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Biomedical subjects

J Sobesky

Publications and source records attributed to J Sobesky.

15 recordsLinked to original sources
PubMed2006

Primary stroke unit treatment followed by very early carotid endarterectomy for carotid artery stenosis after acute stroke.

BACKGROUND: Although it is recognized that carotid endarterectomy (CEA) is the treatment of choice in symptomatic internal carotid artery (ICA) stenosis, in the past, very early CEA has been shown to carry substantial risks. We assessed an interdisciplinary concept of very early CEA in patients with high-grade (>70%) symptomatic ICA stenosis at a single center. PATIENTS AND METHODS: The course of treatment and outcomes of patients who underwent CEA as early as possible after being referred to the stroke unit for symptoms of transient ischemic attack and stroke were prospectively evaluated, including the following parameters: age, severity of ischemia-related symptoms according to the modified Rankin scale, duration of symptoms until admission, multimodal imaging findings (color-coded duplex, cranial computed tomography, magnetic resonance imaging, positron emission tomography), duration until CEA, perioperative course and complications, as well as duration of in-hospital care. RESULTS: Fifty consecutive patients (median age 68 years, range 44-90) with clinical and imaging signs of transient ischemic attack (n = 19) or stroke (n = 31) were included from January 2000 until December 2004. All except 1 patient showed a preoperative Rankin < 4. There was a median time period of 6 h between the onset of symptoms and admission (range 1 h to 15 days) and a median duration of 4 days after admission until operation (range 1-21 days). Seven patients underwent CEA of the contralateral, severely stenosed ICA after symptomatic ipsilateral ICA occlusion. Four out of 5 patients who primarily underwent systemic thrombolysis recovered almost completely. Three patients (6%) experienced a clinical deterioration before surgery. In the majority of patients (43/50), CEA was performed under local anesthesia with selective shunt use which became necessary in 26%. Three patients (6%) had postoperative worsening due to new infarcts. In 2 cases, an intracerebral hemorrhage occurred, of which 1 remained asymptomatic. In 1 case, surgical revision was necessary because of an ICA thrombosis without permanent neurological decline. Patients were discharged after a median time of 14.5 days (range 4-44). CONCLUSIONS: After careful selection and preparation in a stroke unit, patients with acute stroke due to carotid stenosis can undergo very early CEA under local anesthesia with a perioperative risk comparable with the risk of later endarterectomy, therefore preventing very early stroke recurrences.

Adult↗
PubMed2004

Which time-to-peak threshold best identifies penumbral flow? A comparison of perfusion-weighted magnetic resonance imaging and positron emission tomography in acute ischemic stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, the hypoperfused but viable tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP) maps are frequently used to estimate the hemodynamic compromise and to calculate the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral flow by comparison with positron emission tomography (PET). METHODS: Magnetic resonance imaging (MRI) and PET were performed in 11 patients with acute ischemic stroke (median 8 hours after stroke onset, 60 minutes between MRI and PET imaging). The volumes defined by increasing TTP thresholds (relative TTP delay of >2, >4, >6, >8, and >10 seconds) were compared with the volume of hypoperfusion (<20 mL/100 g per min) assessed by 15O-water PET. In a volumetric analysis, each threshold's sensitivity, specificity, and predictive values were calculated. RESULTS: The median hypoperfusion volume was 34.5 cm3. Low TTP thresholds included large parts of the hypoperfused but also large parts of normoperfused tissue (median sensitivity/specificity: 93%/60% for TTP >2) and vice versa (50%/91% for TTP >10). TTP >4 seconds best identifies hypoperfusion (84%/77%). The positive predictive values increased with the size of hypoperfusion. CONCLUSIONS: This first comparison of quantitative PET-CBF with TTP maps in acute ischemic human stroke indicates that the TTP threshold is crucial to reliably identify the tissue at risk; TTP >4 seconds best identifies penumbral flow; and TTP maps overestimate the extent of true hemodynamic compromise depending on the size of ischemia. Only if methodological restrictions are kept in mind, relative TTP maps are suitable to estimate the mismatch volume.

Adult↗
PubMed2003

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

Alzheimer Disease↗
PubMed2003

Identification of malignant brain edema after hemispheric stroke by PET-imaging and microdialysis.

