Pial Collateral Research Articles

A Grading Scale for Pial Collaterals in Middle Cerebral Artery Total Occlusion Based on Time-of-flight MR Angiography Source Images.

Purpose:To verify whether a new grading based on time-of-flight magnetic resonance angiography source images (TOF-MRAsi) can reflect the abundance of pial collaterals, in patients with total occlusion of M1 segment of middle cerebral artery in the chronic stage.Methods:In this single-center retrospective study, consecutive patients with total occlusion of M1 segment of middle cerebral artery, with both magnetic resonances angiography and digital subtraction angiography image were included. Time-of-flight magnetic resonance angiography source images were evaluated in a blinded fashion for pial collaterals (PCs) that were graded on a four-point scale. Good and poor PCs were defined as TOF-MRAsis grade <2 and ≥2, respectively. Receiver operating characteristic curve analysis was done to calculate the area under curve, sensitivity, and specificity.Results:A total of 26 patients were included. The inter-reader agreement for time TOF-MRAsi and digital subtraction angiography images were 0.930 and 0.843, respectively. Compared with digital subtraction angiography grading, the area under curve of pial collateral grading based on TOF-MRAsi was 0.830 (0.636–1.000; P = 0.006). The sensitivity and specificity were 0.700 and 0.933, respectively. The modified Rankin Scale at follow-up was lower in patients with good PCs than in those with poor PCs (0[0, 1] vs. 1[1, 3], P = 0.055), although statistical significance was not reached.Conclusion:The grading scale based on TOF-MRAsi could be a new empirical approach for pial collateral evaluation. The clinical use of the proposed approach for identifying patients with total occlusion of middle cerebral artery with a high risk of poor outcome requires evaluation in further studies.

Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis.

Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in the severity of tissue injury in obstructive disease. Evidence in animals and humans indicates that differences in the extent of PComs, i.e., their anatomic lumen diameter and whether they are present bilaterally, unilaterally, or absent, are a major factor. These differences arise during development since they are present at birth. However, the causal mechanisms are unknown. We used angiography after maximal dilation to examine involvement of genetic, environmental, and stochastic factors. The extent of PComs varied widely among seven genetically diverse strains of mice. Like pial collaterals in the microcirculation, aging and hypertension reduced PCom diameter, while in contrast, obesity, hyperlipidemia, metabolic syndrome, and diabetes mellitus had no effect. Naturally occurring intrauterine growth restriction had no effect on extent of PCom or pial collaterals in the adult. The number and diameter of PComs evidenced much larger apparent stochastic-dependent variation than pial collaterals. In addition, both PComs underwent flow-mediated outward remodeling after unilateral permanent MCA occlusion that varied with genetic background and was greater on the ipsilesional side. These findings indicate that variation in the number and diameter of PCom collateral arteries arises from stochastic factors and naturally occurring genetic variants that differ from those that cause variation in pial collateral arterioles. Environmental factors also contribute: aging and hypertension reduce PCom diameter. Our resultssuggest possible sources of variation of PComs in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease.

Temporal remodeling of pial collaterals and functional deficits in a murine model of ischemic stroke

BackgroundLeptomeningeal anastomoses play a critical role in regulating reperfusion following cerebrovascular obstruction; however, methods to evaluate their temporospatial remodeling remains under investigation. New methodWe combined arteriole-specific vessel painting with histological evaluation to assess the density and diameter of inter-collateral vessels between the middle cerebral artery and anterior cerebral artery (MCA-ACA) or posterior cerebral artery (MCA-PCA) in a murine model of permanent middle cerebral artery occlusion (pMCAO). ResultsWhile the overall density was not influenced by pMCAO, the size of MCA-ACA and MCA-PCA vessels had significantly increased 2days post-pMCAO and peaked by 4days compared to the un-injured hemisphere. Using a combination of vessel painting and immunofluorescence, we uniquely observed an induction of cellular division and a remodeling of the smooth muscle cells within the collateral niche following post-pMCAO on whole mount tissue sections. Vessel painting was also applied to pMCAO-injured Cx3cr1GFP mice, in order to identify the spatial relationship between Cx3cr1-positive peripheral-derived monocyte/macrophages and the vessel painted collaterals. Our histological findings were supplemented with analysis of cerebral blood flow using laser Doppler imaging and behavioral changes following pMCAO. Comparison with existing methodsCompared to polyurethane and latex methods for collateral labeling, this new method provides detailed cell-type specific analysis within the collateral niche at the microscopic level, which has previously been unavailable. ConclusionsThis simple and reproducible combination of techniques is the first to dissect the temporospatial remodeling of pial collateral arterioles. The method will advance investigations into the underlying mechanisms governing the intricate processes of arteriogenesis.

