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Our aim was to determine whether the contrast between white matter lesions and normal-appearing white matter in fast spin-echo fluid-attenuated inversion recovery (FLAIR) images can be improved by lengthening the effective TE and the echo train length.Thirty patients with various white matter lesions were imaged using fast spin-echo FLAIR sequences (TR = 10,002 msec; inversion time = 2200) on a 1.5-T MR imaging system. For 14 patients, fast spin-echo FLAIR sequences with a TE of 165 msec and echo train length of 32 (fast spin-echo FLAIR 165/32) were compared with fast spin-echo FLAIR sequences with a TE of 125 msec and echo train length of 24 (fast spin-echo FLAIR 125/24). For 16 other patients, fast spin-echo FLAIR 165/32 sequences were compared with fast spin-echo FLAIR sequences with a TE of 145 msec and echo train length of 28 (fast spin-echo FLAIR 145/28). Signal difference-to-noise ratios were calculated between the lesions and normal-appearing white matter for a typical lesion in each patient.In both groups, a small but statistically significant increase in the signal difference-to-noise ratio was found on the fast spin-echo FLAIR sequences using the longer TE and echo train length. In the first group, signal difference-to-noise ratio increased from 18.7 +/- 4.7 (mean +/- SD) for fast spin-echo FLAIR 125/24 to 20.1 +/- 4.5 for fast spin-echo FLAIR 165/32 (p.05). In the second group, the signal difference-to-noise ratio increased from 15.4 +/- 4.0 for fast spin-echo FLAIR 145/28 to 16.8 +/- 4.6 for fast spin-echo FLAIR 165/32 (p.01). In addition, fast spin-echo FLAIR sequences with a longer TE and echo train length were obtained more rapidly (6 min for fast spin-echo FLAIR 125/24, 5 min 20 sec for fast spin-echo FLAIR 145/28, and 4 min 41 sec for fast spin-echo FLAIR 165/32).Lengthening the TE to 165 msec and echo train length to 32 in fast spin-echo FLAIR imaging allows both a mild improvement in the contrast between white matter lesions and normal-appearing white matter and shorter imaging times.

We read with interest Whitney Pope's recent editorial1 in Neuro-Oncology on the paper by Kickingereder et al2 addressing the utility of relative cerebral blood volume (rCBV) derived from susceptibility-contrast perfusion-weighted MRI for determining therapeutic response in bevacizumab-treated recurrent glioblastoma multiforme (GBM). Kickingereder and Pope contend that although pretreatment rCBV may be a predictive marker of overall survival (OS), there is no evidence supporting post-bevacizumab change in rCBV from baseline as an early response marker. We caution against premature dismissal of rCBV change as an early predictor of treatment response.

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.

As intracranial MR angiography becomes more widely used and spatial resolution improves, anomalies at the Circle of Willis which have been previously well described on angiographic studies and anatomic dissections will become more frequently appreciated by MR angiography. Recognition of these variants is important to avoid confusion of the anomalies with aneurysms, evaluate collateral pathways in the intracerebral circulation, and enhance pre-operative planning in patients undergoing surgery at the skull base. In this review, we illustrate several of the more common types of anomalies at the Circle of Willis and discuss the possible clinical significance of each.

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.

We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 9 10-6mm2/s ± 224 (SD), and mean LCP was 0.71 ± 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L\1,209 and LCP[0.71 versus ADC-L[1,209 and LCP \0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multicenter (BRAIN) study. © 2012 Springer Science+Business Media, LLC.

