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Background: Diffuse optical tomography (DOT) provides three-dimensional image reconstruction of chromophore perturbations within a turbid volume. Two leading strategies to optimize DOT image quality include, (i) arrays of regular, interlacing, high-density (HD) grids of sources and detectors with closest spacing less than 15 mm, or (ii) source modulated light of order ∼100 MHz., Purpose: However, the general principles for how these crucial design parameters of array density and modulation frequency may interact to provide an optimal system design have yet to be elucidated., Methods: Herein, we systematically evaluated how these design parameters effect image quality via multiple key metrics. Specifically, we simulated 32 system designs with realistic measurement noise and quantified localization error, spatial resolution, signal-to-noise, and localization depth of field for each of ∼85 000 point spread functions in each model., Results: We found that array density had a far stronger effect on image quality metrics than modulation frequency. Additionally, model fits for image quality metrics revealed that potential improvements diminish with regular arrays denser than 9 mm closest spacing. Further, for a given array density, 300 MHz source modulation provided the deepest reliable imaging compared to other frequencies., Conclusions: Our results indicate that both array density and modulation frequency affect the spatial sampling of tissue, which asymptotically saturates due to photon diffusivity within a turbid volume. In summary, our results provide comprehensive perspectives for optimizing future DOT system designs in applications from wearable functional brain imaging to breast tumor detection., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Significance: Optical mammography as a promising tool for cancer diagnosis has largely fallen behind expectations. Modern machine learning (ML) methods offer ways to improve cancer detection in diffuse optical transmission data., Aim: We aim to quantitatively evaluate the classification of cancer-positive versus cancer-negative patients using ML methods on raw transmission time series data from bilateral breast scans during subjects' rest., Approach: We use a support vector machine (SVM) with hyperparameter optimization and cross-validation to systematically explore a range of data preprocessing and feature-generation strategies. We also apply an automated ML (AutoML) framework to validate our findings. We use receiver operating characteristics and the corresponding area under the curve (AUC) to quantify classification performance., Results: For the sample group available ( N = 63 , 18 cancer patients), we demonstrate an AUC score of up to 93.3% for SVM classification and up to 95.0% for the AutoML classifier., Conclusions: ML offers a viable strategy for clinically relevant breast cancer diagnosis using diffuse-optical transmission measurements. The diagnostic performance of ML on raw data can outperform traditional statistical biomarkers derived from reconstructed image time series. To achieve clinically relevant performance, our ML approach requires simultaneous bilateral scanning of the breasts with spatially dense channel coverage., (© 2024 The Authors.)

Rationale and Objectives: Shear Wave Elastography (SWE) and Ultrasound-guided Diffuse Optical Tomography (US-guided DOT) demonstrate promise in distinguishing between benign and malignant breast lesions. This study aims to assess the feasibility and correlation of SWE and US-guided DOT in evaluating the biological characteristics of breast cancer., Materials and Methods: A cohort of 235 breast cancer patients with 238 lesions, scheduled for surgery within one to three days, underwent B-mode ultrasound (US), US-guided DOT, and SWE. Parameters such as Total Hemoglobin Concentration (THC), Maximal Elasticity (E max ), Mean Elasticity (E mean ), Standard Deviation of Elasticity (E sd ), and Area Ratio were measured. Correlation with post-surgical pathology reports was examined to explore associations between THC, SWE Parameters, and pathology characteristics., Results: Lesions in patient groups with ER-, PR-, HER2 + , high Ki67, LVI+ , and ALN+ exhibited higher THC, E max , and E sd compared to groups with ER+ , PR+ , HER2-, low Ki67, LVI-, and ALN-. The increase was seen in all grades of IDC-I to -III. THC significantly correlated with S max (r = 0.340, P < 0.001), E max (r = 0.339, P < 0.001), E mean (r = 0.201, P = 0.003), and E sd (r = 0.313, P < 0.001)., Conclusion: US-guided DOT and SWE prove valuable for the quantitative assessment of breast cancer's biological characteristics, with THC positively correlated with E max , E mean , and E sd ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Significance: Traditional diffuse optical tomography (DOT) reconstructions are hampered by image artifacts arising from factors such as DOT sources being closer to shallow lesions, poor optode-tissue coupling, tissue heterogeneity, and large high-contrast lesions lacking information in deeper regions (known as shadowing effect). Addressing these challenges is crucial for improving the quality of DOT images and obtaining robust lesion diagnosis., Aim: We address the limitations of current DOT imaging reconstruction by introducing an attention-based U-Net (APU-Net) model to enhance the image quality of DOT reconstruction, ultimately improving lesion diagnostic accuracy., Approach: We designed an APU-Net model incorporating a contextual transformer attention module to enhance DOT reconstruction. The model was trained on simulation and phantom data, focusing on challenges such as artifact-induced distortions and lesion-shadowing effects. The model was then evaluated by the clinical data., Results: Transitioning from simulation and phantom data to clinical patients' data, our APU-Net model effectively reduced artifacts with an average artifact contrast decrease of 26.83% and improved image quality. In addition, statistical analyses revealed significant contrast improvements in depth profile with an average contrast increase of 20.28% and 45.31% for the second and third target layers, respectively. These results highlighted the efficacy of our approach in breast cancer diagnosis., Conclusions: The APU-Net model improves the image quality of DOT reconstruction by reducing DOT image artifacts and improving the target depth profile., (© 2024 The Authors.)

