Ischemic Area Research Articles

The diagnostic value of quantitative parameters on dual-layer detector-based spectral CT in identifying ischaemic stroke.

To investigate the diagnostic value of quantitative parameters of spectral computed tomography (CT) in ischaemic stroke areas. The medical records of 57 patients with acute ischaemic stroke (AIS) who underwent plain computed tomography (CT) head scans, CT angiography (CTA), and CT perfusion (CTP) were retrospectively reviewed. The ischaemic areas (including the core infarct area and penumbra) and non-ischaemic areas in each patient were quantitatively analyzed using F-STROKE software. Two independent readers measured the corresponding values of the spectroscopic quantitative parameters (effective atomic number [Zeff value], iodine density value, and iodine-no-water value) in the ischaemic area and contralateral normal area alone. The differences in spectroscopic quantitative parameters between the two groups were compared, and their diagnostic efficacy was obtained. The Zeff, iodine-no-water value, and iodine density value of the ischaemic area all showed significant lower than those of non-ischaemic tissue (P < 0.001). For differentiating the ischaemic area from non-ischaemic tissue, the area under the curve (AUC) of the Zeff value reached 0.869 (cut-off value: 7.385; sensitivity: 93.0%; specificity: 70.2%), the AUC of the iodine density value reached 0.932 (cut-off value: 0.235; sensitivity: 91.2%; specificity: 82.5%), and the AUC of the iodine-no-water value reached 0.922 (cut-off value: 0.205; sensitivity: 96.5%; specificity: 78.9%). The study showed the spectral CT would be a potential novel rapid method for identifying AIS. The spectral CT quantitative parameters (Zeff, iodine density values, and iodine-no-water values) can effectively differentiate the ischaemic area from non-ischaemic tissue in stroke patients.

Role of Microaneurysms in the Pathogenesis and Therapy of Diabetic Macular Edema: A Descriptive Review

Background and Objectives: This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. Materials and Methods: We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. Results: MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. Conclusions: MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.

Engineered extracellular vesicles for ischemic stroke treatment

Engineered extracellular vesicles for ischemic stroke treatment

Rod‐Shaped Polymeric Nanoparticles Intervene Neutrophils for Efficient Ischemic Stroke Therapy

AbstractNeutrophils are associated with pro‐inflammation and contribute to pathophysiology of ischemic stroke. Prevention of neutrophils from infiltrating into ischemic area can be a potential approach for stroke therapy. In this study, a rod‐shaped polylactic acid polyglycolic acid (PLGA) nanoparticles encapsulated with piceatannol is developed to target and intervene the interaction of neutrophils with inflamed endothelial cells. In contrast to macrophages, neutrophils exhibit enhanced endocytosis of elongated particles. The nanoparticles with aspect ratio (AR) of 5 display higher internalization by neutrophils compared to other nanoparticles. Thus, AR5 nanoparticles are screened out to load with piceatannol (Pic@AR5) for investigating the therapeutic effect against middle cerebral artery occlusion model. It is demonstrated that Pic@AR5 can block the adherence of neutrophils to endothelial cells, inhibiting the infiltration of neutrophils into blood‐brain barrier (BBB). Besides, the inflammatory cytokine of ischemic brain can also be reduced even if a small part of Pic@AR5‐carried neutrophils enter BBB. The nanoparticles release piceatannol within the ischemic region, which inhibit microglial Syk signal and result in alleviation of neuroinflammation. This strategy provides new insights into ischemic stroke therapy.

