Contralateral Normal-appearing White Matter Research Articles

High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study.

The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival.

Mean Diffusional Kurtosis in Patients with Glioma: Initial Results with a Fast Imaging Method in a Clinical Setting.

Diffusional kurtosis imaging is an MR imaging technique that provides microstructural information in biologic systems. Its application in clinical studies, however, is hampered by long acquisition and postprocessing times. We evaluated a new and fast (2 minutes 46 seconds) diffusional kurtosis imaging method with regard to glioma grading, compared it with conventional diffusional kurtosis imaging, and compared the diagnostic accuracy of fast mean kurtosis (MK') to that of the widely used mean diffusivity. MK' and mean diffusivity were measured in the contrast-enhancing tumor core, the perifocal hyperintensity (indicated on T2 FLAIR images), and the contralateral normal-appearing white and gray matter of 34 patients (22 with high-grade and 12 with low-grade gliomas). MK' and mean diffusivity in the different tumor grades were compared by using a Wilcoxon rank sum test. Receiver operating characteristic curves and the areas under the curve were calculated to determine the diagnostic accuracy of MK' and mean diffusivity. MK' in the tumor core, but not mean diffusivity, differentiated high-grade from low-grade gliomas, and MK' differentiated glioblastomas from the remaining gliomas with high accuracy (area under the curveMK' = 0.842; PMK' < .001). MK' and mean diffusivity identified glioblastomas in the group of high-grade gliomas with similar significance and accuracy (area under the curveMK' = 0.886; area under the curvemean diffusivity = 0.876; PMK' = .003; Pmean diffusivity = .004). The mean MK' in all tissue types was comparable to that obtained by conventional diffusional kurtosis imaging. The diffusional kurtosis imaging approach used here is considerably faster than conventional diffusional kurtosis imaging methods but yields comparable results. It can be accommodated in clinical protocols and enables exploration of the role of MK' as a biomarker in determining glioma subtypes or response evaluation.

A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma

The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (p<0.05). We also established a relationship between the tensor and kurtosis parameters of CNAWM and the glioma proliferative activity index (p<0.05). The correlation between all the absolute and normalized diffusion parameters and the glioma proliferative activity index, except absolute and normalized FA and RA values, was found to be statistically significant (p<0.05). Kurtosis (MK, AK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.

Detection of demyelination in multiple sclerosis by analysis of [Formula: see text] relaxation at 7 T.

Multiple sclerosis (MS) is a relatively common cause of inflammatory demyelinating lesions of the central nervous system. In an attempt to detect and characterize ongoing demyelination in MS patient brains, we used a novel magnetic resonance imaging (MRI) technique, involving the fitting of a three-component model to the relaxation behavior at high-field (7 T). This model allowed estimation of the amount of myelin water (and thus indirectly myelin content), axonal water, and interstitial water. In this study, 25 relapsing–remitting MS patients underwent a 7 T MRI from which 12 gadolinium-enhancing lesions, 61 non-enhancing lesions, and their corresponding contralateral normal appearing white matter (NAWM) regions were analyzed. In both enhancing and non-enhancing lesions, the amplitude of myelin water was significantly decreased, and interstitial and axonal water were increased relative to the contralateral NAWM. Longer relaxation time of interstitial and axonal water, and lower frequency shift of axonal water, were also observed in both enhancing and non-enhancing lesions when compared to the contralateral NAWM. No significant difference was found between enhancing lesions and non-enhancing lesions. These findings suggest that the fitting of a three-component model to the decay curve in MS lesions may help to quantify myelin loss.

MR imaging, apparent diffusion coefficient and histopathological features of desmoplastic infantile tumors-own experience and review of the literature.

Desmoplastic infantile tumors are rare supratentorial brain lesions occurring in children under 18 months of age. We report characteristic neuroimaging with DWI and the histopathological features of these neoplasms. Magnetic resonance (MR) examinations of nine patients, aged 0-18 months (median age 3.5 months), were retrospectively analyzed. Analysis of MR images included location and tumor size, signal intensity, contrast enhancement, presence of edema, and hemorrhage. Minimum and mean value of apparent diffusion coefficient (ADC) in the solid component of the tumor and contralateral normal-appearing white matter (NAWM) were measured, and ADC/NAWM ratios were calculated. All patients underwent tumor resection, and diagnosis of grade I desmoplastic tumors was confirmed. The tumors were located in the temporal lobe in seven patients, the parietal lobe in three, and in the frontal lobe in one case (in two children, tumors invaded more than one lobe). Suprasellar localization was observed in two patients; one child had multifocal brain lesions. In five cases, signal intensity of the solid component was hypointense on T2-WI. The measured minimum ADC value of solid tumor varied from 0.606 to 1.020 × 10(-3) mm(2)/s, with a mean value of 0.921 × 10(-3) mm(2)/s. The mean ADC value of NAWM was 1.121 × 10(-3) mm(2)/s. The mean ADC ratio was 0.858 × 10(-3) mm(2)/s. From our series, we can assume that restricted diffusion is observed not only in malignant but also in benign brain tumors. Diffusion signals and ADC values in these neoplasms appear to depend on their cellularity and components of the extracellular matrix.

