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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In this paper, I study the nature of adnumerative or numerative forms; i.e. morphologically dedicated inflectional forms that can only be used with numerals or quantifiers (e.g. Russian dva časá ‘two o'clock’ vs. [gen sg] čása). Adnumeratives are cross‐linguistically very rare; yet they raise some interesting theoretical discussions. This work is based on the framework of Canonical Typology, which assumes the existence of a handful of discrete and cross‐linguistically recurrent morphosyntactic features. Nevertheless, adnumerative forms present a challenge to that distribution, because, as I argue, adnumeratives lie between case and number values. This might well represent a theoretically undesirable scenario, and thus, be diachronically unstable. However, the data I have gathered prove that there are adnumerative forms that have survived in this penumbra for centuries and one can also adduce more evidence of diachronically stable cross‐linguistic phenomena between two feature values (e.g. the anterior). Therefore, I propose that this theoretical space may not be as dark previously depicted and I ask questions for further exploration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Flat-panel detector computed tomography (FDCT) is increasingly used in (neuro)interventional angiography suites. This study aimed to compare FDCT perfusion (FDCTP) with conventional multidetector computed tomography perfusion (MDCTP) in patients with acute ischemic stroke. Methods: In this study, 19 patients with large vessel occlusion in the anterior circulation who had undergone mechanical thrombectomy, baseline MDCTP and pre-interventional FDCTP were included. Hypoperfused tissue volumes were manually segmented on time to maximum (Tmax) and time to peak (TTP) maps based on the maximum visible extent. Absolute and relative thresholds were applied to the maximum visible extent on Tmax and relative cerebral blood flow (rCBF) maps to delineate penumbra volumes and volumes with a high likelihood of irreversible infarcted tissue ("core"). Standard comparative metrics were used to evaluate the performance of FDCTP. Results: Strong correlations and robust agreement were found between manually segmented volumes on MDCTP and FDCTP Tmax maps (r = 0.85, 95% CI 0.65–0.94, p < 0.001; ICC = 0.85, 95% CI 0.69–0.94) and TTP maps (r = 0.91, 95% CI 0.78–0.97, p < 0.001; ICC = 0.90, 95% CI 0.78–0.96); however, direct quantitative comparisons using thresholding showed lower correlations and weaker agreement (MDCTP versus FDCTP Tmax 6 s: r = 0.35, 95% CI −0.13–0.69, p = 0.15; ICC = 0.32, 95% CI 0.07–0.75). Normalization techniques improved results for Tmax maps (r = 0.78, 95% CI 0.50–0.91, p < 0.001; ICC = 0.77, 95% CI 0.55–0.91). Bland-Altman analyses indicated a slight systematic underestimation of FDCTP Tmax maximum visible extent volumes and slight overestimation of FDCTP TTP maximum visible extent volumes compared to MDCTP. Conclusion: FDCTP and MDCTP provide qualitatively comparable volumetric results on Tmax and TTP maps; however, direct quantitative measurements of infarct core and hypoperfused tissue volumes showed lower correlations and agreement. [ABSTRACT FROM AUTHOR]

Objectives: Stroke is a condition with high morbidity and mortality. This study aims to investigate whether the effectiveness of Computed Tomography (CT) and diffusionweighted Magnetic Resonance Imaging (MRI), the techniques that have a significant place in the diagnosis of ischemic stroke, the most common form of stroke, are affected by the physiological changes of advanced age. Methods: A total of 436 patients were included in the study. The study population was divided into two groups depending on age: those above 65 and those under 65 years of age. Medical files, both the emergency department and clinical ward files, of the patients who were admitted to the emergency department in nine months and admitted to the neurology clinic with the diagnosis of ischemic stroke were retrospectively analyzed. The time from admission to imaging was determined depending on patient files and the Hospital Management Information System (HBYS). The CT and MRI reports interpreted by radiologists were also reviewed. While recording the data, the presence of a lesion, its direction, and localization were also noted. Results: CT positivity was 21.3%, and the positivity of diffusion-weighted imaging was 82.1% in the study population. The time was shorter in the group of patients with positive CT results than in the group with negative CT results. In subjects under 65, the time between onset and imaging was shorter in the group with positive CT results than in the group with negative CT results. In subjects over 65, the time with positive CT results was not different from the group with negative CT results. It was determined that the mean time was shorter in the group with positive MRI results than in the group with negative results. In both the groups under the age of 65 and over the age of 65, the time interval was shorter in the patients with positive MRI results compared to those with negative MRI results. Conclusions: Regardless of the positivity or negativity of CT and MRI results, the mean time from symptom onset to imaging was shorter in the group under 65 years of age compared to the group over 65 years. Aging prolongs the time to admission and the neuroradiological response of geriatric patients. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary embolism is the third most common cardiovascular cause of death. Patients with the highest risk of death are hemodynamically unstable patients who require aggressive reperfusion therapy. Systemic thrombolysis is the most common method of reperfusion therapy used in clinical practice, however, it is associated with high risk of bleeding complications. Surgical embolectomy is another modality of reperfusion therapy, which is associated with significant invasiveness into body. Endovascular treatment options are a relatively new alternative of reperfusion therapy. Endovascular treatment of pulmonary embolism has shown to be safe and effective in several clinical trials. Compared to surgical embolectomy, the method is less invasive and compared to systemic thrombolysis, it is associated with a lower risk of bleeding complications. Objective: The primary objective of this thesis is to determine the impact of endovascular treatment on the early mortality of patients with high-risk pulmonary embolism. Methods: This is a retrospective analysis with the inclusion of patients who were hospitalized at the Department of Internal Medicine of Trnava University Hospital with high-risk pulmonary embolism from January 2015 to December 2021. 45 patients were included in the analysis. Patients were divided into two groups. The first group “ATE(-)” included patients hospitalized before endovascular treatment- aspiration thrombectomy was available (January 2015 – June 2018). The second group “ATE(+)” included patients after the implementation of aspiration thrombectomy with the Indigo aspiration system (July 2018 – December 2021). We compared both groups in terms of early mortality. Conclusion: Aspiration thrombectomy is an effective and safe reperfusion method. With the use of aspiration thrombectomy, we managed to reduce the early mortality of high-risk pulmonary embolism from 38.46% to 18.75%. It´s efficacy was seen especially in patients in whom systemic thrombolysis failed, or was contraindicated. [ABSTRACT FROM AUTHOR]

