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

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Reperfusion rates following intra-arterial thrombolysis for acute ischemic stroke: the influence of the method for alteplase delivery.

BACKGROUND AND PURPOSE: Because alteplase does not penetrate thrombus effectively, this study examined whether a method thought to maximize surface distribution of alteplase on the offending thrombus during IATT would result in greater reperfusion rates in acute ischemic stroke. MATERIALS AND METHODS: Clinical information, arteriograms, and CT scans following treatment from 85 consecutive patients who underwent IATT by using alteplase within 6 hours of stroke symptom onset were reviewed. Alteplase was delivered through a microcatheter embedded within the thrombus at 1 mg per minute in all cases, and the delivery never exceeded 100 mg of alteplase. Patients who underwent microcatheter contrast injections confirming that alteplase surrounded the thrombus were compared with patients who did not. RESULTS: Greater than 50% vascular territory reperfusion occurred in 82.2% of patients who underwent IATT with the intention of optimizing alteplase delivery versus 30.0% in patients without this intention (P < .0001, Pearson correlation) with an odds ratio of 15.8 based on nominal regression analysis. Hemorrhagic complication rates between methods were similar. The mRS at 1-3 months, infarct volume, change in NIHSS score by 24 hours, and hospital discharge were positively affected by optimizing alteplase delivery. CONCLUSIONS: A method that intends to evenly distribute alteplase around a thrombus resulted in better reperfusion rates and clinical outcomes compared with methods without this intention. Other predictors positively influencing reperfusion included the presence of slow antegrade flow distal to the clot, earlier time to treatment, lower presenting NIHSS score, and proximal occlusion site.

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.

Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: a multicenter study.

BACKGROUND AND PURPOSE: Although recanalization is the goal of thrombolysis, it is well recognized that it fails to improve outcome of acute stroke in a subset of patients. Our aim was to assess the rate of and factors associated with "futile recanalization," defined by absence of clinical benefit from recanalization, following endovascular treatment of acute ischemic stroke. MATERIALS AND METHODS: Data from 6 studies of acute ischemic stroke treated with mechanical and/or pharmacologic endovascular treatment were analyzed. "Futile recanalization" was defined by the occurrence of unfavorable outcome (mRS score of > or = 3 at 1-3 months) despite complete angiographic recanalization (Qureshi grade 0 or TIMI grade 3). RESULTS: Complete recanalization was observed in 96 of 270 patients treated with IA thrombolysis. Futile recanalization was observed in 47 (49%). In univariate analysis, patients with futile recanalization were older (73 +/- 11 versus 58 +/- 15 years, P < .0001) and had higher median initial NIHSS scores (19 versus 14, P < .0001), more frequent BA occlusion (17% versus 4%, P = .049), less frequent MCA occlusion (53% versus 76%, P = .032), and a nonsignificantly higher rate of symptomatic hemorrhagic complications (2% versus 9%, P = .2). In logistic regression analysis, futile recanalization was positively associated with age > 70 years (OR, 4.4; 95% CI, 1.9-10.5; P = .0008) and initial NIHSS score 10-19 (OR, 3.8; 95% CI, 1.7-8.4; P = .001), and initial NIHSS score > or = 20 (OR, 64.4; 95% CI, 28.8-144; P < .0001). CONCLUSIONS: Futile recanalization is a relatively common occurrence following endovascular treatment, particularly among elderly patients and those with severe neurologic deficits.

Thunderclap headache without subarachnoid hemorrhage associated with regrowth of previously coil-occluded aneurysms.

Thunderclap headache is a sudden, high-intensity headache often associated with subarachnoid hemorrhage secondary to a ruptured intracerebral aneurysm. A variety of less common causes have now been described. This report presents the cases of 2 patients who experienced thunderclap headache after regrowth of an aneurysm, without hemorrhage of previously coiled aneurysms. Thunderclap headache after endovascular occlusion of a ruptured intracranial aneurysm may be a symptom of aneurysm regrowth and may warrant angiographic investigation.

Predictors of hemorrhage following intra-arterial thrombolysis for acute ischemic stroke: the role of pial collateral formation.

