Comparing the Precision and Reliability Between Three Radiographic Techniques for Measuring Sporadic Vestibular Schwannomas.

RATIONALE AND OBJECTIVES: Several methods exist for measuring vestibular schwannoma (VS) size radiographically. Our aim was to compare the precision and reproducibility of three different radiographic measurement techniques for assessing VS tumor size. MATERIAL AND METHODS: Twenty patients with unilateral, sporadic VS previously untreated were identified. All patients had thin-slice T1 weighted, postcontrasted magnetization prepared rapid acquisition gradient echo images. Three measurement techniques were performed using within-subject and between-subject comparison. Experimental comparison of interobserver agreement between techniques was calculated. Interobserver intraclass correlation coefficients, repeatability coefficients, and relative smallest detectable difference were calculated and compared. RESULTS: Mean tumor measurements were: 10.3 mm (maximum linear dimension, [MLD]), 495.9 mm3 (orthogonal volumetric analysis, [OVA]), and 572.1 mm3 (segmented volumetric analysis, [SVA]). Interobserver correlation coefficient was excellent for all measurement techniques, but highest for segmented volumetric analysis. Repeatability coefficient was 1.44 mm for MLD, 298.9 mm3 for OVA, and 174.8 mm3 for SVA. The smallest detectable difference was 13.9% for MLD, 60.2% for OVA, and 30.6% for SVA. A subgroup analysis was performed for small tumors (<14 mm) and large tumors (>14 mm) and demonstrated increased precision of segmented volumetric analysis for larger tumors. CONCLUSION: Semi-automated segmented volumetric analysis appears more precise than either linear measurement or orthogonal volumetric analysis for reporting VS tumor size, and becomes increasingly precise for larger tumors. Tumor volume and tumor volume change over time using SVA may be more sensitive in surveilling VS than current measurement techniques.

ACR Appropriateness Criteria® Suspected Spine Infection.

Spine infection is both a clinical and diagnostic imaging challenge due to its relatively indolent and nonspecific clinical presentation. The diagnosis of spine infection is based upon a combination of clinical suspicion, imaging evaluation and, when possible, microbiologic confirmation performed from blood cultures or image-guided percutaneous or open spine biopsy. With respect to the imaging evaluation of suspected spine infection, MRI without and with contrast of the affected spine segment is the initial diagnostic test of choice. As noncontrast MRI of the spine is often used in the evaluation of back or neck pain not responding to conservative medical management, it may show findings that are suggestive of infection, hence this procedure may also be considered in the evaluation of suspected spine infection. Nuclear medicine studies, including skeletal scintigraphy, gallium scan, and FDG-PET/CT, may be helpful in equivocal or select cases. Similarly, radiography and CT may be appropriate for assessing overall spinal stability, spine alignment, osseous integrity and, when present, the status of spine instrumentation or spine implants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells.

Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19+ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFNγ, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity.Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404-19. ©2017 AACR.See related commentary by Mackall and Miklos, p. 1371This article is highlighted in the In This Issue feature, p. 1355.

Radiographic and Clinical Predictors of Cardiac Dysfunction Following Isolated Traumatic Brain Injury.

INTRODUCTION: Although cardiac dysfunction after traumatic brain injury (TBI) has been described, there is little data regarding the association of radiographic severity and particular lesions of TBI with the development of cardiac dysfunction. We hypothesize that the Rotterdam or Marshall scores and particular TBI lesions are associated with the development of cardiac dysfunction after isolated TBI. METHODS: We performed a retrospective cohort study. Adult patients with isolated TBI who underwent echocardiography between 2003 and 2010 were included. A board-certified neuroradiologist assessed the first computed tomography head, assigning the Rotterdam and Marshall scores and the type of TBI. Cardiac dysfunction was defined as either systolic or all cause based on the first echocardiogram after TBI. Demographic, radiological, and clinical variables were used in our analysis. RESULTS: A total of 139 patients were identified, with 20 having isolated systolic dysfunction. The Marshall and Rotterdam scores were not associated with the development of cardiac dysfunction. Only head Abbreviated Injury Scale was found to be an independent predictor of systolic cardiac dysfunction (relative risk: 2.70, 95% confidence interval: 1.19-6.13; P = .02). CONCLUSIONS: No specific radiographic variable was found to be an independent predictor of cardiac dysfunction. Further study into clinical or radiological features that would warrant an echocardiogram is warranted, as it may direct patient management.

Perimesencephalic Hemorrhage: Yield of Single versus Multiple DSA Examinations-A Single-Center Study and Meta-Analysis.

