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M A Jacobs

Publications and source records attributed to M A Jacobs.

At least 19 recordsLinked to original sources
PubMed2006

Double-balloon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease.

BACKGROUND AND STUDY AIMS: Until recently, only the proximal small bowel was accessible for diagnostic and therapeutic endoscopy. This paper describes experience in the first 275 patients examined and treated with the new method of double-balloon enteroscopy (DBE), which is expected to make full-length enteroscopy possible. PATIENTS AND METHODS: Between November 2003 and May 2005, double-balloon enteroscopy was conducted in 275 consecutive patients presenting at two tertiary referral hospitals. The characteristics of the patients, indications for the procedures, procedural parameters, and diagnostic yield are described here. All conventional treatment options were available. The tolerability of the procedure was assessed in a small subset of the patients. After the procedure, the patients were monitored in a recovery room for at least 2h. They were discharged afterwards, provided there were no signs of complications or complaints. RESULTS: The main indication for DBE was suspected small-bowel bleeding (n=168), and the lesions responsible for the bleeding were found in 123 patients (73 %) and treated in 61 (55 %). In patients with refractory celiac disease (n=25), DBE revealed a high proportion (six patients, 23 %) of enteropathy-associated T-cell lymphomas that had not been suspected on other tests. Further DBE indications were surveillance and treatment of hereditary polyposis syndromes (n=20); and suspected Crohn's disease, which was diagnosed with DBE in four of 13 patients (30 %). No relevant pathology was found in 24 % of the patients. Panenteroscopy was successfully performed in 26 of 62 patients (42 %) in whom it was attempted, in either one or two sessions. The average duration of the procedures was 90 min (range 30 - 180 min, SD 42), and the average insertion length was 270 cm (range 60 - 600 cm, SD 104). Patients' tolerance of the procedure was excellent. Severe complications were recognized in three cases (1 %), all involving pancreatitis. CONCLUSIONS: This large pilot series shows that DBE is a well-tolerated and safe new endoscopic technique with a high diagnostic yield in selected patients.

Adolescent↗
PubMed2003

Perfusion-weighted MRI as a marker of response to treatment in acute and subacute stroke.

We carried out baseline and short-term follow-up MRI, including perfusion-weighted imaging (PWI) and tests of neurologic and cognitive function on 15 consecutive patients with large-vessel ischemic stroke who showed a persistent large perfusion-diffusion mismatch at enrollment up to seven days after the onset of symptoms. Of these, ten underwent induced blood pressure elevation with phenylephrine and oral medications (in eight) or intravenous fluids (in two) with the goal of improving perfusion; five had no such treatment. Significant functional improvement was defined by a reduction of 3 or more points on the NIH stroke scale (NIHSS). Significant improvement in perfusion was defined by a reduction in the volume of hypoperfused brain by 30 cc on PWI using time-to-peak (TTP) maps, without enlargement of the infarct. There was a strong, statistically significant association between improved function and improved perfusion: six (75%) of eight patients who improved in function, but none of the seven who did not, showed a reduction in volume of hypoperfused brain. All six patients who met the perfusion goal, and only two (22%) of nine who did not showed significant functional improvement (Fisher's exact: P < 0.01). There were no differences between patients who improved functionally and those who did not with respect to age, initial volume of abnormality on DWI or PWI, initial NIHSS, or changes on DWI. These findings indicate that reduction in volume of hypoperfused brain on PWI is a marker of response to treatment to improve perfusion even in subacute stroke and that partial reperfusion of regions of salvageable but dysfunctional tissue is a mechanism of improved function associated with induced blood pressure elevation.

Adult↗
PubMed2002

Childhood invasive pneumococcal disease in Tasmania, 1994-2000.

