Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

Differential and correlational tractography as tract-based biomarkers in mild traumatic brain injury: A longitudinal MRI study.

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.

Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease: In Vivo Neuroimaging Study of 11C-DTBZ PET Combined with Correlational Tractography.

Previous histopathologic and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. 11C-dihydrotetrabenazine (11C-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion MRI can incorporate ligand-specific information provided by 11C-DTBZ PET into the fiber-tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on 11C-DTBZ PET. Methods: The study involved 30 subjects with mild to moderate PD (23 men and 7 women; mean age, 66 ± 6.2 y; disease duration, 6.4 ± 4.0 y; Hoehn and Yahr stage, 2.1 ± 0.6; Movement Disorder Society [MDS]-revised Unified Parkinson Disease Rating Scale [UPDRS] [I-III] total score, 43.4 ± 17.8) and 30 control subjects (18 men and 12 women; mean age, 62 ± 10.3 y). 11C-DTBZ PET was performed using standard synthesis and acquisition protocols. Correlational tractography was performed to assess quantitative anisotropy (QA; a measure of tract integrity) of white matter fibers correlating with information derived from striatal 11C-DTBZ data using the DSI Studio toolbox. Scans were realigned according to least and most clinically affected cerebral hemispheres. Results: Nigrostriatal tracts were identified in both hemispheres of PD patients. Higher mean QA values along the identified tracts were significantly associated with higher striatal 11C-DTBZ distribution volume ratios (least affected: r = 0.57, P = 0.001; most affected: r = 0.44, P = 0.02). Lower mean QA values of the identified tract in the LA hemisphere associated with increased severity of bradykinesia sub-score derived from MDS-UPDRS part III (r = -0.42; P = 0.02). Cross-validation revealed the generalizability of these results. Conclusion: These findings suggest that impaired integrity of dopaminergic nigrostriatal nerve terminals is associated with nigrostriatal axonal dysfunction in mild to moderate PD. Assessment of nigrostriatal tract integrity may be suitable as a biomarker of early- or even prodromal-stage PD.