Radiation-induced brain injury in patients with meningioma treated with proton or photon therapy.

INTRODUCTION: Radiation therapy is often used to treat meningioma with adverse features or when unresectable. Proton therapy has advantages over photon therapy in reducing integral dose to the brain. This study compared the incidence of radiological and clinical adverse events after photon versus proton therapy in the treatment of meningioma. METHODS: A retrospective review was conducted on patients with meningioma treated with proton or photon therapy at two high-volume tertiary cancer centers. Patients with a history of prior radiation therapy (RT) or less than 3 months of follow-up were excluded. Post-RT imaging changes were categorized into abnormal T2 signal intensities (T2 changes) or abnormal T1 post-contrast and T2 signal intensities (T1c+T2 changes) on magnetic resonance imaging (MRI). Clinical outcomes of adverse events and survival were compared between the proton and photon therapies. RESULTS: Among the total of 77 patients, 38 patients received proton therapy and 39 patients received photon therapy. The median age at diagnosis was 55 years and median follow-up was 2.2 years. No significant differences in symptomatic adverse events were observed between the two groups: grade ≥ 2 adverse events were seen in 4 (10.5%) patients in the proton group and 3 (7.7%) patients in the photon group (p = 0.67). The 2-year cumulative incidences of T2 changes were 38.3% after proton therapy and 47.7% after photon therapy (p = 0.53) and the 2-year cumulative incidences of T1c+T2 changes were 26.8% after proton therapy and 5.3% after photon therapy (p = 0.02). One patient experienced grade ≥ 4 adverse event in each group (p = 0.99). Estimated 2-year progression-free survival was 79.5% (proton therapy 76.0% vs. photon therapy 81.3%, p = 0.66) and 2-year overall survival was 89.7% (proton therapy 86.6% vs. photon therapy 89.3%, p = 0.65). CONCLUSIONS: Following RT, high rates of T2 changes were seen in meningioma patients regardless of treatment modality. Proton therapy was associated with significantly higher rates of T1c+T2 changes compared with photon therapy, but severe adverse events were uncommon in both groups and survival outcomes were comparable between the two groups. Future studies will aim at correlating the MRI changes with models that can be incorporated into RT planning to avoid toxicity.

Spontaneous bilateral orbital subperiosteal hemorrhage resulting from thoracoabdominal crush injury.

Orbital subperiosteal hemorrhage in the absence of facial fractures is uncommon. We report an unusual case of spontaneous bilateral orbital subperiosteal hemorrhage from a thoracoabdominal crush injury. To our knowledge, this is the second case report of this entity occurring in the setting of thoracic compression. Recognition and management of orbital subperiosteal hemorrhage is important to prevent optic nerve compromise and blindness.

Assessment of the Prognostic Value of Radiomic Features in 18F-FMISO PET Imaging of Hypoxia in Postsurgery Brain Cancer Patients: Secondary Analysis of Imaging Data from a Single-Center Study and the Multicenter ACRIN 6684 Trial.

Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model..

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.

PURPOSE: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma. EXPERIMENTAL DESIGN: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival. RESULTS: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year. CONCLUSIONS: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.

Multimodality Brain Tumor Imaging: MR Imaging, PET, and PET/MR Imaging.

Standard MR imaging and CT are routinely used for anatomic diagnosis in brain tumors. Pretherapy planning and posttreatment response assessments rely heavily on gadolinium-enhanced MR imaging. Advanced MR imaging techniques and PET imaging offer physiologic, metabolic, or functional information about tumor biology that goes beyond the diagnostic yield of standard anatomic imaging. With the advent of combined PET/MR imaging scanners, we are entering an era wherein the relationships among different elements of tumor metabolism can be simultaneously explored through multimodality MR imaging and PET imaging. The purpose of this review is to provide a practical and clinically relevant overview of current anatomic and physiologic imaging of brain tumors as a foundation for further investigations, with a primary focus on MR imaging and PET techniques that have demonstrated utility in the current care of brain tumor patients.

18F-Fluoromisonidazole Quantification of Hypoxia in Human Cancer Patients Using Image-Derived Blood Surrogate Tissue Reference Regions.

