PubMed Health⌕ Search

Biomedical subjects

Hans Herzog

Publications and source records attributed to Hans Herzog.

At least 19 recordsLinked to original sources

Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.

Adult↗

Concepts of registration and correction of head motion in positron emission tomography.

The long acquisition times (up to hours) in PET brain imaging bear a high risk of head motion, which results in artefacts like blurred images and may even lead to misinterpretation and useless data. With the increased resolution of high performance PET scanners, the influence of head movements becomes more and more relevant. Especially in the analysis of small brain structures, e.g. during ROI-analysis, head motion results in inaccuracies of quantified data. This may also influence the kinetic analysis and generate artifacts in parametric images calculated from a motion-affected image sequence. This work presents the feasibility of head motion registration using an external motion tracking system. The implementation of the multi acquisition frame method and an event-by-event method to correct PET data for motion are described. The effects of motion correction are demonstrated on the basis of phantom measurements and patient data. The influence of motion correction on parametric imaging is described in a receptor study.

Artifacts↗

Analytical calculation of volumes-of-intersection for iterative, fully 3-D PET reconstruction.

Use of iterative algorithms to reconstruct three-dimensional (3-D) positron emission tomography (PET) data requires the computation of the system probability matrix. The pure geometrical contribution can easily be approximated by the length-of-intersection (LOI) between lines-of-response (LOR) and individual voxels. However, more accurate geometrical projectors are desirable. Therefore, we have developed a fast method for the analytical calculation of the 3-D shape and volume of volumes-of-intersection (VOI). This method provides an alternative robust projector with a uniformly continuous sampling of the image space. The enhanced calculation effort is facilitated by using several speedup techniques. Exploiting intrinsic symmetry relations and the sparseness of the system matrix allows to create an efficiently compressed matrix which can be precomputed and completely stored in memory. In addition, a new voxel addressing scheme has been implemented. This scheme avoids time-consuming symmetry transformations of voxel addresses by using an octant-wise symmetrically ordered field of voxels. The above methods have been applied for a fully 3-D, iterative reconstruction of 3-D sinograms recorded with a Siemens/CTI ECAT HR+ PET scanner. A comparison of the performance of the reconstruction using LOI weighting and VOI weighting is presented.

Algorithms↗

Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia.

The brain serotonin-2A receptor (5-HT(2A)R) has been implicated in both the pathology of schizophrenia and the therapeutic action of atypical antipsychotics. However, little is known about the 5-HT(2A)R status before the onset of schizophrenia and before the exposure to antipsychotics. We used [18F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT(2A)R binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT(2A)R availability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormalities of serotonergic neurotransmission that antecede the onset of schizophrenia.

Adult↗

Preferred stereoselective transport of the D-isomer of cis-4-[18F]fluoro-proline at the blood-brain barrier.

Generally, L-amino acids are preferably transported into mammalian cells compared with their D-isomers, and only L-amino acids are incorporated into proteins. Former studies, however, indicated that D-[H]proline is accumulated in the brain of mice after injection, while L-[3H]proline is not. We investigated the differential cerebral uptake of the D- and L-isomers of the PET tracer cis-4-[18F]fluoroproline (D-/L-cis-FPro) and of D-/L-[3H]proline (D-/L-Pro) in rats by dual tracer autoradiography and the uptake of D-cis-FPro in two human subjects by PET. The standardized uptake value (SUV) of D-cis-FPro in the cerebral cortex of rats 2 h p.i. was 3.05+/-1.18 (n=9) versus 0.06+/-0.01 (n=4) for L-cis-FPro (P<0.001) and 1.29+/-0.27 (n=4) for D-Pro versus 0.30+/-0.14 (n=9) for L-Pro (P<0.001). Analysis of the rat brain tissue after injection of D-cis-FPro (n=3) revealed no radioactivity in the proteins but a relevant part in the form of L-trans-FPro. The PET studies yielded a four- to five-fold higher SUV and influx rate constant in the human cortex for D-cis-FPro than for L-cis-FPro. We conclude that D-cis-FPro and D-Pro are preferably transported at the blood-brain barrier compared with their L-isomers and isomerized to the L-form within the brain. Thus, D-Pro in the plasma might be a source of intracerebral L-proline, which has been shown to act as a modulator of excitatory neurotransmission.

