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.

Robo1-specific CAR-NK Immunotherapy Enhances Efficacy of 125I Seed Brachytherapy in an Orthotopic Mouse Model of Human Pancreatic Carcinoma.

BACKGROUND/AIM: The aim of the current study was to investigate the synergistic efficacy of Robo1 bichimeric antigen receptor-natural killer cell (BiCAR-NK) immunotherapy and 125I seed brachytherapy in an orthotopic pancreatic cancer mouse model. MATERIALS AND METHODS: The orthotopic pancreatic tumor model was established with human pancreatic cancer BxPC-3 cells expressing red fluorescent protein. The mice were treated with 125I seed implantation alone or the combination of 125I seeds with Robo1-specific CAR-NK cells. To assess tumor inhibition, in vivo fluorescence imaging was conducted. 7 Tesla magnetic resonance (7T-MR) scanning was applied to measure the changes in the metabolic profiles of tumor tissues. RESULTS: Tumor size was significantly reduced in the 125I and 125I +CAR-NK treated group compared to the untreated group (p<0.05). The 125I seed +CAR-NK treated group showed significantly higher tumor reduction than 125I seed treatment alone (p<0.05). T1 diffusion weighted imaging (T1DWI) sequence showed that the tumors of the 125I +BiCAR-NK treated group had a significantly higher grey scale value than the tumors from the untreated control and the group treated with 125I seed alone (p<0.05). CONCLUSION: Robo1 specific CAR-NK immunotherapy enhances efficacy of 125I seed brachytherapy in an orthotopic pancreatic cancer mouse model.

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.

Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index.

INTRODUCTION: This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. METHODS: Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm(2)) and 22 b values (≤5000 s/mm(2)), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. RESULTS: On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (×10(-3) mm(2)/s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (×10(-3) mm(2)/s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (×10(-3) mm(2)/s) and 0.76 ± 0.04, respectively] (all P < 0.001). The parameter α showed the highest AUCs of 0.950 and 0.922 in discriminating HGG from LGG and GBM from OGG, respectively. Significant correlations with histologic grade and MI were observed for the MRI parameters. CONCLUSION: The non-Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy.

The value of Turbo inversion recovery magnitude (TIRM) magnetic resonance neurography for sacral plexus injury / 中华显微外科杂志

Objective To evaluate the capability of Turbo inversion recovery magnitude (TIRM) magnetic resonance neurography (MRN) in the diagnosie of sacral plexus injury by comparing MRN findings with surgical results.Methods Ten patients with sacral plexus injury confirmed surgically underwent conventional T1WI,T2WI,TIRM and coronal TIRM MRN before operations from June,2011 to December,2012.The MRI data and surgical data were analyzed retrospectively to observe nerve injury.Results The coronal TIRM MRN images displayed 93 trunks of sacral plexus,of which 37 were confirmed injury by operation.The MRI findings were as follows:6 trunks involved continuous nerves,but with thickening and blurred margin,as well as abnormal high signal intensity;22 trunks were continuous,but with distortion,stiffness and adhesion accompanied by heterogeneous signal intensity and structural disorder;3 trunks showed complete loss of continuity,absence of normal signal,accompanied by retraction;and 3 trunks involved formation of traumatic neurofibroma.The coincidence of injured nerve trunks diagnosed by MRN with surgical findings amounts to 81.08％ (30/37).Conclusion MR with coronal TIRM imaging is effective in the diagnosis and depiction of sacral plexus injury,therefore it can be used as conventional sequence in sacral plexus examination to detect sacral plexus avulsion.

Resting-state functional MRI on regional homogeneity changes of brain in the heavy smokers / 中华放射学杂志

Objective To explore the mechanism of self-awareness in the heavy smokers(HS)by using regional homogeneity(ReHo)combined with resting-state functional MRI(fMRI).Methods Thirty HS and 31 healthy non-smokers(NS)matched for age and sex underwent a 3.0 T resting-state fMRI.The data were post-processed by SPM 5 and then the ReHo values were calculated by REST software.The ReHo values between the two groups were compared by two-sample t-test.The brain map with significant difference of ReHo value was obtained.Results Compared with that in NS group,the regions with decreased ReHo value included the bilateral precuneus,superior frontal gyrus,medial prefrontal cortex,right angular gyrus,inferior frontal gyrus,inferior occipital gyrus,cerebellum,and left middle frontal gyrus in HS group.The regions of increased ReHo value included the bilateral insula,parahippocampal gyrus,white matter of parietal lobe,pons,left inferior parietal lobule,lingual gyrus,thalamus,inferior orbital gyrus,white matter of temporal-frontal lobe,and cerebellum.The difference was more obvious in the left hemisphere.Conclusions In HS,abnormal ReHo on a resting state which reflects network of smoking addiction.This method may be helpful in understanding the mechanism of self-awareness in HS.