Pulsed Reduced Dose Rate Radiotherapy in Conjunction With Bevacizumab or Bevacizumab Alone in Recurrent High-grade Glioma: Survival Outcomes.

Purpose: Dismal prognosis and limited treatment options for recurrent high-grade glioma have provoked interest in various forms of reirradiation. Pulsed reduced dose rate radiation therapy (pRDR) is a promising technique that exploits low-dose hyper-radiosensitivity of proliferating tumor cells while sparing adjacent nonproliferating normal brain tissue. Large radiation treatment volumes can thus be used to target both contrast-enhancing and FLAIR abnormalities thought to harbor recurrent gross and microscopic disease, respectively.

Acid ceramidase and its inhibitors: a drug target and a new class of drugs for killing glioblastoma cancer stem cells with high efficiency.

Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure.

Acid ceramidase confers radioresistance to glioblastoma cells.

Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment.

Acid ceramidase is a novel drug target for pediatric brain tumors.

Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance.

Magnetic Resonance Imaging-Based Radiomic Profiles Predict Patient Prognosis in Newly Diagnosed Glioblastoma Before Therapy.

Magnetic resonance imaging (MRI) is used to diagnose and monitor brain tumors. Extracting additional information from medical imaging and relating it to a clinical variable of interest is broadly defined as radiomics. Here, multiparametric MRI radiomic profiles (RPs) of glioblastoma (GBM) brain tumors is related with patient prognosis.

Spinal osteoblastic meningioma with hematopoiesis: radiologic-pathologic correlation and review of the literature.

Spinal meningiomas associated with bone formation and hematopoiesis are rare tumors with only 3 prior case reports in the literature. We describe a case report of a woman who presented with back pain and an isolated event of urinary incontinence. A calcified spinal canal mass at T8 was identified on computed tomographic and magnetic resonance imaging.

Quantifying metal-induced susceptibility artifacts of the instrumented spine at 1.5T using fast-spin echo and 3D-multispectral MRI.

Purpose: To evaluate magnetic resonance imaging (MRI) artifacts near metallic spinal instrumentation using both conventional metal artifact reduction sequences (MARS) and 3D multispectral imaging sequences (3D-MSI).

Materials And Methods: Both MARS and 3D-MSI images were acquired in 10 subjects with titanium spinal hardware on a 1.5T GE 450W scanner.

Changes in perfusion and diffusion in the endplate regions of degenerating intervertebral discs: a DCE-MRI study.

Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) was used to investigate the associations between intervertebral disc degeneration and changes in perfusion and diffusion in the disc endplates.

Methods: 56 participants underwent MRI scans. Changes in DCE-MRI signal enhancement in the endplate regions were analyzed.

Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma.

Background: Recent conflicting reports have found both brain tumor hypercellularity and necrosis in regions of restricted diffusion on MRI-derived apparent diffusion coefficient (ADC) images. This study precisely compares ADC and cell density voxel by voxel using postmortem human whole brain samples.

Methods: Patients with meningioma were evaluated to determine a normative ADC distribution within benign fluid attenuated inversion recovery (FLAIR) T2/hyperintensity surrounding tumor.

Comprehensive characterization of glioblastoma tumor tissues for biomarker identification using mass spectrometry-based label-free quantitative proteomics.

Cancer is a complex disease; glioblastoma (GBM) is no exception. Short survival, poor prognosis, and very limited treatment options make it imperative to unravel the disease pathophysiology. The critically important identification of proteins that mediate various cellular events during disease is made possible with advancements in mass spectrometry (MS)-based proteomics.

Dynamic-susceptibility contrast agent MRI measures of relative cerebral blood volume predict response to bevacizumab in recurrent high-grade glioma.

Background: The anti-VEGF antibody, bevacizumab, is standard treatment for patients with recurrent glioblastoma. In this setting, traditional anatomic MRI methods such as post-contrast T1-weighted and T2-weighted imaging are proving unreliable for monitoring response. Here we evaluate the prognostic significance of pre- and posttreatment relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast MRI to predict response to bevacizumab.

The role of pre-treatment white matter abnormalities in developing white matter changes following whole brain radiation: a volumetric study.

White matter injury is a known complication of whole brain radiation (WBRT). Little is known about the factors that predispose a patient to such injury. The current study used MR volumetrics to examine risk factors, in particular the influence of pre-treatment white matter health, in developing white matter change (WMC) following WBRT.

Effects of perfusion on diffusion changes in human brain tumors.

Purpose: To characterize the influence of perfusion on the measurement of diffusion changes over time when ADC is computed using standard two-point methods.

Materials And Methods: Functional diffusion maps (FDMs), which depict changes in diffusion over time, were compared with rCBV changes in patients with brain tumors. The FDMs were created by coregistering and subtracting ADC maps from two time points and categorizing voxels where ADC significantly increased (iADC), decreased (dADC), or did not change (ncADC).

Vascular change measured with independent component analysis of dynamic susceptibility contrast MRI predicts bevacizumab response in high-grade glioma.

Background: Standard pre- and postcontrast (T1 + C) anatomical MR imaging is proving to be insufficient for accurately monitoring bevacizumab treatment response in recurrent glioblastoma (GBM). We present a novel imaging biomarker that detects abnormal tumor vasculature exhibiting both arterial and venous perfusion characteristics. We hypothesized that a decrease in the extent of this abnormal vasculature after bevacizumab treatment would predict treatment efficacy and overall survival.