Animals↗

Common and differential neural mechanisms supporting imitation of meaningful and meaningless actions.

Neuropsychological studies indicate that, after brain damage, the ability to imitate meaningful or meaningless actions can be selectively impaired. However, the neural bases supporting the imitation of these two types of action are still poorly understood. Using PET, we investigated in 10 healthy individuals the neural mechanisms of imitating novel, meaningless actions and familiar, meaningful actions. Data were analyzed using SPM99. During imitation, a significant positive correlation (p < .05, corrected) of regional cerebral blood flow with the amount of meaningful actions was observed in the left inferior temporal gyrus only. In contrast, a significant positive correlation (p < .05, corrected) with the amount of meaningless movements was observed in the right parieto-occipital junction. The direct categorical comparison of imitating meaningful (100%) relative to meaningless (100%) actions showed differential increases in neural activity (p < .001, uncorrected) in the left inferior temporal gyrus, the left parahippocampal gyrus, and the left angular gyrus. The reverse categorical comparison of imitating meaningless (100%) relative to meaningful (100%) actions revealed differential increases in neural activity (p < .001, uncorrected) in the superior parietal cortex bilaterally, in the right parieto-occipital junction, in the right occipital-temporal junction (MT, V5), and in the left superior temporal gyrus. Increased neural activity common to imitation of meaningless and meaningful actions compared to action observation was observed in a network of areas known to be involved in imitation of actions including the primary sensorimotor cortex, the supplementary motor area, and the ventral premotor cortex. These results are compatible with the two-route model of action imitation which suggests that there are at least two mechanisms involved in imitation of actions: a direct mechanism transforming a novel action into a motor output, and a semantic mechanism, on the basis of stored memories, that allows reproductions of known actions. Our results indicate that, in addition to shared neural processes, the direct and the semantic mechanisms that underlie action imitation also draw upon differential neural mechanisms. The direct mechanism underlying imitation of meaningless actions differentially involves visuospatial transformation processes as evidenced by activation of areas belonging to the dorsal stream. In contrast, imitation of meaningful actions differentially involves semantic processing as evidenced by activation of areas belonging to the ventral stream.

Adult↗

PET with O-(2-18F-Fluoroethyl)-L-Tyrosine in peripheral tumors: first clinical results.

UNLABELLED: O-(2-18F-Fluoroethyl)-L-Tyrosine (18F-FET) PET has shown promising results in brain tumor diagnosis. The aim of this prospective study was to evaluate 18F-FET PET in comparison with 18F-FDG PET in patients with peripheral tumors. METHODS: Forty-four consecutive patients with suspected malignant tumors underwent 18F-FET PET and 18F-FDG PET within 7 d. Whole-body PET studies were performed 1 h after intravenous injection of 370 MBq of 18F-FET or 18F-FDG. Six patients were excluded from the analysis because a malignant tumor could not be verified. In 38 patients (7 with colorectal cancer, 6 with pancreatic cancer, 9 with head-neck cancer, 4 with lymphomas, 3 with lung cancer, 3 with ovarian cancer, 4 with breast cancer, and 2 with prostatic cancer), 18F-FET PET and 18F-FDG PET were compared. RESULTS: 18F-FET was positive in only 13 of 38 patients (8 with head-neck cancer, 3 with breast cancer, and 2 with lung cancer), whereas 18F-FDG exhibited increased uptake in 37 of 38 patients. All squamous cell carcinomas were found to be 18F-FET-positive tumors (8 head-neck cancer and 2 lung cancer), whereas most adenocarcinomas were found to be 18F-FET-negative tumors. In patients with colorectal cancer, pancreatic cancer, ovarian cancer, prostatic cancer, and lymphomas, no increased 18F-FET uptake could be identified. All lesions that exhibited increased 18F-FET uptake also showed increased 18F-FDG uptake. No additional lesion was identified by 18F-FET PET but not by 18F-FDG PET. A subgroup analysis of patients with head-neck carcinomas allowed a better distinction between malignant and inflammatory tissues with 18F-FET than with 18F-FDG. CONCLUSION: 18F-FET is inferior to 18F-FDG as a PET tracer for general tumor diagnosis. Our preliminary results suggest rather selective uptake of 18F-FET in squamous cell carcinomas. Compared with 18F-FDG PET, 18F-FET PET may allow a better distinction between tumors and inflammatory tissues in patients with squamous cell carcinomas.