Aerobic exercise prevents rarefaction of pial collaterals and increased stroke severity that occur with aging

Variation in extent of the brain’s collateral circulation is an important determinant of variation in the severity of stroke and efficacy of revascularization therapies. However, the number and diameter of pial collateral “arterioles” decrease with aging in associated with reduced eNOS and increased oxidative stress. We tested whether exercise reduces this aging-induced rarefaction. Twelve-month-old mice were randomized to sedentary or voluntary wheel-running. At 26 months’ age, permanent MCA occlusion was followed 72 h later by determination of infarct volume and vascular casting after maximal dilation. The decline in collateral number and diameter and 2.4-fold increase in infarct volume evident in 26-versus 3-month-old sedentary mice were prevented by exercise-training. In contrast, number and diameter of the posterior communicating collateral “arteries” were unaffected by aging or exercise. Interestingly, diameter of the primary intracranial arteries increased with aging. Mechanistically, genetic overexpression of eNOS inhibited age-induced collateral rarefaction, and exercise increased eNOS and SOD2 and decreased the inflammatory marker NFkB assessed in hindlimb arteries. In conclusion, exercise prevented age-induced rarefaction of pial collaterals and reduced infarct volume. Aging also promoted outward remodeling of intracranial arteries. These effects were associated with increased eNOS and reduced markers of inflammation and aging in the vascular wall.

Abstract TMP120: Genetic, Environmental and Stochastic Factors Contribute to Variation in the Posterior Communicating Collaterals of the Circle of Willis

Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in severity of tissue injury in obstructive disease. The “extent” of PCom collaterals (lumen diameter &amp;/or number—ie, presence bilaterally, unilaterally or absent) varies widely in humans and other species due in part to developmental differences, since well-known patterns of variation are present at birth. However, mechanisms underlying this variation have not been examined. Herein we used angiography to probe involvement of genetic, environmental and stochastic factors. PCom extent varied widely among 7 mouse strains with different genetic backgrounds that was unrelated to differences in PCA diameter or brain weight. The pattern differed strongly from that previously reported by us for differences in extent of pial collateral arterioles. Like pial collaterals, PCom diameter was reduced by advanced aging (-28±3%, n=11-16, p&lt;0.01; opposite seen for PCA diameter) and hypertension (-14±8%, n=7-9, p&lt;0.05; -18% for PCA diameter). In contrast to pial collaterals, obesity, hyperlipidemia, metabolic syndrome and diabetes had no effect on PCom extent (or PCA diameter). Intrauterine growth restriction reduced PCom diameter 55±4% (n=6-17, p&lt;0.05; -24% for PCA) in the adult despite catch-up growth of brain after birth, while pial collaterals were unaffected. Compared to pial collaterals (and PCA), PCom extent evidenced &gt;8-fold larger stochastic variation (n=16, p&lt;0.01). In addition, PComs underwent outward remodeling after MCA occlusion that varied with genetic background (12-133% lumen enlargement among 5 strains; n=5-14, p&lt;0.05-0.001) and was greater on the side of occlusion in most strains. In conclusion, variation in number and diameter of PCom collateral arteries arises from genetic, environmental and stochastic factors. The responsible genetic polymorphisms appear to differ from those that contribute to variation in extent of pial collateral arterioles. Extent of PComs is also adversely affected by intrauterine growth restriction, aging and hypertension. These findings suggest possible sources of PCom variation in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease.

