Biomedical subjects

Sabine Heiland

Publications and source records attributed to Sabine Heiland.

30 records · Page 2Linked to original sources

PubMed2003

Topographically graded postischemic presence of metalloproteinases is inhibited by hypothermia.

To test the hypothesis that presence of metalloproteases (MMPs), their inhibitors (TIMPs) and their substrate laminin-5 differs between the ischemic core and the surrounding tissue, we examined the impact of middle cerebral artery occlusion/reperfusion (MCA:O/R) on these molecules in different regions of the infarct. We also investigated the influence of hypothermia on the progression of the ischemic lesion and MMP activity. Brain sections from 64 Wistar rats subjected to MCA:O/R were examined by means of cytohistochemistry and zymography. The artery was occluded for 2 h followed by 3, 5, 8 and 12 h of reperfusion. Well characterized antibodies against laminin-5, MMPs and TIMP-2 were used. A total of 32 rats were treated with hypothermia. The presence of each antigen was related to the following regions of interest: ischemic core with BBB breakdown (I(c)), surrounding ischemic tissue without BBB breakdown (I(r)), and the contralateral non-ischemic region (N). Regions of interest were defined by MRI. The I(c) increased over time at the cost of the I(r). BBB breakdown occurred early in the ischemic core and increased over time. Hypothermia reduced the BBB breakdown at all time points. A graded decreased presence of laminin-5 was observed with 16.5+/-3.7(N)>10+/-2.8(I(r))>4+/-1.4(I(c)) immunopositive microvessels/mm(2) at 3 h of reperfusion. MMP-9 showed a reverse pattern with 0 (N)<4+/-0.8(I(r))<10+/-1.5(I(c)) immunopositive microvessels/mm(2). Hypothermia decreased the MMP activity measured by zymography. Laminin-5 and MMP presence relate directly to the degree of postischemic injury. Hypothermia reduces the conversion from the I(r) to ischemic core and the degree of BBB as well as MMP abundance.

Animals↗

PubMed2003

Differentiating primary central nervous system lymphoma from glioma in humans using localised proton magnetic resonance spectroscopy.

In order to characterise primary central nervous system lymphomas (PCNSL) and to evaluate if 1H spectroscopy improves the preoperative differential diagnosis of PCNSL and glioma, seven immunocompetent patients with PCNSL and 21 patients with glioma were examined using single voxel, short echo time magnetic resonance spectroscopy (MRS; 1.5 T, STEAM 1500/20). All PCNSL demonstrated massively elevated lipid resonances and markedly elevated choline. Similarly increased lipid resonances were only found in seven necrotic glioblastomas, PCNSL differing from all solid astrocytomas by massively elevated lipid resonances. Additionally, PCNSL had higher Cho/Cr ratios than all grades of astrocytoma. In conclusion, we found that massively elevated lipid resonances are a hallmark of PCNSL in immunocompetent patients. Together with a markedly elevated Cho/Cr ratio, MRS provides metabolic information which may improve the preoperative differentiation of PCNSL and glioma.

Central Nervous System Neoplasms↗

PubMed2003

Distinguishing of primary cerebral lymphoma from high-grade glioma with perfusion-weighted magnetic resonance imaging.

To assess the usefulness of perfusion-weighted echo-planar magnetic resonance imaging in the differential diagnosis of primary supratentorial lymphoma (PCNSL) and glioblastoma (GBM), 12 patients with a PCNSL and 12 with a GBM were examined using a 1.5 T magnetic resonance (MR) imager. With dynamic-susceptibility contrast MR imaging the intensity-time curves of each tumor were analyzed, and we determined the relative regional cerebral blood volume ratios (rrCBV [tumor/contralateral white matter (WM)]) to find out whether these parameters could be used to separate PCNSL from GBM. The maximum rrCBV ratio in the PCNSL was significantly lower than that of the GBM (P<0.0001). Comparing the intensity-time curves for the two tumor groups, the PCNSL showed a characteristic type of curve with a significant increase in signal intensity above the baseline due to massive leakage of contrast media into the interstitial space. PCNSL tend to have low maximum CBV ratios and typical intensity-time curves. These two parameters may be useful in distinguishing PCNSL from GBM.

Brain Neoplasms↗

PubMed2003

Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities.

