Biomedical subjects

A Kleinschmidt

Publications and source records attributed to A Kleinschmidt.

At least 55 records · Page 3Linked to original sources

PubMed1995

[Strategies for data analysis of brain activation studies with functional MR tomography].

The sensitivity of gradient-echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation has been introduced for mapping functional brain activation. To benefit from the high spatial and temporal resolution of the respective dynamic MRI data sets, their analysis requires algorithms that are capable of both precisely delineating task-related activation patterns and demonstrating functional connectivity of interacting areas. Here, we present various strategies for data evaluation by means of correlational analyses that surpass the quality of subtraction-based activation maps by improving both sensitivity and robustness. On a pixel-by-pixel basis the approach correlates signal time courses with a reference function, reflecting the temporal sequence of activated and control states. Extended versions employ the calculation of auto- or cross-correlation functions that increase sensitivity, but require periodic stimulations. Following individual correction for non-specific but correlated signal fluctuations, mapping of task-related coherent activation can be improved using neighborhood principles. Such refined strategies are expected to enhance the usefulness of oxygenation-sensitive MRI for studying the functional anatomy of the human brain under both physiological and pathological conditions.

Algorithms↗

PubMed1994

Brain or vein--oxygenation or flow? On signal physiology in functional MRI of human brain activation.

Stimulus-related signal changes in functional MRI of human brain activation not only reflect associated adjustments of cerebral blood flow and oxygen consumption, but strongly depend on the MRI technique chosen and the actual experimental setting. A list of relevant parameters includes static field homogeneity of the magnet, MR pulse sequence and signal type, TE, TR, flip angle, gradient strengths, gradient waveforms, receiver bandwidth and voxel size. In principle, a local signal increase during functional activation may reflect a regional change in cerebral blood flow or deoxyhemoglobin concentration or both. This ambiguity was demonstrated using long TE FLASH MRI at high spatial resolution. Subsequently, experimental strategies were evaluated that either discriminate MRI effects in large vessels from those in the cortical microvasculature or separate changes in blood flow velocity from those in blood oxygenation. Examples comprise studies of the human visual and motor cortex.

Brain↗

PubMed1994

Dysfunctional activation of subcortical nuclei in palatal myoclonus detected by high-resolution MRI.

Magnetic resonance images that were sensitized to changes in cerebral blood oxygenation state demonstrated dysfunctional activation of the dentate nuclei, the left inferior olivary nucleus and the left red nucleus in a 56-year-old patient with palatal myoclonus. These findings represent the first demonstration of movement-related activation of cerebellar, brainstem and midbrain nuclei in a single subject and at a spatial resolution comparable to that of anatomic MR images.

Brain Stem↗

PubMed1994

Pharmacokinetics and radiation dose of oxygen-15 labelled butanol in rCBF studies in humans.

In this positron emission tomography (PET) study in humans we determined the pharmacokinetics and radiation dose of oxygen-15 labelled butanol, a recently introduced tracer for regional cerebral blood flow (rCBF). This report includes a description of the automated preparation of 15O-butanol which allows repetitive activation studies, each 15 min apart. Dynamic rCBF studies were extended by prolonged measurements up to 15 min after injection over different organs such as brain, liver, kidneys and bladder. All measurements were done with a whole-body PET camera PC4096-15WB. Based on the pharmacokinetic data in 13 subjects the radiation doses to single organs were calculated according to MIRD pamphlet No. 11 and the effective dose defined by ICRP 60 as an indicator of radiation dose to the total body. The liver received the highest radiation dose of about 2.2 mGy per 1500 MBq of injected 15O-butanol, which is the typical amount of administered tracer in one rCBF measurement. The dose to the kidneys was 1.6 mGy, to the stomach 0.8 mGy, and to the brain 0.16 mGy. The effective dose was 0.54 mGy, which was similar to that of H2(15)O, but lower than the effective dose from C15O2 in amounts typically applied in human rCBF studies.