TRPV4 channels promote vascular permeability in retinal vascular disease

This study aimed to determine the role of transient receptor potential vanilloid 4 (TRPV4), a calcium (Ca2+)-permeable cation channel, in the pathophysiology of retinal vascular disease. The retinal vein occlusion (RVO) murine model was created by irradiating retinal veins using lasers. TRPV4 expression and localization were evaluated in RVO mice retinas. In addition, we examined the effects of TRPV4 antagonists (RQ-00317310, HC-067047, GSK2193874, and GSK2798745) on retinal edema, blood flow, and ischemic areas in RVO mice. Furthermore, changes in the retinal expression of tumor necrosis factor (TNF)-α and aquaporin4 (AQP4) by RQ-00317310 were analyzed using Western blot. We also assessed the barrier integrity of epithelial cell monolayers using trans-endothelial electrical resistance (TEER) in Human Retinal Microvascular Endothelial Cells (HRMECs). The expression of TRPV4 was significantly increased and co-localized with glutamine synthetase (GS), a Müller glial marker, in the ganglion cell layer (GCL) of the RVO mice. Moreover, RQ-00317310 administration ameliorated the development of retinal edema and ischemia in RVO mice. In addition, the up regulation of TNF-α and down-regulation of AQP4 were lessened by the treatment with RQ-00317310. Treatment with GSK1016790A, a TRPV4 agonist, increased vascular permeability, while RQ-00317310 treatment decreased vascular endothelial growth factor (VEGF)- or TRPV4-induced retinal vascular hyperpermeability in HRMECs. These findings suggest that TRPV4 plays a role in the development of retinal edema and ischemia. Thus, TRPV4 could be a new therapeutic target against the pathological symptoms of retinal vascular diseases.

Friends or foes: The mononuclear phagocyte system in ischemic stroke.

Ischemic stroke (IS) is a major cause of disability and death in adults, and the immune response plays an indispensable role in its pathological process. After the onset of IS, an inflammatory storm, with the infiltration and mobilization of the mononuclear phagocyte system (MPS), is triggered in the brain. Microglia are rapidly activated in situ, followed by waves of circulating monocytes into the ischemic area. Activated microglia and monocytes/macrophages are mainly distributed in the peri-infarct area. These cells have similar morphology and functions, such as secreting cytokines and phagocytosis. Previously, the presence of the MPS was considered a marker of an exacerbated inflammatory response that contributes to brain damage. However, recent studies have suggested a rather complicated role of the MPS in IS. Here, we reviewed articles focusing on various functions of the MPS among different phases of IS, including recruitment, polarization, phagocytosis, angiogenesis, and interaction with other types of cells. Moreover, due to the characteristics of the MPS, we also noted clinical research addressing alterations in the MPS as potential biomarkers for IS patients for the purposes of predicting prognosis and developing novel therapeutic strategies.

Bilateral Branch Retinal Vein Occlusion after mRNA-SARS-CoV-2 Booster Dose Vaccination

We report a case of a patient with a bilateral branch retinal vein occlusion (BRVO) 24 h after a booster vaccination with the mRNA-1237 vaccine. Fluorescein angiography, performed at three weeks follow-up, showed vascular leakage and blockage, corresponding to hemorrhage areas associated with ischemic areas in the macula and along the arcades involved in the occlusion. The patient was scheduled for urgent injections of intravitreal ranibizumab and laser photocoagulation of the ischemic areas. To the best of our knowledge, this is the first case described of concomitant bilateral RVO after COVID-19 vaccination. The rapid onset of the side effects in a patient with multiple risk factors for thrombotic events suggests that vulnerable microvascular conditions require detailed investigations before administration of a COVID-19 vaccine.

Clinical-Therapeutic Orientation in Retinal Venous Obstruction

Retinal vein occlusion (RVO) is a retinal vascular disease that can affect the central retinal vein in central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO), which causes decreased vision (the second leading cause of blindness after diabetic retinopathy). CRVO is accompanied by retinomacular edema and retinal / peripapillary / iris neovascularization that cause serious complications: absolute neovascular secondary glaucoma, vitreous hemorrhage, retinal traction detachment, possibly present in both forms of CRVO. Branch retinal vein occlusion (BRVO) is often asymptomatic and can be diagnosed accidentally or by retinal control, and is 5 times more common than CRVO. CRVO prophylaxis is done by identifying and appropriate treatment of risk factors (multiple): hypertension, diabetes, smoking, obesity, Primary Open Angle Glaucoma (POAG), hypercoagulability. RVO treatment, the non-ischemic form, requires the treatment of macular edema with: intravitreal AntiVEGF - Ranibizumab, Aflibercept, Bevacizumab, repeatedly, cortisone therapy with intravitreal Triamcinolone or Dexamethasone implant, focal / grid laser photocoagulation and / or panretinal photocoagulation. In all cases of RVO, the non-ischemic form, the following are required: clinical surveillance, fluorescein angiography (FA), OCT for immediate detection of progression to the ischemic form. The treatment of RVO, ischemic form, is the treatment of macular edema with repeated intravitreal antiVEGF treatment, corticosteroids, focal laser photocoagulation, grid, pan-photocoagulation indicated in the treatment of exudative ischemic areas with neovessels proliferation. Panretinal photocoagulation (PRP) is an effective treatment for iris peripapillary retinal neovascularization and secondary complications. The current prognosis of RVO is improved by regular examination of OCT-SD, antiVEGF medication, intravitreal cortisone and laser photocoagulation that provide prophylactic and curative treatment of RVO and complications: vitreous hemorrhage, neovascular glaucoma, retinal traction detachment.