Novel portable diffuse optical tomography (DOT) devices for breast cancer lesions hold great promise for non-invasive, non-ionizing breast cancer screening. Critical to this capability is not just the identification of lesions but rather the complex problem of discriminating between malignant and benign lesions. To accurately reconstruct the highly heterogeneous tissue of a cancer lesion in healthy breast tissue using DOT, multiple wavelengths can be leveraged to maximize signal penetration while minimizing sensitivity to noise. However, these wavelength responses can overlap, capture common information, and correlate, potentially confounding reconstruction and downstream end tasks. We show that an orthogonal fusion loss regularizes multi-wavelength DOT leading to improved reconstruction and accuracy of end-to-end discrimination of malignant versus benign lesions. We further show that our raw-to-task model significantly reduces computational complexity without sacrificing accuracy, making it ideal for real-time throughput, desired in medical settings where handheld devices have severely restricted power budgets. Furthermore, our results indicate that image reconstruction is not necessary for unbiased classification of lesions with a balanced accuracy of 77% and 66% on the synthetic dataset and clinical dataset, respectively, using the raw-to-task model. Code is available at https://github.com/sfu-mial/FuseNet., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanene Ben Yedder reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Touch is an essential form of mother-child interaction, instigating better social bonding and emotional stability., Methods: We used diffuse optical tomography to explore the relationship between total haemoglobin (HbT) responses to affective touch in the child's brain at two years of age and maternal self-reported prenatal depressive symptoms (EPDS). Affective touch was implemented via slow brushing of the child's right forearm at 3 cm/s and non-affective touch via fast brushing at 30 cm/s and HbT responses were recorded on the left hemisphere., Results: We discovered a cluster in the postcentral gyrus exhibiting a negative correlation (Pearson's r = -0.84, p = 0.015 corrected for multiple comparisons) between child HbT response to affective touch and EPDS at gestational week 34. Based on region of interest (ROI) analysis, we found negative correlations between child responses to affective touch and maternal prenatal EPDS at gestational week 14 in the precentral gyrus, Rolandic operculum and secondary somatosensory cortex. The responses to non-affective touch did not correlate with EPDS in these regions., Limitations: The number of mother-child dyads was 16. However, by utilising high-density optode arrangements, individualised anatomical models, and video and accelerometry to monitor movement, we were able to minimize methodological sources of variability in the data., Conclusions: The results show that maternal depressive symptoms during pregnancy may be associated with reduced child responses to affective touch in the temporoparietal cortex. Responses to affective touch may be considered as potential biomarkers for psychosocial development in children. Early identification of and intervention in maternal depression may be important already during early pregnancy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Significance: We evaluate the efficiency of integrating ultrasound (US) and diffuse optical tomography (DOT) images for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. The ultrasound-diffuse optical tomography (USDOT)-Transformer model represents a significant step toward accurate prediction of pCR, which is critical for personalized treatment planning., Aim: We aim to develop and assess the performance of the USDOT-Transformer model, which combines US and DOT images with tumor receptor biomarkers to predict the pCR of breast cancer patients under NAC., Approach: We developed the USDOT-Transformer model using a dual-input transformer to process co-registered US and DOT images along with tumor receptor biomarkers. Our dataset comprised imaging data from 60 patients at multiple time points during their chemotherapy treatment. We used fivefold cross-validation to assess the model's performance, comparing its results against a single modality of US or DOT., Results: The USDOT-Transformer model demonstrated excellent predictive performance, with a mean area under the receiving characteristic curve of 0.96 (95%CI: 0.93 to 0.99) across the fivefold cross-validation. The integration of US and DOT images significantly enhanced the model's ability to predict pCR, outperforming models that relied on a single imaging modality (0.87 for US and 0.82 for DOT). This performance indicates the potential of advanced deep learning techniques and multimodal imaging data for improving the accuracy (ACC) of pCR prediction., Conclusion: The USDOT-Transformer model offers a promising non-invasive approach for predicting pCR to NAC in breast cancer patients. By leveraging the structural and functional information from US and DOT images, the model offers a faster and more reliable tool for personalized treatment planning. Future work will focus on expanding the dataset and refining the model to further improve its accuracy and generalizability., (© 2024 The Authors.)

Significance: Frequency-domain diffuse optical tomography (FD-DOT) could enhance clinical breast tumor characterization. However, conventional diffuse optical tomography (DOT) image reconstruction algorithms require case-by-case expert tuning and are too computationally intensive to provide feedback during a scan. Deep learning (DL) algorithms front-load computational and tuning costs, enabling high-speed, high-fidelity FD-DOT., Aim: We aim to demonstrate a simultaneous reconstruction of three-dimensional absorption and reduced scattering coefficients using DL-FD-DOT, with a view toward real-time imaging with a handheld probe., Approach: A DL model was trained to solve the DOT inverse problem using a realistically simulated FD-DOT dataset emulating a handheld probe for human breast imaging and tested using both synthetic and experimental data., Results: Over a test set of 300 simulated tissue phantoms for absorption and scattering reconstructions, the DL-DOT model reduced the root mean square error by 12 % ± 40 % and 23 % ± 40 % , increased the spatial similarity by 17 % ± 17 % and 9 % ± 15 % , increased the anomaly contrast accuracy by 9 % ± 9 % ( μ a ), and reduced the crosstalk by 5 % ± 18 % and 7 % ± 11 % , respectively, compared with model-based tomography. The average reconstruction time was reduced from 3.8 min to 0.02 s for a single reconstruction. The model was successfully verified using two tumor-emulating optical phantoms., Conclusions: There is clinical potential for real-time functional imaging of human breast tissue using DL and FD-DOT., (© 2024 The Authors.)

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes., Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT., Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers., Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles ( p = 0.042 ). In addition, the change in normalized tumor StO 2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle ( p = 0.038 ). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI., Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens., (© 2024 The Authors.)

Introduction: Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three-dimensional capabilities., Methods: Twenty-five delirious and matched non-delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium., Results: Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post-resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls., Discussion: These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias., Highlights: We developed a portable diffuse optical tomography (DOT) system for bedside three-dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task-focused seed-based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Ultrasound (US)-guided diffuse optical tomography (DOT) has demonstrated potential for breast cancer diagnosis, in which real-time or near real-time diagnosis with high accuracy is desired. However, DOT's relatively slow data processing and image reconstruction speeds have hindered real-time diagnosis. Here, we propose a real-time classification scheme that combines US breast imaging reporting and data system (BI-RADS) readings and DOT frequency domain measurements. A convolutional neural network is trained to generate malignancy probability scores from DOT measurements. Subsequently, these scores are integrated with BI-RADS assessments using a support vector machine classifier, which then provides the final diagnostic output. An area under the receiver operating characteristic curve of 0.978 is achieved in distinguishing between benign and malignant breast lesions in patient data without image reconstruction., (© 2024 Wiley‐VCH GmbH.)

Significance: Accurate spatial registration of probes (e.g., optodes and electrodes) for measurement of brain activity is a crucial aspect in many neuroimaging modalities. It may increase measurement precision and enable the transition from channel-based calculations to volumetric representations., Aim: This technical note evaluates the efficacy of a commercially available infrared three-dimensional (3D) scanner under actual experimental (or clinical) conditions and provides guidelines for its use., Method: We registered probe positions using an infrared 3D scanner and validated them against magnetic resonance imaging (MRI) scans on five volunteer participants., Results: Our analysis showed that with standard cap fixation, the average Euclidean distance of probe position among subjects could reach up to 43 mm, with an average distance of 15.25 mm [standard deviation (SD) = 8.0]. By contrast, the average distance between the infrared 3D scanner and the MRI-acquired positions was 5.69 mm (SD = 1.73), while the average difference between consecutive infrared 3D scans was 3.43 mm (SD = 1.62). The inter-optode distance, which was fixed at 30 mm, was measured as 29.28 mm (SD = 1.12) on the MRI and 29.43 mm (SD = 1.96) on infrared 3D scans. Our results demonstrate the high accuracy and reproducibility of the proposed spatial registration method, making it suitable for both functional near-infrared spectroscopy and electroencephalogram studies., Conclusions: The 3D infrared scanning technique for spatial registration of probes provides economic efficiency, simplicity, practicality, repeatability, and high accuracy, with potential benefits for a range of neuroimaging applications. We provide practical guidance on anonymization, labeling, and post-processing of acquired scans., (© 2024 The Authors.)

