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However, the local effect of TMS propagates via the white\u2010matter network to different areas of the brain, and currently there is no commercial or research neuronavigation system that can highlight in real time the brain's structural connections during TMS. This lack of real\u2010time visualization may overlook critical inter\u2010individual differences in brain connectivity and does not provide the opportunity to target brain networks. In contrast, real\u2010time tractography enables on\u2010the\u2010fly parameter tuning and detailed exploration of connections, which is computationally inefficient and limited with offline methods. To target structural brain connections, particularly in network\u2010based treatments like major depressive disorder, a real\u2010time tractography\u2010based neuronavigation solution is needed to account for each individual's unique brain connectivity. The objective of this work is to develop a real\u2010time tractography\u2010assisted TMS neuronavigation system and investigate its feasibility. We propose a modular framework that seamlessly integrates offline (preparatory) analysis of diffusion MRI data with online (real\u2010time) probabilistic tractography using the parallel transport approach. For tractography and neuronavigation, we combine our open source software Trekker and InVesalius, respectively. We evaluate our system using synthetic data and MRI scans of four healthy volunteers obtained using a multi\u2010shell high\u2010angular resolution diffusion imaging protocol. The feasibility of our online approach is assessed by studying four major TMS targets via comparing streamline count and overlap against offline tractography results based on filtering of one hundred million streamlines. Our development of a real\u2010time tractography\u2010assisted TMS neuronavigation system showcases advanced tractography techniques, with interactive parameter tuning and real\u2010time visualization of thousands of streamlines via an innovative uncertainty visualization method. Our analysis reveals considerable variability among subjects and TMS targets in the streamline count, for example, while 15,000 streamlines were observed for the TMS target on the visual cortex (V1) of subject #4, in the case of subject #3's V1, no streamlines were obtained. Overlap analysis against offline tractograms demonstrated that real\u2010time tractography can quickly cover a substantial part of the target areas' connectivity, often surpassing the coverage of offline approaches within seconds. For instance, significant portions of Broca's area and the primary motor cortex were effectively visualized after generating tens of thousands of streamlines, highlighting the system's efficiency and feasibility in capturing brain connectivity in real\u2010time. Overall, our work shows that real\u2010time tractography\u2010assisted TMS neuronavigation is feasible. With our system, it is possible to target specific brain regions based on their structural connectivity, and to aim for the fiber tracts that make up the brain's networks. Real\u2010time tractography provides new opportunities for TMS targeting through novel visualization techniques without compromising structural connectivity estimates when compared to the offline approach.<\/jats:p>","DOI":"10.1002\/hbm.70122","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T02:08:36Z","timestamp":1735610916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Real\u2010Time Tractography\u2010Assisted Neuronavigation for Transcranial Magnetic Stimulation"],"prefix":"10.1002","volume":"46","author":[{"given":"Dogu Baran","family":"Aydogan","sequence":"first","affiliation":[{"name":"A.I. Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"},{"name":"Department of Neuroscience and Biomedical Engineering, School of Science Aalto University  Espoo Finland"},{"name":"Aalto NeuroImaging, School of Science Aalto University  Espoo Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0254-4322","authenticated-orcid":false,"given":"Victor H.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Biomedical Engineering, School of Science Aalto University  Espoo Finland"},{"name":"Aalto NeuroImaging, School of Science Aalto University  Espoo Finland"},{"name":"Graduate Program in Rehabilitation Sciences and Functional Physical Performance, School of Physiotherapy Federal University of Juiz de Fora  Juiz de Fora Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan H.","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Biomedical Engineering, School of Science Aalto University  Espoo Finland"},{"name":"Department of Physics, School of Philosophy, Science and Letters at Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelis","family":"Lioumis","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Biomedical Engineering, School of Science Aalto University  Espoo Finland"},{"name":"Aalto NeuroImaging, School of Science Aalto University  Espoo Finland"},{"name":"BioMag Laboratory, HUS Medical Imaging Center University of Helsinki, Helsinki University Hospital and Aalto University  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risto J.","family":"Ilmoniemi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Biomedical Engineering, School of Science Aalto University  Espoo Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2019.10.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-012-3117-5"},{"key":"e_1_2_11_5_1","first-page":"1","article-title":"Advanced Normalization Tools (ANTS)","volume":"2","author":"Avants B. 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