A Diffusion Tensor Imaging Study For Whiter Matter Microstructure In Heroin Dependent And Methadone Maintenance Treatment Patients

ObjectiveDrug dependence has been associated with the impaired neuronal functional connectivity and cognitive deficits, additionally it may result in whiter matter deficits. Abnormalities of whiter matter connectivity is likely to be the potential pathological basis of alterations in function and ethology. Many studies indicate that heroin dependent and methadone maintenance treatment patients shown deficits in functional connectivity and congnition, however, it remains unclear whether it do harm to brain whiter matter microstructure. Here, we investigated whiter matter integrality in heroin dependent patients and whom they undergoing methadone maintenance treatment using diffusion tensor imaging(DTI) and the correlation between DTI measurements and clinical medical consumption has been determined. The results may reveal the potential alteration of whiter matter in heroin dependence, and may contribute to the clinical therapeutic strategy making. Methods1. 17 chronic heroin dependent subjects and 15 matched healthy controls participated in this study. DTI was used to identify white matter integrity, Voxel-based analysis was performed with DTIstudio and SPM8 software. Fractional anisotropy (FA) and eigenvalues (λ⊥andλ∥) were measured, and the statistical difference was defined when P<0.001 and the cluster size >20 voxels. DTI measurements in identified regions were correlated with heroin exposure features.2. Compared the whiter matter integrity in the bilateral frontal lobe, temporal lobe, splenium and genu of corpus callosum between methadone maintenance treatment (MMT) patients(n=13), former heroin dependence (n=11) in prolonged abstinence (PA), and healthy control subjects (n=15) using DTI. FA, apparent diffusion coefficient (ADC) and eigenvalues (λ⊥andλ∥) were measured. The correlation between DTI measurements and accumulated former heroin dose, total methadone consumption, and PA duration were determined by partial correlation analysis. Statistical difference was defined when P<0.05.Results1. Several white matter regions with significantly FA reductions in heroin dependent subjects when compared with healthy controls, including bilateral frontal regions, cingulate gyrus, left temporal lobe and extra-nuclear. There was no region in which the heroin dependent subjects had higher FA values. Compared with controls,λ⊥increased in the bilateral frontal lobe sub-gyrus, the cingulate gyrus and the extra-nuclear in heroin dependent subjects. There were no regions showed reducedλ⊥and there were no difference inλ∥between groups. Correlated analysis showed no significant correlations between the duration or dosage of heroin use and FA values orλ⊥in any clusters.2. Compared with the controls, the MMT subjects showed a decreased FA in the left genu of corpus callosum, as well as the increased ADC in the left splenium of corpus callosum andλ⊥in the left genu of corpus callosum. There are no statistical difference between PA group and controls. Compared with the PA, the MMT subjects had a significant increased ADC value in the bilateral splenium of corpus callosum. The partial correlation analysis revealed that the accumulated dosage of methadone had a negative correlation with the FA in the left splenium of corpus callosum and in the right frontal lobe in the MMT subjects. In the PA subjects, the accumulated heroin consumption was positive correlated with the ADC andλ⊥in the bilateral splenium of corpus callosum, and negative correlated with the FA in the left splenium of corpus callosum and the left frontal lobe. Moreover, the whiter matter integrity in the ROI was not associated with the PA duration.Conclusion1. Chronic heroin dependent patients showed impaired whiter matter integrity in the frontal lobe, the cingulate, the left temporal lobe and the extra-nuclear, myelin pathology is the primary alteration, and there are tendency of axonal injury in long-term and high-dosage users. The findings point to a widespread disruption of white matter integrity in heroin dependent subjects and it may be important to understand cognitive and functional imaging abnormalities. 2. This study found that the whiter matter would be impaired in long-term methadone use in MMT subjects, and associate with methadone consumption. The white matter integrity could be partially recovered after a period of protracted abstinence. These results might contribute to the clinical therapeutic strategy making, especially in managing methadone doses and length of treatment.