scholarly journals Influence of metabolic syndrome on post-stroke outcome, angiogenesis and vascular function in old rats determined by dynamic contrast enhanced MRI

2020 ◽  
pp. 0271678X2097641
Author(s):  
Jesús M Pradillo ◽  
Macarena Hernández-Jiménez ◽  
María E Fernández-Valle ◽  
Violeta Medina ◽  
Juan E Ortuño ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vascular Function ◽  
Infarct Volume ◽  
Stroke Recovery ◽  
Contrast Imaging ◽  
Dce Mri ◽  
Post Stroke ◽  
Non Invasive ◽  
Contrast Enhanced ◽  
Old Rats

Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes.

Pharmacokinetic (PK) and pharmacodynamic (PD) study of the effect of imatinib (Ima) on tumor (T) vascularity (V) and on gemcitabine (Ge) uptake (U) using non-invasive dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and spectroscopy (MRS)—Study BUS228

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12006-12006
Author(s):  
W. Wolf ◽  
C. A. Presant ◽  
V. Waluch ◽  
E. J. Chen
Keyword(s):  
Accumulation Rate ◽  
Phase 1 ◽  
Fluid Pressure ◽  
Post Contrast ◽  
Dce Mri ◽  
Chemotherapy Drugs ◽  
Non Invasive ◽  
Contrast Enhanced ◽  
Magnetic Resonance Imaging Mri ◽  
Moderate Nausea

12006 Background: Ima has been reported to increase T U of other chemotherapy drugs and to reduce interstitial fluid pressure (IFP) in experimental animals. Poplin et al performed a phase 1 analysis of Ima plus Ge in solid tumors (AACR 95:405, 2004). We tested ImaGe to determine the T PK and PD effects of Ima, Ge, and the ImaGe combination using DCE-MRI and MRS. Methods: Patients (pt) with measurable and MRI-imagible refractory solid T possibly responsive to Ge were randomized to receive either: one course of Ima with PK/PD, followed by one course of Ge with PK/PD, followed by the combination ImaGe; or one course of Ge with PK/PD followed by one course of Ima with PK/PD, followed by ImaGe. Ge was given at 900 mg/m2 IV over 30 min. for PK/PD and at 10 mg/m2/min. for continued therapy. Ima was given at 400 mg daily for 5 d. with Ge given on day 3. Doses were adjusted for toxicity. T V was measured by the use of DCE-MRI, as described previously (AACR 95:490,2004), where the initial contrast accumulation rate (ICAR) was calculated as the slope of the influx curve, and the delayed contrast accumulation rate (DCAR), measured between 2–20 min post contrast administration, as an approximation of IFP. Ge U was measured by serial 19F-MRS for ∼ 1hr post Ge administration. Results: To date 7 pts have been evaluated for the trial. Two pts have entered the trial and completed one cycle of therapy for PK/PD evaluation. Ima produced moderate nausea in both pts. Other toxicity was negligible. In the first pt Ima produced an 18% increase in the ICAR and a 72% increase in the DCAR but there was no significant change observed in the Ge uptake. In the second pt, Ima produced a 60% increase in the ICAR and a 21% increase in the DCAR. Neither of the 2 pts responded to treatment. Further pts are under study and their PK/PD results will be presented. Conclusions: PK and PD can be measured using DCE MRI together with MRS to determine the clinical affects of Ima, Ge, and the Ima-Ge combination. Current results indicate that Ima has a measurable effect on T V, but its relation to drug U and pt response require further pt evaluations to be definitive. [Table: see text]

scholarly journals The Asparaginyl Endopeptidase Legumain after Experimental Stroke