UNLABELLED: (18)F-fluoromisonidazole ((18)F-FMISO) is the most widely used PET agent for imaging hypoxia, a condition associated with resistance to tumor therapy. (18)F-FMISO equilibrates in normoxic tissues but is retained under hypoxic conditions because of reduction and binding to macromolecules. A simple tissue-to-blood (TB) ratio is suitable for quantifying hypoxia. A TB ratio threshold of 1.2 or greater is useful in discriminating the hypoxic volume (HV) of tissue; TBmax is the maximum intensity of the hypoxic region and does not invoke a threshold. Because elimination of blood sampling would simplify clinical use, we tested the validity of using imaging regions as a surrogate for blood sampling. METHODS: Patients underwent 20-min (18)F-FMISO scanning during the 90- to 140-min interval after injection with venous blood sampling. Two hundred twenty-three (18)F-FMISO patient studies had detectable surrogate blood regions in the field of view. Quantitative parameters of hypoxia (TBmax, HV) derived from blood samples were compared with values using surrogate blood regions derived from the heart, aorta, or cerebellum. In a subset of brain cancer patients, parameters from blood samples and from the cerebellum were compared for their ability to independently predict outcome. RESULTS: Vascular regions of heart showed the highest correlation to measured blood activity (R(2) = 0.84). For brain studies, cerebellar activity was similarly correlated to blood samples. In brain cancer patients, Kaplan-Meier analysis showed that image-derived reference regions had predictive power nearly identical to parameters derived from blood, thus obviating the need for venous sampling in these patients. CONCLUSION: Simple static analysis of (18)F-FMISO PET captures both the intensity (TBmax) and the spatial extent (HV) of tumor hypoxia. An image-derived region to assess blood activity can be used as a surrogate for blood sampling in quantification of hypoxia.

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.

Carboplatin and bevacizumab for recurrent malignant glioma.

Over 65,000 primary brain tumors are diagnosed annually in the US alone. Malignant gliomas represent more than one-third of such cases. Despite advances in neuroimaging, surgical techniques, radiotherapy and chemotherapy, the survival rate of this disease remains poor. The introduction of agents which disrupt the function of vascular endothelial growth factor (VEGF) and its receptors to glioma therapy has resulted in an unusually high percentage of patients experiencing radiographic responses. Bevacizumab, approved by the Food and Drug Administration for the treatment of recurrent glioblastoma in 2009, has changed the field of neuro-oncology. The drug has been utilized as a single agent and in combination with the classic cytotoxic agents typically applied in this setting. Numerous studies have reported high response rates and encouraging extensions of time-to-progression. The optimal schedule and combination of bevacizumab with alternative drugs has not been identified. The current study presents the results of a retrospective analysis of the combination therapy utilizing bevacizumab with the alkylating agent carboplatin in patients with recurrent malignant glioma.

Comparison of 3 Tesla proton MR spectroscopy, MR perfusion and MR diffusion for distinguishing glioma recurrence from posttreatment effects.

PURPOSE: To compare 3 Tesla (3T) multi-voxel and single-voxel proton MR spectroscopy (MRS), dynamic susceptibility contrast perfusion MRI (DSC), and diffusion-weighted MRI (DWI) for distinguishing recurrent glioma from postradiation injury. MATERIALS AND METHODS: We reviewed all 3T MRS, DSC and DWI studies performed for suspicion of malignant glioma recurrence between October 2006 and December 2008. Maximum Cho/NAA and Cho/Cr peak-area and peak-height ratios were recorded for both multi-voxel and single-voxel MRS. Maximum cerebral blood volume (CBV) and minimum apparent diffusion coefficient (ADC) were normalized to white matter. Histopathology and clinical-radiologic follow-up served as reference standards. Receiver operating characteristic curves for each parameter were compared. RESULTS: Forty lesions were classified as glioma recurrence (n = 30) or posttreatment effect (n = 10). Diagnostic performance was similar for CBV ratio (AUC = 0.917, P < 0.001), multi-voxel Cho/Cr peak-area (AUC = 0.913, P = 0.002), and multi-voxel Cho/NAA peak-height (AUC = 0.913, P = 0.002), while ADC ratio (AUC = 0.726, P = 0.035) did not appear to perform as well. Single-voxel MRS parameters did not reliably distinguish tumor recurrence from posttreatment effects. CONCLUSION: A 3T DSC and multi-voxel MRS Cho/Cr peak-area and Cho/NAA peak-height appear to outperform DWI for distinguishing glioma recurrence from posttreatment effects. Single-voxel MRS parameters do not appear to distinguish glioma recurrence from posttreatment effects reliably, and therefore should not be used in place of multi-voxel MRS.

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.

Detection of ventricular shunt malfunction in the ED: relative utility of radiography, CT, and nuclear imaging.

The study objective was to determine the relative diagnostic utility of the radiographic shunt series (SS), head computed tomography (CT), and nuclear imaging performed in our Emergency Department (ED) for evaluating ventricular shunt malfunction. We retrospectively reviewed medical records, head CT (if performed), and nuclear imaging (if performed) for all ED patients with suspected shunt malfunction from 2002 to 2007 who underwent plain film shunt evaluation (296 cases/186 individuals) to determine if surgical shunt revision was performed. Logistic regression analysis was applied. Four percent (12/296) of radiographic SS were abnormal. Only 0.3% (1/296) underwent surgical revision in the absence of an abnormal head CT or nuclear imaging. Eighteen percent (51/282) of head CT exams were positive and 19% (24/128) of nuclear imaging exams were positive for shunt malfunction. Twenty-three percent (67/296) underwent surgical shunt revisions. Statistical analysis demonstrated that SS evaluation was not significantly associated with surgical shunt revision (OR 0.92; 95% CI, 0.7-1.2; p=0.47). Head CT demonstrated a significant association with surgical revision (OR 1.4; 95% CI, 1.2-1.5; p<0.001), as did nuclear imaging (OR 1.4; 95% CI, 1.2-1.6; p<0.001). Patients with suspected ventricular shunt malfunction frequently require surgical revision. Abnormal radiographic SS was not associated with progression to surgical shunt revision, whereas abnormal head CT and abnormal nuclear imaging were significantly associated with surgical revision. We conclude that radiographic SS in the ED is of low diagnostic utility and that patients with suspected shunt malfunction should instead initially undergo CT and/or nuclear imaging.

