Perfusion Deficits Research Articles

Abstract TP41: Assessing The Relationship Between The Los Angeles Motor Scale And Computed Tomography Perfusion Parameters In Acute Ischemic Stroke Secondary To Large Vessel Occlusion

The Los Angeles Motor Scale (LAMS) is a rapid pre-hospital scale used to predict stroke severity. LAMS has also been shown to accurately predict large vessel occlusions (LVOs), however, to date there is no study exploring whether LAMS correlates with CT perfusion (CTP) parameters used to decide mechanical thrombectomy (MT) candidacy. The aim of this study is to elucidate the potential relationship between LAMS and these CTP parameters. We retrospectively reviewed patients with LVO between September 2019 and October 2021. Patients were included if they had available CTP data and neurologic exam on admission. LAMS was documented based on EMS exam or scored retrospectively based on admission neurologic exam. CTP data was processed by RAPID (IschemaView, Menlo Park, CA) with ischemic core volume (rCBF < 30%), Tmax volume (Tmax > 6 second delay), hypoperfusion index (HI), and CBV index. Spearman’s correlations were performed between LAMS and the aforementioned CTP parameters. Eighty-five patients were included, of which 11 had intracranial internal carotid artery (ICA) occlusions, 52 had M1 occlusions, and 22 had proximal M2 occlusions. Of all patients, 26 had LAMS of 0-3, and 59 had LAMS of 4-5. In all cases, LAMS was positively correlated with CBF <30% (Correlation Coefficient (CC): 0.32, p < 0.01), Tmax > 6 s (CC:0.23, p< 0.04), HI (CC:0.27, p < 0.01), and negatively correlated with CBV index (CC:-0.24, p < 0.05). These relationships between LAMS and CBF < 30% and HI were more pronounced in M1 occlusions (CC:0.42, p< 0.01; 0.34, p< 0.01 respectively) and proximal M2 occlusions (CC:0.53, p<0.01; 0.48, p< 0.03 respectively). LAMS also correlated with Tmax > 6 s in M1 occlusions (CC:0.42, p< 0.01), and negatively correlated with CBV index in M2 occlusions (CC:-0.69, p< 0.01). There was no significant correlation between LAMS and CTP parameters in intracranial ICA occlusions. Our results indicate that LAMS is positively correlated with estimated ischemic core, perfusion deficit, and HI, and negatively correlated with CBV index in patients with LVO. Vessel based analyses reveal stronger correlations with M1 and M2 occlusions. This is the first study showing that the LAMS may be correlated with estimated ischemic core and collateral status parameters in patients with LVO.

Worsened Stroke Outcome in a Model of Preeclampsia is Associated With Poor Collateral Flow and Oxidative Stress.

Preeclampsia increases the incidence of maternal stroke, a devastating condition that is on the rise. We investigated stroke outcome in a model of experimental preeclampsia with and without treatment with clinically relevant doses of magnesium sulfate (experimental preeclampsia+MgSO4) compared to normal late-pregnant and nonpregnant rats. Transient middle cerebral artery occlusion was used to induce focal stroke for either 1.5 or 3 hours. Infarct volume and hemorrhagic transformation were determined as measures of stroke outcome. Changes in core middle cerebral artery and collateral flow were measured by dual laser Doppler. The relationship between middle cerebral artery perfusion deficit and infarction was used as a measure of ischemic tolerance. Oxidative stress and endothelial dysfunction were measured by 3-nitrotyrosine and 8-isoprostane, in brain and serum, respectively. Late-pregnant animals had robust collateral flow and greater ischemic tolerance of brain tissue, whereas experimental preeclampsia had greater infarction that was related to poor collateral flow, endothelial dysfunction, and oxidative stress. Importantly, pregnancy appeared preventative of hemorrhagic transformation as it occurred only in nonpregnant animals. MgSO4 did not provide benefit to experimental preeclampsia animals for infarction. Stroke outcome was worse in a model of preeclampsia. As preeclampsia increases the risk of future stroke and cardiovascular disease, it is worth understanding the influence of preeclampsia on the material brain and factors that might potentiate injury both during the index pregnancy and years postpartum.

Case Report: Successful Anterior Circulation Thrombectomy After 24 Hours in an Adolescent

BackgroundArterial ischemic stroke in children comes with the potential for morbidity and mortality and can result in high cost of care and decreased quality of life among survivors. Children with arterial ischemic stroke are increasingly being treated with mechanical thrombectomy, but little is known about the risks and benefits 24 hours after a patient’s last known well (LKW) time. MethodsA 16-year-old female presented with acute onset of dysarthria and right hemiparesis with LKW time 22 hours prior. Pediatric National Institutes of Health Stroke Scale score was 12. Magnetic resonance imaging showed diffusion restriction and T2 hyperintensity primarily in the left basal ganglia. Magnetic resonance angiography revealed left M1 occlusion. Arterial spin labeling showed a large apparent perfusion deficit. She underwent thrombectomy with TICI3 recanalization 29.5 hours after LKW time. ResultsAt 2-month follow-up, her examination showed moderate right-hand weakness and mild diminished sensation of the right arm. ConclusionsAdult thrombectomy trials include patients up to 24 hours from their LKW time and suggest that some patients maintain a favorable perfusion profile for over 24 hours. Without intervention many go on to experience infarct expansion. The persistence of a favorable perfusion profile likely reflects robust collateral circulation. We hypothesized our patient was relying on collateral circulation to maintain the noninfarcted areas of her left middle cerebral artery territory. Owing to concern for eventual collateral failure, thrombectomy outside of the 24-hour window was performed. This case serves as a call to action to better understand the impact of collateral circulation on cerebral perfusion in children with large vessel occlusions and delineate which children may benefit from thrombectomy in a delayed time window.