Abstract 222: Exercise Training Prevents Rarefaction of Pial Collaterals, Promotes Cerebral Arterial Remodeling, and Lessens Severity of Stroke in Aging Brain

Variation in anatomic extent of the collateral circulation is an important determinant of variation in the severity of ischemic stroke and efficacy of revascularization therapies. Yet pial collateral number and lumen diameter decrease with age, at least in mice. It is not known if this can be mitigated. We tested whether exercise training can accomplish this and if it also affects diameter of the posterior communicating collalterals (PComs) and primary cerebral arteries (ICA, BA, MCA, ACA, PCA). We randomized 30 male and 30 female, 12 months-old (~40 human years, hy) C57BL/6J mice to either sedentary or voluntary wheel-running (daily distance run was measured). At 25 mos-age (~70 hy), permanent MCA occlusion was followed 24h later by vascular casting after maximal dilation and by determination of infarct volume. Controls for aging were 3 mos-old sedentary mice (~16 hy). Training effect was confirmed by muscle fiber-type switching, body weight and cardiac hypertrophy (all p&lt;0.05). Exercise prevented age-associated loss of collateral number and diameter (p=0.049 and 0.005, n=13-14) and reduced infarct volume by 50%, ie, to that seen in 3 months-old mice (p=0.01, n=7). Unlike pial collaterals, PCom diameter and number (ie, present bilaterally, unilaterally or absent) were unaffected by exercise. Of further interest, diameter of the primary cerebral arteries increased with aging alone (119 ± 1 vs 134 ± 5 μm averaged combined diameter, p=0.02, n=10-14); this effect tended to increase further with exercise (143 ± 4 μm, p=0.07, n=13). Mechanistically, exercise increased vascular expression (assessed by immunohisto-chemistry) of total eNOS (p=0.03, n=5-6), phospho-eNOS (p=0.004, n=5) and a marker of anti-oxidative stress (SOD, p=0.008, n=5-6; but not HO-1, p=0.40, n=6). It did not alter a marker of aging (p16, p=0.42, n=5); analysis of additional targets is underway. In conclusion, exercise training prevented age-induced rarefaction of pial collaterals and reduced infarct volume. In addition and unexpectedly, aging also caused outward remodeling of the primary cerebral arteries, and exercise training tended to further augment this. These benefits of regular aerobic exercise were associated with increased eNOS bioavailability and reduced oxidative stress.

Abstract 62: Sanguinate TM Opens Collaterals, Improves Reperfusion and Decreases Infarct in Hypertensive Rats

Background: The PEGylated cell-free carboxyhemoglobin gas exchanger Sanguinate TM (SG) has multiple beneficial actions that may improve stroke outcome including anti-inflammatory, vasodilatory and oxygen delivery capacity. We investigated the ability of SG to improve infarction in spontaneously hypertensive rats (SHR) that are known to have vasoconstricted pial collaterals and poor stroke outcome. Methods: SHR were treated IV with SG (8 ml/kg; n=8) or vehicle (Lactated Ringer’s; n=6) plus tPA (0.9 mg/ml) after 30 min of proximal middle cerebral artery occlusion (MCAO) by filament occlusion. Pial collateral and reperfusion flow were measured for 2 hrs of occlusion and 2 hrs reperfusion using dual laser Doppler probes in the core (Bregma -2mm, lateral +4mm) and collateral (Bregma +2mm, lateral +3mm) territories. Collateral openings (number and duration (min)) were assessed off cerebral blood flow (CBF) tracings, defined as independent of changes in blood pressure (Fig. 1; arrows show openings). Infarction was measured using triphenyltetrazolium chloride (TTC). Animals were anesthetized with chloral hydrate and ventilated to maintain blood gases within normal ranges. Results: Vehicle-treated SHR had incomplete reperfusion and poor collaterals that was improved by SG. During MCAO, SG increased the number of collateral openings from 1.0±0.8 to 3.1±0.8 (p=0.03) and duration of openings from 6.0±5.8 to 35.4±9.8 min (p=0.04; Fig. 2). Reperfusion CBF was -43±6% of baseline in vehicle-treated, but only -7±19% of baseline in SG-treated animals. Improved collateral and reperfusion flow with SG was associated with decreased infarct volume vs. vehicle (28.8±3.2% vs. 18.8±2.3%; p&lt;0.05). The presence of tPA had no effect in either group. Conclusions: Smaller infarction with early SG treatment may be related to its ability to open constricted collaterals in SHR and improve reperfusion. Thus, SG may be able to extend the time window for endovascular or tPA treatment.

