Abstract
Background At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in PD. Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function. However, precise tractography modelling is required to identify the optimal target for neurosurgical planning. Individualized tractography approaches have been shown to be highly effective for accurately identifying DBS targets but have yet to be developed for the NBM.
Methods Using structural and diffusion weighted imaging, we developed a tractography pipeline for precise individualized identification of the lateral NBM target tract. Using dice similarity coefficients, the reliability of the tractography outputs was assessed across three cohorts to investigate: 1) whether this manual pipeline is more reliable than an existing automated pipeline currently used in the literature; 2) the inter- and intra-rater reliability of our pipeline in research scans of patients with PD; and 3) the reliability and practicality of this pipeline in clinical scans of DBS patients.
Results The individualized manual pipeline was found to be significantly more reliable than the existing automated pipeline for both the segmentation of the NBM region itself (p<0.001) and the reconstruction of the target lateral tract (p=0.002). There was also no significant difference between the reliability of two different raters in the PD cohort (p=0.25), which showed high inter- (mean Dice coefficient >0.6) and intra-rater (mean Dice coefficient >0.7) reliability across runs. Finally, the pipeline was shown to be highly reliable within the clinical scans (mean Dice coefficient = 0.77). However, accurate reconstruction was only evident in 7/10 tracts.
Conclusion We have developed a reliable tractography pipeline for the identification and analysis of the NBM lateral tract in research and clinical grade imaging of healthy young adult and PD patient scans.
Competing Interest Statement
JMH is a consultant for Neuralink, serves on the Medical Advisory Board of Enspire DBS, and is a shareholder in Maplight Therapeutics.
Funding Statement
Data were provided in part by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. PPMI - a public-private partnership - is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including, Abbvie, AcureX, Allergan, Amathus, Therapeutics, Asap, Avid, Biogen, Bial Biotech, Biolegend, BlueRock Therapeutics, Bristol-Myers, Calico, Celgene, Cerevel, Coave Therapeutics, Dacapo BrainScience, Jenali Therapeutics, 4D Pharma plc, GE Healthcare, Edmond J. Safra Philanthropic Foundation, Genentech, GlaxoSmithKline, Golub Capital, Gain Therapeutics, Handl Therapeutics, Insitro, Janssen Neuroscience, Lilly, Lundbeck, Merch, MSD Veso Scale Discovery, Neuroscine Biosciences, Pfizer, Piramal Healthcare, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, and Yumanity Therapeutics. This work was also supported in part by Michael J Fox Foundation (9605) and NIH: National Institute of Neurological Disorders and Stroke (NINDS) grants (R21 NS096398) to HBS. The authors are funded by two NIH: NINDS research grants (RAC, KBW, JMH, and HMBS: UG3NS128150; HMBS: UH3NS107709).
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Data used in the preparation of this article were obtained from the Human Connectome Project (https://www.humanconnectome.org/study/hcp-young-adult/data-releases) and Parkinson's Progression Markers Initiative (PPMI) database (www.ppmi-info.org/access-data-specimens/download-data). For up-to-date information on the study, visit www.ppmi-info.org. For the cohort 3 clinical data referenced in this project, the IRB of Stanford University gave ethical approval for this work.
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Data Availability
Data from the Human Connectome Project can be requested from: www.humanconnectome.org/study/hcp-young-adult/data-releases Data from the Parkinson's Progression Marker's Initiative can be requested from: www.ppmi-info.org/access-data-specimens/download-data
https://www.humanconnectome.org/study/hcp-young-adult/data-releases
https://www.ppmi-info.org/access-data-specimens/download-data