Creutzfeldt-Jakob disease is a rare dementing illness that usually affects older adults. Currently, neuroradiologic examinations play a minor role in the diagnosis of Creutzfeldt-Jakob disease. Several single case reports have noted a distinctive finding of hyperintense signal abnormalities in the basal ganglia on T2-weighted MR images of patients with Creutzfeldt-Jakob disease. In order to assess the diagnostic utility of this finding, we studied the imaging features of four patients with Creutzfeldt-Jakob disease in whom this MR finding was present.Two neuroradiologists retrospectively reviewed the MR images of four patients who had pathologically proved Creutzfeldt-Jakob disease and signal abnormalities in the basal ganglia on T2-weighted MR images. The patients' clinical findings were also analyzed.The four patients had MR examinations between 6 months and 1 year after the onset of symptoms. In all four cases, the hyperintense signal abnormalities in the basal ganglia on T2-weighted images were diffuse and bilaterally symmetric. The T1-weighted images were normal. A CT scan was obtained on a single patient and was normal.Although a lack of signal abnormality in the basal ganglia on MR imaging cannot be used to rule out a diagnosis of Creutzfeldt-Jakob disease, our experience and review of published reports suggest that in the proper clinical setting, bilaterally symmetric, diffuse hyperintense abnormalities in the basal ganglia on T2-weighted images may be a specific sign of Creutzfeldt-Jakob disease.

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.

Here, we describe an automated nonparametric method for evaluating gadolinium-diethylene triamine pentaacetic acid (GdDTPA) kinetics, based on dynamic contrast-enhanced–MRI scans of glioblastoma patients taken before and after treatment with bevacizumab; no specific model or equation structure is assumed or used. Tumor and venous blood concentration-time profiles are smoothed, using a robust algorithm that removes artifacts due to patient motion, and then deconvolved, yielding an impulse response function. In addition to smoothing, robustness of the deconvolution operation is assured by excluding data that occur prior to the plasma peak; an exhaustive analysis was performed to demonstrate that exclusion of the prepeak plasma data does not significantly affect results. All analysis steps are executed by a single R script that requires blood and tumor curves as the sole input. Statistical moment analysis of the Impulse response function yields the area under the curve (AUC) and mean residence time (MRT). Comparison of deconvolution results to fitted Tofts model parameters suggests that AUC and AUC of the Impulse response function closely approximate fractional clearance from plasma to tissue (K trans ) and fractional interstitial volume (ve). Intervisit variability is shown to be comparable when using the deconvolution method (11%[ AUC ] and 13%[AUC]) compared to the Tofts model (14%[K trans ] and 24%[ve]). AUC and AUC both exhibit a statistically significant decrease (P < 0.005) 1 day after administration of bevacizumab. Magn Reson Med 63:1366–1375, 2010. © 2010 Wiley-Liss, Inc.

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.

Quantitative analysis of dynamic contrast-enhanced MR imaging (DCE-MR imaging) has the power to provide information regarding physiologic characteristics of the microvasculature and is, therefore, of great potential value to the practice of oncology. In particular, these techniques could have a significant impact on the development of novel anticancer therapies as a promising biomarker of drug activity. Standardization of DCE-MR imaging acquisition and analysis to provide more reproducible measures of tumor vessel physiology is of crucial importance to realize this potential. The purpose of this article is to review the pathophysiologic basis and technical aspects of DCE-MR imaging techniques.

2024 Background: Tumor hypoxia is a potent mediator of treatment resistance because of the negative impact on the efficacy of radiation and associated poor tumor delivery of cytotoxic chemotherapy....