Purpose: Residual or undertreated inflow disease is a major cause of stent occlusion following endovascular thrombectomy for iliofemoral deep venous thrombosis (DVT). The profunda femoral vein (PFV) is an important inflow vessel alongside the femoral vein but is traditionally challenging to treat via an antegrade popliteal approach. This technical note describes a novel approach for PFV clearance in iliofemoral thrombectomy via the popliteal vein. Materials and Methods: Eight patients underwent PFV clearance as part of iliofemoral DVT thrombectomy via an antegrade popliteal approach. In seven patients, a popliteal-profunda communicating vessel was identified permitting PFV access and thrombectomy. In one patient, a popliteal-profunda communicator was not identified and an 'up and over' approach via the femoral bifurcation from the same popliteal access was utilised. Thrombectomy was performed using the Inari ClotTriever device or Penumbra's Indigo system. Results: Technical success in PFV thrombectomy was 100%. Six patients (75%) underwent stenting for an iliac stenotic lesion or May Thurner compression point. At the four-week ultrasound follow-up, the pelvic iliofemoral segment was patent in 7 patients (87.5%). The PFV was patent in 7 patients (87.5%) whereas the FV was only patent in 4 patients (50%). One patient underwent reintervention for iliofemoral stent occlusion. No PFV injury occurred and no post-procedure profunda reflux was identified. Conclusion: PFV clearance can be achieved via an antegrade popliteal approach in iliofemoral thrombectomy to optimise inflow, negating the need for alternative or additional venous access. PFV may maintain upstream iliofemoral vein patency even with an occluded femoral vein. Level of Evidence: Level 4, Case Series. [ABSTRACT FROM AUTHOR]

This study focuses on understanding the role of c-Myc, a cancer-associated transcription factor, in the penumbra following ischemic stroke. While its involvement in cell death and survival is recognized, its post-translational modifications, particularly acetylation, remain understudied in ischemia models. Investigating these modifications could have significant clinical implications for controlling c-Myc activity in the central nervous system. Although previous studies on c-Myc acetylation have been limited to non-neuronal cells, our research examines its expression in perifocal cells during stroke recovery to explore regulatory mechanisms via acetylation. We found that in peri-infarct neurons, c-Myc is upregulated with acetylation at K148 but not K323 during the acute phase of stroke, with SIRT2 deacetylase primarily affecting K148 acetylation. Molecular dynamics simulations suggest that lysine 148 plays a crucial role in stabilizing c-Myc spatial structure. Increased acetylation at K148 reduces c-Myc compaction, potentially limiting its nuclear penetration, promoting calpain-mediated cleavage, and decreasing nuclear localization. Additionally, cytoplasmic acetylation at K148 may alter c-Myc's interaction with unidentified proteins, potentially influencing its pro-apoptotic effects and promoting cytoplasmic accumulation. Targeting SIRT2 with selective inhibitors could be a promising avenue for future stroke therapy strategies. [ABSTRACT FROM AUTHOR]

ObjectiveWe tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated.Materials and methodsMale SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1-7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 µg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or vehicle. In the therapeutic window, vehicle, LAU (60 mg/kg), AT-NPD1 (222 µg/kg), and LAU+AT-NPD1 were administered at 3, 4, 5, and 6 hours after onset of MCAo.ResultsLAU and AT-NPD1 treatments alone improved behavior by 40-42% and 20-30%, respectively, and LAU+AT-NPD1 by 40% compared to the vehicle group. T2-weighted imaging (T2WI) volumes were reduced with all doses of LAU and AT-NPD1 by 73-90% and 67-83% and LAU+AT-NPD1 by 94% compared to vehicle. In the therapeutic window, LAU+AT-NPD1, when administered at 3, 4, 5, and 6 hours, improved behavior by 50, 56, 33, and 26% and reduced T2WI volumes by 93, 90, 82, and 84% compared to vehicle.ConclusionsWe have shown here for the first time that LAU plus AT-NPD1 treatment affords high-grade neuroprotection in MCAo, equaling or exceeding that afforded by LAU or AT-NPD1 alone at considerably moderate doses. It has a broad therapeutic window extending to 6 hours after stroke onset.

