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Biomedical subjects

M Rausch

Publications and source records attributed to M Rausch.

At least 19 recordsLinked to original sources

A study paradigm allowing comparison of multiple high-resolution rCBV-maps for the examination of drug effects.

Owing to the neuro-vascular coupling, measurement of changes in regional cerebral blood flow and blood volume (rCBV) can be used as surrogates reflecting the effects of central nervous system active drugs on neural transmission. As most such drugs are administered orally or intramuscularly and, in many cases, beneficial effects due to drug treatment can be observed only after chronic administration for days or weeks, the evaluation of drug efficacy requires the development of acquisition and analysis tools that allow for comparison of imaging data sets obtained in multiple sessions and for multiple subjects. In the present study, high-resolution susceptibility contrast MR perfusion imaging using a super-paramagnetic contrast agent (CA) was applied to study the effect of a single oral administration of the acetylcholine-esterase inhibitor rivastigmine (Exelon) on rCBV in rats. rCBV maps were calculated from two T2-weighted three-dimensional fast-spin-echo scans recorded before and after the injection of the CA, respectively. All MRI data sets were mapped to a reference data set obtained from a normal male Sprague-Dawley rat using an automated co-registration procedure prior to the analysis for drug effects. Rivastigmine was orally administered at doses of 2, 4 or 8 mg/kg 1 h prior to the rCBV measurement. Rivastigmine increased rCBV in several brain areas including cortex, caudate putamen and hippocampus. The observed effects were dose-dependent and the changes reached the order of 5-12% as compared with baseline levels. Vehicle-treated animals showed no significant alterations of blood volume, demonstrating the reproducibility and stability of rCBV measurements.

Administration, Oral↗

The clinical significance of diffusion-weighted MR imaging in infratentorial strokes.

OBJECTIVE: To study the association between diffusion-weighted imaging (DWI) characteristics and stroke etiology, stroke severity, and functional outcome in patients with infratentorial strokes. METHODS: The authors prospectively studied 22 consecutive patients with acute infratentorial strokes. They used a blinded comparison of DWI features (number, distribution, and volume of lesions) with clinical characteristics, namely, stroke etiology (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] classification), severity (NIH Stroke Scale [NIHSS]), length of stay (LOS), and functional 3-month outcome using modified Rankin Scale, Barthel Index, and a dichotomized outcome status (living at home vs institutionalization or death). RESULTS: Acute infratentorial DWI lesions were detected in 95% (21/22) of the patients. The number (p = 0.01) and the distribution (p < 0.001) of DWI lesions were correlated with stroke etiology. Patients with cardioembolic strokes (n = 5) had more DWI lesions (8.0 +/- 6.0) than those with other stroke etiologies (n = 17; 1.3 +/- 0.9; p < 0.001). Their lesion distribution differed from that of patients with noncardioembolic strokes (p < 0.001). Clinically silent, acute DWI lesions in the anterior circulation in addition to their infratentorial lesions were visualized in 3 of 5 patients with cardioembolic stroke and in none of 17 patients without sources of cardioembolism (p < 0.001). Pure infratentorial lesions were present in 15 of 17 patients with noncardioembolic strokes and in none of 5 cardioembolic stroke patients (p < 0.001). DWI lesion volume was not correlated with NIHSS score, LOS, outcome scores, or outcome status. CONCLUSION: In infratentorial strokes, multiple DWI lesions and a distribution of subsidiary, clinically silent DWI lesions in the anterior circulation suggest a cardioembolic stroke etiology. However, DWI lesion volume did not correlate with the NIHSS score and was no predictor of outcome.

Adult↗

MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE.

Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model that in several respects mimics human multiple sclerosis (MS), and can be used to design or validate new strategies for treatment of this disease. In the present study, different MRI techniques (macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), blood-brain barrier (BBB) breakdown, and magnetization transfer imaging (MTI)), as well as immunohistological staining were used to study the burden of disease in Lewis rats immunized by guinea pig myelin. The resulting imaging data was compared with behavioral readouts. Animals were studied during the acute phase and the first relapse. Activated monocytes were detected during both episodes in the brain stem or cortex. These areas coincided in part with areas of BBB breakdown. Significant changes of the magnetization transfer ratios (MTRs) of up to 35% were observed in areas of USPIO accumulation. This suggests that infiltrating monocytes are the major source of demyelination in EAE, but monocyte infiltration and breakdown of the BBB are temporally or spatially independent inflammatory processes.

