Differentiation between intramedullary spinal ependymoma and astrocytoma: comparative MRI analysis.

AIM: To investigate magnetic resonance imaging (MRI) findings that could be used to differentiate intramedullary spinal ependymoma from astrocytoma, and to determine predictors for this differentiation. MATERIALS AND METHODS: MRI images of 43 consecutive patients with pathologically proven intramedullary spinal ependymoma (n = 24) and astrocytoma (n = 19) were comparatively evaluated with regard to size, location, margin, signal intensity, contrast enhancement, presence of syringohydromyelia, tumoural cyst, non-tumoural cyst, and haemorrhage. MRI findings and demographic data were compared between the two tumour groups using univariate and multivariate logistic regression analyses. RESULTS: In patients with ependymoma, older age and a larger solid component were more often observed than in astrocytoma. Central location, presence of enhancement, diffuse enhancement, syringohydromyelia, haemorrhage, and cap sign were more frequently observed in ependymoma. However, multivariate analysis revealed that syringohydromyelia was the only variable able to independently differentiate ependymoma from astrocytoma, with an odds ratio of 62.9 (95% CI: 4.38-903.22; p = 0.002). CONCLUSION: Among the various findings, the presence of syringohydromyelia is the main factor distinguishing ependymoma from astrocytoma.

Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy.

Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

Predicting the optimal depth of left-sided central venous catheters in children.

The aim of this study was to predict the optimal depth for insertion of a left-sided central venous catheter in children. Using 3D chest computed tomography angiography, we measured the distance from a point where the internal jugular vein is at the superior border of the clavicle, and from a point where the subclavian vein is inferior to the anterior border of the clavicle, to the junction of the superior vena cava and the right atrium in 257 children. Linear regression analysis revealed that the distances correlated with age, weight and height. Simple formulae for the depth of a central venous catheter via the left internal jugular vein (0.07 × height (cm)) and the left subclavian vein (0.08 × height (cm)) were developed to predict placement of the central venous catheter tip at the junction of the superior vena cava with the right atrium. Using these fomulae, the proportion of catheter tips predicted to be correctly located was 98.5% (95% CI 96.8-100%) and 94.0% (95% CI 90.8-97.3%), respectively.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

MGMT Promoter Methylation Status in Initial and Recurrent Glioblastoma: Correlation Study with DWI and DSC PWI Features.

BACKGROUND AND PURPOSE: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate MGMT promoter methylation status changes with DWI and DSC PWI features in patients with recurrent glioblastoma after standard treatment. MATERIALS AND METHODS: Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the MGMT promoter methylation status for the initial and recurrent tumors: 2 groups whose MGMT promoter methylation status remained, group methylated (n = 13) or group unmethylated (n = 18), and 1 group whose MGMT promoter methylation status changed from methylated to unmethylated (n = 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The t test and Mann-Whitney U test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups. RESULTS: Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all P < .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (P < .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594. CONCLUSIONS: MGMT promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the MGMT promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.

A single T cell receptor recognizes structurally distinct MHC/peptide complexes with high specificity.

The 2C T cell is a CD8+, alloreactive T cell, which recognizes cells bearing Ld and Kbm3 class I major histocompatability complex molecules. Here, we characterize an allopeptide, designated dEV-8, that is a ligand in the Kbm3 molecule for the 2C TCR but is not a ligand in the Ld molecule. By biochemical and immunological properties, dEV-8 is distinct from P2Ca, the Ld allopeptide that is also recognized by the 2C TCR. Using the deduced amino acid sequence of dEV-8, we isolate a candidate endogenous source of the peptide. The endogenous protein, MLRQ, contains a peptide sequence identical to dEV-8. This degenerate recognition of two distinct peptide/MHC complexes by a single TCR has important implications for understanding allorecognition.

A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase.

