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Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40–50 ms at 1.5 T, 20–35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.

A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The “minimum standard” recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)–prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An “ideal” protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.

Validated biomarkers that more accurately predict prognosis and/or measure disease burden in patients with high-grade gliomas would help triage which treatment strategies are most promising for evaluation in Phase III multicenter trials. Multicenter trials to evaluate imaging biomarkers in this group face particular challenges; these trials have historically been slow to accrue and have not recently succeeded in validating new imaging biomarkers useful in treatment development. Due to variability in image acquisition protocols, scanner hardware, image analysis, and interpretive schemes, promising results obtained in single centers are poor predictors of success in the multicenter setting. Multicenter preliminary data to support further evaluation of imaging biomarkers is rarely available. The need for more efficient trial designs that bring multicenter data earlier into the process of biomarker development has become increasingly clear. In this presentation, the planning process within ECOG-ACRIN’s Brain Tumor Working Group for a platform multicenter trial called GABLE (Glioblastoma Accelerated Biomarker Learning Environment trial) designed to evaluate biomarkers for distinguishing pseudoprogression from true progression in patients with newly diagnosed GBM is described. In our planning process, it was determined that efficiencies can be gained from evaluating multiple biomarker types in parallel rather than serially; in the context of the proposed trial, not only conventional imaging biomarkers but plasma biomarkers and radiomic biomarkers can be evaluated simultaneously. Patient tolerance limits the feasibility of evaluating multiple non-standard-of-care imaging biomarkers in parallel. For this group of biomarkers, a “fast-switching” serial evaluation strategy using multiple interim analyses was developed to triage out biomarkers unlikely to succeed in identifying patient groups with clinically significant differences in median survival. For biomarker triage, an endpoint of event-free survival (events of either death or NANO progression) was proposed. Simulations were used to evaluate alpha and beta error using this evaluation strategy.

BACKGROUND AND PURPOSE: Brain tumor clinical trials requiring solid tumor assessment typically rely on the 2D manual delineation of enhancing tumors by ≥2 expert readers, a time-consuming step with poor interreader agreement. As a solution, we developed quantitative dT1 maps for the delineation of enhancing lesions. This retrospective analysis compares dT1 with 2D manual delineation of enhancing tumors acquired at 2 time points during the post therapeutic surveillance period of the American College of Radiology Imaging Network 6677/Radiation Therapy Oncology Group 0625 (ACRIN 6677/RTOG 0625) clinical trial. MATERIALS AND METHODS: Patients enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized Phase II trial of bevacizumab in recurrent glioblastoma, underwent standard MR imaging before and after treatment initiation. For 123 patients from 23 institutions, both 2D manual delineation of enhancing tumors and dT1 datasets were evaluable at weeks 8 (n = 74) and 16 (n = 57). Using dT1, we assessed the radiologic response and progression at each time point. Percentage agreement with adjudicated 2D manual delineation of enhancing tumor reads and association between progression status and overall survival were determined. RESULTS: For identification of progression, dT1 and adjudicated 2D manual delineation of enhancing tumor reads were in perfect agreement at week 8, with 73.7% agreement at week 16. Both methods showed significant differences in overall survival at each time point. When nonprogressors were further divided into responders versus nonresponders/nonprogressors, the agreement decreased to 70.3% and 52.6%, yet dT1 showed a significant difference in overall survival at week 8 (P = .01), suggesting that dT1 may provide greater sensitivity for stratifying subpopulations. CONCLUSIONS: This study shows that dT1 can predict early progression comparable with the standard method but offers the potential for substantial time and cost savings for clinical trials.

TPS2577 Background: Patients diagnosed with malignant high-grade gliomas (WHO grade III-IV) experience significant morbidity and mortality associated with these cancers. While the mainstay of therapy for patients with newly diagnosed high-grade glioma is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain very poor. BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. Early preclinical studies demonstrated BMX-001’s ability to act as a radioprotectant to healthy tissue such as a central nervous white matter and as a radiosensitizer to cancer cells, in particular, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase I study of newly diagnosed high-grade glioma patients, and we found that BMX-001 is safe and well-tolerated in this population. The maximum tolerated dose of BMX-001 during concurrent RT and TMZ was determined to be 28 mg delivered subcutaneously (SC) followed by 16 biweekly SC doses at 14 mg (Peters et al., Neuro-Oncology 2018). Methods: For this multi-site, open-label, phase II study (NCT02655601), we will randomize approximately 160 patients 1:1 to concurrent RT and TMZ with BMX-001 versus concurrent RT and TMZ alone. Key eligibility criteria include newly diagnosed histologically confirmed high-grade glioma (WHO III-IV), 18 ≥ years, and Karnofsky performance status ≥ 70%. The primary endpoint is overall survival. Secondary endpoints include cognitive performance as assessed by standardized cognitive testing, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are health-related quality of life (as assessed by Functional Assessment of Cancer Therapy–Brain, Functional Assessment of Cancer Therapy-Cognition, and Functional Assessment of Chronic Illness Therapy-Fatigue), qualitative hair loss, and white matter integrity (as measured by MRI diffusion tensor/susceptibility imaging). Since November 2018, this phase II study has enrolled 64 of 160 high-grade glioma patients at six sites with future sites planned to be implemented. Clinical trial information: NCT02655601 .