Despite early antiviral treatment, herpes simples virus encephalitis (HSVE) still remains a life-threatening sporadic disease with high mortality and morbidity. In patients and in experimental disease, chronic progressive magnetic resonance imaging (MRI) abnormalities have been found even after antiviral therapy. Secondary autoimmune-mediated and not directly virus-mediated mechanisms might play a key role for the outcome of disease. This study aimed to evaluate a possible beneficial effect of a therapy of acyclovir and corticosteroids versus acyclovir only. In a mouse model of HSVE (intranasal inoculation with 10(5) pfu [plaque-forming units] of HSV-1 strain F), a long-term MRI study was realized. Cranial MRI was performed serially at days 2, 7, 14, 21, 60, and 180 in different therapy groups: 1, saline; 2, acyclovir; 3, acyclovir, subsequently methylprednisolone; 4, sham-infected with saline. Brain viral load peaked at day 7 to decline thereafter to a low baseline value. Viral load in group 1 was significantly higher than in animals with antiviral therapy. In group 4, no viral DNA was detectable. Viral load did not differ significantly between acyclovir and acyclovir/corticosteroid-treated groups, suggesting that the use of corticosteroids in addition to acyclovir does not increase viral burden. MRI findings in untreated and acyclovir-treated animals revealed chronic progressive changes. In contrast, there was a significant reduction of the severity of long-term MRI abnormalities in acyclovir/corticosteroid-treated animals. With respect to abnormal MRI findings, this study demonstrates a clear beneficial effect of an acyclovir and corticosteroid therapy without influencing brain viral load.

Acyclovir↗

PubMed2003

Acute encephalitis, a poliomyelitis-like syndrome and neurological sequelae in a hamster model for flavivirus infections.

Infection of hamsters with the murine flavivirus Modoc results in (meningo)encephalitis, which is, during the acute phase, frequently associated with flaccid paralysis, as also observed in patients with West Nile virus encephalitis. Twenty percent of the hamsters that recover from the acute encephalitis develop life-long neurological sequelae, reminiscent of those observed, for example, in survivors of Japanese encephalitis. Magnetic resonance imaging and histology revealed severe lesions predominantly located in the olfactory-limbic system, both in hamsters with acute encephalitis as in survivors. Prominent pathology was also detected in the spinal cord of hamsters with paralysis. Modoc virus infections in hamsters provide a unique model for the study of encephalitis, a poliomyelitis-like syndrome and neurological sequelae following flavivirus infection.

Animals↗

PubMed2003

Small-vessel stents for intracranial angioplasty: in vitro comparison of different stent designs and sizes by using CT angiography.

BACKGROUND AND PURPOSE: Our purpose was to evaluate whether CT angiography is a suitable alternative to conventional angiography in the evaluation of small-vessel stents for intracranial angioplasty. METHODS: CT angiographic appearances of 23 stents of different designs and sizes (2.0, 3.0, and 4.0 mm) were investigated after they were filled with a solution of 0.9% NaCl or diluted contrast medium. For each stent, artificial lumen narrowing (ALN) was measured, and the difference in the number of pixels with a Hounsfield value below 200 HU between the two filling states, DIFF(HU<200), was calculated to provide an objective indicator of the size of the evaluable stent diameter. RESULTS: With a window width of 1500 HU at a window level of 400 HU, ALN ranged from 66.8% to 97.7% in the group of 2.0-mm stents and from 38.6% to 66.8% in the groups of 3.0- and 4.0-mm stents. For the 2.0-mm stents, DIFF(HU<200) was zero. In the groups of 3.0- and 4.0-mm stents, DIFF(HU<200) ranged from 0.3 to 6.7, corresponding to a diameter of 0.13-3.0 mm, when the pixel size was presupposed to be 0.449 mm. CONCLUSION: CT angiographic evaluation of small-vessel patency after stent placement is considerably impaired by ALN. Stent manufacturers should be aware of potential artifacts caused by their stents during noninvasive diagnostic studies such as CT angiography.

Angioplasty, Balloon↗

PubMed2002

In vivo monitoring of age-related changes in rat brain using quantitative diffusion magnetic resonance imaging and magnetic resonance relaxometry.