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. Trial registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31. [ABSTRACT FROM AUTHOR]

Progressive ischemic stroke is the most frequent form of stroke with neurologic deterioration. The pathogenesis of progressive ischemic stroke is based on the expansion of the brain infarction zone and reduction of the "penumbra" zone in the area of focal ischemia. The leading role in maintaining the balance between irreversible and reversible ischemia belongs to cerebral collateral blood flow. Being a multifactorial phenomenon, collateral blood flow is caused by both morphological and functional characteristics of the collateral arterial channel and systemic factors, among which hemodynamics is of great importance. The tactic of purposeful increase in blood pressure to improve cerebral perfusion is called drug-induced arterial hypertension. A number of experimental studies have demonstrated the safety and efficacy of this method, but the small number and heterogeneity of data in the studies do not allow us to conduct a meta-analysis and form an optimal protocol for drug-induced arterial hypertension. In this article we want to describe the clinical observation of a patient with ischemic stroke on the background of critical stenosis of stroke-related internal carotid artery and atrial fibrillation, in the treatment of which we applied drug-induced arterial hypertension.

Abstract Objectives To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients. Methods The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with approval from the institutional review board. The patients had undergone CTP imaging, NIHSS and ASPECTS grading. convolutional neural network (CNN) model was trained to fit a raw AIF curve to a gamma variate function. CNN AIF was utilized to estimate the core and penumbra volumes which were further validated with clinical scores. Results Penumbra estimated by CNN AIF correlated positively with the NIHSS score (r = 0.69; p 20) and lower ASPECT score ( 10 s, Tmax > 10 s volumes were statistically significantly higher (p

Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-13C]pyruvate is an emerging technology that directly images metabolism. Here, we investigated its potential to detect viable tissue in ischemic stroke. Stroke was induced in pigs by intracerebral injection of endothelin 1. During ischemia, the rate constant of pyruvate-to-lactate conversion, kPL, was 52% larger in penumbra and 85% larger in the infarct compared to the contralateral hemisphere (P = 0.0001). Within the penumbra, the kPL was 50% higher in the regions that later infarcted compared to non-progressing regions (P = 0.026). After reperfusion, measures of pyruvate-to-lactate conversion were slightly decreased in the infarct compared to contralateral. In addition to metabolic imaging, we used hyperpolarized pyruvate for perfusion-weighted imaging. This was consistent with conventional imaging for assessment of infarct size and blood flow. Lastly, we confirmed the translatability of simultaneous assessment of metabolism and perfusion with hyperpolarized MRI in healthy volunteers. In conclusion, hyperpolarized [1-13C]pyruvate may aid penumbral characterization and increase access to reperfusion therapy for late presenting patients.

Background and Purpose: The effort to translate clinical findings across institutions employing different relative biological effectiveness (RBE) models of ion radiotherapy has rapidly grown in recent years. Nevertheless, even for a chosen RBE model, different implementations exist. These approaches might consider or disregard the dose-dependence of the RBE and the radial variation of the radiation quality around the beam axis. This study investigated the theoretical impact of disregarding these effects during the RBE calculations. Materials and Methods: Microdosimetric simulations were carried out using the Monte Carlo code PHITS along the spread out Bragg peaks of 1H, 4He, 12C, 16O, and 20Ne ions in a water phantom. The RBE was computed using different implementations of the Mayo Clinic Florida microdosimetric kinetic model (MCF MKM) and the modified MKM, considering or not the radial variation of the radiation quality in the penumbra of the ion beams and the dose-dependence of the RBE. Results: For an OAR located 5 mm laterally from the target volume, disregarding the radial variation of the radiation quality or the dose-dependence of the RBE could result in an overestimation of the RBE-weighted dose up to a factor of ∼ 3.5 or ∼ 1.7, respectively. Conclusions: The RBE-weighted dose to OARs close to the tumor volume was substantially impacted by the approach employed for the RBE calculations, even when using the same RBE model and cell line. Therefore, care should be taken in considering these differences while translating clinical findings between institutions with dissimilar approaches.

Background and Purpose: This study was dedicated to investigating the agreement of the calculated results of two CT perfusion (CTP) postprocessing software packages, including parameter maps and ischemic volume, focusing on the infarct core volume (ICV) and penumbra volume (PV). Methods: A retrospective collection of 235 patients with acute ischemic stroke who underwent CTP examination were enrolled. All images had been analyzed with two software pipelines, RAPID CTP and AccuCTP, and the comparative analysis was based on ICV and PV results calculated by both software packages. The agreement of parameter maps was evaluated by root mean square error and Bland‐Altman analysis. The ICV and PV agreement was evaluated by intraclass correlation coefficient (ICC) and Bland‐Altman analysis. The accuracy of ICV and PV based on multiple thresholds was also analyzed. Results: The ICV and PV of AccuCTP and RAPID CTP show excellent agreement. The relative differences of the parameter maps were all within 10% and the Bland‐Altman analysis also showed a strong agreement. From ordinary least squares fitting results, both ICV and PV had a remarkably high goodness of fit (ICV, R2= 0.975 [p<.001]; PV, R2= 0.964 [p<.001]). For the ICC analysis, both had high ICC scores (ICV ICC 0.984, 95% CI [confidence interval] 0.973‐0.989; PV ICC 0.955, 95% CI 0.947‐0.964). Furthermore, multi‐threshold analysis on the basis of ICV and PV also achieved reliable analytical accuracy. Conclusions: The image analysis results of AccuCTP are in excellent agreement with RAPID CTP and can be used as an alternative analysis tool to RAPID CTP software in stroke clinical practice. [ABSTRACT FROM AUTHOR]