OBJECTIVE: To describe the burden of invasive pneumococcal disease in Tasmanian children, including age-specific incidence and antibiotic-resistance pattern. METHODS: A population-based retrospective study was carried out, examining cases of childhood disease associated with isolates of Streptococcus pneumoniae from normally sterile sites, identified via scrutiny of laboratory records at all major Tasmanian laboratories during a 7-year period between January 1994 and December 2000. Medical records were sub-sequently examined for information describing the clinical syndrome and course of disease. RESULTS: Invasive pneumococcal disease was identified in 76 children during the 7-year period. The incidence per 100 000 children was 28.5 (95% CI 22.0-36.3) in children under 5 years and 54.3 (95% CI 40.2-71.8) in children under 2 years. The incidence of meningitis in children younger than 2 years was 12.2 (95% CI 6.1-21.8). Penicillin resistance was observed in 2.6% of cases, with no high level resistance. Predisposing conditions were identified in 34% of children with invasive disease. CONCLUSIONS: The incidence of invasive pneumococcal disease was comparable to many urban populations in Australia. The high rate of predisposing conditions supports the recommendations of the Australian Technical Advisory Group on Immunisation for targeted immunization in this group. The paucity of data describing Indigenous status is an argument for improved data collection in this area. The low level of penicillin resistance necessitates ongoing surveillance, and the lack of serotype information requires prospective data collection.

Adolescent↗
PubMed2001

Hypoperfusion of Wernicke's area predicts severity of semantic deficit in acute stroke.

Based on earlier findings that the presence of word comprehension impairment (a deficit in the meaning of words, or lexical semantics) in acute stroke was strongly associated with the presence of hypoperfusion or infarct in Wernicke's area, we tested the hypothesis that the severity of word comprehension impairment was correlated with the magnitude of delay in perfusion of Wernicke's area on magnetic resonance perfusion-weighted imaging. Eighty patients were prospectively studied within 24 hours of onset or progression of acute left hemisphere stroke symptoms, with diffusion-weighted imaging, perfusion-weighted imaging, and detailed language tests. For 50 patients without infarct in Wernicke's area, we found a strong Pearson correlation between the rate of errors on a word comprehension test and the mean number of seconds of delay in time-to-peak concentration of contrast in Wernicke's area, relative to the homologous region on the right. These results add further evidence for the crucial role of Wernicke's area (Brodmann's area 22) in word comprehension and indicate that the magnitude of delay on PWI may be a gross indicator of tissue dysfunction.

Adult↗
PubMed2001

Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem.

Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to investigate regional metabolite levels and ratios in the normal adult human posterior fossa. Six normal volunteers (36 +/- 3 years, five male, one female) were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280 msec). The entire cerebellum was covered using three oblique-axial slice locations, which also included the pons, mid-brain, insular cortex, and parieto-occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were estimated using the phantom replacement technique. Regional variations of the concentrations were assessed using ANOVA (P < 0.05). High-resolution MRSI data was obtained in all subjects and brain regions examined. Metabolite concentrations (mM) (mean +/- SD) were as follows: cerebellar vermis: 2.3 +/- 0.4, 8.8 +/- 1.7 and 7.6 +/- 1.0 for Cho, Cr, and NAA respectively; cerebellar hemisphere: 2.2 +/- 0.6, 8.9 +/- 2.1, 7.5 +/- 0.8; pons 2.2 +/- 0.5, 4.3 +/- 1.1, 8.3 +/- 0.9; insular cortex, 1.8 +/- 0.5, 7.8 +/- 2, 8.0 +/- 1.1, parieto-occipital gray matter, 1.3 +/- 0.3, 5.7 +/- 1.1, 7.2 +/- 0.9, and occipital white matter, 1.4 +/- 0.3, 5.3 +/- 1.3, 7.5 +/- 0.8. Consistent with previous reports, significantly higher levels of Cr were found in the cerebellum compared to parieto-occipital gray and occipital white matter, and pons (P < 0.0001). NAA was essentially uniformly distributed within the regions chosen for analysis, with the highest level in the pons (P < 0.04). Cho was significantly higher in the cerebellum and pons than parieto-occipital gray and occipital white matter (P < 0.002) and was also higher in the pons than in the insular cortex (P < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and significant regional differences in metabolite concentrations were found.

Adult↗
PubMed2001

A model for multiparametric mri tissue characterization in experimental cerebral ischemia with histological validation in rat: part 1.