Functional near-infrared spectroscopy (fNIRS) is a widely used imaging method for mapping brain activation based on cerebral hemodynamics. The accurate quantification of cortical activation using fNIRS data is highly dependent on the ability to correctly localize the positions of light sources and photodetectors on the scalp surface. Variations in head size and shape across participants greatly impact the precise locations of these optodes and consequently, the regions of the cortical surface being reached. Such variations can therefore influence the conclusions drawn in NIRS studies that attempt to explore specific cortical regions. In order to preserve the spatial identity of each NIRS channel, subject-specific differences in NIRS array registration must be considered. Using high-density diffuse optical tomography (HD-DOT), we have demonstrated the inter-subject variability of the same HD-DOT array applied to ten participants recorded in the resting state. We have also compared three-dimensional image reconstruction results obtained using subject-specific positioning information to those obtained using generic optode locations. To mitigate the error introduced by using generic information for all participants, photogrammetry was used to identify specific optode locations per-participant. The present work demonstrates the large variation between subjects in terms of which cortical parcels are sampled by equivalent channels in the HD-DOT array. In particular, motor cortex recordings suffered from the largest optode localization errors, with a median localization error of 27.4 mm between generic and subject-specific optodes, leading to large differences in parcel sensitivity. These results illustrate the importance of collecting subject-specific optode locations for all wearable NIRS experiments, in order to perform accurate group-level analysis using cortical parcellation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Srinivasan, Acharya, Butters, Collins-Jones, Mancini and Bale.)

Background and Aim: The occurrence of brain lesions in preterm infants is common and can result in lasting disabilities. To prevent these and to safeguard the brain through therapeutic measures or neuroprotective treatments, it is important to identify cerebral ischaemia/hypoxia and haemorrhage at an early stage. For this purpose, we have successfully developed a cutting-edge time-domain near-infrared optical tomography (TD-NIROT) system, which offers diagnostic imaging for neonatal brain oxygenation. Our objective is to validate the effectiveness of the TD-NIROT in detecting deep ischaemia/hypoxia and haemorrhages through phantom experiments., Methods: Spherical silicone phantoms were fabricated to replicate the head of preterm infant. To simulate the lesions, we made two head phantoms and embedded small inclusions mimicking ischaemia and haemorrhage at the depth of 30 mm. Additionally, a spherical interface was constructed to connect the spherical phantom to the imaging system, allowing us to collect time-domain data. Following the data acquisition, we proceeded with image reconstruction. Dice similarity was used as an indicator of the accuracy and similarity between the reconstructed images and the ground truth., Results and Discussion: The resulting images exhibited an accurate location of haemorrhage and detected the ischaemia with a slightly shifted position with Dice similarity of 0.47 and 0.27., Conclusion: Our experiment validates the capability of our TD-NIROT system in successfully detecting deep haemorrhages and ischaemia within the phantom model. The achieved results suggest a promising level of accuracy in the imaging process. These findings are encouraging to continue this work to ultimately achieve clinical application of the TD-NIROT system in diagnosing and monitoring neonatal brain injuries., (© 2024. Oxygen Transport to Tissue International.)

Significance: To effectively apply functional near-infrared spectroscopy (fNIRS)/diffuse optical tomography (DOT) devices, a three-dimensional (3D) model of the position of each optode on a subject's scalp and the positions of that subject's cranial landmarks are critical. Obtaining this information accurately in infants, who rarely stop moving, is an ongoing challenge., Aim: We propose a smartphone-based registration system that can potentially achieve a full-head 3D scan of a 6-month-old infant instantly., Approach: The proposed system is remotely controlled by a custom-designed Bluetooth controller. The scanned images can either be manually or automatically aligned to generate a 3D head surface model., Results: A full-head 3D scan of a 6-month-old infant can be achieved within 2 s via this system. In testing on a realistic but static infant head model, the average Euclidean error of optode position using this device was 1.8 mm., Conclusions: This low-cost 3D registration system therefore has the potential to permit accurate and near-instant fNIRS/DOT spatial registration., (© 2023 The Authors.)

Optical imaging involves the propagation of light through tissue. Current optical breast imaging technologies, including diffuse optical spectroscopy, diffuse optical tomography, and photoacoustic imaging, capitalize on the selective absorption of light in the near-infrared spectrum by deoxygenated and oxygenated hemoglobin. They provide information on the morphological and functional characteristics of different tissues based on their varied interactions with light, including physiologic information on lesion vascular content and anatomic information on tissue vascularity. Fluorescent contrast agents, such as indocyanine green, are used to visualize specific tissues, molecules, or proteins depending on how and where the agent accumulates. In this review, we describe the physical principles, spectrum of technologies, and clinical applications of the most common optical systems currently being used or developed for breast imaging. Most notably, US co-registered photoacoustic imaging and US-guided diffuse optical tomography have demonstrated efficacy in differentiating benign from malignant breast masses, thereby improving the specificity of diagnostic imaging. Diffuse optical tomography and diffuse optical spectroscopy have shown promise in assessing treatment response to preoperative systemic therapy, and photoacoustic imaging and diffuse optical tomography may help predict tumor phenotype. Lastly, fluorescent imaging using indocyanine green dye performs comparably to radioisotope mapping of sentinel lymph nodes and appears to improve the outcomes of autologous tissue flap breast reconstruction.

Electroencephalography (EEG) and diffuse optical tomography (DOT) are imaging methods which are widely used for neuroimaging. While the temporal resolution of EEG is high, the spatial resolution is typically limited. DOT, on the other hand, has high spatial resolution, but the temporal resolution is inherently limited by the slow hemodynamics it measures. In our previous work, we showed using computer simulations that when using the results of DOT reconstruction as the spatial prior for EEG source reconstruction, high spatio-temporal resolution could be achieved. In this work, we experimentally validate the algorithm by alternatingly flashing two visual stimuli at a speed that is faster than the temporal resolution of DOT. We show that the joint reconstruction using both EEG and DOT clearly resolves the two stimuli temporally, and the spatial confinement is drastically improved in comparison to reconstruction using EEG alone., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Significance: Ultrasound (US)-guided diffuse optical tomography (DOT) has demonstrated great potential for breast cancer diagnosis in which real-time or near real-time diagnosis with high accuracy is desired., Aim: We aim to use US-guided DOT to achieve an automated, fast, and accurate classification of breast lesions., Approach: We propose a two-stage classification strategy with deep learning. In the first stage, US images and histograms created from DOT perturbation measurements are combined to predict benign lesions. Then the non-benign suspicious lesions are passed through to the second stage, which combine US image features, DOT histogram features, and 3D DOT reconstructed images for final diagnosis., Results: The first stage alone identified 73.0% of benign cases without image reconstruction. In distinguishing between benign and malignant breast lesions in patient data, the two-stage classification approach achieved an area under the receiver operating characteristic curve of 0.946, outperforming the diagnoses of all single-modality models and of a single-stage classification model that combines all US images, DOT histogram, and imaging features., Conclusions: The proposed two-stage classification strategy achieves better classification accuracy than single-modality-only models and a single-stage classification model that combines all features. It can potentially distinguish breast cancers from benign lesions in near real-time., (© 2023 The Authors.)