PURPOSE: To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material–enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. MATERIALS AND METHODS: A total of 18 patients (mean age, 57 years ± 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (K(trans)) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (v(e)), and initial area under the gadolinium concentration curve (IAUGC). Two independently trained teams consisting of a neuroradiologist and a technologist segmented the enhancing tumor on three-dimensional spoiled gradient-recalled acquisition in the steady-state images. Mean and median parameter values in the enhancing tumor were extracted after registering segmentations to parameter maps. The effect of imaging time relative to treatment, map quality, imager magnet and sequence, average tumor volume, and reader variability in tumor volume on IRV was studied by using intraclass correlation coefficients (ICCs) and linear mixed models. RESULTS: Mean interreader variations (± standard deviation) (difference as a percentage of the mean) for mean and median IAUGC, mean and median K(trans), and median v(e) were 18% ± 24, 17% ± 23, 27% ± 34, 16% ± 27, and 27% ± 34, respectively. ICCs for these metrics ranged from 0.90 to 1.0 for baseline and from 0.48 to 0.76 for posttreatment examinations. Variability in reader-derived tumor volume was significantly related to IRV for all parameters. CONCLUSION: Differences in reader tumor segmentations are a significant source of interreader variation for all dynamic contrast-enhanced MRI parameters. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Wolf in this issue.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides quantitative metrics (e.g. Ktrans, ve) via pharmacokinetic models. We tested inter-algorithm variability in these quantitative metrics with 11 published DCE-MRI algorithms, all implementing Tofts-Kermode or extended Tofts pharmacokinetic models. Digital reference objects (DROs) with known Ktrans and ve values were used to assess performance at varying noise levels. Additionally, DCE-MRI data from 15 head and neck squamous cell carcinoma patients over 3 time-points during chemoradiotherapy were used to ascertain Ktrans and ve kinetic trends across algorithms. Algorithms performed well (less than 3% average error) when no noise was present in the DRO. With noise, 87% of Ktrans and 84% of ve algorithm-DRO combinations were generally in the correct order. Low Krippendorff’s alpha values showed that algorithms could not consistently classify patients as above or below the median for a given algorithm at each time point or for differences in values between time points. A majority of the algorithms produced a significant Spearman correlation in ve of the primary gross tumor volume with time. Algorithmic differences in Ktrans and ve values over time indicate limitations in combining/comparing data from distinct DCE-MRI model implementations. Careful cross-algorithm quality-assurance must be utilized as DCE-MRI results may not be interpretable using differing software.

Purpose Dynamic contrast–enhanced (DCE) MRI-extracted parameters measure tumor microvascular physiology and are usually calculated from an intratumor region of interest (ROI). Optimal ROI delineation is not established. The valid clinical use of DCE-MRI requires that the variation for any given parameter measured within a tumor be less than that observed between tumors in different patients. This work evaluates the impact of tumor ROI selection on the assessment of intra- and interpatient variability. Method and Materials Head and neck cancer patients received initial targeted therapy (TT) treatment with erlotinib and/or bevacizumab, followed by radiotherapy and concurrent cisplatin with synchronous TT. DCE-MRI data from Baseline and the end of the TT regimen (Lead-In) were analyzed to generate the vascular transfer function (K trans ), the extracellular volume fraction (v e ), and the initial area under the concentration time curve (iAUC 1 min ). Four ROI sampling strategies were used: whole tumor or lymph node (Whole), the slice containing the most enhancing voxels (SliceMax), three slices centered in SliceMax (Partial), and the 5% most enhancing contiguous voxels within SliceMax (95Max). The average coefficient of variation (aCV) was calculated to establish intrapatient variability among ROI sets and interpatient variability for each ROI type. The average ratio between each intrapatient CV and the interpatient CV was calculated (aRCV). Results Baseline primary/nodes aRCVs for different ROIs not including 95Max were, for all three MR parameters, in the range of 0.14–0.24, with Lead-In values between 0.09 and 0.2, meaning a low intrapatient vs. interpatient variation. For 95Max, intrapatient CVs approximated interpatient CVs, meaning similar data dispersion and higher aRCVs (0.6–1.27 for baseline) and 0.54–0.95 for Lead-In. Conclusion Distinction between different patient’s primary tumors and/or nodes cannot be made using 95Max ROIs. The other three strategies are viable and equivalent for using DCE-MRI to measure head and neck cancer physiology.

Purpose: Calculation of the precontrast longitudinal relaxation times T10 is an integral part of the Tofts-based pharmacokinetic PK analysis of dynamic contrast enhanced–magnetic resonance images. The purpose of this study was to investigate the interpatient and over time variability of T10 in head and neck primary tumors and involved nodes and to determine the median T10 for primary and nodes T 10 p,n . The authors also looked at the implication of using voxel-based T10 values versus region of interest ROI-based T10 on the calculated values for vascular permeability K trans and extracellular volume fraction ve. Methods: Twenty head and neck cancer patients receiving concurrent chemoradiation and molecularly targeted agents on a prospective trial comprised the study population. Voxel-based T10’s were generated using a gradient echo sequence on a 1.5 T MR scanner using the variable flip angle method with two flip angles J. A. Brookes et al., “Measurement of spin-lattice relaxation times with FLASH for dynamic MRI of the breast,” Br. J. Radiol. 69, 206–214 1996. The voxel-based T10, K trans , and ve were calculated using iCAD’s ® Nashua, NH software. The mean T10’s in muscle and fat ROIs were calculated T10 m,f . To assess reliability of ROI drawing, T10 p,n values from ROIs delineated by 2 users A and B were calculated as the average of the T10’s for 14 patients. For a subset of three patients, the T10 variability from baseline to end of treatment was also investigated. The K trans and ve from primary and node ROIs were calculated using voxel-based T10 values and T 10 p,n and differences reported. Results: The calculated T 10 values for fat and muscle are within the range of values reported in literature for 1.5 T, i.e., T 10 m = 0.958 s and T 10 f = 0.303 s. The average over 14 patients of the T10’s based on drawings by users A and B were T 10 pA = 0.804 s, T 10 nA = 0.760 s, T 10 pB = 0.849 s, and T10 nB = 0.810 s. The absolute percentage difference between K trans and ve calculated with voxelbased T10 versus T 10 p,n ranged from 6% to 81% and from 2% to 24%, respectively. Conclusions: There is a certain amount of variability in the median T10 values between patients, but the differences are not significant. There were also no statistically significant differences between the T10 values for primary and nodes at baseline and the subsequent time points p = 0.94 Friedman test. Voxel-based T10 calculations are essential when quantitative Tofts-based PK analysis in heterogeneous tumors is needed. In the absence of T10 mapping capability, when a relative, qualitative analysis is deemed sufficient, a value of T 10 p,n = 0.800 s can be used as an estimate for T10 for both the primary tumor and the affected nodes in head and neck cancers at all the time points considered. © 2010 American Association of Physicists in Medicine. DOI: 10.1118/1.3427487