BACKGROUND AND PURPOSE: After stroke, brain tissue undergoes time-dependent heterogeneous histopathological change. These tissue alterations have MRI characteristics that allow segmentation of ischemic from nonischemic tissue. Moreover, MRI segmentation generates different zones within the lesion that may reflect heterogeneity of tissue damage. METHODS: A vector tissue signature model is presented that uses multiparametric MRI for segmentation and characterization of tissue. An objective (unsupervised) computer segmentation algorithm was incorporated into this model with the use of a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). The ability of the model to characterize ischemic tissue after permanent middle cerebral ischemia occlusion in the rat was tested. Multiparametric ISODATA measurements of the ischemic tissue were compared with quantitative histological characterization of the tissue from 4 hours to 1 week after stroke. RESULTS: The ISODATA segmentation of tissue identified a gradation of cerebral tissue damage at all time points after stroke. The histological scoring of ischemic tissue from 4 hours to 1 week after stroke on all the animals was significantly correlated with ISODATA segmentation (r=0.78, P<0.001; n=20) when a multiparametric (T2-, T1-, diffusion-weighted imaging) data set was used, less correlated (r=0.70, P<0.01; n=20) when a T2- and T1-weighted data set was used, and not correlated (r=-0.12, P>0.47; n=20) when only a diffusion-weighted imaging data set was used. CONCLUSIONS: Our data indicate that an integrated set of MRI parameters can distinguish and stage ischemic tissue damage in an objective manner.

Algorithms↗
PubMed2001

Multiparametric MRI tissue characterization in clinical stroke with correlation to clinical outcome: part 2.

BACKGROUND AND PURPOSE: Multiparametric MRI generates different zones within the lesion that may reflect heterogeneity of tissue damage in cerebral ischemia. This study presents the application of a novel model of tissue characterization based on an angular separation between tissues obtained with the use of an objective (unsupervised) computer segmentation algorithm implementing a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). We test the utility of this model to identify ischemic tissue in clinical stroke. METHODS: MR parameters diffusion-, T2-, and T1-weighted imaging (DWI, T2WI, and T1WI, respectively) were obtained from 10 patients at 3 time points (30 studies) after stroke: acute (</=12 hours), subacute (3 to 5 days), and chronic (3 months). The National Institutes of Health Stroke Scale (NIHSS) was measured, and volumes were obtained from the ISODATA, DWI, and T2WI maps on patients at each time point. RESULTS: The acute (</=12 hours) multiparametric ISODATA volume was significantly correlated with the acute (</=12 hours) DWI (r=0.96, P<0.05; n=10) and chronic (3 months) T2WI volume (r=0.69, P<0.05; n=10). The ISODATA-defined tissue regions exhibited MR indices consistent with ischemic and/or infarcted tissue at each time point. The acute (</=12 hours) multiparametric ISODATA volumes were significantly correlated (r=0.82, P<0.009; n=10) with the final NIHSS score. In comparison, the acute (</=12 hours) DWI volumes were less correlated (r=0.77, P<0.05; n=10) and T2WI volume (</=12h) exhibited a marginal correlation (r=0.66, P<0.05; n=10) with the final NIHSS score. CONCLUSIONS: The integrated ISODATA approach to tissue segmentation and classification discriminated abnormal from normal tissue at each time point. The ISODATA volume was significantly correlated with the current MR standards used in the clinical setting and the 3-month clinical status of the patient.

Adult↗
PubMed2000

Disruption of the developmentally regulated Rev3l gene causes embryonic lethality.

The REV3 gene encodes the catalytic subunit of DNA polymerase (pol) zeta, which can replicate past certain types of DNA lesions [1]. Saccharomyces cerevisiae rev3 mutants are viable and have lower rates of spontaneous and DNA-damage-induced mutagenesis [2]. Reduction in the level of Rev31, the presumed catalytic subunit of mammalian pol zeta, decreased damage-induced mutagenesis in human cell lines [3]. To study the function of mammalian Rev31, we inactivated the gene in mice. Two exons containing conserved DNA polymerase motifs were replaced by a cassette encoding G418 resistance and beta-galactosidase, under the control of the Rev3l promoter. Surprisingly, disruption of Rev3l caused mid-gestation embryonic lethality, with the frequency of Rev3l(-/-) embryos declining markedly between 9.5 and 12.5 days post coitum (dpc). Rev3l(-/-) embryos were smaller than their heterozygous littermates and showed retarded development. Tissues in many areas were disorganised, with significantly reduced cell density. Rev3l expression, traced by beta-galactosidase staining, was first detected during early somitogenesis and gradually expanded to other tissues of mesodermal origin, including extraembryonic membranes. Embryonic death coincided with the period of more widely distributed Rev3l expression. The data demonstrate an essential function for murine Rev31 and suggest that bypass of specific types of DNAlesions by pol zeta is essential for cell viability during embryonic development in mammals.

