Evaluation of the Ischemic Penumbra and Prognosis in acute Cerebral Infarction Using Cerebral Blood Flow and Delay Time Derived from Multi-delay pCASL Imaging.

PURPOSE: The purpose of this study was to evaluate the ischemic penumbra and prognosis in acute cerebral infarction using cerebral blood flow (CBF) and delay time (DT) derived from multi-delay pseudo-continuous arterial spin-labeling (pCASL) imaging and to estimate the possible use of such indices to predict prognosis. METHOD: Our subjects comprised 25 patients who were diagnosed with cerebral infarction in our stroke center between September 2017 and December 2018 and underwent pCASL perfusion MRI. The time from onset to MRI was 0.6 to 20 h (mean, 6 h) and was less than 4.5 h in 16 patients. Twelve patients received conservative treatment, three were treated with tPA, and the remaining 10 patients underwent invasive treatment (e.g., thrombectomy). They were subdivided by recanalization:18 patients were non-recanalized and 7 were recanalized. We evaluated the mean cerebral blood flow (CBF) and mean arterial transit DT at the infarct core and penumbra and the infarct size at the initial and follow-up examinations and calculated the infarct enlargement ratio (ER) from the initial and final infarct sizes. We also assessed clinical prognosis by using the initial and final NIHSS scores. We investigated the relationship among the ASL, ER, and NIHSS parameters and determined predictors of infarct enlargement using logistic analysis. RESULT: The degree of the CBF decrease was related to the size of the initial infarct lesion (CBF at core:r=-0.4060, p=0.044;CBF at penumbra:r=-0.4970, p=0.012) and initial NIHSS (r=-0.451, p=0.024;CBF at penumbra:r=-0.491, p=0.013). Because no parameters were correlated with the ER in all patients. Specifically in the non-recanalization group, the DT at the penumbra was positively correlated with the ER (r=-0.496, p=0.034). Moreover, by logistic regression analysis, the DT at the penumbra was the only independent predictor of infarct enlargement in all patients (p=0.047) and in non-recanalization patients (p=0.036). CONCLUSION: The only parameter predicting the ER was the mean DT at the penumbra, and the tendency was affected by recanalization status. DT obtained by multi-delay ASL may become a prognostic index of acute cerebral infarction. J. Med. Invest. 71 : 286-292, August, 2024.

Multi-Target and Multi-Phase Adjunctive Cerebral Protection for Acute Ischemic Stroke in the Reperfusion Era.

Stroke remains the leading cause of death and disability in some countries, predominantly attributed to acute ischemic stroke (AIS). While intravenous thrombolysis and endovascular thrombectomy are widely acknowledged as effective treatments for AIS, boasting a high recanalization rate, there is a significant discrepancy between the success of revascularization and the mediocre clinical outcomes observed among patients with AIS. It is now increasingly understood that the implementation of effective cerebral protection strategies, serving as adjunctive treatments to reperfusion, can potentially improve the outcomes of AIS patients following recanalization therapy. Herein, we reviewed several promising cerebral protective methods that have the potential to slow down infarct growth and protect ischemic penumbra. We dissect the underlying reasons for the mismatch between high recanalization rates and moderate prognosis and introduce a novel concept of "multi-target and multi-phase adjunctive cerebral protection" to guide our search for neuroprotective agents that can be administered alongside recanalization therapy.

Early penumbral FLAIR changes predict tissue fate in patients with large vessel occlusions.