BACKGROUND AND PURPOSE: The extent of pial collateral formation during acute ischemic stroke has been shown to influence outcomes. This study examines whether angiographic assessment of pial collateral formation is predictive of hemorrhagic transformation following intra-arterial thrombolysis (IAT) for acute ischemic stroke. MATERIALS AND METHODS: Rates of any hemorrhage and significant hemorrhage (>25 mL) were reviewed in 104 consecutive patients who underwent IAT following acute ischemic stroke. The influence of the anatomic extent of pial collateral formation on the rates of hemorrhage and significant hemorrhage relative to known predictors for hemorrhagic transformation (presenting systolic blood pressure, blood glucose level, platelet level, and National Institutes of Health Stroke Scale [NIHSS] score, history of diabetes, time to treatment, age, sex, occlusion site, and extent of reperfusion) was analyzed by using logistic regression models. RESULTS: Rates of any hemorrhage and significant hemorrhage were 25.2% (26/104) and 9.7% (10/104), respectively. The rate of significant hemorrhage was 25.0% (8/32) in patients with poor pial collaterals and 2.78% (2/72) in those with good pial collaterals (P = .0004, Pearson correlation). The rate of any hemorrhage was also significantly higher in patients with poor pial collaterals (40.6% versus 18.1%; P = .0142, Pearson correlation). Logistic regression analyses revealed that pial collateral formation (odds ratio [OR] = 3.04), history of diabetes (OR = 4.83), platelets <200,000/microL (OR = 2.95), and time to treatment <3 hours (OR = 12.0) were statistically significant predictors of hemorrhage, whereas pial collateral formation (OR = 13.1) and platelets <200,000/microL (OR = 8.1) were statistically significant predictors of significant hemorrhage. CONCLUSIONS: Poor pial collateral formation is associated with higher incidence and larger size of hemorrhage following IAT.

Arteriographic demonstration of slow antegrade opacification distal to a cerebrovascular thromboembolic occlusion site as a favorable indicator for intra-arterial thrombolysis.

PURPOSE: This study sought to determine whether the angiographic demonstration of slow antegrade contrast opacification of an occluded cerebral artery distal to the thrombus (clot outline sign) on cerebral arteriograms performed immediately before thrombolytic treatment is associated with higher recanalization rates relative to patients without antegrade contrast opacification distal to the occlusion site. METHODS: The angiographic images of 100 consecutive arteriograms performed before thrombolysis in patients eligible for intra-arterial thrombolysis from May 1995 to February 2005 were reviewed. A modified Thrombolysis in Myocardial Infarction flow grade (mTIMI) was adapted to grade recanalization after cerebral thrombolysis. Clot outline sign was defined as slow antegrade contrast opacification distal to the thrombus on the delayed images of the presenting arteriogram. Logistic regression analysis for mTIMI grade included the following potential predictors: presence of outline sign, age, time to treatment, sex, site of occlusion, presenting National Institutes of Health Stroke Scale (NIHSS) score, presenting platelets, presenting systolic blood pressure, presence of pial collaterals, and admitting glucose value. RESULTS: Eighty-seven arteriograms were reviewed. Of these, 19 (22%) displayed the clot outline sign. Thirteen (69%) of 19 had clot outline sign, and 16 of 68 (29%) were not completely recanalized (mTIMI = 3); 95% with clot outline sign and 54% without were associated with either mTIMI 2 or 3 (P = .0055, Pearson correlation). Logistic regression analysis for recanalization relative to other predictors indicates that only the clot outline sign could act as a statistically significant predictor for recanalization (P = .0007). CONCLUSION: Prethrombolysis cerebral arteriograms demonstrating delayed antegrade contrast opacification distal to the occlusion site are associated with higher recanalization rates.

Imaging and nanomedicine for diagnosis and therapy in the central nervous system: report of the eleventh annual Blood-Brain Barrier Disruption Consortium meeting.

The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. The Eleventh Annual Blood-Brain Barrier Disruption Consortium Meeting was convened to discuss recent advances and future directions in imaging and nanomedicine. Two sessions, one on Cell and Molecular Imaging in the CNS and another on Nanotechnology, Nanobiology, and Nanomedicine, were held March 17-18, 2005, in Portland, Ore. CNS imaging presentations targeted differentiating tumor, neural lesions, and necrosis from healthy brain tissue; methods of delivery of imaging agents across the BBB; and new iron oxide-based nanoparticle contrast agents for MR imaging. Nanobiology presentations covered the development of new nanotechnology and its use in imaging, diagnosis, and therapy in the CNS. Discussions at this meeting stressed the role of biotechnology in the convergence of CNS imaging and nanomedicine and are summarized in this article.

Identification of the ascending middle cerebral artery branches on digital subtraction angiography.

We aimed to establish a method for identifying the ascending convexity branches of the middle cerebral artery on digital subtraction arteriography. We reviewed 100 randomly chosen lateral internal carotid arteriograms of patients with aneurysms. After identifying the Sylvian triangle, the posterior internal frontal, paracentral, superior internal parietal and pericallosal arteries, we formulated templates in order to assess the position of the angular, posterior parietal, central, precentral and prefrontal arteries. Using the Sylvian triangle as a template, we identified the angular and posterior parietal arteries in 91% and 96% of cases, respectively. Using a combination of the posterior internal frontal, paracentral, superior internal frontal and pericallosal arteries a template could be formulated in 87% of cases. This was successfully used to identify the central arteries. A template derived from the pericallosal artery and Sylvian triangle was used to identify the prefrontal arteries in 83% of cases. Templates can be formulated on the basis of the Sylvian triangle and anterior cerebral artery branches for consistent identification of branches of the ascending complex of the middle cerebral artery on digital subtraction angiography.

Lacunar infarct during pallidotomy: case report.

A symptomatic lacunar infarct is an unusual complication which may develop during stereotactically guided pallidotomy using radiofrequency thermoablation. We describe a 54-year-old man with Parkinson's disease involving predominantly the right side, progressively deteriorating under medical management. He underwent stereotactically guided radiofrequency thermoablation of the posteroventral globus pallidus interna. Despite intraoperative microelectrode recording and stimulation, the patient developed right facial weakness and pronator drift during the procedure. MRI showed a small lacunar infarct in the left internal capsule, in addition to the appropriately placed ablative lesion. We discuss the potential mechanisms for this type of injury.

High resolution MRI of the deep brain vascular anatomy at 8 Tesla: susceptibility-based enhancement of the venous structures.

PURPOSE: The purpose of this work was to describe the deep vascular anatomy of the human brain using high resolution MR gradient echo imaging at 8 T. METHOD: Gradient echo images were acquired from the human head using a transverse electromagnetic resonator operating in quadrature and tuned to 340 MHz. Typical acquisition parameters were as follows: matrix = 1,024 x 1,024, flip angle = 45 degrees, TR = 750 ms, TE = 17 ms, FOV = 20 cm, slice thickness = 2 mm. This resulted in an in-plane resolution of approximately 200 microm. Images were analyzed, and vascular structures were identified on the basis of location and course. RESULTS: High resolution ultra high field magnetic resonance imaging (UHFMRI) enabled the visualization of many small vessels deep within the brain. These vessels were typically detected as signal voids, and the majority represented veins. The prevalence of the venous vasculature was attributed largely to the magnetic susceptibility of deoxyhemoglobin. It was possible to identify venous structures expected to measure below 100 microm in size. Perforating venous drainage within the deep gray structures was identified along with their parent vessels. The course of arterial perforators was more difficult to follow and not as readily identified as their venous counterparts. CONCLUSION: The application of high resolution gradient echo methods in UHFMRI provides a unique detailed view of particularly the deep venous vasculature of the human brain.

High resolution MRI of the deep gray nuclei at 8 Tesla.

PURPOSE: High resolution MR images obtained from a normal human volunteer at 8 T are utilized to describe the appearance of iron-containing deep gray nuclei at this field strength. METHOD: High resolution (1,024 x 1,024 matrix) near-axial gradient echo images of the deep gray nuclei were acquired on a human volunteer by using an 8 T scanner. The images were acquired using a transverse electromagnetic resonator operating in quadrature. The following parameters were utilized: TR = 750 ms, TE = 17 ms, flip angle = 45 degrees, receiver bandwidth = 50 kHz, slice thickness = 2 mm, FOV = 20 cm. The 8 T images were reviewed and correlated to the known anatomy of the deep nuclei by comparing them with images observed at lower field strength, published diagrams, and histologic sections. In addition, the appearance of the nuclei was related to the known imaging characteristics of brain iron at lower fields. RESULTS: The caudate, globus pallidus, putamen, thalami, substantia nigra, and red nuclei were clearly identified. The structures with the highest levels of iron, the globus pallidus, substantia nigra, and red nuclei, demonstrated significantly decreased signal, providing a map of iron distribution in the human brain. CONCLUSION: Preliminary imaging at 8 T demonstrates the ability to acquire ultra high resolution images of the deep nuclei, with signal characteristics believed to represent the distribution of brain iron. This may prove to be important in the early diagnosis of several neurodegenerative disorders.

Human leptomeningeal and cortical vascular anatomy of the cerebral cortex at 8 Tesla.

PURPOSE: The purpose of this work was to describe the human leptomeningeal and cortical vascular anatomy as seen at high resolution on an 8 T UHFMRI system. METHOD: With a 1024 x 1024 matrix, axial gradient echo images of the cerebral cortex were acquired on a human volunteer at 8 T with TR 500 ms, TE 16 ms, flip angle 22.5 degrees, bandwidth 53 kHz, and slice thickness 2.84 mm. The same subject was evaluated at 1.5 T using similar parameters. The images were then reviewed in detail and compared with known cortical and leptomeningeal vascular anatomy. RESULTS: Two hundred forty micron in-plane resolution images of the human brain were acquired at 8 T without evident artifact from susceptibility distortions, RF penetration, or dielectric resonances. The CSF, gray matter, and white matter structures were well discerned. The microscopic leptomeningeal vascular anatomy was well visualized, and the course of small perforating cortical vessels could be followed from the cortical surface to the white matter junction. CONCLUSION: Initial 8 T images of the brain demonstrate detailed leptomeningeal and cortical vascular anatomy.

MR of CNS sarcoidosis: correlation of imaging features to clinical symptoms and response to treatment.

BACKGROUND AND PURPOSE: Sarcoidosis is an idiopathic systemic granulomatous disease, recognized in a patient when clinical and radiologic findings are confirmed by histopathologic analysis. The objective was to identify a relationship between MR imaging and clinical findings in CNS sarcoidosis. METHODS: The clinical charts of 461 patients with biopsy-proved sarcoidosis were reviewed retrospectively. Criteria for including patients in the study included those with symptoms referable to the CNS, excluding those with another explanation for their symptoms, those with headaches or other subjective complaints without accompanying objective findings, and those with peripheral neuropathy other than cranial nerve involvement or myopathy without CNS manifestations. Thirty-four of 38 patients whose conditions met the criteria for CNS sarcoidosis underwent a total of 82 MR examinations. The positive imaging findings were divided into categories as follows: pachymeningeal, leptomeningeal, nonenhancing brain parenchymal, enhancing brain parenchymal, cranial nerve, and spinal cord and nerve root involvement. Treatment response, clinical symptomatology, and any available histopathologic studies were analyzed with respect to imaging manifestations in each of the categories. RESULTS: Eighty-two percent of the patients with sarcoidosis with neurologic symptoms referable to the CNS had findings revealed by MR imaging. However, eight (40%) of 20 cranial nerve deficits seen at clinical examination of 13 patients were not seen at contrast-enhanced MR imaging, and 50% of the patients with symptoms referable to the pituitary axis had no abnormal findings on routine contrast-enhanced MR images. In contradistinction, 44% of 18 cranial nerves in nine patients with MR evidence of involvement had no symptoms referable to the involved cranial nerve. Clinical and radiologic deterioration occurred more commonly with leptomeningeal and enhancing brain parenchymal lesions. CONCLUSION: MR imaging can be used to confirm clinical suspicion and to show subclinical disease and the response of pathologic lesions to treatment.

Spontaneous intracranial hypotension: report of four cases and review of the literature.

Spontaneous intracranial hypotension is an unusual syndrome of postural headache and low cerebrospinal fluid pressure without an established cause. We present four cases, analyze those previously reported in the literature, examine the MRI, CT, angiographic and cisternographic finding and discuss the clinical picture, proposed pathophysiologic mechanisms and potential treatment.

Acute eosinophilic pneumonia: radiologic and clinical features.

PURPOSE: To determine the radiographic and computed tomographic (CT) characteristics of acute eosinophilic pneumonia. MATERIALS AND METHODS: Twelve consecutive patients with acute eosinophilic pneumonia were included in the study. The diagnosis was based on clinical symptoms and results of bronchoalveolar lavage. Plain chest radiographs were obtained in all patients; CT scans were obtained in three patients. Two thoracic radiologists reviewed the radiographs and CT scans. RESULTS: Ten patients had bilateral areas of air-space opacity on images obtained at presentation; in seven of these patients, interstitial areas of opacity were also present. Two patients had bilateral interstitial areas of opacity and no areas of air-space opacity. Interlobular septal thickening and ground-glass attenuation were present on CT scans in two patients; patchy bilateral consolidation was present on CT scans in one patient. Pleural effusion was present on radiographs in seven patients (58%) and was bilateral in five. Pleural effusion was present at some point during the course of disease in all patients. In all patients, air-space disease markedly improved within 3 days of initiation of treatment with corticosteroids. CONCLUSION: Acute eosinophilic pneumonia should be considered as a possible diagnosis when a previously healthy person presents with acute respiratory failure of unknown origin.