Blocking of PI3-kinase beta protects against cerebral ischemia/reperfusion injury by reducing platelet activation and downstream microvascular thrombosis in rats

Phosphoinositide 3-kinase beta (PI3Kβ) plays an important role in platelet activation and thrombosis, but its role in stroke pathology remains unknown. In this study, we investigated whether inhibition of PI3Kβ protects against cerebral ischemia/reperfusion (I/R) injury by preventing circulating platelet activation and downstream microvascular thrombosis. We used a rat intraluminal filament model of transient middle cerebral artery occlusion (tMCAO) because the rapid restoration of cerebral blood flow to the ischemic area in both tMCAO and endovascular thrombectomy provides clinical relevance for this model. The results showed that TGX221, a selective PI3Kβ inhibitor, treatment immediately before the onset of reperfusion dose-dependently reduced infarct volume and improved neurological function. The protective effects were associated with blocking platelet activation and thrombotic response, thereby reducing downstream microvascular thrombosis, and maintaining reperfusion efficiency. These results suggest that PI3Kβ might be a promising target for treating downstream microvascular thrombosis induced by cerebral I/R injury and offer a novel adjunctive treatment to improve reperfusion therapy for acute ischemic stroke.

Longitudinal Quantitative Ultrawide-field Fluorescein Angiography Dynamics in the RUBY Diabetic Macular Edema Study

The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics. This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb). Subjects with DME that underwent UWFA across all treatment groups (n= 44). A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery. Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated. Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT. Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point. Proprietary or commercial disclosure may be found after the references.

DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps.

Neutrophil extracellular traps (NETs) play an important role in ischemia-reperfusion injury (IRI) of the hindlimb. The aim of this study was to investigate the effect of recombinant DNase I and sivelestat in eliminating NETs and their effects on IRI limbs. An air pump was used to apply a pressure of 300 mmHg to the root of the right hindlimb of the rat for 2 h and then deflated to replicate the IRI model. The formation of NETs was determined by the detection of myeloperoxidase (MPO), neutrophil elastase (NE), and histone H3 in the skeletal muscles of the hindlimbs. Animals were administered 2.5 mg/kg bw/d DNase I, 15 or 60 mg/kg bw/d sivelestat by injection into the tail vein or intramuscularly into the ischemic area for 7d. Elimination of NETs, hindlimb perfusion, muscle fibrosis, angiogenesis and motor function were assessed. DNase I reduced NETs, attenuated muscle fibrosis, promoted angiogenesis in IRI area and improved limb motor function. Local administration of DNase I improved hindlimb perfusion more than intravenous administration. Sivelestat at a dose of 15 mg/kg bw/d increased perfusion, counteracted skeletal muscle fibrosis, promoted angiogenesis and enhanced motor function. However, sivelestat at a dosage of 60 mg/kg bw/d had an adverse effect on tissue repair, especially when injected locally. Both DNase I and moderate doses of sivelestat can eliminate IRI-derived NETs. They improve hindlimb function by improving perfusion and angiogenesis, preventing muscle fibrosis. Appropriate administration mode and dosage is the key to prevent IRI by elimination of NETs. DNase I is more valid when administered topically and sivelestat is more effective when administered intravenously. These results will provide a better strategy for the treatment of IRI in clinical.