Purpose To quantify the rate of detection of aneurysms at follow-up digital subtraction angiography (DSA) after initial DSA with results negative for aneurysms in subjects with perimesencephalic (PM) nonaneurysmal subarachnoid hemorrhage. Materials and Methods This single-center retrospective study and meta-analysis was approved by the institutional review board. At a single institution from 2000 to 2013, 252 consecutive patients with subarachnoid hemorrhage at computed tomography (CT) and two DSA examinations negative for aneurysm within 10 days were evaluated for inclusion in the study, and 131 met CT criteria for PM nonaneurysmal subarachnoid hemorrhage (53 women; mean age, 53 years [range, 33-88 years]). DS angiographic reports were reviewed for causative abnormalities. Three reviewers searched MEDLINE and electronic databases for studies that reported detection of aneurysm in subjects with PM hemorrhage who had undergone multiple DSA examinations. Main inclusion criteria were PM hemorrhage at CT per van Gijn classification, head CT performed within 72 hours of symptom onset, initial DS angiographic results negative for aneurysm, and two DSA examinations within 10 days. Studies with fewer than 25 subjects were excluded. Methodology was assessed by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The summary rate of aneurysm detection for subsequent DSA was calculated by using a fixed-effects model. Results Six studies with 298 subjects and a single-institution study with 131 subjects were included. No aneurysms were seen at follow-up DSA in the single-center study (0.0%). Three aneurysms were detected at follow-up DSA in three of six studies from the literature (one of 29 [3.4%], one of 65 [1.5%], and one of 34 [2.9%] patients). Two occurred in cases that likely preceded the use of the current DSA technique. The summary aneurysm detection rate at subsequent DSA was 1.6% (95% confidence interval: 0.7%, 3.8%; range of individual study detection rate: 0.0%-3.4%). Conclusion In patients with PM nonaneurysmal subarachnoid hemorrhage and initial DSA negative for aneurysms, the yield of follow-up DSA for detection of causative aneurysms is very low. © RSNA, 2016 Online supplemental material is available for this article.

Imaging of Nontraumatic Neuroradiology Emergencies.

Imaging of acute neurologic disease in the emergency department can be challenging because of the wide range of possible causes and the overlapping imaging appearance of many of these entities on nonenhanced computed tomography (CT). The key to formulating a succinct, pertinent differential diagnosis includes characterizing the pattern of abnormalities on CT and identifying key features that suggest a particular diagnosis. This article divides neurologic emergencies into 5 scenarios based on the CT findings, including subarachnoid hemorrhage, intraparenchymal hemorrhage, vasogenic edema without and with underlying mass lesion, and acute hydrocephalus. Specific common or important diagnoses in each category are discussed.

Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.

BACKGROUND: Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored. METHODS: Periostin expression levels and patterns were examined in human glioma cells and tissues by quantitative real-time PCR and immunohistochemistry and correlated with glioma grade, type, recurrence, and survival. Functional assays determined the impact of altering periostin expression and function on cell invasion, migration, adhesion, and glioma stem cell activity and tumorigenicity. The prognostic and functional relevance of periostin and its associated genes were analyzed using the TCGA and REMBRANDT databases and paired recurrent glioma samples. RESULTS: Periostin expression levels correlated directly with tumor grade and recurrence, and inversely with survival, in all grades of adult human glioma. Stromal deposition of periostin was detected only in grade IV gliomas. Secreted periostin promoted glioma cell invasion and adhesion, and periostin knockdown markedly impaired survival of xenografted glioma stem cells. Interactions with αvß3 and αvß5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the αvß3/ß5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. CONCLUSION: Periostin is a robust marker of glioma malignancy and potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after periostin inhibition provides support for exploring the therapeutic impact of targeting periostin.

Blunt traumatic occlusion of the internal carotid and vertebral arteries.

OBJECT: The stroke rate, management, and outcome after blunt cerebrovascular occlusion (Biffl Grade IV injury) is not well defined, given the rarity of the disease. Both hemodynamic failure and embolic mechanisms have been implicated in the pathophysiology of subsequent stroke after blunt cerebrovascular occlusion. In this study, the authors evaluated their center's experience with Biffl Grade IV injuries, focusing on elucidating the mechanisms of stroke and their optimal management. METHODS: A retrospective review identified all internal carotid artery (ICA) or vertebral artery (VA) Biffl Grade IV injuries over a 7-year period at a single institution. RESULTS: Fifty-nine Biffl Grade IV injuries were diagnosed affecting 11 ICAs, 44 unilateral VAs, and 2 bilateral VAs. The stroke rates were 64%, 9%, and 50%, respectively. Of the 11 Biffl Grade IV ICA injuries, 5 presented with stroke while 2 developed delayed stroke. An ipsilateral posterior communicating artery greater than 1 mm on CT angiography was protective against stroke due to hemodynamic failure (p = 0.015). All patients with Biffl Grade IV injuries affecting the ICA who had at least 8 emboli per hour on transcranial Doppler (TCD) ultrasonography developed an embolic pattern of stroke (p = 0.006). Treatment with aspirin versus dual antiplatelet therapy had a similar effect on stroke rate in the ICA group (p = 0.5) and all patients who suffered stroke either died (n = 3) or required a decompressive hemicraniectomy with subsequent poor outcome (n = 4). All 10 strokes associated with Biffl Grade IV VA injuries were embolic and clinically asymptomatic. In VA Biffl Grade IV injury, neither the presence of emboli nor treatment with antiplatelet agents affected stroke rates. CONCLUSIONS: At the authors' institution, traumatic ICA occlusion is rare but associated with a high stroke rate. Robust collateral circulation may mitigate its severity. Embolic monitoring with TCD ultrasonography and prophylactic antiplatelet therapy should be used in all ICA Biffl Grade IV injuries. Unilateral VA Biffl Grade IV injury is the most common type of traumatic occlusion and is associated with significantly less morbidity. Embolic monitoring using TCD and prophylactic antiplatelet therapy do not appear to be beneficial in patients with traumatic VA occlusion.