Significance: We present a fiberless, portable, and modular continuous wave-functional near-infrared spectroscopy system, Spotlight, consisting of multiple palm-sized modules-each containing high-density light-emitting diode and silicon photomultiplier detector arrays embedded in a flexible membrane that facilitates optode coupling to scalp curvature., Aim: Spotlight's goal is to be a more portable, accessible, and powerful functional near-infrared spectroscopy (fNIRS) device for neuroscience and brain-computer interface (BCI) applications. We hope that the Spotlight designs we share here can spur more advances in fNIRS technology and better enable future non-invasive neuroscience and BCI research., Approach: We report sensor characteristics in system validation on phantoms and motor cortical hemodynamic responses in a human finger-tapping experiment, where subjects wore custom 3D-printed caps with two sensor modules., Results: The task conditions can be decoded offline with a median accuracy of 69.6%, reaching 94.7% for the best subject, and at a comparable accuracy in real time for a subset of subjects. We quantified how well the custom caps fitted to each subject and observed that better fit leads to more observed task-dependent hemodynamic response and better decoding accuracy., Conclusions: The advances presented here should serve to make fNIRS more accessible for BCI applications., (© 2023 The Authors.)

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., (© 2023 The Authors.)

Significance: Short-separation (SS) regression and diffuse optical tomography (DOT) image reconstruction, two widely adopted methods in functional near-infrared spectroscopy (fNIRS), were demonstrated to individually facilitate the separation of brain activation and physiological signals, with further improvement using both sequentially. We hypothesized that doing both simultaneously would further improve the performance., Aim: Motivated by the success of these two approaches, we propose a method, SS-DOT, which applies SS and DOT simultaneously., Approach: The method, which employs spatial and temporal basis functions to represent the hemoglobin concentration changes, enables us to incorporate SS regressors into the time series DOT model. To benchmark the performance of the SS-DOT model against conventional sequential models, we use fNIRS resting state data augmented with synthetic brain response as well as data acquired during a ball squeezing task. The conventional sequential models comprise performing SS regression and DOT., Results: The results show that the SS-DOT model improves the image quality by increasing the contrast-to-background ratio by a threefold improvement. The benefits are marginal at small brain activation., Conclusions: The SS-DOT model improves the fNIRS image reconstruction quality., (© 2023 The Authors.)

Diffuse optical tomography (DOT) is a non-invasive method for detecting breast cancer; however, it struggles to produce high-quality images due to the complexity of scattered light and the limitations of traditional image reconstruction algorithms. These algorithms can be affected by boundary conditions and have a low imaging accuracy, a shallow imaging depth, a long computation time, and a high signal-to-noise ratio. However, machine learning can potentially improve the performance of DOT by being better equipped to solve inverse problems, perform regression, classify medical images, and reconstruct biomedical images. In this study, we utilized a machine learning model called "XGBoost" to detect tumors in inhomogeneous breasts and applied a post-processing technique based on genetic programming to improve accuracy. The proposed algorithm was tested using simulated DOT measurements from complex inhomogeneous breasts and evaluated using the cosine similarity metrics and root mean square error loss. The results showed that the use of XGBoost and genetic programming in DOT could lead to more accurate and non-invasive detection of tumors in inhomogeneous breasts compared to traditional methods, with the reconstructed breasts having an average cosine similarity of more than 0.97 ± 0.07 and average root mean square error of around 0.1270 ± 0.0031 compared to the ground truth.

Significance: The machine learning (ML) approach plays a critical role in assessing biomedical imaging processes especially optical imaging (OI) including segmentation, classification, and reconstruction, intending to achieve higher accuracy efficiently., Aim: This research aims to develop an end-to-end deep learning framework for diffuse optical imaging (DOI) with multiple datasets to detect breast cancer and reconstruct its optical properties in the early stages., Approach: The proposed Periodic-net is a nondestructive deep learning (DL) algorithm for the reconstruction and evaluation of inhomogeneities in an inverse model with high accuracy, while boundary measurements are calculated by solving a forward problem with sources/detectors arranged uniformly around a circular domain in various combinations, including 16 × 15 , 20 × 19 , and 36 × 35 boundary measurement setups., Results: The results of image reconstruction on numerical and phantom datasets demonstrate that the proposed network provides higher-quality images with a greater amount of small details, superior immunity to noise, and sharper edges with a reduction in image artifacts than other state-of-the-art competitors., Conclusions: The network is highly effective at the simultaneous reconstruction of optical properties, i.e., absorption and reduced scattering coefficients, by optimizing the imaging time without degrading inclusions localization and image quality., (© 2023 The Authors.)

Objective . Spontaneous fluctuations of cerebral hemodynamics measured by functional magnetic resonance imaging (fMRI) are widely used to study the network organization of the brain. The temporal correlations among the ultra-slow, <0.1 Hz fluctuations across the brain regions are interpreted as functional connectivity maps and used for diagnostics of neurological disorders. However, despite the interest narrowed in the ultra-slow fluctuations, hemodynamic activity that exists beyond the ultra-slow frequency range could contribute to the functional connectivity, which remains unclear. Approach . In the present study, we have measured the brain-wide hemodynamics in the human participants with functional near-infrared spectroscopy (fNIRS) in a whole-head, cap-based and high-density montage at a sampling rate of 6.25 Hz. In addition, we have acquired resting state fMRI scans in the same group of participants for cross-modal evaluation of the connectivity maps. Then fNIRS data were deliberately down-sampled to a typical fMRI sampling rate of ∼0.5 Hz and the resulted differential connectivity maps were subject to a k-means clustering. Main results . Our diffuse optical topographical analysis of fNIRS data have revealed a default mode network (DMN) in the spontaneous deoxygenated and oxygenated hemoglobin changes, which remarkably resemble the same fMRI network derived from participants. Moreover, we have shown that the aliased activities in the down-sampled optical signals have altered the connectivity patterns, resulting in a network organization of aliased functional connectivity in the cerebral hemodynamics. Significance. The results have for the first time demonstrated that fNIRS as a broadly accessible modality can image the resting-state functional connectivity in the posterior midline, prefrontal and parietal structures of the DMN in the human brain, in a consistent pattern with fMRI. Further empowered by the fast sampling rate of fNIRS, our findings suggest the presence of aliased connectivity in the current understanding of the human brain organization., (Creative Commons Attribution license.)

Significance: Rapid estimation of the depth and margins of fluorescence targets buried below the tissue surface could improve upon current image-guided surgery techniques for tumor resection., Aim: We describe algorithms and instrumentation that permit rapid estimation of the depth and transverse margins of fluorescence target(s) in turbid media; the work aims to introduce, experimentally demonstrate, and characterize the methodology., Approach: Spatial frequency domain fluorescence diffuse optical tomography (SFD-FDOT) technique is adapted for rapid and computationally inexpensive estimation of fluorophore target depth and lateral margins. The algorithm utilizes the variation of diffuse fluorescence intensity with respect to spatial-modulation-frequency to compute target depth. The lateral margins are determined via analytical inversion of the data using depth information obtained from the first step. We characterize method performance using fluorescent contrast targets embedded in tissue-simulating phantoms., Results: Single and multiple targets with significant lateral size were imaged at varying depths as deep as 1 cm. Phantom data analysis showed good depth-sensitivity, and the reconstructed transverse margins were mostly within ∼30 % error from true margins., Conclusions: The study suggests that the rapid SFD-FDOT approach could be useful in resection surgery and, more broadly, as a first step in more rigorous SFD-FDOT reconstructions. The experiments permit evaluation of current limitations.