Impact of Pial Collaterals on Infarct Growth Rate in Experimental Acute Ischemic Stroke.

Cerebral infarction evolves at different rates depending on available blood flow suggesting that treatment time windows vary depending on the degree of pial collateral recruitment. This work sought to mathematically model infarct growth and determine whether infarct volume growth can be predicted by angiographic assessment of pial collateral recruitment in an experimental MCA occlusion animal model. Pial collateral recruitment was quantified by using DSA, acquired 15 minutes following permanent MCA occlusion in 6 canines based on a scoring system (average pial collateral score) and arterial arrival time. MR imaging-based infarct volumes were measured 60, 90, 120, 180, 240 and 1440 minutes following MCA occlusion and were parameterized in terms of the growth rate index and final infarct volume (VFinal) as V(t) = VFinal [1 - e(-G × t)] (t = time). Correlations of the growth rate index and final infarct volume to the average pial collateral score and arterial arrival time were assessed by linear bivariate analysis. Correlations were used to generate asymptotic models of infarct growth for average pial collateral score or arterial arrival time values. Average pial collateral score- and arterial arrival time-based models were assessed by F tests and residual errors. Evaluation of pial collateral recruitment at 15 minutes postocclusion was strongly correlated with 24-hour infarct volumes (average pial collateral score: r2 = 0.96, P < .003; arterial arrival time: r2 = 0.86, P < .008). Infarct growth and the growth rate index had strong and moderate linear relationships to the average pial collateral score (r2 = 0.89; P < .0033) and arterial arrival time (r2 = 0.69; P < .0419), respectively. Final infarct volume and the growth rate index were algebraically replaced by angiographically based collateral assessments to model infarct growth. The F test demonstrated no statistical advantage to using the average pial collateral score- over arterial arrival time-based predictive models, despite lower residual errors in the average pial collateral score-based model (P < .03). In an experimental permanent MCA occlusion model, assessment of pial collaterals correlates with the infarct growth rate index and has the potential to predict asymptotic infarct volume growth.

Sex Differences in the Cerebral Collateral Circulation.

Premenopausal women and intact female rodents sustain smaller cerebral infarctions than males. Several sex-dependent differences have been identified as potential contributors, but many questions remain unanswered. Mice exhibit wide variation in native collateral number and diameter (collateral extent) that is dependent on differences in genetic background, aging, and other comorbidities and that contributes to their also-wide differences in infarct volume. Likewise, variation in infarct volume correlates with differences in collateral-dependent blood flow in patients with acute ischemic stroke. We examined whether extent of pial collateral arterioles and posterior communicating collateral arteries (PComAs) differ depending on sex in young, aged, obese, hypertensive, and genetically different mice. We combined new data with meta-analysis of our previously published data. Females of C57BL/6J (B6) and BALB/cByJ (BC) strains sustained smaller infarctions than males after permanent MCA occlusion. This protection was unchanged in BC mice after introgression of the B6 allele of Dce1, the major genetic determinant of variation in pial collaterals among mouse strains. Consistent with this, collateral extent in these and other strains did not differ with sex. Extent of PComAs and primary cerebral arteries also did not vary with sex. No dimorphism was evident for loss of pial collateral number and/or diameter (collateral rarefaction) caused by aging, obesity, and hypertension, nor for collateral remodeling after pMCAO. However, rarefaction was greater in females with long-standing hypertension. We conclude that smaller infarct volume in female mice is not due to greater collateral extent, greater remodeling, or less rarefaction caused by aging, obesity, or hypertension.

Adaptation of the cerebrocortical circulation to carotid artery occlusion involves blood flow redistribution between cortical regions and is independent of eNOS.

