Glymphatic Insights in Opioid dependent patients on Buprenorphine Treatment Using DTI-ALPS Index.
Poster No:
371
Submission Type:
Abstract Submission
Authors:
Nisha Chauhan1, Anju Dhawan2, Biswadip Chatterjee2, Siddarth Sarkar2, S Senthil Kumaran3
Institutions:
1Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences, Delhi, India, 2National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, Delhi, Delhi, 3Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences, Delhi, Delhi
First Author:
Nisha Chauhan
Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences
Delhi, India
Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences
Delhi, India
Co-Author(s):
Anju Dhawan
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences
Delhi, Delhi
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences
Delhi, Delhi
Biswadip Chatterjee
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences
Delhi, Delhi
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences
Delhi, Delhi
Siddarth Sarkar
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences
Delhi, Delhi
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences
Delhi, Delhi
S Senthil Kumaran
Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences
Delhi, Delhi
Department of Nuclear Magnetic Resonance, All India Institute of Medical Sciences
Delhi, Delhi
Introduction:
The glymphatic system plays a crucial role in clearing metabolic waste from the brain, and its dysfunction is linked to neurotoxicity and cognitive decline (Tarasoff-Conway et al., 2015). Chronic opioid dependence disrupts brain clearance pathways, leading to neuroinflammation, neural damage, and cognitive deficits (Andersen et al., 2020). While buprenorphine is an established treatment for opioid dependence (Hutchinson et al., 2017), its effects on glymphatic function remain underexplored. This study evaluates glymphatic function using the DTI-ALPS (Along-the-Perivascular Space) index in opioid-dependent (OD) patients at baseline and three months post-buprenorphine maintenance treatment (BMT), with comparisons to healthy controls.
Methods:
13 healthy controls (HC) and 13 OD patients meeting ICD-11 criteria were recruited from Community clinic of NDDTC. Patients underwent BMT and were assessed at two timepoints: baseline (within 2–5 days of treatment initiation) and follow-up (after three months). All subjects underwent clinical, cognitive assessments (MOCA and SCWT), and MR scans after informed written consent. MRI was performed on 3T MR Scanner (Ingenia, Philips) with 32 channel head coil at AIIMS hospital. A spin-echo echo-planar sequence for diffusion-tensor-imaging (DTI) was used , with TR 1000ms, TE 83ms, 64 directions, matrix size: 76x76, FOV: 224 mm, NSA:1, Slice thickness:2.3 mm with no gap, and b-value: 0, 1000 s/mm...2.
The DTI-ALPS index assesses glymphatic function by leveraging the spatial alignment of fiber tracts and perivascular spaces in the corona radiata. It calculates water diffusivity along the perivascular space relative to perpendicular diffusion. Pre-processed DTI data (motion and eddy current correction, skull stripping) were analyzed using FSL to generate FA maps. Spherical ROIs were placed on association and projection fibers at fixed MNI152 coordinates (Figure 1) (Taoka et al., 2017; Xiaodan et al., 2024). Paired t-tests compared DTI-ALPS index and cognitive scores between baseline and follow-up in patients. Independent t-tests compared HC with patients at baseline and follow-up. Spearman correlations assessed changes in DTI-ALPS index with SCWT and MOCA. Significance was set at p < 0.05 using SPSS v26.
The DTI-ALPS index assesses glymphatic function by leveraging the spatial alignment of fiber tracts and perivascular spaces in the corona radiata. It calculates water diffusivity along the perivascular space relative to perpendicular diffusion. Pre-processed DTI data (motion and eddy current correction, skull stripping) were analyzed using FSL to generate FA maps. Spherical ROIs were placed on association and projection fibers at fixed MNI152 coordinates (Figure 1) (Taoka et al., 2017; Xiaodan et al., 2024). Paired t-tests compared DTI-ALPS index and cognitive scores between baseline and follow-up in patients. Independent t-tests compared HC with patients at baseline and follow-up. Spearman correlations assessed changes in DTI-ALPS index with SCWT and MOCA. Significance was set at p < 0.05 using SPSS v26.
Results:
The DTI-ALPS index and MOCA scores were significantly lower, SCWT were higher in OD patients at baseline on comparison with healthy controls (Table 1), and improved significantly at follow-up study, almost reaching normative values after 3-months (Table 1, Figure 2). ALPS index score at the baseline-to-follow-up difference revealed significant positive correlation with SCWT scores (R2 = 0.623) and MOCA (R2 = 0.533) (Figure 2).
Conclusions:
Discussion: Lower DTI-ALPS index findings at baseline (in comparison to controls) align with existing evidence that chronic opioid exposure disrupts brain clearance pathways, contributing to neuroinflammation and neurotoxicity (Andersen et al., 2020). Following 3 months of BMT, the ALPS index showed significant improvement and reached levels comparable to healthy controls, suggesting a potential recovery of glymphatic dysfunction. This recovery supports the role of buprenorphine in mitigating opioid-induced brain clearance impairments, potentially through its known anti-inflammatory and neuroprotective effects (Tarasoff-Conway et al., 2015). Cognitive improvements observed in global cognition (MOCA) and executive function (SCWT) were consistent with glymphatic recovery. These results are in line with the hypothesis that enhanced glymphatic clearance reduces the neurotoxic burden, which may alleviate cognitive deficits (Iliff et al., 2012).
Conclusion: BMT significantly improves glymphatic function, as reflected by the DTI-ALPS index, and enhances cognitive performance in opioid-dependent patients. The recovery of glymphatic function to levels comparable to healthy controls highlights buprenorphine's potential in mitigating opioid-induced neurotoxicity.
Conclusion: BMT significantly improves glymphatic function, as reflected by the DTI-ALPS index, and enhances cognitive performance in opioid-dependent patients. The recovery of glymphatic function to levels comparable to healthy controls highlights buprenorphine's potential in mitigating opioid-induced neurotoxicity.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Keywords:
Addictions
Neurological
Psychiatric
STRUCTURAL MRI
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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2. Hutchinson, M. R., et al. (2017). Buprenorphine maintenance therapy and cognitive function. Journal of Addiction Medicine, 11(5), 381–388.
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5. Tarasoff-Conway, J. M., et al. (2015). Clearance systems in the brain—implications for Alzheimer disease. Nature Reviews Neurology, 11(9), 457–470.
6. Xiaodan, L., et al. (2024). Cross-vendor test-retest validation of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating glymphatic system function. NeuroImage, 15(4), 1885–1898.
7. Yang, Y., et al. (2020). Buprenorphine regulates neuroinflammation and improves cognitive function. Molecular Neurobiology, 57(10), 4324–4335.