High-Resolution Diffusion-Weighted Imaging of C6 Glioma on a 7T BioSpec MRI Scanner: Correlation of Tumor Cellularity and Nuclear-to-Cytoplasmic Ratio with Apparent Diffusion Coefficient.

RATIONALE AND OBJECTIVES: To determine the association of the apparent diffusion coefficient (ADC) with quantitative cellularity and the nuclear-to-cytoplasmic ratio in C6 glioma. MATERIALS AND METHODS: Animal models bearing C6 gliomas underwent MR scans with T1 rapid acquisition with relaxation enhancement (RARE), T2 RARE, and high-resolution diffusion-weighted imaging sequences. For each model, three consecutive sections were used to draw regions of interest (ROIs) and measure ADC values; the middle section was localized in the plane with the maximal solid tumor area. The minimal, mean, and maximal ADC values were recorded for each ROI. GFAP-immunostained sections coregistered with ADC measurements were used to calculate tumor cellularity and the nuclear-to-cytoplasmic (N/C) ratio. Spearman's correlation was used to assess the relationship between ADC values and quantitative tumor cellularity as well as N/C ratios with a significance level of p < 0.05. RESULTS: Thirty-three sections from 11 glioma-bearing rats were analyzed. The median values of the minimal, mean, and maximal ADC were 0.443 × 10-3, 0.744 × 10-3, and 1.140 × 10-3 mm2/s, respectively. The median cellularity and N/C ratio were 2151.234 per 0.025 mm2 and 0.857, respectively. The minimal, mean, and maximal ADCs were all significantly associated with cellularity, with correlation coefficients of -0.712 (p < 0.001), -0.631 (p < 0.001), and -0.460 (p = 0.007), respectively. The minimal and mean ADC had significant negative relationships with the N/C ratio, with correlation coefficients of -0.565 (p =  0.001) and -0.426 (p = 0.013), respectively. CONCLUSION: The minimal ADC correlated well with cellularity and N/C ratios in C6 glioma and may be used as a biomarker of these two pathological features.

Diffusion kurtosis imaging differs between primary central nervous system lymphoma and high-grade glioma and is correlated with the diverse nuclear-to-cytoplasmic ratio: a histopathologic, biopsy-based study.

OBJECTIVES: To determine whether water kurtosis and diffusional metrics derived from diffusional kurtosis imaging (DKI) within primary central nervous system lymphomas (PCNSLs) and high-grade gliomas (HGGs) correlate with cellularity and/or nuclear-to-cytoplasmic (N/C) ratio. METHODS: Forty-four and 43 pathologically confirmed high-grade glioma and primary central nervous system lymphoma specimens between May 2013 and November 2016 were retrospectively reviewed. Diffusional metrics, kurtosis metrics, cellularity, and N/C ratios in PCNSLs and HGGs were compared using the Mann-Whitney U test (significant level, p < 0.007 [0.05/7]); Bonferroni correction). RESULTS: Mean kurtosis (MK), axial kurtosis (K//), and radial kurtosis (K⊥) in PCNSLs were 0.857 (0.693-0.924), 0.837 (0.660-0.941), and 0.834 (0.685-0.937), respectively; and 0.629 (0.524-0.716), 0.575 (0.511-0.689), and 0.675 (0.532-0.766), respectively, in HGGs (all p < 0.001). No significant differences in fractional anisotropy (FA), mean diffusion (MD), axial diffusion (λ//), and radial diffusion (λ⊥) were found between HGGs and PCNSLs. Cellularity was higher in PCNSLs than in HGGs (p = 0.125); whereas, the N/C ratio in PCNSLs was significantly higher than that in HGGs (p < 0.001). All DKI metrics (FA, MD, λ//, λ⊥, MK, K//, and K⊥) were significantly correlated with N/C ratio in PCNSLs with correlation coefficients being rho = 0.418, - 0.722, - 0.525, - 0.768, 0.704, 0.579, and 0.686, respectively. Cellularity in PCNSLs and HGGs did not correlate with any kurtosis or diffusional metrics. CONCLUSIONS: Difference of kurtosis parameters between PCNSLs and HGGs is correlated with their diverse N/C ratio. KEY POINTS: • DKI has considerable value in differentiating between PCNSLs and HGGs. • DKI can provide important information on nuclear-to-cytoplasmic ratio. • Difference of kurtosis parameters between PCNSLs and HGGs correlated well with their diverse N/C ratios.

Perfusion imaging of brain gliomas using arterial spin labeling: correlation with histopathological vascular density in MRI-guided biopsies.

INTRODUCTION: This study was designed to determine if cerebral blood flow (CBF) derived from arterial spin labeling (ASL) perfusion imaging could be used to quantitatively evaluate the microvascular density (MVD) of brain gliomas on a "point-to-point" basis by matching CBF areas and surgical biopsy sites as accurate as possible. METHODS: The study enrolled 47 patients with treatment-naive brain gliomas who underwent preoperative ASL, 3D T1-weighted imaging with gadolinium contrast enhancement (3D T1C+), and T2 fluid acquisition of inversion recovery (T2FLAIR) sequences before stereotactic surgery. We histologically quantified MVD from CD34-stained sections of stereotactic biopsies and co-registered biopsy locations with localized CBF measurements. The correlation between CBF and MVD was determined using Spearman's correlation coefficient. P ≤ .05 was considered statistically significant. RESULTS: Of the 47 patients enrolled in the study, 6 were excluded from the analysis because of brain shift or poor co-registration and localization of the biopsy site during surgery. Finally, 84 biopsies from 41 subjects were included in the analysis. CBF showed a statistically significant positive correlation with MVD (ρ = 0.567; P = .029). CONCLUSION: ASL can be a useful noninvasive perfusion MR method for quantitative evaluation of the MVD of brain gliomas.