Cerebral circulation is secured by feed-forward and feed-back control pathways to maintain and eventually reestablish the optimal oxygen and nutrient supply of neurons in case of disturbances of the cardiovascular system. Using the high temporal and spatial resolution of laser-speckle imaging we aimed to analyze the pattern of cerebrocortical blood flow (CoBF) changes after unilateral (left) carotid artery occlusion (CAO) in anesthetized mice to evaluate the contribution of macrovascular (circle of Willis) vs. pial collateral vessels as well as that of endothelial nitric oxide synthase (eNOS) to the cerebrovascular adaptation to CAO. In wild-type mice CoBF reduction in the left temporal cortex started immediately after CAO, reaching its maximum (-26%) at 5-10 s. Thereafter, CoBF recovered close to the preocclusion level within 30 s indicating the activation of feed-back pathway(s). Interestingly, the frontoparietal cerebrocortical regions also showed CoBF reduction in the left (-17-19%) but not in the right hemisphere, although these brain areas receive their blood supply from the common azygos anterior cerebral artery in mice. In eNOS-deficient animals the acute CoBF reduction after CAO was unaltered, and the recovery was even accelerated compared with controls. These results indicate that 1) the Willis circle alone is not sufficient to provide an immediate compensation for the loss of one carotid artery, 2) pial collaterals attenuate the ischemia of the temporal cortex ipsilateral to CAO at the expense of the blood supply of the frontoparietal region, and 3) eNOS, surprisingly, does not play an important role in this CoBF redistribution.

Endothelial-Specific EphA4 Negatively Regulates Native Pial Collateral Formation and Re-Perfusion following Hindlimb Ischemia.

Leptomeningeal anastomoses play a critical role in regulating vascular re-perfusion following obstruction, however, the mechanisms regulating their development remains under investingation. Our current findings indicate that EphA4 receptor is a novel negative regulator of collaterogenesis. We demonstrate that EphA4 is highly expressed on pial arteriole collaterals at post-natal day (P) 1 and 7, then significantly reduced by P21. Endothelial cell (EC)-specific loss of EphA4, EphA4f/f/Tie2::Cre (KO), resulted in an increase in the density but not diameter of pial collaterals compared to WT mice. ECs isolated from KO mice displayed a 3-fold increase in proliferation, enhanced migration, tube formation and elevated levels of phospho(p)-Akt compared to WT ECs. Attenuating p-Akt, using LY294002, reduced the proliferative and migration effects in the KO ECs. RNAseq analysis also revealed altered expression patterns for genes that regulate cell proliferation, vascular development, extracellular matrix and immune-mediate responses, namely MCP-1, MMP2 and angiopoietin-1. Lastly, we show that induction of hindlimb ischemia resulted in accelerated re-perfusion, collateral remodeling and reduced tissue necrosis in the absence of EC-specific EphA4 compared to WT mice. These findings demonstrate a novel role for EphA4 in the early development of the pial collateral network and suggests a role in regulating vascular remodeling after obstruction.

A novel method to assess pial collateralization from stroke perfusion MRI:subdividing Tmax into anatomical compartments.

To develop and validate a quantitative and observer-independent method to evaluate pial collateral circulation by DSC-perfusion MRI and test whether this novel method delivers diagnostic information which is redundant to or independent from conventional penumbra imaging by the mismatch approach. We retrospectively identified 47 patients with M1 occlusion who underwent MR diffusion/perfusion imaging and mechanical thrombectomy at our facility. By automated registration and segmentation, Tmax delays were attributed specifically to the pial, cortical and parenchymal compartments. The resulting pial volumes at delay were defined as the pial Tmax map-assessed collateral score (TMACS) and correlated with gold standard digital subtraction angiography (DSA). Mismatch ratio was assessed by conventional penumbra defining MRI criteria. Strong correlation was found between TMACS and angiographically assessed collateral score (Pearson ρ = -0.74, p < 0.001). In multiple logistic regression, both good collaterals according to TMACS [OR 4.3 (1.1-19, p = 0.04)] and mismatch ratio ≥ 3.5 [OR 12.3 (1.88-249, p = 0.03)] were independent predictors of favourable clinical outcome. Perfusion delay in the pial compartment, as evaluated by TMACS, closely reflects the extent of pial collaterals in gold-standard DSA. TMACS and mismatch ratio were found to be complementary predictors of a favourable clinical outcome, each adding independent predictive information. • MRI-DSC perfusion delay specific in the pial compartment reflects leptomeningeal collateralization. • A novel quantitative- and observer-independent marker of collateral status (TMACS) is introduced. • Quantification of collateral status leads to an independent predictor of neurological outcome.