Acute Disease↗

MRI and color-coded duplex sonography: diagnosis of partial priapism.

A case of partial priapism is reported diagnosed by contrast-enhanced MR imaging and color-coded duplex sonography. Follow-up examinations after 4 weeks and 3 months were performed. According to the results of color-coded duplex sonography and MRI, a partial priapism with development from the subacute stage to a fibrous residuum after spontaneous lysis was diagnosed. There are only very few cases of partial priapism reported in the literature and this is the first case report that demonstrates diagnosis and follow-up both by color-coded duplex sonography and contrast-enhanced MR imaging.

Diagnosis, Differential↗

In-vivo visualization of phagocytotic cells in rat brains after transient ischemia by USPIO.

Cerebral ischemia provokes tissue damage by two major patho-physiological mechanisms. Direct cell necrosis is induced by diminished access of neurons and glia to essential nutrients such as glucose and oxygen leading to energy failure. A second factor of cellular loss is related to the activation of immune-competent cells within and around the primary infarct. While granulocytes and presumably monocytes are linked to the no-reflow phenomenon, activated microglia cells and monocytes can release cytotoxic substrates, which cause delayed cell death. As a consequence the infarct volume will increase, despite restoration of cerebral perfusion. In the past, visualization of immune competent cells was only possible by histological analysis of post-mortem tissue. However, contrast agents based on small particles of iron oxide are known to accumulate in organs rich in cells with phagocytotic function. These particles can be tracked in vivo by MRI methods based on their relaxation properties. In the present study, the spatio-temporal distribution of USPIO particles was monitored in a rat model of transient cerebral infarction using T1- and T2-weighted MRI sequences. USPIO were detected in vessels at 24 h after administration. At later time points specific accumulation of USPIO was observed within the infarcted hemisphere, with maximal signal enhancement on day 2. Their detectability based on T1-contrast disappeared between day 4 and day 7. Immuno-histochemically (IHC) stains confirmed the presence of macrophages, presumably blood-derived monocytes within areas of T1 signal enhancement. Direct visualization of iron-burdened macrophages by IHC was only possible later than day 3 after occlusion.

Animals↗

Characterization of a new HLA-A allele, A*0256, identified in a Caucasian individual.

HLA-A typing by the PCR-SSP method in a male 21-year-old Caucasian individual revealed a very rare allele combination corresponding to a unique reaction pattern. Therefore, the result was examined using sequence-based typing. Sequencing of exons 2 and 3 of the HLA-A locus after allelic separation with specific primers revealed the sequence of a new allele, similar to A*0245. Sequencing of exons 1 and 4 resulted in no additional inconclusive positions. The sequence pattern of the new allele HLA-A*0256 might have been generated as a result of a double crossing over recombination of an A*0201 and either an A*03 or an A*11.

Adult↗

Topography of orientation centre connections in the primary visual cortex of the cat.

The functional topography of lateral connections to orientation-centre zones was studied by optical imaging of intrinsic signals in combination with tracer injections (fluorescent beads and biocytin) and electrophysiological recordings. Three-dimensional reconstruction of anterogradely labelled axon terminals and retrogradely labelled somata revealed a uniform distribution across all orientations in a non-patchy manner. The overall lateral extent of the labelling was 3-4 mm in layer 3, that is about half of the extent observed for orientation domain connections in the same layer. These bulk injection data are in contrast with the reportedly sharp orientation tuning of neurons of centre zones and suggest that orientation specificity here does not require highly specific connections. Nonetheless, another plausible scenario is that orientation centre connections are orientation specific but their specificity present at the single cell level cannot be revealed by bulk labelling due to their large spatial overlap.

Animals↗

Bicuculline-induced brain activation in mice detected by functional magnetic resonance imaging.

