Advances in Hyperspectral and Multispectral Optical Spectroscopy and Imaging of Tissue

The purpose of this SI is to provide an overview of recent advances made in the methods used for tissue imaging and characterization, which benefit from using a large range of optical wavelengths. Guerouah et al. has contributed a profound study of the responses of the adult human brain to breath-holding challenges based on hyperspectral near-infrared spectroscopy (hNIRS). Lange et al. contributed a timely and comprehensive review of the features and biomedical and clinical applications of supercontinuum laser sources. Blaney et al. reported the development of a calibration-free hNIRS system that can measure the absolute and broadband absorption and scattering spectra of turbid media. Slooter et al. studied the utility of measuring multiple tissue parameters simultaneously using four optical techniques operating at different wavelengths of light—optical coherence tomography (1300 nm), sidestream darkfield microscopy (530 nm), laser speckle contrast imaging (785 nm), and fluorescence angiography (~800 nm)—in the gastric conduit during esophagectomy. Caredda et al. showed the feasibility of accurately quantifying the oxy- and deoxy-hemoglobin and cytochrome-c-oxidase responses to neuronal activation and obtaining spatial maps of these responses using a setup consisting of a white light source and a hyperspectral or standard RGB camera. It is interest for the developers and potential users of clinical brain and tissue optical monitors, and for researchers studying brain physiology and functional brain activity

Correlation of Acute Radiation Dermatitis to Tissue Oxygenation in Radiation Therapy treated Breast Cancer Subjects

Over 95% of radiation therapy (RT) treated breast cancer subjects undergo an adverse skin reaction known as radiation dermatitis (RD). Assessment of severity or grading of RD is clinically visual and hence subjective. Our objective is to determine sub-clinical tissue oxygenation (StO2) changes in response to RT treatment in breast cancer subjects using near-infrared spectroscopic imaging and correlate these changes to RD grading. A WIRB approved 6-8 week longitudinal pilot study was carried out on 10 RT-treated subjects at Miami Cancer Institute. Significant changes (p \u3c 0.05) in StO2 of irradiated and contralateral chest wall and axilla regions with weeks of treatment were observed. The overall drop in StO2 was higher in irradiated regions compared to its contralateral region. This drop was negatively correlated to RD scaling. Pre-RT assessment of StO2 also related to severity in RD. The long-term goal is physiological based prediction of RD severity via tissue oxygenation measurements

Design and development of optical reflectance spectroscopy and optical coherence tomography catheters for myocardial tissue characterization

Catheter ablation therapy attempts to restore sinus rhythm in arrhythmia patients by producing site-specific tissue modification along regions which cause abnormal electrical activity. This treatment, though widely used, often requires repeat procedures to observe long-term therapeutic benefits. This limitation is driven in part by challenges faced by conventional schemes in validating lesion adequacy at the time of the procedure. Optical techniques are well-suited for the interrogation and characterization of biological tissues. In particular, optical coherence tomography (OCT) relies on coherence gating of singly-scattered light to enable high-resolution structural imaging for tissue diagnostics and procedural guidance. Alternatively, optical reflectance spectroscopy (ORS) is a point measurement technique which makes use of incoherent, multiply-scattered light to probe tissue volumes and derive important data from its optical signature. ORS relies on the fact that light-tissue interactions are regulated by absorption and scattering, which directly relate to the intrinsic tissue biochemistry and cellular organization. In this thesis, we explore the integration of these modalities into ablation catheters for obtaining procedural metrics which could be utilized to guide catheter ablation therapy. We first present the development of an accelerated computational light transport model and its application for guiding ORS catheter design. A custom ORS-integrated ablation catheter is then implemented and tested within porcine specimens in vitro. A model is proposed for real-time estimation of lesion size based on changes in spectral morphology acquired during ablation. We then fabricated custom integrated OCT M-mode RF catheters and present a model for detecting contact status based on deep convolutional neural networks trained on endomyocardial images. Additionally, we demonstrate for the first time, tracking of RF-induced lesion formation employing OCT Doppler micro-velocimetry; this response is shown to be commensurate with the degree of treatment. We further demonstrate for the first time spectroscopic tracking of kinetics related to the heme oxidation cascade during thermal treatment, which are linked to tissue denaturation. The pairing of these modalities into a single RF catheter was also validated for guiding lesion delivery in vitro and within live pigs. Finally, we conclude with a proof-of-concept demonstration of ORS as a mapping tool to guide epicardial ablation in human donor hearts. These results showcase the vast potential of ORS and OCT empowered RF catheters for aiding intraprocedural guidance of catheter ablation procedures which could be utilized alongside current practices