Anticoagulation is mainstay therapy for patients with acute pulmonary embolism while systemic thrombolysis is reserved for those with hemodynamic instability. Over the last decade, percutaneous interventional options have entered the landscape aimed to achieve rapid pharmacomechanical pulmonary artery recanalization. The Penumbra Indigo® Aspiration System (Penumbra Inc., CA, USA) is a US FDA-approved large-bore aspiration thrombectomy device for the treatment of pulmonary embolism. Recent data has demonstrated improved radiographic end points with low rates of major adverse events in cases of intermediate-risk pulmonary embolism. In this review article, we outline device technology, applications, evidence and future directions. A pulmonary embolism, or a blood clot in the blood vessels of the lungs, can cause symptoms of chest pain and difficulty breathing. While blood thinners have been the main treatment for pulmonary embolism, procedures aimed to rapidly remove clots have become available as treatment options. In this article we review these procedural options for pulmonary embolism with a focus on the Indigo® Aspiration System by Penumbra Inc. This device has shown that it works and is very safe compared with other similar devices. In the future, more studies need to be performed to compare how well this device works compared with blood thinners alone, and whether it can lower the chances of long-term symptoms of these clots such as chronic shortness of breath and heart failure. Percutaneous thrombectomy for pulmonary embolism with Penumbra's Indigo® Aspiration System has demonstrated improved radiographic end points with a great safety profile. [ABSTRACT FROM AUTHOR]

Background and purpose: Computed tomography perfusion (CTP) has successfully extended the time window for reperfusion therapies in ischemic stroke. However, the published perfusion parameters and thresholds vary between studies. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines, we conducted a systematic review to investigate the accuracy of parameters and thresholds for identifying core and penumbra in adult stroke patients. Methods: We searched Medline, Embase, the Cochrane Library, and reference lists of manuscripts up to April 2022 using the following terms "computed tomography perfusion," "stroke," "infarct," and "penumbra." Studies were included if they reported perfusion thresholds and undertook co-registration of CTP to reference standards. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and Standards for Reporting of Diagnostic Accuracy (STARD) guidelines. Results: A total of 24 studies were included. A meta-analysis could not be performed due to insufficient data and significant heterogeneity in the study design. When reported, the mean age was 70.2 years (SD+/-3.69), and the median NIHSS on admission was 15 (IQR 13-17). The perfusion parameter identified for the core was relative cerebral blood flow (rCBF), with a median threshold of <30% (IQR 30, 40%). However, later studies reported lower thresholds in the early time window with rapid reperfusion (median 25%, IQR 20, 30%). A total of 15 studies defined a single threshold for all brain regions irrespective of collaterals and the gray and white matter. Conclusion: A single threshold and parameter may not always accurately differentiate penumbra from core and oligemia. Further refinement of parameters is needed in the current era of reperfusion therapy. [ABSTRACT FROM AUTHOR]

Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra. Further, it has been shown that SS mice develop poorer neo-collateral perfusion after limb ischemia. We used the middle cerebral artery (MCA)-targeted photothrombosis model in this study, since it is better tolerated by SS mice and creates a clear infarct core versus peri-infarct area. Compared to AA mice, SS mice showed enlarged infarction and lesser endothelial proliferation after photothrombosis. SS-chimera showed anemia, hypoxia-induced erythrocyte sickling, and attenuated recovery of blood flow in the ipsilateral cortex after photothrombosis. In AA chimera, cerebral blood flow in the border area between MCA and the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) trees improved from 44% of contralateral level after stroke to 78% at 7d recovery. In contrast, blood flow in the MCA-ACA and MCA-PCA border areas only increased from 35 to 43% at 7d post-stroke in SS chimera. These findings suggest deficits of post-stroke collateral circulation in SCA. Better understanding of the underpinnings may suggest novel stroke therapies for SCA patients. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are abundantly and stably expressed in the brain of mammals and humans. Some circRNAs are implicated in ischemic stroke. Therefore, we aimed to detect how circRNAs change in the key penumbra area during cerebral ischemia-reperfusion (CI/R) injury. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), during which the permanent blocking period was 2 h and reperfusion time was 24 or 72 h. Then modified neurologic severity score (mNSS), triphenyl tetrazolium chloride (TTC) staining and HE staining were used to exhibiting damage between rats in different groups. The penumbra regions of all rats were dissected and total RNA was further processed for high-throughput sequencing. CircRNA expression profiles were screened and bioinformatics analyses were conducted to investigate these differentially expressed circRNAs. Some of them were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the establishment of a circRNA-miRNA-mRNA network and the detection of their downstream molecules. A total of 99 and 98 circRNAs were differentially expressed at CI/R 24 h and CI/R 72 h, respectively. Notably, 21 circRNAs significantly changed at both reperfusion points. Three circRNAs, namely circ.7225, circ.5415, and circ.20623 were found to be associated with CI/R injury and might be preferred targets. Common downstream miR-298-5p and Bcl-3 were found to make up the circRNA-miRNA-mRNA network. Novel circRNA targets came to light in the penumbra of rats during CI/R injury and might establish the circRNA-miRNA-mRNA relationship, thus serving as potential biomarkers for ischemic stroke treatment. [ABSTRACT FROM AUTHOR]