Diffusion-weighted magnetic resonance imaging (MRI) has been proven to be a sensitive diagnostic tool to examine age associated acute and chronic changes in brain tissue. The aim of our study was to examine whether there are differences in brain diffusion and transverse relaxation time between young and adult rats. In an experimental MR scanner, 24 young (age: 3 months) and 26 adult rats (age: 12 months) were examined using diffusion-weighted and transverse relaxation time (T2)-weighted MRI sequences. There were no differences in the T2 relaxation time between the two animal groups, either local or global. However, the mean apparent diffusion coefficient (ADC) within the whole brain was significantly lower (P<0.0005) in the adult animals (765+/-35 x 10(-6) mm(2)/s) than in the young animals (829+/-45 x 10(-6) mm(2)/s). ADC decrease was mainly found in the cerebral cortex. These results can be attributed to an activity-related or central nervous system damage-related internal water shift from the extracellular to the intracellular space without a net increase in water content in brain tissue. Our study also shows that age-related changes in diffusion should be considered when performing longitudinal studies in rats.

Aging↗

PubMed2002

An automated method for volumetric quantification of magnetization transfer of the brain.

Cerebral white matter damages can be detected and characterized using magnetization transfer (MT) imaging. In this study a fully automated method of measuring and analyzing the MT of the whole human brain is presented and assessed. A 3D-FLASH sequence with off-resonance RF pulse was optimized for fast, volumetric MT measurements. The postprocessing software developed for this purpose includes a SPM99-based segmentation algorithm, a visualization tool, and a histogram-based MT parameter analysis. The reproducibility of the method was tested with phantom measures and in studies on nine healthy volunteers. Small variances (0-1.6%) and therefore, a high reproducibility of MT parameter measurements were found in vitro, slightly higher variances in volunteer investigations (0.7-4.0%). With our technique, we expect to be able to better recognize and follow up the progression of white matter diseases. Due to the high reproducibility, this volumetric approach is specifically suitable for longitudinal MT studies.

Adult↗

PubMed2002

Comparison of CT and CT angiography source images with diffusion-weighted imaging in patients with acute stroke within 6 hours after onset.

BACKGROUND AND PURPOSE: Although stroke MRI has advantages over other diagnostic imaging modalities in acute stroke patients, most of these individuals are admitted to emergency units without MRI facilities. There is a need for an accurate diagnostic tool that rapidly and reliably detects hemorrhage, extent of ischemia, and vessel status and potentially estimates tissue at risk. We sought to determine the diagnostic accuracy of the combination of non-contrast-enhanced CT, CT angiography (CTA), and CTA source images (CTA-SI, showing early parenchymal contrast enhancement) in comparison with a multiparametric stroke MRI protocol in patients with acute stroke within 6 hours after onset. METHODS: Non-contrast-enhanced CT, CTA, stroke MRI including diffusion-weighted imaging (DWI), and MR angiography (MRA) were performed in patients with symptoms of acute stroke within 6 hours after onset. We analyzed infarct volumes on days 1 and 5 as shown on CTA-SI, DWI, and T2-weighted images (Wilcoxon, Mann-Whitney, Spearman tests), estimated the collateral status, and assessed clinical outcome (modified Rankin Scale, Barthel Index, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale). RESULTS: We analyzed the data of 20 stroke patients who underwent CT and MRI scanning within 6 hours (mean, 2.83 and 3.38 hours, respectively). Vessel occlusion was present in 16 of 20 patients. CTA-SI volumes did not differ from DWI volumes (P=0.601). Furthermore, the CTA-SI lesion volumes significantly correlated with the initial DWI lesion volumes (P<0.0001, r=0.922) and with outcome lesion volumes (P=0.013 r=0.736). Patients with poor collaterals experienced infarct growth (P=0.0058) and had a significantly worse clinical outcome (all P<0.012); patients with good collaterals did not (P=0.176). CONCLUSIONS: The combination of non-contrast-enhanced CT (exclusion of intracranial hemorrhage), CTA (vessel status), and early contrast-enhanced CTA-SI (demarcation of irreversible infarct) allows diagnostic assessment of acute stroke with a quality comparable to that of stroke MRI. Furthermore, it is possible to distinguish patients at risk of infarct growth from those who are not according to the collateral status, in analogy with the stroke MRI mismatch concept.

Acute Disease↗

PubMed2002

Dose-response curves and tolerance doses for late functional changes in the normal rat brain after stereotactic radiosurgery evaluated by magnetic resonance imaging: influence of end points and follow-up time.