Pial Collateral Reactivity During Hypertension and Aging: Understanding the Function of Collaterals for Stroke Therapy.

We investigated vasoactive properties of leptomeningeal arterioles (LMAs) under normotensive conditions and during hypertension and aging that are known to have poor collateral flow and little salvageable tissue. LMAs, identified as distal anastomotic arterioles connecting middle and anterior cerebral arteries, were studied isolated and pressurized from young (18 weeks) or aged (48 weeks) normotensive Wistar Kyoto (WKY18, n=14; WKY48, n=6) rats and spontaneously hypertensive rats (SHR18, n=16; SHR48, n=6). Myogenic tone and vasoactive responses to pressure as well as endothelial function and ion channel activity were measured. LMAs from WKY18 had little myogenic tone at 40 mm Hg (8±3%) that increased in aged WKY48 (30±6%). However, LMAs from both WKY groups dilated to increased pressure and demonstrated little myogenic reactivity, a response that would be conducive to collateral flow. In contrast, LMAs from both SHR18 and SHR48 displayed considerable myogenic tone (56±8% and 43±7%; P<0.01 versus WKY) and constricted to increased pressure. LMAs from both WKY and SHR groups had similar basal endothelial nitric oxide and IK channel activity that opposed tone. However, dilation to sodium nitroprusside, diltiazem and 15 mmol/L KCl was impaired in LMAs from SHR18. This study shows for the first time that LMAs from young and aged SHR are vasoconstricted and have impaired vasodilatory responses that may contribute to greater perfusion deficit and little penumbral tissue. These results also suggest that therapeutic opening of pial collaterals is possible during middle cerebral artery occlusion to create penumbral tissue and prevent infarct expansion.

Prevention of the collapse of pial collaterals by remote ischemic perconditioning during acute ischemic stroke

Collateral circulation is a key variable determining prognosis and response to recanalization therapy during acute ischemic stroke. Remote ischemic perconditioning (RIPerC) involves inducing peripheral ischemia (typically in the limbs) during stroke and may reduce perfusion deficits and brain damage due to cerebral ischemia. In this study, we directly investigated pial collateral flow augmentation due to RIPerC during distal middle cerebral artery occlusion (MCAo) in rats. Blood flow through pial collaterals between the anterior cerebral artery (ACA) and the MCA was assessed in male Sprague Dawley rats using in vivo laser speckle contrast imaging (LSCI) and two photon laser scanning microscopy (TPLSM) during distal MCAo. LSCI and TPLSM revealed that RIPerC augmented collateral flow into distal MCA segments. Notably, while control rats exhibited an initial dilation followed by a progressive narrowing of pial arterioles 60 to 150-min post-MCAo (constricting to 80–90% of post-MCAo peak diameter), this constriction was prevented or reversed by RIPerC (such that vessel diameters increased to 105–110% of post-MCAo, pre-RIPerC diameter). RIPerC significantly reduced early ischemic damage measured 6 h after stroke onset. Thus, prevention of collateral collapse via RIPerC is neuroprotective and may facilitate other protective or recanalization therapies by improving blood flow in penumbral tissue.