2010 ◽  
Vol 30 (10) ◽  
pp. 1756-1766 ◽  
Author(s):  
Taku Ishizaki ◽  
Agnes Erickson ◽  
Enida Kuric ◽  
Mehrdad Shamloo ◽  
Ikuko Hara-Nishimura ◽  
...  
Keyword(s):  
Immune Cell ◽  
Infarct Volume ◽  
Recovery Period ◽  
Gene Array ◽  
Stroke Recovery ◽  
Experimental Stroke ◽  
Post Stroke ◽  
Asparaginyl Endopeptidase ◽  
Infarct Area ◽  
Deficient Mice

Various proteases in the brain contribute to ischemic brain injury. We investigated the involvement of the asparaginyl endopeptidase legumain after experimental stroke. On the basis of gene array studies and in situ hybridizations, we observed an increase of legumain expression in the peri-infarct area of rats after transient occlusion of the middle cerebral artery (MCAO) for 120 mins with a maximum expression at 24 and 48 h. Immunohistochemical analyses revealed the expression of legumain in Iba1+ microglial cells and glial fibrillary acidic protein-positive astrocytes of the peri-infarct area in mice after MCAO. Post-stroke recovery was also studied in aged legumain-deficient mice (45 to 58 weeks old). Legumain-deficient mice did not show any differences in physiologic parameters compared with respective littermates before, during MCAO (45 mins), and the subsequent recovery period of 8 days. Moreover, legumain deficiency had no effect on mortality, infarct volume, and the neurologic deficit determined by the rotating pole test, a standardized grip strength test, and the pole test. However, a reduced number of invading CD74+ cells in the ischemic hemisphere indicates an involvement in post-stroke inflammation. We conclude that legumain is not essential for the functional deficit after MCAO but may be involved in mechanisms of immune cell invasion.

scholarly journals Vascular Sema3E-Plexin-D1 Signaling Reactivation Promotes Post-stroke Recovery through VEGF Downregulation in Mice

2021 ◽  
Author(s):  
Ri Yu ◽  
Nam-Suk Kim ◽  
Yan Li ◽  
Jin-Young Jeong ◽  
Sang-Joon Park ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Knockout Mice ◽  
Vascular Remodeling ◽  
Infarct Volume ◽  
Brain Infarction ◽  
Adult Brain ◽  
Stroke Recovery ◽  
Neurological Deficits ◽  
Post Stroke ◽  
Vegf Signaling

AbstractPost-stroke vascular remodeling, including angiogenesis, facilitates functional recovery. Proper vascular repair is important for efficient post-stroke recovery; however, the underlying mechanisms coordinating the diverse signaling pathways involved in vascular remodeling remain largely unknown. Recently, axon guidance molecules were revealed as key players in injured vessel remodeling. One such molecule, Semaphorin 3E (Sema3E), and its receptor, Plexin-D1, control vascular development by regulating vascular endothelial growth factor (VEGF) signaling. In this study, using a mouse model of transient brain infarction, we aimed to investigate whether Sema3E-Plexin-D1 signaling was involved in cerebrovascular remodeling after ischemic injury. We found that ischemic damage rapidly induced Sema3e expression in the neurons of peri-infarct regions, followed by Plexin-D1 upregulation in remodeling vessels. Interestingly, Plexin-D1 reemergence was concurrent with brain vessels entering an active angiogenic process. In line with this, Plxnd1 ablation worsened neurological deficits, infarct volume, neuronal survival rate, and blood flow recovery. Furthermore, reduced and abnormal vascular morphogenesis was caused by aberrantly increased VEGF signaling. In Plxnd1 knockout mice, we observed significant extravasation of intravenously administered tracers in the brain parenchyma, junctional protein downregulation, and mislocalization in regenerating vessels. This suggested that the absence of Sema3E-Plexin-D1 signaling is associated with blood–brain barrier (BBB) impairment. Finally, the abnormal behavioral performance, aberrant vascular phenotype, and BBB breakdown defects in Plxnd1 knockout mice were restored following the inhibition of VEGF signaling during vascular remodeling. These findings demonstrate that Sema3E-Plexin-D1 signaling can promote functional recovery by downregulating VEGF signaling in the injured adult brain.