Adult↗

PubMed1994

In vivo morphometry of planum temporale asymmetry in first-episode schizophrenia.

Magnetic resonance imaging is a promising tool for in vivo analysis of the neuropathology underlying schizophrenia. One of the most consistent features emerging from the majority of published studies is the lateralization of pathological findings, and this has led to hypotheses of impaired hemispheric specialization in schizophrenia. In previous work, we have validated morphometry of supratemporal language-related cortex using high-resolution magnetic resonance imaging and analyzed the relation of the so defined planum temporale to functional parameters of hemispheric specialization. In the present study, we examined planum temporale structural asymmetry in first-episode schizophrenics. Asymmetry coefficients obtained in these patients did not differ significantly from those in equally right-handed controls and were not correlated to standard psychopathological measures. These data are contrasted with other studies reporting lateralized brain pathology in schizophrenia with special emphasis on methodological considerations in neuroimaging procedures.

Adult↗

PubMed1994

Correlational imaging of thalamocortical coupling in the primary visual pathway of the human brain.

While the anatomy of the human brain is well defined, the functional connectivity of its structures is far less understood. Modern neuroimaging techniques offer the unique opportunity of visualizing physiologic activation in central nervous structures and of identifying the elements underlying distributed networks for information processing. Following improved spatial resolution of deoxyhemoglobin-sensitive magnetic resonance imaging, we were able to detect simultaneous signal changes in the lateral geniculate nucleus and primary visual cortex during periodic photic stimulation. Visualization of coupled activation by cross-correlation analysis resulted in the first demonstration of thalamocortical interaction in the primary visual pathway of the intact human brain.

Adult↗

PubMed1994

The effect of acetazolamide on regional cerebral blood oxygenation at rest and under stimulation as assessed by MRI.

The sensitivity of gradient echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation (CBO) has been introduced for mapping functional brain activation. Here, we report that this approach allows monitoring autoregulation in the human brain under vasodilatory stress. Following the administration of acetazolamide, signal intensities of deoxyhemoglobin-sensitive images increased in cortical and subcortical gray matter and to a lesser extent in white matter. This result reflects a venous hyperoxygenation stemming from an increase in cerebral perfusion with oxygen consumption remaining constant. In addition, pharmacologic induction of vasodilation attenuated activity-related MRI signal changes in the visual cortex under photic stimulation. Although intersubject variability was high, this finding indicates individually persisting autoregulatory responsiveness to functional challenge despite an "exhausted" reserve capacity. It is suggested that recording CBO by MRI will foster our understanding of modulation of vasomotor tone and cerebral perfusion. Furthermore, this technique may prove valuable for assessing the cerebrovascular reserve capacity in patients with carotid artery occlusive disease.

Acetazolamide↗

PubMed1994

Tactile exploration of shape after subcortical ischaemic infarction studied with PET.

We studied the cerebral activations related to restitution of hand function in five patients with first hemiplegic subcortical stroke due to ischaemic infarction in the area of the basal ganglia or thalamus. In two subjects, involvement of the cortico-spinal tract was demonstrated by magnetic evoked potentials. The subjects were requested to discriminate rectangular parallelepipeda of identical mass with their affected hands. Regional cerebral blood flow (rCBF) was measured with PET after intravenous bolus injection of [15O]butanol, at rest and during task execution. Evaluation of the rCBF changes was based on pixel-by-pixel t statistics of spatially standardized and averaged PET images and on a statistical distribution analysis of regions of interest in the individual subjects. For anatomical localization of the significant rCBF changes, a computerized brain atlas (Greitz et al. J Comput Assist Tomogr 1991; 15: 26-38) and a matching procedure that directly aligns individual PET and high resolution magnetic resonance images were used. The rCBF at rest and the task-induced rCBF changes varied from subject to subject, as did the residual neurological deficits at the time of PET scanning. In all subjects there were large activation areas in the motor and the sensory hand area contralateral to the affected hand. Poor performance of the task was correlated with a low rCBF in the contralateral sensorimotor cortex at rest and a bilateral activation of the primary sensorimotor cortex during task performance. The premotor cortex, ipsilateral and anterior cerebellum, contralateral to the affected hand, were also significantly activated. Further activations were observed in the contralateral premotor cortex, supplementary motor area and bilaterally in the posterior cingulate cortex, but were less consistent among the subjects. Our data suggest that recovery from hemiplegic stroke is associated with a marked reorganization of the cerebral activation patterns, including common and subject-specific activation sites. With respect to task-specific information processing a lower discrimination rate of objects compared with controls was associated with diminished activations in parietal lobe.