Brain-wide patterns in resting human brains, as either structured functional connectivity (FC) or recurring brain states, have been widely studied in the neuroimaging literature. In particular, resting-state FCs estimated over windowed timeframe neuroimaging data from sub-minutes to minutes using correlation or blind source separation techniques have reported many brain-wide patterns of significant behavioral and disease correlates. The present pilot study utilized a novel whole-head cap-based high-density diffuse optical tomography (DOT) technology, together with data-driven analysis methods, to investigate recurring transient brain-wide patterns in spontaneous fluctuations of hemodynamic signals at the resolution of single timeframes from thirteen healthy adults in resting conditions. Our results report that a small number, i.e., six, of brain-wide coactivation patterns (CAPs) describe major spatiotemporal dynamics of spontaneous hemodynamic signals recorded by DOT. These CAPs represent recurring brain states, showing spatial topographies of hemispheric symmetry, and exhibit highly anticorrelated pairs. Moreover, a structured transition pattern among the six brain states is identified, where two CAPs with anterior-posterior spatial patterns are significantly involved in transitions among all brain states. Our results further elucidate two brain states of global positive and negative patterns, indicating transient neuronal coactivations and co-deactivations, respectively, over the entire cortex. We demonstrate that these two brain states are responsible for the generation of a subset of peaks and troughs in global signals (GS), supporting the recent reports on neuronal relevance of hemodynamic GS. Collectively, our results suggest that transient neuronal events (i.e., CAPs), global brain activity, and brain-wide structured transitions co-exist in humans and these phenomena are closely related, which extend the observations of similar neuronal events recently reported in animal hemodynamic data. Future studies on the quantitative relationship among these transient events and their relationships to windowed FCs along with larger sample size are needed to understand their changes with behaviors and diseased conditions., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Transcranial magnetic stimulation (TMS) has been established as an important and effective treatment for various psychiatric disorders. However, its effectiveness has likely been limited due to the dearth of neuronavigational tools for targeting purposes, unclear ideal stimulation parameters, and a lack of knowledge regarding the physiological response of the brain to TMS in each psychiatric condition. Modern optical imaging modalities, such as functional near-infrared spectroscopy and diffuse optical tomography, are promising tools for the study of TMS optimization and functional targeting in psychiatric disorders. They possess a unique combination of high spatial and temporal resolutions, portability, real-time capability, and relatively low costs. In this mini-review, we discuss the advent of optical imaging techniques and their innovative use in several psychiatric conditions including depression, panic disorder, phobias, and eating disorders. With further investment and research in the development of these optical imaging approaches, their potential will be paramount for the advancement of TMS treatment protocols in psychiatry., (© 2022. The Author(s).)

Significance: "Difference imaging," which reconstructs target optical properties using measurements with and without target information, is often used in diffuse optical tomography (DOT) in vivo imaging. However, taking additional reference measurements is time consuming, and mismatches between the target medium and the reference medium can cause inaccurate reconstruction., Aim: We aim to streamline the data acquisition and mitigate the mismatch problems in DOT difference imaging using a deep learning-based approach to generate data from target measurements only., Approach: We train an artificial neural network to output data for difference imaging from target measurements only. The model is trained and validated on simulation data and tested with simulations, phantom experiments, and clinical data from 56 patients with breast lesions., Results: The proposed method has comparable performance to the traditional approach using measurements without mismatch between the target side and the reference side, and it outperforms the traditional approach using measurements when there is a mismatch. It also improves the target-to-artifact ratio and lesion localization in patient data., Conclusions: The proposed method can simplify the data acquisition procedure, mitigate mismatch problems, and improve reconstructed image quality in DOT difference imaging.

Cochlear implants are neuroprosthetic devices that can restore hearing in people with severe to profound hearing loss by electrically stimulating the auditory nerve. Because of physical limitations on the precision of this stimulation, the acoustic information delivered by a cochlear implant does not convey the same level of acoustic detail as that conveyed by normal hearing. As a result, speech understanding in listeners with cochlear implants is typically poorer and more effortful than in listeners with normal hearing. The brain networks supporting speech understanding in listeners with cochlear implants are not well understood, partly due to difficulties obtaining functional neuroimaging data in this population. In the current study, we assessed the brain regions supporting spoken word understanding in adult listeners with right unilateral cochlear implants (n=20) and matched controls (n=18) using high-density diffuse optical tomography (HD-DOT), a quiet and non-invasive imaging modality with spatial resolution comparable to that of functional MRI. We found that while listening to spoken words in quiet, listeners with cochlear implants showed greater activity in the left prefrontal cortex than listeners with normal hearing, specifically in a region engaged in a separate spatial working memory task. These results suggest that listeners with cochlear implants require greater cognitive processing during speech understanding than listeners with normal hearing, supported by compensatory recruitment of the left prefrontal cortex., Competing Interests: AS, ND, AB, MH, AE, JF, JC No competing interests declared, JP Reviewing editor, eLife, (© 2022, Sherafati et al.)

A computationally simpler algorithm to reconstruct the optical property distribution of turbid media using diffuse optical tomographic principles is presented. The proposed algorithm eliminates the requirement of large Jacobian matrix inversion which otherwise is essential for tomographic imaging. The most significant Jacobians are identified based on proper thresholding of the measurement and the intersection of these Jacobians gives the approximate spatial location of the inhomogeneity. The algorithm is tested and optimized using simulations and further validated using tissue-mimicking phantom-based experiments and in-vivo small-animal experiments., (© 2022 IOP Publishing Ltd.)