Prognostic Significance Of Parameters Of Dynamic Contrast-Enhanced MRI Detecting Increased Bone Marrow Microcirculation In Monoclonal Plasma Cell Disorders

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3146-3146
Author(s):  
Jens Hillengass ◽  
Judith Ritsch ◽  
Maximilian Merz ◽  
Hartmut Goldschmidt ◽  
Christina Kunz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Exchange Rate ◽  
Rate Constant ◽  
Prognostic Significance ◽  
Lumbar Vertebrae ◽  
Dce Mri ◽  
Non Invasive ◽  
Contrast Enhanced ◽  
Plasma Cell Disorders ◽  
Exchange Rate Constant

Abstract Introduction Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging technique allowing the detection of changes in local microcirculation reflecting increased angiogenesis. DCE-MRI parameters Amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) are increased in bone marrow exams of patients with active multiple myeloma (MM) compared to healthy controls. In the current prospective study we analyzed the prognostic significance of the DCE-MRI parameters in 289 patients with monoclonal plasma cell disorders and 33 healthy controls. Methods The patient group consisted of 68 individuals with monoclonal gammopathy of undetermined significance (MGUS), 90 patients with smoldering MM (sMM) and 131 patients with symptomatic MM according to IMWG criteria. All patients and controls underwent standardized DCE-MRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine (symptomatic patients before start of therapy). Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Values of the DCE-MRI parameters of the 5 lumbar vertebrae were summarized per patient in median values. Log transformation was used for median kep values. Results Significant differences in Amplitude A were found between sMM and controls (P=0.004), sMM and MGUS (P=0.01), and MM and all other groups (P<0.001 respectively). For exchange rate constant kep differences were significant between sMM and controls (P=0.01), sMM and MGUS (P=0.01) and MM and all other groups (P<0.001 respectively). P-values were adjusted for multiple testing by Holm's method. Comparison of DCE-MRI- and clinical parameters revealed a significant positive correlation of Amplitude A with beta2-microglobulin (P<0.001), high risk cytogenetics (P=0.009), immunoparesis (P<0.001) and a negative correlation with albumin, hemoglobin and age (P<0.001, respectively). For exchange rate constant kep the following significant correlation were found: positive correlation with beta2-microglobulin (P<0.001), LDH (P=0.03), immunoparesis (P<0.001) and negative correlation with albumin (P=0.03), hemoglobin (P<0.001) and age (P=0.03). Application of univariate and multivariate Cox models revealed a significant prognostic impact for median of DCE-MRI parameter Amplitude A for progression free survival of patients with MGUS (univariate P=0.02), sMM (univariate P=0.002; multivariate P=0.03) and for overall survival of MM patients (multivariate P=0.05). Log transformed arameter kep showed prognostic significance for PFS of MM patients (univariate P=0.04). The multivariate Cox model was adjusted for the following additional factors: plasma cells in bone marrow, M-Protein, IgG-subtype, presence of immunoparesis and age. M-protein (P=0.004), age (P=0.03) and a non-IgG-type (P=0.006) also were revealed as significant prognostic factors. Conclusion DCE-MRI is a non-invasive imaging tool delivering parameters on bone marrow microcirculation which are correlated to clinical markers of disease activity as well stage of disease. In all groups of patients especially DCE-MRI parameter Amplitude A is of significant prognostic value for progression free and in symptomatic patients also for overall survival. Disclosures: No relevant conflicts of interest to declare.

