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Biomedical subjects

Z G Zhang

Publications and source records attributed to Z G Zhang.

At least 19 recordsLinked to original sources
PubMed2007

Ultraviolet upconversion fluorescence in rare-earth-ion-doped Y2O3 induced by infrared diode laser excitation.

Room-temperature ultraviolet emission of Tm(3+) ions at 298 ((1)I(6)-->(3)H(6)), 364 ((1)D(2)-->(3)H(6)), and 391 nm ((1)I(6)-->(3)H(5)) was obtained in Y(2)O(3):Yb(3+)-Tm(3+) by continuous-wave diode laser excitation of 980 nm. Power dependence analysis demonstrates that five- and six-photon upconversion processes populate the (1)D(2) and (1)I(6) states, respectively. We believe that the (1)D(2) population originates from the cross relaxation (1)G(4)+(3)F(4)-->(3)H(4)+(1)D(2) of the Tm(3+) ions, while subsequent energy transfer from Yb(3+) to Tm(3+) excites the (1)D(2) state to the upper (1)I(6) state. High multiphoton-induced ultraviolet emission is also expected for other trivalent rare-earth ions similar to Tm(3+).

Journal Article↗
PubMed2006

Molecular mapping of two cultivar-specific avirulence genes in the rice blast fungus Magnaporthe grisea.

Rice blast, caused by the fungus Magnaporthe grisea, is a globally important disease of rice that causes annual yield losses. The segregation of genes controlling the virulence of M. grisea on rice was studied to establish the genetic basis of cultivar specificity in the interaction of rice and M. grisea. The segregation of avirulence and virulence was studied in 87 M. grisea F(1) progeny isolates from a cross of two isolates, Guy11 and JS153, using resistance-gene-differential rice cultivars. The segregation ratio indicated that avirulence and virulence in the rice cultivars Aichi-asahi and K59, respectively, are controlled by single major genes. Genetic analyses of backcrosses and full-sib crosses in these populations were also performed. The chi(2 )test of goodness-of-fitness for a 1:1 ratio indicated that one dominant gene controls avirulence in Aichi-asahi and K59 in this population. Based on the resistance reactions of rice differential lines harboring known resistance genes to the parental isolates, two genetically independent avirulence genes, AVR-Pit and AVR-Pia, were identified. Genetic linkage analysis showed that the SSR marker m355-356 is closely linked to AVR-Pit, on the telomere of chromosome 1 at a distance of approximately 2.3 cM. The RAPD marker S487, which was converted to a sequence-characterized amplified region (SCAR) marker, was found to be closely linked to AVR-Pia, on the chromosome 7 telomere at a distance of 3.5 cM. These molecular markers will facilitate the positional cloning of the two AVR genes, and can be applied to molecular-marker-assisted studies of M. grisea populations.

Chromosome Mapping↗
PubMed2005

Semi-automated brain tumor and edema segmentation using MRI.

PURPOSE: Manual segmentation of brain tumors from magnetic resonance images is a challenging and time-consuming task. A semi-automated method has been developed for brain tumor and edema segmentation that will provide objective, reproducible segmentations that are close to the manual results. Additionally, the method segments non-enhancing brain tumor and edema from healthy tissues in magnetic resonance images. METHODS AND MATERIALS: In this study, a semi-automated method was developed for brain tumor and edema segmentation and volume measurement using magnetic resonance imaging (MRI). Some novel algorithms for tumor segmentation from MRI were integrated in this medical diagnosis system. We exploit a hybrid level set (HLS) segmentation method driven by region and boundary information simultaneously, region information serves as a propagation force which is robust and boundary information serves as a stopping functional which is accurate. Ten different patients with brain tumors of different size, shape and location were selected, a total of 246 axial tumor-containing slices obtained from 10 patients were used to evaluate the effectiveness of segmentation methods. RESULTS: This method was applied to 10 non-enhancing brain tumors and satisfactory results were achieved. Two quantitative measures for tumor segmentation quality estimation, namely, correspondence ratio (CR) and percent matching (PM), were performed. For the segmentation of brain tumor, the volume total PM varies from 79.12 to 93.25% with the mean of 85.67+/-4.38% while the volume total CR varies from 0.74 to 0.91 with the mean of 0.84+/-0.07. For the segmentation of edema, the volume total PM varies from 72.86 to 87.29% with the mean of 79.54+/-4.18% while the volume total CR varies from 0.69 to 0.85 with the mean of 0.79+/-0.08. The HLS segmentation method perform better than the classical level sets (LS) segmentation method in PM and CR. CONCLUSIONS: The results of this research may have potential applications, both as a staging procedure and a method of evaluating tumor response during treatment, this method can be used as a clinical image analysis tool for doctors or radiologists.