Spatially quantifying microscopic tumor invasion and proliferation using a voxel-wise solution to a glioma growth model and serial diffusion MRI.

The purpose of this study was to develop a voxel-wise analytical solution to a glioma growth model using serial diffusion MRI. These cell invasion, motility, and proliferation level estimates (CIMPLE maps) provide quantitative estimates of microscopic tumor growth dynamics. After an analytical solution was found, noise simulations were performed to predict the effects that perturbations in apparent diffusion coefficient values and the time between apparent diffusion coefficient map acquisitions would have on the accuracy of CIMPLE maps.

3D visualization of subdural electrode shift as measured at craniotomy reopening.

Purpose: Subdural electrodes are implanted for recording intracranial EEG (iEEG) in cases of medically refractory epilepsy as a means to locate cortical regions of seizure onset amenable to surgical resection. Without the aid of imaging-derived 3D electrode models for surgical planning, surgeons have relied on electrodes remaining stationary from the time between placement and follow-up resection. This study quantifies electrode shift with respect to the cortical surface occurring between electrode placement and subsequent reopening.

Three-dimensional visualization of subdural electrodes for presurgical planning.

Background: Accurate localization and visualization of subdural electrodes implanted for intracranial electroencephalography in cases of medically refractory epilepsy remains a challenging clinical problem.

Objective: We introduce a technique for creating accurate 3-dimensional (3D) brain models with electrode overlays, ideal for resective surgical planning.

Methods: Our procedure uses postimplantation magnetic resonance imaging (MRI) and computed tomographic (CT) imaging to create 3D models of compression-affected brain combined with intensity-thresholded CT-derived electrode models using freely available software.

Volumetric analysis of functional diffusion maps is a predictive imaging biomarker for cytotoxic and anti-angiogenic treatments in malignant gliomas.

Anti-angiogenic agents targeting brain tumor neovasculature may increase progression-free survival in patients with recurrent malignant gliomas. However, when these patients do recur it is not always apparent as an increase in enhancing tumor volume on MRI, which has been the standard of practice for following patients with brain tumors. Therefore alternative methods are needed to evaluate patients treated with these novel therapies.

Validation of functional diffusion maps (fDMs) as a biomarker for human glioma cellularity.

Purpose: To present comprehensive examinations of the assumptions made in functional diffusion map (fDM) analyses and provide a biological basis for fDM classification.

Materials And Methods: Sixty-nine patients with gliomas were enrolled in this study. To determine the sensitivity of apparent diffusion coefficients (ADCs) to cellularity, cell density from stereotactic biopsy specimens was correlated with preoperative ADC maps.

Utility of functional diffusion maps to monitor a patient diagnosed with gliomatosis cerebri.

Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive imaging biomarker for tumor cellularity. Functional diffusion maps (fDMs), which examine voxel-by-voxel changes in the apparent diffusion coefficient (ADC) calculated from serial DWIs, have previously been applied to regions of contrast-enhancement; however, application of fDMs to non-enhancing brain tumors has not been pursued. In this case study we demonstrate the utility of applying fDMs to regions of abnormal FLAIR signal intensity in a patient diagnosed with gliomatosis cerebri: a relatively rare, infiltrative, non-enhancing brain tumor.

Initial experience of FDG-PET/CT guided IMRT of head-and-neck carcinoma.

Purpose: The purpose of this study is to evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) fused with planning computed tomography (CT) on tumor localization, which guided intensity-modulated radiotherapy (IMRT) of patients with head-and-neck carcinoma.

Methods And Materials: From October 2002 through April 2005, we performed FDG-PET/CT guided IMRT for 28 patients with head-and-neck carcinoma. Patients were immobilized with face masks that were attached with five fiducial markers.

Sample size calculation for clinical trials using magnetic resonance imaging for the quantitative assessment of carotid atherosclerosis.

Purpose: To provide sample size calculation for the quantitative assessment of carotid atherosclerotic plaque using non-invasive magnetic resonance imaging in multi-center clinical trials. METHODS. As part of a broader double-blind randomized trial of an experimental pharmaceutical agent, 20 asymptomatic placebo-control subjects were recruited from 5 clinical sites for a multi-center study.

Feasibility of in vivo, multicontrast-weighted MR imaging of carotid atherosclerosis for multicenter studies.

Purpose: To test the image quality (ImQ) and interscan coverage of MRI for measuring carotid atherosclerosis across multiple centers.

Materials And Methods: Thirty-nine subjects from five clinical sites (site 1: n=11; site 2: n=16; site 3: n=2; site 4: n=3; site 5: n=7) were imaged on GE 1.5T scanners using a standardized carotid imaging protocol with five weightings (T1, proton density (PD), T2, time-of-flight (TOF), and contrast-enhanced (CE) T1).

Dexamethasone normalizes brain tumor hemodynamics as indicated by dynamic susceptibility contrast MRI perfusion parameters.

The purpose of this study is to demonstrate the utility of dynamic susceptibility contrast (DSC) MRI-derived perfusion parameters to characterize the hemodynamic effects of dexamethasone in a 9L gliosarcoma tumor model. Twenty-four rats underwent intracerebral inoculation with 9L tumor cells. Fifteen were treated with a total of 3mg/kg of dexamethasone on days 10-14 post-inoculation, while the remaining 9 rats served as controls.