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Biomedical subjects

B J Krause

Publications and source records attributed to B J Krause.

At least 19 recordsLinked to original sources

[18F-FDG-PET in therapy response of esophageal cancer].

PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been evaluated in several studies to monitor tumor response in patients undergoing chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of residual tumor and therapy induced fibrosis has been documented for esophageal cancer. Furthermore, there are now several reports suggesting that quantitative assessment of therapy induced changes in tumor FDG-uptake may allow prediction of tumor response and patient outcome very early in the course of therapy. This suggests that FDG-PET may be used to identify non-responders early during neoadjuvant chemoradiotherapy allowing for early modifications of the treatment protocol.

Esophageal Neoplasms↗

PET and PET/CT studies of tumor tissue oxygenation.

Hypoxia has been identified as a major adverse prognostic factor for tumor progression and for resistance to anticancer treatment. Various approaches have been evaluated to assess tumor hypoxia in vivo. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumor oxygenation, thus offering the potential to optimize and individualize a therapy for patients suffering from cancer. The current PET tracers and animal models for the study of tissue hypoxia including aspects of small animal PET imaging are reviewed in this paper. Special emphasis is placed on human PET studies assessing tumor hypoxia in patients with different tumor entities, various anticancer therapies (chemotherapy, radiation therapy, hypoxia targeting chemotherapy) as well as studies deriving prognostic factors and outcome data. Methodological advantages underpinning PET/CT in the imaging of hypoxia are discussed. The great promise of PET/CT is its potential as a single imaging modality for whole body staging providing both anatomical and biological information on the tumor as a whole. It allows a more precise estimation of the hypoxic tumor volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). Finally, PET and PET/CT are discussed in the framework of individualized therapies with its special significance for intensity modulated radiation therapy and selective dose escalation in hypoxic tumor regions as well as more systemic approaches such as hypoxia-directed cytotoxins.

Biomarkers, Tumor↗

Myocardial perfusion/metabolism mismatch and ventricular arrhythmias in the chronic post infarction state.

AIM: Ventricular arrhythmias have been shown to originate in the myocardial peri-infarct region due to irregular heterotopic conduction. Hypoperfused but viable myocardium is often localised in those areas and may be involved in the pathogenesis of arrhythmias. We tested the hypothesis that these myocardial perfusion/metabolism mismatches (MM) are significantly associated with ventricular arrhythmias in the chronic post infarction state. PATIENTS, METHODS: 47 post infarction patients were included in the study. 33 suffered from ventricular arrhythmia whereas 14 did not. All patients underwent (99m)Tc tetrofosmin SPECT and (18)F-FDG PET. A region-of-interest(ROI)-analysis was used to assess viable myocardium based on predefined MM-criteria. Univariate analyses as well as a logistic regression model for the multivariate analysis were carried out. RESULTS: 94% of the arrhythmic patients displayed at least one MM-segment as compared to 64% of the non-arrhythmic patients. MM-segments and arrhythmia showed a statistically significant relation (p = 0.018). The logistic regression model predicted the occurrence or absence of arrhythmia in 85% of all cases. Multivariate analysis gave consistent results, after adjusting for symptomatic chronic heart failure (CHF), aneurysms and age. CONCLUSION: Our results support the hypothesis that hypoperfused but viable myocardium represents an arrhythmogenic substrate and is a relevant risk factor for developing ventricular arrhythmias following myocardial infarction. Therefore, the detection of MM-segments allows the identification of patients with a higher risk for future cardiac events.

Coronary Disease↗

The influence of filtered back-projection and iterative reconstruction on partial volume correction in PET.

AIM: We assess the influence of the reconstruction algorithms [OS-EM for the iterative one vs. a filtered back-projection in Fourier space (DiFT)] on partial volume correction in PET employing a fully 3D 3-compartment MR based PV-correction algorithm. The gray matter voxels in the PET image -- after removal of the white matter and cerebrospinal fluid contribution -- are corrected voxel-by-voxel using the image resolution. MATERIAL, METHODS: Phantom measurements and one healthy human brain FDG study were carried out. For the OSEM reconstruction, a combination of iteration steps and subset numbers (It/Sub) was used, whereby in case of no-convergence the image resolution had to be fitted. The RESULTS from the DiFT reconstruction were equivalent to those obtained from the OSEM reconstruction with 10/32 combination for objects with widespread activity concentration. For the sphere phantom, the mean recovery based on the actual values achieved 99.2% +/- 1.8 for all spheres and all reconstruction modes and It/sub combinations (except for 2/8). In case of the Hoffman 3D brain phantom the mean recovery of the cortical regions was 101% +/- 1.2 (the increase based on the uncorrected values: 35.5% +/- 1.5), while the subcortical regions reached a mean recovery of 80% with an increase of 43.9% +/- 2.5. For the human data, an increase of the metabolized values of several cortical regions ranged between 42% and 48% independent from the reconstruction mode. CONCLUSIONS: Our data show that the 3-compartment fully 3-D MR based PV-correction is sensitive to the choice of reconstruction algorithms and to the parameter choice. They indicate that despite improved spatial resolution, the use of the iterative reconstruction algorithm for PV-correction results in similar recovery factors when compared to a correction using DiFT reconstruction, insofar the image resolution values are fitted at the It/Sub combinations.