Analysis of diffusion tensor imaging metrics for gliomas grading at 3 T

ObjectivesTo assess the diagnostic accuracy of axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values derived from DTI for grading of glial tumors, and to estimate the correlation between DTI parameters and tumor grades. MethodsSeventy-eight patients with glial tumors underwent DTI. AD, RD, ADC and FA values of tumor, peritumoral edema and contralateral normal-appearing white matter (NAWM) and AD, RD, ADC and FA ratios: lowest average AD, RD, ADC and FA values in tumor or peritumoral edema to AD, RD, ADC and FA of NAWM were calculated.DTI parameters and tumor grades were analyzed statistically and with Pearson correlation. Receiver operating characteristic (ROC) curve analysis was also performed. ResultsThe differences in ADC, AD and RD tumor values, and ADC and RD tumor ratios were statistically significant between grades II and III, grades II and IV, and between grades II and III–IV. The AD tumor ratio differed significantly among all tumor grades.Tumor ADC, AD, RD and glial tumor grades were strongly correlated. In the ROC curve analysis, the area under the curve (AUC) of the parameter tumor ADC was the largest for distinguishing grade II from grades III to IV (98.5%), grade II from grade IV (98.9%) and grade II from grade III (97.0%). ConclusionADC, RD and AD are useful DTI parameters for differentiation between low- and high-grade gliomas with a diagnostic accuracy of more than 90%. Our study revealed a good inverse correlation between ADC, RD, AD and WHO grades II–IV astrocytic tumors.

The Role of Dynamic Susceptibility Contrast-Enhanced Perfusion MR Imaging in Differentiating between Infectious and Neoplastic Focal Brain Lesions: Results from a Cohort of 100 Consecutive Patients

Background and PurposeDifferentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI) may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI) may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI) to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes.Materials and MethodsDSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54) and infectious (n = 46) lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium) was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV) values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value.ResultsNeoplastic lesions had higher rCBV values (4.28±2.11) than infectious lesions (0.63±0.49) (p<0.001). When using an rCBV value <1.3 as the parameter to define infectious lesions, the sensitivity of the method was 97.8% and the specificity was 92.6%, with a positive predictive value of 91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%.ConclusionPWI is a useful complementary tool in distinguishing between infectious and neoplastic brain lesions; an elevated discriminatory value for diagnosis of infectious brain lesions was observed in this sample of patients when the rCBV cutoff value was set to 1.3.

Association of Metabolite Concentrations and Water Diffusivity in Normal Appearing Brain Tissue with Glioma Grade

Studies of brain tumors have identified altered tissue metabolism and water diffusion in MRI normal appearing tissue regions. In this retrospective study the relationship of these imaging measures with tumor grade in gliomas was investigated. MR spectroscopic imaging of whole brain and mean diffusivity (MD) measurements were obtained in subjects with untreated glioma and from normal control subjects. Mean metabolite values for N-acetylaspartate (NAA), total creatine (Cre), and total choline (Cho) were obtained in gray- and white-matter regions for the hemisphere contralateral to the tumor location, and MD values were obtained from contralateral normal-appearing white matter. Analyses tested for differences in mean values between subject groups while accounting for age. Analysis demonstrated increased NAA/Cre and MD, and decreased Cho/NAA for all tumor grades relative to control values. Differences between tumor grades were also observed for NAA, NAA/Cre, and Cho/NAA. Abnormal values of water diffusion were also observed, but with only a weak association between alterations in diffusion and tissue metabolites. This study supports previous observations of altered tissue metabolism and water diffusion in normal-appearing white matter while additionally finding differences of metabolite values in gray matter and an association with tumor grade.

