Restriction Spectrum Imaging Improves Risk Stratification in Patients with Glioblastoma.

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC. MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models. RESULTS: Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P = .036) and overall survival (P = .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P = .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P = .063). CONCLUSIONS: Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.

In vivo prostate cancer detection and grading using restriction spectrum imaging-MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

Genome-wide association study of shared components of reading disability and language impairment.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Recovery of white matter tracts in regions of peritumoral FLAIR hyperintensity with use of restriction spectrum imaging.

BACKGROUND AND PURPOSE: DTI is being increasingly used to visualize critical white matter tracts adjacent to brain tumors before neurosurgical resection. However, brain tumors, particularly high-grade gliomas, are typically surrounded by regions of FLAIR hyperintensity that include edema, which increase isotropic diffusion, degrading the ability of standard DTI to uncover orientation estimates within these regions. We introduce a new technique, RSI, which overcomes this limitation by removing the spherical, fast diffusion component introduced by edema, providing better analysis of white matter architecture. MATERIALS AND METHODS: A total of 10 patients with high-grade gliomas surrounded by FLAIR-HI that at least partially resolved on follow-up imaging were included. All patients underwent RSI and DTI at baseline (FLAIR-HI present) and at follow-up (FLAIR-HI partially resolved). FA values obtained with RSI and DTI were compared within regions of FLAIR-HI and NAWM at both time points. RESULTS: RSI showed higher FA in regions of FLAIR-HI and NAWM relative to DTI, reflecting the ability of RSI to specifically measure the slow, restricted volume fraction in regions of edema and NAWM. Furthermore, a method by time interaction revealed that FA estimates increased when the FLAIR-HI resolved by use of standard DTI but remained stable with RSI. Tractography performed within the region of FLAIR-HI revealed the superior ability of RSI to track fibers through severe edema relative to standard DTI. CONCLUSIONS: RSI improves the quantification and visualization of white matter tracts in regions of peritumoral FLAIR-HI associated with edema relative to standard DTI and may provide a valuable tool for neurosurgical planning.

Improved conspicuity and delineation of high-grade primary and metastatic brain tumors using "restriction spectrum imaging": quantitative comparison with high B-value DWI and ADC.

BACKGROUND AND PURPOSE: Restriction spectrum imaging is a sensitive DWI technique for probing separable water diffusion compartments in tissues. Here, we evaluate RSI-CMs derived from the spherically-restricted water compartment for improved tumor conspicuity and delineation from nontumor tissue and reduced sensitivity to edema compared with high-b-value DWI and ADC. MATERIALS AND METHODS: RSI was performed in 10 presurgical patients: 4 with glioblastoma, 3 with primary CNS lymphoma, and 3 with metastatic brain tumors. Multidirectional DWI data were collected at b = 500, 1500, and 4000 s/mm(2). Quantification of tumor conspicuity, edema conspicuity, and relative sensitivity to edema for RSI-CMs; DWI at b = 4000 (DWI-4000); and ADC were compared in manually drawn VOIs. Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of each method for delineating tumor from normal-appearing WM. RESULTS: Significant TC was seen with both RSI-CMs and DWI-4000, but not ADC. Significant EC was seen with ADC, but not RSI-CMs or DWI-4000. Significantly greater TC was seen with RSI-CMs compared with DWI-4000. Significantly reduced RSE was seen with RSI-CMs compared with both DWI-4000 and ADC. Greater sensitivity and specificity for delineating tumor from normal-appearing WM were seen with RSI-CMs (AUC = 0.91) compared with both DWI-4000 (AUC = 0.77) and ADC (AUC = 0.66). CONCLUSIONS: RSI-CMs offer improved conspicuity and delineation of high-grade primary and metastatic brain tumors and reduced sensitivity to edema compared with high-b-value DWI and ADC.

Contrasting gray and white matter changes in preclinical Huntington disease: an MRI study.

BACKGROUND: In Huntington disease (HD), substantial striatal atrophy precedes clinical motor symptoms. Accordingly, neuroprotection should prevent major cell loss before such symptoms arise. To evaluate neuroprotection, biomarkers such as MRI measures are needed. This requires first establishing the best imaging approach. METHODS: Using a cross-sectional design, we acquired T1-weighted and diffusion-weighted scans in 39 preclinical (pre-HD) individuals and 25 age-matched controls. T1-weighted scans were analyzed with gross whole-brain segmentation and voxel-based morphometry. Analysis of diffusion-weighted scans used skeleton-based tractography. For all imaging measures, we compared pre-HD and control groups and within the pre-HD group we examined correlations with estimated years to clinical onset. RESULTS: Pre-HD individuals had lower gross gray matter (GM) and white matter (WM) volume. Voxel-wise analysis demonstrated local GM volume loss, most notably in regions consistent with basal ganglia-thalamocortical pathways. By contrast, pre-HD individuals showed widespread reductions in WM integrity, probably due to a loss of axonal barriers. Both GM and WM imaging measures correlated with estimated years to onset. CONCLUSIONS: Using automated, observer-independent methods, we found that GM loss in pre-HD was regionally specific, while WM deterioration was much more general and probably the result of demyelination rather then axonal degeneration. These findings provide important information about the nature, relative staging, and topographic specificity of brain changes in pre-HD and suggest that combining GM and WM imaging may be the best biomarker approach. The empirically derived group difference images from this study are provided as regions-of-interest masks for improved sensitivity in future longitudinal studies.