Dynamic measurements of local changes in relative cerebral blood volume (CBV(rel)) during a pharmacological stimulation paradigm were performed in mice. Using magnetite nanoparticles as an intravascular contrast agent, high-resolution CBV(rel) maps were obtained. Intravenous administration of the GABA(A) antagonist bicuculline prompted increases in local CBV(rel) as assessed by MRI with a high spatial resolution of 0.2 x 0.2 mm(2) and a temporal resolution of 21 s. Signal changes occurred 20-30 s after the onset of drug infusion in the somatosensory and motor cortex, followed by other cortical and subcortical structures. The magnitudes of the CBV(rel) increases were 18% +/- 4%, 46% +/- 14%, and 67% +/- 7%, as compared to prestimulation values for the cortex, and 9% +/- 3%, 25% +/- 4%, and 36% +/- 7% for the caudate putamen for bicuculline doses of 0.6, 1.25, and 1.5 mg/kg, respectively. On-line monitoring of transcutaneous carbon dioxide tension PtcCO(2) reflecting arterial PaCO(2) did not show any alteration during the stimulation paradigm. One of five of the mice receiving the highest bicuculline dose, and three of seven receiving the intermediate dose displayed a different cortical response pattern. After a CBV(rel) increase of 40% lasting for approximately 1 min, significant CBV(rel)reductions by 80% have been observed. Subcortical structures did not display this behavior. The present study suggests that this noninvasive approach of functional MRI (fMRI) can be applied to study drug-induced brain activation by central nervous system (CNS) drugs in mice under normal and pathological situations.

Animals↗

Dynamic patterns of USPIO enhancement can be observed in macrophages after ischemic brain damage.

Cells of the mononuclear phagocytotic system (MPS) are often found near to or within ischemic tissue and can potentially aggravate cellular damage. Hence, visualization of those cells would allow demarcation of putatively affected from intact tissue. Experimental MRI studies have shown that ultrasmall particles of dextran-coated iron oxide (USPIO) are internalized into cells of the MPS. To test if this cell tagging method may be also applied to cerebral infarction, USPIOs were administered to Fisher rats 5.5 h after permanent occlusion of the middle cerebral artery (pMCAO). During the first 2 days USPIO were preferentially found in patches within the lesion and in surrounding areas. On day 4, USPIOs expanded within the core of the lesion. On day 7 they were found predominantly within the boundary area. Histological analysis showed large populations of macrophages containing iron particles in the infarcted tissue. We conclude, therefore, that it is possible to monitor MPS activity after focal cerebral ischemia using USPIOs.

Animals↗

Enhanced responsiveness of human extravisual areas to photic stimulation in patients with severely reduced vision.

Lesions in the primary visual cortex induce severe loss of visual perception. Depending on the size of the lesion, the visual field might be affected by small scotomas, hemianopia, or complete loss of vision (cortical blindness). In many cases, the whole visual field of the patient is affected by the lesion, but diffuse light-dark discrimination remains (residual rudimentary vision, RRV). In other cases, a sparing of a few degrees can be found (severely reduced vision, SRV). In a follow-up study, we mapped visually induced cerebral activation of three subjects with SRV using functional magnetic resonance imaging. We were especially interested in the visual areas that would be activated if subjects could perceive the stimulus consciously although information flow from V1 to higher visual areas was strongly reduced or virtually absent. Because subjects were only able to discriminate strong light from darkness, we used goggles flashing intense red light at a frequency of 3 Hz for full visual field stimulation. Besides reduced activation in V1, we found activation in the parietal cortex, the frontal eye fields (FEF), and the supplementary eye fields (SEF). In all patients, FEF activation was pronounced in the right hemisphere. These patterns were never seen in healthy volunteers. In a patient who recovered completely, we observed that extrastriate activation disappeared in parallel with the visual field restitution. This result suggests that damage to the primary visual cortex changes the responsiveness of parietal and extravisual frontal areas in patients with SRV. This unexpected result might be explained by increased stimulus-related activation of attention-related networks.

Adult↗

Analysis of input functions from different arterial branches with gamma variate functions and cluster analysis for quantitative blood volume measurements.

Regional cerebral blood volume (rCBV) provides valuable information about the nature and progress of diseases of the central nervous system. While relative rCBV maps can be derived directly from dynamic susceptibility contrast data, the arterial input function (AIF) has to be measured for absolute rCBV quantification. For determination of the AIF pixels located completely within a feeding artery must be selected. However, by using a region-of-interest (ROI) based selection some confounding effects can occur, especially if single shot echo planar imaging (EPI) with low spatial resolution is used. In this study we analyzed the influence of partial volume effects and spatial misregistration due to frequency shifts induced by paramagnetic contrast agents. We analyzed AIFs from the internal carotid artery (ICA), the vertebral artery (VA) and the middle cerebral artery (MCA) using gamma variate function based parameterization. The concentration time curves (CTC) of several pixels which were selected on the basis of strong signal drop appeared distorted during the bolus passage. Moreover, the amplitudes of input functions derived from the MCA were smaller by a factor of three as compared to those of the ICA and VA. Simulations revealed that these effects can be attributed to a spatial shift of the vessel along phase-encoding direction during the passage of the bolus. We therefore developed a procedure for a pixel selection based on cluster analysis which classifies pixels according to the parameters of the fitted gamma variate functions. This approach accounted for misregistration of the vessel and yielded very consistent results for a group of normal subjects.