Algorithms↗

When planning fails: individual differences and error-related brain activity in problem solving.

The neuronal processes underlying correct and erroneous problem solving were studied in strong and weak problem-solvers using functional magnetic resonance imaging (fMRI). During planning, the right dorsolateral prefrontal cortex was activated, and showed a linear relationship with the participants' performance level. A similar pattern emerged in right inferior parietal regions for all trials, and in anterior cingulate cortex for erroneously solved trials only. In the performance phase, when the pre-planned moves had to be executed by means of an fMRI-compatible computer mouse, the right dorsolateral prefrontal cortex was again activated jointly with right parahippocampal cortex, and displayed a similar positive relationship with the participants' performance level. Incorrectly solved problems elicited stronger bilateral prefrontal and left inferior parietal activations than correctly solved trials. For both individual ability and trial-specific performance, our results thus demonstrate the crucial involvement of right prefrontal cortex in efficient visuospatial planning.

Adult↗

Chronometry of parietal and prefrontal activations in verbal working memory revealed by transcranial magnetic stimulation.

We explored the temporal dynamics of parietal and prefrontal cortex involvement in verbal working memory employing single-pulse transcranial magnetic stimulation (TMS). In six healthy volunteers the left or right inferior parietal and prefrontal cortex was stimulated with the aid of a frameless stereotactic system. TMS was applied at 10 different time points 140-500 ms into the delay period of a two-back verbal working memory task. A choice reaction task was used as a control task. Interference with task accuracy was induced by TMS earlier in the parietal cortex than in the prefrontal cortex and earlier over the right than the left hemisphere. This suggests a propagation of information flow from posterior to anterior cortical sites converging in the left prefrontal cortex. Significant interference with reaction time was observed after 180 ms with left prefrontal cortex stimulation. These effects were not observed in the control task, underlining the task specificity of our results. We propose that the interference with right-sided prefrontal cortex stimulation leads to impaired performance due to disturbed input into the left prefrontal cortex, whereas left-sided TMS interferes directly with the final information processing. Left- and right-sided brain areas might be involved in parallel processing of semantic and object features of the stimuli, respectively.

Adult↗

[Neurocognition and PET. Strategies for data analysis in activation studies on working memory].

AIM: In cognitive neuroscience regional cerebral blood flow (rCBF) imaging with positron-emission-tomography (PET) is a powerful tool to characterize different aspects of cognitive processes by using different data analysis approaches. By use of an n-back verbal working memory task (varied from 0- to 3-back) we present cognitive subtraction analysis as basic strategy as well as parametric and covariance analyses and discuss the results. METHODS: Correlation analyses were performed using the individual performance rate as an external covariate, computing inter-regional correlations, and as network analysis applying structural equation modelling to evaluate the effective connectivity between the involved brain regions. RESULTS: Subtraction analyses revealed a fronto-parietal neuronal network also including the anterior cingulate cortex and the cerebellum. With higher memory load the parametric analysis evidenced linear rCBF increases in prefrontal, pre-motor and inferior parietal areas including the precuneus as well as in the anterior cingulate cortex. The rCBF correlation with the individual performance as external covariate depicted negative correlations in bilateral prefrontal and inferior parietal regions, in the precuneus and the anterior cingulate cortex. The network analysis demonstrated mainly occipito-frontally directed interactions which were predominantly left-hemispheric. Additionally, strong linkages were found between extrastriate and parietal regions as well as within the parietal cortex. CONCLUSION: The data analysis approaches presented here contribute to an extended and more elaborated understanding of cognitive processes and their different sub-aspects.

Brain↗

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans.

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.

Adult↗

PET studies on the memory processing of word pairs in bilingual Finnish-English subjects.

