Imaging plays a key role in the diagnosis of central nervous system (CNS) metastasis. Imaging is used to detect metastases in patients with known malignancies and new neurological signs or symptoms, as well as to screen for CNS involvement in patients with known cancer. Computed tomography (CT) and magnetic resonance imaging (MRI) are the key imaging modalities used in the diagnosis of brain metastases. In difficult cases, such as newly diagnosed solitary enhancing brain lesions in patients without known malignancy, advanced imaging techniques including proton magnetic resonance spectroscopy (MRS), contrast enhanced magnetic resonance perfusion (MRP), diffusion weighted imaging (DWI), and diffusion tensor imaging (DTI) may aid in arriving at the correct diagnosis. This image-rich review discusses the imaging evaluation of patients with suspected intracranial involvement and malignancy, describes typical imaging findings of parenchymal brain metastasis on CT and MRI, and provides clues to specific histological diagnoses such as the presence of hemorrhage. Additionally, the role of advanced imaging techniques is reviewed, specifically in the context of differentiating metastasis from high-grade glioma and other solitary enhancing brain lesions. Extra-axial CNS involvement by metastases, including pachymeningeal and leptomeningeal metastases is also briefly reviewed.

In this small series combining 3-T DWI, DSC, and MRS diagnostic results using a simple, multiparametric scoring system has potential to improve overall diagnostic accuracy in distinguishing glioma progression from post-radiation change beyond that of each technique alone.

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 (GBM). Experimental Design Prior to start of chemoradiation, GBM patients 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 pre-treatment 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 pre-treatment 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%CI 0.59 to 0.91), nRCBV (AUC=0.72, 95% CI0.56–0.89) and nCBF (AUC = 0.72, 95%CI 0.56 to 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 GBM patients and these important physiological markers can be measured safely and reliably using MRI and 18F-FMISO PET.

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Purpose: To compare 3 Tesla (3T) multi-voxel and singlevoxel proton MR spectroscopy (MRS), dynamic susceptibility contrast perfusion MRI (DSC), and diffusionweighted MRI (DWI) for distinguishing recurrent glioma from postradiation injury. Materials and Methods:We reviewed all 3T MRS, DSC and DWI studies performed for suspicion of malignant glioma recurrence between October 2006 and December 2008. Maximum Cho/NAA and Cho/Cr peak-area and peak-height ratios were recorded for both multi-voxel and single-voxel MRS. Maximum cerebral blood volume (CBV) and minimum apparent diffusion coefficient (ADC) were normalized to white matter. Histopathology and clinicalradiologic follow-up served as reference standards. Receiver operating characteristic curves for each parameter were compared.Results: Forty lesions were classified as glioma recurrence (n ¼ 30) or posttreatment effect (n ¼ 10). Diagnostic performance was similar for CBV ratio (AUC ¼ 0.917, P < 0.001), multi-voxel Cho/Cr peak-area (AUC ¼ 0.913, P ¼ 0.002), and multi-voxel Cho/NAA peak-height (AUC ¼ 0.913, P ¼ 0.002), while ADC ratio (AUC ¼ 0.726, P ¼ 0.035) did not appear to perform as well. Single-voxel MRS parameters did not reliably distinguish tumor recurrence from posttreatment effects. Conclusion:A 3T DSC and multi-voxel MRS Cho/Cr peak-area and Cho/NAA peak-height appear to outperform DWI for distinguishing glioma recurrence from posttreatment effects. Single-voxel MRS parameters do not appear to distinguish glioma recurrence from posttreatment effects reliably, and therefore should not be used in place of multi-voxel MRS.

18F-FMISO is the most widely used PET agent for imaging hypoxia, a condition associated with resistance to tumor therapy. 18F-FMISO equilibrates in normoxic tissues, but is retained under hypoxic conditions because of reduction and binding to macromolecules. A simple tissue-to-blood ratio (TB) is suitable for quantifying hypoxia. A threshold of TB ≥ 1.2 is useful in discriminating the hypoxic volume (HV) of tissue; TBmax is the maximum intensity of the hypoxic region and does not invoke a threshold. Because elimination of blood sampling would simplify clinical use, we tested the validity of using imaging regions as a surrogate for blood sampling. Methods Patients underwent 20 min 18F-FMISO scans during the 90–140 min interval post-injection with venous blood sampling. 223 18F-FMISO patient studies had detectable surrogate blood regions in the field-of-view. Quantitative parameters of hypoxia (TBmax, HV) derived from blood samples were compared to values using surrogate blood regions derived from heart, aorta and/or cerebellum. In a subset of brain cancer patients, parameters from blood samples and from cerebellum were compared for their ability to independently predict outcome. Results Vascular regions of heart showed the highest correlation to measured blood activity (R2 = 0.84). For brain studies, cerebellar activity was similarly correlated to blood samples. In brain cancer patients, Kaplan-Meier analysis showed that image-derived reference regions had nearly identical predictive power as parameters derived from blood, thus obviating the need for venous sampling in these patients. Conclusions Simple static analysis of 18F-FMISO PET captures both the intensity (TBmax) and spatial extent (HV) of tumor hypoxia. An image-derived region to assess blood activity can be used as a surrogate for blood sampling in quantification of hypoxia.

For the purposes of this review, we classify SAH into three main patterns, defined by the distribution of blood on unenhanced CT: diffuse, perimesencephalic, and convexal. The epicenter of the hemorrhage further refines the differential diagnosis and guides subsequent imaging. Additionally, we review multiple clinical conditions that can simulate the appearance of SAH on CT or MRI, an imaging artifact known as pseudo-SAH.

Radiation injury to the central nervous system (CNS) manifests in multiple forms and is divided into three categories termed acute, early-delayed, and late-delayed injury patterns. Late-delayed radiation injury, primarily manifesting as leukoencephalopathy or radiation necrosis, is often progressive and may have a negative impact on quality of life. Radiation injury is believed to be a consequence of cell membrane and DNA injury with a pathological expression as vascular injury, depletion of oligodendroglial progenitor cells, and failure of cell-cell interactions that constitute the cellular network of the CNS. In addition, radiation injury results in activation of the inflammatory cascade with perturbation of cytokines, production of reactive oxygen species and vascular endothelial growth factor. Medical treatment of CNS radiation injury and in particular radiation necrosis remains problematic as there is a paucity of clinical trial data to inform treatment decisions, and aside from surgery and corticosteroids only bevacizumab appears to have a compelling therapeutic role.