BACKGROUND: In patients with an acute ischemic stroke, the penumbra is defined as ischemic tissue that remains salvageable when reperfusion occurs. However, the expected clinical recovery congruent with penumbral salvage is not always observed. AIMS: We aimed to determine whether the magnetic resonance imaging (MRI)-defined penumbra includes irreversible neuronal loss that impedes expected clinical recovery after reperfusion. METHODS: In the prospective French Acute Multimodal Imaging Study to Select Patients for Mechanical Thrombectomy (FRAME) and an observational cohort of patients with large vessel occlusions undergoing endovascular treatment, we quantified penumbral integrity by fluid-attenuated inversion recovery (FLAIR) changes. We studied the influence of recanalization status on the evolution of penumbral FLAIR changes and studied penumbral FLAIR changes as predictor of tissue fate and functional outcome on the 90-day modified Rankin Scale (mRS). RESULTS: Recanalization status did not modify the evolution of rFLAIR signal intensity (SI) over time in the total cohort, but was associated with lower SI in the FRAME subset (b = -0.06, p for interaction = 0.04). Median rFLAIR SI was higher at baseline in the subsequently infarcted penumbra compared to the salvaged (ratio = 1.07, standard deviation (SD) = 0.07 vs 1.03, SD = 0.06 p < 0.0001, n = 150). The severity and extent of rFLAIR SI changes did not predict 90-day functional outcome in univariate (p = 0.09) and multivariate logistic regression (p = 0.4). CONCLUSIONS: Recanalization status did not influence the evolution of penumbral FLAIR changes. FLAIR SI changes in the baseline penumbra were associated with tissue fate, but not functional outcome.

Effects of intracranial artery stenosis of anterior circulation on cognition-A CT perfusion-based study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool. METHODS: This study recruited 82 patients who suffer from non-disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters-Tmax. The correlations between cognitive function and abnormal perfusion were explored. RESULTS: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color-word test-dot (Stroop-D) and Montreal Cognitive Assessment (MoCA) sub-items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop-D is lower, and the MoCA sub-items are higher than the IP group. There is no correlation between CTP parameters and cognitive function. CONCLUSION: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI.

Endovascular clot removal in small and tortuous arteries: a case series.

Acute limb ischemia (ALI) due to arterial thromboembolic occlusion is a critical emergency in vascular medicine, requiring attention for rapid diagnosis and intervention, to prevent limb loss and major amputation, which is associated with patient disability in the long term. Traditionally, surgical embolectomy has been used for the treatment of ALI. Endovascular treatment of ALI traditionally involved catheter-directed thrombolysis. This option, however, poses some limitations, including an increased risk for access site and systemic bleeding complications, especially in patients with high bleeding risk. Therefore, in the last decades, several devices have been developed and tested for the mechanical endovascular treatment of ALI. Such devices involve either rotational thrombectomy or continuous thrombus aspiration. While rotational thrombectomy is limited in rather large arteries due to the risk of dissection and perforation in arteries <3 mm, continuous thrombus aspiration can be applied in smaller vessels and tortuous anatomies. In our case series we present a minimal-invasive endovascular approach for the treatment of two patients with ALI due to thrombotic occlusion of tortious and small diameter arteries. Minimal-invasive mechanical thrombectomy using the Penumbra Aspiration System emerged as a successful alternative to surgical embolectomy, enabling prompt treatment and with a short hospital stay for both patients. Our article therefore highlights the use of continuous thrombus aspiration in small diameter vessels and tortuous anatomies, which may represent a contraindication for the use of rotational thrombectomy. In addition, this technique may be applied even in patients with higher bleeding risk since additional lysis is not necessary in patients, where complete thrombus removal can be achieved by this device.

Artificial intelligence software for assessing brain ischemic penumbra/core infarction on computed tomography perfusion: A real-world accuracy study.

BACKGROUND: With the increasingly extensive application of artificial intelligence (AI) in medical systems, the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation. AIM: To investigate the accuracy of AI diagnostic software (Shukun) in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion. METHODS: From November 2021 to March 2022, consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy (MT) post-Shukun AI penumbra assessment were included. Computed tomography angiography (CTA) and perfusion exams were analyzed by AI, reviewed by senior neurointerventional experts. In the case of divergences among the three experts, discussions were held to reach a final conclusion. When the results of AI were inconsistent with the neurointerventional experts' diagnosis, the diagnosis by AI was considered inaccurate. RESULTS: A total of 22 patients were included in the study. The vascular recanalization rate was 90.9%, and 63.6% of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up. The computed tomography (CT) perfusion diagnosis by Shukun (AI) was confirmed to be invalid in 3 patients (inaccuracy rate: 13.6%). CONCLUSION: AI (Shukun) has limits in assessing ischemic penumbra. Integrating clinical and imaging data (CT, CTA, and even magnetic resonance imaging) is crucial for MT decision-making.

Mass Gathering Events at an Event Hall in Osaka Are a Non-direct Risk of Admission to a Neighboring Emergency Hospital.

BACKGROUND: The influence of planned mass gathering events on surrounding residents is not understood sufficiently. OBJECTIVES: The purpose of this study was to investigate how events at an event hall affect a neighboring emergency hospital throughout the year. METHODS: This was a single-center, retrospective, observational study conducted on all patients who presented to the emergency department from January 1 to December 31, 2019. The event hall is located 200 meters from the hospital, and various events such as music concerts and professional baseball games are held at the hall throughout the year. We collected patient information from the electronic medical records. The factors associated with hospitalization were assessed using a multivariable logistic regression analysis. RESULTS: This study comprised 18,907 patients who visited our emergency department. The number of patients on event days was 9,981 and that on no-event days was 8,922. The mean (SD) number of patients visiting on event days was 56.4 (14.9), and that on no-event days was 47.5 (14.1) (p<0.05). The multivariable logistics regression analysis showed age (adjusted odds ratio (AOR): 1.03; 95% confidence interval (CI): 1.03-1.04), male gender (AOR: 1.21; 95% CI: 1.13-1.31), transportation by emergency medical services (AOR: 2.56; 95% CI: 2.37-2.75), rain days (AOR: 1.14; 95% CI: 1.04-1.23), and event day (AOR: 1.11; 95% CI: 1.02-1.20) to be independent risk factors of hospitalization. CONCLUSIONS: In this study, we found that event day was one of the independent risk factors of admission to the hospital from the emergency department.

A Projection Integration Method for X-ray Collimator Design.

One of the recent trends in radiation therapy is to increase conformal and accurate dose delivery such as in stereotactic radiosurgery (SRS). Treating small lesions and brain disorders requires the accurate placement of small radiation fields deep inside the human cranium. To design a collimator meeting these requirements, a new numerical concept was developed, which is presented here. The algorithm proposed here can generate beam profiles of plural collimation apertures and arbitrary initial beam spot distributions in a time-efficient method. It is an ideal tool to optimize collimator design for penumbra, dose rate, and field size. The intensity of the source beam spot is divided into slices, and each slice is projected onto the treatment plane at the isocenter through the collimator apertures. The illuminated field range and intensity are determined by geometry and the intensity of that slice of beam source, respectively. By integrating the projected intensity across all the slices of the source profile, the profile on the treatment plane is obtained. The algorithm is used to generate beam profiles of a conical pencil beam collimator system and compare them to the Monte Carlo simulation as well as measurements. It can also be used to demonstrate the impact of collimator shape on the beam penumbra, dose rate, and field size. The projection integration method provides a quick and informative tool for collimator design. The results were validated with the Monte Carlo simulation and measurements. This method was demonstrated to be effective for optimizing beam characteristics.

Challenges, Recommendations, and Epidemiology of Pulmonary Embolism in India: A Narrative Review.

An embolized clot that travels to the lungs from the legs or, less commonly, other parts of the body (known as deep vein thrombosis or DVT) causes pulmonary embolism (PE), which is characterized by obstruction of blood flow to the pulmonary artery. As PE has the propensity to masquerade as various illnesses affecting both the cardiovascular (CV) and the respiratory system, it is crucial to identify PE at the earliest. Appropriate diagnosis of PE may lead to earlier treatment and improved patient outcomes. While pulmonary angiography remains the established gold standard for diagnosing PE, the contemporary standard of care for this condition is the computed tomography pulmonary angiogram (CTPA). Anticoagulation therapy is the fundamental strategy for managing PE, with the forefront of treatment being the use of novel and upcoming oral anticoagulants known as non-vitamin K antagonist oral anticoagulants (NOACs). The NOACs provide a practical single-drug treatment strategy, which does not hinder the patient's lifestyle and domestic responsibilities. Although PE may be fatal, early detection may lead to effective management. Despite that, mortality and morbidity associated with PE are very high in India. The awareness among Indian healthcare professionals about PE should be improved, and unified pan-country diagnostic and management guidelines should be formulated to tackle the country's PE burden.

Investigation of a novel 2.5 MV sintered diamond target beam for intracranial linac-based stereotactic treatments.