We have identified and characterized a novel src homology 2 (SH2) and pleckstrin homology (PH) domain-containing adaptor protein, designated Bam32 (for B cell adaptor molecule of 32 kD). cDNAs encoding the human and mouse Bam32 coding sequences were isolated and the human bam32 gene was mapped to chromosome 4q25-q27. Bam32 is expressed by B lymphocytes, but not T lymphocytes or nonhematopoietic cells. Human germinal center B cells show increased Bam32 expression, and resting B cells rapidly upregulate expression of Bam32 after ligation of CD40, but not immunoglobulin M. Bam32 is tyrosine-phosphorylated upon B cell antigen receptor (BCR) ligation or pervanadate stimulation and associates with phospholipase Cgamma2. After BCR ligation, Bam32 is recruited to the plasma membrane through its PH domain. Membrane recruitment requires phosphatidylinositol 3-kinase (PI3K) activity and an intact PI(3,4, 5)P(3)-binding motif, suggesting that membrane association occurs through binding to 3-phosphoinositides. Expression of Bam32 in B cells leads to a dose-dependent inhibition of BCR-induced activation of nuclear factor of activated T cells (NF-AT), which is blocked by deletion of the PH domain or mutation of the PI(3,4,5)P(3)-binding motif. Thus, Bam32 represents a novel B cell-associated adaptor that regulates BCR signaling downstream of PI3K.

GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation.

Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain-containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL-SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells.

Comparison of higher dose and lower dose ganciclovir for cytomegalovirus prophylaxis in seropositive heart transplant recipients.

BACKGROUND: We performed a retrospective historical cohort study to compare the efficacy of higher dose (HD, 10 mg/kg/day for 2 weeks, followed by 5 mg/kg/day intravenously for 2 weeks) and lower dose (LD, 5 mg/kg/day for 4 weeks) ganciclovir (GCV) for cytomegalovirus (CMV) prophylaxis in seropositive heart transplant recipients. METHODS: All consecutive patients undergoing heart transplantation (HT) between June 1999 and January 2008 at our institution were enrolled. All recipients were seropositive for CMV before HT. Before October 2005, 72 patients received the HD regimen and after October 2005, 36 patients received the LD regimen. We followed up all patients for 1 year. RESULTS: In the HD group 43 of 72 patients (60%) developed CMV infections vs. 21 of 36 patients (58%) in the LD group (P=0.89). CMV diseases occurred in 4 patients of the HD group (6%) and 4 patients of the LD group (11%) (P=0.44). The incidence of acute rejection was not significantly different between the 2 groups (14% vs. 6%; P=0.33). Among patients who completed 4-week courses of prophylaxis, 32 of 58 patients (55%) in the HD group developed CMV infections vs. 18 of 30 patients (60%) in the LD group (P=0.66). CMV diseases occurred in 3 patients of the HD group (5%) and 4 of the LD group (13%) (P=0.22). Acute rejection incidence did not differ significantly between the 2 groups (17% vs. 7%; P=0.21). CONCLUSIONS: LD GCV for CMV prophylaxis may not be inferior to the HD regimen in seropositive HT recipients.

Dynamic Contrast-Enhanced MR Imaging of Nonenhancing T2 High-Signal-Intensity Lesions in Baseline and Posttreatment Glioblastoma: Temporal Change and Prognostic Value.

BACKGROUND AND PURPOSE: The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. MATERIALS AND METHODS: This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant [K trans], volume of extravascular extracellular space [v e], and blood plasma volume [vp ]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. RESULTS: Baseline median K trans, baseline first quartile K trans, and posttreatment median K trans were significant independent variables, as determined by univariate analysis (P < .05). By multivariate Cox regression analysis including methylation status of O6-methylguanine-DNA methyltransferase, baseline median K trans was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48, P = .003). CONCLUSIONS: Baseline median K trans from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.

Can Arterial Spin-Labeling with Multiple Postlabeling Delays Predict Cerebrovascular Reserve?