Injectable Supramolecular Hybrid Hydrogel Delivers IL-1β-Stimulated Exosomes to Target Neuroinflammation

Long-term neuroinflammation is a major barrier to neurological recovery after cerebral ischemia-reperfusion injury (CIRI). Here, a thermosensitive injectable supramolecular hybrid hydrogel is developed to sustainably deliver exosomes derived from interleukin-1β-stimulated bone marrow stromal cells (BMSCs) (βExos) with improved exosome production and anti-inflammatory capacity for neuroinflammation inhibition and neurological recovery. The supramolecular hydrogel displays self-healing and injectable features, along with high biocompatibility and tissue-like softness. The βExos effectively reduce the lipopolysaccharide-induced inflammatory responses in the immortalized mouse microglia (BV2) cell line, and the in situ formed hydrogel improves the exosome retention in the ischemic core area. More remarkably, in the middle cerebral artery occlusion in vivo model, glial scar formation and neuronal loss are significantly reduced by regulating neuroinflammation using the released βExos. Therefore, the combination of interleukin-1β-stimulated exosomes with injectable supramolecular hydrogel provides an appealing strategy for treating central nervous system diseases.

Predicting a Favorable (mRS 0–2) or Unfavorable (mRS 3–6) Stroke Outcome by Arterial Spin Labeling and Amide Proton Transfer Imaging in Post-Thrombolysis Stroke Patients

(1) Background: The objective of this study was to determine whether arterial spin labeling (ASL), amide proton transfer (APT), or their combination could distinguish between patients with a low and high modified Rankin Scale (mRS) and forecast the effectiveness of the therapy; (2) Methods: Fifty-eight patients with subacute phase ischemic stroke were included in this study. Based on cerebral blood flow (CBF) and asymmetry magnetic transfer ratio (MTRasym) images, histogram analysis was performed on the ischemic area to acquire imaging biomarkers, and the contralateral area was used as a control. Imaging biomarkers were compared between the low (mRS 0-2) and high (mRS 3-6) mRS score groups using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the potential biomarkers in differentiating between the two groups; (3) Results: The rAPT 50th had an area under the ROC curve (AUC) of 0.728, with a sensitivity of 91.67% and a specificity of 61.76% for differentiating between patients with low and high mRS scores. Moreover, the AUC, sensitivity, and specificity of the rASL max were 0.926, 100%, and 82.4%, respectively. Combining the parameters with logistic regression could further improve the performance in predicting prognosis, leading to an AUC of 0.968, a sensitivity of 100%, and a specificity of 91.2%; (4) Conclusions: The combination of APT and ASL may be a potential imaging biomarker to reflect the effectiveness of thrombolytic therapy for stroke patients, assisting in guiding treatment approaches and identifying high-risk patients such as those with severe disability, paralysis, and cognitive impairment.

Effect of erythropoietin on inflammatory response and ischemic brain damage after carotid artery clamp in rat

Introduction: Erythropoietin (EPO) is reported to have a minimizing effect on the ischemic condition, but the detailed association between EPO and the ischemic upshot is still not clearly understood. We aimed to evaluate the effect of EPO on inflammatory response and ischemic brain damage after carotid artery clamp in rats. Methods: In this experimental, animal trial study, which was conducted at the Animal Facility and laboratory at Tabriz University of Medical Sciences, 50 adult male Wistar rats with (250 to 300 g) were randomly allocated to intervention and control groups. The intervention and control groups were administered intraperitoneally with equal volumes of EPO (5000 U/kg) and normal saline, respectively. Both groups had common carotid arteries clamped for 20 minutes. Using the Nissl staining technique, the slides of brain ischemic areas were observed and the rate of ischemic injury in both groups was determined. The blood level of inflammatory cytokines was also measured. Results: The levels of inflammatory markers including creatine phosphokinase (CPK), interleukin (IL)-6, IL-1B and tumor necrosis factor alpha (TNF)-α in the intervention group were significantly lower than that of control group. Mean percentage of the ischemic area in the intervention group with an amount of 4.30±2.15%, was significantly lower than that of control group (11.20±2.35%, P=0.023). Conclusion: Findings of this study showed that the injection of EPO before carotid clamping is effective in preventing cerebral ischemic injury in rats.

Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke

BackgroundMesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke.MethodsWistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups.ResultsSB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05).ConclusionsThis study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.