Touch is an important component of early parent-child interaction and plays a critical role in the socio-emotional development of children. However, there are limited studies on touch processing amongst children in the age range from one to three years. The present study used frequency-domain diffuse optical tomography (DOT) to investigate the processing of affective and non-affective touch over left frontotemporal brain areas contralateral to the stimulated forearm in two-year-old children. Affective touch was administered by a single stroke with a soft brush over the child's right dorsal forearm at 3 cm/s, while non-affective touch was provided by multiple brush strokes at 30 cm/s. We found that in the insula, the total haemoglobin (HbT) response to slow brushing was significantly greater than the response to fast brushing (slow > fast). Additionally, a region in the postcentral gyrus, Rolandic operculum and superior temporal gyrus exhibited greater response to fast brushing than slow brushing (fast > slow). These findings confirm that an adult-like pattern of haemodynamic responses to affective and non-affective touch can be recorded in two-year-old subjects using DOT. To improve the accuracy of modelling light transport in the two-year-old subjects, we used a published age-appropriate atlas and deformed it to match the exterior shape of each subject's head. We estimated the combined scalp and skull, and grey matter (GM) optical properties by fitting simulated data to calibrated and coupling error corrected phase and amplitude measurements. By utilizing a two-compartment cerebrospinal fluid (CSF) model, the accuracy of estimation of GM optical properties and the localization of activation in the insula was improved. The techniques presented in this paper can be used to study neural development of children at different ages and illustrate that the technology is well-tolerated by most two-year-old children and not excessively sensitive to subject movement. The study points the way towards exciting possibilities in functional imaging of deeper functional areas near sulci in small children., Competing Interests: Declaration of Competing Interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Significance: Deep learning (DL) models are being increasingly developed to map sensor data to the image domain directly. However, DL methodologies are data-driven and require large and diverse data sets to provide robust and accurate image formation performances. For research modalities such as 2D/3D diffuse optical imaging, the lack of large publicly available data sets and the wide variety of instrumentation designs, data types, and applications leads to unique challenges in obtaining well-controlled data sets for training and validation. Meanwhile, great efforts over the last four decades have focused on developing accurate and computationally efficient light propagation models that are flexible enough to simulate a wide variety of experimental conditions., Aim: Recent developments in Monte Carlo (MC)-based modeling offer the unique advantage of simulating accurately light propagation spatially, temporally, and over an extensive range of optical parameters, including minimally to highly scattering tissue within a computationally efficient platform. Herein, we demonstrate how such MC platforms, namely "Monte Carlo eXtreme" and "Mesh-based Monte Carlo," can be leveraged to generate large and representative data sets for training the DL model efficiently., Approach: We propose data generator pipeline strategies using these platforms and demonstrate their potential in fluorescence optical topography, fluorescence optical tomography, and single-pixel diffuse optical tomography. These applications represent a large variety in instrumentation design, sample properties, and contrast function., Results: DL models trained using the MC-based in silico datasets, validated further with experimental data not used during training, show accurate and promising results., Conclusion: Overall, these MC-based data generation pipelines are expected to support the development of DL models for rapid, robust, and user-friendly image formation in a wide variety of applications.

Significance: Diffuse optical tomography is an ill-posed problem. Combination with ultrasound can improve the results of diffuse optical tomography applied to the diagnosis of breast cancer and allow for classification of lesions., Aim: To provide a simulation pipeline for the assessment of reconstruction and classification methods for diffuse optical tomography with concurrent ultrasound information., Approach: A set of breast digital phantoms with benign and malignant lesions was simulated building on the software VICTRE. Acoustic and optical properties were assigned to the phantoms for the generation of B-mode images and optical data. A reconstruction algorithm based on a two-region nonlinear fitting and incorporating the ultrasound information was tested. Machine learning classification methods were applied to the reconstructed values to discriminate lesions into benign and malignant after reconstruction., Results: The approach allowed us to generate realistic US and optical data and to test a two-region reconstruction method for a large number of realistic simulations. When information is extracted from ultrasound images, at least 75% of lesions are correctly classified. With ideal two-region separation, the accuracy is higher than 80%., Conclusions: A pipeline for the generation of realistic ultrasound and diffuse optics data was implemented. Machine learning methods applied to a optical reconstruction with a nonlinear optical model and morphological information permit to discriminate malignant lesions from benign ones.

Significance: Biomedical optics system design, image formation, and image analysis have primarily been guided by classical physical modeling and signal processing methodologies. Recently, however, deep learning (DL) has become a major paradigm in computational modeling and has demonstrated utility in numerous scientific domains and various forms of data analysis., Aim: We aim to comprehensively review the use of DL applied to macroscopic diffuse optical imaging (DOI)., Approach: First, we provide a layman introduction to DL. Then, the review summarizes current DL work in some of the most active areas of this field, including optical properties retrieval, fluorescence lifetime imaging, and diffuse optical tomography., Results: The advantages of using DL for DOI versus conventional inverse solvers cited in the literature reviewed herein are numerous. These include, among others, a decrease in analysis time (often by many orders of magnitude), increased quantitative reconstruction quality, robustness to noise, and the unique capability to learn complex end-to-end relationships., Conclusions: The heavily validated capability of DL's use across a wide range of complex inverse solving methodologies has enormous potential to bring novel DOI modalities, otherwise deemed impractical for clinical translation, to the patient's bedside.

Diffuse optical tomography is a non-invasive and non-irradiating medical imaging technique that is particularly suitable for cerebral monitoring of newborns since it can be used at the bedside of the patient. Here, a new model for optical tomography in the neonatal brain is presented that takes into account the presence of arachnoid trabeculae in the cerebrospinal fluid (CSF). It is known that the classical diffusion approximation (DA) for light propagation is at the limit of validity in the CSF layer due to the low values of the absorption and scattering coefficients. The new model is obtained by the DA of the homogenized radiative transfer equation and is rigorously justified. Numerical results in two and three dimensions attest for the improved sensitivity of the new model to the presence of perturbations in the brain layer., (© 2021 John Wiley & Sons Ltd.)

Diffuse optical tomography is emerging as a non-invasive optical modality used to evaluate tissue information by obtaining the optical properties' distribution. Two procedures are performed to produce reconstructed absorption and reduced scattering images, which provide structural information that can be used to locate inclusions within tissues with the assistance of a known light intensity around the boundary. These methods are referred to as a forward problem and an inverse solution. Once the reconstructed image is obtained, a subjective measurement is used as the conventional way to assess the image. Hence, in this study, we developed an algorithm designed to numerically assess reconstructed images to identify inclusions using the structural similarity (SSIM) index. We compared four SSIM algorithms with 168 simulated reconstructed images involving the same inclusion position with different contrast ratios and inclusion sizes. A multiscale, improved SSIM containing a sharpness parameter (MS-ISSIM-S) was proposed to represent the potential evaluation compared with the human visible perception. The results indicated that the proposed MS-ISSIM-S is suitable for human visual perception by demonstrating a reduction of similarity score related to various contrasts with a similar size of inclusion; thus, this metric is promising for the objective numerical assessment of diffuse, optically reconstructed images.