Glial cell activity in cardiovascular diseases and risk of acute myocardial infarction

Growing evidence indicates that the pathophysiological link between the brain and heart underlies cardiovascular diseases, specifically acute myocardial infarction (AMI). Astrocytes are the most abundant glial cells in the central nervous system and provide support/protection for neurons. Astrocytes and peripheral glial cells are emerging as key modulators of the brain-heart axis in AMI, by affecting sympathetic nervous system activity (centrally and peripherally). This review, therefore, aimed to gain an improved understanding of glial cell activity and AMI risk. This includes discussions on the potential role of contributing factors in AMI risk, i.e., autonomic nervous system dysfunction, glial-neurotrophic and ischemic risk markers [glial cell line-derived neurotrophic factor (GDNF), astrocytic S100 calcium-binding protein B (S100B), silent myocardial ischemia, and cardiac troponin T (cTnT)]. Consideration of glial cell activity and related contributing factors in certain brain-heart disorders, namely, blood-brain barrier dysfunction, myocardial ischemia, and chronic psychological stress, may improve our understanding regarding the pathological role that glial dysfunction can play in the development/onset of AMI. Here, findings demonstrated perturbations in glial cell activity and contributing factors (especially sympathetic activity). Moreover, emerging AMI risk included sympathovagal imbalance, low GDNF levels reflecting prothrombic risk, hypertension, and increased ischemia due to perfusion deficits (indicated by S100B and cTnT levels). Such perturbations impacted blood-barrier function and perfusion that were exacerbated during psychological stress. Thus, greater insights and consideration regarding such biomarkers may help drive future studies investigating brain-heart axis pathologies to gain a deeper understanding of astrocytic glial cell contributions and unlock potential novel therapies for AMI.

Novel transdermal curcumin therapeutic preserves endothelial barrier function in a high-dose LPS rat model

Sepsis is a devastating complication of infection and injury that, through widespread endothelial dysfunction, can cause perfusion deficits and multi-organ failure. To address the recognised need for therapeutics targetting the endothelial barrier, a topical formulation (CUR; VASCEPTOR™; Vascarta Inc, Summit, NJ) was developed to transdermally deliver bio-active concentrations of curcumin—an anti-inflammatory and nitric oxide promoter. Male, Sprague Dawley rats were treated daily with lipopolysaccharide (LPS, 10 mg/kg, IP) to induce endotoxemia, and topical applications of Vehicle Control (LPS + VC; N = 7) or Curcumin (LPS + CUR; N = 7). A third group received neither LPS nor treatment (No-LPS; N = 8). After 72 h, animals were surgically prepared for measurements of physiology and endothelial dysfunction in the exteriorised spinotrapezius muscle through the extravasation of 67 kDa TRITC-BSA (albumin) and 500 kDa FITC-dextran (dextran). At 72 h, LPS + VC saw weight loss, and increases to pulse pressure, lactate, pCO2, CXCL5 (vs No-LPS) and IL-6 (vs 0 h; p < 0.05). LPS + CUR was similar to No-LPS, but with hypotension. Phenylephrine response was increased in LPS + CUR. Regarding endothelial function, LPS + CUR albumin and dextran extravasation were significantly reduced versus LPS + VC suggesting that Curcumin mitigated endotoxemic endothelial dysfunction. The speculated mechanisms are nitric oxide modulation of the endothelium and/or an indirect anti-inflammatory effect.

Long-term lung perfusion changes related to COVID-19: a dual energy computed tomography study

Although the findings of acute new coronavirus disease (COVID-19) infection on dual-energy computed tomography (DECT) have recently been defined, the long-term changes in lung perfusion associated with COVID-19 pneumonia have not yet been clarified. We aimed to examine the longterm course of lung perfusion in COVID-19 pneumonia cases using DECT and to compare changes in lung perfusion to clinical and laboratory findings. On initial and follow-up DECT scans, the presence and extent of perfusion deficit (PD) and parenchymal changes were assessed. The associations between PD presence and laboratory parameters, initial DECT severity score, and symptoms were evaluated. The study population included 18 females and 26 males with an average age of 61.32 ± 11.3 years. Follow-up DECT examinations were performed after the mean of 83.12 ± 7.1 (80-94 days) days. PDs were detected on the follow-up DECT scans of 16 (36.3%) patients. These 16 patients also had ground-glass parenchymal lesions on the follow-up DECT scans. Patients with persistent lung PDs had significantly higher mean initial D-dimer, fibrinogen, and C-reactive protein values than patients without PDs. Patients with persistent PDs also had significantly higher rates of persistent symptoms. Ground-glass opacities and lung PDs associated with COVID-19 pneumonia can persist for up to 80-90 days. Dual-energy computed tomography can be used to reveal long-term parenchymal and perfusion changes. Persistent PDs are commonly seen together with persistent COVID-19 symptoms.