Animals↗
PubMed2000

Unsupervised segmentation of multiparameter MRI in experimental cerebral ischemia with comparison to T2, diffusion, and ADC MRI parameters and histopathological validation.

This study presents histological validation of an objective (unsupervised) computer segmentation algorithm, the iterative self-organizing data analysis technique (ISODATA), for analysis of multiparameter magnetic resonance imaging (MRI) data in experimental focal cerebral ischemia. T2-, T1-, and diffusion (DWI) weighted coronal images were acquired from 4 to 168 hours after stroke on separate groups of animals. Animals were killed immediately after MRI for histological analysis. MR images were coregistered/warped to histology. MRI lesion areas were defined using DWI, apparent diffusion coefficient (ADC) maps, T2-weighted images, and ISODATA. The last techniques clearly discriminated between ischemia-altered and morphologically intact tissue. ISODATA areas were congruent and significantly correlated (r = 0.99, P < 0.05) with histologically defined lesions. In contrast, DWI, ADC, and T2 lesion areas showed no significant correlation with histologically evaluated lesions until subacute time points. These data indicate that multiparameter ISODATA methodology can accurately detect and identify ischemic cell damage early and late after ischemia, with ISODATA outperforming ADC, DWI, and T2-weighted images in identification of ischemic lesions from 4 to 168 hours after stroke.

Algorithms↗
PubMed2000

Boundary-based warping of brain MR images.

The goal of this work was to develop a warping technique for mapping a brain image to another image or atlas data, with minimum user interaction and independent of gray level information. We have developed and tested three different methods for warping magnetic resonance (MR) brain images. We utilize a deformable contour to extract and warp the boundaries of the two images. A mesh-grid coordinate system is constructed for each brain, by applying a distance transformation to the resulting contours, and scaling. In the first method (MGC), the first image is mapped to the second image based on a one-to-one mapping between different layers defined by the mesh-grid. In the second method (IDW), the corresponding pixels in the two images are found using the above mesh-grid system and a local inverse-distance weights interpolation. In the third proposed method (TSB), a subset of grid points is used for finding the parameters of a spline transformation, which defines the global warping. The warping methods were applied to clinical MR consisting of diffusion-weighted and T2-weighted images of the human brain. The IDW and TSB methods were superior in ranking of diagnostic quality of the warped MR images to the MGC (P < 0.01) as defined by a neuroradiologist. The deformable contour warping produced excellent diagnostic quality for the diffusion-weighted images coregistered and warped to T2 weighted images. J. Magn. Reson. Imaging 2000;12:417-429.

Aged↗
PubMed1999

Identification of cerebral ischemic lesions in rat using Eigenimage filtered magnetic resonance imaging.

An accurate noninvasive time-independent identification of an ischemic cerebral lesion is an important objective of magnetic resonance imaging (MRI). This study describes a novel application of a multiparameter MRI analysis algorithm, the Eigenimage (EI) filter, to experimental stroke. The EI is a linear filter that maximizes the projection of a desired tissue (ischemic tissue) while it minimizes the projection of undesired tissues (nonischemic tissue) onto a composite image called an eigenimage. Rats (n=26) were subjected to permanent middle cerebral artery occlusion. T2- and T1-weighted coronal MRI were acquired on separate groups of animals. The animals were immediately sacrificed after each imaging session for histopathological analysis of tissue at 4-8 h, 16-24 h, and 48-168 h after stroke onset. Lesion areas from MRI were defined using EI. The EI defined lesion areas were coregistered and warped to the corresponding histopathological sections. The ischemic lesion as defined by EI exhibited ischemic cell damage ranging from scattered acute cell damage to pan necrosis. Ischemic cellular damage was not detected in homologous contralateral hemisphere regions. EI lesion areas overlaid on histopathological sections were significantly correlated (r=0.92, p<0.05) acutely, (r=0.98, p<0.05) subacutely, and (r=0.99, p<0.05) chronically. These data indicate that EI methodology can accurately segment ischemic damage after MCA occlusion from 4-168 h after stroke.

