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Computational Methods for Improved Interpretation of High-Density Diffuse Optical Tomography Data https://doi.org/10.17863/CAM.119267 Srinivasan, Sruthi 0000000277014879 Bale, Gemma High-density diffuse optical tomography (HD-DOT) is a promising neuroimaging technique that can be used to produce three-dimensional reconstructions of brain activity. However, analysis methods applied to this data are not yet standardised, and often do not take advantage of the higher data resolution achievable with HD-DOT. Additionally, machine learning models, which are regularly applied to other neuroimaging modalities, have only been applied to HD-DOT in very limited ways. As such, this thesis primarily describes the development and adaptation of several data analysis methods for HD-DOT, along with the application of wearable HD-DOT in large scale data collection. First, this technology is applied to study the intra- and inter-subject variability of cortical sensitivity across healthy adults and develop a processing pipeline for dimensionality reduction of HD-DOT data. Then, the collection of a large HD-DOT dataset is described, comprising 160 adult participants performing an auditory task. Employing this data, a novel method of feature extraction is explained, using inherently interpretable and physiologically relevant features to perform machine learning classification. Finally, the adaptation of a common neuroimaging analysis method, the general linear model, is described in the context of HD-DOT, using an event-related paradigm to identify how prediction confidence may modulate brain responses in the prefrontal cortex. The research described in this thesis highlights how to improve interpretation of HD-DOT data while maintaining the benefits that this imaging modality offers. The processing methods developed demonstrate the potential for more complex modelling of neural responses using HD-DOT data, and should enable access to HD-DOT computational tools that are relevant across several application areas. University of Cambridge 2024-11-24 Thesis Doctoral Doctor of Philosophy (PhD) https://www.repository.cam.ac.uk/handle/1810/385787 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/2d67f237-9c58-461d-b5f6-2a978acd7c38/download 8c3af970e16b9219ef0f39f2517444e5 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/1b0ce0cd-4c89-4c36-a86e-58f9d478907b/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by/4.0/ brain imaging neuroimaging machine learning image reconstruction functional imaging fNIRS HD-DOT