This investigation aimed to measure and commission small unflat photon beams using the detectors described in our previous study10. Furthermore, the dosimetric parameters of small-field unflat and flat photon beams were compared to provide a better interpretation of beam energy and spectrum. The TrueBeam linear accelerator (TrueBeam LINAC, Varian Medical Systems) was employed in this study. The 10 and 6 MV unflat and flat photon beams were used to measure the output factor, depth dose, and beam profile of small-fields ranging in size from 1 cm x 1 cm to 6 cm x 6 cm. All measurements were performed according to the TRS-483 protocols established by the International Atomic Energy Agency. For both 10 and 6 MV, the output factors in unflat beam were significantly higher than in flat beam. The study found that unflat beam penumbras were slightly smaller than flat beam penumbras for both photon energies, which may improve tumor conformity and reduce doses to normal organs. The unflat photon beams had higher suface doses and lower depth doses at 10 cm than the flat photon beams for both energies, leading to considerably more beam energy degradation for unflat beams. The findings of this work are consistent with previously published data, and they will be useful for future research and LINAC commissioning. [ABSTRACT FROM AUTHOR]

The concept of the ischemic penumbra was originally defined as the area around a necrotic stroke core and seen as the tissue at imminent risk of further damage. Today, the penumbra is generally considered as time-sensitive hypoperfused brain tissue with decreased oxygen and glucose availability, salvageable tissue as treated by intervention, and the potential target for neuroprotection in focal stroke. The original concept entailed electrical failure and potassium release but one short of neuronal cell death and was based on experimental stroke models, later confirmed in clinical imaging studies. However, even though the basic mechanisms have translated well, conferring brain protection, and improving neurological outcome after stroke based on the pathophysiological mechanisms in the penumbra has yet to be achieved. Recent findings shape the modern understanding of the penumbra revealing a plethora of molecular and cellular pathophysiological mechanisms. We now propose a new model of the penumbra, one which we hope will lay the foundation for future translational success. We focus on the availability of glucose, the brain's central source of energy, and bioenergetic failure as core pathophysiological concepts. We discuss the relation of mitochondrial function in different cell types to bioenergetics and apoptotic cell death mechanisms, autophagy, and neuroinflammation, to glucose metabolism in what is a dynamic ischemic penumbra. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients. Methods: The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with approval from the institutional review board. The patients had undergone CTP imaging, NIHSS and ASPECTS grading. convolutional neural network (CNN) model was trained to fit a raw AIF curve to a gamma variate function. CNN AIF was utilized to estimate the core and penumbra volumes which were further validated with clinical scores. Results: Penumbra estimated by CNN AIF correlated positively with the NIHSS score (r = 0.69; p < 0.001) and negatively with the ASPECTS (r = − 0.43; p < 0.001). The CNN AIF estimated penumbra and core volume matching the patient symptoms, typically in patients with higher NIHSS (> 20) and lower ASPECT score (< 5). In group analysis, the median CBF < 20%, CBF < 30%, rCBF < 38%, Tmax > 10 s, Tmax > 10 s volumes were statistically significantly higher (p <.05). Conclusions: With inclusion of the CNN AIF in perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke. Critical relevance statement: With CNN AIF perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke. Key points: CNN-based AIF improves the estimation of penumbra and infarct core volumes. CNN AIF identifies patients with core regions which were ignored by conventional approaches. Core and penumbra assessment with CNN AIF correlates well with clinical scores. [ABSTRACT FROM AUTHOR]

After spinal cord injury (SCI) or ischemia, timely intervention in the penumbra, such as recanalization and tissue reperfusion, is essential for preservation of its function. However, limited by imaging resolution and micro-blood flow sensitivity, golden standard angiography modalities, including magnetic resonance angiography (MRA) and digital subtraction angiography (DSA), are still not applicable for spinal cord microvascular imaging. Regarding spinal cord penumbra, to the best of authors' knowledge, currently, there is no efficient in vivo imaging modality for its evaluation. With tens-of-micrometer resolution and deep penetration, advanced ultrasound localization microscopy (ULM) could potentially meet the needs of emergent diagnosis and long-term monitoring of spinal cord penumbra. ULM microvasculature imaging was performed on rats with all laminae removed to obtain the blood supply in major spinal cord segments (C5-L5). For adult rats with spinal cord penumbra induced by compression injury (1 s, 10 s and 15 s), ULM imaging was conducted. The corresponding angiography results are investigated in terms of microvessel saturation, morphology, and flow velocity. The Basso/Beattie/Bresnahan (BBB) locomotor rating scale and hematoxylin and eosin staining were utilized for model validation and comparison. The feasibility of ULM enabling spinal cord penumbra imaging and development monitoring was demonstrated. The focal injury core and penumbra can be clearly identified using the proposed method. Significant difference of perfusion can be observed after 1 s, 10 s and 15 s compression. Quantitative results show a high correlation between in vivo ultrasonic angiography, BBB functional evaluation and ex vivo histology assessment under different compression duration. It is demonstrated that the super-resolution ULM micro-vasculature imaging can be used to evaluate the penumbra in spinal cord at acute and early stage of chronic phase, providing an efficient modality for micro-hemodynamics monitoring of the spinal cord. [ABSTRACT FROM AUTHOR]