Purpose To quantify the repeatability of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in patients with glioblastoma multiforme. Materials and Methods IRB approval and informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant study. Sixteen patients with glioblastoma multiforme underwent MR imaging at two time points without interval intervention. ADC and FA maps were registered to the contrast-enhanced and fluid-attenuated inversion recovery (FLAIR) image volumes. Volumes of tumor-related enhancement (TRE) and FLAIR signal abnormality (FSA) were defined using a semiautomated segmentation technique. Results Repeated observations of mean ADC and mean FA were highly consistent within both TRE (ADC: r = 0.947,P < 0.0001; FA: r = 0.947, P < 0.0001) and FSA (ADC: r = 0.979, P < 0.0001; FA: r = 0.972, P < 0.0001). Within TRE, repeatability coefficients and 95% confidence intervals (CIs) for change measured 0.104 × 10−3 mm2S−1 and 7.4% (ADC) and 0.0196 and 13.9% (FA), respectively. Within FSA, repeatability coefficients and 95% CI for change measured 0.071 × 10−3 mm2S−1 and 5.2% (ADC) and 0.0159 and 8.7% (FA), respectively. To detect 10% changes in mean ADC, sample sizes of nine (TRE) and six (FSA) patients would be required. The same change in mean FA would require sample sizes of 21 (TRE) and 10 (FSA) patients, respectively. Conclusion Changes after therapy greater than the repeatability coefficient or 95% CI for change are unlikely to be related to variability in the measurement of ADC and FA. J. Magn. Reson. Imaging 2009;29:1199–1205. © 2009 Wiley-Liss, Inc.

The objective of our study was to test the hypothesis that the finding of hyperintense hippocampal signal intensity on T2-weighted MR images soon after febrile status epilepticus is associated with subsequent hippocampal volume loss and persistent abnormal signal intensity on T2-weighted images (i.e., mesial temporal sclerosis).Eleven children (mean age, 25 months) underwent initial MRI that included coronal temporal lobe imaging within 72 hours of febrile status epilepticus and follow-up imaging from 3 to 23 months later (mean, 9 months). A neuroradiologist blinded to clinical history graded initial and follow-up hippocampal signal intensity on a scale from 0 (normal) to 4 (markedly increased). Two blinded observers measured hippocampal volumes on initial and follow-up MR studies using commercially available software and volumes from 30 healthy children (mean age, 6.3 years). Initial signal intensity and hippocampal volume changes were compared using Kendall tau correlation coefficients.On initial imaging, hyperintense signal intensity ranging from 1 (minimally increased) to 4 (markedly increased) was seen in seven children. Four children had at least one hippocampus with moderate or marked signal abnormality, three children had a hippocampus with mild or minimal abnormality, and four children had normal signal intensity. The Kendall tau correlation coefficient between signal intensity increase and volume change was -0.68 (p0.01). Five children (two with temporal lobe epilepsy and two with complex partial seizures) had hippocampal volume loss and increased signal intensity on follow-up imaging, meeting the criteria for mesial temporal sclerosis.MRI findings of a markedly hyperintense hippocampus in children with febrile status epilepticus was highly associated with subsequent mesial temporal sclerosis.

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.

A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR systems.

BACKGROUND AND PURPOSE: For more widespread clinical use advanced imaging methods such as relative cerebral blood volume must be both accurate and repeatable. The aim of this study was to determine the repeatability of relative CBV measurements in newly diagnosed glioblastoma multiforme by using several of the most commonly published estimation techniques. MATERIALS AND METHODS: The relative CBV estimates were calculated from dynamic susceptibility contrast MR imaging in double-baseline examinations for 33 patients with treatment-naive and pathologically proved glioblastoma multiforme (men = 20; mean age = 55 years). Normalized and standardized relative CBV were calculated by using 6 common postprocessing methods. The repeatability of both normalized and standardized relative CBV, in both tumor and contralateral brain, was examined for each method with metrics of repeatability, including the repeatability coefficient and within-subject coefficient of variation. The minimum sample size required to detect a parameter change of 10% or 20% was also determined for both normalized relative CBV and standardized relative CBV for each estimation method. RESULTS: When ordered by the repeatability coefficient, methods using postprocessing leakage correction and ΔR2*(t) techniques offered superior repeatability. Across processing techniques, the standardized relative CBV repeatability in normal-appearing brain was comparable with that in tumor ( P = .31), yet inferior in tumor for normalized relative CBV ( P = .03). On the basis of the within-subject coefficient of variation, tumor standardized relative CBV estimates were less variable (13%–20%) than normalized relative CBV estimates (24%–67%). The minimum number of participants needed to detect a change of 10% or 20% is 118–643 or 30–161 for normalized relative CBV and 109–215 or 28–54 for standardized relative CBV. CONCLUSIONS: The ΔR2* estimation methods that incorporate leakage correction offer the best repeatability for relative CBV, with standardized relative CBV being less variable and requiring fewer participants to detect a change compared with normalized relative CBV.

Diffusion-weighted magnetic resonance (MR) imaging and perfusion MR imaging are advanced techniques that provide information not available from conventional MR imaging. In particular, these techniques have a number of applications with regard to characterization of tumors and assessment of tumor response to therapy. In this review, the authors describe the fundamental principles of diffusion-weighted and perfusion MR imaging and provide an overview of the ways in which these techniques are being used to characterize tumors by helping distinguish tumor types, assess tumor grade, and attempt to determine tumor margins. In addition, the role of these techniques for evaluating response to tumor therapy is outlined.