BACKGROUND AND PURPOSE: The effect of delayed transit time is the main source of error in the quantitative measurement of CBF in arterial spin-labeling. In the present study, we evaluated the usefulness of the transit time-corrected CBF and arterial transit time delay from multiple postlabeling delays arterial spin-labeling compared with basal/acetazolamide stress technetium Tc99m-hexamethylpropylene amineoxime (Tc99m-HMPAO) SPECT in predicting impairment in the cerebrovascular reserve. MATERIALS AND METHODS: Transit time-corrected CBF maps and arterial transit time maps were acquired in 30 consecutive patients with unilateral ICA or MCA steno-occlusive disease (severe stenosis or occlusion). Internal carotid artery territory-based ROIs were applied to both perfusion maps. Additionally, impairment in the cerebrovascular reserve was evaluated according to both qualitative and quantitative analyses of the ROIs on basal/acetazolamide stress Tc99m-HMPAO SPECT using a previously described method. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of arterial spin-labeling in depicting impairment of the cerebrovascular reserve. The correlation between arterial spin-labeling and cerebrovascular reserve was evaluated. RESULTS: The affected hemisphere had a decreased transit time-corrected CBF and increased arterial transit time compared with the corresponding values of the contralateral normal hemisphere, which were statistically significant (P < .001). The percentage change of transit time-corrected CBF and the percentage change of arterial transit time were independently differentiating variables (P < .001) for predicting cerebrovascular reserve impairment. The correlation coefficient between the arterial transit time and cerebrovascular reserve index ratio was -0.511. CONCLUSIONS: Our results demonstrate that the transit time-corrected CBF and arterial transit time based on arterial spin-labeling perfusion MR imaging can predict cerebrovascular reserve impairment.

Application of 3D Fast Spin-Echo T1 Black-Blood Imaging in the Diagnosis and Prognostic Prediction of Patients with Leptomeningeal Carcinomatosis.

BACKGROUND AND PURPOSE: Contrast-enhanced 3D fast spin-echo T1 black-blood imaging selectively suppresses the signal of blood flow and could provide a higher contrast-to-noise ratio compared with contrast-enhanced 3D ultrafast gradient recalled echo (contrast-enhanced gradient recalled echo) and 2D spin-echo T1WI (contrast-enhanced spin-echo). The purpose of our study was to evaluate whether black-blood imaging can improve the diagnostic accuracy for leptomeningeal carcinomatosis compared with contrast-enhanced gradient recalled-echo and contrast-enhanced spin-echo and, furthermore, to determine whether the grade of leptomeningeal carcinomatosis evaluated on black-blood imaging is a significant predictor of progression-free survival. MATERIALS AND METHODS: Leptomeningeal carcinomatosis (n = 78) and healthy (n = 31) groups were enrolled. Contrast-enhanced gradient recalled-echo, contrast-enhanced spin-echo, and black-blood imaging were separately reviewed, and a diagnostic rating (positive, indeterminate, or negative) and grading of leptomeningeal carcinomatosis were assigned. The diagnostic accuracies of the 3 imaging sequences were compared in terms of leptomeningeal carcinomatosis detection. The Kaplan-Meier and the Cox proportional hazards model analyses were performed to determine the relationship between the leptomeningeal carcinomatosis grade evaluated on black-blood imaging and progression-free survival. RESULTS: Black-blood imaging showed a significantly higher sensitivity (97.43%) than contrast-enhanced gradient recalled-echo (64.1%) and contrast-enhanced spin-echo (66.67%) (P < .05). In terms of specificities, we did not find any significant differences among contrast-enhanced gradient recalled-echo (90.32%), contrast-enhanced spin-echo (90.32%), and black-blood imaging (96.77%) (P > .05). A Cox proportional hazards model identified the time to metastasis, Karnofsky Performance Scale status, and a combination of the leptomeningeal carcinomatosis grade with a linear pattern as independent predictors of progression-free survival (P < .05). CONCLUSIONS: Black-blood imaging can improve the diagnostic accuracy and predict progression-free survival in patients with leptomeningeal carcinomatosis.