Cerebral blood flow (CBF) and extent of irreversible tissue damage as well as the time course of extracellular concentration of amino acids, substrates of energy metabolism, and purine metabolites, intracranial pressure and tissue oxygen tension were assessed in 34 patients with large strokes covering more than 50% of the MCA territory. The results were compared to findings in the experimental model of transient (for 3 hours) MCA occlusion in cats. In the experimental model as well as in the clinical setting development of malignant brain infarcts (due to formation of space occupying brain edema) was predicted by the size of critically hypoperfused tissue and the volume of irreversibly damaged tissue. The course of malignant infarcts was characterized by progressive increase in concentrations of excitatory amino acids, lactate, pyruvate, glycerol, hypoxanthine and in intracranial pressure, while cerebral perfusion pressure and tissue oxygen tension decreased. These results clearly differentiate a malignant from a benign course of large hemispheric infarction. The methods can be used to identify patients at risk for formation of space occupying edema and to select patients who could benefit from invasive therapeutic strategies.

Amino Acids↗
PubMed2002

Impaired benzodiazepine receptor binding in peri-lesional cortex of patients with symptomatic epilepsies studied by [(11)C]-flumazenil PET.

Individual benzodiazepine receptor (BZR) binding of peri-lesional cortex was investigated in symptomatic epilepsies. Eleven patients aged 19-44 years were studied whose diagnosis was established by medical history, clinical, electroencephalographic, and magnetic resonance imaging (MRI) findings. Three-dimensional [11C]-flumazenil (FMZ) positron emission tomography and MRI scans were obtained and coregistered. Lesions (five low-grade brain tumours, one AV malformation, one cavernoma, one cystic lesion of unknown aetiology, one traumatic brain injury, one post-operative and one post-haemorrhagic defect) were outlined on individual MRI scans. Adjacent to those lesions, and in homologous contralateral structures, FMZ binding was analysed in four pairs of cortical 9 x 9-mm regions of interest (ROIs) placed on transaxial and coronal slices, respectively, as well as in the lesion volume and its mirror region. Percentage asymmetry ratios were calculated and those at or outside the 90-110% range were operationally defined significant. Peri-lesional FMZ binding asymmetries ranged from 70 to 125%, lesional asymmetries from 38 to 82%. Only one patient showed no significant change, whilst nine exhibited significant reductions of FMZ binding in at least one ROI (3 x 1, 4 x 2, 1 x 3, 1 x 4), and significant increases were observed in two ROIs of another patient. Therefore, peri-lesional disturbances of BZR binding are common but variable in location. Because a close correlation between regional decreases in FMZ binding and spiking activity was recently demonstrated in neocortical epilepsies, abnormal peri-lesional FMZ binding may bear some relation to the mechanisms of epileptogenesis in symptomatic epilepsies.

Adult↗
PubMed2002

The correlation between cerebral glucose metabolism and benzodiazepine receptor density in the acute vegetative state.

This paper compares the results of parallel positron emission tomography (PET) studies of regional cerebral glucose metabolism with the radiotracer 18F-fluorodeoxyglucose (FDG) and benzodiazepine receptor (BZR) density by PET using the BZR ligand 11C-flumazenil (FMZ), a tracer of neuronal integrity, in nine patients with acute vegetative state (AVS, duration <1 month). Overall glucose utilization was significantly reduced in AVS in comparison with age-matched controls (global metabolic rate for glucose 26 micromol/100 g/min in AVS vs. 31 micromol/100 g/min in controls). FMZ-PET demonstrated a considerable reduction of BZR binding sites in all cortical regions that grossly corresponded to the extent of reduction of cerebral glucose metabolism assessed with FDG-PET, whilst the cerebellum was spared from neuronal loss. In controls, cortical relative flumazenil binding was not lower than five times the average white matter activity, whilst in AVS, nearly all values were below this threshold. There was no relevant overlap of the data of relative flumazenil binding between both groups. The comparison of FDG- and FMZ-PET findings in AVS demonstrates that alterations of cerebral glucose consumption do not represent mere functional inactivation, but irreversible structural brain damage.

Acute Disease↗
PubMed2002

Differentiating multiple system atrophy from Parkinson's disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging.