Purpose: The white matter hyperintensity penumbra (WMH-P) is the subtly changed normal-appearing white matter (NAWM) that surrounds white matter hyperintensities (WMHs). The goal of this study was to define WMH-P in cerebral small vessel disease (CSVD) by arterial spin labeling (ASL) and diffusion tensor imaging (DTI)/diffusion kurtosis imaging (DKI). Materials and methods: We prospectively analyzed 42 patients with CSVD. To determine the range of cerebral blood flow (CBF) and DTI/DKI penumbras around white matter hyperintensities, we generated NAWM layer masks from periventricular WMHs (PVWMHs) and deep WMHs (DWMHs). Mean values of CBF, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis, and radial kurtosis within the WMHs and their corresponding NAWM layer masks were analyzed. Paired sample t tests were used for analysis, and differences were considered statistically significant if the associated p value was ≤ 0.05. Results: For DWMHs, the CBF penumbras were 13 mm, and the DTI/DKI penumbras were 8 mm. For PVWMHs, the CBF penumbras were 14 mm, and the DTI/DKI penumbras were 14 mm. Conclusions: Our findings revealed that DTI/DKI and ASL can show structural and blood flow changes in brain tissue surrounding WMHs. In DWMHs, the blood flow penumbra was larger than the structural penumbra, while in PVWMHs, the blood flow penumbra was almost the same as the structural penumbra. [ABSTRACT FROM AUTHOR]

This paper enquires into the relationship between the rigorous graphic construction of penumbra and shadow and the idea of a developable surface circumscribed to two cores (whether these are curves or surfaces). The first rigorously constructed graphic representations of shadow and penumbra appearing in different historical treatises are contextualised and contrasted with the first works addressing the mathematical description of such surfaces. We describe how artisans and artists have employed physical and mechanical models to construct circumscribed developable surfaces, examining both their formal exploration and constructive formalisation. Next we extrapolate the mechanisms for generating circumscribed surfaces to digital and parametric models. The two procedures presented here evince the existing geometric limits of this way of generating a surface, thus influencing its constructive applications. Lastly, several examples of ephemeral architecture based on such procedures are offered, in which the digital design and manufacturing of experimental pavilions with circumscribed developable surfaces are addressed. [ABSTRACT FROM AUTHOR]

Background and purposeComputed tomography perfusion (CTP) has successfully extended the time window for reperfusion therapies in ischemic stroke. However, the published perfusion parameters and thresholds vary between studies. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines, we conducted a systematic review to investigate the accuracy of parameters and thresholds for identifying core and penumbra in adult stroke patients.MethodsWe searched Medline, Embase, the Cochrane Library, and reference lists of manuscripts up to April 2022 using the following terms “computed tomography perfusion,” “stroke,” “infarct,” and “penumbra.” Studies were included if they reported perfusion thresholds and undertook co-registration of CTP to reference standards. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and Standards for Reporting of Diagnostic Accuracy (STARD) guidelines.ResultsA total of 24 studies were included. A meta-analysis could not be performed due to insufficient data and significant heterogeneity in the study design. When reported, the mean age was 70.2 years (SD+/−3.69), and the median NIHSS on admission was 15 (IQR 13–17). The perfusion parameter identified for the core was relative cerebral blood flow (rCBF), with a median threshold of

Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra. Further, it has been shown that SS mice develop poorer neo-collateral perfusion after limb ischemia. We used the middle cerebral artery (MCA)-targeted photothrombosis model in this study, since it is better tolerated by SS mice and creates a clear infarct core versus peri-infarct area. Compared to AA mice, SS mice showed enlarged infarction and lesser endothelial proliferation after photothrombosis. SS-chimera showed anemia, hypoxia-induced erythrocyte sickling, and attenuated recovery of blood flow in the ipsilateral cortex after photothrombosis. In AA chimera, cerebral blood flow in the border area between MCA and the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) trees improved from 44% of contralateral level after stroke to 78% at 7 d recovery. In contrast, blood flow in the MCA-ACA and MCA-PCA border areas only increased from 35 to 43% at 7 d post-stroke in SS chimera. These findings suggest deficits of post-stroke collateral circulation in SCA. Better understanding of the underpinnings may suggest novel stroke therapies for SCA patients.

Ischemic stroke is one of the leading causes of disability and mortality. The collaterals provide an alternative pathway to preserve the ischemic brain tissue, and determine the penumbra range, where the neurons are salvageable. Therefore, accurately monitoring the collaterals and identifying the penumbra are crucial. Herein, a low-immunogenic nanoprobe-based MRI strategy is developed to simultaneously identify the infarct core, collaterals distribution, and ischemic penumbra distributions. The low-immunogenic nanoprobe was constructed by covalently attaching self-peptide on the surface of biocompatible Fe3O4 nanoparticles as a stealth coating. Both in vitro and in vivo experiments clearly revealed that the nanoprobes can effectively avoid capture by macrophages, and exhibited prolonged blood half-life to continuously enhance the contrast of blood vessels in a longer time window in susceptibility-weighted imaging (SWI), which enabled the delineation of the collaterals and ischemic penumbra. More importantly, combined with the diffusion-weighted imaging (DWI), the infarct core, collateral vessels, and the ischemic penumbra range can be identified simultaneously. In this context, the stroke progress including infarct core growth, collateral vessel formation, and penumbra distribution, can be better understood. This nanoprobe-based strategy thus offers a practical route for precise diagnosis of ischemic stroke, which remains a challenge for conventional MRI strategies.