Unusual mutation clusters provide insight into class I gene conversion mechanisms.

Genetic diversity among the K and D alleles of the mouse major histocompatibility complex is generated by gene conversion among members of the class I multigene family. The majority of known class I mutants contain clusters of nucleotide changes that can be traced to linked family members. However, the details of the gene conversion mechanism are not known. The bm3 and bm23 mutations represent exceptions to the usual pattern and provide insight into intermediates generated during the gene conversion process. Both of these variants contain clusters of five nucleotide substitutions, but they differ from the classic conversion mutants in the important respect that no donor gene for either mutation could be identified in the parental genome. Nevertheless, both mutation clusters are composed of individual mutations that do exist within the parent. Therefore, they are not random and appear to be templated. Significantly, the bm3 and bm23 mutation clusters are divided into overlapping regions that match class I genes which have functioned as donor genes in other characterized gene conversion events. The unusual structure of the mutation clusters indicates an underlying gene conversion mechanism that can generate mutation clusters as a result of the interaction of three genes in a single genetic event. The unusual mutation clusters are consistent with a hypothetical gene conversion model involving extrachromosomal intermediates.

Added Value of Arterial Spin-Labeling MR Imaging for the Differentiation of Cerebellar Hemangioblastoma from Metastasis.

BACKGROUND AND PURPOSE: In adults with only cerebellar masses, hemangioblastoma and metastasis are the 2 most important differential diagnoses. Our aim was to investigate the added value of arterial spin-labeling MR imaging for differentiating hemangioblastoma from metastasis in patients with only cerebellar masses. MATERIALS AND METHODS: This retrospective study included a homogeneous cohort comprising patients with only cerebellar masses, including 16 hemangioblastomas and 14 metastases. All patients underwent enhanced MR imaging, including arterial spin-labeling. First, the presence or absence of a hyperperfused mass was determined. Next, in the hyperperfused mass, relative tumor blood flow (mean blood flow in the tumor divided by blood flow measured in normal-appearing cerebellar tissue) and the size ratio (size in the arterial spin-labeling images divided by size in the postcontrast T1WI) were measured. To validate the arterial spin-labeling findings, 2 observers independently evaluated the conventional MR images and the combined set of arterial spin-labeling images. RESULTS: All patients with hemangioblastomas and half of the patients with metastases presented with a hyperperfused mass (P < .001). The size ratio and relative tumor blood flow were significantly larger for hemangioblastomas than for metastases (P < .001 and P = .039, respectively). The size ratio revealed excellent diagnostic power (area under the curve = 0.991), and the relative tumor blood flow demonstrated moderate diagnostic power (area under the curve = 0.777). The diagnostic accuracy of both observers was significantly improved after the addition of arterial spin-labeling; the area under the curve improved from 0.574 to 0.969 (P < .001) for observer 2 and from 0.683 to 1 (P < .001) for observer 2. CONCLUSIONS: Arterial spin-labeling imaging can aid in distinguishing hemangioblastoma from metastasis in patients with only cerebellar masses.

Comparison between the Prebolus T1 Measurement and the Fixed T1 Value in Dynamic Contrast-Enhanced MR Imaging for the Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Concurrent Radiation Therapy and Temozolomide Chemotherapy.