Preferential delivery of lipid-ligand conjugated DNA/RNA heteroduplex oligonucleotide to ischemic brain in hyperacute stage

Antisense oligonucleotide (ASO) is a major tool used for silencing pathogenic genes. For stroke in the hyperacute stage, however, the ability of ASO to regulate genes is limited by its poor delivery to the ischemic brain owing to sudden occlusion of the supplying artery. Here we show that, in a mouse model of permanent ischemic stroke, lipid-ligand conjugated DNA/RNA heteroduplex oligonucleotide (lipid-HDO) was unexpectedly delivered 9.6 times more efficiently to the ischemic area of the brain than to the contralateral non-ischemic brain and achieved robust gene knockdown and change of stroke phenotype, despite a 90% decrease in cerebral blood flow in the 3h after occlusion. This delivery to neurons was mediated via receptor-mediated transcytosis by lipoprotein receptors in brain endothelial cells, the expression of which was significantly upregulated after ischemia. This study provides proof-of-concept that lipid-HDO is a promising gene-silencing technology for stroke treatment in the hyperacute stage.

Novel 2,6-disubstituted benzofuran-3-one analogues improve cerebral ischemia/reperfusion injury via neuroprotective and antioxidative effects

There are no highly effective and safe medicines for clinical treatment of ischemic stroke, although the natural product 3-n-butylphthalide (NBP) has been approved in China for mild and moderate ischemic stroke. To discover more potent anti-cerebral ischemic agents and overcome the low stability by phthalide derivatives, benzofuran-3-one was selected as a core moiety and two types of nitric oxide (NO)-donating groups were incorporated into the structure. In this work, a series of 2,6-disubstituted benzofuran-3-one derivatives were designed and synthesised as NBP analogues, and tested as neuroprotective and antioxidative agents. Compounds 5 (without an NO donor) and 16 (with an NO donor) displayed more potent neuroprotective effects than the established clinical drugs Edaravone and NBP. More importantly, 5 and 16 also exhibited good antioxidative activity without cytotoxicity in rat primary neuronal and PC12 cells. Most active compounds showed good blood–brain barrier permeability in a parallel artificial membrane permeability assay. Furthermore, compound 5 reduced the ischemic infarct area significantly in rats subjected to ischemia/reperfusion injury, downregulated ionised calcium-binding adaptor molecule 1 and glial fibrillary acidic protein in inflammatory cells, and upregulated nerve growth factor.

Effect of Temporal Sampling Rate on Estimates of the Perfusion Parameters for Patients with Moyamoya Disease Assessed with Simultaneous Multislice Dynamic Susceptibility Contrast-enhanced MR Imaging.

The effect of temporal sampling rate (TSR) on perfusion parameters has not been fully investigated in Moyamoya disease (MMD); therefore, this study evaluated the influence of different TSRs on perfusion parameters quantitatively and qualitatively by applying simultaneous multi-slice (SMS) dynamic susceptibility contrast-enhanced MR imaging (DSC-MRI). DSC-MRI datasets were acquired from 28 patients with MMD with a TSR of 0.5 s. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and time to maximum tissue residue function (Tmax) were calculated for eight TSRs ranging from 0.5 to 4.0 s in 0.5-s increments that were subsampled from a TSR of 0.5 s datasets. Perfusion measurements and volume for chronic ischemic (Tmax ≥ 2 s) and non-ischemic (Tmax < 2 s) areas for each TSR were compared to measurements with a TSR of 0.5 s, as was visual perfusion map analysis. CBF, CBV, and Tmax values tended to be underestimated, whereas MTT and TTP values were less influenced, with a longer TSR. Although Tmax values were overestimated in the TSR of 1.0 s in non-ischemic areas, differences in perfusion measurements between the TSRs of 0.5 and 1.0 s were generally minimal. The volumes of the chronic ischemic areas with a TSR ≥ 3.0 s were significantly underestimated. In CBF and CBV maps, no significant deterioration was noted in image quality up to 3.0 and 2.5 s, respectively. The image quality of MTT, TTP, and Tmax maps for the TSR of 1.0 s was similar to that for the TSR of 0.5 s but was significantly deteriorated for the TSRs of ≥ 1.5 s. In the assessment of MMD by SMS DSC-MRI, application of TSRs of ≥ 1.5 s may lead to deterioration of the perfusion measurements; however, that was less influenced in TSRs of ≤ 1.0 s.