The prognostic value of single photon emission computed tomography (SPECT) myocardial perfusion imaging is independent of left ventricular size.

Many variables have been shown to impact accuracy and prognostic power of myocardial perfusion imaging (MPI); however, effects of left ventricular size have not been extensively studied. In particular, perfusion defects in smaller hearts could be overlooked due to partial volume averaging, potentially reducing the prognostic power of MPI. We determined stress total perfusion deficit (TPD) and rest end diastolic volume (REDV) from single photon emission computed tomography (SPECT) MPI in consecutive patients without pathologically dilated left ventricles. Area under the curve (AUC) and Cox regression analysis were used to assess prediction of subsequent major adverse cardiac events [MACE-death, hospitalized acute myocardial infarction (AMI), hospitalized unstable angina, late revascularization]. Analyses were stratified by sex and REDV tertile. The analytic population included 2,503 patients (965 men and 1,538 women). Outcomes were assessed over an average of 6.4±2.3 years. MACE was observed in 254 (26.3%) of 965 men and 261 (17.0%) of 1,538 women. Stress TPD showed significant AUCs for stratifying MACE risk regardless of sex and REDV tertile (all P<0.05). In Cox regression analysis, increasing stress TPD (but not REDV) was associated with MACE in both men and women. There was no significant TPD*REDV interaction. In conclusion, we found the prognostic power of SPECT MPI to be independent of left ventricular size.

The first application of intraoperative mri for analysis of cerebral perfusion in surgical brain revascularization

Effectiveness of surgical revascularization in patients with chronic cerebral ischemia depends on restoration of circulation in the damaged artery. Modern methods do not take into account dynamic changes in cerebral perfusion after extra-intracranial microvascular anastomosis (EICMA) and do not allow timely localizing the areas of persistent perfusion deficit. We propose a new method for determining the tactics of surgical cerebral revascularization based on intraoperative MRI (iMRI) perfusion data. This method provides the earliest information on intraoperative brain reperfusion. To develop the principles of dynamic assessment of cerebral blood flow using intraoperative ASL perfusion during surgical revascularization in patients with chronic cerebral ischemia and to determine the indications for additional anastomoses. Surgical revascularization with intraoperative MRI perfusion was performed in 27 patients between March 2022 and April 2023. There were 10 patients with post-thrombotic occlusion of internal carotid artery, 4 patients with occlusion of middle cerebral artery and 13 patients with moyamoya disease. All patients underwent MRI before surgery. After imposing the first EICMA, all patients underwent ASL perfusion for analysis of residual hypoperfusion zones, signs of local hyperperfusion and indications or contraindications for additional revascularization with the second donor branch. In all cases, iMRI made it possible to determine the tactics of brain revascularization using one or two EICMA. In 17 cases, ASL perfusion confirmed the targeted improvement of cerebral blood flow (CBF) in the entire hemisphere or middle cerebral artery basin. Only one EICMA was imposed in these cases. In 10 cases, a single anastomosis was insufficient for restoration of blood flow. These patients underwent additional revascularization with the second donor branch (35.7%). In all cases, we achieved significant quantitative improvement in CBF and volume of brain tissue with restored blood flow (ASPECTS scale). A single EICMA was followed by increase in CBF and areas of restored blood flow by almost 2 times (22.7±9.6 ml/100 g/min and 4.7±1.8 scores (ASPECTS) before surgery vs. 39.4±16.4 ml/100 g/min and 4.7±1.8 scores after EICMA). In the double EICMA group, these parameters increased by almost 3 times (18±3.1 ml/100 g/min and 3.8±0.9 scores before surgery vs. 57±11.4 ml/100 g/min and 7.7±1.5 scores after double EICMA). All patients had no complications. Neurological status improved immediately after surgery in 9 patients (33.3%), stable postoperative period was observed in 12 cases (44.4%). Six (22.2%) patients had transient neurological deficit associated with hyperperfusion syndrome that regressed within a few days after surgery. There were no persistent ischemic complications. Intraoperative ASL perfusion is an effective and informative tool for determining the degree of restoration of blood flow. We can timely adjust surgical strategy, determine the indications or contraindications for additional revascularization and exclude early ischemic complications using this method.