Rationale and Objectives To estimate the gain in signal-to-noise ratio (SNR) in first-pass contrast-enhanced (CE) abdominal magnetic resonance angiography (MRA) at 3.0 T compared with 1.5 T. Materials and Methods Three protocols were simulated using six contrast agents: gadopentetate dimeglumine (Magnevist, Berlex, Wayne, NJ), gadoteridol (Prohance, Bracco, Princeton, NJ), gadobenate dimeglumine (Multihance, Bracco, Princeton, NJ), gadodiamide (Omniscan, Amersham Health, Princeton, NJ), gadoversetamide (Optimark, Mallinckrodt, St. Louis, MO), and gadofosveset trisodium (MS-325, EPIX Medical, Cambridge, MA). Contrast concentrations were calculated for five abdominal vessels. Based on these data, the gain in SNR during CE abdominal MRA at 3.0 T over 1.5 T was estimated. Results In these simulations, peak concentrations in all five target vessels were about 5 mM, 10 mM, and 0.7 mM for protocol 1, protocol 2, and protocol 3, respectively. A gain in SNR at 3 T over 1.5 T during CE abdominal MRA of at least 94% in all five target vessels could be achieved by applying protocol 1 or protocol 2, whereas protocol 3 provided a gain in SNR of 70%. Conclusions Although five of the contrast agents studied fulfill the expectation of providing approximately twice the SNR at 3.0 T versus 1.5 T during CE abdominal MRA, MS-325 offers a gain in SNR of 70% only.

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.

The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy.Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients.This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival.This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

The demand for image-processing software for radiology applications has been increasing, fueled by advancements in both image-acquisition and image-analysis techniques. The utility of existing image-processing software is often limited by cost, lack of flexibility, and/or specific hardware requirements. In particular, many existing packages cannot directly utilize images formatted using the specifications in part 10 of the DICOM standard (“DICOM images”). We show how image analyses can be performed directly on DICOM images by using ImageJ, a free, Java-based image-processing package (http://rsb.info.nih.gov/ij/). We demonstrate how plug-ins written in our laboratory can be used along with the ImageJ macro script language to create flexible, low-cost, multiplatform image-processing applications that can be directed by information contained in the DICOM image header.

To determine prospectively the diffusibility of water in normal lumbar disks in adults by using the mean apparent diffusion coefficient (ADC) and to determine if a relationship exists between disk ADC and magnetic resonance (MR) findings of disk degeneration.The study was approved by the Institutional Review Board, and all participants gave written informed consent prior to enrollment. Diffusion-weighted MR imaging of the lumbar spine was performed in 39 patients (all men; mean age, 53 years) and five volunteers (all men; mean age, 31 years). ADC values were recorded for each disk. All disks were visually graded by two independent observers as being normal or as showing at least one of three MR findings of degeneration on sagittal T2-weighted images. Mean ADC values of normal disks were compared with those of degenerated disks and were correlated with age and anatomic location. Data were analyzed by using Kendall correlation statistics, Mantel-Haenszel statistics, and a paired two-tailed Student t test.The mean ADC value was 2.27 x 10(-3) mm(2)/sec +/- 0.58 (+/- standard deviation) in normal disks and 2.06 x 10(-3) mm(2)/sec +/- 0.47 in abnormal disks (9% reduction, P = .006). A statistically significant dependence of lumbar disk ADC on anatomic location was reported (analysis of variance, P.001), with lower ADC values seen in more caudal disks. There was no association between age and mean disk ADC.A statistically significant decrease was seen in the ADC values of degenerated lumbar disks when compared with ADC values of normal disks. More caudal disks, even when normal, showed lower ADC values than more cephalic disks.

BACKGROUND AND PURPOSE: Compared with MR imaging, dynamic CT perfusion imaging covers only a fraction of the whole brain. An important assumption is that CT perfusion abnormalities correlate with total ischemic volume. The purpose of our study was to measure the degree of correlation between abnormalities seen on CT perfusion scans and the volumes of abnormality seen on MR diffusion and perfusion images in patients with acute large-vessel stroke. METHODS: Fourteen patients with acute hemispheric stroke symptoms less than 12 hours in duration were studied with single-slice CT perfusion imaging and multislice MR diffusion and perfusion imaging. CT and MR perfusion studies were completed within 2.5 hours of one another (mean, 77 minutes) and were reviewed independently by two neuroradiologists. Hemodynamic parameters included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Extents of abnormality on images were compared by using Kendall correlation. RESULTS: Statistically significant correlation was found between CT-CBF and MR-CBF abnormalities (τ = 0.60, P = .003) and CT-MTT and MR-MTT abnormalities (τ = 0.65, P = .001). Correlation of CT-CBV with MR-CBV approached significance (τ = 0.39, P = .06). Extent of initial hyperintensity on diffusion-weighted images correlated best with extent of MR-CBV abnormality (τ = 0.69, P = .001), extent of MR-MTT abnormality (τ = 0.67, P = .002), and extent of CT-CBV abnormality (τ = 0.47, P = .02). CONCLUSION: Good correlation was seen between CT and MR for CBF and MTT abnormalities. It remains uncertain whether CT perfusion CBV abnormalities correspond well to whole-brain abnormalities.