Algorithms↗
PubMed1999

A conserved His-Asp signal response regulator-like gene in Heterosigma akashiwo chloroplasts.

Regulation of gene expression in plastids may involve molecular components conserved from cyanobacteria-like ancestors. Among prokaryotes, genes are commonly regulated at the transcriptional level by 'two-component' or 'His-Asp' signal transducers, consisting of a 'sensor kinase', which autophosphorylates at a conserved histidine residue, and a cognate response regulator, which is phosphorylated by the sensor kinase at a conserved aspartate residue. A putative His-Asp response regulator gene (trg1: transcriptional regulatory gene 1) has been identified in the estuarine raphidophytic alga Heterosigma akashiwo. The chloroplast-encoded trg1 is 693 bp in length, contains no introns, and yields a conceptual translation product of 231 amino acids, with a predicted mass of 27 kDa. Homology searches suggest that Heterosigma trgl has an omnpR-like identity within the DNA-binding His-Asp family of response regulators. trg1 contains both the phosphorylation and DNA-binding domains which are present in prokaryote response regulators. Quantitative competitive RT-PCR showed that Heterosigma trg1 is expressed at low levels (5 microg per g total RNA). In contrast, psbA (a photosystem II component) transcript is abundant (60 mg per g total RNA). Cell cycle analysis showed that psbA abundance oscillates in response to light but trg1 mRNA levels are invariant. We hypothesize that a His-Asp phosphorelay mechanism may affect chloroplast genome transcription in a manner similar to bacterial signal transduction pathways in which 'sensor kinase' and cognate 'response regulator' proteins interact.

Algal Proteins↗
PubMed1999

Registration and warping of magnetic resonance images to histological sections.

We present a method for coregistration and warping of magnetic resonance images (MRI) to histological sections for comparison purposes. This methodology consists of a modified head and hat surface-based registration algorithm followed by a new automated warping approach using nonlinear thin plate splines to compensate for distortions between the data sets. To test the methodology, 15 male Wistar rats were subjected to focal cerebral ischemia via permanent occlusion of the middle cerebral artery. The MRI images were acquired in separate groups of animals at 16-24 h (n = 9) and 48-168 h (n = 6) postocclusion. After imaging, animals were immediately sacrificed and hematoxylin- and eosin-stained brain sections were obtained for histological analysis. The MRI was coregistered and warped to histological sections. The MRI lesion areas were defined using the Eigenimage (EI) filter technique. The EI is a linear filter that maximizes the projection of a desired tissue (ischemic tissue) while it minimizes the projection of undesired tissues (nonischemic tissue) onto a composite image called an EI. When using coregistration without warping the MRI lesion area demonstrated poor correlation (r = 0.55, p > 0.01) with a percent difference between the two lesion areas of 22.5% +/- 10.8%. After warping, the MRI and histology had significant correlation (r = 0.97, p < 0.01) and a decreased percent difference of 5.56% +/- 4.31%. This methodology is simple and robust for coregistration and warping of MRI to histological sections and can be utilized in many applications for comparison of MRI to histological data.

Algorithms↗
PubMed1998

Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero.

Two B-type cyclins, B1 and B2, have been identified in mammals. Proliferating cells express both cyclins, which bind to and activate p34(cdc2). To test whether the two B-type cyclins have distinct roles, we generated lines of transgenic mice, one lacking cyclin B1 and the other lacking cyclin B2. Cyclin B1 proved to be an essential gene; no homozygous B1-null pups were born. In contrast, nullizygous B2 mice developed normally and did not display any obvious abnormalities. Both male and female cyclin B2-null mice were fertile, which was unexpected in view of the high levels and distinct patterns of expression of cyclin B2 during spermatogenesis. We show that the expression of cyclin B1 overlaps the expression of cyclin B2 in the mature testis, but not vice versa. Cyclin B1 can be found both on intracellular membranes and free in the cytoplasm, in contrast to cyclin B2, which is membrane-associated. These observations suggest that cyclin B1 may compensate for the loss of cyclin B2 in the mutant mice, and implies that cyclin B1 is capable of targeting the p34(cdc2) kinase to the essential substrates of cyclin B2.

