One-shot skill assessment in high-stakes domains with limited data via meta learning.

Deep Learning (DL) has achieved robust competency assessment in various high-stakes fields. However, the applicability of DL models is often hampered by their substantial data requirements and confinement to specific training domains. This prevents them from transitioning to new tasks where data is scarce. Therefore, domain adaptation emerges as a critical element for the practical implementation of DL in real-world scenarios. Herein, we introduce A-VBANet, a novel meta-learning model capable of delivering domain-agnostic skill assessment via one-shot learning. Our methodology has been tested by assessing surgical skills on five laparoscopic and robotic simulators and real-life laparoscopic cholecystectomy. Our model successfully adapted with accuracies up to 99.5 % in one-shot and 99.9 % in few-shot settings for simulated tasks and 89.7 % for laparoscopic cholecystectomy. This study marks the first instance of a domain-agnostic methodology for skill assessment in critical fields setting a precedent for the broad application of DL across diverse real-life domains with limited data.

Contrast-enhanced photon-counting micro-CT of tumor xenograft models.

OBJECTIVE: Photon-counting micro-computed tomography (micro-CT) is a major advance in small animal preclinical imaging. Small molecule- and nanoparticle-based contrast agents have been widely used to enable the differentiation of liver tumors from surrounding tissues using photon-counting micro-CT. However, there is a notable gap in the application of these market-available agents to the imaging of breast and ovarian tumors using photon-counting micro-CT. Herein, we have used photon-counting micro-CT to determine the effectiveness of these contrast agents in differentiating ovarian and breast tumor xenografts in live, intact mice. Approach. Nude mice carrying different types of breast and ovarian tumor xenografts (AU565, MDA-MB-231 and SKOV-3 human cancer cells) were injected with ISOVUE-370 (a small molecule-based agent) or Exitrone Nano 12000 (a nanoparticle-based agent) and subjected to photon-counting micro-CT. To improve tumor visualization using photon-counting micro-CT, we developed a novel color visualization method, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Main results. Our in vivo experiments confirm the effectiveness of this color visualization approach, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggest that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 delivers a more comprehensive tumor enhancement but with significant variance between scans due to its short blood half-time. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based contrast agent (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemical analysis. Significance. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor progression and response to treatments. .

Fluorescence Lifetime Imaging for Quantification of Targeted Drug Delivery in Varying Tumor Microenvironments.

Rationale: Trastuzumab (TZM) is a monoclonal antibody that targets the human epidermal growth factor receptor (HER2) and is clinically used for the treatment of HER2-positive breast tumors. However, the tumor microenvironment can limit the access of TZM to the HER2 targets across the whole tumor and thereby compromise TZM's therapeutic efficacy. An imaging methodology that can non-invasively quantify the binding of TZM-HER2, which is required for therapeutic action, and distribution within tumors with varying tumor microenvironments is much needed. Methods: We performed near-infrared (NIR) fluorescence lifetime (FLI) Forster Resonance Energy Transfer (FRET) to measure TZM-HER2 binding, using in vitro microscopy and in vivo widefield macroscopy, in HER2 overexpressing breast and ovarian cancer cells and tumor xenografts, respectively. Immunohistochemistry was used to validate in vivo imaging results. Results: NIR FLI FRET in vitro microscopy data show variations in intracellular distribution of bound TZM in HER2-positive breast AU565 and AU565 tumor-passaged XTM cell lines in comparison to SKOV-3 ovarian cancer cells. Macroscopy FLI (MFLI) FRET in vivo imaging data show that SKOV-3 tumors display reduced TZM binding compared to AU565 and XTM tumors, as validated by ex vivo immunohistochemistry. Moreover, AU565/XTM and SKOV-3 tumor xenografts display different amounts and distributions of TME components, such as collagen and vascularity. Therefore, these results suggest that SKOV-3 tumors are refractory to TZM delivery due to their disrupted vasculature and increased collagen content. Conclusion: Our study demonstrates that FLI is a powerful analytical tool to monitor the delivery of antibody drug tumor both in cell cultures and in vivo live systems. Especially, MFLI FRET is a unique imaging modality that can directly quantify target engagement with potential to elucidate the role of the TME in drug delivery efficacy in intact live tumor xenografts.

Contrast-enhanced photon-counting micro-CT of tumor xenograft models.