This study examined the fundamental question whether verbal memory processing in two unrelated languages is mediated by a common neural system or by distinct cortical areas. Ten right-handed, male Finnish--English adult late bilinguals who had acquired the second language after the age of 10 were scanned whilst either encoding/retrieving word pairs in their mother tongue (Finnish) or in a foreign language (English). Within each language, subjects had to encode and retrieve four sets of 12 visually presented paired word associates which were not semantically related. Two sets consisted of highly imageable words (e.g. monkey-table; koira-lasi) and the other two sets of abstract word pairs (e.g. freedom-moral; uhka-suure). Presentation of pseudowords served as a reference condition. An emission scan was recorded after each intravenous administration of O-15 water. Encoding was associated with prefrontal and hippocampal activation. During memory retrieval, precuneus showed a consistent activation in both languages and for both highly imageable and abstract words. Although the brain mechanisms of the two languages share common components, differential activations were found in Broca's area and in the cerebellum as well as in the angular/supramarginal gyri according to the language used.

Adult↗

[The (11C) acetate positron emission tomography in prostatic carcinoma. New prospects in metabolic imaging].

The exact staging of prostate cancer is mandatory to allow selection of the appropriate primary therapy. In addition, if the PSA level rises again it is extremely important to find the site(s) of local recurrence or metastatic spread as soon as possible. However, with the morphological and metabolic imaging techniques currently available it is often not possible to answer these questions with adequate sensitivity and specificity, since small metastases < or = 1 cm in diameter are likely to remain undetected by them. In the last few years new radioactive labelled tracers have been introduced for use in positron emission tomography (PET), and it is hoped that the shortcomings in the diagnostic procedures used for prostate carcinoma might be compensated by their use. Besides 11C- or 18F-labelled choline, [11C]Acetate is also attracting attention as a promising PET tracer. In this paper we review the various PET tracers available and evaluate the advantages and the drawbacks of [11C]Acetate in three case studies by comparing [11C]Acetate-PET with histology and with other imaging techniques. The use of [11C]Acetate appears to be feasible and helpful in the diagnosis of prostate carcinoma. However, its final value relative to other imaging techniques needs further investigation, with special reference to initial lymph node involvement, early localisation of recurrence and possible noninvasive differentiation between prostate cancer, prostatis and benign hyperplasia of the prostate.

Acetates↗

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Adult↗

Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS.

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. Storage and processing functions might be segregated in ventral and dorsal areas of the prefrontal cortex, respectively. If so, storage functions might be spared, irrespective of informational domain, following damage or dysfunction in dorsolateral areas. Alternatively, WM and prefrontal function in general might be segregated according to informational domains (e.g. spatial versus object-based information). In the present study we used repetitive transcranial magnetic stimulation (rTMS) to directly test these competing hypotheses. We applied rTMS to transiently and selectively disrupt the function of the dorsomedial, dorsolateral or ventral prefrontal cortex in normal human volunteers performing either a spatial or a face-recognition delayed-response task. Performance in the spatial task was impaired by rTMS of the dorsomedial prefrontal cortex. Performance in the face-recognition (non-spatial) task was impaired by rTMS of the ventral prefrontal cortex. Transient disruption of the dorsolateral prefrontal cortex affected performance in both tasks. These findings provide evidence of domain-specific segregation of WM functions in widely separated areas of prefrontal cortex.

Adult↗

The motion aftereffect: more than area V5/MT? Evidence from 15O-butanol PET studies.

The motion aftereffect is a perceptual phenomenon which has been extensively investigated both psychologically and physiologically. Neuroimaging techniques have recently demonstrated that area V5/MT is activated during the perception of this illusion. The aim of this study was to test the hypothesis if a more broadly distributed network of brain regions subserves the motion aftereffect. To identify the neuronal structures involved in the perception of the motion aftereffect, regional cerebral blood flow (rCBF) measurements with positron emission tomography were performed in six normal volunteers. Data were analysed using SPM96. The motion-sensitive visual areas including area V5/MT were activated in both hemispheres. Additionally, the lateral parietal cortex bilaterally, the right dorsolateral prefrontal cortex, the anterior cingulate cortex and the left cerebellum showed significant increases in rCBF values during the experience of the waterfall illusion. In a further reference condition with identical attentional demand but no perception of a motion aftereffect elevated rCBF were found in these regions as well. In conclusion, our findings support the notion that the perceptual illusion of motion arises exclusively in the motion-sensitive visual area V5/MT. In addition, a more widespread network of brain regions including the prefrontal and parietal cortex is activated during the waterfall illusion which represents a non-motion aftereffect-specific subset of brain areas but is involved in more basic attentional processing and cognition.