Angiographic perfusion imaging: real-time assessment of endovascular treatment for cerebral vasospasm.

BACKGROUND AND PURPOSE: Cerebral perfusion analysis is useful in the diagnosis and treatment of cerebral vasospasm. A new modality of real-time cerebral perfusion imaging and analysis has been developed using standard 2-dimensional angiography. We report our initial experience with this technique to assess response to therapy during endovascular vasospasm procedures. METHODS: Colorized angiographic perfusion maps were obtained immediately before and after endovascular vasospasm treatment. Semiquantitative perfusion parameters (cerebral blood flow, cerebral blood volume, mean transit time, and time to peak) were calculated from time-density curves obtained from intraarterial contrast injection. The effects of intraarterial vasospasm therapy were assessed. RESULTS: Eight vascular territories in 4 patients with vasospasm underwent interventional angiography and angiographic perfusion analysis. Pretreatment perfusion maps demonstrated variable perfusion deficits in specific vascular territories. After endovascular treatment in 6 vessels, improvement was seen to varying degrees in both angiographic appearance and perfusion parameters. Clinical improvement and reduction in transcranial Doppler velocity was also observed. CONCLUSIONS: Real-time angiographic perfusion imaging is feasible during endovascular procedures for vasospasm. Perfusion analysis may aid in assessment of efficacy of the intervention. Comparison with traditional perfusion imaging is needed to validate this technique.

Subarachnoid hemorrhage: beyond aneurysms.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH) typically prompts a search for an underlying ruptured saccular aneurysm, which is the most common nontraumatic cause. Depending on the clinical presentation and pattern of SAH, the differential diagnosis may include a diverse group of causes other than aneurysm rupture. CONCLUSION: For the purposes of this review, we classify SAH into three main patterns, defined by the distribution of blood on unenhanced CT: diffuse, perimesencephalic, and convexal. The epicenter of the hemorrhage further refines the differential diagnosis and guides subsequent imaging. Additionally, we review multiple clinical conditions that can simulate the appearance of SAH on CT or MRI, an imaging artifact known as pseudo-SAH.

Imaging of brain metastases.

Imaging plays a key role in the diagnosis of central nervous system (CNS) metastasis. Imaging is used to detect metastases in patients with known malignancies and new neurological signs or symptoms, as well as to screen for CNS involvement in patients with known cancer. Computed tomography (CT) and magnetic resonance imaging (MRI) are the key imaging modalities used in the diagnosis of brain metastases. In difficult cases, such as newly diagnosed solitary enhancing brain lesions in patients without known malignancy, advanced imaging techniques including proton magnetic resonance spectroscopy (MRS), contrast enhanced magnetic resonance perfusion (MRP), diffusion weighted imaging (DWI), and diffusion tensor imaging (DTI) may aid in arriving at the correct diagnosis. This image-rich review discusses the imaging evaluation of patients with suspected intracranial involvement and malignancy, describes typical imaging findings of parenchymal brain metastasis on CT and MRI, and provides clues to specific histological diagnoses such as the presence of hemorrhage. Additionally, the role of advanced imaging techniques is reviewed, specifically in the context of differentiating metastasis from high-grade glioma and other solitary enhancing brain lesions. Extra-axial CNS involvement by metastases, including pachymeningeal and leptomeningeal metastases is also briefly reviewed.

Safety and efficacy of concomitant chemotherapeutic wafers and iodine-125 seeds for recurrent glioblastoma.