Algorithms↗
PubMed2003

Migration and differentiation of adult rat subventricular zone progenitor cells transplanted into the adult rat striatum.

Adult brain subventricular zone progenitor cells undergo neurogenesis in the olfactory bulb. We tested the hypothesis that cultured adult subventricular zone progenitor cells migrate and differentiate into neurons when transplanted into the adult striatum. Cells in the adult rat subventricular zone were isolated and cultured for 8 days in medium containing basic fibroblast growth factor. These cells proliferated as assayed by bromodeoxyuridine immunostaining, and the majority of them were neuron-specific class III beta-tubulin (TuJ1) immunoreactive at 8 days of culture. These cultured cells were labeled in vitro with bromodeoxyuridine or with lipophilic dye-coated particles and were transplanted into the adult rat striatum. Twenty-eight days after transplantation, the cells migrated 0.5-1.5 mm from the midline of the graft to the surrounding host striatum. Migration of grafted cells in the host striatum was also detected on magnetic resonance imaging in living rats. Morphological analysis revealed that many of these migrated cells exhibited multibranched processes from the cell soma resembling host medium-size striatal projection neurons. Only a few astrocyte-like cells were detected. Double immunostaining showed that many bromodeoxyuridine immunoreactive cells were microtubule-associated protein 2 or immunoreactive with a mouse monoclonal antibody against neuronal nuclear protein, whereas only a few bromodeoxyuridine immunoreactive cells had glial fibrillary acidic protein immunoreactivity. Morphology of bromodeoxyuridine and microtubule-associated protein 2 immunoreactive cells was similar to those of host microtubule-associated protein 2 immunoreactive cells. These results suggest that transplanted cultured adult subventricular zone progenitor cells can migrate and differentiate in response to guidance cues within the adult striatum.

Age Factors↗
PubMed2003

Kinetics of beta-mannanase fermentation by Bacillus licheniformis.

Bacterial growth, konjac powder utilization and beta-mannanase production by Bacillus licheniformis NK-27 in batch fermentation were used to develop a model of the process. The optimal set of parameters was estimated by fitting the model to experimental data. The results predicted by the model were in good agreement with the experimental data. NOMENCLATURE: fs, fraction parameter; Kp, constant in Equation (6) (g l(-1)); Ks, Monod constant for bacteria growth (g l(-1)); m, maintenance coefficient (g g(-1) h(-1)); P, beta-mannanase concentration (g 1(-1)); qm, constant in Equation (6) (h(-1)); S, substrate concentration (g l(-1)); S0, initial substrate concentration (g l(-1)); Si, insoluble substrate concentration (g l(-1)); Ss, soluble substrate concentration (g l(-1)); t, fermentation time (h); tL, lag time (h); mu, specific growth rate (h(-1)); mu(max), maximum specific growth rate (h(-1)); X, biomass concentration (g l(-1)); YP/S, beta-mannanase yield on carbon substrate (g g(-1)); YX/S, biomass yield on carbon substrate (g g(-1)).

Bacillus↗
PubMed2003

[Effect of fasting on gastric mucosa thickness: experimental study in laboratory rats].

BACKGROUND: It has been proven that damage to the gastric mucosa is the result of the combined effects of acidopeptic agents including infection with Helicobacter pylori and insufficient protective mechanisms of the mucosa. Thickness of gastric mucus is very important protective factor. We can hypothetically expect that fasting may cause changes in the thickness of gastric mucus layer, which may in certain circumstances contribute to the conditions for mucosal injury. We have therefore conducted an experimental study on laboratory rats, aiming to assess the changes in the thickness of gastric mucus after 8 and 24-hour periods of fasting. METHODS AND RESULTS: We measured gastric mucus thickness with the aid of microelectrodes in 279 laboratory rats (group I) after 8 hours of fasting (2 measurements each, total of 558 measurements), followed by the same measurement in 70 laboratory rats (group II) after a 24-hour fasting. Group I had a gastric mucus thickness of 595 +/- 10 (mean +/- SD, microns); in group II the thickness was 502 +/- 10 (mean +/- SD, microns). After statistical analysis of the homogeneity of the two populations (Fisher's analysis), it has been proven that both groups belong to the same basic population sample. The statistical evaluation of the thickness of gastric mucus in both groups showed thinning of the mucus layer to 1% of the significant statistical difference. The difference between both groups is statistically significant. CONCLUSIONS: The thickness of gastric mucus is reduced after 24 hours' fasting in laboratory rats. This change is statistically significant (P < 0.01). It can be hypothesized that--under the specific conditions--this process can facilitate the injury of gastric mucosa.