Adult↗

PubMed1994

Functional cooperativity of human cortical motor areas during self-paced simple finger movements. A high-resolution MRI study.

Magnetic resonance imaging of changes in cerebral blood oxygenation (CBO) delineated areas of neural activation during self-paced unilateral middle finger tapping in five normal volunteers. Four contiguous imaging sections parallel to the bicommissural plane covered the hand area of the primary sensori-motor cortex bilaterally. All measurements were performed at 2.0 T using rapid gradient-echo sequences (TR/TE = 63/30 ms) with high spatial resolution (0.8 x 1.6 x 4 mm) and both strong (40 degrees flip angle) and weak (10 degrees) radiofrequency excitation pulses. This allows differentiation of flow and CBO contributions to the observed signal alterations. Functional cooperativity was analysed by a pixel-by-pixel correlation of signal intensity time courses with the stimulus protocol. Areas of activation included the contralateral primary motor cortex, the homologue part of the primary sensory cortex, the supplementary motor area (SMA) and the lateral premotor areas in all volunteers. Task-related activation of ipsilateral primary motor cortex above a threshold correlation coefficient of 0.5 was seen in two out of five volunteers (at 40 degrees) and one out of five (at 10 degrees) when performing the right-hand task. The present MRI findings readily demonstrate in single subjects that the SMA is involved in self-paced finger tapping. Only sparse activation in the ipsilateral primary motor cortex is consistent with the motor paradigm used.

Adult↗

PubMed1994

Cerebral microembolism in symptomatic and asymptomatic high-grade internal carotid artery stenosis.

Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (> or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent (< 121 days) ischemic symptoms attributable to the diseased ICA. In the so-defined neurologically symptomatic group (n = 33 patients), silent microembolic events occurred in 27 subjects (overall mean rate, 14/h +/- 29). Among 56 neurologically asymptomatic patients matched for the degree of ICA stenosis, only nine showed such events (overall mean rate, 0.35/h +/- 1.4). Across all 89 patients studied, an individual microembolic event rate > or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of "unstable ICA disease."

Aged↗

PubMed1993

Balo's concentric sclerosis followed by MRI and positron emission tomography.

We report a case of Balo's concentric sclerosis diagnosed in vivo by characteristic MRI changes and stereotactic biopsy. Follow-up after 6 months of immunosuppressive treatment demonstrated virtually complete clinical remission, reduction of the white matter lesions on MRI and normalisation of regional cerebral glucose metabolism as assessed by positron emission tomography not only in white matter but also in the cerebral grey matter structures with input from the affected regions.

Adult↗

PubMed1993

Productive expression state confers resistance of human immunodeficiency virus (HIV)-2-infected lymphoma cells against superinfection by HIV-1.

In the past, positive as well as negative results pertaining to HIV-1/HIV2 interference have been obtained. Therefore, in the present study attention was paid to the viral expression state of preinfected cells at the time of exposure to secondary virus. A clonal HIV-2 infected HUT-78 cell line was derived by endpoint dilution and subsequently inoculated with cell-free HIV-1. Superinfection with HIV-1 was ruled out by Western blot and PCR analysis. The chronically HIV-2 infected cells used for these studies showed a highly productive expression state, as evidenced by immunoperoxidase staining (IPS), Western blot profile and levels of reverse transcriptase (RT) activity. We discuss several mechanisms of interference in productively infected cells, which may confer resistance to superinfection with secondary virus.