Photon-counting micro computed tomography (micro-CT) offers new potential in preclinical imaging, particularly in distinguishing materials. It becomes especially helpful when combined with contrast agents, enabling the differentiation of tumors from surrounding tissues. There are mainly two types of contrast agents in the market for micro-CT: small molecule-based and nanoparticle-based. However, despite their widespread use in liver tumor studies, there is a notable gap in research on the application of these commercially available agents for photon-counting micro-CT in breast and ovarian tumors. Herein, we explored the effectiveness of these agents in differentiating tumor xenografts from various origins (AU565, MDA-MB-231, and SKOV-3) in nude mice, using photon-counting micro-CT. Specifically, ISOVUE-370 (a small molecule-based agent) and Exitrone Nano 12000 (a nanoparticle-based agent) were investigated in this context. To improve tumor visualization, we proposed a novel color visualization method for photon-counting micro-CT, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Our in vivo experiments confirm its effectiveness, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggested that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 gives more comprehensive tumor enhancement but with a significant variance between scans due to its short blood half-time. This variability leads to high sensitivity to timing and individual differences among mice. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemistry. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor development and response to treatments.

Distinguishing Laparoscopic Surgery Experts from Novices Using EEG Topographic Features.

The study aimed to differentiate experts from novices in laparoscopic surgery tasks using electroencephalogram (EEG) topographic features. A microstate-based common spatial pattern (CSP) analysis with linear discriminant analysis (LDA) was compared to a topography-preserving convolutional neural network (CNN) approach. Expert surgeons (N = 10) and novice medical residents (N = 13) performed laparoscopic suturing tasks, and EEG data from 8 experts and 13 novices were analysed. Microstate-based CSP with LDA revealed distinct spatial patterns in the frontal and parietal cortices for experts, while novices showed frontal cortex involvement. The 3D CNN model (ESNet) demonstrated a superior classification performance (accuracy > 98%, sensitivity 99.30%, specificity 99.70%, F1 score 98.51%, MCC 97.56%) compared to the microstate based CSP analysis with LDA (accuracy ~90%). Combining spatial and temporal information in the 3D CNN model enhanced classifier accuracy and highlighted the importance of the parietal-temporal-occipital association region in differentiating experts and novices.

Assessment of Surgical Tasks Using Neuroimaging Dataset (ASTaUND).

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging tool for studying brain activity in mobile subjects. Open-access fNIRS datasets are limited to simple and/or motion-restricted tasks. Here, we report a fNIRS dataset acquired on mobile subjects performing Fundamentals of Laparoscopic Surgery (FLS) tasks in a laboratory environment. Demonstrating competency in the FLS tasks is a prerequisite for board certification in general surgery in the United States. The ASTaUND data set was acquired over four different studies. We provide the relevant information about the hardware, FLS task execution protocols, and subject demographics to facilitate the use of this open-access data set. We also provide the concurrent FLS scores, a quantitative metric for surgical skill assessment developed by the FLS committee. This data set is expected to support the growing field of assessing surgical skills via neuroimaging data and provide an example of data processing pipeline for use in realistic, non-restrictive environments.

Performance and learning rate prediction models development in FLS and RAS surgical tasks using electroencephalogram and eye gaze data and machine learning.

OBJECTIVE: This study explored the use of electroencephalogram (EEG) and eye gaze features, experience-related features, and machine learning to evaluate performance and learning rates in fundamentals of laparoscopic surgery (FLS) and robotic-assisted surgery (RAS). METHODS: EEG and eye-tracking data were collected from 25 participants performing three FLS and 22 participants performing two RAS tasks. Generalized linear mixed models, using L1-penalized estimation, were developed to objectify performance evaluation using EEG and eye gaze features, and linear models were developed to objectify learning rate evaluation using these features and performance scores at the first attempt. Experience metrics were added to evaluate their role in learning robotic surgery. The differences in performance across experience levels were tested using analysis of variance. RESULTS: EEG and eye gaze features and experience-related features were important for evaluating performance in FLS and RAS tasks with reasonable results. Residents outperformed faculty in FLS peg transfer (p value = 0.04), while faculty and residents both excelled over pre-medical students in the FLS pattern cut (p value = 0.01 and p value < 0.001, respectively). Fellows outperformed pre-medical students in FLS suturing (p value = 0.01). In RAS tasks, both faculty and fellows surpassed pre-medical students (p values for the RAS pattern cut were 0.001 for faculty and 0.003 for fellows, while for RAS tissue dissection, the p value was less than 0.001 for both groups), with residents also showing superior skills in tissue dissection (p value = 0.03). CONCLUSION: Findings could be used to develop training interventions for improving surgical skills and have implications for understanding motor learning and designing interventions to enhance learning outcomes.