Assessment of perfusion deficit with early phases of [18F]PI-2620 tau-PET versus [18F]flutemetamol-amyloid-PET recordings

PurposeCharacteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan. However, there has hitherto been no comparison of early-phase amyloid- and tau-PET as surrogates for deficits in perfusion/metabolism. Therefore, we undertook to compare [18F]flutemetamol-amyloid-PET and [18F]PI-2620 tau-PET as “one-stop shop” dual purpose tracers for the detection of neurodegenerative disease.MethodsWe obtained early-phase PET recordings with [18F]PI-2620 (0.5–2.5 min p.i.) and [18F]flutemetamol (0–10 min p.i.) in 64 patients with suspected neurodegenerative disease. We contrasted global mean normalized images (SUVr) in the patients with a normal cohort of 15 volunteers without evidence of increased pathology to β-amyloid- and tau-PET examinations. Regional group differences of tracer uptake (z-scores) of 246 Brainnetome volumes of interest were calculated for both tracers, and the correlations of the z-scores were evaluated using Pearson’s correlation coefficient. Lobar compartments, regions with significant neuronal injury (z-scores < − 3), and patients with different neurodegenerative disease entities (e.g., Alzheimer’s disease or 4R-tauopathies) served for subgroup analysis. Additionally, we used partial regression to correlate regional perfusion alterations with clinical scores in cognition tests.ResultsThe z-scores of perfusion-weighted images of both tracers showed high correlations across the brain, especially in the frontal and parietal lobes, which were the brain regions with pronounced perfusion deficit in the patient group (R = 0.83 ± 0.08; range, 0.61–0.95). Z-scores of individual patients correlated well by region (R = 0.57 ± 0.15; range, 0.16–0.90), notably when significant perfusion deficits were present (R = 0.66 ± 0.15; range, 0.28–0.90).ConclusionThe early perfusion phases of [18F]PI-2620 tau- and [18F]flutemetamol-amyloid-PET are roughly equivalent indices of perfusion defect indicative of regional and lobar neuronal injury in patients with various neurodegenerative diseases. As such, either tracer may serve for two diagnostic channels by assessment of amyloid/tau status and neuronal activity.

Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection

BackgroundThe definition of sudden sensorineural hearing loss (SSNHL) is broadly accepted as acute sensorineural hearing loss of more than 30 dB over at least three consecutive frequencies in a pure-tone audiogram (PTA). Acute audiovestibular loss is common with ischaemic stroke in the territory of the anterior inferior cerebellar artery (AICA). However, cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction.Case presentationA 51-year-old man suddenly developed acute hearing loss (AHL) in his left ear and vertigo. On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had apogeotropic nystagmus during head turns to either side. The head impulse test (HIT) was normal. PTA showed mild unilateral SSNHL in the left ear. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed territorial perfusion deficits in the left posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) without infarction. Two months later, the patient had no vertigo but still had hearing impairment in his left ear. A follow-up PTA documented persistent unilateral SSNHL in the left ear. Additionally, perfusion computed tomography (CT) showed that perfusion deficits remained in the left cerebellum along the PICA and AICA territories.ConclusionsOur case highlights a case of AHL and vertigo presented by isolated cerebellar hypoperfusion without infarction. It is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm this possibility through brain magnetic resonance imaging (MRI), including PWI, and magnetic resonance angiography (MRA).

Can angiographic Flat Detector Computed Tomography blood volume measurement be used to predict final infarct size in acute ischemic stroke?

Introduction and purposeFlat detector computed tomography (FD-CT) technology is becoming more widely available in the angiography suites of comprehensive stroke centers. In patients with acute ischemic stroke (AIS), who are referred for endovascular therapy (EVT), FD-CT generates cerebral pooled blood volume (PBV) maps, which might help in predicting the final infarct area. We retrospectively analyzed pre- and post-recanalization therapy quantitative PBV measurements in both the infarcted and hypoperfused brain areas of AIS patients referred for EVT. Materials and methodsWe included AIS patients with large vessel occlusion in the anterior circulation referred for EVT from primary stroke centers to our comprehensive stroke center. The pre- and post-recanalization FD-CT regional relative PBV (rPBV) values were measured between ipsilateral lesional and contralateral non-lesional areas based on final infarct area on post EVT follow-up cross-sectional imaging. Statistical analysis was performed to identify differences in PBV values between infarcted and non-infarcted, recanalized brain areas. ResultsWe included 20 AIS patients. Mean age was 63 years (ranging from 36 to 86 years). The mean pre- EVT rPBV value was 0.57 (±0.40) for infarcted areas and 0.75 (±0.43) for hypoperfusion areas. The mean differences (Δ) between pre- and post-EVT rPBV values for infarcted and hypoperfused areas were respectively 0.69 (±0.59) and 0.69 (±0.90). We found no significant differences (p > 0.05) between pre-EVT rPBV and ΔrPBV values of infarct areas and hypoperfusion areas. ConclusionAngiographic PBV mapping is useful for the detection of cerebral perfusion deficits, especially in combination with the fill run images. However, we were not able to distinguish irreversibly infarcted tissue from potentially salvageable, hypoperfused brain tissue based on quantitative PBV measurement in AIS patients.

Long term outcomes of 'Christmas Tree' banding for haemodialysis access induced distal ischemia: A 13-year experience.