Amide proton transfer imaging in grading tumors of the neuroepithelial tissue

Objective To investigate the role of the amide proton transfer (APT) MR sequence in grading tumors of the neuroepithelial tissue,and its application in identifying the different components of the tumors.Methods 33 patients (18 male,15 female,age was from 18 to 71 with mean age of 46 years) were investigated and confirmed to be tumors of neuroepithelial tissue (glioma) by postoperative pathology,in whom 3T MRI with T2-weighted,FLAIR,pre-and post-contrast T1-weighted and APT sequences were performed.For each patient,APT signal intensities of each regions of interest (ROI) was defined and used for grading.Comparisons of APT signal intensities of high grade were done among tumor core,peritumoral edema and the contralateral normal-appearing white matter (CNAWM) and the APT signal intensities of tumor core were also compared between high and low grade glioma.Results 33 patients included 10 grade Ⅱ tumors,11 grade Ⅲ tumors,and 12 grade Ⅳ tumors.The average APT signal intensities were significantly higher in the tumor cores both in high and low grade than the peritumoral edema (P ＜ 0.05)and the contralateral normal-appearing white matter (P ＜ 0.01).Moreover,the APT signal intensities of the tumor cores of high-grade brain tumors were significantly higher than those of low-grade (P ＜ 0.01).Conclusions Amide proton transfer contrast can differentiate the tumor core from peritumoral edema,and combined with routine MRI is of clinical application value in grading of glioma. Key words: Magnetic resonance imaging; Amide proton transfer; Neoplasms, neuroepithelial; Pathology

The value of magnetic resonance spectroscopy and diffusion tensor imaging in characterization of gliomas growth patterns and treatment efficiency

The objective of the study was to assess the usefulness of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in detection of vital tumor cell infiltration presence in peritumoral brain areas and determination of biochemical changes in the brain parenchyma after received treatment. 73 patients with present, morphologically conformed brain gliomas and 77 gliomas patients in remission stage after combined therapy underwent magnetic resonance imaging (MRI) including MRS and DTI. Fractional anisotropy (FA) and metabolite ratios—choline/creatine (Cho/Cr), myoinositol/creatine (MI/Cr), lactate-lipid/creatine (LL/Cr), N-acetyl aspartate/creatine (NAA/Cr)—were measured in the tumor, perifocal edema zone, distant and contra-lateral normal appearing white matter. We observed gradual reduction of Cho/Cr, MI/Cr, LL/Cr mean ratios and step-by-step increase of NAA/Cr, FA mean values in the direction from the tumor to the distant and contra-lateral normal-appearing white matter. LL/Cr ratios within distal normal appearing white matter decreased in patients after radiotherapy/chemotherapy. Our study suggests that MRS and DTI in combination with structural MRI sequences enhance vital glial tumor cells areas and possible infiltration border. MRS and DTI quantitative measurements in the glioma peritumoral area reveal pathological changes, despite the normal signal intensity in structural MRI. We suggest that increased LL/Cr ratios and decreased FA values may have the superior implications in the detecting of glial tumors extent along the white matter tracts. NAA/Cr reduction and Cho/Cr increase may provide additional diagnostic value. LL/Cr ratio in distal normal signal intensity area could be used as radiation/chemotherapy effectiveness criteria, as this will reduce after the received treatment and in remission period.

Magnetic Resonance Study on Fractional Anisotropy and Neuronal Metabolite Ratios in Peritumoral Area of Cerebral Gliomas

Cerebral gliomas have a tendency to infiltrate the surrounding brain tissue for several centimeters from the core of tumor. The usefulness of structural magnetic resonance (MR) sequences is limited because of their insensitivity for the detection of tumor cells outside the visible tumor border. The aim of this study was to investigate the validity and the repeatability of 2 functional MR methods: fractional anisotropy (FA) and spectroscopy in the assessment of the peritumoral area of cerebral gliomas. Forty-five patients with histologically verified brain gliomas underwent diffusion tensor imaging (DTI) and MR spectroscopy (MRS). Metabolic ratios were calculated from choline (Cho), creatine (Cr), N-acetylaspartate (NAA), lactate/lipids (LL), myo-inositol (MI) spectroscopic values obtained within the tumor center, perifocal edema, and distant and contralateral normal-appearing white matter. DTI maps of FA were calculated at the same locations. A significant gradual increase of FA and a decrease of LL/Cr ratios from the tumor center to the normal-appearing white matter were observed. The Cho/Cr ratio was significantly lower in the distant normal-appearing white matter than in the perifocal edema and the tumor center. The NAA/Cr ratio was significantly reduced in the tumor center, perifocal edema, and distant normal-appearing white matter compared with the contralateral hemisphere. MRS and DTI measurements of glioma and peritumoral area had a high degree of repeatability. Our study shows that MRS and DTI measurements are reproducible. The combined use of Cho/Cr, LL/Cr, and FA measurements is a promising MR technique that provides valuable additional information about the location of glioma potential border.