Cerebral collateral circulation is a network of blood vessels which stabilizes blood flow and maintains cerebral perfusion whenever the main arteries fail to provide an adequate blood supply, as happens in ischemic stroke. These arterial networks are able to divert blood flow to hypoperfused cerebral areas. The extent of the collateral circulation determines the volume of the salvageable tissue, the so-called "penumbra". Clinically, this is associated with greater efficacy of reperfusion therapies (thrombolysis and thrombectomy) in terms of better short- and long-term functional outcomes, lower incidence of hemorrhagic transformation and of malignant oedema, and smaller cerebral infarctions. Recent advancements in brain imaging techniques (CT and MRI) allow us to study these anastomotic networks in detail and increase the likelihood of making effective therapeutic choices. In this narrative review we will investigate the pathophysiology, the clinical aspects, and the possible diagnostic and therapeutic role of collateral circulation in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost. Here, we review the focal cerebral ischemia models with an emphasis on the middle cerebral artery occlusion technique, a "gold standard" in surgical ischemic stroke models. Also, we highlight several histologic, genetic, and in vivo imaging approaches, including mouse stroke MRI techniques, that have the potential to enhance the rigor of preclinical stroke evaluation. Together, these efforts will pave the way for clinical interventions that can mitigate the negative impact of this devastating disease. [ABSTRACT FROM AUTHOR]

The pathophysiology of lacunar infarction is an evolving and debated field, where relevant information comes from histopathology, old anatomical studies and animal models. Only in the last years, have neuroimaging techniques allowed a sufficient resolution to directly or indirectly assess the dynamic evolution of small vessel occlusion and to formulate hypotheses about the tissue status and the mechanisms of damage. The core–penumbra concept was extensively explored in large vessel occlusions (LVOs) both from the experimental and clinical point of view. Then, the perfusion thresholds on one side and the neuroimaging techniques studying the perfusion of brain tissue were focused and optimized for LVOs. The presence of a perfusion deficit in the territory of a single small perforating artery was negated for years until the recent proposal of the existence of a perfusion defect in a subgroup of lacunar infarcts by using magnetic resonance imaging (MRI). This last finding opens pathophysiological hypotheses and triggers a neurovascular multidisciplinary reasoning about how to image this perfusion deficit in the acute phase in particular. The aim of this review is to summarize the pathophysiological issues and the application of the core–penumbra hypothesis to lacunar stroke. [ABSTRACT FROM AUTHOR]

By developing an analytical model considering the J 2 perturbation and small eccentricity, the effects of an in-track maneuver on the umbra and penumbra arcs of near-circular orbits are analyzed. The effectiveness of the analytical model is validated by comparing it with the numerical difference and a published model for the cylindrical eclipse. Three major conclusions are draw. First, the proposed analytical model agrees well with the numerical difference method in common situations, and the effect of an in-track maneuver on the eclipse arc center is much smaller than that on the eclipse arc length. Second, although the precision of the proposed analytical model decreases as the eccentricity increases, the effects of a small in-track maneuver on the orbital eclipse could be considered as small values in common situations. Those effects could be notable as the maneuver magnitude increases. Third, when the orbital sun angle approaches the critical angle defined by the ratio of the Earth radius to the satellite's semimajor axis, the effects of an in-track maneuver on the penumbra arc length could not be a small value any more, the precision of the analytical model would be considerably degraded. In the neighborhood of the critical angle, the differences between the effects of an in-track maneuver on the umbra, penumbra and cylindrical eclipse reach the maximum. Moreover, the reasons for the properties presented above are successfully explained by the analytical partial derivatives in the developed model. [ABSTRACT FROM AUTHOR]

Ischemic stroke is the most common cause of adult disability and one of the leading causes of death worldwide, with a serious socio-economic impact. In the present work, we used a new thromboembolic model, recently developed in our lab, to induce focal cerebral ischemic (FCI) stroke in rats without reperfusion. We analyzed selected proteins implicated in the inflammatory response (such as the RNA-binding protein HuR, TNFα, and HSP70) via immunohistochemistry and western blotting techniques. The main goal of the study was to evaluate the beneficial effects of a single administration of minocycline at a low dose (1 mg/kg intravenously administered 10 min after FCI) on the neurons localized in the penumbra area after an ischemic stroke. Furthermore, given the importance of understanding the crosstalk between molecular parameters and motor functions following FCI, motor tests were also performed, such as the Horizontal Runway Elevated test, CatWalk™ XT, and Grip Strength test. Our results indicate that a single administration of a low dose of minocycline increased the viability of neurons and reduced the neurodegeneration caused by ischemia, resulting in a significant reduction in the infarct volume. At the molecular level, minocycline resulted in a reduction in TNFα content coupled with an increase in the levels of both HSP70 and HuR proteins in the penumbra area. Considering that both HSP70 and TNF-α transcripts are targeted by HuR, the obtained results suggest that, following FCI, this RNA-binding protein promotes a protective response by shifting its binding towards HSP70 instead of TNF-α. Most importantly, motor tests showed that reduced inflammation in the brain damaged area after minocycline treatment directly translated into a better motor performance, which is a fundamental outcome when searching for new therapeutic options for clinical practice. [ABSTRACT FROM AUTHOR]