The purpose of our study was to determine the degree to which carotid canal fracture and other CT findings are associated with internal carotid artery (ICA) injury in patients with head trauma.Three neuroradiologists retrospectively evaluated CT scans and cerebral angiograms of 43 patients who underwent cerebral angiography within 7 days after blunt cranial trauma over a 5-year period. Seventeen patients underwent unilateral and 26 had bilateral carotid angiography. Angiograms were evaluated for ICA injury and CT scans were evaluated for carotid canal fracture, brain contusion, subarachnoid hemorrhage, basilar skull fracture, subdural hematoma, soft-tissue swelling, sphenoid sinus air-fluid level, and other skull fracture. We recorded the number of true-positive (+CT, +angiogram), true-negative (-CT, -angiogram), false-positive (+CT, -angiogram), and false-negative (-CT, +angiogram) studies. We determined the sensitivity, specificity, positive predictive value, and negative predictive value for each CT finding.We identified 21 carotid canal fractures in 17 patients. Eleven ICA injuries were seen in 10 patients. Six patients with ICA injury had a carotid canal fracture. The presence of a carotid canal fracture had a sensitivity of 60% and specificity of 67% for detection of injury to the ICA passing through that canal. These values were similar to those for other CT findings.Sensitivity, specificity, positive predictive value, and negative predictive value of carotid canal fracture were only moderately good for determining the presence of ICA injury and were similar to other CT findings not typically associated with ICA injury.

The advent of diffusion-weighted MR imaging and diffusion tensor MR imaging has had little impact on brain tumor detection. Diffusion-weighted imaging has been effective in characterizing specific types of masses, particularly in distinguishing epidermoids from arachnoid cysts, and cystic tumors from intracerebral abscesses. Presurgical planning using tractography with diffusion tensor MR imaging, and perhaps the evaluation of tumor response to chemotherapy and radiation therapy with diffusion-weighted imaging, may become important applications in the near future.

To compare fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) with the current standard, magnetic resonance (MR) imaging, to determine the sensitivity and specificity of FDG PET for detection of cerebral metastases and to determine the factors that may affect lesion conspicuity.Forty patients underwent brain PET and contrast material-enhanced brain MR imaging, with a maximum of 30 days between examinations. PET and MR images were each retrospectively reviewed by two independent readers who were blinded to the clinical history and results of the other technique. Presence of metastatic disease was recorded for each modality. Sensitivity and specificity of FDG PET were determined with MR imaging as the standard. Statistical analysis was performed with the Fisher exact test and the logistic regression model.Sixteen patients had cerebral metastases at MR imaging, and in 12 of these, PET scans were interpreted as showing metastatic disease (in four, scans were false-negative). Twenty-four patients had no cerebral metastases at MR imaging, and 20 of these had PET scans interpreted as normal (in four, scans were false-positive). For identification of patients with cerebral metastases, FDG PET had a sensitivity of 75% (12 of 16) and a specificity of 83% (20 of 24). Thirty-eight metastatic lesions were seen at MR imaging; 23 (61%) of these were identified at PET. Size was a statistically significant factor that influenced lesion detection at PET (P.001).Only 61% of metastatic lesions in the brain were identified at PET. In particular, detection of small lesions was difficult.

CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials. The Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group is an international, multidisciplinary effort to develop standard response and progression criteria for use in clinical trials of treatment for brain metastases. Previous efforts have focused on aspects of trial design, such as patient population, variations in existing response and progression criteria, and challenges when incorporating neurological, neuro-cognitive, and quality-of-life endpoints into trials of patients with brain metastases. Here, we present our recommendations for standard response and progression criteria for the assessment of brain metastases in clinical trials. The proposed criteria will hopefully facilitate the development of novel approaches to this difficult problem by providing more uniformity in the assessment of CNS metastases across trials.

To measure mean cerebral blood flow (CBF) in ischemic and nonischemic territories and in low-attenuation regions in patients with acute stroke by using deconvolution-derived hemodynamic imaging.Twelve patients with acute middle cerebral artery stroke and 12 control patients were examined by using single-section computed tomography (CT) perfusion scanning. Analysis was performed with a deconvolution-based algorithm. Comparisons of mean CBF, cerebral blood volume (CBV), and mean transit time (MTT) were determined between hemispheres in all patients and between low- and normal-attenuation regions in patients with acute stroke. Two independent readers examined the images for extent of visually apparent regional perfusion abnormalities. The data were compared with extent of final infarct in seven patients with acute stroke who underwent follow-up CT or magnetic resonance imaging.Significant decreases in CBF (-50%, P =.001) were found in the affected hemispheres of patients with acute stroke. Significant changes in CBV (-26%, P =.03) and MTT (+111%, P =.004) were also seen. Significant alterations in perfusion were also seen in low- compared with normal-attenuation areas. Pearson correlation between readers for extent of CBF abnormality was 0.94 (P =.001). Intraobserver variation was 8.9% for CBF abnormalities.Deconvolution analysis of CT perfusion data is a promising method for evaluation of cerebral hemodynamics in patients with acute stroke.