Diffusion tensor imaging of acute inflammatory lesion evolution in multiple sclerosis

The initiating events in multiple sclerosis (MS) plaque formation are poorly understood. Retrospective analysis of serial imaging data can improve the understanding of tissue changes characterising acute MS lesion evolution. This study aimed to assess lesion evolution using diffusion tensor imaging data from serially acquired scans from 22 patients with MS. Mean diffusivity (MD) and fractional anisotropy (FA) were measured from 13 suitable plaques from five patients and carefully matched regions of contralateral normal-appearing white matter. Measurement times were on average: 5months and 1month prior to, during, and 1month and 2months post gadolinium-enhancement. A significant increase in MD (7.25%) but no change in FA was observed in white matter areas that exhibited enhancement 5months later. The pre-lesional MD increase was significantly correlated with the MD increase 2months subsequent to enhancement (R=0.73, p=0.04) but not to the MD increase during enhancement (R=0.11). These results suggest that MD is sensitive to tissue changes that precede blood–brain barrier (BBB) breakdown by at least 5months and that MD assessments may predict injury following BBB restoration.

Three-Dimensional Turbo-Spin-Echo Amide Proton Transfer MR Imaging at 3-Tesla and Its Application to High-Grade Human Brain Tumors

Amide proton transfer (APT) imaging is able to extend the achievable magnetic resonance imaging (MRI) contrast to the protein level. In this study, we demonstrate the feasibility of applying a turbo-spin-echo (TSE)-based, three-dimensional (3D) APT sequence into routine clinical practice for patients with brain tumors. Experiments were performed on a Philips 3-Tesla (3-T) MRI scanner using an eight-channel phased-array coil for reception. A fast 3D APT sequence with a TSE acquisition was proposed (saturation power, 2μT; saturation time, 500ms; 8 slices). The gradient echo (GRE)-based field-mapping technique or water-saturation-shift-referencing (WASSR) technique was used to acquire B(0) maps to correct for B(0)-induced artifacts in APT images. The test was performed on a box of homogenous protein solution, four healthy volunteers, and eight patients with high-grade gliomas. The experimental data from a homogenous, protein-containing phantom and healthy volunteers show that the sequence produced a uniform contrast across all slices. The average MTR(asym)(3.5ppm) values with GRE B(0)-corrected 3D APT imaging and WASSR-corrected 3D APT imaging were both comparable to the values obtained using the undemanding single-slice acquisition. The average APT image intensity was consistently higher in the tumor core than in the peripheral edema and in the contralateral normal-appearing white matter (both P < 0.001). 3D APT imaging of brain tumors can be performed in about 5min at 3-T using a routine, commercial eight-channel SENSE coil.

Gliomas: Diffusion Kurtosis MR Imaging in Grading

To assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters in grading gliomas. The institutional review board approved this prospective study, and informed consent was obtained from all patients. Diffusion parameters-mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis, and radial and axial kurtosis-were compared in the solid parts of 17 high-grade gliomas and 11 low-grade gliomas (P<.05 significance level, Mann-Whitney-Wilcoxon test, Bonferroni correction). MD, FA, mean kurtosis, radial kurtosis, and axial kurtosis in solid tumors were also normalized to the corresponding values in contralateral normal-appearing white matter (NAWM) and the contralateral posterior limb of the internal capsule (PLIC) after age correction and were compared among tumor grades. Mean, radial, and axial kurtosis were significantly higher in high-grade gliomas than in low-grade gliomas (P = .02, P = .015, and P = .01, respectively). FA and MD did not significantly differ between glioma grades. All values, except for axial kurtosis, that were normalized to the values in the contralateral NAWM were significantly different between high-grade and low-grade gliomas (mean kurtosis, P = .02; radial kurtosis, P = .03; FA, P = .025; and MD, P = .03). When values were normalized to those in the contralateral PLIC, none of the considered parameters showed significant differences between high-grade and low-grade gliomas. The highest sensitivity and specificity for discriminating between high-grade and low-grade gliomas were found for mean kurtosis (71% and 82%, respectively) and mean kurtosis normalized to the value in the contralateral NAWM (100% and 73%, respectively). Optimal thresholds for mean kurtosis and mean kurtosis normalized to the value in the contralateral NAWM for differentiating high-grade from low-grade gliomas were 0.52 and 0.51, respectively. There were significant differences in kurtosis parameters between high-grade and low-grade gliomas; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters.