Adult↗

Motion artifact reduction on parametric PET images of neuroreceptor binding.

UNLABELLED: PET studies of cerebral neuroreceptors are often recorded over periods ranging from 1 to 2 h, and head movements during the studies not only lead to blurred images but also may seriously disturb the kinetic analysis. We report the effect of motion on parametric images of the distribution volume ratio (DVR), as well as possible improvements if the dynamic PET data are corrected for head movements. METHODS: The study was performed with the 5-hydroxytryptamine 2A receptor ligand (18)F-altanserin. During PET scanning, which was performed in list mode for 1 h, the position of the head was monitored by an infrared motion-tracking system. The list mode data were sorted into time frames of between 10 s and 2 min. Motion was corrected using the multiple-acquisition-frame (MAF) approach, which calculates individual attenuation files for each emission frame and its corresponding head position to avoid misalignment of transmission and emission data. After reconstruction of attenuation-corrected emission frames, each image frame was realigned to match the head position of the first frame of the emission scan. The resulting motion-corrected dynamic images were evaluated using the noninvasive Logan plot to obtain parametric images of DVR. RESULTS: DVR images of motion-affected (18)F-altanserin scans showed artifacts whose extent depended on the amount of movement. The artifacts were mainly at the border between gray matter and white matter and at the outer border of gray matter. They were seen as discontinuities and small spots whose values exceeded the expected DVR values or were even negative and that disappeared when motion correction was applied. These effects in human data were also seen on simulated (18)F-altanserin images that contained no statistical noise. CONCLUSION: Whereas the native PET images looked just blurred if the patient moved during the PET scan, parametric images of the Logan DVR, which are calculated by pixelwise linear regression, contained severe discontinuities primarily at the cortical edge. MAF-based motion correction was able to avoid these errors.

Artifacts↗

PET identifies transitional metabolic change in the spinal cord following a subthreshold dose of irradiation.

Positron emission tomographic (PET) investigations were performed to obtain in vivo information on symptomless radiation-induced pathological changes in the human spinal cord. PET investigations were carried out prior to radiotherapy and during the regular follow-up in an early hypopharyngeal cancer patient (the spinal cord was irradiated with a biologically effective dose of 80 Gy2), with [18F]fluorodeoxyglucose (FDG), [11C]methionine and [15O]butanol as tracers; radiosensitivity and electroneuronographic (ENG) studies were also performed. A very low background FDG accumulation (mean standardized uptake values, i.e. SUV: 0.84) was observed in the spinal cord before the initiation of radiotherapy. An increased FDG uptake was measured 2 months after the completion of radiotherapy (mean SUV: 1.69), followed by a fall-off, as measured 7 months later (mean SUV: 1.21). By 44 months after completion of irradiation, the FDG accumulation in the irradiated segments of the spinal cord had decreased to a level very close to the initial value (mean SUV: 1.11). The simultaneous [15O]butanol uptake results demonstrated a set of perfusion changes similar to those observed in connection with the FDG accumulation. The patient exhibited an extremely low [11C]methionine uptake within the irradiated and the nonirradiated spinal cord during the clinical course. She has not had any neurological symptoms, and the results of central ENG measurements before radiotherapy and 2 months following its completion proved normal. Radiobiological investigations did not reveal unequivocal signs of an increased radiosensitivity. A transitory increased spinal cord FDG uptake following radiotherapy may be related to the posttherapeutic mild inflammatory and regenerative processes. The normal [11C]methionine accumulation observed is strong evidence against intensive cell proliferation. The high degree of normalization of the temporarily increased FDG uptake of the irradiated spinal cord segments by 44 months is in good agreement with the results of monkey studies, which demonstrated a nearly complete recovery from radiation-induced spinal cord injury.