Blotting, Southern↗

PubMed1993

Reduction of HIV-1 antigen production by phosphatidylcholine containing formulations via growth inhibition of HIV-1-infected cells.

Phosphatidylcholine (PC) and licensed formulations containing PC were tested for their influence on the proliferation and viability of cells permanently infected with HIV-1 (human immunodeficiency virus type 1). PC alone, as well as pharmaceutical formulations containing PC, selectively inhibited the growth of productively infected lymphoid cells. The strongest growth inhibition was observed with formulations containing PC, glycerol and triglyceride together. The growth inhibition was dose-dependent for HIV-1-infected cells. Additionally, PC-containing formulations dramatically reduced antigen production from peripheral blood mononuclear cells (PBMCs) infected in vitro with HIV-1. In vivo experiments with Rauscher-MuLV-infected mice showed that PC administered either intraperitoneally or orally was able to inhibit Rauscher-virus-induced splenomegaly. PC-containing formulations are currently used in man for supportive therapy at doses, which in vitro induced 50% growth inhibition of HIV-1-infected cells in vitro. Such doses have been used in man without side effects for many years. Thus, PC-containing formulations may be valuable for the treatment of HIV-1-infected individuals.

Animals↗

PubMed1993

Between-method correlation in quantifying internal carotid stenosis.

BACKGROUND AND PURPOSE: The degree of internal carotid stenosis has emerged as the most important predictor of ischemic stroke in extracranial carotid artery disease. The purpose of this study was to assess the validity of the noninvasive techniques for quantifying internal carotid stenosis with respect to the accepted standard of intra-arterial angiography. METHODS: We measured the maximum percentage reduction in luminal diameter on the intra-arterial digital subtraction angiograms of 56 symptomatic patients with extracranial internal carotid stenosis (n = 77) or occlusion (n = 20). These data were compared with independent measurements based on continuous-wave Doppler ultrasonography, pulsed-wave Doppler spectrum analysis, color Doppler-assisted duplex imaging, and magnetic resonance angiography. RESULTS: Correlations with intra-arterial angiography were equally strong (r > .90) for magnetic resonance angiography, continuous-wave Doppler, and color duplex analysis. Positive and negative predictive values for (therapeutically relevant) 70% to 99% stenosis were higher for continuous-wave Doppler (.82, .97) and color duplex (.84, .98) than for magnetic resonance angiography (.79, .81). Also, accuracy in quantifying high-grade stenosis was better for both of these ultrasonographic techniques, mainly due to the frequent occurrence of a "flow gap" on the magnetic resonance angiograms. Continuous-wave Doppler and magnetic resonance angiography, but not color duplex, failed to detect slow residual arterial flow in one and two cases of symptomatic "pseudo-occlusion" of the internal carotid, respectively. CONCLUSIONS: (1) Several noninvasive methods compare well with intra-arterial angiography in identifying and quantifying high-grade internal carotid stenosis; (2) the use of these noninvasive methods may suffice for treatment decisions; and (3) because residual between-method disagreement is partly explained by principles of physics, the validity of continuous-wave Doppler and color duplex in quantifying 60% to 99% stenosis is likely to be underestimated by correlation with intra-arterial angiography.

Blood Flow Velocity↗

PubMed1992

Growth inhibition of HIV-1-infected cells and membrane alterations induced by phosphatidylcholine.

Cultured T-lymphoma cell lines H9 and KE37-1 permanently infected with human immunodeficiency virus (HIV-1, strain HTLV-III B) were exposed to phosphatidylcholine (PC) and a PC-containing formulation "Essentiale" (PC-E). PC and PC-E, but not triglyceride, were found to inhibit growth of virus-infected cells. Additionally, the membrane lipid composition of infected and uninfected H9 cells was investigated upon exposure to PC. The HIV-1-infected cells showed a 25% increase in membrane triglyceride content and a 15% increase in membrane phospholipid saturated fatty acids. In the presence of PC, there is a further increase in triglyceride content up to 180% compared with uninfected control cells, suggesting a possible cause for the selective growth inhibition of HIV-1-infected cells by PC. The PC-E dose range effective in vitro for inhibition of HIV-1-infected cell growth falls within the range that can be reached in vivo. Formulations containing PC are well tolerated by humans and might be applicable at an early stage of HIV-1 infection to reduce the number of virus-producing cells.