Animals↗
PubMed2003

Reconstruction of maxillectomy defect by transport distraction osteogenesis.

The study aimed to explore the feasibility of posterior maxillectomy reconstruction by transport distraction in a primate model. In each of 14 male adult rhesus monkeys, posterior partial maxillectomy was performed on one side of maxilla to create a posterior maxillary deflect. Immediately after the maxillectomy, a dentoalveolar segment anterior to the defect was osteotomized as transport segment and a custom-made transport distractor was fixed on the residual maxilla. After a latency period of 5 days, the distractor was activated 1 mm daily to move the transport segment backward to the defect. This process lasted about 2 weeks. The transport segment was allowed to consolidate and the animals were sacrificed at different defined intervals. Transport distraction was successful in six animals. Three other cases were completed with minor wound dehiscence and one had a small oro-antral fistula with subsequent maxillary sinusitis. New bone bridging the distraction gap was confirmed by radiography and histology in the animals completing distraction. Reconstruction of posterior maxillectomy defect is proven feasible by transport distraction osteogenesis.

Alveolar Process↗
PubMed2002

Angiopoietin-1 reduces cerebral blood vessel leakage and ischemic lesion volume after focal cerebral embolic ischemia in mice.

Angiopoietin-1 (Ang1) is a ligand for the endothelial specific receptor tyrosine kinase, Tie2, that protects the adult peripheral vasculature from vascular leakage. We tested the hypothesis that increases in levels of Ang1 reduce blood-brain barrier (BBB) leakage in ischemic brain. Mice were subjected to embolic middle cerebral artery (MCA) occlusion. Recombinant adenoviruses expressing Ang1 (Ad-Ang1) or a control gene encoding green fluorescent protein (Ad-GFP), or recombinant Ang1 protein, BowAng1, was administered to mice before MCA occlusion. Regional cerebral blood flow (rCBF), the brain tissue content of Evans Blue, and ischemic lesion volume were measured. Serum levels of Ang1 (183+/-31.9 microg/ml, n=4) were detected in mice receiving Ad-Ang1 or in mice treated with BowAng1 (262+/-35.4 microg/ml, n=7) but not in the control mice (n=11). Six hours after MCA occlusion, mice receiving Ad-GFP (n=8) or control protein (n=7) showed large Evans Blue leakage in the ipsilateral hemisphere (0.46+/-0.05 or 0.55+/-0.16 ng/mg tissue) whereas mice receiving Ad-Ang1 (n=6) or BowAng1 (n=7) had significantly (P<0.05) less Evans Blue leakage (0.26+/-0.07 or 0.14+/-0.03 ng/mg tissue). Infusion of recombinant human vascular endothelial growth factor (rhVEGF(165)) to ischemic mice resulted in significant (P<0.05) increases in Evans Blue leakage (1.24+/-0.34 ng/mg tissue, n=7) compared with the control mice. In contrast, infusion of rhVEGF(165) in ischemic mice receiving Ad-Ang1 did not significantly increase Evans Blue dye in the ipsilateral hemisphere (0.22+/-0.06 ng/mg tissue, n=6). Moreover, 24 h after ischemia mice receiving Ad-Ang1 had a significantly smaller ischemic lesion volume (22.6+/-2.7%, n=8) than the lesion volume in mice receiving Ad-GFP (44.7+/-3.7%, n=8), although rCBF reduced to approximately 20% of the contralateral levels in both groups of mice 10 min after ischemia. Our data demonstrate that Ang1 reduces BBB leakage in ischemic brain and consequently decreases ischemic lesion volume.

Angiogenesis Inducing Agents↗
PubMed2001

Time-resolved laser spectroscopy of multiply ionized atoms: natural radiative lifetimes in Ce IV.

Radiative lifetimes have been measured for two excited levels of Ce IV using the time-resolved laser-induced fluorescence technique. Ce3+ ions were produced in a laser-induced plasma. In the measurements, a suitable magnetic field was applied to reduce the recombination between electrons and the ions and thus the background light from the recombination, and special care was exercised to avoid flight-out-of-view effects on the lifetime measurements for the high-velocity ions. The experimental lifetime results, tau = 30(2) ns for the level 49 737 cm(-1) and tau = 30(3) ns for the level 52 226 cm(-1), were compared with relativistic Hartree-Fock calculations (tau = 30.5 and 30.0 ns) indicating a particularly excellent agreement.

