Delineation of recurrent glioblastoma by whole brain spectroscopic magnetic resonance imaging.

BACKGROUND: Glioblastoma (GBM) cellularity correlates with whole brain spectroscopic MRI (sMRI) generated relative choline to N-Acetyl-Aspartate ratio (rChoNAA) mapping. In recurrent GBM (rGBM), tumor volume (TV) delineation is challenging and rChoNAA maps may assist with re-RT targeting. METHODS: Fourteen rGBM patients underwent sMRI in a prospective study. Whole brain sMRI was performed to generate rChoNAA maps. TVs were delineated by the union of rChoNAA ratio over 2 (rChoNAA > 2) on sMRI and T1PC. rChoNAA > 2 volumes were compared with multiparametric MRI sequences including T1PC, T2/FLAIR, diffusion-restriction on apparent diffusion coefficient (ADC) maps, and perfusion relative cerebral blood volume (rCBV). RESULTS: rChoNAA > 2 (mean 27.6 cc, range 6.6-79.1 cc) was different from other imaging modalities (P ≤ 0.05). Mean T1PC volumes were 10.7 cc (range 1.2-31.4 cc). The mean non-overlapping volume of rChoNAA > 2 and T1PC was 29.2 cm3. rChoNAA > 2 was 287% larger (range 23% smaller-873% larger) than T1PC. T2/FLAIR volumes (mean 111.7 cc, range 19.0-232.7 cc) were much larger than other modalities. rCBV volumes (mean 6.2 cc, range 0.2-19.1 cc) and ADC volumes were tiny (mean 0.8 cc, range 0-3.7 cc). Eight in-field failures were observed. Three patients failed outside T1PC but within rChoNAA > 2. No grade 3 toxicities attributable to re-RT were observed. Median progression-free and overall survival for re-RT patients were 6.5 and 7.1 months, respectively. CONCLUSIONS: Treatment of rGBM may be optimized by sMRI, and failure patterns suggest benefit for dose-escalation within sMRI-delineated volumes. Dose-escalation and radiologic-pathologic studies are underway to confirm the utility of sMRI in rGBM.

Prevalence and Clinical Correlates of Intracranial Dolichoectasia in Individuals With Ischemic Stroke.

Background and Purpose: Acute ischemic stroke is a known complication of intracranial dolichoectasia (IDE). However, the frequency of IDE causing brain infarction is unknown. We aim to determine the prevalence and clinical correlates of IDE in acute ischemic stroke by employing an objective IDE definition for major intracranial arteries of the anterior and posterior circulation. Methods: Consecutive patients with acute ischemic stroke admitted to a tertiary-care hospital during a 4-month period were analyzed. Intracranial arterial diameter, length, and tortuosity were determined by semiautomatic vessel segmentation and considered abnormal if ≥2 SDs from the study population mean. Either ectasia (increased diameter) or dolichosis (increased length or tortuosity) of at least one proximal intracranial artery defined IDE. Symptomatic IDE was considered when the infarct was located in the territory supplied by an affected artery in the absence of any alternative pathogenic explanation. Multivariate models were fitted to determine IDE clinical correlates. Results: Among 211 cases screened, 200 patients (mean age 67±14 years, 47.5% men) with available intracranial vessel imaging were included. IDE was identified in 24% cases (5% with isolated ectasia, 9.5% with isolated dolichosis, and 9.5% with both ectasia and dolichosis). IDE was considered the most likely pathogenic mechanism in 12 cases (6% of the entire cohort), which represented 23.5% of strokes initially categorized as undetermined cause. In addition, 21% of small-artery occlusion strokes had the infarct territory supplied by a dolichoectatic vessel (3% of the entire cohort). IDE was independently associated with male sex (odds ratio, 4.2 [95% CI, 1.7­10.6]) and its component of ectasia was associated with advanced age (odds ratio, 3.5 [95% CI, 1.3­9.5]). Vascular risk profile was similar across patients with stroke with and without IDE. Conclusions: Our findings suggest that IDE is an arteriopathy frequently found in patients with acute ischemic stroke and is likely responsible for a sizable fraction of strokes initially categorized as of undetermined cause and perhaps also in those with small-artery occlusion.

Value of diffusion kurtosis imaging in assessing low-grade gliomas.