Is the magnetization transfer ratio a marker for myelin in multiple sclerosis?

To investigate the correlation between water content (WC) and magnetization transfer ratio (MTR) in normal and multiple sclerosis (MS) brain. The MTR has been proposed as a marker for myelin in central nervous system tissue. However, changes in WC due to inflammation and edema may also affect the MTR. Seven MS subjects with active disease and seven age- and gender-matched controls were scanned using quantitative magnetic resonance techniques. WC, myelin water content, T(1) relaxation time, and MTR were calculated from areas of lesion (divided into new lesions less than 2 months old, isointense T(1) lesions, and hypointense T(1) lesions), contralateral normal-appearing white matter (NAWM), and location-matched normal white matter (NWM) in controls. Linear regression was used to determine the correlation between WC and MTR. A significant correlation was found between WC and MTR across all tissue (R = -0.65, P < 0.0005). MTR was correlated with WC in MS tissue, indicating that inflammation and edema influence MTR. Therefore, caution should be used when associating MTR exclusively with myelin content.

Prognostic significance of parameters derived from co-registered18F-fluorodeoxyglucose PET and contrast-enhanced MRI in patients with high-grade glioma

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; p<0.002). Enhancing lesions with an MAR >1.2 were associated with decreased survival (p<0.016). In nine patients who died, the MAR on PET correlated inversely with survival duration (r = -0.43; p<0.01), 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.

Translocator Protein PET Imaging for Glial Activation in Multiple Sclerosis

Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [(11)C]PBR28, a newly developed translocator protein-specific radioligand. The [(11)C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p = 0.019). Focal increases in [(11)C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p = 0.0039). Furthermore, increase in [(11)C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [(11)C]PBR28 binding showed correlation with disease duration (p = 0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.

Measurements of diagnostic examination performance using quantitative apparent diffusion coefficient and proton MR spectroscopic imaging in the preoperative evaluation of tumor grade in cerebral gliomas

Tumor grading is very important both in treatment decision and evaluation of prognosis. While tissue samples are obtained as part of most therapeutic approaches, factors that may result in inaccurate grading due to sampling error (namely, heterogeneity in tissue sampling, as well as tumor-grade heterogeneity within the same tumor specimen), have led to a desire to use imaging better to ascertain tumor grade. The purpose in our study was to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and accuracy of diffusion-weighted MR imaging (DWI), proton MR spectroscopic imaging (MRSI) or both in grading primary cerebral gliomas. We performed conventional MR imaging (MR), DWI, and MRSI in 74 patients with newly diagnosed brain gliomas: 59 patients had histologically verified high-grade gliomas: 37 glioblastomas multiform (GBM) and 22 anaplastic astrocytomas (AA), and 15 patients had low-grade gliomas. Apparent diffusion coefficient (ADC) values of tumor and peritumoral edema, and ADC ratios (ADC in tumor or peritumoral edema to ADC of contralateral white matter, as well as ADC in tumor to ADC in peritumoral edema) were determined from three regions of interest. The average of the mean, maximum, and minimum for ADC variables was calculated for each patient. The metabolite ratios of Cho/Cr and Cho/NAA at intermediate TE were assessed from spectral maps in the solid portion of tumor, peritumoral edema and contralateral normal-appearing white matter. Tumor grade determined with the two methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed to determine optimum thresholds for tumor grading. Measures of diagnostic examination performance, such as sensitivity, specificity, PPV, NPV, AUC, and accuracy for identifying high-grade gliomas were also calculated. Statistical analysis demonstrated a threshold minimum ADC tumor value of 1.07 to provide sensitivity, specificity, PPV, and NPV of 79.7%, 60.0%, 88.7%, and 42.9% respectively, in determining high-grade gliomas. Threshold values of 1.35 and 1.78 for peritumoral Cho/Cr and Cho/NAA metabolite ratios resulted in sensitivity, specificity, PPV, and NPV of 83.3%, 85.1%, 41.7%, 97.6%, and 100%, 57.4%, 23.1% and 100% respectively for determining high-grade gliomas. Significant differences were noted in the ADC tumor values and ratios, peritumoral Cho/Cr and Cho/NAA metabolite ratios, and tumoral Cho/NAA ratio between low- and high-grade gliomas. The combination of mean ADC tumor value, maximum ADC tumor ratio, peritumoral Cho/Cr and Cho/NAA metabolite ratios resulted in sensitivity, specificity, PPV, and NPV of 91.5%, 100%, 100% and 60% respectively. Combining DWI and MRSI increases the accuracy of preoperative imaging in the determination of glioma grade. MRSI had superior diagnostic performance in predicting glioma grade compared with DWI alone. The predictive values are helpful in the clinical decision-making process to evaluate the histologic grade of tumors, and provide a means of guiding treatment.

