteration of the DCTN1 gene may predispose subjects to ALS and FTD.

Amyotrophic Lateral Sclerosis↗

Dissociating neural correlates for nouns and verbs.

Dissociations in the ability to produce words of different grammatical categories are well established in neuropsychology but have not been corroborated fully with evidence from brain imaging. Here we report on a PET study designed to reveal the anatomical correlates of grammatical processes involving nouns and verbs. German-speaking subjects were asked to produce either plural and singular nouns, or first-person plural and singular verbs. Verbs, relative to nouns, activated a left frontal cortical network, while the opposite contrast (nouns-verbs) showed greater activation in temporal regions bilaterally. Similar patterns emerged when subjects performed the task with pseudowords used as nouns or as verbs. These results converge with findings from lesion studies and suggest that grammatical category is an important dimension of organization for knowledge of language in the brain.

Adult↗

Lexical decision of nonwords and pseudowords in humans: a positron emission tomography study.

In this functional positron emission tomography study brain activations during an auditory lexical decision task with two experimental conditions were investigated. First, the subjects had to discriminate between real words and nonwords; second, real words varied with pseudowords. Comparing each of these tasks to an auditory control condition we found bilateral activation of the superior temporal and inferior frontal gyrus, lateralized to the left in the pseudoword condition. The comparison of the lexical decision tasks revealed higher rCBF during the pseudo-/real word decisions within BA 47, adjacent to Broca's area, and the anterior cingulate. The data support the notion that the lexical decision during a nonword task is mainly based on a phonological discrimination process, whereas a pseudoword task more strongly requires lexical access resulting in activation of BA 47.

Acoustic Stimulation↗

Modulation of a brain-behavior relationship in verbal working memory by rTMS.

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.

Adult↗

Bilateral parieto-frontal network for verbal working memory: an interference approach using repetitive transcranial magnetic stimulation (rTMS).

Verbal working memory has been attributed to a left-dominant neuronal network, including parietal, temporal and prefrontal cortical areas. The current study was designed to evaluate the contribution of these brain regions to verbal working memory processes and to assess possible hemispheric asymmetry. The effect of repetitive transcranial stimulation (rTMS) on performance in a verbal working memory task both during, and after an rTMS train (110% of individual motor threshold, 4 Hz) over nine different scalp locations was studied [bilateral middle frontal gyrus (MFG), bilateral supramarginal gyrus (SMG), bilateral inferior parietal cortex (IP) and three different midline control sites]. Significant performance deterioration was observed during rTMS over the left and right MFG and left and right IP. There was no consistent interference effect across subjects over the left or right SMG and the three different midline control sites. The interference effect with the given stimulation parameters did not last beyond the rTMS train itself. The data provide evidence for a symmetrical, bilateral parieto-frontal verbal working memory network. The data are discussed with respect to the competing ideas of a parieto-frontal central executive network vs. a network that processes the inherent semantic and object features of the visually presented verbal stimuli in parallel.

Adult↗