Butanols↗

Functional reorganisation in patients with right hemisphere stroke after training of alertness: a longitudinal PET and fMRI study in eight cases.

In patients with alertness deficits due to right hemispheric vascular brain damage, training induced changes in the individual functional networks involved in intrinsic alertness were assessed in a longitudinal positron emission tomography (PET)/fMRI activation study. Patients were trained by administering the alertness routine of the AIXTENT computerized attention training or, in the control condition, by using a computerized training of verbal and topological memory. Before and after the training, both a PET/fMRI and a neuropsychological assessment were carried out. In this paper, we are presenting four patients after alertness training: three, whose alertness performance improved significantly after training, and one, who did not improve. In the patients showing behavioural improvement, the PET/fMRI activation after training revealed partial restitution of the right hemisphere (RH) functional network known to subserve intrinsic alertness in normal subjects, especially in the right dorsolateral or medial frontal cortex. For the patient without behavioural improvement, the PET activation after training showed an increase of activation only in the left hemisphere. Out of the four patients in the memory training control group only one showed significant improvement of alertness. Another patient had an increase of right frontal activation after the training but this did not correspond to behavioural improvement. In a control group of six normal participants, repetition of the alertness activation paradigm in fMRI revealed a decrease of right frontal and parietal activation from the first to a second measurement after 3 weeks, in contrast to the observed training induced effects in the patients.

Adult↗

Network for auditory intrinsic alertness: a PET study.

Intrinsic alertness designates the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time (RT) measurements without preceding warning stimuli. Until now, cerebral networks subserving alertness after visual and somatosensory stimulation have been reported. Studies concerning other intensity aspects of alertness like sustained attention and vigilance, on the other hand, have been performed in the auditory modality, too. In a 15O-butanol PET-activation study in 10 right-handed young healthy male volunteers an intrinsic alertness network was studied for the auditory modality. In contrast with a sensorimotor control condition we found an extended predominantly right-hemisphere network similar to those reported for other sensory modalities including frontal, cingular, inferior parietal, temporal and thalamic structures, when subjects waited for and rapidly responded to a 1000 Hz tone signal by pressing a response key with the right-hand thumb. There were, however, some differences in the topography of the frontal, temporal and thalamic activations between auditory and visual stimulation which are discussed with respect to similar results for auditory vigilance and auditory selective attention tasks reported in the literature.

Acoustic Stimulation↗

Neural responses to the production and comprehension of syntax in identical utterances.

Following up on an earlier positron emission tomography (PET) experiment (Indefrey et al., 2001), we used a scene description paradigm to investigate whether a posterior inferior frontal region subserving syntactic encoding for speaking is also involved in syntactic parsing during listening. In the language production part of the experiment, subjects described visually presented scenes using either sentences, sequences of noun phrases, or sequences of syntactically unrelated words. In the language comprehension part of the experiment, subjects were auditorily presented with the same kinds of utterances and judged whether they matched the visual scenes. We were able to replicate the previous finding of a region in caudal Broca's area that is sensitive to the complexity of syntactic encoding in language production. In language comprehension, no hemodynamic activation differences due to syntactic complexity were found. Given that correct performance in the judgment task did not require syntactic processing of the auditory stimuli, the results suggest that the degree to which listeners recruit syntactic processing resources in language comprehension may be a function of the syntactic demands of the task or the stimulus material.