Journal Article↗
PubMed2001

Postischemic (6-Hour) treatment with recombinant human tissue plasminogen activator and proteasome inhibitor PS-519 reduces infarction in a rat model of embolic focal cerebral ischemia.

BACKGROUND AND PURPOSE: The proteasome inhibitor PS-519 blocks activation of nuclear factor-kappaB, a major mediator of inflammation. We tested the hypothesis that combination treatment of recombinant human tissue plasminogen activator (rhtPA) and PS-519 extends the therapeutic window for treatment of stroke with rhtPA without increasing incidence of hemorrhagic transformation. METHODS: The middle cerebral artery (MCA) of male Wistar rats (n=56) was occluded by an embolus. After embolization, animals were randomly divided into the following groups: PS-519 treatment groups: PS-519 was given at 2, 4, or 6 hours after MCA occlusion; rhtPA treatment groups: rhtPA was given at 2 or 4 hours after MCA occlusion; combination treatment groups: PS-519 and rhtPA were given at 2, 4, or 6 hours after MCA occlusion; control group: the same volume of saline was given at 2 hours after MCA occlusion. RESULTS: Administration of PS-519 alone at 2 or 4 hours, but not 6 hours, significantly (P<0.05) reduced infarct volume and improved neurological recovery compared with the control group. Administration of rhtPA alone at 2 hours, but not 4 hours, significantly (P<0.05) reduced infarct volume and improved neurological recovery compared with the control group. Furthermore, combination treatment with rhtPA and PS-519 even at 6 hours significantly (P<0.05) reduced infarct volume, improved neurological recovery, and did not increase the incidence of hemorrhagic transformation compared with the control group or the group treated with PS-519 alone. CONCLUSIONS: Our data suggest that combination treatment with PS-519 and rhtPA extends the neuroprotective effect to at least 6 hours after embolization.

Acetylcysteine↗
PubMed2001

Dynamic platelet accumulation at the site of the occluded middle cerebral artery and in downstream microvessels is associated with loss of microvascular integrity after embolic middle cerebral artery occlusion.

Information is lacking regarding dynamic platelet accumulation at the site of the occluded middle cerebral artery (MCA) and the relationship between platelet aggregation in downstream cerebral microvessels and loss of perfusion and vascular integrity of these microvessels. In the present study, we employed a model of embolic MCA occlusion in the rat to simultaneously measure temporal and spatial profiles of platelet accumulation at the site of the embolus occluding the MCA and within downstream cerebral microvessels. We also measured the integrity of microvessels and matrix metalloproteinase (MMP) activity in ischemic brain. Rats (n=36) were subjected to embolic MCA occlusion. Immunohistochemistry was used to detect microvascular integrity, plasminogen activator inhibitor 1 (PAI-1) and the deposition of fibrin. SDS-PAGE zymography was used to measure MMP2 and MMP9 activities. Accumulation of platelets and increases in PAI-1 immunoreactivity at the site of the embolus occluding the MCA were detected 1 h (n=7) and 4 h (n=7) after ischemia, respectively, and numbers of GPIIb/IIIa immunoreactive downstream cerebral microvessels increased significantly (209+/-59; n=7; P<0.05) 4 h after ischemia, suggesting dynamic platelet aggregation. A significant (n=7; P<0.01) diffuse loss of type IV collagen immunoreactivity in microvessels was temporally associated with platelet GPIIb/IIIa immunoreactivity within the vessels. Triple immunostaining revealed that microvessels containing platelet aggregates exhibited loss of type IV collagen immunoreactivity and both intra- and extra-vascular fibrin deposition, suggesting that intravascular platelet aggregation is associated with decreases in the integrity of the microvascular basal lamina and blood-brain barrier leakage. A significant increase (P<0.05) in MMP9 was detected at 4 h (n=3) and 24 h (n=3) after ischemia but levels of MMP2 were not significantly changed in ischemic brain. Our data suggest that dynamic platelet aggregation in ischemic brain may contribute to time-dependent resistance to fibrinolysis. In addition, platelet deposition and increased MMP9 coincided with degradation of type IV collagen and loss of vascular integrity. These data suggest an important role for post-occlusive distal platelet deposition in the pathophysiology of stroke.