Proton magnetic resonance spectroscopy in the distinction of high-grade cerebral gliomas from single metastatic brain tumors

Brain metastases and primary high-grade gliomas, including glioblastomas multiforme (GBM) and anaplastic astrocytomas (AA), may be indistinguishable by conventional magnetic resonance (MR) imaging. Identification of these tumors may have therapeutic consequences. To assess the value of MR spectroscopy (MRS) using short and intermediate echo time (TE) in differentiating solitary brain metastases and high-grade gliomas on the basis of differences in metabolite ratios in the intratumoral and peritumoral region. We performed MR imaging and MRS in 73 patients with histologically verified intraaxial brain tumors: 53 patients with high-grade gliomas (34 GBM and 19 AA) and 20 patients with metastatic brain tumors. The metabolite ratios of Cho/Cr, Cho/NAA, and NAA/Cr at intermediate TE and the presence of lipids at short TE were assessed from spectral maps in the tumoral core, peritumoral edema, and contralateral normal-appearing white matter. The differences in the metabolite ratios between high-grade gliomas/GBM/AA and metastases were analyzed statistically. Cutoff values of Cho/Cr, Cho/NAA, and NAA/Cr ratios in the peritumoral edema, as well as Cho/Cr and NAA/Cr ratios in the tumoral core for distinguishing high-grade gliomas/GBM/AA from metastases were determined by receiver operating characteristic (ROC) curve analysis. Significant differences were noted in the peritumoral Cho/Cr, Cho/NAA, and NAA/ Cr ratios between high-grade gliomas/GBM/AA and metastases. ROC analysis demonstrated a cutoff value of 1.24 for peritumoral Cho/Cr ratio to provide sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 100%, 88.9%, 80.0%, and 100%, respectively, for discrimination between high-grade gliomas and metastases. By using a cutoff value of 1.11 for peritumoral Cho/NAA ratio, the sensitivity was 100%, the specificity was 91.1%, the PPV was 83.3%, and the NPV was 100%. The results of this study demonstrate that MRS can differentiate high-grade gliomas from metastases, especially with peritumoral measurements, supporting the hypothesis that MRS can detect infiltration of tumor cells in the peritumoral edema.

Untreated Glioblastoma Multiforme: IncreasedMyo-inositol and Glutamine Levels in the Contralateral Cerebral Hemisphere at Proton MR Spectroscopy

To use localized in vivo proton magnetic resonance (MR) spectroscopy of the contralateral hemisphere in patients with glioblastoma multiforme (GBM) to detect alterations in cerebral metabolites as potential markers of infiltrating GBM cells. The study was approved by the ethics committee, and written informed consent was obtained. Twenty-two patients with newly diagnosed and untreated GBM underwent in vivo single-voxel short echo time proton MR spectroscopy with a 3-T MR imaging system. Absolute metabolite concentrations in the hemisphere contralateral to the tumor were compared with data from five patients with low-grade gliomas (LGGs) and from a group of 14 age-matched control subjects by using analysis of variance and subsequent t tests or corresponding nonparametric tests. In the contralateral hemisphere, MR spectroscopy revealed increased concentrations of myo-inositol and glutamine. Mean myo-inositol levels were significantly increased in patients with GBM (3.6 mmol/L +/- 0.8 [standard deviation]) relative to levels in control subjects (3.1 mmol/L +/- 0.6; P = .03) and tended to be higher relative to levels in patients with LGG (2.7 mmol/L +/- 0.8; P = .09). Mean glutamine concentrations in patients with GBM (3.4 mmol/L +/- 0.9) differed significantly from those in control subjects (2.7 mmol/L +/- 0.7; P = .01); mean concentrations in patients with GBM differed from those in patients with LGG (2.4 mmol/L +/- 0.5; P = .01). There were no significant differences between data in patients with LGG and in control subjects. Increased concentrations of myo-inositol and glutamine in the contralateral normal-appearing white matter of GBM patients are consistent with mild astrocytosis and suggest the detectability of early neoplastic infiltration by using proton MR spectroscopy in vivo.