Intracranial Pressure Elevation Reduces Flow through Collateral Vessels and the Penetrating Arterioles they Supply. a Possible Explanation for ‘Collateral Failure’ and Infarct Expansion after Ischemic Stroke

Recent human imaging studies indicate that reduced blood flow through pial collateral vessels ('collateral failure') is associated with late infarct expansion despite stable arterial occlusion. The cause for 'collateral failure' is unknown. We recently showed that intracranial pressure (ICP) rises dramatically but transiently 24 hours after even minor experimental stroke. We hypothesized that ICP elevation would reduce collateral blood flow. First, we investigated the regulation of flow through collateral vessels and the penetrating arterioles arising from them during stroke reperfusion. Wistar rats were subjected to intraluminal middle cerebral artery (MCA) occlusion (MCAo). Individual pial collateral and associated penetrating arteriole blood flow was quantified using fluorescent microspheres. Baseline bidirectional flow changed to MCA-directed flow and increased by >450% immediately after MCAo. Collateral diameter changed minimally. Second, we determined the effect of ICP elevation on collateral and watershed penetrating arteriole flow. Intracranial pressure was artificially raised in stepwise increments during MCAo. The ICP increase was strongly correlated with collateral and penetrating arteriole flow reductions. Changes in collateral flow post-stroke appear to be primarily driven by the pressure drop across the collateral vessel, not vessel diameter. The ICP elevation reduces cerebral perfusion pressure and collateral flow, and is the possible explanation for 'collateral failure' in stroke-in-progression.

SU-C-18C-07: Quantitative Measurement of Arterial Arrival Time in Pial Collaterals: Effect of Physical Parameters On Performance

Introduction: During Middle Cerebral Artery Occlusion (MCAO), the presence pial collateral capillaries can affect a stroke's severity and subsequent recovery Arterial arrival time (AAT) is the difference in contrast arrival time between a reference artery and a measured vessel, and can serve as an indirect angiographic measure of pial collateral recruitment during acute ischemic stroke. No automated method for AAT assessment is currently available on digital subtraction angiography. We report on an automated method for AAT maps derived from DSA and potential pitfalls that confound the accuracy of these maps. Methods: Our dataset consisted of digital angiographic images of five canines obtained on a GE OEC 9800 Plus Cardiac system using, 490 × 492 pixel images and iohexol, Images had been obtained after an induced MCAO. Our automatic method corrects for drift in x-ray output and measured noise in a region with no contrast. For each pixel, contrast arrival time was calculated using thresholding. AAT is the difference in contrast arrival time between a reference artery and a measured vessel, and yields information on the extent of pial collateralization in a measured vessel. This method was also validated against a manual determination of AAT. Deviations between manual and automatic methods were assessed across various physical parameters. Results: Factors that degrade the automatic determination of the AAT included motion, vessel orientation, the partial volume effect, pixel location from the vessel's center, and contrast agent dispersion. For example, contrast agent dispersion caused errors in the AAT from 33 to 891 milliseconds, across three dogs, for arrival times between a reference artery of the middle cerebral artery and a pial collateral vessel. Conclusions: For parameters studied, temporal distance can be validated down to milliseconds, thus allowing for the objective assessment of AAT and the potential appraisal of a stroke's severity.

Hemiplegic migraine: An atypical presentation of Moyamoya disease.