Purpose. This work investigates the small-field dosimetric characteristics of a 2.5 MV sintered diamond target beam and its feasibility for use in linac-based intracranial stereotactic treatments. Due to the increased proportion of low energy photons in the low-Z beam, it was hypothesized that this novel beam would provide sharper dose fall-off compared to the 6 MV beam owing to the reduced energy, and therefore range, of secondary electrons.Methods. Stereotactic treatments of ocular melanoma and trigeminal neuralgia were simulated for 2.5 MV low-Z and 6 MV beams using Monte Carlo to calculate dose in a voxelized anatomical phantom. Two collimation methods were investigated, including a 5 × 3 mm2HDMLC field and a 4 mm cone to demonstrate isolated and combined effects of geometric and radiological contributions to the penumbral width.Results. The measured 2.5 MV low-Z dosimetric profiles demonstrated reduced penumbra by 0.5 mm in both the inline and crossline directions across all depths for both collimation methods, compared to 6 MV. In both treatment cases, the 2.5 MV low-Z beam collimated with the 4 mm cone produced the sharpest dose fall off in profiles captured through isocenter. This improved fall-off resulted in a 59% decrease to the maximum brainstem dose in the trigeminal neuralgia case for the 2.5 MV low-Z MLC collimated beam compared to 6 MV. Reductions to the maximum and mean doses to ipsilateral and contralateral OARs in the ocular melanoma case were observed for the 2.5 MV low-Z beam compared to 6 MV with both collimation methods.Conclusions. While the low dose rate of this novel beam prohibits immediate clinical translation, the results of this study support the further development of this prototype beam to decrease toxicity in intracranial SRS treatments.

A Minimalist Iron Oxide Nanoprobe for the High-Resolution Depiction of Stroke by Susceptibility-Weighted Imaging.

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 â€‹h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 â€‹h. Within 6 â€‹h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

Amide proton transfer MRI at 9.4 T for differentiating tissue acidosis in a rodent model of ischemic stroke.

PURPOSE: Differentiating ischemic brain damage is critical for decision making in acute stroke treatment for better outcomes. We examined the sensitivity of amide proton transfer (APT) MRI, a pH-weighted imaging technique, to achieve this differentiation. METHODS: In a rat stroke model, the ischemic core, oligemia, and the infarct-growth region (IGR) were identified by tracking the progression of the lesions. APT MRI signals were measured alongside ADC, T1, and T2 maps to evaluate their sensitivity in distinguishing ischemic tissues. Additionally, stroke under hyperglycemic conditions was studied. RESULTS: The APT signal in the IGR decreased by about 10% shortly after stroke onset, and further decreased to 35% at 5 h, indicating a progression from mild to severe acidosis as the lesion evolved into infarction. Although ADC, T1, and T2 contrasts can only detect significant differences between the IGR and oligemia for a portion of the stroke duration, APT contrast consistently differentiates between them at all time points. However, the contrast to variation ratio at 1 h is only about 20% of the contrast to variation ratio between the core and normal tissues, indicating limited sensitivity. In the ischemic core, the APT signal decreases to about 45% and 33% of normal tissue level at 1 h for the normoglycemic and hyperglycemic groups, respectively, confirming more severe acidosis under hyperglycemia. CONCLUSION: The sensitivity of APT MRI is high in detecting severe acidosis of the ischemic core but is much lower in detecting mild acidosis, which may affect the accuracy of differentiation between the IGR and oligemia.

Pial collaterals limit stroke progression and metabolic stress in hypoperfused tissue: An MRI perfusion and mq-BOLD study.