To quantify the test-retest repeatability of mean diffusivity (MD) and fractional anisotropy (FA) derived from diffusion tensor imaging (DTI) tractography in a cohort of paediatric patients with localization-related epilepsy.30 patients underwent 2 DTI acquisitions [repetition time/echo time (ms), 7000/90; flip, 90°; b-value, 1000 s mm(-2); voxel (mm), 2 × 2 × 2]. Two observers used Diffusion Toolkit and TrackVis ( www.trackvis.org ) to segment and analyse the following tracts: corpus callosum, corticospinal tracts, arcuate fasciculi, inferior longitudinal fasciculi and inferior fronto-occipital fasciculi. Mean MD and mean FA were calculated for each tract. Each observer independently analysed one of the DTI data sets for every patient.Segmentation identified all tracts in all subjects, except the arcuate fasciculus. There was a highly consistent relationship between repeated observations of MD (r = 0.993; p 0.0001) and FA (r = 0.990; p 0.0001). For each tract, coefficients of variation ranged from 0.9% to 2.1% for MD and from 1.5% to 2.8% for FA. The 95% confidence limits (CLs) for change ranged from 2.8% to 6% for MD and from 4.3% to 8.6% for FA. For the arcuate fasciculus, Cohen's κ for agreement between the observers (identifiable vs not identifiable) was 1.0.We quantified the repeatability of two commonly utilized scalar metrics derived from DTI tractography. For an individual patient, changes greater than the repeatability coefficient or 95% CLs for change are unlikely to be related to variability in their measurement.Reproducibility of these metrics will aid in the design of future studies and might one day be used to guide management in patients with epilepsy.

Purpose: Our purpose was to show the computed tomography (CT) and magnetic resonance (MR) imaging features of vertex epidural hematomas (EDHs) and emphasize pitfalls in the diagnosis of this entity. Subjects and methods: The neuroradiologic studies of four patients (CT in four, MR imaging and MR venography in one) were evaluated for EDH shape, size and appearance. Results: EDHs were biconvex in three patients and crescentic in one patient. CT appearances included a collection that was hyperdense (two patients), generally isodense with a few regions of hyperdensity (one patient) and mixed hyperdense and hypodense (one patient). MR imaging findings in one patient consisted of hyperintense signal on T1-weighted images and hypointense signal on T2-weighted images. Inferior displacement of the superior sagittal sinus was seen in two patients. Diagnosis of a small vertex EDH was difficult on routine axial CT in one patient, but apparent on MR imaging and MR venography. Conclusions: Small vertex EDHs can be difficult to diagnose on routine CT. MR imaging or thin section CT should be performed to exclude the diagnosis in patients with trauma to the skull vertex.

This paper reviews published post-mortem brain and in-vivo proton magnetic resonance spectroscopy (1H-MRS) studies in Alzheimer's disease (AD) and focuses on the emerging role of N-acetylaspartate (NAA) as a prognostic marker of neuronal function. Post-mortem brain studies have reported significantly lower NAA levels in AD brains than in control brains, and some have correlated the low levels with neuropathological findings (i.e. amyloid plaques and neurofibrillary tangles). Similarly, almost all published in-vivo studies have reported lower NAA levels in AD patients compared to elderly controls. While some studies have found changes in metabolite levels that were considered useful for the diagnosis of AD, most have found that 1H-MRS provided little or no advantages over other, more common diagnostic tools. Instead, recent studies in AD and other neuropsychiatric disorders suggest that NAA may be more useful as a prognostic marker for monitoring neurodegeneration, stabilization, or improvement, and for evaluating therapeutic response to novel drugs.

A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR systems.

To assess the patterns of abnormal neuroradiologic findings in patients with a hypercoagulable state related to activated protein C (APC) resistance.Records in 23 patients with a hypercoagulable state related to APC resistance (18 women, five men; average age, 44.5 years) were reviewed for cerebrovascular disease risk factors and other causes of a hypercoagulable state. Computed tomographic scans, magnetic resonance (MR) images, angiograms, and transesophageal echocardiograms were also reviewed.Stroke risk factors or other causes of a hypercoagulable state were found in 12 patients. Arterial infarcts were seen in 18 patients. Hyperintense white matter foci were seen on MR images in six patients. Dural sinus thrombosis was found in four patients. Angiograms of intracranial circulation in six patients showed major artery occlusions in four. MR angiograms in four patients showed internal carotid artery occlusion in one. No major abnormalities were seen in extracranial cerebral vasculature in 15 patients. Transesophageal echocardiograms in 11 patients showed a patent foramen ovale in one patient but no systemic source of embolism. Seven patients had non-central nervous system thrombotic events.Patients with APC resistance and stroke appear to differ from the general stroke population in terms of age and frequency of extracranial sources of cerebrovascular disease.

The purpose of this study was to determine the spectrum of neuroradiologic findings in patients with antiphospholipid antibodies (APA) and to compare findings in systemic lupus erythematosus (SLE) and non-SLE patients.We identified 110 patients with APA who underwent CT or MR imaging, of whom 59 (54%) had abnormal studies. Of these 59 patients, abnormalities were categorized as large infarcts, cortical infarcts, lacunar infarcts, hyperintense white matter foci on T2-weighted images, or dural sinus thrombosis. White matter foci were designated as small (5mm) or large (5 mm).Large infarcts were the most common abnormality, seen in 24 of 110 (22%) patients, followed in frequency by hyperintense white matter foci, seen in 19 of 110 (17%) patients. Ninety-five percent of patients with hyperintense white matter foci had at least one large lesion, and 76% had five or more small foci, three or more large foci, or both. Small cortical infarcts and lacunar infarcts were seen in 11 of 110 (10%) and 10 of 110 (9%) patients, respectively. Dural sinus thrombosis was seen in five patients. The frequency of abnormalities was high in both the SLE (57%) and the non-SLE (41%) groups. Large infarcts were more common in the non-SLE group (26%) than in the SLE group (5%). Although hyperintense white matter foci and cortical infarcts were more common in SLE patients, the differences were not statistically significant.Infarcts of various sizes and hyperintense white matter foci are the most common abnormalities seen on CT and MR imaging in patients with APA. We found no significant differences in frequencies of abnormalities seen between non-SLE and SLE patients.

We present a female with premature birth, polyhydramnios, congenital apnea, cranial nerve palsies, orofacial and limb anomalies. Neuroimaging revealed calcifications along the vental margin of the caudal fourth ventricle. Neuropathologic findings at postmortem examination were consistent with brainstem tegmental necrosis and olivary hypoplasia, a rare lethal entity that should be considered in the differential diagnosis of congenital apnea.