Brain↗

[Detection of central auditory compensation in unilateral deafness with functional magnetic resonance tomography].

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a noninvasive method to detect focal brain activity at high spatial resolution. Acoustic stimulation induces an increase of regional cerebral blood flow in the primary auditory cortex. This entails an increased concentration of diamagnetic oxyhemoglobin in the capillaries and the venous system. The resulting decrease of the local magnetic susceptibility was detected as a signal increase in T2*-weighted images. The central auditory pathways predominantly cross to the contralateral hemisphere in normally hearing subjects. The aim of the present study was to investigate the primary auditory cortex after acoustic stimulation in unilateral deaf patients using fMRI. METHODS: Magnetic resonance images were acquired on a 1.5 T Siemens Vision scanner. For fMRI, a single shot gradient recalled, echo planar imaging (EPI) sequence with decreasing excitation order was used, allowing the aquisition of 9 slices within 1.8 s. The 9 slices covered a slab of 3.6 cm in cranio-caudal extension in the region of the temporal lobes. For statistical processing of the raw image data the SPM96 software package was used. A p-value of p < 0.01 was applied to differentiate between activated and non-activated. The resulting functional activation maps were superimposed onto the EPI scan. The number of activated pixels was used to quantitate the cortical response upon acoustic stimulation. Stimulation consisted of a 1000-Hz sine tone (100 dB SPL at the distal end of the head phone, pulsed at 6 Hz) to which the patients were asked to listen passively. A piezoelectric loudspeaker was mounted on the subject table and connected to a plastic tube system leading to a combination of bilateral ear- and headphones. Auditory paradigms require disentangling experimental excitation from the scanner noise that approximates 90 dB. Headphones suppress noise by approximately 30 dB. To decrease the acoustic background-to-stimulation ratio and to keep background noise constant during stimulation and resting, we employed short scanning (1.8 s) and long resting periods (10.2 s; TR = 12 s). This acquisition mode allows sufficient recovery during off-periods and sufficient excitation during on-periods. 14 unilateral deaf patients were examined. The mean duration of deafness was 22.5 years. RESULTS: Acoustic stimulation of the deaf ear revealed only weak cortical activation which could be explained by sound transmission via bone conduction to the other ear. A significant increase of BOLD (blood oxygen level dependent)-activation in the primary auditory cortex could be demonstrated in all patients after stimulation of the hearing ear. However, remarkable individual differences were noticed concerning the absolute number of activated pixels. The lateralization ratio was calculated by the number of activated pixels on the hearing side divided by the number of activated pixels on the deaf side. A mean lateralization ratio of 0.9 (Stdv +/- 0.6) was found. The mean lateralization ratio for patients with a right deaf ear (n = 8) and those with a left deaf ear (n = 5) was 1.1 (Stdv +/- 0.7) and 0.6 (Stdv +/- 0.3) respectively. However, the difference was not significant (Wilcoxon test: p = 0.08). CONCLUSIONS: Central-auditory compensation by bilateral cortical activation was demonstrated in unilateral deaf patients. Moreover, a tendency towards a dominance of the left primary auditory cortex was found, although the difference between both hemispheres was not significant. The lateralization ratio in unilateral deaf patients is similar to findings after binaural stimulation in normally hearing subjects.

Acoustic Stimulation↗

Developing realistic treatment standards in today's economic climate: stroke survivor education.

Teaching people about the risk factors and early symptom identification of stroke significantly decreases the incidence of both first time and recurrent strokes. Patient teaching has traditionally been a nursing responsibility. However, in the fiscal constraints of today's health care delivery system, nurses' time for teaching is highly restricted. This pilot study was designed to evaluate the impact of a short 1(1/2) hour stroke education programme in a population of hospitalized stroke survivors prior to their discharge. The first session focused on the disease process of stroke and its warning signs. A second session addressed risk factors and behavioural strategies for exercise, stress management, or smoking cessation. Responses to the teaching programme were evaluated through patient interviews immediately following the teaching session and 3 weeks later. Responses indicated that short-session patient teaching, in and of itself, is not always successful in changing behaviour but is successful for knowledge attainment. The findings from this pilot study suggests a need to consider new teaching strategies and a need to identify opportunities for reinforcement, support and encouragement that will meet the realities of today's time constraints while still meeting our professional responsibilities for patient education.