Abstract TP113: Delayed (21 Days) Post Stroke Treatment With RPh201, A Botany-Derived Compound, Improves Neurological Functional Recovery in a Rat Model of Embolic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Chunyang Wang ◽  
Michael Chopp ◽  
Rui Huang ◽  
Yi Zhang ◽  
William Golembieski ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Infarct Volume ◽  
Experimental Models ◽  
Stroke Recovery ◽  
Female Rats ◽  
Male Rats ◽  
Acute Stroke Care ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Male And Female Rats

Introduction: Despite the recent advances in the acute stroke care, treatment options for long-term disability are limited. RPh201 is a botany-derived bioactive compound that has been shown to exert beneficial effects in various experimental models of neural injury. However, the effect of RPh201 on stroke recovery has not been investigated. The present study evaluated the effect of RPh201 on functional recovery after stroke. Methods: Young adult Wistar rats subjected to embolic middle cerebral artery occlusion (MCAO) were randomized into the following experimental groups stratified by sex (n=20/group): 1) RPh201 treatment, and 2) vehicle (cottonseed oil). RPh201 (20 μl) or vehicle were subcutaneously administered twice a week for 16 consecutive weeks starting at 21 days after MCAO. An array of behavioral tests were performed during 120 days after treatment initiation. Results: Male, but not female, ischemic rats treated with RPh201 exhibited significant (p<0.05) improvement of neurological function measured by adhesive removal test, foot-fault test, and modified neurological severity score at 90 and 120 days after initiation of treatment. Immunohistochemistry analysis showed that RPh201 treatment robustly increased neurofilament heavy chain positive axons and myelin basic protein densities in the peri-infarct area by 61% and 31% in the male rats, respectively, when compared to the vehicle treatment, which were further confirmed by Western blot analysis. The RPh201 treatment did not reduce infarct volume in both male and female rats. Conclusions: Our data demonstrated that RPh201 has a therapeutic effect on improvement of functional recovery in male ischemic rats even when the treatment was initiated 21 days post stroke. Enhanced axonal and myelination densities by RPh201 in ischemic brain may contribute to improved stroke recovery.

scholarly journals Radiomics for Tumor Characterization in Breast Cancer Patients: A Feasibility Study Comparing Contrast-Enhanced Mammography and Magnetic Resonance Imaging

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 492
Author(s):  
Maria Adele Marino ◽  
Doris Leithner ◽  
Janice Sung ◽  
Daly Avendano ◽  
Elizabeth A. Morris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Resonance Imaging ◽  
Tumor Grade ◽  
Hormone Receptor Status ◽  
Breast Cancers ◽  
Resonance Imaging ◽  
Dce Mri ◽  
Tumor Invasiveness ◽  
Non Invasive ◽  
Contrast Enhanced

The aim of our intra-individual comparison study was to investigate and compare the potential of radiomics analysis of contrast-enhanced mammography (CEM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast for the non-invasive assessment of tumor invasiveness, hormone receptor status, and tumor grade in patients with primary breast cancer. This retrospective study included 48 female patients with 49 biopsy-proven breast cancers who underwent pretreatment breast CEM and MRI. Radiomics analysis was performed by using MaZda software. Radiomics parameters were correlated with tumor histology (invasive vs. non-invasive), hormonal status (HR+ vs. HR−), and grading (low grade G1 + G2 vs. high grade G3). CEM radiomics analysis yielded classification accuracies of up to 92% for invasive vs. non-invasive breast cancers, 95.6% for HR+ vs. HR− breast cancers, and 77.8% for G1 + G2 vs. G3 invasive cancers. MRI radiomics analysis yielded classification accuracies of up to 90% for invasive vs. non-invasive breast cancers, 82.6% for HR+ vs. HR− breast cancers, and 77.8% for G1+G2 vs. G3 cancers. Preliminary results indicate a potential of both radiomics analysis of DCE-MRI and CEM for non-invasive assessment of tumor-invasiveness, hormone receptor status, and tumor grade. CEM may serve as an alternative to MRI if MRI is not available or contraindicated.

scholarly journals Early Progressive Changes in White Matter Integrity Are Associated with Stroke Recovery