Objective Our goal was to demonstrate the spectrum of neuroradiologic (CT, MR, and angiographic) findings in craniocervical arterial dissection (CAD) related to exercise or sporting activities and compare the diagnostic utility of CT, MRI, and MR angiography (MRA). Materials and methods The neuroradiologic examinations of 11 patients with CAD was performed: CT was performed in 10 patients, cranial MRI in 9, cranial and cervical MRA in 4, and contrast angiography in 10. The CT examinations were assessed for the presence of an infarction or a hyperdense artery (consistent with intraluminal thrombus), MRI examinations for the presence of infarction or abnormal periarterial signal, and contrast angiograms for arterial stenosis or occlusion, luminal irregularity, pseudoaneurysm, intimal flap, or distal branch occlusions. Results Computed tomography demonstrated infarction in four patients. At contrast angiography, a dissection was found in the artery supplying the region of infarction in all cases. A hyperdense artery was found by CT in two patients, which correlated with dissection of the artery or its parent artery on contrast angiography. Cranial MRI findings were seen in six patients (infarction in five, periarterial signal abnormality in five). Dissection was confirmed in all four patients with abnormal periarterial signal who underwent contrast angiography. Two patients with abnormal intracranial periarterial signal had corresponding abnormalities on MRA. False-negative cranial and cervical MRI and MRA studies were performed in one patient because the imaging volumes used for the cervical and intracranial MR examinations did not overlap. Four patients with normal intracranial arterial signal had dissection in the neck demonstrated by contrast angiography. Conclusion Neuroradiologic findings of CAD can include infarction, a hyperdense artery on CT, abnormal periarterial signal on MRI, and a narrowed arterial signal column on MRA. Computed tomography is an insensitive screening examination. Proper use of MRI and MRA involves examination of both the head and the neck with overlapping imaging volumes of the two regions.

The aim of this study was to determine the prognostic significance of the volume and intensity of abnormal (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) accumulation within areas of contrast enhancement on post-therapeutic volumetric MRI.A total of 10 patients with Grade III or IV glioma were treated with resection followed by intracavitary radiation therapy with (131)I-labelled antitenascin monoclonal antibody. Patients underwent serial FDG-PET and 1.5 T MR imaging. For each patient, MR and FDG-PET image volumes at each time point were aligned using a rigid-body normalised mutual information algorithm. Contrast-enhancing regions of interest (ROIs) were defined using a semi-automated k-means clustering technique. Activity within the ROI on the co-registered PET scan was calculated as a ratio (mean activity ratio; MAR) to activity in contralateral normal-appearing white matter (NAWM). The PET lesion was defined as the portion of the ROI associated with activity greater than two standard deviations above the mean in NAWM. Survival was assessed using the logrank test.Larger contrast-enhancing ROIs were strongly associated with an increased MAR (r = 0.51; p0.002). Enhancing lesions with an MAR1.2 were associated with decreased survival (p0.016). In nine patients who died, the MAR on PET correlated inversely with survival duration (r = -0.43; p0.01), whereas PET lesion volume did not.Following intracavitary radiation therapy, the development of contrast-enhancing lesions that are associated with high mean FDG-PET accumulation suggests poor prognosis.

Dynamic contrast enhanced MRI contrast agent kinetics in malignant tumors are typically complex, requiring multicompartment tumor models for adequate description. For consistent comparisons among tumors or among successive studies of the same tumor, we propose to estimate the total contrast agent-accessible volume fraction of tumor, including blood plasma, v(pe), and an average transfer rate constant across all tumor compartments, K(trans.av), by fitting a three-compartment tumor model and then calculating the area under the tumor impulse-response function (= v(pe)) and the ratio area under the tumor impulse response function over mean residence time in tumor (= K(trans.av)). If the duration of dynamic contrast enhanced MRI was too short to extrapolate the tumor impulse-response function to infinity with any confidence, then conditional parameters v(pe)(*) and K(trans.av*) should be calculated from the available incomplete impulse response function. Median decreases of 33% were found for both v(pe)(*) and K(trans.av*) in glioblastoma patients (n = 16) 24 hours after the administration of bevacizumab (P < 0.001). Median total contrast-enhancing tumor volume was reduced by 18% (P < 0.0001). The combined changes of tumor volume, v(pe)(*), and K(trans.av*) suggest a reduction of true v(pe), possibly accompanied by a reduction of true K(trans.av). The proposed method provides estimates of a scale and a shape parameter to describe contrast agent kinetics of varying complexity in a uniform way.

Trichothiodystrophy (TTD) is a rare group of autosomal recessive disorders of DNA repair unified by the presence of sulfur-deficient brittle hair. We report a 3-year-old boy with classic clinical features of TTD, including ichthyosis, alopecia, developmental delay, and tiger-tail banding of the hair shaft on polarizing microscopy. Brain MR imaging showed both diffuse dysmyelination and osteosclerosis, findings that, in combination, may be specific for TTD.

Effective cancer chemotherapy depends on the delivery of therapeutic drugs to cancer cells at cytotoxic concentrations. However, physiologic barriers, such as variable vessel permeability, high interstitial fluid pressure, and heterogeneous perfusion, make it difficult to achieve that goal. Efforts to improve drug delivery have been limited by the lack of noninvasive tools to evaluate intratumoral drug concentration and distribution. Here we demonstrate that tumor drug concentration can be measured in vivo using T1-weighted MRI, following systemic administration of liposomes containing both drug (doxorubicin (DOX)) and contrast agent (manganese (Mn)). Mn and DOX concentrations were calculated using T1 relaxation times and Mn:DOX loading ratios, as previously described. Two independent validations by high-performance liquid chromatography (HPLC) and histologic fluorescence in a rat fibrosarcoma (FSA) model indicate a concordant linear relationship between DOX concentrations determined using T1 and those measured invasively. This method of imaging exhibits potential for real-time evaluation of chemotherapeutic protocols and prediction of tumor response on an individual patient basis. Magn Reson Med 56: 1011–1018, 2006. © 2006 Wiley-Liss, Inc.