Cell Division↗

PubMed1992

Biological markers associated with prolonged survival in African children maternally infected by the human immunodeficiency virus type 1.

Sixteen children over the age of 5 years (Group 1) have been identified out of 537 children infected by human immunodeficiency virus and born to HIV-infected mothers, in Kigali, Rwanda. They were followed up for 2 years and compared with 16 younger AIDS patients (Group 2) and with 16 age- and gender-matched HIV-1 seronegative children (Group 3). Fourteen Group 1 subjects had anti-HIV-1 IgM which persisted during the entire study period, in 11 cases directed to HIV-1 envelope proteins. In vitro, immortalization of B lymphocytes by the Epstein-Barr virus confirmed a high production of IgM to envelope proteins. All these patients had anti-p 17 IgG which was not observed in 7 patients from Group 2. All 16 children mounted significant titers of neutralizing antibodies to HTLV-IIIB, and, in 8 patients tested, against two other HIV-1 strains, RII and MN. HIV-1-specific major histocompatibility complex (MHC)-restricted cytotoxic T cells were demonstrated in 3 of 5 of the subgroup who were tested. Prolonged survival over 5 years in children with maternally acquired HIV-1 infection is associated with a high titer of neutralizing antibodies, a persistent production of IGM to HIV-1 envelope proteins and of IgG to p 17.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1992

Sex but no hand difference in the isthmus of the corpus callosum.

We performed high-resolution magnetic resonance morphometry of the total midsagittal area and seven midsagittal subareas of the corpus callosum in healthy young adult dextrals and sinistrals (N = 52). There was no influence of handedness on these anatomic measurements. However, an effect of sex emerged, with women (N = 26) having a larger proportional isthmus segment of the callosum. This may reflect a sex-specific difference in the interhemispheric connectivity and functional organization of the temporoparietal association cortex.

Adult↗

PubMed1992

Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines.

OBJECTIVE: To study expression of HIV-1 in human glial cell lines. DESIGN: Chronically HIV-1-infected glial cell lines were established to evade potential artefacts resulting from unphysiological viral entry (i.e., transfection). These cell lines were used to study viral expression and regulation. METHODS: Chronically infected glial cell lines were established by terminal dilution cloning of human glioma cells exposed to HIV-1. Virus production and expression were assayed by measuring reverse transcriptase activity, p24-antigen levels and syncytia-inducing capacity in C8166 target cells (extracellular), or by indirect immunoperoxidase staining, immunoblot analysis, and p24- and Nef-antigen-capture enzyme-linked immunosorbent assays (intracellular). HIV-long terminal repeat (LTR)-dependent expression of the chloramphenicol acetyltransferase reporter gene was determined in transient transfection assays. RESULTS: Culture supernatant from chronically HIV-1-infected glial cells contained only low levels of virus compared with chronically HIV-infected fibroblasts and T-lymphoma cells. Detailed study of HIV-antigen expression in representative glial cell line TH4-7-5 indicated the presence of all major structural proteins, albeit at low levels, and of Vif, Tat, Rev and Nef. Intracellular levels of Nef exceeded p24-antigen levels by approximately 10-fold. Virus was recovered from TH4-7-5 cells by cocultivation with blood-derived target cells, indicating that low-level virus production is not due to defective provirus. Prominent negative regulatory element (NRE)-mediated suppression of exogenous HIV-LTR activity was observed in TH4-7-5 cells and was unequalled by chronically HIV-producing fibroblast cells or by uninfected fibroblast and glial cells. CONCLUSIONS: Our results suggest that restricted virus production by chronically infected glial cells involves LTR-mediated regulation of virus expression.

Base Sequence↗