Animals↗
PubMed2001

The synthesis, discovery, and development of a highly promising class of microtubule stabilization agents: curative effects of desoxyepothilones B and F against human tumor xenografts in nude mice.

We have evaluated two synthetic epothilone analogues lacking the 12,13-epoxide functionality, 12,13-desoxyepothilone B (dEpoB), and 12,13-desoxyepothilone F (dEpoF). The concentrations required for 50% growth inhibition (IC(50)) for a variety of anticancer agents were measured in CCRF-CEM/VBL1000 cells (2,048-fold resistance to vinblastine). By using dEpoB, dEpoF, aza-EpoB, and paclitaxel, the IC(50) values were 0.029, 0.092, 2.99, and 5.17 microM, respectively. These values represent 4-, 33.5-, 1,423- and 3,133-fold resistance, respectively, when compared with the corresponding IC(50) in the parent [nonmultiple drug-resistant (MDR)] CCRF-CEM cells. We then produced MDR human lung carcinoma A549 cells by continuous exposure of the tumor cells to sublethal concentrations of dEpoB (1.8 yr), vinblastine (1.2 yr), and paclitaxel (1.8 yr). This continued exposure led to the development of 2.1-, 4,848-, and 2,553-fold resistance to each drug, respectively. The therapeutic effect of dEpoB and paclitaxel was also compared in vivo in a mouse model by using various tumor xenografts. dEpoB is much more effective in reducing tumor sizes in all MDR tumors tested. Analysis of dEpoF, an analog possessing greater aqueous solubility than dEpoB, showed curative effects similar to dEpoB against K562, CCRF-CEM, and MX-1 xenografts. These results indicate that dEpoB and dEpoF are efficacious antitumor agents with both a broad chemotherapeutic spectrum and wide safety margins.

Animals↗
PubMed2001

Magnetization transfer MRI: application to treatment of middle cerebral artery occlusion in rat.

The temporal profiles of MRI parameters which use quantitative estimates of magnetization transfer were measured in 22 male Wistar rats subjected to middle cerebral artery occlusion, with and without therapeutic intervention with an anti-ICAM-1 monoclonal antibody. Two measures were used: the value of a magnetization transfer-related parameter in a predetermined region of interest, and the area of damage, as measured by changes in this parameter. In both groups, the value and area of damage of the inverse of the apparent forward transfer rate for magnetization transfer (1/k(fa)) significantly increased from the preischemic values (P < 0.05), as did T1 under an off-resonance partial saturation of the macromolecular pool (T1sat), and T1 (P < 0.05). Moreover, the increase in the value and total area of damage, as measured by 1/k(fa), T1, and T1sat in the treated group, was smaller compared to that of the untreated group, with significant differences detected between groups at 5, 24, and 48 hours. Our data suggest that a quantitative measure of MT may provide a sensitive and early method to detect the efficacy of therapeutic intervention in experimental stroke.

Animals↗
PubMed2001

Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia.

Progenitor cells in the subventricular zone of the lateral ventricle and in the dentate gyrus of the hippocampus can proliferate throughout the life of the animal. To examine the proliferation and fate of progenitor cells in the subventricular zone and dentate gyrus after focal cerebral ischemia, we measured the temporal and spatial profiles of proliferation of cells and the phenotypic fate of proliferating cells in ischemic brain in a model of embolic middle cerebral artery occlusion in the adult rat. Proliferating cells were labeled by injection of bromodeoxyuridine (BrdU) in a pulse or a cumulative protocol. To determine the temporal profile of proliferating cells, ischemic rats were injected with BrdU every 4 h for 12 h on the day preceding death. Rats were killed 2-14 days after ischemia. We observed significant increases in numbers of proliferating cells in the ipsilateral cortex and subventricular zone 2-14 days with a peak at 7 days after ischemia compared with the control group. To maximize labeling of proliferating cells, a single daily injection of BrdU was administered over a 14-day period starting the day after ischemia. Rats were killed either 2 h or 28 days after the last injection of BrdU. A significant increase in numbers of BrdU immunoreactive cells in the subventricular zone was coincident with a significant increase in numbers of BrdU immunoreactive cells in the olfactory bulb 14 days after ischemia and numbers of BrdU immunoreactive cells did not significantly increase in the dentate gyrus. However, 28 days after the last labeling, the number of BrdU labeled cells decreased by 90% compared with number at 14 days. Clusters of BrdU labeled cells were present in the cortex distal to the infarction. Numerous cells immunostained for the polysialylated form of the neuronal cell adhesion molecule were detected in the ipsilateral subventricular zone. Only 6% of BrdU labeled cells exhibited glial fibrillary acidic protein immunoreactivity in the cortex and subcortex and no BrdU labeled cells expressed neuronal protein markers (neural nuclear protein and microtubule associated protein-2). From these data we suggest that focal cerebral ischemia induces transient and regional specific increases in cell proliferation in the ipsilateral hemisphere and that proliferating progenitor cells may exist in the adult cortex.