BACKGROUND AND PURPOSE: In acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), the relationship between cerebral oxygen extraction fraction (OEF) as the hallmark of the ischemic penumbra and leptomeningeal collateral supply is not well established. We aimed to investigate the relationship between pial collateralization and tissue oxygen extraction in patients with LVO using magnetic resonance imaging (MRI). METHODS: Data from 14 patients with anterior circulation LVO who underwent MRI before acute stroke treatment were analyzed. In addition to diffusion-weighted imaging and perfusion-weighted imaging (PWI), the protocol comprised sequences for multiparametric quantitative blood-oxygen-level-dependent imaging for the calculation of relative OEF (rOEF). Pial collateral supply was quantitatively assessed by analyzing the signal variance in T2*-weighted PWI time series. Relationships between collateral supply, infarct volume, rOEF in peri-infarct hypoperfused tissue, and clinical stroke severity were assessed. RESULTS: The PWI-based parameter quantifying collateral supply was negatively correlated with baseline ischemic core volume and rOEF in the hypoperfused peri-infarct area (p < .01). Both reduced collateral supply and increased rOEF correlated significantly with higher scores on the National Institutes of Health Stroke Scale (p < .05). Increased rOEF within hypoperfused tissue was associated with higher baseline (p = .043) and follow-up infarct volume (p = .009). CONCLUSIONS: Signal variance-based mapping of collaterals with PWI depicts pial collateral supply, which is closely tied to tissue pathophysiology and clinical and imaging outcomes. Magnetic-resonance-derived mapping of cerebral rOEF reveals penumbral characteristics of hypoperfused tissue and might provide a promising imaging biomarker in AIS.

Assessment of peripheral dose as a function of distance and depth from cobalt-60 beam in water phantom using TLD-100.

BACKGROUND: Innovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100). METHODS: The PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm. RESULTS: The results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor. CONCLUSION: It is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.

Ischemia-reperfusion injury in a salvaged penumbra: Longitudinal high-tesla perfusion magnetic resonance imaging in a rat model.

INTRODUCTION: Although ischemia-reperfusion (I/R) injury varies between cortical and subcortical regions, its effects on specific regions remain unclear. In this study, we used various magnetic resonance imaging (MRI) techniques to examine the spatiotemporal dynamics of I/R injury within the salvaged ischemic penumbra (IP) and reperfused ischemic core (IC) of a rodent model, with the aim of enhancing therapeutic strategies by elucidating these dynamics. MATERIALS AND METHODS: A total of 17 Sprague-Dawley rats were subjected to 1 h of transient middle cerebral artery occlusion with a suture model. MRI, including diffusion tensor imaging (DTI), T2-weighted imaging, perfusion-weighted imaging, and T1 mapping, was conducted at multiple time points for up to 5 days during the I/R phases. The spatiotemporal dynamics of blood-brain barrier (BBB) modifications were characterized through changes in T1 within the IP and IC regions and compared with mean diffusivity (MD), T2, and cerebral blood flow. RESULTS: During the I/R phases, the MD of the IC initially decreased, normalized after recanalization, decreased again at 24 h, and peaked on day 5. By contrast, the IP remained relatively stable. Both the IP and IC exhibited hyperperfusion, with the IP reaching its peak at 24 h, followed by resolution, whereas hyperperfusion was maintained in the IC until day 5. Despite hyperperfusion, the IP maintained an intact BBB, whereas the IC experienced persistent BBB leakage. At 24 h, the IC exhibited an increase in the T2 signal, corresponding to regions exhibiting BBB disruption at 5 days. CONCLUSIONS: Hyperperfusion and BBB impairment have distinct patterns in the IP and IC. Quantitative T1 mapping may serve as a supplementary tool for the early detection of malignant hyperemia accompanied by BBB leakage, aiding in precise interventions after recanalization. These findings underscore the value of MRI markers in monitoring ischemia-specific regions and customizing therapeutic strategies to improve patient outcomes.

Developing targeted antioxidant nanomedicines for ischemic penumbra: Novel strategies in treating brain ischemia-reperfusion injury.

During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress, constitute the main pathological mechanism behind ischemia-reperfusion damage. Swiftly reinstating blood perfusion in the ischemic penumbra zone and suppressing neuronal oxidative injury are key to effective treatment. Presently, antioxidants in clinical use suffer from low bioavailability, a singular mechanism of action, and substantial side effects, severely restricting their therapeutic impact and widespread clinical usage. Recently, nanomedicines, owing to their controllable size and shape and surface modifiability, have demonstrated good application potential in biomedicine, potentially breaking through the bottleneck in developing neuroprotective drugs for ischemic strokes. This manuscript intends to clarify the mechanisms of cerebral ischemia-reperfusion injury and provides a comprehensive review of the design and synthesis of antioxidant nanomedicines, their action mechanisms and applications in reversing neuronal oxidative damage, thus presenting novel approaches for ischemic stroke prevention and treatment.

