Search PubMed⌕ Search

Biomedical subjects

A G Sorensen

Publications and source records attributed to A G Sorensen.

At least 19 recordsLinked to original sources
PubMed2006

Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke.

BACKGROUND: Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models. The authors investigated plasma MMP9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP1), in tPA-treated and -untreated stroke patients. METHODS: Nonstroke control subjects and consecutive ischemic stroke patients presenting within 8 hours of onset were enrolled. Blood was sampled within 8 hours and at 24 hours, 2 to 5 days and 4 to 6 weeks. MMP9 and TIMP1 were analyzed by ELISA and gel zymography. RESULTS: Fifty-two cases (26 tPA treated, 26 tPA untreated) and 27 nonstroke control subjects were enrolled. Hyperacute MMP9 was elevated in tPA-treated vs tPA-untreated patients (medians 43 vs 28 ng/mL; p = 0.01). tPA therapy independently predicted hyperacute MMP9 after adjustment for stroke severity, volume, and hemorrhagic transformation (p = 0.01). There was a trend toward lower hyperacute TIMP1 levels in tPA-treated vs tPA-untreated patients (p = 0.06). Hyperacute MMP9 was correlated to poor 3-month modified Rankin Scale outcome (r = 0.58, p = 0.0005). CONCLUSION: Tissue plasminogen activator independently predicted plasma matrix metalloproteinase-9 (MMP9) in the first 8 hours after human ischemic stroke. As MMP9 may be an important mediator of hemorrhagic transformation, alternative thrombolytic agents or therapeutic MMP9 inhibition may increase the safety profile of acute stroke thrombolysis.

Aged↗
PubMed2006

Neuroanatomic correlates of stroke-related myocardial injury.

BACKGROUND: Myocardial injury can occur after ischemic stroke in the absence of primary cardiac causes. The neuroanatomic basis of stroke-related myocardial injury is not well understood. OBJECTIVE: To identify regions of brain infarction associated with myocardial injury using a method free of the bias of an a priori hypothesis as to any specific location. METHODS: Of 738 consecutive patients with acute ischemic stroke, the authors identified 50 patients in whom serum cardiac troponin T (cTnT) elevation occurred in the absence of any apparent cause within 3 days of symptom onset. Fifty randomly selected, age- and sex-matched patients with ischemic stroke without cTnT elevation served as controls. Diffusion-weighted images with outlines of infarction were co-registered to a template, averaged, and then subtracted to find voxels that differed between the two groups. Voxel-wise p values were determined using a nonparametric permutation test to identify specific regions of infarction that were associated with cTnT elevation. RESULTS: The study groups were well balanced with respect to stroke risk factors, history of coronary artery disease, infarction volume, and frequency of right and left middle cerebral artery territory involvement. Brain regions that were a priori associated with cTnT elevation included the right posterior, superior, and medial insula and the right inferior parietal lobule. Among patients with right middle cerebral artery infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). CONCLUSIONS: Infarctions in specific brain regions including the right insula are associated with elevated serum cardiac troponin T level indicative of myocardial injury.

Aged↗
PubMed2005

Visualization of the pyramidal tract in glioma surgery by integrating diffusion tensor imaging in functional neuronavigation.

OBJECT: The aim of this study was to investigate whether diffusion tensor imaging (DTI) can be integrated into functional navigation for the intraoperative visualization of the pyramidal tract. METHODS: A single-shot spin-echo diffusion-weighted echo planar imaging sequence on a 1.5 T magnetic resonance (MR) scanner was used for DTI. One null image and six diffusion-weighted images (high B value 1 000 mm/s (2)) were obtained. Color-encoded fractional anisotropy maps of the principal eigenvector rendered as a boxoid within each voxel were used for segmentation of the pyramidal tract. The segmented images were rigidly registered with a T(1)-weighted gradient echo 3D dataset for navigation in 16 patients with gliomas. In tumors adjacent to the motor cortex (n = 6) data from functional MR imaging were co-registered. RESULTS: The whole DTI processing lasted about 25-30 minutes in each case. In all cases DTI could be integrated into the navigational dataset resulting in an intraoperative visualization of the pyramidal tract by microscope-based navigation. Navigational accuracy measured as the target registration error was 1.2 +/- 0.46 mm. Registration of fractional anisotropy maps with the 3D navigational dataset was possible with an error of less than 2 mm. Co-registration with fMRI was consistent with DTI data. A neurological deterioration was observed only in one patient. CONCLUSIONS: DTI can be reliably integrated into navigational datasets. Thus, microscope-based neuronavigation can be used for an intraoperative visualization of the course of the pyramidal tract. However, a possible shifting of the pyramidal tract has to be taken into account after major tumor parts are removed.