BACKGROUND: Diffusion kurtosis imaging (DKI) measures have been shown to provide increased sensitivity relative to diffusion tensor imaging (DTI) in detecting pathologies. PURPOSE: To compare the sensitivity of DKI-derived kurtosis and diffusion maps for assessment of low-grade gliomas (LGG). STUDY TYPE: Prospective study. POPULATION: In all, 19 LGG patients and 26 healthy control subjects were recruited. FIELD STRENGTH/SEQUENCE: Echo-planar-imaging diffusion-weighted MR images (b-values = 0, 1000, and 2000 with 30 diffusion gradient directions) were acquired on a 3T scanner. ASSESSMENT: Maps for mean, axial, and radial diffusivity (MD, AD, and RD) and kurtosis (MK, AK, and RK), and fractional anisotropy (FA) were evaluated in the tumor, perilesional white matter, and contralateral normal-appearing white matter regions. STATISTICAL TESTING: General linear models (GLM), Cohen's d for effect size estimates, false discovery rate (FDR) for multiple corrections, Cochran Q-test. RESULTS: Pairwise differences were observed for all diffusion and kurtosis measures between the studied regions (FDR P < 0.001), except an FA map that failed to show significant differences between the lesion and perilesional white matter (FDR P = 0.373). Effect size analysis showed that kurtosis metrics were found to be 18.8% (RK, P = 0.144) to 29.1% (AK, P < 0.05) more sensitive in discriminating perilesional regions from the lesion than corresponding diffusion metrics, whereas AK provided a 25.0% (P < 0.05) increase in sensitivity in discriminating perilesional and contralateral white matter. RK was found to be the most sensitive to contralateral white matter differences between low-grade gliomas and controls, with MK and RK providing a significantly greater sensitivity of 587.2% (P < 0.001) and 320.7% (P < 0.001) than MD and RD, respectively. DATA CONCLUSION: Kurtosis maps showed increased sensitivity, as compared to counterpart diffusion maps, for evaluation of microstructural changes in gliomas with a 3-6-fold increment in assessing changes in contralateral white matter. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1551-1558.

Spectral decomposition for resolving partial volume effects in MRSI.

PURPOSE: Estimation of brain metabolite concentrations by MR spectroscopic imaging (MRSI) is complicated by partial volume contributions from different tissues. This study evaluates a method for increasing tissue specificity that incorporates prior knowledge of tissue distributions. METHODS: A spectral decomposition (sDec) technique was evaluated for separation of spectra from white matter (WM) and gray matter (GM), and for measurements in small brain regions using whole-brain MRSI. Simulation and in vivo studies compare results of metabolite quantifications obtained with the sDec technique to those obtained by spectral fitting of individual voxels using mean values and linear regression against tissue fractions and spectral fitting of regionally integrated spectra. RESULTS: Simulation studies showed that, for GM and the putamen, the sDec method offers < 2% and 3.5% error, respectively, in metabolite estimates. These errors are considerably reduced in comparison to methods that do not account for partial volume effects or use regressions against tissue fractions. In an analysis of data from 197 studies, significant differences in mean metabolite values and changes with age were found. Spectral decomposition resulted in significantly better linewidth, signal-to-noise ratio, and spectral fitting quality as compared to individual spectral analysis. Moreover, significant partial volume effects were seen on correlations of neurometabolite estimates with age. CONCLUSION: The sDec analysis approach is of considerable value in studies of pathologies that may preferentially affect WM or GM, as well as smaller brain regions significantly affected by partial volume effects. Magn Reson Med 79:2886-2895, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Effects of tissue susceptibility on brain temperature mapping.

A method for mapping of temperature over a large volume of the brain using volumetric proton MR spectroscopic imaging has been implemented and applied to 150 normal subjects. Magnetic susceptibility-induced frequency shifts in gray- and white-matter regions were measured and included as a correction in the temperature mapping calculation. Additional sources of magnetic susceptibility variations of the individual metabolite resonance frequencies were also observed that reflect the cellular-level organization of the brain metabolites, with the most notable differences being attributed to changes of the N-Acetylaspartate resonance frequency that reflect the intra-axonal distribution and orientation of the white-matter tracts with respect to the applied magnetic field. These metabolite-specific susceptibility effects are also shown to change with age. Results indicate no change of apparent brain temperature with age from 18 to 84 years old, with a trend for increased brain temperature throughout the cerebrum in females relative for males on the order of 0.1°C; slightly increased temperatures in the left hemisphere relative to the right; and a lower temperature of 0.3°C in the cerebellum relative to that of cerebral white-matter. This study presents a novel acquisition method for noninvasive measurement of brain temperature that is of potential value for diagnostic purposes and treatment monitoring, while also demonstrating limitations of the measurement due to the confounding effects of tissue susceptibility variations.

Regional distributions of brain glutamate and glutamine in normal subjects.

Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS-observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short-TE whole-brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high-SNR spectra from atlas-registered anatomic regions or interest. By spectral fitting of high-SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray-matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white-matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white-matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray-matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd.