Tissue-Based Thrombolysis for Wake-Up Stroke With Basilar Artery Occlusion: A Case Report.

Stroke from basilar artery occlusion is associated with a poor natural history with high rates of death and disability. Intravenous thrombolysis administered within 4.5 hours of last known well time improves the odds of a good neurological outcome after ischemic stroke, including in patients with basilar artery occlusion. Thrombectomy for basilar artery occlusion has had mixed outcomes. The WAKE-UP randomized clinical trial demonstrated that administration of intravenous thrombolysis can benefit select patients with wake-up strokes whose brain MRI shows restricted diffusion but no accompanying T2 FLAIR change. We report a case of a wake-up acute ischemic stroke presenting with acute vertigo followed by progressive brainstem dysfunction from a basilar artery occlusion. The patient was successfully treated with intravenous thrombolysis beyond 4.5 hours of last known well and symptom discovery time according to an MRI tissue-based approach resulting in partial recanalization of her basilar artery and recovery to near normal. This case suggests that hyperacute MRI can serve as a tissue clock to select patients with wake-up stroke for acute reperfusion therapy even if they do not meet standard trial inclusion criteria, including patients with basilar artery occlusion.

Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study).

BACKGROUND AND PURPOSE: Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors. MATERIALS AND METHODS: This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included 279 patients. Both contrast agents (dose = 0.1 mmol/kg of body weight) were assessed with 2 identical MRIs at a time interval of 2-14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from "poor" to "excellent." Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site. RESULTS: For all 3 readers, images of most patients (>90%) were scored good or excellent for overall lesion visualization and characterization with either contrast agent; and the noninferiority of gadoterate meglumine versus gadobutrol was statistically demonstrated. No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentage enhancement being higher with gadobutrol (P < .001). Diagnostic confidence was high/excellent for all readers in >81% of the patients with both contrast agents. Similar percentages of patients with adverse events related to the contrast agents were observed with gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain. CONCLUSIONS: The noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors was demonstrated.

Synthetic MRI for Clinical Neuroimaging: Results of the Magnetic Resonance Image Compilation (MAGiC) Prospective, Multicenter, Multireader Trial.

BACKGROUND AND PURPOSE: Synthetic MR imaging enables reconstruction of various image contrasts from 1 scan, reducing scan times and potentially providing novel information. This study is the first large, prospective comparison of synthetic-versus-conventional MR imaging for routine neuroimaging. MATERIALS AND METHODS: A prospective multireader, multicase noninferiority trial of 1526 images read by 7 blinded neuroradiologists was performed with prospectively acquired synthetic and conventional brain MR imaging case-control pairs from 109 subjects (mean, 53.0 ± 18.5 years of age; range, 19-89 years of age) with neuroimaging indications. Each case included conventional T1- and T2-weighted, T1 and T2 FLAIR, and STIR and/or proton density and synthetic reconstructions from multiple-dynamic multiple-echo imaging. Images were randomized and independently assessed for diagnostic quality, morphologic legibility, radiologic findings indicative of diagnosis, and artifacts. RESULTS: Clinical MR imaging studies revealed 46 healthy and 63 pathologic cases. Overall diagnostic quality of synthetic MR images was noninferior to conventional imaging on a 5-level Likert scale (P < .001; mean synthetic-conventional, -0.335 ± 0.352; Δ = 0.5; lower limit of the 95% CI, -0.402). Legibility of synthetic and conventional morphology agreed in >95%, except in the posterior limb of the internal capsule for T1, T1 FLAIR, and proton-density views (all, >80%). Synthetic T2 FLAIR had more pronounced artifacts, including +24.1% of cases with flow artifacts and +17.6% cases with white noise artifacts. CONCLUSIONS: Overall synthetic MR imaging quality was similar to that of conventional proton-density, STIR, and T1- and T2-weighted contrast views across neurologic conditions. While artifacts were more common in synthetic T2 FLAIR, these were readily recognizable and did not mimic pathology but could necessitate additional conventional T2 FLAIR to confirm the diagnosis.

Dynamic Susceptibility Contrast-Enhanced MR Perfusion Imaging in Assessing Recurrent Glioblastoma Response to Superselective Intra-Arterial Bevacizumab Therapy.

BACKGROUND AND PURPOSE: Recurrent glioblastoma currently has no established standard of care. We evaluated the response of recurrent glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab by using dynamic susceptibility contrast-enhanced MR perfusion imaging. We hypothesized that treatment response would be associated with decreased relative CBV and relative CBF. MATERIALS AND METHODS: Patients were accrued for this study from larger ongoing serial Phase I/II trials. Twenty-five patients (14 men, 11 women; median age, 55 years) were analyzed. Four distinct ROIs were chosen: 1) normal-appearing white matter on the contralateral side, 2) the location of the highest T1 enhancement in the lesion (maximum enhancing), 3) the location of highest relative CBV in the lesion (maximum relative CBV), and 4) nonenhancing T2 hyperintense signal abnormality surrounding the tumor (nonenhancing T2 hyperintensity). RESULTS: There was a statistically significant median percentage change of -32.34% (P = .001) in relative CBV in areas of maximum relative CBV following intra-arterial bevacizumab therapy. There was also a statistically significant median percentage decrease in relative CBF of -30.67 (P = .001) and -27.25 (P = .037) in areas of maximum relative CBV and maximum tumor enhancement, respectively. Last, a trend toward statistical significance for increasing relative CBV in nonenhancing T2 hyperintense areas (median percent change, 30.04; P = .069) was noted. CONCLUSIONS: Dynamic susceptibility contrast-enhanced MR perfusion imaging demonstrated a significant decrease in tumor perfusion metrics within recurrent glioblastomas in response to superselective intra-arterial cerebral infusion of bevacizumab; however, these changes did not correlate with time to progression or overall survival.

A Novel Methodology for Applying Multivoxel MR Spectroscopy to Evaluate Convection-Enhanced Drug Delivery in Diffuse Intrinsic Pontine Gliomas.

BACKGROUND AND PURPOSE: Diffuse intrinsic pontine gliomas are inoperable high-grade gliomas with a median survival of less than 1 year. Convection-enhanced delivery is a promising local drug-delivery technique that can bypass the BBB in diffuse intrinsic pontine glioma treatment. Evaluating tumor response is critical in the assessment of convection-enhanced delivery of treatment. We proposed to determine the potential of 3D multivoxel (1)H-MR spectroscopy to evaluate convection-enhanced delivery treatment effect in these tumors. MATERIALS AND METHODS: We prospectively analyzed 3D multivoxel (1)H-MR spectroscopy data for 6 patients with nonprogressive diffuse intrinsic pontine gliomas who received convection-enhanced delivery treatment of a therapeutic antibody (Phase I clinical trial NCT01502917). To compare changes in the metabolite ratios with time, we tracked the metabolite ratios Cho/Cr and Cho/NAA at several ROIs: normal white matter, tumor within the convection-enhanced delivery infusion site, tumor outside of the infused area, and the tumor average. RESULTS: There was a comparative decrease in both Cho/Cr and Cho/NAA metabolite ratios at the tumor convection-enhanced delivery site versus tumor outside the infused area. We used MR spectroscopy voxels with dominant white matter as a reference. The difference between changes in metabolite ratios became more prominent with increasing time after convection-enhanced delivery treatment. CONCLUSIONS: The comparative change in metabolite ratios between the convection-enhanced delivery site and the tumor site outside the infused area suggests that multivoxel (1)H-MR spectroscopy, in combination with other imaging modalities, may provide a clinical tool to accurately evaluate local tumor response after convection-enhanced delivery treatment.

Imaging evidence and recommendations for traumatic brain injury: advanced neuro- and neurovascular imaging techniques.

SUMMARY: Neuroimaging plays a critical role in the evaluation of patients with traumatic brain injury, with NCCT as the first-line of imaging for patients with traumatic brain injury and MR imaging being recommended in specific settings. Advanced neuroimaging techniques, including MR imaging DTI, blood oxygen level-dependent fMRI, MR spectroscopy, perfusion imaging, PET/SPECT, and magnetoencephalography, are of particular interest in identifying further injury in patients with traumatic brain injury when conventional NCCT and MR imaging findings are normal, as well as for prognostication in patients with persistent symptoms. These advanced neuroimaging techniques are currently under investigation in an attempt to optimize them and substantiate their clinical relevance in individual patients. However, the data currently available confine their use to the research arena for group comparisons, and there remains insufficient evidence at the time of this writing to conclude that these advanced techniques can be used for routine clinical use at the individual patient level. TBI imaging is a rapidly evolving field, and a number of the recommendations presented will be updated in the future to reflect the advances in medical knowledge.

Appropriate use of CT perfusion following aneurysmal subarachnoid hemorrhage: a Bayesian analysis approach.

BACKGROUND AND PURPOSE: In recent years CTP has been used as a complementary diagnostic tool in the evaluation of delayed cerebral ischemia and vasospasm. Our aim was to determine the test characteristics of CTP for detecting delayed cerebral ischemia and vasospasm in SAH, and then to apply Bayesian analysis to identify subgroups for its appropriate use. MATERIALS AND METHODS: Our retrospective cohort comprised consecutive patients with SAH and CTP performed between days 6 and 8 following aneurysm rupture. Delayed cerebral ischemia was determined according to primary outcome measures of infarction and/or permanent neurologic deficits. Vasospasm was determined by using DSA. The test characteristics of CTP and its 95% CIs were calculated. Graphs of conditional probabilities were constructed by using Bayesian techniques. Local treatment thresholds (posttest probability of delayed cerebral ischemia needed to initiate induced hypertension, hypervolemia, and hemodilution or intra-arterial therapy) were determined via a survey of 6 independent neurologists. RESULTS: Ninety-seven patients with SAH were included in the study; 39% (38/97) developed delayed cerebral ischemia. Qualitative CTP deficits were seen in 49% (48/97), occurring in 84% (32/38) with delayed cerebral ischemia and 27% (16/59) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.84 (0.73-0.96), 0.73 (0.62-0.84), 0.67 (0.51-0.79), and 0.88 (0.74-0.94), respectively. A subgroup of 57 patients underwent DSA; 63% (36/57) developed vasospasm. Qualitative CTP deficits were seen in 70% (40/57), occurring in 97% (35/36) with vasospasm and 23% (5/21) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.97 (0.92-1.0), 0.76 (0.58-0.94), 0.88 (0.72-0.95), and 0.94 (0.69-0.99), respectively. Treatment thresholds were determined as 30% for induced hypertension, hypervolemia, and hemodilution and 70% for intra-arterial therapy. CONCLUSIONS: Positive CTP findings identify patients who should be carefully considered for induced hypertension, hypervolemia, and hemodilution and/or intra-arterial therapy while negative CTP findings are useful in guiding a no-treatment decision.

Evaluating CT perfusion using outcome measures of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH and remains a leading cause of morbidity and mortality. Our aim was to evaluate CTP in aneurysmal SAH by using outcome measures of DCI. MATERIALS AND METHODS: This was a retrospective study of consecutive patients with SAH enrolled in a prospective institutional review board-approved clinical accuracy trial. Qualitative CTP deficits were determined by 2 neuroradiologists blinded to clinical and imaging data. Quantitative CTP was performed by using a standardized protocol with region-of-interest placement sampling of the cortex. Primary outcome measures were permanent neurologic deficits and infarction. The secondary outcome measure was DCI, defined as clinical deterioration. CTP test characteristics (95% CI) were determined for each outcome measure. Statistical significance was calculated by using the Fisher exact and Student t tests. ROC curves were generated to determine accuracy and threshold analysis. RESULTS: Ninety-six patients were included. Permanent neurologic deficits developed in 33% (32/96). CTP deficits were seen in 78% (25/32) of those who developed permanent neurologic deficits and 34% (22/64) of those without (P < .0001). CTP deficits had 78% (61%-89%) sensitivity, 66% (53%-76%) specificity, and 53% (39%-67%) positive and 86% (73%-93%) negative predictive values. Infarction occurred in 18% (17/96). CTP deficits were seen in 88% (15/17) of those who developed infarction and 41% (32/79) of those without (P = .0004). CTP deficits had an 88% (66%-97%) sensitivity, 59% (48%-70%) specificity, and 32% (20%-46%) positive and 96% (86%-99%) negative predictive values. DCI was diagnosed in 50% (48/96). CTP deficits were seen in 81% (39/48) of patients with DCI and in 17% (8/48) of those without (P < .0001). CTP deficits had 81% (68%-90%) sensitivity, 83% (70%-91%) specificity, and 83% (70%-91%) positive and 82% (69%-90%) negative predictive values. Quantitative CTP revealed significantly reduced CBF and prolonged MTT for DCI, permanent neurologic deficits, and infarction. ROC analysis showed that CBF and MTT had the highest accuracy. CONCLUSIONS: CTP may add prognostic information regarding DCI and poor outcomes in aneurysmal SAH.

Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study.

BACKGROUND AND PURPOSE: SIACI of bevacizumab has emerged as a promising novel therapy in the treatment of recurrent GB. This study assessed the potential of (1)H-MRS as an adjunctive technique in detecting metabolic changes reflective of antiproliferative effects of targeted infusion of bevacizumab in the treatment of GB. MATERIALS AND METHODS: Eighteen patients enrolled in a phase I/II study of SIACI of bevacizumab for treatment of recurrent GB were included. Concurrent MR imaging and (1)H-MRS scans were performed before and after treatment. Five distinct morphologic ROIs were evaluated for structural and metabolic changes on MR imaging and (1)H-MRS, which included enhancing, nonenhancing T2 hyperintense signal abnormality, and multiple control regions. Pre- and post-SIACI of bevacizumab peak areas for NAA, tCho, tCr, as well as tCho/tCr and tCho/NAA ratios, were derived for all 5 ROIs and compared using the Wilcoxon signed-rank test. RESULTS: A significant median decrease of 25.99% (range -55.76 to 123.94; P = .006) in tCho/NAA was found post-SIACI of bevacizumab relative to pretreatment values in regions of enhancing disease. A trend-level significant median decrease of 6.45% (range -23.71 to 37.67; P = .06) was noted in tCho/NAA posttreatment in regions of nonenhancing T2-hyperintense signal abnormality. CONCLUSIONS: The results of this (1)H-MRS analysis suggest that GB treatment with SIACI of bevacizumab may be associated with a direct antiproliferative effect, as demonstrated by significant reductions of tCho/NAA after the intervention.

Using quantitative CT perfusion for evaluation of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH leading to permanent neurologic deficits, infarction, and death. Our aim was to prospectively evaluate the diagnostic accuracy of CTP and to determine a quantitative threshold for DCI in aneurysmal SAH. MATERIALS AND METHODS: Patients with SAH were prospectively enrolled in a protocol approved by the institutional review board. CTP was performed during the typical time period for DCI, between days 6 and 8 following SAH. Quantitative CBF, CBV, and MTT values were obtained by using standard region-of-interest placement sampling of gray matter. The reference standard for DCI is controversial and consisted of clinical and imaging criteria in this study. In a subanalysis of vasospasm, DSA was used as the reference standard. ROC curves determined the diagnostic accuracy by using AUC. Optimal threshold values were calculated by using the patient population utility method. RESULTS: Ninety-seven patients were included; 41% (40/97) had DCI. Overall diagnostic accuracy was 93% for CBF, 88% for MTT, and 72% for CBV. Optimal threshold values were 35 mL/100 g/min (90% sensitivity, 68% specificity) for CBF and 5.5 seconds (73% sensitivity, 79% specificity) for MTT. In the subanalysis (n = 57), 63% (36/57) had vasospasm. Overall diagnostic accuracy was 94% for CBF, 85% for MTT, and 72% for CBV. Optimal threshold values were 36.5 mL/100 g/min (95% sensitivity, 70% specificity) for CBF and 5.4 seconds (78% sensitivity, 70% specificity) for MTT. CONCLUSIONS: CBF and MTT have the highest overall diagnostic accuracy. Threshold values of 35 mL/100 g/min for CBF and 5.5-second MTT are suggested for DCI on the basis of the patient population utility method. Absolute threshold values may not be generalizable due to differences in scanner equipment and postprocessing methods.

Endovascular treatment of spinal arteriovenous lesions: beyond the dural fistula.

During the past few decades, there have been significant advances in the understanding of spinal vascular lesions, mainly because of the evolution of imaging technology and selective spinal angiography techniques. In this article, we discuss the classification, pathophysiology, and clinical manifestations of spinal vascular lesions other than DAVFs and provide a review of the endovascular approach to treat these lesions.

Balloon-assisted superselective intra-arterial cerebral infusion of bevacizumab for malignant brainstem glioma. A technical note.

Malignant brainstem gliomas (BSG) are rare tumors in adults, associated with a grim prognosis and limited treatment options. Currently, radiotherapy represents the mainstay of treatment, although new studies suggest an increased role for certain chemotherapeutic agents. Intravenous (IV) administration of bevacizumab (Avastin, Genentech Pharmaceuticals) has been shown to be active in the treatment of some enhancing malignant brainstem gliomas. The IV route of administration, however, carries a risk of systemic side effects such as bowel perforation, wound disrepair and pulmonary embolism. In addition, the percentage of IV drug that reaches the tumor site is restricted by the blood brain barrier (BBB).Weill Cornell Brain Tumor Center, Department of Neurosurgery, Weill Cornell Medical College of Cornell University: New York, NY, USA. This technical report describes our protocol in performing superselective intra-arterial cerebral infusion (SIACI) of bevacizumab using endovascular balloon-assistance in the top of the basilar artery in a patient with a recurrent malignant brainstem glioma. It represents the first time such a technique has been performed for this disease. This method of drug delivery may have important implications in the treatment of both adult and pediatric brainstem gliomas.

Effect of training and experience on qualitative and quantitative CT perfusion data.

BACKGROUND AND PURPOSE: To evaluate interobserver reliability of obtaining CT perfusion (CTP) data for qualitative identification of perfusion abnormality and quantitative assessment through regions-of-interest (ROIs) placement. MATERIALS AND METHODS: Six observers participated in the study (neuroradiology attending physician, neurology attending physician, neuroradiology fellow, radiology resident physician, senior and junior CT technologists). After a brief training session, each observer evaluated 20 CTP datasets for qualitative identification of a right- or left-sided perfusion abnormality or symmetric perfusion. Observers also placed a single ROI of standard size to obtain quantitative data on the most severely hypoperfused region. An additional 10 ROIs were placed on the cortex to quantitatively evaluate global cortical perfusion. Mean quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values were analyzed. RESULTS: The kappa values for qualitative assessment of a perfusion abnormality ranged from 0.55 to 1.0. Coefficients of variation for quantitative assessment of ischemia/infarct region were 27.10% for CBF, 13.33% for CBV, and 4.66% for MTT. Coefficients of variation for quantitative assessment of global cortical perfusion were 11.88% for CBF, 13.66% for CBV, and 3.55% for MTT. The junior CT technologist and neuroradiology fellow showed significant differences compared with other observers for the ischemia/infarct region and global cortical perfusion, respectively. CONCLUSION: Overall, quantitative differences seen in this study would not necessarily affect quality of interpretation of ischemia/infarct region or global cortical perfusion. Therefore, obtaining qualitative and quantitative CTP data can reliably be performed in the clinical setting among observers with various levels of skill and experience when using a uniform and standard technique.