Late reaction of normal tissue is still a limiting factor in radiotherapy and radiosurgery of patients with brain tumors. Few quantitative data in terms of dose-response curves are available. In the present study, 99 animals were irradiated stereotactically at the right frontal lobe using a linear accelerator and single doses between 26 and 50 Gy. The diameter of the spherical dose distribution was 4.7 mm (80% isodose). Dose-response curves for late changes in the normal brain at 20 months were measured using T1- and T2-weighted magnetic resonance imaging (MRI). The dependence of the dose-response curves on the follow-up time and the definition of the biological end point were determined. Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were found to be dependent on dose and progressive in time. At 20 months, the tolerance doses at a 50% effect probability level were 39.6 +/- 1.0 Gy and 42.4 +/- 1.4 Gy for changes in T1- and T2-weighted images, respectively. These dose-response curves can be used for further quantitative investigations on the influence of various treatment parameters, such as the application of charged particles, radiopharmaceuticals or the variation of tissue oxygenation.

Animals↗

PubMed2002

Dose-response curves for late functional changes in the normal rat brain after single carbon-on doses evaluated by magnetic resonance imaging: influence of follow-up time and calculation of relative biological effectiveness.

This study investigated late effects in the brain after irradiation with carbon ions using a rat model. Thirty-six animals were irradiated stereotactically at the right frontal lobe using an extended Bragg peak with maximum doses between 15.2 and 29.2 Gy. Dose-response curves for late changes in the normal brain were measured using T1- and T2-weighted magnetic resonance imaging (MRI). Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were progressive in time up to 17 months and remained stationary after that time. At 20 months the tolerance doses at the 50% effect probability level were 20.3 +/- 2.0 Gy and 22.6 +/- 2.0 Gy for changes in T1- and T2-weighted MRI, respectively. The relative biological effectiveness (RBE) was calculated on the basis of a previous animal study with photons. Using tolerance doses at the 50% effect probability level, RBE values of 1.95 +/- 0.20 and 1.88 +/- 0.18 were obtained for T1- and T2-weighted MRI. A comparison with data in the literature for the spinal cord yielded good agreement, indicating that the RBE values for single-dose irradiations of the brain and the spinal cord are the same within the experimental uncertainty.

Animals↗

PubMed2002

Perfusion- and diffusion-weighted magnetic resonance imaging for monitoring decompressive craniectomy in animals with experimental hemispheric stroke.

OBJECT: The aim of this study was to use two types of serial magnetic resonance (MR) imaging-perfusion-weighted (PW) and diffusion-weighted (DW)-to monitor craniectomy in rats with hemispheric stroke. METHODS: Focal cerebral ischemia was induced in 36 rats by using an endovascular method of occlusion of the middle cerebral artery (MCAO). Craniectomy was performed 4 or 24 hours later in 12 animals each. Twelve control animals underwent occlusion but did not receive treatment. Perfusion-weighted, DW, and T2-weighted MR images were obtained at 4, 24, 48, 72, and 168 hours postocclusion in all animals. Relative regional cerebral blood volumes and apparent diffusion coefficients (ADCs) were calculated for the cortex and basal ganglia. Hemispheric lesion volumes (expressed as percentages of total brain volumes; %HLV) as they appeared on DW and T2-weighted MR images and on histological slices stained with 2,3,5-triphenyltetrazolium chloride were compared. Neurological performances and infarct volumes measured 7 days postocclusion were used as study end points. Both PW and DW images demonstrated ischemic tissue 4 hours after MCAO in all animals. Early treatment by performing craniectomy significantly improved cortical perfusion (p < 0.01), whereas the same procedure conveyed no benefit to the basal ganglia. Compared with findings in control animals, the DW image-derived %HLV was significantly reduced (p < 0.01) and the cortical ADCs at 4 and 24 hours postocclusion were significantly higher in animals treated early (p < 0.05). Late treatment with craniectomy did not significantly affect cerebral perfusion. The correlation between the DW imaging-derived %HLV and the histologically derived %HLV at 4 to 72 hours postocclusion was good (r = 0.74), whereas at Day 7 postocclusion the %HLV was underestimated up to 41% on DW imaging. At 4 hours postocclusion T-weighted imaging failed to demonstrate the ischemic lesion, whereas from 24 to 72 hours postocclusion the correlation between the T2-weighted imaging-derived %HLV and the histologically derived %HLV was good (r > 0.81). Neurological performance was significantly improved in animals treated using craniectomy. CONCLUSIONS: Early craniectomy significantly improves cortical perfusion through leptomeningeal collateral vessels, significantly reduces infarct size, and improves neurological performance in animals with experimental acute hemispheric infarction. Both PW and DW imaging are suitable for noninvasive monitoring of the effects of decompressive craniectomy.

Acute Disease↗