Whether or not severe febrile seizures in infancy cause hippocampal injury and subsequent medial temporal sclerosis is an often debated question in epilepsy. Recent magnetic resonance imaging (MRI) of infants suffering from febrile seizures has provided preliminary evidence that abnormally increased T2 signal intensity can be seen in the hippocampi of infants following prolonged and focal febrile seizures. Follow-up MRIs in a few of these infants have confirmed that medial temporal sclerosis can develop following these acute MRI signal changes. In this article, we review the hypotheses and MRI evidence relating to hippocampal injury during prolonged febrile seizures and the later development of medial temporal sclerosis.

Signal intensity (SI) values of gray- and white-matter brain regions of interest (ROIs) were obtained from T 2 - and proton density-weighted magnetic resonance (MR) images of 58 normal subjects aged 22–82 years (31 females, 52.3±18.8 years; 27 males, 54.1±18.1 years). Sampled ROIs included the caudate, putamen, thalamus, orbitofrontal gyrus, gyrus rectus, uncus, frontal white matter, anterior and posterior corpus callosum, cranial–cervical junction fat, and retroorbital fat. Effects of age and sex on SI were examined using repeated-measures analysis of covariance. For both T 2 - and proton density-weighted acquisitions, a significant inverse relationship between age and SI was observed for the ratio of all summed gray-matter ROIs divided by summed white-matter ROIs. This relationship was additionally observed for ratios of both subcortical gray/white matter and cortical gray/white matter. Females compared with males had significantly lower cortical gray/white matter ratios on T 2 -weighted scans. Differences in SI were observed between cranial–cervical junction fat and retroorbital fat on both acquisitions, with females showing significantly higher values for cranial–cervical junction fat and males showing higher values for retroorbital fat. Implications for brain morphometry, the use of fat as a reference standard, and other issues in neuroimaging are discussed.

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.

Background There is no effective therapy for recurrent GBM pts following progression on the vascular endothelial growth factor (VEGF)-targeting agent bevacizumab (BV), with historical series reporting progression-free survival at 6 months (PFS-6) of only 2%. Several mechanisms of tumor adaptation following anti-VEGF therapy have been proposed, including upregulation of alternative angiogenic cytokines. We therefore performed a single-arm phase 2 study to evaluate lenvatinib (L), an oral tyrosine kinase inhibitor targeting FGFR1-4, PDGFRβ, VEGFR1-3, RET, and KIT, in pts with recurrent GBM progressing on BV. Methods 32 pts with recurrent GBM (≤2 prior progressions) and progression on BV received L 24 mg once daily in 28-day cycles until PD or unacceptable toxicity. Dynamic contrast-enhanced MRI was performed before and after 1 day of L on a subset of pts (n = 16). Response was assessed using Response Assessment in Neuro-Oncology criteria. Primary endpoint was PFS-6. This cohort has completed enrollment; 1 pt is still ongoing. Results Median age was 52 y, 56% were male, and 19% had a KPS Conclusions Lenvatinib has modest activity and a similar toxicity profile when compared with other tyrosine kinase inhibitors. Further study of VEGF therapy failure mechanisms as well as biomarkers of outcome is needed. Disclosure D.A. Reardon: D. Reardon discloses reimbursement for serving as an advisory board member for Genentech/Roche and Schering/Merck in the past year. E. Pan: E. Pan has been reimbursed as an advisory board member for Genentech in the past year. He has also been on the Speakers' Bureau for Genentech, Merck, and Sigma Tau in the past year. J. Fan: J. Fan is an Eisai employee. J. Mink: J. Mink is an employee of Eisai. D.P. Barboriak: D. Barboriak discloses receiving imaging core lab support from Eisai Pharmaceuticals, ACRIN, NIBIB / RSNA QIBA Member of GE Medical Systems Neuro MRI advisory board Pulse sequence support from Siemens Healthcare. J.J. Vredenburgh: J.J. Vredenburgh received financial compensation from Genentech/Roche for Speakers Bureau participation and consultation. A. Desjardins: A. Desjardins received financial compensation from Genentech/Roche for Speakers Bureau participation. J.P. O'Brien: J. P. O'Brien is an employee of Eisai. P.Y. Wen: P. Wen discloses research support from Eisai. All other authors have declared no conflicts of interest.