BACKGROUND AND PURPOSE: Glioblastoma is the most common primary brain malignancy and differentiation of true progression from pseudoprogression is clinically important. Our purpose was to compare the diagnostic performance of dynamic contrast-enhanced pharmacokinetic parameters using the fixed T1 and measured T1 on differentiating true from pseudoprogression of glioblastoma after chemoradiation with temozolomide. MATERIALS AND METHODS: This retrospective study included 37 patients with histopathologically confirmed glioblastoma with new enhancing lesions after temozolomide chemoradiation defined as true progression (n = 15) or pseudoprogression (n = 22). Dynamic contrast-enhanced pharmacokinetic parameters, including the volume transfer constant, the rate transfer constant, the blood plasma volume per unit volume, and the extravascular extracellular space per unit volume, were calculated by using both the fixed T1 of 1000 ms and measured T1 by using the multiple flip-angle method. Intra- and interobserver reproducibility was assessed by using the intraclass correlation coefficient. Dynamic contrast-enhanced pharmacokinetic parameters were compared between the 2 groups by using univariate and multivariate analysis. The diagnostic performance was evaluated by receiver operating characteristic analysis and leave-one-out cross validation. RESULTS: The intraclass correlation coefficients of all the parameters from both T1 values were fair to excellent (0.689-0.999). The volume transfer constant and rate transfer constant from the fixed T1 were significantly higher in patients with true progression (P = .048 and .010, respectively). Multivariate analysis revealed that the rate transfer constant from the fixed T1 was the only independent variable (OR, 1.77 × 105) and showed substantial diagnostic power on receiver operating characteristic analysis (area under the curve, 0.752; P = .002). The sensitivity and specificity on leave-one-out cross validation were 73.3% (11/15) and 59.1% (13/20), respectively. CONCLUSIONS: The dynamic contrast-enhanced parameter of rate transfer constant from the fixed T1 acted as a preferable marker to differentiate true progression from pseudoprogression.

Antiangiogenic Effect of Bevacizumab: Application of Arterial Spin-Labeling Perfusion MR Imaging in a Rat Glioblastoma Model.

BACKGROUND AND PURPOSE: The usefulness of arterial spin-labeling for the evaluation of the effect of the antiangiogenic therapy has not been elucidated. Our aim was to evaluate the antiangiogenic effect of bevacizumab in a rat glioblastoma model based on arterial spin-labeling perfusion MR imaging. MATERIALS AND METHODS: DSC and arterial spin-labeling perfusion MR imaging were performed by using a 9.4T MR imaging scanner in nude rats with glioblastoma. Rats were randomly assigned to the following 3 groups: control, 3-day treatment, and 10-day treatment after bevacizumab injection. One-way analysis of variance with a post hoc test was used to compare perfusion parameters (eg, normalized CBV and normalized CBF from DSC MR imaging and normalized CBF based on arterial spin-labeling) with microvessel area on histology. The Pearson correlations between perfusion parameters and microvessel area were also determined. RESULTS: All of the normalized CBV from DSC, normalized CBF from DSC, normalized CBF from arterial spin-labeling, and microvessel area values showed significant decrease after treatment (P < .001, P < .001, P = .005, and P < .001, respectively). In addition, normalized CBV and normalized CBF from DSC and normalized CBF from arterial spin-labeling strongly correlated with microvessel area (correlation coefficient, r = 0.911, 0.869, and 0.860, respectively; P < .001 for all). CONCLUSIONS: Normalized CBF based on arterial spin-labeling and normalized CBV and normalized CBF based on DSC have the potential for evaluating the effect of antiangiogenic therapy on glioblastomas treated with bevacizumab, with a strong correlation with microvessel area.

Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging, Focusing on Putaminal Change and Lesion Asymmetry.

BACKGROUND AND PURPOSE: Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry. MATERIALS AND METHODS: This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values. RESULTS: The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001). CONCLUSIONS: 3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity. Furthermore, it clearly demonstrates the dominant side of putaminal changes, which correlate with the contralateral symptomatic side of patients.

Independent Poor Prognostic Factors for True Progression after Radiation Therapy and Concomitant Temozolomide in Patients with Glioblastoma: Subependymal Enhancement and Low ADC Value.

