These findings suggest that DSC perfusion MR imaging may be used to differentiate recurrent GBM from EBRT-induced radiation necrosis.

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Key Points• CXCL13 and CXCL12 mediate chemotaxis of CNS lymphoma cells, and CXCL13 concentration in CSF is prognostic.• CXCL13 plus IL-10 is highly specific for the diagnosis of CNS lymphoma.Establishing the diagnosis of focal brain lesions in patients with unexplained neurologic symptoms represents a challenge. The goal of this study is to provide evidence supporting functional roles for CXC chemokine ligand (CXCL)13 and interleukin (IL)-10 in central nervous system (CNS) lymphomas and to evaluate the utility of each as prognostic and diagnostic biomarkers. We demonstrate for the first time that elevated CXCL13 concentration in cerebrospinal fluid (CSF) is prognostic and that CXCL13 and CXCL12 mediate chemotaxis of lymphoma cells isolated from CNS lymphoma lesions. Expression of the activated form of Janus kinase 1 supported a role for IL-10 in prosurvival signaling. We determined the concentration of CXCL13 and IL-10 in CSF of CNS lymphoma patients and control cohorts including inflammatory and degenerative neurologic disease in a multicenter study involving 220 patients. Bivariate elevated CXCL13 plus IL-10 was 99.3% specific for primary and secondary CNS lymphoma, with sensitivity significantly greater than reference standard CSF tests. These results identify CXCL13 and IL-10 as potentially important biomarkers of CNS lymphoma that merit further evaluation and support incorporation of CXCL13 and IL-10 into diagnostic algorithms for the workup of focal brain lesions in which lymphoma is a consideration. (Blood. 2013;121(23):4740-4748) IntroductionDetermination of the pathological basis of focal brain lesions in patients with unexplained neurologic symptoms is a major clinical challenge. Persistent symptoms or rapid neurologic decline often mandates stereotactic brain biopsy, a highly invasive procedure with a 10% to 35% rate of diagnostic failure.1-3 Moreover, many lesions are not amenable to biopsy because of small size, location in deep brain structures, risk of hemorrhage, and other comorbidities.The diagnosis of central nervous system (CNS) involvement of non-Hodgkin lymphoma is a particular challenge because of lesional response to glucocorticoids and features on magnetic resonance imaging (MRI) that are shared with other pathologies including astrocytic neoplasms, demyelination, neurosarcoid, vasculitis, infections, and leptomeningeal dissemination of systemic cancer. Although flowcytometric and cytological analysis of cerebrospinal fluid (CSF) is useful in the evaluation of leptomeningeal disease, these tests are usually insensitive to pathological processes based in deep brain structures and rarely provide information that eliminates the need for brain biopsy; the sensitivity of CSF cytological analysis in the evaluation of primary CNS lymphoma (PCNSL) is ;15%. 4Advances that facilitate diagnosis and early treatment of CNS lymphoma would likely be cost-effective, minimize repeat diagnostic CSF and MRI evaluations and brain biopsies, and also lead to improved outcomes. [5][6][7] The molecular const...

Contrast-enhanced magnetic resonance imaging (MRI) is a commonly used diagnostic tool. Compared to the standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of intravenous (IV) ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacological, metabolic and imaging properties, ferumoxytol may play a crucial role in future MR imaging of the central nervous system (CNS), various organs outside the CNS, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in MRI. In order to more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available as supplementary material online.

BACKGROUND AND PURPOSE: MR imageϪguided gamma knife radiosurgery is often used to treat intra-axial metastatic neoplasms. Following treatment, it is often difficult to determine whether a progressively enhancing lesion is due to metastatic tumor recurrence or radiation necrosis. The purpose of our study was to determine whether relative cerebral blood volume (rCBV), relative peak height (rPH), and percentage of signal-intensity recovery (PSR) derived from dynamic susceptibilityweighted contrast-enhanced perfusion MR imaging can distinguish recurrent metastatic tumor from radiation necrosis.