BACKGROUND: Patients with recurrent malignant gliomas have a uniformly poor prognosis. However, further treatment is often warranted at the time of recurrence. Low-activity implanted brachytherapeutic devices, such as iodine-125 seeds, and implantable chemotherapeutic devices such as 1, 3-bis (2-chloroethyl)-nitrosourea (BCNU) impregnated polymer wafers (Gliadel(®)) have been shown to be safe and modestly effective, but a comparison of combination therapy versus Gliadel(®) implantation alone has not been performed. METHODS: We retrospectively examined 24 patients following re-resection of recurrent glioblastoma, with 17 patients undergoing implantation of both Gliadel(®) and iodine-125 seeds, and 7 patients undergoing implantation of Gliadel(®) only. Outcomes examined included adverse events, survival after re-resection (SAR), and time to tumor progression after re-resection (PAR). RESULTS: Implantation of both Gliadel(®) and low activity iodine-125 seeds is safe with only two wound infections noted, a complication rate comparable to previous reports. The combination appears to confer a median SAR benefit if the activity per tumor resection volume exceeds 0.8 mCi/mL (60 versus 31 weeks, P = 0.02), and this benefit remained significant on multivariate analysis (HR =0.26 [CI:0.07-0.93], P = 0.03). Gross total resection of tumor was also significantly associated with longer time to PAR (HR =5.4 [CI: 1.13-26.0], P = 0.03). CONCLUSIONS: The concomitant use of Gliadel(®) and low activity iodine-125 seeds following re-resection of recurrent glioblastoma is safe. Our study demonstrated a significant benefit in SAR if the iodine-125 activity per tumor volume is greater than 0.8 mCi/mL. While our sample size is small, our results are in agreement with previous studies demonstrating the efficacy of combination treatment.

Imaging of trauma: Part 1, Pseudotrauma of the spine--osseous variants that may simulate injury.

OBJECTIVE: Anatomic variants and incomplete ossification and fusion of the developing spine may result in an erroneous diagnosis of injury or disease. This article reviews some of the more common imaging findings that may present as pseudotrauma. Normal development of the spine is reviewed, including synchondroses and ossification centers. Imaging of common variants is presented, with a focus on CT. CONCLUSION: Recognition of the normal developing spine and variants can prevent an incorrect diagnosis of injury and inappropriate treatment.

Cervical collaterals may protect against stroke after blunt vertebral artery injury.

The incidence of ischemic stroke reported after blunt vertebral artery injury is lower than that reported after blunt carotid artery injury. Unlike the carotid arteries, the vertebral arteries receive collateral blood flow through ascending cervical branches in addition to a convergent arterial supply with the contralateral vertebral artery. We hypothesize that the incidence of stroke after vertebral artery injury is less than after carotid artery injury in part because of reconstitution of vertebral arteries by cervical collaterals. A retrospective blinded interpretation of angiographic studies in 46 patients with blunt vertebral injury was performed to assess for presence and grade of vertebral artery injury and for the presence of reconstitution of the vessel via cervical collaterals. Follow-up CT scans from the same patients were evaluated for the presence of posterior circulation strokes. There were 55 injured vertebral arteries in the 46 patients, of whom 8 experienced posterior fossa strokes. Two-tailed Fisher exact probability test evaluating the hypothesis that patients with vertebral artery collaterals were less likely to experience posterior fossa strokes reached significance, p < 0.05. Of patients with occlusive (grades IV and V) injuries, those with collateral vessels were significantly less likely to experience posterior fossa strokes (p < 0.01). This result may be considered when weighing the potential risks and benefits of antiplatelet or anticoagulation therapy in patients with occlusive blunt vertebral artery injury.

Neuroimaging of pediatric central nervous system cytomegalovirus infection.

Cytomegalovirus (CMV) is a ubiquitous virus that usually results in asymptomatic or clinically benign infection. However, there are two groups of patients whose response to CMV infection is much more severe: those who are infected during fetal development and those who are immunocompromised. Although the manifestations of these types of infection differ, both often result in substantial neurologic sequelae. Imaging plays a key role in the diagnosis of both congenital and acquired CMV infection. Neurologic findings of congenital CMV infection include intracranial calcification, migrational abnormalities, cerebral and cerebellar volume loss, ventriculomegaly, and white matter disease. The presence of these findings in children with neurodevelopmental delays is suggestive of congenital CMV infection, even if the child was asymptomatic at birth. Certain imaging features also may indicate future neurologic deficits in symptomatic infants. Acquired CMV infection is potentially deadly in immunocompromised patients such as those infected with human immunodeficiency virus or with acquired immune deficiency syndrome and those with a history of solid organ or bone marrow transplantation. Imaging findings of acquired CMV infection often are nonspecific; however, they may indicate a need for further serologic analysis to determine if CMV infection is present. Early recognition and treatment of central nervous system CMV infection is vital for effective treatment, and familiarity with the imaging findings of this common infection is important for accurate diagnosis.