We evaluated commercially available software that rapidly and automatically registers brain MR images on a clinical workstation, and we studied the accuracy of these registrations.Ten patients with a diagnosis of glioblastoma multiforme underwent contrast-enhanced inversion recovery prepared three-dimensional (3D) volumetric spoiled gradient-recalled acquisition in the steady state (SPGR) MR imaging (contiguous 1.5-mm slice thickness, 96-104 slices). After this imaging sequence, each patient was brought out of the head coil into a sitting position and then repositioned in the coil. The inversion recovery prepared 3D SPGR sequence was then repeated. A commercially available software program operating on a clinical workstation was used to automatically register the second inversion recovery prepared SPGR series to the first. The speed of registration was recorded. The accuracy of each registration was estimated by recording the coordinates of eight anatomic landmarks on the registered and reference series and by calculating the mean error among matching landmarks.In nine of 10 patients, the registration software produced a visually satisfactory registration. In one patient, a second registration was necessary to produce a satisfactory registration. The processing time for each iteration was 48.3 +/- 3.8 sec (mean +/- SD). The mean error in aligning matching anatomic landmarks ranged from 0.67 to 1.41 mm, with an overall mean of 1.18 mm. The largest error among matching landmarks was 2.3 mm.Commercially available registration software can automatically register 3D imaging volumes in less than 1 min. The mean error in registration was approximately equivalent to the dimensions of a single voxel.

Deficits in delayed recall of learned information may be an early marker of Alzheimer's disease (AD). The apolipoprotein E E4 allele and a positive family history (FH) are both genetic risk factors for AD. The authors cross-sectionally compared performance on the California Verbal Learning Test (CVLT) in 153 prospectively recruited normal elderly subjects (mean age 67 years, mean MMSE=28) stratified by genetic risk into four groups (E4+/FH+, E4+/FH-, E4-/FH+, E4-/FH-). Neither FH nor E4 status affected performance, except on List B (a distraction word list), on which the FH+ group performed worse. The high-risk group (E4+/FH+) also performed worse on List B than the low-risk group (E4-/FH-) but did not differ on other measures. Memory impairments associated with genetic or family history risk may not manifest until the person is much closer to the onset age of AD.

The purpose of this study was to examine the frequency of change in size of pineal cysts on serial MR studies.Thirty-two patients (19 females, 13 males) with a diagnosis of pineal cyst at any time who underwent brain MR imaging more than once in a period of at least 6 months were identified by computerized search of radiology reports. Four patients underwent MR imaging to follow up pineal cysts, whereas the remaining patients were imaged for a variety of indications, including intracerebral neoplasms. Measurements of maximal cyst dimension on both initial and latest follow-up studies were obtained in all patients, and cyst volumes were calculated in 23 patients.Length of follow-up ranged from 6 months to 9 years. All cysts were considered incidental and none were treated. Maximal cyst dimensions ranged from 0.5 to 2.2 cm. On average, there was no significant change in cyst volume. The maximal dimension of the cyst did not change in 24 (75%) of 32 patients. Two cysts resolved completely on follow-up, three cysts decreased by 2-4 mm, two cysts enlarged by 2-3 mm, and one cyst formed and grew to 1.2 cm.Whereas the size of pineal cysts as a whole remained unchanged on serial MR studies, cysts may either form or involute in individual patients. Small increases in cyst size did occur but were not associated with specific clinical findings. These findings suggest that typical pineal cysts may be followed up on a clinical basis alone rather than on imaging.

The purpose of this study was to compare MR imaging features of gangliogliomas in children less than 10 years old with those seen in patients at least 10 years old.Our study population consisted of 15 female patients and 10 male patients with a mean age of 20 years. The early childhood group was composed of six children with a mean age of 5.5 years. The older group was composed of 19 patients with a mean age of 25.6 years. We assessed tumor volume, tumor location, percentage of tumor that was cystic, pattern of contrast enhancement, and degree of edema.The temporal lobe was the most common tumor location in both groups. Mean tumor volume in the early childhood group was 83 cm3, which was significantly larger than the mean tumor volume (9.78 cm3) for the older group (p = 0.001). Cystic tumors were more common in the early childhood group (83%) than in the older group (63%), and the average percentage of cysts in the cystic tumors was much higher in the early childhood group (67%) than in the older group (30%). Contrast enhancement was seen in five of six early childhood tumors and 13 of 16 tumors in older patients. Four of six tumors in the early childhood group and five of 19 tumors in the older patient group had associated edema.The mean tumor volume of gangliogliomas in the early childhood group was significantly larger than that of the older patient group. This finding may be indicative of differences in tumor growth patterns in the two groups, ability of the hemicranium to adjust to mass effect in childhood, or sampling error as a result of a relatively small sample size.

SUMMARY: This study describes a case of a patient with traumatic rupture of a maxillary sinus retention cyst, which had an interesting clinical presentation of unilateral rhinorrhea, mimicking a CSF leak. The diagnosis was made fortuitously by comparison of a posttraumatic CT brain examination with a CT sinus study performed 1 day earlier.

L imbic encephalitis is a rare neurologic disorder characterized clinically by behavioral changes and memory loss [I]. Patients with limbic encephalitis typically (but not always) have an underlying malignancy, most commonly small cell carcinoma of the lung [I 1. In this setting, the neurologic changes represent a paraneoplastic syndrome. The MR imaging findings of limbic encephalitis have been well described in a number of case reports 12-61 and during the acute phase of the illness include hyperintense signal abnormality on T2-weighted images within medial temporal lobe structures such as the hippocampi and amygdalae and, on occasion, the hypothalamus. We report the 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) findings oflimbic encephalitis during the acute phase of the illness.