The reduction in distal arterial flow following arteriovenous fistula (AVF) creation can cause a perfusion deficit known as haemodialysis access induced distal ischemia (HAIDI). Various techniques have been advocated to treat this difficult problem with varying success. We present the long-term outcomes following a novel banding technique. 46 patients in this cohort from 2008 to 2021 underwent a novel banding procedure using a Dacron™ patch shaped with one slit-end and saw-tooth edges (resulting in a 'Christmas-tree' pattern) to provide a ratchet mechanism to progressively constrict the fistula outflow. Real-time finger perfusion pressure monitoring allowed an accurate reduction in AVF flow whilst increasing distal arterial perfusion pressure. Baseline characteristic were recorded and Kaplan-Meier survival curves were obtained to calculate the post-intervention primary, assisted primary and secondary patency. 29 patients presented with rest pain and 11 presented with tissue loss due to distal ischemia. The post-intervention primary access patency was 100%, 98%, 78% and 61% at 30, 60 and 180 days and 1 year respectively. Complete resolution of symptoms was achieved in 74% (n = 34) of patients and a partial response needing no further intervention was achieved in 11% (n = 5) of patients. A Youden index calculation suggested that digital pressures of 41 mm Hg or lower in an open AVF were highly sensitive for symptomatic hand ischemia whereas pressures greater than 65 mm Hg ruled out distal ischemia. 'Christmas-tree' banding with on table finger systolic pressures is not only an efficacious and durable method for treating HAIDI but also preserves fistula patency.

Perfusion Deficits in Patients with Posterior Reversible Encephalopathy Syndrome: a Retrospective, Two-Center Study.

Posterior reversible encephalopathy syndrome (PRES) is manifested by acute neurological symptoms in patients with varied predisposing factors and characteristic findings on brain imaging. Cerebrovascular autoregulation is thought to be altered in PRES. However, it remains unclear whether cerebral hypoperfusion or hyperperfusion is the initiating event. We aimed to describe the brain perfusion status in untreated patients with PRES. Patients with PRES who underwent cerebral perfusion studies on presentation were retrospectively identified from (1) a prospective database of patients with PRES admitted to Saint Mary's Hospital, Mayo Clinic, Rochester from January 2005 to December 2021 and (2) University of Nebraska Medical Center electronic database from January 2010 to December 2021. Demographics, past medical history, presenting symptoms, cause of PRES, and clinical outcomes were recorded. Brain imaging studies were reviewed. We recorded the location of brain lesions, the time from symptoms onset to perfusion study, blood pressure at the time of the perfusion study, and blood pressure lowering treatments. Five patients (four women, median age 66years) were included. Causes of PRES were acute hypertension (n = 3), perioperative blood pressure fluctuations, and treatment with pazopanib. Four patients had chronic hypertension. Presenting symptoms were encephalopathy (n = 5), focal neurological symptoms (n = 4), and seizures (n = 2). All patients underwent computed tomography (CT) perfusion performed within 12h of symptoms onset. All but one patient was hypertensive at the time of CT perfusion. Scans showed diffuse cerebral hypoperfusion, more pronounced in the corona radiata and areas with brain edema. No patient had critical cerebral ischemia or arterial vasoconstriction on CT angiogram. Patients with PRES can have cerebral hypoperfusion despite severe hypertension. A perfusion study in the acute setting may be helpful to better understand the perfusion status and guide blood pressure treatment.

Brain involvement in glaucoma: A new target in neuroprotection

AbstractGlaucoma is one of the leading causes of blindness worldwide. The mechanisms underlying glaucomatous involvement of the central nervous system are still not completely known. It has been hypothesized that glaucomatous degeneration may be the result of anterograde transsynaptic neurodegeneration triggered by ganglion cells' death. However, it has been also postulated that in some cases it may be the consequence of neurodegenerative diseases of the central nervous system such as Alzheimer's' Disease. Autophagy and perfusion deficits have been also implicated in the etiopathogenesis of glaucoma. The introduction of new neuroimaging techniques may help to extend the knowledge about this disease, consent early diagnosis and could be a valuable tool for assessing the therapeutic efficacy of novel neuroprotective strategies.

Endothelial mitochondrial dysfunction during Cerebral Amyloid Angiopathy and Hyperhomocysteinemia

