OBJECTIVE: 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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

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 ​h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 ​h. Within 6 ​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.

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.
CONCLUSIONS: 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.

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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

OBJECTIVE: 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.
CONCLUSIONS: 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.

BACKGROUND: The use of the Indigo CAT RX Aspiration System (Penumbra Inc.) during percutaneous coronary intervention has received limited study.
METHODS: We retrospectively examined the clinical, angiographic, and procedural characteristics, outcomes, and follow-up of patients who underwent mechanical aspiration thrombectomy with the Indigo CAT RX system (Penumbra Inc.) at a large tertiary care hospital between January 2019 and April 2023.
RESULTS: During the study period, 83 patients (85 lesions) underwent thrombectomy with the Indigo CAT RX. Mean patient age was 64.9 ± 14.48 years and 31.2% were women. The most common presentations were ST-segment elevation myocardial infarction (MI) (66.2%) and non-ST-segment elevation MI (26.5%). A final thrombolysis in MI flow grade of 3 and final myocardial blush grade of 3 were achieved in 76% and 46% of the cases, respectively. Technical success was achieved in 88.9% of the cases that included Indigo CAT RX treatment only, compared with 57.1% of the cases that also included manual aspiration. There were no device-related serious adverse events. At 30-day postprocedure, the incidence of major adverse cardiac events (composite of cardiovascular death, recurrent MI, cardiogenic shock, new or worsening New York Heart Association Class IV heart failure, stroke) was 8.5%: 1.3% stroke (postprocedure, in-hospital), 1.3% MI, 6.1% cardiac death, and 7.5% developed cardiogenic shock.
CONCLUSIONS: Use of the Indigo CAT RX system is associated with high technical success and acceptable risk of complications, including stroke.