Attention↗

Imaging of gliomas with Cis-4-[18F]fluoro-L-proline.

Tumor imaging with cis-4-[18F]fluoro-L-proline (cis-FPro) was compared to that of L-[3H]proline and L-[3H]methionine in F98 rat gliomas by dual-tracer autoradiography. All tracers exhibited high accumulation in the tumors but in the normal brain significant uptake was observed for L-[3H]methionine only. Tumor extent on autoradiograms with L-[3H]proline and L-[3H]methionine was identical to that of histological staining while autoradiograms of cis-FPro showed diffuse uptake in the penumbra of some tumors. First PET studies in 7 patients with cerebral gliomas demonstrated accumulation of cis-FPro in tumor areas with enhancement of Gd-DTPA on MR scans. Uptake of cis-FPro in normal brain tissue was negligible. In one patient with a glioblastoma accumulation of cis-FPro was also found in two brain areas without enhancement of Gd-DTPA on MR scans. Control of MRI suggested tumor growth in these areas at further follow up. Our results indicate that in most gliomas increased cis-FPro uptake is restricted to areas with disruption of the BBB which limits its clinical utility.

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↗

Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine.

The whole-body distribution of O-(2-[(18)F]fluoroethyl)- l-tyrosine (FET) was studied in seven patients with brain tumours by positron emission tomography (PET). Based on the IMEDOSE and MIRDOSE procedures, radiation absorbed doses were estimated from whole-body PET scans acquired approximately 70 and 200 min after i.v. injection of 400 MBq FET. After injection of FET, the peak of radioactivity in the blood was observed after 1.5 min, and a plateau of nearly constant radioactivity was reached at 20 min. The whole-body distribution of FET showed the highest activities in the urinary tract. All other organs exhibited only moderate FET uptake (SUV </=1.6) which remained constant between early and late PET scans. No increased uptake was seen in the bone, the biliary tract or the pancreas. Twenty-two percent of the injected activity was excreted 5 h p.i. (approx. 5.3% ID/h). The highest absorbed dose was found for the urinary bladder wall. The effective dose according to ICRP 60 was 16.5 micro Sv/MBq for adults, which would lead to an effective dose of 6.1 mSv in a PET study using 370 MBq FET.

Adult↗

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↗

In vivo imaging of adenosine A1 receptors in the human brain with [18F]CPFPX and positron emission tomography.

The important roles played by the A(1) adenosine receptor (A(1)AR) in brain physiology and pathology make this receptor a target for in vivo imaging. Here we describe the distribution of A(1)ARs in the living human brain with PET, made possible for the first time by the highly potent and selective A(1)AR antagonist 8-cyclopentyl-3-(3-[(18)F]fluoropropyl)-1-propylxanthine ([(18)F]CPFPX). In vivo data demonstrate a rapid cerebral uptake, peaking at 2.9 +/- 0.6% injected dose/liter at 3.3 +/- 1.3 min, followed by a gradual washout. Consistent with the results of autoradiography, high receptor densities occurred in the putamen and the mediodorsal thalamus. Neocortical regions showed regional differences in [(18)F]CPFPX binding, with high accumulation in temporal > occipital > parietal > frontal lobes and a lower level of binding in the sensorimotor cortex. Ligand accumulation was low in cerebellum, midbrain, and brain stem. Metabolism of [(18)F]CPFPX is rapid outside the central nervous system, but the metabolites do not penetrate the blood-brain barrier. In conclusion, in vivo application of [(18)F]CPFPX, a highly potent and selective PET ligand, for the first time allows the imaging of A(1)ARs in the living human brain.

Adult↗