AbstractBackgroundHyperhomocysteinemia (HHcy), or high levels of homocysteine, is considered a risk factor for vascular disease. Cardiovascular (CV) risk factors, such as HHcy, may lead to exacerbation of cerebral amyloid angiopathy (CAA) due to their detrimental effects on cerebrovascular function. Cerebrovascular function is regulated, in part, by endothelial cells (EC), the most important cellular component of the blood‐brain barrier (BBB). Dysfunctional ECs may lead to deficits in vascular perfusion, clearance, and may eventually result in neuroinflammation, microhemorrhages, and neurodegeneration. EC mitochondria serve as sensors of cellular damage and mediate downstream pathways such as cell death and inflammation. In ECs, mitochondrial dysfunction may lie as the point of convergence of CV risk factors and amyloid β (Aβ)‐induced neurovascular dysfunction. Understanding the mitochondrial deficits elicited by CV risk factors, Aβ, or their combination, may open roads to new therapeutics aimed at preserving mitochondrial function. Indeed, we have previously shown that carbonic anhydrase inhibitors (CAi) reduce amyloid‐induced cell death and mitochondrial dysfunction. Here, we aim to understand the changes occurring in EC mitochondria during Aβ‐ and mixed (Aβ+HHcy)‐ vascular pathologies. In addition, we will assess the therapeutic potential of CAi in such pathologies.MethodHuman brain microvascular ECs were challenged with Aβ, Hcy, or the combination in the presence or absence of CAi. EC barrier properties and changes in mitochondrial function were assessed.ResultThe presence of Aβ or Hcy independently increased BBB permeability, and, when both present, Hcy worsened Aβ‐induced barrier permeability; these effects were prevented by CAi. Preliminary data suggests that the mitochondrial ATP production is impaired in the presence of Aβ40‐E22Q (Dutch mutant) but not in the presence of Hcy. These results may be a reflection of the observed deficits in mitochondrial oxygen consumption rate (OCR).ConclusionThe EC barrier is negatively affected by the presence of Aβ, and Hcy aggravates Aβ‐induced BBB permeability. The presence of Aβ40‐E22Q affects mitochondrial OCR and ATP production, indicative of changes in cellular metabolism and mitochondrial dysfunction. These results suggest a central role of the mitochondria as a mediator of vascular dysfunction in the presence of Aβ.

Arterial spin labeling magnetic resonance imaging quantifies tissue perfusion around foot ulcers.

Tools that quantify tissue perfusion of the foot are deficient, contributing to the uncertainty in predicting ulcer healing potential. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths using a novel application of pseudo-continuous arterial spin labeling magnetic resonance imaging. Ten diabetic patients with neuropathic wounds and 20 healthy volunteers without wounds were recruited. Wounds were graded according to the Wound, Ischemia, Foot Infection (WIfI) system. All subjects underwent a noncontrasted ASL MRI of the foot for perfusion measurements. For healthy volunteers, perfusion was compared at rest and during sustained toe flexion between four regions: lateral plantar, medial plantar, lateral calcaneal, and medial calcaneal. Evaluations of diabetic volunteers compared perfusion between four zones: wound, near border, far border, and remote. Remote zone perfusion in diabetics was compared with perfusion in the plantar foot of healthy volunteers. There were 11 wounds, which were located over the metatarsal heads in five, the stump of a transmetatarsal amputation in three, the heel in two, and the mid foot in one. The median WIfI stage was 2. One patient had a WIfI ischemia grade of 1; the remaining patients' grades were 0. The mean ankle-brachial index was 1.0± 0.3. There were two patients with a WIfI foot infection grade of 1; the remaining patients' grades were 0. In healthy volunteers, plantar foot perfusion with sustained toe flexion was 43.9± 1.7mL/100g/min and significantly higher than perfusion at rest (27.3± 2.7mL/100g/min; P< .001). In diabetic patients, perfusion at the wound, near border, far border, and remote regions was 96.1± 10.7, 92.7± 9.4, 73.4± 8.2, and 62.8± 2.7mL/100g/min. Although this perfusion pattern persisted throughout the depth of the wound, perfusion decreased with tissue depth. In the near border, perfusion at 20% of the wound depth was 124.0± 35.6mL/100g/min and 69.9± 10.1mL/100g/min at 100% (P= .006). Lastly, remote perfusion in diabetics was 2.3 times the plantar perfusion in healthy volunteers (27.3± 2.7mL/100g/min; P< .001). The pattern of resting tissue perfusion around nonischemic diabetic foot ulcers was successfully quantified with arterial spin labeling magnetic resonance imaging. Diabetic patients with wounds were hyperemic compared withhealthy volunteers. There was a 1.5-fold increase in peri-wound tissue perfusion relative to the rest of the foot. This study is the first step in developing a tool to assess the perfusion deficit in ischemic wounds.

IBC-Ox24 Routine Oversewing of Staple Lines to Prevent Leaks is Unnecessary in Patients with Normal Iintraoperative Indocyanine Green (ICG) Perfusion Studies Undergoing Sleeve Gastrectomy