PS-B03-4: A NOVEL SOLUBLE EPOXIDE HYDROLASE VACCINE PROTECTS MURINE CARDIAC MUSCLE AGAINST MYOCARDIAL INFARCTION

Objective: Myocardial infarction is still a life-threatening disease, even though its prognosis has been improved through the development of percutaneous coronary intervention and pharmacotherapy. In addition, heart failure due to remodeling after myocardial infarction requires lifelong management. The aim of this study was to develop a novel treatment suppressing the myocardial damage done by myocardial infarction. Design and method: We focused on inhibition of soluble epoxide hydrolase to prolong the activation of epoxyeicosatrienoic acids (EETs), which have vasodilatory and anti-inflammatory properties. The several amino acid sequence of Soluble Epoxide Hydrolase (sEH) protein was designed as peptide vaccine. The 40 rats were injected the vaccine subcutaneously and the other 30 rats were injected the saline solution and adjuvant four times in every two weeks. The left anterior descending artery was ligated in both groups as myocardial infarction model, and those hearts were evaluated by cardiac echography and cardiac tissue were examined histologically on day7 after the surgery. Results: In the vaccine group, the ischemic area was significantly reduced, and systolic cardiac function was significantly preserved. Vaccine treatment clearly increased microvessels in the border area and suppressed fibrosis in the cardiac tissue secondary to myocardial infarction. Furthermore, VEGF and eNOS expression were upregulated in the cardiac tissue of the vaccine group, suggesting induced EETs caused neovascularization through modifying protein expression. Conclusions: We successfully made a new vaccine to inactivate soluble epoxide hydrolase, and we have evaluated the effect of the vaccine in a rat myocardial infarction model. The soluble epoxide hydrolase vaccine is a novel treatment for improving cardiac function following myocardial infarction.

Comparison of Diabetic Retinopathy Lesions Identified Using Ultrawide Field Imaging and Optical Coherence Tomography Angiography

Introduction: Optical coherence tomography (OCT) angiography (OCTA) has the potential to influence the diagnosis and management of diabetic eye disease. This study aims to determine the correlation between diabetic retinopathy (DR) findings on ultrawide field (UWF) color photography (UWF-CP), UWF fluorescein angiography (UWF-FA), and OCTA. Methods: This is a cross-sectional, prospective study. One hundred and fourteen eyes from 57 patients with diabetes underwent mydriatic UWF-CP, UWF-FA, and OCTA. DR severity was assessed. Ischemic areas were identified on UWF-FA using ImageJ and the nonperfusion index (NPI) was calculated. Diabetic macular edema (DME) was assessed using OCT. Superficial capillary plexus vessel density (VD), vessel perfusion (VP), and foveal avascular zone (FAZ) area were automatically measured on OCTA. Pearson correlation coefficient between the imaging modalities was determined. Results: Forty-five eyes were excluded due to non-DR findings or prior laser photocoagulation; 69 eyes were analyzed. DR severity was associated with larger NPI (r = 0.55944, p < 0.0001) even after distinguishing between cones (Cone Nonperfusion Index [CPI]: r = 0.55617, p < 0.0001) and rods (Rod Nonperfusion Index [RPI]: r = 0.55285, p < 0.0001). In eyes with nonproliferative DR (NPDR), NPI is correlated with DME (r = 0.51156, p = 0.0017) and central subfield thickness (CST) (r = 0.67496, p < 0.0001). UWF-FA macular nonperfusion correlated with NPI (r = 0.42899, p = 0.0101), CPI (r = 0.50028, p = 0.0022), and RPI (r = 0.49027, p = 0.0028). Central VD and VP correlated with the DME presence (r = 0.52456, p < 0.0001; r = 0.51952, p < 0.0001) and CST (r = 0.50133, p < 0.0001; r = 0.48731, p < 0.0001). Central VD and VP were correlated with macular nonperfusion (r = 0.44503, p = 0.0065; r = 0.44239, p = 0.0069) in eyes with NPDR. Larger FAZ was correlated with decreased central VD (r = −0.60089, p = 0.0001) and decreased central VP (r = −0.59224, p = 0.0001). Conclusion: UWF-CP, UWF-FA, and OCTA findings provide relevant clinical information on diabetic eyes. Nonperfusion on UWF-FA is correlated with DR severity and DME. OCTA metrics of the superficial capillary plexus correlate with the incidence of DME and macular ischemia.