3T3 Cells↗
PubMed1998

Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM.

In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean+/-SEM): 16.1+/-3.1 vs 23.6+/-3.3) episodes during the last 6 weeks of treatment, p=0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA1c 7.2+/-0.2 vs 7.1+/-0.2 %, p=0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study.

Adult↗
PubMed1998

Is malnutrition overdiagnosed in older hospitalized patients? Association between the soluble interleukin-2 receptor and serum markers of malnutrition.

BACKGROUND: Many researchers have speculated that markers of malnutrition such as albumin, prealbumin, cholesterol, and transferrin are influenced by inflammation. The mechanism of this interaction has not been well understood. METHODS: This was a prospective cross-sectional study. We evaluated 72 male patients older than 60 years admitted to a geriatric rehabilitation unit. Subjects with severe hepatic or renal diseases were excluded. We measured body mass index, caloric intake, serum albumin, prealbumin, cholesterol, transferrin, hemoglobin, and total lymphocyte count. To detect inflammation, we measured C-reactive protein, Westergren sedimentation rate, fibrinogen, and cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-2, and the soluble IL-2 receptor. RESULTS: Soluble IL-2 receptor was negatively associated with albumin (r = -.479, p < .0001), prealbumin (r = -.520, p = < .0001), cholesterol (r = -.487, p = .0001), transferrin (r = -.455, p = .0002), and hemoglobin (r = -.371, p = .002). TNF-alpha, IL-1 beta, IL-6, and IL-2 were not associated with these measures. CONCLUSIONS: Inflammation increases the incidence of hypoalbuminemia and hypocholesterolemia, potentially leading to overdiagnosis of malnutrition. We suggest that albumin, cholesterol, prealbumin, and transferrin be used with caution when assessing the nutritional status of older hospitalized patients. In the future, soluble IL-2 receptor levels might be used to correct for the impact of inflammation on these markers of malnutrition.

Aged↗
PubMed1998

Prediction of impending hemorrhagic transformation in ischemic stroke using magnetic resonance imaging in rats.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) of ischemic brain tissue may occur in stroke patients either spontaneously or after thrombolysis. A method to assess the risk of HT in ischemic tissue after stroke would improve the safety of thrombolytic therapy. As a means of predicting HT, we investigated the role of contrast-enhanced MRI at acute time points in a rat middle cerebral artery occlusion model with reperfusion. METHODS: Intraluminal suture occlusion of the middle cerebral artery was used to produce transient ischemia in male Wistar rats (n=11). Reperfusion was performed by withdrawal of the occluding filament after 2 (n=4), 3 (n=6), or 4 (n=1) hours. MRI studies were performed before and after reperfusion with the use of conventional T1-weighted imaging, with and without gadolinium (Gd-DTPA) contrast agent, and T2-weighted imaging. Follow-up MRI and histological studies were obtained at 24 hours. RESULTS: Petechial hemorrhage occurred by 24 hours in 9 of 11 animals. All animals showed brain swelling and cellular death throughout the ischemic region at 24 hours. A hyperintense region in the preoptic area became visible after Gd-DTPA injection within minutes after reperfusion in animals with subsequent HT. All animals showing acute Gd-DTPA enhancement subsequently developed petechial hemorrhage (or died) by 24 hours. In these animals, statistically significant differences in signal intensity (P=.0005) between the ipsilateral enhancing region and a homologous contralateral region were detected on post-Gd-DTPA T1-weighted imaging. There was also a statistically significant correlation (P=.01) between the rate of Gd-DTPA uptake and the size of the enhancing area. Two animals did not enhance with Gd-DTPA and did not exhibit hemorrhage on histological examination or MRI at 24 hours. No abnormalities were seen on precontrast T1-weighted images before and shortly after reperfusion or postcontrast T1-weighted images before reperfusion. CONCLUSIONS: The primary finding of this study was the detection of early Gd-DTPA parenchymal enhancement in 82% of the animals after reperfusion. Enhancement was seen before any detectable hemorrhage, suggesting that early endothelial ischemic damage occurs before gross brain infarction and hemorrhage. Thus, we suggest that acute Gd-DTPA enhancement may provide an early prediction of petechial hemorrhage.

Animals↗