OBJECTIVE: The purpose of this study was to report the association of dural sinus thrombosis with a hypercoagulable state associated with activated protein C resistance. CONCLUSION: In our small study population, hemorrhagic venous infarction was common (three of four patients) among patients with dural sinus thrombosis and activated protein C resistance. Four of five patients with dural sinus thrombosis had positive tests for activated protein C resistance. This finding, in conjunction with data from other studies, suggests that patients with dural sinus thrombosis may need to be studied for the presence of activated protein C resistance. A positive finding for activated protein C resistance can be important not only in helping to explain the cause of thrombosis in affected individuals but also in identifying families at risk for thrombosis.

The causes of stroke in young adults differ substantially from those in older adults. In many instances, the diagnosis can be made by taking a clinical history and performing laboratory studies (e.g., in patients who have multiple thromboses associated with anti-phospholipid antibodies). In other circumstances, clues to the diagnosis can be found on routine CT and MR studies. However, in many circumstances, imaging tailored to a specific diagnosis is important (e.g., MR imaging of the neck in patients with suspected arterial dissection). In yet other cases, additional studies (e.g., echocardiography in suspected cardiogenic embolism) are important to establish the cause.

and OS for the entire cohort were 88.0%, 69.5%, and 78.4%, respectively. Of the 85 patients, there were 7 locoregional failures (LRF), 13 distant failures (DF), 4 LRF and DF, and 4 deaths from intercurrent illness. Among the 16 patients with locoregional ordistantfailure,mediantimefromendofradiotherapytofirstfailurewas9.8months.OnCoxproportionalhazardsregressionanalysis, an increase in integrated SUV of 209.2 SUV$ml (difference between the 75th and 25th percentiles) was associated with a statistically significant increased hazard of recurrence (2.2-fold, p\0.0001), even after controlling for Karnofsky performance status (2.0-fold, p = 0.0007), and of death (1.7-fold, p = 0.0037). An increase in MTV was also associated with increased hazard of progression (1.9-fold, p = 0.002) and of death (2.1-fold, p = 0.001). We did not find a significant relationship between maximum SUV and DFS or OS. Conclusions: High metabolic tumor burden as measured by MTV or integrated SUV are adverse prognostic factors for disease recurrence and death in head and neck cancer. MTV and integrated SUV retained significance after controlling for KPS, another significant adverse prognostic factor in this cohort. These metabolic parameters are potentially valuable tools for risk stratification and guiding treatment in future clinical trials.

2026 Background: DCE-MRI can determine vascular permeability using Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space. We report a p...

2029 Background: Significant responses seen in GBM patients treated with BEV and CPT-11 generated the need to develop ways to predict clinical benefit. DCE-MRI can be used to evaluate the microvasculature within tumors. DCE-MRI uses Ktrans, a volume transfer constant of contrast agent between blood plasma and the extravascular extracellular space, to determine vascular permeability. A 50% reduction in Ktrans is clinically meaningful. We report a phase II trial to determine the correlation between vascular permeability and radiographic response in GBM patients treated with the combination. Methods: Eligibility included patients with recurrent GBM. Both agents were given every 14 days. All patients received BEV at 10 mg/kg IV. CPT-11 was dosed at 340 mg/m2 for patients on enzyme inducing antiepileptic drugs (EIAED) and 125 mg/m2 for patients not on EIAED. Radiographic responses were assessed every 6 weeks. DCE-MRIs were performed before administration of chemotherapy, one day after treatment and after the first cycle. The primary endpoint was to examine the effect of BEV and CPT-11 treatment on vascular permeability as measured by percent change from baseline in Ktrans. Results: Twenty patients were enrolled, with a median age of 49.5 years. Fifteen patients are assessable for response. Best responses include one patient with complete response, 8 with partial response (response rate=60%), six patients with stable disease, and one with disease progression. Ktrans values are available for 13 patients; data are not available for seven patients (too early: 4, technical difficulty: 3). A reduction in Ktrans by 50% was observed in 6 patients one day after treatment and in 12 patients at the end of cycle 1. Changes in Ktrans value were highly correlated with the percentage decline in tumor volume from baseline to end of cycle one (Pearson correlation = 0.82; p=0.0006). Fifteen patients are still on study. Five patients came off due to disease progression. Conclusions: The utilization of DCE-MRI to determine a reduction in vascular permeability following a combination of BEV and CPT-11 is feasible and correlates significantly with the degree of tumor volume decrease. No significant financial relationships to disclose.

Purpose: To evaluate the use of DCE‐MRI to measure changes in tumorphysiology in LAHN cancer patients receiving TT and cisplatin based concurrent chemoradiation (ChemoRT). Material and Methods: Eligible patients with LAHN were enrolled on an IRB approved clinical trial to establish the safety and efficacy of adding TT (bevacizumab and erlotinib) to ChemoRT. To quantify this efficacy, DCE‐MR images were acquired on a 1.5T GE Signa Exite scanner before treatment started, at the end of the lead‐in phase (2 weeks of TT alone), at the end of week 1 of ChemoRT, and at the end of the ChemoRT (70 Gy). The images were analyzed using a full Time Point (fTP) pharmacokinetic analysis implemented by CAD Sciences® (White Plains, NY) that measures the vascular permeability (PERM) and extracellular volume fraction (EVF). The T10 for the primary and nodes was determined from series acquired with varying TRs. A dynamic 3D spoiled gradient echo sequence was used before and after bolus injection of Gd DTPA (Magnevist®). Regions of interest (ROIs) were defined over the entire extent of the tumor and LN, respectively. Enhancement curve analysis, PERM and EVF statistics and ROI volume comparisons were performed. Results: The T10 for tumor was 1500 msec, and 2000 msec for LN. All the fTP analyses used these values. Fifteen patients have been imaged to date. We found that coronal imaging allows better ROI selection without vascular averaging for this type of subjects.. Detailed analyses of all time points have been completed on three patients, all with clinical complete response. Combined PERM and EVF analyses showed marked decreases with treatment (p