Imaging of cerebellopontine angle masses: self-assessment module.

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging features of cerebellopontine angle (CPA) masses and the role of advanced MRI in the differential diagnosis of CPA masses.

Distinction between glioma progression and post-radiation change by combined physiologic MR imaging.

INTRODUCTION: Magnetic resonance (MR) diffusion-weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion imaging (DSC), and MR spectroscopy (MRS) techniques provide specific physiologic information that may distinguish malignant glioma progression from post-radiation change, yet no single technique is completely reliable. We propose a simple, multiparametric scoring system to improve diagnostic accuracy beyond that of each technique alone. METHODS: Fifteen subjects with lesions suspicious for glioma progression following radiation therapy who had also undergone 3-tesla DWI, DSC, and MRS studies of the lesion were retrospectively reviewed. Minimum apparent diffusion coefficient (ADC) ratio, maximum regional cerebral blood volume (rCBV) ratio, and maximum MRS choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) metabolic peak-height ratios were quantified within each lesion. Each parameter (ADC ratio, rCBV ratio, and combined Cho/Cr and Cho/NAA ratios) was scored as either glioma progression (one point) or radiation change (zero point) based upon thresholds derived from our own data. For each lesion, the combined parameters yielded a multiparametric score (0 to 3) for prediction of tumor progression or post-radiation change. RESULTS: Optimum thresholds for ADC ratio (1.30), rCBV ratio (2.10), and either combined Cho/Cr (1.29) and Cho/NAA (1.06) yielded diagnostic accuracies of 86.7%, 86.7%, and 84.6%, respectively (p < 0.05). A combined multiparametric score threshold of 2 improved diagnostic accuracy to 93.3% (p < 0.05). CONCLUSION: In this small series combining 3-T DWI, DSC, and MRS diagnostic results using a simple, multiparametric scoring system has potential to improve overall diagnostic accuracy in distinguishing glioma progression from post-radiation change beyond that of each technique alone.

Intradural intramedullary spinal cord metastasis due to mesothelioma.

UNLABELLED: To report the occurrence of intramedullary spinal cord metastases in a patient with a mesothelioma. A case report. SETTING: University medical center. A 67-year old man with mesothelioma developed paraparesis 6-months after diagnostic thoracotomy. MR spine imaging revealed an intramedullary spinal cord metastases. Cyberknife radiotherapy. Intramedullary spinal cord metastases, although rare, is increasingly recognized with spinal cord MRI. Treatment remains unsatisfactory as treatment with surgery or irradiation is only partially effective.

Cerebellopontine angle meningioma presenting with hearing loss.

We present the case of a 48-year-old woman with a cerebellopontine angle meningioma who presented with sensorineural hearing loss. The lesion was nearly 4 cm in maximum dimension and extended into the internal auditory canal. Hearing loss resulting from cerebellopontine angle tumor is most commonly caused by vestibular schwannomas, which arise directly from the sheath of the vestibular nerve (VIII) in the internal auditory canal. Our case provides a review of magnetic resonance imaging features that aid in differentiation of enhancing cerebellopontine angle masses that can have similar clinical presentations.

Acute sensorineural hearing loss resulting from cerebellopontine angle arachnoid cyst.

We present the case of a 49-year-old woman who presented with acute, nonprogressive left sensorineural hearing loss and benign positional vertigo that was associated with an arachnoid cyst of the cerebellopontine angle. The presence of the lesion was documented by MRI examinations that were obtained 7 years apart. Arachnoid cysts at the cerebellopontine angle are usually found incidentally on MRI performed for unrelated reasons. However, if the arachnoid cyst displaces or compresses adjacent cranial nerves, symptoms may result. We review the salient imaging features of arachnoid cysts that allow their differentiation from other lesions of the cerebellopontine angle.

Asymmetric sensorineural hearing loss caused by vestibular schwannoma: Characteristic imaging features before and after treatment with stereotactic radiosurgery.

We report the case of a 71-year-old man who presented with a 2-year history of progressive left-sided hearing loss caused by a cerebellopontine angle mass lesion with classic imaging characteristics of a vestibular schwannoma. Vestibular schwannomas are typically diagnosed on dedicated MRI of the internal auditory canals obtained for asymmetric sensorineural hearing loss, as in this case. We review the characteristic imaging features of vestibular schwannomas that enable their differentiation from other mass lesions of the cerebellopontine angle cistern, allowing for treatment with stereotactic radiosurgery in this case.