Adolescent↗
PubMed2002

Diffusion-weighted MRI in diffuse axonal injury of the brain.

The goal of this study was to identify and describe the different types and patterns of tissue injury which are encountered by diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) of the brain. The DWI data sets of 98 patients who suffered from a closed-head injury were retrospectively evaluated. Medical records were reviewed to rule out pre-existing neurological diseases. Lesions were studied for their DWI signal characteristics and lesion size or extension. Traumatic lesions were classified into three categories depending on their signal characteristica on DWI and apparent diffusion coefficient (ADC) maps: type 1, DWI- and ADC-hyperintense most likely representing lesions with vasogenic edema; type 2, DWI-hyperintense, ADC-hypointense indicating cytotoxic edema; type 3, central hemorrhagic lesion surrounded by an area of increased diffusion. According to the size and extent of lesions, injury was classified into three groups: group A, focal injury; group B, regional/confluent injury; and group C, extensive/diffuse injury. Our study showed that diffusion-weighted imaging differentiates between lesions with decreased and increased diffusion in patients with DAI. Different degrees of tissue injury extent were noticed. Future prospective studies should study if this additional information can be used as a predictor of injury reversibility, final outcome and prognosis.

Adolescent↗
PubMed2001

Mechanisms of migraine aura revealed by functional MRI in human visual cortex.

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 +/- 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex.

Adult↗
PubMed2001

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Brain↗
PubMed2001

Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter.

The brains of six healthy volunteers were scanned with a full tensor diffusion MRI technique to study the effect of a high b value on diffusion-weighted images (DWIs). The b values ranged from 500 to 5000 s/mm(2). Isotropic DWIs, trace apparent diffusion coefficient (ADC) maps, and fractional anisotropy (FA) maps were created for each b value. As the b value increased, ADC decreased in both the gray and white matter. Furthermore, ADC of the white matter became lower than that of the gray matter, and, as a result, the white matter became brighter than the gray matter in the isotropic DWIs. Quantitative analysis showed that these changes were due to nonmonoexponential diffusion signal decay of the brain tissue, which was more prominent in white matter than in gray matter. There was no significant change in relation to the b value in the FA maps. High b value appears to have a dissociating effect on gray and white matter in DWIs.

Adult↗
PubMed2001

[Diffusion weighted MRI: ischemic and traumatic injuries of the central nervous system].

Diffusion weighted magnetic resonance imaging (DWI) represents a recent development that extends imaging from the depiction of the neuroanatomy into the field of functional and physiologic processes. DWI measures a fundamentally different physiologic parameter than conventional MRI. Image contrast is related to differences in the microscopic motion (diffusion) of water molecules within brain tissue rather than a change in total tissue water. Consequently, DWI can reveal pathology where conventional T1- and T2-weighted MR images are negative. DWI has clinically proven its value in the assessment of acute cerebral stroke and trauma by showing cerebral injury early due to ist ability to discriminate between lesions with cytotoxic edema (decreased diffusion) from lesions with vasogenic edema (increased diffusion). Full tensor DWI allows to calculate a variety of functional maps, the most widely used maps include maps of apparent diffusion coefficients and isotropic diffusion. In addition maps of anisotropic diffusion can be calculated which are believed to give information about the integrity and location of fiber tracts. This functional-anatomical information will most probably play an increasingly important role in the early detection of primary and secondary tissue injury from various reasons and could guide and validate current and future neuroprotective treatments.