Near-Infrared Neuroimaging with NinPy

There has been substantial recent growth in the use of non-invasive optical brain imaging in studies of human brain function in health and disease. Near-infrared neuroimaging (NIN) is one of the most promising of these techniques and, although NIN hardware continues to evolve at a rapid pace, software tools supporting optical data acquisition, image processing, statistical modeling, and visualization remain less refined. Python, a modular and computationally efficient development language, can support functional neuroimaging studies of diverse design and implementation. In particular, Python's easily readable syntax and modular architecture allow swift prototyping followed by efficient transition to stable production systems. As an introduction to our ongoing efforts to develop Python software tools for structural and functional neuroimaging, we discuss: (i) the role of non-invasive diffuse optical imaging in measuring brain function, (ii) the key computational requirements to support NIN experiments, (iii) our collection of software tools to support NIN, called NinPy, and (iv) future extensions of these tools that will allow integration of optical with other structural and functional neuroimaging data sources. Source code for the software discussed here will be made available at www.nmr.mgh.harvard.edu/Neural_SystemsGroup/software.html

Characterizing reproducibility of cerebral hemodynamic responses when applying short-channel regression in functional near-infrared spectroscopy

Significance: Functional near-infrared spectroscopy (fNIRS) enables the measurement of brain activity noninvasively. Optical neuroimaging with fNIRS has been shown to be reproducible on the group level and hence is an excellent research tool, but the reproducibility on the single-subject level is still insufficient, challenging the use for clinical applications. Aim: We investigated the effect of short-channel regression (SCR) as an approach to obtain fNIRS measurements with higher reproducibility on a single-subject level. SCR simultaneously considers contributions from long- and short-separation channels and removes confounding physiological changes through the regression of the short-separation channel information. Approach: We performed a test-retest study with a hand grasping task in 15 healthy subjects using a wearable fNIRS device, optoHIVE. Relevant brain regions were localized with transcranial magnetic stimulation to ensure correct placement of the optodes. Reproducibility was assessed by intraclass correlation, correlation analysis, mixed effects modeling, and classification accuracy of the hand grasping task. Further, we characterized the influence of SCR on reproducibility. Results: We found a high reproducibility of fNIRS measurements on a single-subject level ( and correlation ). SCR increased the reproducibility from 0.64 to 0.81 ( ) but did not affect classification (85% overall accuracy). Significant intersubject variability in the reproducibility was observed and was explained by Mayer wave oscillations and low raw signal strength. The raw signal-to-noise ratio (threshold at 40 dB) allowed for distinguishing between persons with weak and strong activations. Conclusions: We report, for the first time, that fNIRS measurements are reproducible on a single-subject level using our optoHIVE fNIRS system and that SCR improves reproducibility. In addition, we give a benchmark to easily assess the ability of a subject to elicit sufficiently strong hemodynamic responses. With these insights, we pave the way for the reliable use of fNIRS neuroimaging in single subjects for neuroscientific research and clinical applications

Characterizing reproducibility of cerebral hemodynamic responses when applying short-channel regression in functional near-infrared spectroscopy.