Adult↗

Neural structures associated with recognition of facial expressions of basic emotions.

People with Huntington's disease and people suffering from obsessive compulsive disorder show severe deficits in recognizing facial expressions of disgust, whereas people with lesions restricted to the amygdala are especially impaired in recognizing facial expressions of fear. This double dissociation implies that recognition of certain basic emotions may be associated with distinct and non-overlapping neural substrates. Some authors, however, emphasize the general importance of the ventral parts of the frontal cortex in emotion recognition, regardless of the emotion being recognized. In this study, we used functional magnetic resonance imaging to locate neural structures that are critical for recognition of facial expressions of basic emotions by investigating cerebral activation of six healthy adults performing a gender discrimination task on images of faces expressing disgust, fear and anger. Activation in response to these faces was compared with that for faces showing neutral expressions. Disgusted facial expressions activated the right putamen and the left insula cortex, whereas enhanced activity in the posterior part of the right gyrus cinguli and the medial temporal gyrus of the left hemisphere was observed during processing of angry faces. Fearful expressions activated the right fusiform gyrus and the left dorsolateral frontal cortex. For all three emotions investigated, we also found activation of the inferior part of the left frontal cortex (Brodmann area 47). These results support the hypotheses derived from neuropsychological findings, that (i) recognition of disgust, fear and anger is based on separate neural systems, and that (ii) the output of these systems converges on frontal regions for further information processing.

Adult↗

Proprioception acts as the main source of input in human S-I activation experiments: a functional MRI study.

During tactile exploration cells in human somatosensory cortex S-I receive input from skin receptors and from proprioceptive feedback. To study the extent to which these sources contribute to cell activation we used functional magnetic resonance imaging (fMRI) in order to visualize the spatial extent and amplitude of activation in S-I during active finger movement and passive stimulation of finger tips. In all subjects (n = 6) we measured activation elicited by unilateral single finger tapping (active task) and mechanical stimulation of the palm of the index finger (passive task). In the finger tapping condition all subjects showed a strict contralateral activation of somatosensory cortex S-I and motor cortex M-I. In the passive stimulation experiment we found activation of the contralateral somatosensory cortex S-I only. Although subjects were trained to perform the finger movement with the same frequency and pressure in comparison to the passive stimulation, the activation within S-I induced by finger movements was always significantly larger than that induced by passive stimulation. This result implies that activation of somatosensory cortex originates to a large extent from proprioception while tactile input plays a minor role in S-I excitation.

Adult↗

Stage I and stage II infiltrating ductal carcinoma of the breast analyzed for chromosome 8 copy number using fluorescent in situ hybridization.

We previously reported the results of 30 informative samples (from a total of 34 specimens gathered) of archival breast cancer tissue, including infiltrating ductal carcinoma (NOS), ductal carcinoma in situ, lobular carcinoma, papillary carcinoma and benign lesions of the breast. The study was conducted using fluorescent in situ hybridization (FISH) and a chromosome 8 alpha-satellite probe. Subsequently, a total of 34 cases of infiltrating ductal carcinoma of the breast (NOS, 17 cases stage I and 17 cases stage II) were studied, again using interphase cytogenetics. The aim of the present study is to confirm and extend the results of our initial study of stage I and stage II disease. Towards this end, 36 additional specimens of formalin-fixed paraffin-embedded breast cancer tissue have been analyzed cytogenetically under blinded conditions for the frequency of abnormal chromosome 8 copy numbers using FISH and the previously described protocol optimized for our laboratory. Of these, 18 were stage I and 18 were stage II. The frequency of trisomy 8 among stage I tumors was found to be 28% (5 out of 18). The frequency of trisomy 8 among stage II tumors was found to be 61% (11 out of 18). These results, while less striking, are consistent with those reported in our initial study of stage I and stage II disease, where the frequencies of trisomy 8 among stage I and stage II tumors were 24% (4 out of 17) and 82% (14 out of 17). These results not only establish that chromosome 8 trisomy is a recurrent finding in breast cancer, but also confirm that a higher frequency of trisomy 8 was observed with a higher clinical stage (stage II) than with a lower stage (stage I). It will be of interest to extend the findings in stage I and stage II breast cancer to other stages as well.

Adult↗