Abstract Anastomotic staple line leaks following laparoscopic sleeve gastrectomy is a devastating complication. Gastric ischemia and poor tissue perfusion has been hypothesized to be a contributing factor. Various interventions including oversewing of staple lines are commonly used hoping to decrease staple line leaks. Indocyanine green (ICG) can be used to assess bowel perfusion and anastomotic viability following laparoscopic surgery. 50 consecutive patients underwent laparoscopic sleeve gastrectomy utilizing intravenous administration of ICG to assess tissue perfusion and the need for staple line oversewing. Methods 50 consecutive patients undergoing laparoscopic sleeve gastrectomy were studied intraoperatively after completion of sleeve gastrectomy using intravenous administration of ICG. 7.5 mg of ICG was administered intravenously. Arterial perfusion and end stage tissue perfusion of the completed sleeve gastrectomy was then evaluated. Vascular arterial inflow of the gastric cardia, body and antrum was carefully evaluated both anteriorly and posteriorly for evidence of delayed tissue perfusion or tissue ischemia. Results In all cases the staple line was examined for staple line formation and evidence of poor tissue perfusion using ICG. Both anterior and posterior evaluation was performed of the distal esophagus, gastric cardia, gastric body and antrum. Absence of tissue perfusion in the resected gastric body was used as a comparison control in all cases. ICG perfusion of the gastric cardia, body and antrum was found to be excellent and brisk in all patients. There were no areas of decreased perfusion or tissue ischemia. Oversewing of the staple line was avoided in all cases. Hemostatic clips were deployed as needed for staple line bleeding until there was no evidence of bleeding on visual inspection and final ICG administration. Patients were followed for evidence of leakage or obstruction for 30 days following completion of the sleeve gastrectomy. There were no leaks, there were no deaths. There were no obstructions and no readmissions. There were no complications related to administration of ICG. Average operative time was 48.7 minutes. Conclusions Our series of 50 consecutive sleeve gastrectomies utilizing ICG to assess for tissue perfusion demonstrated no evidence of tissue perfusion deficiencies along the staple line or at the angle of His. Staple line oversewing was not used in any patients. Staple line oversewing in cases without evidence of tissue perfusion deficits on ICG evaluation following sleeve gastrectomy is unnecessary. Further multicenter studies and prospective randomized series are necessary to confirm these initial findings.

Abstract 10514: Compromised Cerebral Artery Integrity is Associated With Brain Tissue Injury and Cognition Deficits in Adolescents With Complex Congenital Heart Disease

Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injury in regions associated with cognitive deficits. Alteration in cerebral artery integrity (CAI), as measured by arterial transit time (ATT), may lead to perfusion deficits, and be a potential cause of brain injury in CCHD. To date, there are no reports of CAI in CCHD or associations between CAI, brain tissue integrity, and cognition in CCHD. Methods: 70 subjects (37 CCHD / 33 controls), 14-18 years of age, undergone surgical palliation (CCHD), and no contraindications for a magnetic resonance imaging (MRI) and healthy controls (age- and sex-matched) participated. Participants completed cognitive testing (Montreal Assessment of Cognition [MoCA] and the Wide Range Assessment of Memory and Learning [General Memory Index, GMI]) and brain MRI using 3.0 Tesla scanner. ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures), and regional brain mean diffusivity [MD] (measure of tissue integrity) were computed in whole brain. Descriptive, partial correlations, and ANCOVA analyses used (covariates, age and sex). Results: Mean MoCA [23.1 ± 4.1 vs. 28.1 ± 2.3; p &lt;.001] and GMI scores [86.8 ± 15.4 vs. 110.3 ± 14.5; p&lt;.001] show significant cognitive deficits in CCHD compared to controls. ATT was significantly increased in CCHD vs controls (mean ± SD, sec, 1.3±0.13 vs 1.22±0.13, p=0.02), respectively, indicating compromised CAI. Partial correlations between ATT, MD values, and cognition (covariates, age and sex, p&lt; 0.005) showed significant associations in various areas including the hippocampus, prefrontal cortices, cerebellum, frontal white matter, anterior and posterior cingulate, frontal cortex, temporal cortices, and midbrain. Conclusion: Adolescents with CCHD have prolonged ATTs compared to controls indicative of compromised CAI and altered cerebral perfusion. CAI is significantly associated with alterations in regional brain tissue integrity and cognitive impairment. Further evaluation is needed to test interventions to increase cerebral perfusion and to protect neural tissue.

99mTc-sestamibi and 18F-fluorodeoxyglucose imaging in patients with cardiogenic shock: A pilot study.

Whether perfusion/metabolism imaging differs between matched ST-segment elevation myocardial infarction (STEMI) patients with and without cardiogenic shock (CS) remains unknown. Seventeen STEMI patients with CS (13 men, 60 ± 12 years) and 16 matched STEMI patients without CS (15 men, 54 ± 15 years) were prospectively recruited. All patients underwent baseline 99mTc-sestamibi/18F-fluorodeoxyglucose (FDG) imaging and echocardiography 6 ± 2 days post-infarction. Nine patients with CS and seven without CS had repeated imaging 98 ± 7 days post-infarction. The total perfusion deficit (TPD) and total FDG uptake deficit (TFD) were calculated to assess the percentages of impaired perfusion and metabolism over the left ventricle. Patients were followed up for 337 days (213-505 days) and the major adverse cardiac events (MACE) were recorded. TPD was greater in patient with CS and was independently related to the presence of CS (OR: 4.36, p = 0.013). Both acute- and convalescent TFD were inversely related to the improvement ratio of LVEF (r-values: -0.62, -0.73; both p < 0.05). MACE occurred in 16 patients (10 CS and 6 non-CS), and acute TFD was predictive of MACE in those with CS (HR: 2.06, p = 0.038). In this pilot study, we demonstrated that STEMI patients with CS had a significantly increased TPD, which was relevant to the presence of CS. Acute TFD was associated with improvement in LVEF, and was predictive of MACE in patients with CS.