Adult↗

Integrating electrophysiology and neuroimaging of spatial selective attention to simple isolated visual stimuli.

Visual-spatial attention involves modulations of activity in human visual cortex as indexed by electrophysiological and functional neuroimaging measures. Prior studies investigating the time course and functional anatomy of spatial attention mechanisms in visual cortex have used higher-order discrimination tasks with complex stimuli (e.g. symbol matching in bilateral stimulus arrays, or letter discrimination), or simple detection tasks but in the presence of complex distracting information (e.g. luminance detection with superimposed symbols as distractors). Here we tested the hypothesis that short-latency modulations of incoming sensory signals in extrastriate visual cortex reflect an early spatially specific attentional mechanism. We sought evidence of attentional modulations of sensory input processing for simple, isolated stimuli requiring only an elementary discrimination (i.e. size discrimination). As in prior studies using complex symbols, we observed attention-related changes in regional cerebral blood flow in extrastriate visual cortex that were associated with changes in event-related potentials at a specific latency range. These findings support the idea that early in cortical processing, spatially-specific attentional selection mechanisms can modulate incoming sensory signals based on their spatial location and perhaps independently of higher-order stimulus form.

Adult↗

The translating brain: cerebral activation patterns during simultaneous interpreting.

Brain activation was measured in professional interpreters during simultaneous interpreting (SI) vs. repetition (shadowing) of auditorily presented text by positron emission tomography (PET). SI into the native language (Finnish) elicited left frontal activation increases. SI into the non-native language (English) elicited much more extensive left-sided fronto-temporal activation increases. Our results indicate that SI activates predominantly left-hemispheric structures (particularly the left dorsolateral frontal cortex) previously related to lexical search, semantic processing and verbal working memory. Brain activation patterns were clearly modulated by direction of translation, with more extensive activation during translation into the non-native language which is often considered to a be more demanding task.

Adult↗

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation.

We studied the effect of repetitive transcranial magnetic stimulation (rTMS) on changes in regional cerebral blood flow (rCBF) as revealed by positron emission tomography (PET) while subjects performed a 2-back verbal working memory (WM) task. rTMS to the right or left dorsolateral prefrontal cortex (DLPFC), but not to the midline frontal cortex, significantly worsened performance in the WM task while inducing significant reductions in rCBF at the stimulation site and in distant brain regions. These results for the first time demonstrate the ability of rTMS to produce temporary functional lesions in elements of a neuronal network thus changing its distributed activations and resulting in behavioral consequences.

Adult↗

[Comparison of PET and fMRI activation patterns durnig declarative memory processes].

AIM: In this study neuronal correlates of encoding and retrieval in paired association learning were compared using two different neuroimaging methods: positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). METHODS: 6 right-handed normal male volunteers took part in the study. Each subject underwent six 0-15-butanol PET scans and on fMRI study comprising four single epochs on a different day. The subjects had to learn and retrieve 12 word pairs which were visually presented (highly imaginable words, not semantically related). RESULTS: Mean recall accuracy was 93% in the PET as well as in the fMRI experiment. During encoding and retrieval we found anterior cingulate cortex activation, and bilateral prefrontal cortex activation in both imaging modalities. Furthermore, we demonstrate the importance of the precuneus in episodic memory. With PET the results demonstrate frontopolar activations whereas fMRI fails to show activations in this area probably due to susceptibility artifacts. In fMRI we found additionally parahippocampal activation and due to the whole-brain coverage cerebellar activation during encoding. The distance between the center-of-mass activations in both modalities was 7.2 +/- 6.5 mm. CONCLUSION: There is a preponderance of commonalities in the activation patterns yielded with fMRI and PET. However, there are also important differences. The decision to choose one or the other neuroimaging modality should among other aspects depend on the study design (single subject vs. group study) and the task of interest.

Adult↗

Left hemisphere activation during processing of morphologically complex word forms in adults.

Functional neuroanatomy of the processing of morphologically complex words was studied by measuring regional brain activity by positron emission tomography (PET) during encoding of auditorily presented inflected versus monomorphemic Finnish nouns. Significant increases of activation occurred particularly in the left inferior posterior frontal lobe, corresponding to Broca's area. This suggests that besides their role in the production of grammatical morphology documented earlier, Broca's area and adjacent regions are important for the input processing of morphologically complex words.

Adult↗