Purpose:To determine whether magnetic resonance (MR) imaging is infl uenced by genetic and cellular features of glioblastoma multiforme (GBM) aggressiveness. Materials and Methods:In this HIPAA-compliant institutional review boardapproved study, multiple enhancing and peritumoral nonenhancing stereotactic neurosurgical biopsy samples from treatment-naïve GBMs were collected prospectively, with guidance from cerebral blood volume (CBV) MR imaging measurements. By using monoclonal antibodies, tissue specimens were examined for microvascular expression, hypoxia, tumor and overall cellular density, and histopathologic features of GBM aggressiveness. Genetic expression patterns were investigated with RNA microarrays. Imaging and histopathologic variables were compared with the Welch t test and Pearson correlations. Microarray analysis was performed by using false discovery rate (FDR) statistics. Results:Tumor biopsy of 13 adult patients yielded 16 enhancing and 14 peritumoral nonenhancing specimens. Enhancing regions had elevated relative CBV and reduced relative apparent diffusion coeffi cient (ADC) measurements compared with peritumoral nonenhancing biopsy regions ( P , .01). A positive correlation was found between relative CBV and all histopathologic features of aggressiveness ( P , .04). An inverse correlation was found between relative ADC and all histopathologic features of aggressiveness ( P , .05). RNA expression patterns between tumor regions were found to be signifi cantly different (FDR , 0.05), with hierarchical clustering by biopsy region only. Conclusion:These fi ndings suggest MR imaging is signifi cantly infl uenced by GBM genetic and cellular biologic features of aggressiveness and imply physiologic MR imaging may be useful in pinpointing regions of highest malignancy within heterogeneous tissues, thus facilitating histologic grading of primary glial brain tumors.q RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup /suppl

BACKGROUND AND PURPOSE There is evidence that increased tumor cellular density within diagnostic specimens of primary central nervous system lymphoma (PCNSL) may have significant prognostic implications. Because cellular density may influence measurements of apparent diffusion coefficient (ADC) by using diffusion-weighted MR imaging (DWI), we hypothesized that ADC measured from contrast-enhancing regions might correlate with clinical outcome in patients with PCNSL. MATERIALS AND METHODS PCNSL tumors from 18 immunocompetent patients, treated uniformly with methotrexate-based chemotherapy, were studied with pretherapeutic DWI. Enhancing lesions were diagnosed by pathologic analysis as high-grade B-cell lymphomas. Regions of interest were placed around all enhancing lesions allowing calculation of mean, 25th percentile (ADC25%), and minimum ADC values. Histopathologic tumor cellularity was quantitatively measured in all patients. High and low ADC groups were stratified by the median ADC value of the cohort. The Welch t test assessed differences between groups. The Pearson correlation examined relationships between ADC measurements and tumor cellular density. Single and multivariable survival analysis was performed. RESULTS We detected significant intra- and intertumor heterogeneity in ADC measurements. An inverse correlation between cellular density and ADC measurements was observed (P < .05). ADC25% measurements less than the median value of 692 (low ADC group) were associated with significantly shorter progression-free and overall survival. Patients with improved clinical outcome were noted to exhibit a significant decrease in ADC measurements following high-dose methotrexate chemotherapy. CONCLUSIONS Our study provides evidence that ADC measurements within contrast-enhancing regions of PCNSL tumors may provide noninvasive insight into clinical outcome.

Histopathologic evaluation of glioblastoma multiforme (GBM) at initial diagnosis is typically performed on tissue obtained from regions of contrast enhancement (CE) as depicted on gadolinium-enhanced, T1-weighted images. The non-enhancing (NE) portion of the lesion, which contains both reactive edema and infiltrative tumor, is only partially removed due to concerns about damaging functioning brain. The purpose of this study was to evaluate histopathologic and physiologic MRI features of image-guided tissue specimens from CE and NE regions to investigate correlations between imaging and histopathologic parameters. One hundred nineteen tissue specimens (93 CE and 26 NE regions) were acquired from 51 patients with newly diagnosed GBM by utilizing stereotactic image-guided sampling. Variables of anatomic, diffusion-weighted imaging (DWI), and dynamic susceptibility-weighted, contrast-enhanced perfusion imaging (DSC) from each tissue sample location were obtained and compared with histopathologic features such as tumor score, cell density, proliferation, architectural disruption, hypoxia, and microvascular hyperplasia. Tissue samples from CE regions had increased tumor score, cellular density, proliferation, and architectural disruption compared with NE regions. DSC variables such as relative cerebral blood volume, peak height, and recovery factor were significantly higher, and the percentage of signal intensity recovery was significantly lower in the CE compared with the NE regions. DWI variables were correlated with histopathologic features of GBM within NE regions. Image-guided tissue acquisition and assessment of residual tumor from treatment-naive GBM should be guided by DSC in CE regions and by DWI in NE regions.