2020 ◽  
Vol 11 (6) ◽  
pp. 1264-1272 ◽  
Author(s):  
Daniela Pinter ◽  
Thomas Gattringer ◽  
Simon Fandler-Höfler ◽  
Markus Kneihsl ◽  
Sebastian Eppinger ◽  
...  
Keyword(s):  
White Matter ◽  
Corpus Callosum ◽  
Infarct Volume ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Acute Stage ◽  
Stroke Recovery ◽  
White Matter Integrity ◽  
Post Stroke ◽  
Acute Infarction

Abstract Information on microstructural white matter integrity has been shown to explain post-stroke recovery beyond clinical measures and focal brain damage. Especially, knowledge about early white matter changes might improve prediction of outcome. We investigated 42 acute reperfused ischemic stroke patients (mean age 66.5 years, 40% female, median admission NIHSS 9.5) with a symptomatic MRI-confirmed unilateral middle cerebral artery territory infarction 24–72 h post-stroke and after 3 months. All patients underwent neurological examination and brain MRI. Fifteen older healthy controls (mean age 57.3 years) were also scanned twice. We assessed fractional anisotropy (FA), mean diffusivity (MD), axial (AD), and radial diffusivity (RD). Patients showed significantly decreased white matter integrity in the hemisphere affected by the acute infarction 24–72 h post-stroke, which further decreased over 3 months compared with controls. Less decrease in FA of remote white matter tracts was associated with better stroke recovery even after correcting for infarct location and extent. A regression model including baseline information showed that the modified Rankin Scale and mean FA of the genu of the corpus callosum explained 53.5% of the variance of stroke recovery, without contribution of infarct volume. Furthermore, early dynamic FA changes of the corpus callosum within the first 3 months post-stroke independently predicted stroke recovery. Information from advanced MRI measures on white matter integrity at the acute stage, as well as early dynamic white matter degeneration beyond infarct location and extent, improve our understanding of post-stroke reorganization in the affected hemisphere and contribute to an improved prediction of recovery.

Abstract T P223: Post-stroke Body Weight Loss Predicts Acute Stroke Outcome In Mice

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jiwon Yang ◽  
Sunghee Cho
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Brain Injury ◽  
Infarct Volume ◽  
Body Weight Loss ◽  
Stroke Recovery ◽  
Physiological Parameter ◽  
Ischemic Time ◽  
Post Stroke ◽  
Longitudinal Imaging

Background and Purpose: Longitudinal imaging studies in stroke demonstrated that infarct development is a dynamic process and it matures over several days, even weeks depending on the severity of stroke. However, due to high cost and multiple exposure of anesthesia associated with repeated imaging, infarct volume has been typically measured at a fixed time point in preclinical studies, which prevent further assessment of behaviors during stroke recovery. In identifying a non-invasive physiological parameter that predicts the extent of stroke-induced brain injury, the study investigated whether acute body weight loss predicts the extent of brain injury and swelling. Methods: C57 male mice (10-12 wk old, 25-30 gr) were subjected to the proximal middle cerebral artery (MCA) occlusion for 30 min. Body weight was recorded daily. Infarct volume corrected with swelling (IVInd) and percent hemispheric swelling (%SW) were determined at 1, 3 and 7d after MCAO. In a retrospective study, we analyzed correlations between 3d %body weight reduction (%BWred) and stroke outcomes (IVInd & %SW) in C57 male animals that were subjected to MCAO by 3 different individuals over 8 years (n=91-96). Results: Stroke induced acute BW loss (%BWred; 1d, 88.9±3.3; 3d, 84.5±8.6; 5d, 86.8±10.6; 7d, 88.9±8.9). Correlation analyses in the post-ischemic time points showed IVind and %SW were significantly correlated with only at 3d BW reduction, but not 1d and 7d (Fig.1). A retrospective analysis in C57 mice also showed a significant correlation between 3d %BWred and IVInd & %SW (Fig.2). Conclusions: The study showed that acute post-stroke BWred is a simple and suitable index to predict the extent of stroke injury in C57 mice. Whether the prediction can be generalized across different strains and in comorbid conditions warrant further investigation.

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