Animals↗
PubMed2001

Ischemic stroke: effects of etiology and patient age on the time course of the core apparent diffusion coefficient.

PURPOSE: To determine whether the evolution of the core apparent diffusion coefficient (ADC) of water in ischemic stroke varies with patient age or infarct etiology. MATERIALS AND METHODS: One hundred forty-seven patients with stroke underwent 236 diffusion-weighted magnetic resonance imaging examinations. Etiologies of lesions were classified according to predefined criteria; in 224 images, the diagnosis of lacune could be firmly established or excluded. ADC was measured in the center of each lesion and in contralateral normal-appearing brain. A model was used to describe the time course of relative ADC (rADC), which is calculated by dividing the lesion ADC by the contralateral ADC, and to test for age- or etiology-related differences in this time course. RESULTS: Transition from decreasing to increasing rADC was estimated at 18.5 hours after stroke onset. In subgroup analysis, transition was earlier in nonlacunes than in lacunes (P =.02). There was a trend toward earlier transition in patients older than the median age of 66.0 years, compared with younger patients (P =.06). Pseudonormalization was estimated at 216 hours. Among nonlacunes, the rate of subsequent rADC increase was more rapid in younger patients than in older patients (P =.001). Within the smaller sample of lacunes, however, no significant age-related difference in this rate was found. CONCLUSION: Differences in ADC depending on the patient's age and infarct etiology suggest differing rates of ADC progression.

Adult↗
PubMed2001

Frequency and clinical context of decreased apparent diffusion coefficient reversal in the human brain.

PURPOSE: To determine the probability that regions of decreased apparent diffusion coefficient (ADC) return to normal without persistent symptoms or T2 change and the settings in which these ADC reversals occur. MATERIALS AND METHODS: Three hundred magnetic resonance (MR) imaging studies were selected at random from a database of 7,147 examinations to determine the probability of a pathologically decreased ADC. In cases with decreased ADC, the clinical history was recorded and, if available, follow-up MR imaging findings were evaluated. Five cases of ADC reversal became known during the same period and were evaluated to determine the initial ADC decrease, clinical outcome, and findings at follow-up imaging. RESULTS: Findings in 116 of 300 MR imaging studies revealed regions of decreased ADC. In 49 of 116 studies, follow-up MR imaging examinations were performed at least 4 weeks after the onset of symptoms; ADC did not reverse. Five cases of ADC reversal were identified in the same period, giving an estimated 0.2%-0.4% probability of ADC reversal. Clinical settings were venous sinus thrombosis and seizure (n = 3), hemiplegic migraine (n = 1), and hyperacute arterial infarction (n = 1). Both white matter (n = 3) and gray matter (n = 3) regions were involved. CONCLUSION: Reversal of ADC lesions is rare, occurs in complicated clinical settings, and can involve white or gray matter.

Adolescent↗
PubMed2001

Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. METHODS: Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. RESULTS: At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P=0.02) but no significant improvement over algorithms utilizing PWI alone (P=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P=0.02) or PWI (P=0.04). The performances of thresholding and GLM algorithms were comparable (P>0.2). CONCLUSIONS: Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.

Acute Disease↗
PubMed2001

Technology and archives in radiology research: a sampling analysis of articles published in the AJR and Radiology. American Journal of Roentgenology.

OBJECTIVE: Our aim was to determine the use of advanced technology and archiving and the contribution of countries other than United States in the articles published in the American Journal of Roentgenology (AJR) and Radiology. We analyzed the association of these features with the type of research, the main technical features of the modalities used, and the countries of origin. MATERIALS AND METHODS: We determined the proportion of articles published in 18 randomly selected issues of the AJR and Radiology that required advanced imaging techniques and relied on the analysis of archived data. "Advanced technology" was defined as imaging techniques that serve a purpose other than simple anatomic imaging or that are not widely available because of the high cost of the technology, such as functional imaging and computer programming designed for an individual study or simulation studies. We analyzed the association of these features with the country of origin, the topic, and the methodology used. RESULTS: Sixteen percent of the studies required advanced technology. MR imaging, CT, and sonography were the most frequently used modalities (31%, 27%, and 15% of studies, respectively). Archiving was used in 37% of the studies, and 67% of the original articles were prospective. The articles most commonly originated in North America (67%), Europe (20%), and Asia (12%). CONCLUSION: Only a small percentage of published research studies required advanced technology and approximately one third of the studies used archiving. These results may suggest that other criteria, such as the design of the study, its relevance for daily clinical use, and the originality of the paper, have a major impact on the acceptance of papers in clinically oriented radiology journals.