Amide proton transfer-weighted (APTw) imaging was an effective tool to reveal the tissue acidosis of acute ischemic stroke. This study aimed to evaluate the ability of APTw MRI to distinguish progressive penumbra and benign oligemia in the diffusion-perfusion mismatch region. 38 acute cerebral infarction patients who underwent a comprehensive MRI examination, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), APT imaging, and a follow-up scan in one week were recruited. There were 12 DWI/PWI match cases. The DWI/PWI mismatch patients were divided into 10 progressive cases and 16 stable cases according to the lesion size on the follow-up DWI image compared to the admission scan. Three ROIs: infarction lesion, peripheral, and contralateral normal regions were measured on each subject's MTRasym map. The Friedman test was used to compare the changes of MTRasym among three different regions within each group. The Kruskal-Wallis ANOVA test was used to compare them among the same region of different groups. The correlation between the MTRasym of the peripheral region and the lesion enlargement was analyzed by the Spearman test. The MTRasym at the infarction lesion of all three groups showed significant decrease to the contralateral normal tissue. In the progressive mismatch group, the MTRasym at the peripheral region within the DWI/PWI mismatch showed a significant difference with the contralateral normal region and no difference with the infarct core. Whereas both the MTRasym at the peripheral region of the stable mismatch and match groups had no significant difference with the contralateral side, but the differences were significant from those of the central core. When comparing the peripheral region of three groups, the MTRasym of the progressive mismatch group showed a significant decrease to that of the stable mismatch and match groups. The MTRasym of the peripheral region showed a negative correlation with lesion enlargement. APTw imaging is promising to stratify the heterogeneous PWI/DWI mismatch region and benefit the clinical treatment. [ABSTRACT FROM AUTHOR]

Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients. Absolute OEF was elevated in the affected (29.3 ± 3.4%) versus the contralateral hemisphere (25.5 ± 3.1%) of patients with large diffusion-perfusion lesion mismatch (P = 0.032). In these patients, OEF negatively correlated with relative CBF measured by dynamic susceptibility contrast MRI (P = 0.004), suggesting compensation for reduced flow. Patients with perfusion-diffusion match or no hypo-perfusion showed less OEF difference between hemispheres. Nine patients received longitudinal assessment and showed OEF ratio (affected to contralateral) of 1.2 ± 0.1 at baseline that normalized (decreased) to 1.0 ± 0.1 at follow-up three days later (P = 0.03). Our feasibility study demonstrates that QSM MRI can non-invasively quantify OEF in stroke patients, relates to perfusion status, and is sensitive to OEF changes over time. Clinical trial registration: Longitudinal MRI examinations of patients with brain ischemia and blood brain barrier permeability; clinicaltrials.org : NCT02077582.

Abstract Background Arterial spin labeling (ASL) is a recently used magnetic resonance imaging (MRI) perfusion technique in acute cerebrovascular stroke conditions; it can detect the hypo perfused areas on basis of qualitative and quantitative measurements and also identify the area at risk known as penumbra by detecting the diffusion/perfusion mismatch. The purpose of this study was to assess the role of ASL perfusion technique in management of acute ischemic stroke and its ability to predict the clinical outcome of acute stroke patients. The study was prospectively carried out on 33 patients clinically presented with acute stroke from the first of August 2020 till the first of August 2021. All cases were clinically assessed by stroke consultant followed by brain imaging including conventional MRI and ASL perfusion technique, based upon which management was established. These imaging data were correlated with the clinical outcome after 3 months using Modified Rankin Scale. Results Sixteen cases (48.48%) showed ischemic penumbra with diffusion perfusion mismatch with three cases presenting within the first 4 h managed by intravenous thrombolytic therapy and 13 cases presenting later than 4 h, 10 of whom were managed by endovascular intervention. The group with ischemic penumbra showed significant positive correlation with favorable clinical outcome while the group without ischemic penumbra showed significant positive correlation with poor clinical outcome. Quantitative ASL values were statistically significantly higher (p ≤ 0.05) in patients with favorable clinical outcome than those with poor clinical outcome. The estimated cut off values of ASL absolute cerebral blood flow and relative cerebral blood flow to predict favorable or poor outcome using ROC curve analysis were 19 ml/100gm/min and 74% compared to the contralateral side respectively. Conclusion The use of MRI as a primary diagnostic tool in arterial ischemic stroke with the application of non-contrast ASL perfusion sequence allows precise detection of perfusion deficit and diffusion perfusion mismatch (penumbra) and provides a reliable insight into outcome prediction.

Cerebral collateral circulation refers to the auxiliary vascular structures which compensate cerebral blood flow when it has been compromised due to stenosis or occlusion of the principal supplying arteries. They play a vital role in sustaining blood flow to the ischemic areas in acute, subacute or chronic phases of ischemic stroke or TIA. Good collateral circulation has shown protective effects towards a favorable functional outcome and a lower risk of recurrence of stroke. The benchmark mechanical thrombectomy trials utilized these collateral scoring methods to guide patient selection and prognosticate favorable outcome models. This shows a promising future of the collateral circulation for extending the time frame of the reperfusion therapies by optimally guiding patient selection and moving from a “time window” to a “tissue window.”