TPS10635 Background: Glioblastoma (GBM) is an aggressive type of primary malignant brain tumor and despite treatment with surgery, radiation, and temozolomide (TMZ) chemotherapy, median overall survival (OS) remains poor. A pathologic hallmark of GBM is tumor necrosis, a suspected result from endogenous tumor hypoxia. Angiogenesis is stimulated by hypoxia-driven signaling cascades and is required for tumor proliferation. The inefficient blood supply of these hypoxic tumors also limits the efficacy of chemotherapy and radiotherapy. Surviving hypoxic tumor cells may be selected out and proliferate as a more aggressive tumor subtype, therefore hindering OS. 18F-Fluoromisonidazole (FMISO) is a PET radiotracer whose uptake in hypoxic tissues can be measured radiographically. The degree of tumor hypoxia has been negatively associated with time to tumor progression and survival (Spence et al, 2008). Knowledge of the degree/distribution of tumor hypoxia by PET uptake and perfusion MRI parameters may provide prognostic information and help guide therapy for patients with GBM. Methods: In this phase II prospective single arm multi-institution study, patients will undergo baseline FMISO PET and MR imaging two weeks prior to chemoradiotherapy (CRT). A subset of patients will receive a second FMISO PET one week prior to CRT to assess reproducibility. Clinical outcomes of OS and 6-month progression-free survival (PFS-6) will be correlated to PET and MRI parameters. Eligibility: Pathologically confirmed GBM with residual tumor after surgery (including T2/FLAIR hyperintensity consistent with tumor) scheduled to receive standard fractionated radiation therapy and temozolomide alone or with an anti-VEGF agent or PARP inhibitor. Current enrollment: 22 patients of 50 sample size Contact information: Please contact the PI, Elizabeth R. Gerstner, MD ( egerstner@partners.org ) for additional information. Significance: With a better understanding of the extent of tumor hypoxia and changes in hypoxia levels from treatment, more effective therapies could be developed to inhibit GBM growth, target hypoxic areas and individualize patient care.