Sir, Migraine is a common disorder causing attacks of disabling headaches that can be accompanied by an aura in a third of patients. Few patients having motor weakness during the aura qualify for hemiplegic migraine.[1] This can occur as a sporadic or familial disorder; the latter type is characterized by affection of one first or second degree relative, and then known as familial hemiplegic migraine.[2] Moyamoya disease is a progressive cerebrovascular occlusive disease identified by stenosis of distal internal carotid arteries (ICA) and their branches. Dilation of small cerebral vessels in an attempt to compensate for the decreased blood flow in the anterior circulation produces the characteristic “puff of smoke” appearance on angiography.[3] Headache is one of the common presentations of moyamoya disease in children.[4] Pathophysiological mechanisms for headache remain unclear, but presumed to be closely related to the intracranial oligemic state, as reflected by the disappearance of headache after the improvement of cerebral bold flow augmentation surgery, that is, vascular anastomosis.[5] Familial hemiplegic migraine could be a rare presentation of moyamoya disease. We describe a case of moyamoya disease presented as familial hemiplegic migraine. An 11-year-old girl presented to the pain clinic with periodic throbbing pain over right forehead associated with complete hemiparesis of left half of the body since last 2 years. Frequency of headache was 1-2 times/month with intermittent symptom free periods up to 3 months. Headache was not related to any particular time of the day and any precipitating, aggravating or relieving factors were absent. Initially, her complaints began with nausea, circumoral paresthesia and paresthesia of the left half of the body lasting for 20-30 min. Initial aura symptoms were followed by pain and hemiparesis for 4-10 h with spontaneous and complete recovery thereafter. She was treated for migraine without any effect. There were no past histories of head injury, seizures, involuntary movements, developmental delay, central nervous system infections, or other significant medical illness. On examination, she was afebrile, with normal vitals, pupils were equal (7 mm) and reactive to light, cranial nerve examination was normal and disc margins were sharp on fundoscopy. Tone, power, and reflexes were within normal ranges; bilaterally in both the extremities. Patient's elder sister (15-year-old) had similar symptoms but never underwent treatment. Magnetic resonance imaging brain showed bilateral periventricular deep white matter ischemia with mild cortical atrophy. Cerebral angiography revealed the occlusion of supra-clinoid segments of ICA bilaterally with evidences of moyamoya vessels [Figure 1]. Pial to pial collateral circulation from bilateral posterior cerebral artery to anterior cerebral artery and middle cerebral artery noted through pericallosal collateral vessels [Figure 1]. Considering moyamoya disease is the primary pathology responsible for the headache patient was referred for neurosurgical management. Figure 1 (a) Digital subtraction angiography image showing pial collaterals. (b) Choroidal to choroidal pial collaterals (c) Moyamoya vessels This particular case report and the review of the existing literatures suggest that pediatric patients presenting with migraineous or cluster headache refractory to prophylactic and abortive medical therapies should be evaluated further with cerebral angiography. If moyamoya disease is responsible, an early revascularization procedure will alter the prognosis and life expectancy in such patients.

Factors associated with rapid neurological improvement 24 h following intra-arterial thrombolytic treatment for acute ischemic stroke

Background and PurposeSignificant 24 h improvement is the strongest indicator of functional recovery following thrombolytic treatment for acute ischemic stroke. This study sought to analyze factors contributing to rapid neurological...

The impact of diabetes on the extent of pial collaterals in acute ischemic stroke patients

IntroductionThe threatened vascular territory in ischemic stroke is maintained by pial collateral circulation. Neovascularization varies among organ systems in diabetic patients. The effect of diabetes on the extent of pial...

Hemorrhage Rates and Outcomes When Using up to 100 mg Intra-Arterial t-PA for Thrombolysis in Acute Ischemic Stroke

This work presents a unique single center experience with intra-arterial delivery of tissue plasminogen activator (t-PA) doses as high as 100mg for thrombolysis. Hemorrhage volumes, hemorrhage rates, clinical outcomes and radiographic outcomes were assessed. Prospectively collected angiographic, clinical and laboratory information on 67 consecutive patients with acute ischemic stroke involving either the m1 segment of the middle cerebral artery, the intracranial internal carotid artery or the basilar artery were retrospectively analyzed. Patients who received more than 50 mg t-PA were compared with those patients receiving 50 mg or less. Outcome measures included: symptomatic hemorrhage, significant hemorrhage volume (greater than 25 ml), hemorrhage rate, change in National Institutes of Health stroke scale score at 24 hours and at hospital discharge, modified Rankin score at 90 days, in-hospital deaths, death within 90 days, reperfusion rate, and infarct volume. Multivariate logistic regression analysis demonstrated that t-PA dose over 50 mg was associated with higher rates of hemorrhage and larger hemorrhages. Poor pial collateral formation, poor reperfusion (less than 50% of the territory involved), and platelet count below 200 K/μL influenced hemorrhage. Limiting t-PA dose to 100mg rather than 50mg improved documented reperfusion rates from 37% to 61%. Restricting intra-arterial t-PA administration to 100mg rather than 50mg, is associated with higher overall reperfusion rates and improves overall outcomes, however, the hemorrhage rate is also elevated. Poor pial collateral formation and platelet count less than 200 K/μL may be reasons to curtail the use of higher t-PA dose to reduce hemorrhage rate.