November 2022 Stroke Highlights

HomeStrokeVol. 53, No. 11November 2022 Stroke Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBNovember 2022 Stroke Highlights José Rafael Romero José Rafael RomeroJosé Rafael Romero https://orcid.org/0000-0002-1101-2950 Search for more papers by this author Originally published24 Oct 2022https://doi.org/10.1161/STROKEAHA.122.041383Stroke. 2022;53:3249is related toPrevalence and Predictors of Food Insecurity Among Stroke Survivors in the United StatesIs It About the Destination or About the Journey?Importance of Delayed Reperfusions in Patients With Incomplete ThrombectomyPrevalence and Predictors of Food Insecurity Among Stroke Survivors in the United StatesFood insecurity (FI) may interfere with adequate secondary stroke prevention. Kim-Tenser and colleagues assessed FI prevalence and trends using data from the US National Health and Nutrition Examination Survey survey (1999–2015). Food security was categorized as full, marginal, low, or very low, with the last 2 categories constituting FI. Stroke data were based on self-report. Among 48 242 participants, 1877 reported a stroke. FI was reported in 17% of participants with stroke and 12% of those without stroke. Predictors of FI included Black race, Hispanic ethnicity, low education, low income, non-married status, diabetes, smoking, and obesity. In age-adjusted analysis, FI increased over the study period from 7.8% to 42.1% in stroke survivors, and 8% to 17% in stroke-free participants. This study highlights FI as a growing adverse social determinant of health and modifiable social factor for stroke prevention targeting vulnerable groups. See p 3369.Yield of Dual Therapy with Statin and Ezetimibe in the Treat Stroke to Target TrialAmarenco and colleagues conducted a post-hoc analysis of the Treat Stroke to Target trial which randomized patients to dual therapy (statin and ezetimibe) versus statin monotherapy to achieve target LDL (low-density lipoprotein) <100 or LDL <70 mg/dl and assessed recurrent major cardiovascular events. Patients had ischemic stroke or transient ischemic attack and established atherosclerotic disease (aortic, intra or extracranial large artery or coronary arteries). There were differences in statin intensity between the LDL target groups, and other lipid-lowering treatments were allowed in the monotherapy group. Target LDL levels were achieved in the groups, but there was higher compliance in the dual therapy group. Overall, the dual therapy group targeting LDL <70 mg/dL had lower event rates across all major adverse cardiovascular outcomes, including intracerebral hemorrhage. Although this study suggests a benefit of dual therapy over monotherapy and target of lower LDL levels, confirmatory randomized clinical trials are needed. See p 3260.Importance of Delayed Reperfusions in Patients with Incomplete ThrombectomyIncomplete revascularization after mechanical thrombectomy in acute large vessel occlusion ischemic strokes occurs in a substantial proportion of patients. Mujanovic and colleagues conducted a single-center study to assess the relation of delayed reperfusion (DR) with tissue and functional outcomes after incomplete recanalization with mechanical thrombectomy for the treatment of acute ischemic stroke due to large vessel occlusion. Incomplete recanalization was defined as extended Thrombolysis in Cerebral Infarction (eTICI) score 2a or lower. Patients included also had a follow-up cerebral perfusion study at 24 hours. DR was defined as absence of a focal perfusion delay with values of Tmax≥4 seconds on contrast-enhanced follow-up perfusion imaging within the territory of the initially occluded vessel. Among 566 patients studied, DR occurred in 40.3% patients with incomplete recanalization and in none of the patients with complete recanalization (eTICI 3). DR and persistent perfusion deficits were related to eTICI score with higher DR rates associated with higher eTICI score. DR was related to preserved tissue (ie, no new infarction) while persistent perfusion deficit was related to new infarct on follow-up imaging. In multivariable analysis adjusted for relevant confounders, patients with DR had better functional outcomes regardless of eTICI score achieved (adjusted odds ratio, 2.37 [95% CI, 1.34–4.23]) and lower mortality (adjusted hazard ratio, 0.60 [95% CI, 0.39–0.91]). This study needs replication but suggests that DR is an important measure of tissue fate and correlated with functional outcome. DR may be a relevant marker for patient selection, and potential target for randomized clinical trials in patients with acute ischemic stroke undergoing mechanical thrombectomy. See p 3350. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesPrevalence and Predictors of Food Insecurity Among Stroke Survivors in the United StatesAmytis Towfighi, et al. Stroke. 2022;53:3369-3374Is It About the Destination or About the Journey?Dylan Blacquiere, et al. Stroke. 2022;53:3268-3269Importance of Delayed Reperfusions in Patients With Incomplete ThrombectomyAdnan Mujanovic, et al. Stroke. 2022;53:3350-3358 November 2022Vol 53, Issue 11 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.122.041383 Originally publishedOctober 24, 2022 PDF download Advertisement SubjectsCerebrovascular Disease/StrokeRevascularization