Age Factors↗
PubMed2001

Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke.

Vascular endothelial growth factor (VEGF), an angiogenic factor produced in response to ischemic injury, promotes vascular permeability (VP). Evidence is provided that Src kinase regulates VEGF-mediated VP in the brain following stroke and that suppression of Src activity decreases VP thereby minimizing brain injury. Mice lacking pp60c-src are resistant to VEGF-induced VP and show decreased infarct volumes after stroke whereas mice deficient in pp59c-fyn, another Src family member, have normal VEGF-mediated VP and infarct size. Systemic application of a Src-inhibitor given up to six hours following stroke suppressed VP protecting wild-type mice from ischemia-induced brain damage without influencing VEGF expression. This was associated with reduced edema, improved cerebral perfusion and decreased infarct volume 24 hours after injury as measured by magnetic resonance imaging and histological analysis. Thus, Src represents a key intermediate and novel therapeutic target in the pathophysiology of cerebral ischemia where it appears to regulate neuronal damage by influencing VEGF-mediated VP.

Animals↗
PubMed2001

Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in the adult rat.

During development, neuropilin-1 is a receptor for semaphorin 3a-mediated axonal guidance and for vascular endothelial growth factor (VEGF) promotion of angiogenesis. The authors measured neuropilin-1 expression in the adult ischemic brain using Northern blot, in situ hybridization, and immunohistochemistry. Neuropilin-1 mRNA was significantly up-regulated as early as 2 hours and persisted at least 28 days after focal cerebral ischemia. Acute up-regulation of neuropilin-1 mRNA primarily localized to the ischemic neurons. A marked increase in both mRNA and protein of neuropilin-1 was detected in endothelial cells of cerebral blood vessels at the border and in the core of the ischemic lesion 7 days after ischemia, and neuropilin-1 gene expression persisted on these vessels for at least 28 days after ischemia. In these areas, neovascularization was detected using three-dimensional reconstructed images obtained from laser scanning confocal microscopy. Activated astrocytes also exhibited neuropilin-1 immunoreactivity during 7 to 28 days of ischemia. Double immunofluorescent staining showed colocalization of neuropilin-1 and VEGF to cerebral blood vessels and activated astrocytes. These data suggest that in addition to its role in axonal growth, up-regulation of neuropilin-1, in concert with VEGF and its receptors, may contribute to neovascular formation in the adult ischemic brain.

Animals↗
PubMed2001

Automated three-dimensional signature model for assessing brain injury in emergent stroke.

This presentation will focus on the value of established and newer MR methods that can be applied to the diagnosis and management of ischemic stroke with emphasis on future applications of MR to provide previously unmet needs of the treating clinician and clinical trials. Time alone is an inadequate indicator of the therapeutic window, especially when the time of stroke onset is uncertain. Thus, there is a need to predict the evolution of stroke in a way that more precisely and with greater resolution identifies the progression of cellular damage at the moment of investigation. This also would be of value for thrombolysis when knowledge of the degree and extent of tissue necrosis and the consequent potential for brain hemorrhage is of the utmost importance. To provide this, we perform postprocessing of diffusion-, T(1)- and T(2)-weighted images to produce the apparent diffusion coefficient of water, and T(1) and T(2) maps that are then further processed to provide maps and quantitation of the tissue signatures of ischemic histopathology. By these means, we can accomplish objective volumetric analysis of infarct size and of the proportions of potentially viable and salvageable tissue. We will show how this has the potential to predict long-term stroke outcome and facilitate decision-making in terms of safety of reperfusion strategies and the appropriateness of cytoprotective treatment. The value of our approach is to replace time as the therapeutic window and extend the opportunity of treatment to those patients presenting beyond the stringent time limits employed in current investigative clinical trials. Further, used as a surrogate marker of clinical outcome, this form of stroke analysis may speed proof of principle clinical trials in small numbers of stroke patients.

Brain↗