Significance: Functional near-infrared spectroscopy (fNIRS) enables the measurement of brain activity noninvasively. Optical neuroimaging with fNIRS has been shown to be reproducible on the group level and hence is an excellent research tool, but the reproducibility on the single-subject level is still insufficient, challenging the use for clinical applications. Aim: We investigated the effect of short-channel regression (SCR) as an approach to obtain fNIRS measurements with higher reproducibility on a single-subject level. SCR simultaneously considers contributions from long- and short-separation channels and removes confounding physiological changes through the regression of the short-separation channel information. Approach: We performed a test-retest study with a hand grasping task in 15 healthy subjects using a wearable fNIRS device, optoHIVE. Relevant brain regions were localized with transcranial magnetic stimulation to ensure correct placement of the optodes. Reproducibility was assessed by intraclass correlation, correlation analysis, mixed effects modeling, and classification accuracy of the hand grasping task. Further, we characterized the influence of SCR on reproducibility. Results: We found a high reproducibility of fNIRS measurements on a single-subject level ( and correlation ). SCR increased the reproducibility from 0.64 to 0.81 ( ) but did not affect classification (85% overall accuracy). Significant intersubject variability in the reproducibility was observed and was explained by Mayer wave oscillations and low raw signal strength. The raw signal-to-noise ratio (threshold at 40 dB) allowed for distinguishing between persons with weak and strong activations. Conclusions: We report, for the first time, that fNIRS measurements are reproducible on a single-subject level using our optoHIVE fNIRS system and that SCR improves reproducibility. In addition, we give a benchmark to easily assess the ability of a subject to elicit sufficiently strong hemodynamic responses. With these insights, we pave the way for the reliable use of fNIRS neuroimaging in single subjects for neuroscientific research and clinical applications

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest

The NIRS Analysis Package: Noise Reduction and Statistical Inference

Near infrared spectroscopy (NIRS) is a non-invasive optical imaging technique that can be used to measure cortical hemodynamic responses to specific stimuli or tasks. While analyses of NIRS data are normally adapted from established fMRI techniques, there are nevertheless substantial differences between the two modalities. Here, we investigate the impact of NIRS-specific noise; e.g., systemic (physiological), motion-related artifacts, and serial autocorrelations, upon the validity of statistical inference within the framework of the general linear model. We present a comprehensive framework for noise reduction and statistical inference, which is custom-tailored to the noise characteristics of NIRS. These methods have been implemented in a public domain Matlab toolbox, the NIRS Analysis Package (NAP). Finally, we validate NAP using both simulated and actual data, showing marked improvement in the detection power and reliability of NIRS

Improving the analysis of near-infrared spectroscopy data with multivariate classification of hemodynamic patterns: a theoretical formulation and validation

Objective. The statistical analysis of functional near infrared spectroscopy (fNIRS) data based on the general linear model (GLM) is often made difficult by serial correlations, high inter-subject variability of the hemodynamic response, and the presence of motion artifacts. In this work we propose to extract information on the pattern of hemodynamic activations without using any a priori model for the data, by classifying the channels as 'active' or 'not active' with a multivariate classifier based on linear discriminant analysis (LDA). Approach. This work is developed in two steps. First we compared the performance of the two analyses, using a synthetic approach in which simulated hemodynamic activations were combined with either simulated or real resting-state fNIRS data. This procedure allowed for exact quantification of the classification accuracies of GLM and LDA. In the case of real resting-state data, the correlations between classification accuracy and demographic characteristics were investigated by means of a Linear Mixed Model. In the second step, to further characterize the reliability of the newly proposed analysis method, we conducted an experiment in which participants had to perform a simple motor task and data were analyzed with the LDA-based classifier as well as with the standard GLM analysis. Main results. The results of the simulation study show that the LDA-based method achieves higher classification accuracies than the GLM analysis, and that the LDA results are more uniform across different subjects and, in contrast to the accuracies achieved by the GLM analysis, have no significant correlations with any of the demographic characteristics. Findings from the real-data experiment are consistent with the results of the real-plus-simulation study, in that the GLM-analysis results show greater inter-subject variability than do the corresponding LDA results. Significance. The results obtained suggest that the outcome of GLM analysis is highly vulnerable to violations of theoretical assumptions, and that therefore a data-driven approach such as that provided by the proposed LDA-based method is to be favored.EC/H2020/641858/EU/Understanding and predicting developmental language abilities and disorders in multilingual Europe/PREDICTABL