We introduce a novel image reconstruction method for time-resolved diffuse optical tomography (DOT) that yields submillimeter resolution in less than a second. This opens the door to high-resolution real-time DOT in imaging of the brain activity. We call this approach the sensitivity equation based noniterative sparse optical reconstruction (SENSOR) method. The high spatial resolution is achieved by implementing an asymptotic l 0 -norm operator that guarantees to obtain sparsest representation of reconstructed targets. The high computational speed is achieved by employing the nontruncated sensitivity equation based noniterative inverse formulation combined with reduced sensing matrix and parallel computing. We tested the new method with numerical and experimental data. The results demonstrate that the SENSOR algorithm can achieve 1 mm 3 spatial-resolution optical tomographic imaging at depth of ∼60 mean free paths (MFPs) in 20∼30 milliseconds on an Intel Core i9 processor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: To assess the impact of adjunctive ultrasound guided diffuse optical tomography (US-guided DOT) on BI-RADS assessment in women undergoing US-guided breast biopsy., Method: This prospective study enrolled women referred for US-guided breast biopsy between 3/5/2019 and 3/19/2020. Participants underwent US-guided DOT immediately before biopsy. The US-guided DOT acquisition generated average maximum total hemoglobin (HbT) spatial maps and quantitative HbT values. Four radiologists blinded to histopathology assessed conventional imaging (CI) to assign a CI BI-RADS assessment and then integrated DOT information in assigning a CI&DOT BI-RADS assessment. HbT was compared between benign and malignant lesions using an ANOVA test and Tukey's test. Benign biopsies were tabulated, deeming BI-RADS ≥ 4A as positive. Reader agreement was assessed., Results: Among 61 included women (mean age 48 years), biopsy demonstrated 15 (24.6%) malignant and 46 (75.4%) benign lesions. Mean HbT was 55.3 ± 22.6 µM in benign lesions versus 85.4 ± 15.6 µM in cancers (p < .001). HbT threshold of 78.5 µM achieved sensitivity 80% (12/15) and specificity 89% (41/46) for malignancy. Across readers and patients, 197 pairs of CI BI-RADS and CI&DOT BI-RADS assessments were assigned. Adjunctive US-guided DOT achieved a net decrease in 23.5% (31/132) of suspicious (CI BI-RADS ≥ 4A) assessments of benign lesions (34 correct downgrades and 3 incorrect upgrades). 38.3% (31/81) of 4A assessments were appropriately downgraded. No cancer was downgraded to a non-actionable assessment. Interreader agreement analysis demonstrated kappa = 0.48-0.53 for CI BI-RADS and kappa = 0.28-0.44 for CI&DOT BI-RADS., Conclusions: Integration of US-guided DOT information achieved a 23.5% reduction in suspicious BI-RADS assessments for benign lesions. Larger studies are warranted, with attention to improved reader agreement., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diffuse optical tomography (DOT), as a functional near-infrared spectroscopy (fNIRS) technique, can estimate three-dimensional (3D) images of the functional hemodynamic response in brain volume from measured optical signals. In this study, we applied DOT algorithms to the fNIRS data recorded from the surface of macaque monkeys' skulls when the animals performed food retrieval tasks using either the left- or right-hand under head-free conditions. The hemodynamic response images, reconstructed by DOT with a high sampling rate and fine voxel size, demonstrated significant activations at the upper limb regions of the primary motor area in the central sulcus and premotor, and parietal areas contralateral to the hands used in the tasks. The results were also reliable in terms of consistency across different recording dates. Time-series analyses of each brain area revealed preceding activity of premotor area to primary motor area consistent with previous physiological studies. Therefore, the fNIRS-DOT protocol demonstrated in this study provides reliable 3D functional brain images over a period of days under head-free conditions for region-of-interest-based time-series analysis., (© The Author(s) 2021. Published by Oxford University Press.)

Significance: In general, image reconstruction methods used in diffuse optical tomography (DOT) are based on diffusion approximation, and they consider the breast tissue as a homogenous, semi-infinite medium. However, the semi-infinite medium assumption used in DOT reconstruction is not valid when the chest wall is underneath the breast tissue., Aim: We aim to reduce the chest wall's effect on the estimated average optical properties of breast tissue and obtain accurate forward model for DOT reconstruction., Approach: We propose a deep learning-based neural network approach where a convolution neural network (CNN) is trained to simultaneously obtain accurate optical property values for both the breast tissue and the chest wall., Results: The CNN model shows great promise in reducing errors in estimating the optical properties of the breast tissue in the presence of a shallow chest wall. For patient data, the CNN model predicted the breast tissue optical absorption coefficient, which was independent of chest wall depth., Conclusions: Our proposed method can be readily used in DOT and diffuse spectroscopy measurements to improve the accuracy of estimated tissue optical properties.

There has been considerable interest in applying electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) simultaneously for multimodal assessment of brain function. EEG-fNIRS can provide a comprehensive picture of brain electrical and hemodynamic function and has been applied across various fields of brain science. The development of wearable, mechanically and electrically integrated EEG-fNIRS technology is a critical next step in the evolution of this field. A suitable system design could significantly increase the data/image quality, the wearability, patient/subject comfort, and capability for long-term monitoring. Here, we present a concise, yet comprehensive, review of the progress that has been made toward achieving a wearable, integrated EEG-fNIRS system. Significant marks of progress include the development of both discrete component-based and microchip-based EEG-fNIRS technologies; modular systems; miniaturized, lightweight form factors; wireless capabilities; and shared analogue-to-digital converter (ADC) architecture between fNIRS and EEG data acquisitions. In describing the attributes, advantages, and disadvantages of current technologies, this review aims to provide a roadmap toward the next generation of wearable, integrated EEG-fNIRS systems.

The inverse problem of diffuse optical tomography (DOT) is ill-posed. Traditional method cannot achieve high imaging accuracy and the calculation process is time-consuming, which restricts the clinical application of DOT. Therefore, a method based on stacked auto-encoder (SAE) was proposed and used for the DOT inverse problem. Firstly, a traditional SAE method is used to solved the inverse problem. Then, the output structure of SAE neural network is improved to a single output SAE, which reduce the burden on the neural network. Finally, the improved SAE method is used to compare with traditional SAE method and traditional levenberg-marquardt (LM) iterative method. The result shows that the average time to solve the inverse problem of the method proposed in this paper is only 1.67% of the LM method. The mean square error (MSE) value is 46.21% lower than the traditional iterative method, 61.53% lower than the traditional SAE method, and the image correlation coefficient(ICC) value is 4.03% higher than the traditional iterative method, 18.7% higher than the traditional SAE method and has good noise immunity under 3% noise conditions. The research results in this article prove that the improved SAE method has higher image quality and noise resistance than the traditional SAE method, and at the same time has a faster calculation speed than the traditional iterative method, which is conducive to the application of neural networks in DOT inverse problem calculation.

This special issue is the second part of a themed issue that focuses on synergistic tomographic image reconstruction and includes a range of contributions in multiple disciplines and application areas. The primary subject of study lies within inverse problems which are tackled with various methods including statistical and computational approaches. This volume covers algorithms and methods for a wide range of imaging techniques such as spectral X-ray computed tomography (CT), positron emission tomography combined with CT or magnetic resonance imaging, bioluminescence imaging and fluorescence-mediated imaging as well as diffuse optical tomography combined with ultrasound. Some of the articles demonstrate their utility on real-world challenges, either medical applications (e.g. motion compensation for imaging patients) or applications in material sciences (e.g. material decomposition and characterization). One of the desired outcomes of the special issues is to bring together different scientific communities which do not usually interact as they do not share the same platforms such as journals and conferences. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Purpose: Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy., Methods: We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1). We performed DOTBIS at baseline (before initiation of therapy) and post-therapy in the affected breast (tumor volume) and contralateral, unaffected breast, and measured tissue concentrations (in μM) of total hemoglobin (ctTHb), oxyhemoglobin (ctO 2 Hb), and deoxyhemoglobin (ctHHb), as well as water fraction (%)., Results: We found consistent decreases in DOTBIS-measured hemoglobin concentrations in tumor volume, with median percent changes for ctTHb, ctHHb, ctO 2 Hb, and water fraction for the entire cohort of - 27.1% (interquartile range [IQR] 37.5%), - 49.8% (IQR 29.3%), - 33.5% (IQR 47.4%), and - 3.6% (IQR 10.6%), respectively. In the contralateral breast, median percent changes for ctTHb, ctHHb, ctO 2 Hb, and water fraction were + 1.8% (IQR 26.7%), - 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively., Conclusion: We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Significance: Diffuse optical tomography (DOT) uses near-infrared light spectroscopy (NIRS) to measure changes in cerebral hemoglobin concentration. Anatomical interpretations of NIRS data require accurate descriptions of the cranio-cerebral relations and DOT sensitivity to the underlying cortical structures. Such information is limited for pediatric populations because they undergo rapid head and brain development. Aim: We aim to investigate age-related differences in scalp-to-cortex distance and mapping between scalp locations and cortical regions of interest (ROIs) among infants (2 weeks to 24 months with narrow age bins), children (4 and 12 years), and adults (20 to 24 years). Approach: We used spatial scalp projection and photon propagation simulation methods with age-matched realistic head models based on MRIs. Results: There were age-group differences in the scalp-to-cortex distances in infancy. The developmental increase was magnified in children and adults. There were systematic age-related differences in the probabilistic mappings between scalp locations and cortical ROIs. Conclusions: Our findings have important implications in the design of sensor placement and making anatomical interpretations in NIRS and fNIRS research. Age-appropriate, realistic head models should be used to provide anatomical guidance for standalone DOT data in infants., (© 2021 The Authors.)