OBJECTIVES: The differential diagnosis between typical idiopathic Parkinson's disease (PD) and the striatonigral variant of multiple system atrophy (MSA-P) is often difficult because of the presence of signs and symptoms common to both forms of parkinsonism, particularly at symptom onset. This study investigated striatal and midbrain findings in MSA-P and PD patients in comparison with normal controls with the use of positron emission tomography (PET) and three dimensional magnetic resonance imaging (3D MRI) based volumetry to increase the differential diagnostic accuracy between both disease entities. METHODS: Nine patients with MSA-P, 24 patients with PD, and seven healthy controls were studied by MRI and PET with 6-[(18)F]-fluoro-L-dopa (FDOPA), [(18)F]fluoro-deoxyglucose (FDG), and 11-C-Raclopride (RACLO). Striatal and extrastriatal volumes of interest (VOI) were calculated on the basis of the individual MRI data. The PET data were transferred to the VOI datasets and subsequently analysed. RESULTS: MSA-P differed significantly from PD patients in terms of decreased putaminal volume, glucose metabolism, and postsynaptic D2 receptor density. The striatal FDOPA uptake was equally impaired in both conditions. Neither MRI volumetry nor PET imaging of the midbrain region further contributed to the differential diagnosis between PD and MSA-P. CONCLUSIONS: The extent and spatial distribution of functional and morphological changes in the striatum permit the differentiation of MSA-P from PD. Both, multi-tracer PET and 3D MRI based volumetry, may be considered equivalent in the assessment of different striatal abnormality in both disease entities. In contrast, MRI and PET imaging of the midbrain does not provide a further gain in diagnostic accuracy.

Atrophy↗
PubMed2002

Feasibility of source images of computed tomographic angiography to detect the extent of ischemia in hyperacute stroke.

BACKGROUND AND PURPOSE: Computed tomographic angiography (CTA) is suggested to be a promising tool for patient selection for thrombolytic therapy of acute stroke. It does not only provide information on intracranial vasculature, but also on the capacity of the collateral circulation and the pattern of poorly perfused brain tissue. The objective of our study was to evaluate whether the presence and size of critically hypoperfused tissue assessed with flow positron emission tomography (PET) as a gold standard can reliably be identified on CTA source images. METHODS: Fifteen potential candidates for early thrombolysis underwent CTA 65-170 min (mean 107 min) after the onset of acute anterior circulation stroke. Regional cerebral perfusion was measured between 27 and 86 min (mean 59 min) later with [(15)O]-H(2)O and PET, and the volume of critically hypoperfused cortical tissue was assessed. CTA source images were evaluated by a neuroradiologist and an experienced stroke neurologist. The patients were classified into three groups according to the presumed size of the perfusion deficit on CTA (large, small, no perfusion deficit). RESULTS: PET revealed the presence of critical cortical hypoperfusion in 10 patients, 5 had no critical cortical hypoperfusion. The neuroradiologist correctly identified the presence of a perfusion deficit in all patients, the neurologist had two false negative and one false positive ratings. Concerning the size of the perfusion deficit, there was considerable inaccuracy in both raters. CONCLUSIONS: The usefulness of CTA source images in yielding information about the perfusion state of stroke patients in clinical routine should not be overestimated.

Adult↗
PubMed2002

Molecular and functional imaging technology for the development of efficient treatment strategies for gliomas.

Gliomas are the most common types of brain tumors, which invariably lead to death over months or years. Before new and potentially more effective treatment strategies, such as gene therapy, can be effectively introduced into clinical application the following goals must be reached: (1) the determination of localization, extent and metabolic activity of the glioma; (2) the assessment of functional changes within the surrounding brain tissue; (3) the identification of genetic changes on the molecular level leading to disease; and in addition (4) a detailed non-invasive analysis of both endogenous and exogenous gene expression in animal models and in the clinical setting. Non-invasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging techniques may reveal the assessment of the location, magnitude and duration of therapeutic gene expression and its relation to the therapeutic effect. Here, we review the main principles of PET imaging and its key roles in neurooncology research.

Brain Neoplasms↗
PubMed2000

Surgery of intrinsic cerebral neoplasms in eloquent areas under local anesthesia.