BACKGROUND AND PURPOSE: Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide. MATERIALS AND METHODS: Forty-two patients with glioblastoma multiforme with newly developed or enlarged enhancing lesions on the first follow-up MR images obtained within 2 months of concurrent chemoradiotherapy completion were included. Subependymal enhancement was analyzed for the presence, location, and pattern (local or distant relative to enhancing lesions). The mean ADC value and the fifth percentile of the cumulative ADC histogram were determined. A multiple logistic regression analysis was performed to identify independent factors associated with true progression. RESULTS: Distant subependymal enhancement (ie, extending >1 cm or isolated from the enhancing lesion) was significantly more common in true progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth percentile of the cumulative ADC histogram was significantly lower in true progression than in pseudoprogression (P = .014). Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were independent factors associated with true progression (P = .041 and P = .033, respectively). Sensitivity and specificity for the diagnosis of true progression were 83% and 67%, respectively, by using both factors. CONCLUSIONS: Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were significant independent factors predictive of true progression.

Correlation of Asymmetry Indices Measured by Arterial Spin-Labeling MR Imaging and SPECT in Patients with Crossed Cerebellar Diaschisis.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis, not only a secondary result of supratentorial infarction but also an indicator of clinical outcomes, has frequently been reported on PET and SPECT but has been rarely described with arterial spin-labeling MR imaging. The purpose of this study was to determine the ability of arterial spin-labeling MR imaging to evaluate crossed cerebellar diaschisis compared with that of SPECT. To our knowledge, this is the first study to validate arterial spin-labeling in crossed cerebellar diaschisis by using SPECT as a reference standard. MATERIALS AND METHODS: This study included 16 patients in whom crossed cerebellar diaschisis was shown on SPECT and 10 control subjects in whom crossed cerebellar diaschisis was not shown on SPECT. During the qualitative analysis, asymmetric cerebellar perfusion on arterial spin-labeling was divided into 1 of the following 3 grades by 2 blinded observers: the affected cerebellum was isointense compared with the unaffected cerebellum (grade I), it was slightly hypointense (grade II), or it was markedly hypointense (grade III). In the quantitative analysis, asymmetry indices were calculated by using SPECT and arterial spin-labeling images. For statistical analysis, κ statistics, the interobserver correlation coefficient, the independent t test, Pearson correlation, and linear regression analysis were used. RESULTS: Almost all the diagnoses of crossed cerebellar diaschisis on SPECT were noted on arterial spin-labeling in both qualitative and quantitative analyses with good interobserver agreement (κ = 0.961; interobserver correlation coefficient, 0.806). The mean asymmetry index of arterial spin-labeling (26.06 ± 9.00) was significantly larger than that for SPECT (15.28 ± 5.34; P < .001). There was a significant positive correlation between the asymmetry indices obtained for SPECT and those for arterial spin-labeling (r = 0.77 [95% CI, 0.443-0.916]; P < .001). The relationship of asymmetry indices between SPECT and arterial spin-labeling (x, y) was calculated as y = 6.2131 + 1.2986x (R(2) = 0.592; P < .001). CONCLUSIONS: Arterial spin-labeling can be a noninvasive alternative to SPECT for evaluating crossed cerebellar diaschisis.

Clinical utility of arterial spin-labeling as a confirmatory test for suspected brain death.

Diagnosis of brain death is made on the basis of 3 essential findings: coma, absence of brain stem reflexes, and apnea. Although confirmatory tests are not mandatory in most situations, additional testing may be necessary to declare brain death in patients in whom results of specific components of clinical testing cannot be reliably evaluated. Recently, arterial spin-labeling has been incorporated as part of MR imaging to evaluate cerebral perfusion. Advantages of arterial spin-labeling include being completely noninvasive and providing information about absolute CBF. We retrospectively reviewed arterial spin-labeling findings according to the following modified criteria based on previously established confirmatory tests to determine brain death: 1) extremely decreased perfusion in the whole brain, 2) bright vessel signal intensity around the entry of the carotid artery to the skull, 3) patent external carotid circulation, and 4) "hollow skull sign" in a series of 5 patients. Arterial spin-labeling findings satisfied the criteria for brain death in all patients. Arterial spin-labeling imaging has the potential to be a completely noninvasive confirmatory test to provide additional information to assist in the diagnosis of brain death.