Objective. Diffuse optical tomography (DOT) has the potential in reconstructing resting state networks (RSNs) in human brains with high spatio-temporal resolutions and multiple contrasts. While several RSNs have been reported and successfully reconstructed using DOT, its full potential in recovering a collective set of distributed brain-wide networks with the number of RSNs close to those reported using functional magnetic resonance imaging (fMRI) has not been demonstrated. Approach. The present study developed a novel brain-wide DOT (BW-DOT) framework that integrates a cap-based whole-head optode placement system with multiple computational approaches, i.e. finite-element modeling, inverse source reconstruction, data-driven pattern recognition, and statistical correlation tomography, to reconstruct RSNs in dual contrasts of oxygenated (HbO) and deoxygenated hemoglobins (HbR). Main results. Our results from the proposed framework revealed a comprehensive set of RSNs and their subnetworks, which collectively cover almost the entire neocortical surface of the human brain, both at the group level and individual participants. The spatial patterns of these DOT RSNs suggest statistically significant similarities to fMRI RSN templates. Our results also reported the networks involving the medial prefrontal cortex and precuneus that had been missed in previous DOT studies. Furthermore, RSNs obtained from HbO and HbR suggest similarity in terms of both the number of RSN types reconstructed and their corresponding spatial patterns, while HbR RSNs show statistically more similarity to fMRI RSN templates and HbO RSNs indicate more bilateral patterns over two hemispheres. In addition, the BW-DOT framework allowed consistent reconstructions of RSNs across individuals and across recording sessions, indicating its high robustness and reproducibility, respectively. Significance. Our present results suggest the feasibility of using the BW-DOT, as a neuroimaging tool, in simultaneously mapping multiple RSNs and its potential values in studying RSNs, particularly in patient populations under diverse conditions and needs, due to its advantages in accessibility over fMRI., (© 2021 IOP Publishing Ltd.)

Significance: High density diffuse optical tomography (HD-DOT) as applied in functional near-infrared spectroscopy (fNIRS) is largely limited to continuous wave (CW) data. Using a single modulation frequency, frequency domain (FD) HD-DOT has recently demonstrated better localization of focal activation as compared to CW data. We show that combining CW and FD measurements and multiple modulation frequencies increases imaging performance in fNIRS., Aim: We evaluate the benefits of multiple modulation frequencies, combining different frequencies as well as CW data in fNIRS HD-DOT., Approach: A layered model was used, with activation occurring within a cortex layer. CW and FD measurements were simulated at 78, 141, and 203 MHz with and without noise. The localization error, full width half maximum, and effective resolution were evaluated., Results: Across the average of the three metrics, at 141 MHz, FD performed 8.4% better than CW, and the combination of CW and FD was 21.7% better than CW. FD measurements at 203 MHz performed 5% better than 78 MHz. Moreover, the three combined modulation frequencies of FD and CW performed up to 3.92% better than 141 MHz alone., Conclusions: We show that combining CW and FD measurements offers better performance than FD alone, with higher modulation frequencies increasing accuracy. Combining CW and FD measurements at multiple modulation frequencies yields the best overall performance.

Significance : Image reconstruction of fNIRS data is a useful technique for transforming channel-based fNIRS into a volumetric representation and managing spatial variance based on optode location. We present an innovative integrated pipeline for image reconstruction of fNIRS data using either MRI templates or individual anatomy. Aim: We demonstrate a pipeline with accompanying code to allow users to clean and prepare optode location information, prepare and standardize individual anatomical images, create the light model, run the 3D image reconstruction, and analyze data in group space. Approach: We synthesize a combination of new and existing software packages to create a complete pipeline, from raw data to analysis. Results: This pipeline has been tested using both templates and individual anatomy, and on data from different fNIRS data collection systems. We show high temporal correlations between channel-based and image-based fNIRS data. In addition, we demonstrate the reliability of this pipeline with a sample dataset that included 74 children as part of a longitudinal study taking place in Scotland. We demonstrate good correspondence between data in channel space and image reconstructed data. Conclusions: The pipeline presented here makes a unique contribution by integrating multiple tools to assemble a complete pipeline for image reconstruction in fNIRS. We highlight further issues that may be of interest to future software developers in the field., (© 2021 The Authors.)

Tissue optical properties are crucial for determining the light dose delivered to the tumor. Two probes are compared: the two-catheter probe is based on transmittance measurement between one point source and one isotropic detector inside parallel catheters spaced at 0.5 cm along a 1-inch diameter transparent cylinder; and a 1-inch trans-rectal diffuse optical tomography (DOT) probe designed for prostate measurements, using a multiple fiber-array with source-detector separations of 1.4-10 mm. The two-catheter probe uses an empirical model for primary and scatter light fluence rates in the cylindrical cavity condition for anal PDT to determine optical properties along the source catheter using dual motors to move the source and detector along the catheters. The DOT probe uses finite element method (FEM) to obtain distribution of optical properties in 3D. Validations for the two probes were performed in liquid and solid phantoms. For each method, validation was performed in tissue-mimicking liquid phantoms for a range of known optical properties (μ a between 0.05 and 0.9 cm -1 and μ s ' between 5.5 and 16.5 cm -1 ). To cross-check the two methods, solid phantoms were created of known optical properties at the University of Pennsylvania and sent for measurement to Princess Margaret Cancer Centre (PMH) to mimic realistic patient simulating conditions. Measurements were taken and optical properties were then recovered without knowing the expected values to cross-validate each probe. The results show modest agreement between the measured μ a and μ s 'values, but high degree of agreement between the measured μ eff performed independently using the two methods.

Background: The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR)., Methods: In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctO 2 Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO 2 Hb changes across chemotherapy when corrected for pCR status, age, and BMI., Results: Patients who achieved pCR to NAC had an overall decrease of 3.88 μM for ctO 2 Hb (95% CI, 1.39 to 6.37 μM), p = .004, after 2-3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 μM (95% CI, - 1.30 to 1.58 μM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO 2 Hb levels with BMI and age., Conclusions: This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.