Periodicals as Topic↗
PubMed2000

Diffusion- and perfusion-weighted magnetic resonance imaging in human acute ischemic stroke: technical considerations.

Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are recently developed yet steadily evolving magnetic resonance techniques. DWI and PWI typically interrogate the microscopic diffusion and microcirculatory perfusion, and they can provide early, highly sensitive, and specific delineation of ischemic tissue. These techniques also can play a role in selecting patients who may benefit from thrombolytic therapy. This article reviews physical, technical, and pathophysiological background material that can be helpful in the acquisition and interpretation of DWI and PWI.

Brain Ischemia↗
PubMed2000

Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke.

BACKGROUND AND PURPOSE: The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. METHODS: Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. RESULTS: In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. CONCLUSIONS: Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.

Acute Disease↗
PubMed1999

A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group.

This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.

Adult↗
PubMed1999

Modeling cerebral blood flow and flow heterogeneity from magnetic resonance residue data.

Existing model-free approaches to determine cerebral blood flow by external residue detection show a marked dependence of flow estimates on tracer arrival delays and dispersion. In theory, this dependence can be circumvented by applying a specific model of vascular transport and tissue flow heterogeneity. The authors present a method to determine flow heterogeneity by magnetic resonance residue detection of a plasma marker. Probability density functions of relative flows measured in six healthy volunteers were similar among tissue types and volunteers, and were in qualitative agreement with literature measurements of capillary red blood cell and plasma velocities. Combining the measured flow distribution with a model of vascular transport yielded excellent model fits to experimental residue data. Fitted gray-to-white flow-rate ratios were in good agreement with PET literature values, as well as a model-free singular value decomposition (SVD) method in the same subjects. The vascular model was found somewhat sensitive to data noise, but showed far less dependence on vascular delay and dispersion than the model-free SVD approach.

Adult↗
PubMed1999

Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset.

PURPOSE: To evaluate the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging performed within 6 hours of the onset of stroke symptoms. MATERIALS AND METHODS: The authors reviewed the patient records and images from all patients hospitalized in a 10-month period in whom diffusion-weighted imaging was performed within 6 hours of the onset of strokelike symptoms (n = 22). Analyses included comparison of the initial interpretation of the diffusion-weighted images with the final clinical diagnosis; blinded reviews of computed tomographic (CT) scans and conventional and diffusion-weighted images; and determination of lesion contrast-to-noise ratios (CNRs). RESULTS: Diffusion-weighted images indicated stroke in 14 patients, all of whom had a final diagnosis of acute stroke. Diffusion-weighted images were negative in eight patients, all of whom had a final clinical diagnosis other than stroke (100% sensitivity, 100% specificity, chi 2 = 23.00, P < .0001). Blinded reviews yielded 100% sensitivity and 86% specificity for diffusion-weighted MR imaging (chi 2 = 15.43, P < .0005); 18% sensitivity and 100% specificity for conventional MR imaging (chi 2 = 2.85, P > .2); and 45% sensitivity and 100% specificity for CT (chi 2 = 4.40, P > .10). Lesion percentage CNRs were 77% for diffusion-weighted imaging, 5.5% for CT, 9.8% for T2-weighted MR imaging, and 3.1% for proton-density-weighted MR imaging (P < .002 for diffusion-weighted imaging vs others). CONCLUSION: Diffusion-weighted MR imaging is highly accurate for diagnosing stroke within 6 hours of symptom onset and is superior to CT and conventional MR imaging.

Aged↗