2058 Background: To determine the prognostic significance of changes in parameters derived from diffusion tensor imaging (DTI) that occur in response to combination chemotherapy with the antiangiogenesis agent bevacizumab (BEV) in patients with recurrent glioblastoma multiforme (GBM). Methods: 16 patients (10 men, 6 women; age range 38–62 years) with recurrent GBM underwent serial 1.5T MR imaging. Axial single-shot echo planar DTI (TR/TE 6000/100; flip angle 90 degrees; voxel: 1.72 x 1.72 x 5mm; b value of 1000 sec/mm2; 12 directions) was obtained on scans performed 3 days and 1 day prior to and 1 day after initiation of therapy with BEV and irinotecan (CPT-11). Clinical follow-up and survival status was documented up to 20 months after the date of initial MR imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were aligned to whole brain contrast-enhanced 3D FLASH and 3D FLAIR image volumes (1 mm isotropic voxels) using a rigid body normalized mutual information algorithm. Based on two pre-treatment scans, the 95% confidence limits for change (95%CL) in ADC and FA were calculated in volumes of tumor-related contrast-enhancement (TRE) and FLAIR signal abnormality (FSA). A patient was considered to have a change in FA or ADC after therapy if the difference between the pre- and post-treatment values was greater than the 95% CL for that parameter. Progression was defined on contrast-enhanced MRI using MacDonald criteria by neuro-oncologists blinded to the DTI findings. Survival was compared using the log rank test. Results: DTI detected a change in ADC within FSA after therapy in three patients (2 increased, 1 decreased). Patients with a change in ADC within FSA had significantly shorter overall (p < 0.0012) and progression free (p < 0.015) survival than those with no change. Median survival in the patient group with a change in ADC was 24.7 (95% CI [17.3, 39.4]) weeks and 56.4 (95% CI [41.7, 96]) weeks in those patients with no change. Conclusions: In patients with GBM treated with BEV and CPT-11, a change in ADC after therapy in areas of FSA is associated with decreased survival. Parameters derived from DTI may, therefore, potentially serve as early markers of treatment failure in patients with GBM. [Table: see text]

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.

Purpose: To determine the optimal flip angle combination (oFAc) that generates voxel‐based T10 values, the median T10 for primary and nodes ( T 10 p,n ) , and its implications on vascular permeability (PERM) and extracellular volume fraction (EVF) in HN patients treated with targeted therapy and chemoradiation. Method and Materials: To generate voxel‐based T10, a gradient echo sequence was used on a 1.5 T scanner with TR=6.44 msec and FA of 10, 15, 20, 30, 45°. For different FA combinations, the voxel‐based values were calculated using CAD Sciences® (White Plains, NY). The average of the median T10 in muscle and fat ( T 10 m,f ) regions of interest (ROI) in 3 patients was calculated. Criteria for oFAc included minimal variation from published muscle and fat values at 1.5T, and minimum number of FA used for fitting. To determine T 10 p,n , values from ROIs delineated by 2 users (A,B) were calculated. For 3 patients, the PERM and EVF from primary and nodes ROIs were calculated using T10 maps and T 10 p,n . Results: The 10–45° FAc was chosen for subsequent T10 mapping as it had the greatest percentage of fitted pixels (90% for muscle, 100% for fat, % 83 for primary, 72% for nodes) and a T 10 m = 0.923 sec , and T 10 f =0.379 sec , compared to reported 0.870 and 0.260 sec for muscle and fat, respectively. From14 patients, T 10 pA = 0.804, T 10 nA = 0.760, T 10 pB = 0.849, T 10 nB = 0.810 sec . The difference between the PERM and EVF calculated with voxel‐based T10 versus T 10 p,n ranged from 6–81% for PERM, and 2.5–23% for EVF. Conclusion. The 10–45° FAc is fast and accurately describes the known T10 of normal tissue. Voxel‐based T10 calculations are essential for correct Tofts‐based PA in heterogeneous tumors. For HN, primary and nodes T 10 p,n = 0.8 sec is a good estimate for T10 in the absence of T10 mapping capability.

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

B, Unenhanced CT scan shows multiple low-attenuation round splenic lesions, some with central high attenuation (arrow). C, Low-power (x 2.5) micrograph of abscess shows serpiginous fibrotic layer (arrow) surrounding pus (P) and fungus ball (F). D, Higher-power (x 125) micrograph of abscess wall shows normal spleen at bottom and layers of fibrosis (F), chronic inflammatory cells, and histiocytes (H). Pus (P) is at top.

A group of 38 patients with a second revascularization procedure was studied for factors which may have contributed to the reappearance of angina after the first operation. Our data indicate that these patients usually have the first operation at an earlier age and had fewer bypasses at that time. In addition, they had inadequate control of the plasma triglyceride and cholesterol levels.