Longitudinal microstructural alterations surrounding subcortical ischemic stroke lesions detected by free-water imaging.

In this study we explore the spatio-temporal trajectory and clinical relevance of microstructural white matter changes within and beyond subcortical stroke lesions detected by free-water imaging. Twenty-seven patients with subcortical infarct with mean age of 66.73 (SD 11.57) and median initial NIHSS score of 4 (IQR 3-7) received diffusion MRI 3-5 days, 1 month, 3 months, and 12 months after symptom-onset. Extracellular free-water and fractional anisotropy of the tissue (FAT) were averaged within stroke lesions and the surrounding tissue. Linear models showed increased free-water and decreased FAT in the white matter of patients with subcortical stroke (lesion [free-water/FAT, mean relative difference in %, ipsilesional vs. contralesional hemisphere at 3-5 days, 1 month, 3 months, and 12 months after symptom-onset]: +41/-34, +111/-37, +208/-26, +251/-18; perilesional tissue [range in %]: +[5-24]/-[0.2-7], +[2-20]/-[3-16], +[5-43]/-[2-16], +[10-110]/-[2-12]). Microstructural changes were most prominent within the lesion and gradually became less pronounced with increasing distance from the lesion. While free-water elevations continuously increased over time and peaked after 12 months, FAT decreases were most evident 1 month post-stroke, gradually returning to baseline values thereafter. Higher perilesional free-water and higher lesional FAT at baseline were correlated with greater reductions in lesion size (rho = -0.51, p = .03) in unadjusted analyses only, while there were no associations with clinical measures. In summary, we find a characteristic spatio-temporal pattern of extracellular and cellular alterations beyond subcortical stroke lesions, indicating a dynamic parenchymal response to ischemia characterized by vasogenic edema, cellular damage, and white matter atrophy.

Comprehensive Management of Stroke: From Mechanisms to Therapeutic Approaches.

Acute ischemic stroke (AIS) is a challenging disease, which needs urgent comprehensive management. Endovascular thrombectomy (EVT), alone or combined with iv thrombolysis, is currently the most effective therapy for patients with acute ischemic stroke (AIS). However, only a limited number of patients are eligible for this time-sensitive treatment. Even though there is still significant room for improvement in the management of this group of patients, up until now there have been no alternative therapies approved for use in clinical practice. However, there is still hope, as clinical research with novel emerging therapies is now generating promising results. These drugs happen to stop or palliate some of the underlying molecular mechanisms involved in cerebral ischemia and secondary brain damage. The aim of this review is to provide a deep understanding of these mechanisms and the pathogenesis of AIS. Later, we will discuss the potential therapies that have already demonstrated, in preclinical or clinical studies, to improve the outcomes of patients with AIS.

Chronic hypertension alters the relationship between collateral blood flow, cortical cerebral blood flow, and brain tissue oxygenation.

This study measured the relationship between pial collateral (leptomeningeal anastomoses, LMA) flow, intraparenchymal cortical cerebral blood flow (cCBF) and brain tissue oxygenation (btO2) during acute ischemic stroke to investigate how pial flow translates to downstream cCBF and btO2 and examined how this relationship is altered in hypertension. Proximal transient middle cerebral artery occlusion (tMCAO) was performed in male Wistar (n = 8/group) and Spontaneously Hypertensive Rats (SHR, n = 8/group). A combination laser Doppler-oxygen probe was placed within the expected cortical peri-infarct in addition to a surface laser doppler probe which measured LMA flow. Phenylephrine (PE) was infused 30 minutes into tMCAO to increase blood pressure (BP) by 30% for 10 minutes and assessed CBF autoregulation. During the initial 30-minute period of tMCAO, btO2 and cCBF were lower in SHR compared to Wistar rats (btO2: 11.5 ± 10.5 vs 17.5 ± 10.8 mmHg and cCBF: -29.7 ± 23.3% vs -17.8 ± 41.9%); however, LMA flow was similar between groups. The relationship between LMA flow, cCBF and btO2 were interdependent in Wistar rats. However, this relationship was disrupted in SHR rats and partially restored by induced hypertension. This study provides evidence that cCBF and btO2 were diminished during tMCAO in chronic hypertension, and that induced hypertension was beneficial regardless of hypertensive status.