28 patients with a mean age of 43.6 years were operated on for a cerebral neoplasm situated in close proximity to an eloquent area (24 speech area, 4 motor cortex) from 1996 to 1999. Preoperatively, all patients had undergone a detailed neuropsychological examination. In 10 patients aphasic disturbances could be detected. All patients underwent preoperative PET studies (methionine and (15)O-labeled water with activation during speech or finger tapping). These were performed and co-registered with MRI data to demonstrate the topographical relationship between motor or language function and the tumor borders. Anesthesia was induced with i.v. administration of propofol (150-250 mg/h). Craniotomy was performed under local infiltration anesthesia. After opening of the dura, sedation was stopped and operation was continued with the patient being alert and co-operative. With close clinical observation during electrical cortex stimulation, a speech arrest could be triggered or avoided. The motor cortex was identified by recording the phase reversal of the contralateral SEP of the median nerve and by direct cortical stimulation. As soon as aphasic or motor disturbances appeared, the tumor removal was continued with the goal of avoiding these specific regions. In 27 patients, preexisting neuropsychological and neurological deficits did not worsen. Only one patient was left postoperatively with a major permanent aphasic deficit that was present preoperatively to a minor degree. The use of local anesthesia in craniotomy for surgery of intrinsic cerebral neoplasms in eloquent areas allows for a continuous and repetitive monitoring of speech and motor function during the removal of even those tumors that were previously considered inoperable.

Adult↗
PubMed2000

Early x-ray hypoattenuation of brain parenchyma indicates extended critical hypoperfusion in acute stroke.

BACKGROUND AND PURPOSE: The presence of early x-ray hypoattenuation is an important selection criterion for thrombolytic therapy. However, knowledge about the pathophysiological constellation reflected by this hypoattenuation is lacking. Our objective was to study the relationship between the presence of early CT hypoattenuation and the volumes of critical cortical hypoperfusion. METHODS: In 32 patients with acute ischemic stroke, CT was performed 20 to 170 minutes (mean, 94 minutes) after symptom onset, and [(15)O]H(2)O-PET 20 to 120 minutes (mean, 67 minutes) later. CTs were scrutinized for the presence of hypoattenuation. On the PET scans, the volumes of critical cortical hypoperfusion were assessed. RESULTS: CT hypoattenuation was present in 18 patients (56%), all of whom had critical cortical hypoperfusion and developed infarction. Of the 14 patients with normal CTs, critical hypoperfusion was found in 6, and 7 developed infarction. The mean volumes of critically hypoperfused tissue differed significantly (P=0.0001, Wilcoxon test) between the CT normal (mean 13.9 cm(3), range 0 to 71 cm(3)) and the CT abnormal (mean 116.3 cm(3), range 4 to 389 cm(3)) groups. CONCLUSIONS: Early presence of hypoattenuation is indicative of extended volumes of critically hypoperfused cortical tissue. The extent of hypoperfusion may exceed that of hypoattenuation, and some of that tissue might still be salvageable.

Acute Disease↗
PubMed1998

Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke.

BACKGROUND AND PURPOSE: Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. METHODS: In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. RESULTS: In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. CONCLUSIONS: These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.

Aged↗
PubMed1995

Prevention of postoperative adhesions by single intraperitoneal medication.

Postoperative adhesions account for a significant morbidity after abdominal, gynecological, or cardiac surgery. A large number of compounds have been suggested to prevent such adhesions, but none is generally accepted. We have compared eight different substances that could be beneficial for the prevention of postoperative adhesions in a new standardized rabbit model with measurement of the areas of adhesion. In 10 groups of 20 rabbits an area of abrasion of the serosa of the ileum, the appendix, and the abdominal wall measuring 10,000 mm2 was created by an emery piston during celiotomy. The controls received no medication. The treatment groups received a single intraperitoneal administration of 1 ml per 100 g body wt of normal saline (NaCl), 5 mg taurolidine (T), 0.5 U plasmin/300 U DNase (PD), 2000 IU streptokinase/500 IU streptodornase (SS), 7 mg phosphatidylcholine (PC), 4 mg hyaluronic acid (HA), 7 mg sphingolipid (SL), 7 mg galactolipid (GL), or 0.5 ml tetrachlorodecaoxide (TCDO), respectively. Ten days later the extent of adhesions was quantified by morphometry. The total area of adhesions (+/- SEM) was found to be 1998 +/- 124 mm2 in controls. The application of NaCl reduced the adhesions to 1368 +/- 58 mm2, of T to 1012 +/- 48 mm2, of PD to 673 +/- 33 mm2, of SS to 360 +/- 44 mm2, of PC to 335 +/- 84 mm2, of HA to 328 +/- 76 mm2, of SL to 278 +/- 80 mm2, of GL to 261 +/- 67 mm2, and of TCDO to 240 +/- 45 mm2. The effects of PD, SS, PC, HA, SL, GL, and TCDO were significant in comparison to controls and NaCl. Our experimental data suggest that the two new lipid substances, SL and GL, are the most likely candidates for routine clinical use in the prevention of postsurgical adhesions.

Abdominal Muscles↗