High-Density Diffuse Optical Tomography During Passive Movie Viewing: A Platform for Naturalistic Functional Brain Mapping

Human neuroimaging techniques enable researchers and clinicians to non-invasively study brain function across the lifespan in both healthy and clinical populations. However, functional brain imaging methods such as functional magnetic resonance imaging (fMRI) are expensive, resource-intensive, and require dedicated facilities, making these powerful imaging tools generally unavailable for assessing brain function in settings demanding open, unconstrained, and portable neuroimaging assessments. Tools such as functional near-infrared spectroscopy (fNIRS) afford greater portability and wearability, but at the expense of cortical field-of-view and spatial resolution. High-Density Diffuse Optical Tomography (HD-DOT) is an optical neuroimaging modality directly addresses the image quality limitations associated with traditional fNIRS techniques through densely overlapping optical measurements. This thesis aims to establish the feasibility of using HD-DOT in a novel application demanding exceptional portability and flexibility: mapping disrupted cortical activity in chronically malnourished children. I first motivate the need for dense optical measurements of brain tissue to achieve fMRI-comparable localization of brain function (Chapter 2). Then, I present imaging work completed in Cali, Colombia, where a cohort of chronically malnourished children were imaged using a custom HD-DOT instrument to establish feasibility of performing field-based neuroimaging in this population (Chapter 3). Finally, in order to meet the need for age appropriate imaging paradigms in this population, I develop passive movie viewing paradigms for use in optical neuroimaging, a flexible and rich stimulation paradigm that is suitable for both adults and children (Chapter 4)

Mapping cortical activations underlying covert and overt language production using high-density diffuse optical tomography

Gold standard neuroimaging modalities such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and more recently electrocorticography (ECoG) have provided profound insights regarding the neural mechanisms underlying the processing of language, but they are limited in applications involving naturalistic language production especially in developing brains, during face-to-face dialogues, or as a brain-computer interface. High-density diffuse optical tomography (HD-DOT) provides high-fidelity mapping of human brain function with comparable spatial resolution to that of fMRI but in a silent and open scanning environment similar to real-life social scenarios. Therefore, HD-DOT has potential to be used in naturalistic settings where other neuroimaging modalities are limited. While HD-DOT has been previously validated against fMRI for mapping the neural correlates underlying language comprehension and covert (i.e., silent ) language production, HD-DOT has not yet been established for mapping the cortical responses to overt (i.e., out loud ) language production. In this study, we assessed the brain regions supporting a simple hierarchy of language tasks: silent reading of single words, covert production of verbs, and overt production of verbs in normal hearing right-handed native English speakers (n = 33). First, we found that HD-DOT brain mapping is resilient to movement associated with overt speaking. Second, we observed that HD-DOT is sensitive to key activations and deactivations in brain function underlying the perception and naturalistic production of language. Specifically, statistically significant results were observed that show recruitment of regions in occipital, temporal, motor, and prefrontal cortices across all three tasks after performing stringent cluster-extent based thresholding. Our findings lay the foundation for future HD-DOT studies of imaging naturalistic language comprehension and production during real-life social interactions and for broader applications such as presurgical language assessment and brain-machine interfaces

Diffuse optical tomography to investigate the newborn brain

Over the past 15 years, functional near-infrared spectroscopy (fNIRS) has emerged as a powerful technology for studying the developing brain. Diffuse optical tomography (DOT) is an extension of fNIRS that combines hemodynamic information from dense optical sensor arrays over a wide field of view. Using image reconstruction techniques, DOT can provide images of the hemodynamic correlates to neural function that are comparable to those produced by functional magnetic resonance imaging. This review article explains the principles of DOT, and highlights the growing literature on the use of DOT in the study of healthy development of the infant brain, and the study of novel pathophysiology in infants with brain injury. Current challenges, particularly around instrumentation and image reconstruction, will be discussed, as will the future of this growing field, with particular focus on whole-brain, time-resolved DOT

Wearable, high-density fNIRS and diffuse optical tomography technologies: a perspective

Recent progress in optoelectronics has made wearable and high-density functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT) technologies possible for the first time. These technologies have the potential to open new fields of real-world neuroscience by enabling functional neuroimaging of the human cortex at a resolution comparable to fMRI in almost any environment and population. In this perspective article, we provide a brief overview of the history and the current status of wearable high-density fNIRS and DOT approaches, discuss the greatest ongoing challenges, and provide our thoughts on the future of this remarkable technology

High-Density Diffuse Optical Tomography During Passive Movie Viewing: A Platform for Naturalistic Functional Brain Mapping

Human neuroimaging techniques enable researchers and clinicians to non-invasively study brain function across the lifespan in both healthy and clinical populations. However, functional brain imaging methods such as functional magnetic resonance imaging (fMRI) are expensive, resource-intensive, and require dedicated facilities, making these powerful imaging tools generally unavailable for assessing brain function in settings demanding open, unconstrained, and portable neuroimaging assessments. Tools such as functional near-infrared spectroscopy (fNIRS) afford greater portability and wearability, but at the expense of cortical field-of-view and spatial resolution. High-Density Diffuse Optical Tomography (HD-DOT) is an optical neuroimaging modality directly addresses the image quality limitations associated with traditional fNIRS techniques through densely overlapping optical measurements. This thesis aims to establish the feasibility of using HD-DOT in a novel application demanding exceptional portability and flexibility: mapping disrupted cortical activity in chronically malnourished children. I first motivate the need for dense optical measurements of brain tissue to achieve fMRI-comparable localization of brain function (Chapter 2). Then, I present imaging work completed in Cali, Colombia, where a cohort of chronically malnourished children were imaged using a custom HD-DOT instrument to establish feasibility of performing field-based neuroimaging in this population (Chapter 3). Finally, in order to meet the need for age appropriate imaging paradigms in this population, I develop passive movie viewing paradigms for use in optical neuroimaging, a flexible and rich stimulation paradigm that is suitable for both adults and children (Chapter 4)

Functional imaging of the developing brain with wearable high-density diffuse optical tomography: a new benchmark for infant neuroimaging outside the scanner environment

Studies of cortical function in the awake infant are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become increasingly common in developmental neuroscience, but has significant limitations including resolution, spatial specificity and ergonomics. In adults, high-density arrays of near-infrared sources and detectors have recently been shown to yield dramatic improvements in spatial resolution and specificity when compared to typical fNIRS approaches. However, most existing fNIRS devices only permit the acquisition of ∼20-100 sparsely distributed fNIRS channels, and increasing the number of optodes presents significant mechanical challenges, particularly for infant applications. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first study of the infant brain using wearable HD-DOT. Using a well-established social stimulus paradigm, and combining this new imaging technology with advances in cap design and spatial registration, we show that it is now possible to obtain high-quality, functional images of the infant brain with minimal constraints on either the environment or on the infant participants. Our results are consistent with prior low-density fNIRS measures based on similar paradigms, but demonstrate superior spatial localization, improved depth specificity, higher SNR and a dramatic improvement in the consistency of the responses across participants. Our data retention rates also demonstrate that this new generation of wearable technology is well tolerated by the infant population