Spatial topology of organelle is a new breast cancer cell classifier.

Genomics and proteomics have been central to identify tumor cell populations, but more accurate approaches to classify cell subtypes are still lacking. We propose a new methodology to accurately classify cancer cells based on their organelle spatial topology. Herein, we developed an organelle topology-based cell classification pipeline (OTCCP), which integrates artificial intelligence (AI) and imaging quantification to analyze organelle spatial distribution and inter-organelle topology. OTCCP was used to classify a panel of human breast cancer cells, grown as 2D monolayer or 3D tumor spheroids using early endosomes, mitochondria, and their inter-organelle contacts. Organelle topology allows for a highly precise differentiation between cell lines of different subtypes and aggressiveness. These findings lay the groundwork for using organelle topological profiling as a fast and efficient method for phenotyping breast cancer function as well as a discovery tool to advance our understanding of cancer cell biology at the subcellular level.

Changes in functional neuroimaging measures as novices gain proficiency on the fundamentals of laparoscopic surgery suturing task.

Significance: As trainees practice fundamental surgical skills, they typically rely on performance measures such as time and errors, which are limited in their sensitivity. Aim: The goal of our study was to evaluate the use of portable neuroimaging measures to map the neural processes associated with learning basic surgical skills. Approach: Twenty-one subjects completed 15 sessions of training on the fundamentals of laparoscopic surgery (FLS) suture with intracorporeal knot-tying task in a box trainer. Functional near infrared spectroscopy data were recorded using an optode montage that covered the prefrontal and sensorimotor brain areas throughout the task. Average oxy-hemoglobin (HbO) changes were determined for repetitions performed during the first week of training compared with the third week of training. Statistical differences between the time periods were evaluated using a general linear model of the HbO changes. Results: Average performance scores across task repetitions increased significantly from the first day to the last day of training ( p < 0.01 ). During the first day of training, there was significant lateral prefrontal cortex (PFC) activation. On the final day, significant activation was observed in the PFC, as well as the sensorimotor areas. When comparing the two periods, significant differences in activation ( p < 0.05 ) were found for the right medial PFC and the right inferior parietal gyrus. While gaining proficiency, trainees activated the perception-action cycle to build a perceptual model and then apply the model to improve task execution. Conclusions: Learners engaged the sensorimotor areas more substantially as they developed skill on the FLS suturing task. These findings are consistent with findings for the FLS pattern cutting task and contribute to the development of objective metrics for skill evaluation.

In vivo quantitative FRET small animal imaging: Intensity versus lifetime-based FRET.

Förster resonance energy transfer (FRET) microscopy is used in numerous biophysical and biomedical applications to monitor inter- and intramolecular interactions and conformational changes in the 2-10 nm range. FRET is currently being extended to in vivo optical imaging, its main application being in quantifying drug-target engagement or drug release in animal models of cancer using organic dye or nanoparticle-labeled probes. Herein, we compared FRET quantification using intensity-based FRET (sensitized emission FRET analysis with the three-cube approach using an IVIS imager) and macroscopic fluorescence lifetime (MFLI) FRET using a custom system using a time-gated-intensified charge-coupled device, for small animal optical in vivo imaging. The analytical expressions and experimental protocols required to quantify the product fDE of the FRET efficiency E and the fraction of donor molecules involved in FRET, fD, are described in detail for both methodologies. Dynamic in vivo FRET quantification of transferrin receptor-transferrin binding was acquired in live intact nude mice upon intravenous injection of a near-infrared-labeled transferrin FRET pair and benchmarked against in vitro FRET using hybridized oligonucleotides. Even though both in vivo imaging techniques provided similar dynamic trends for receptor-ligand engagement, we demonstrate that MFLI-FRET has significant advantages. Whereas the sensitized emission FRET approach using the IVIS imager required nine measurements (six of which are used for calibration) acquired from three mice, MFLI-FRET needed only one measurement collected from a single mouse, although a control mouse might be needed in a more general situation. Based on our study, MFLI therefore represents the method of choice for longitudinal preclinical FRET studies such as that of targeted drug delivery in intact, live mice.

Roadmap on Deep Learning for Microscopy.

Through digital imaging, microscopy has evolved from primarily being a means for visual observation of life at the micro- and nano-scale, to a quantitative tool with ever-increasing resolution and throughput. Artificial intelligence, deep neural networks, and machine learning are all niche terms describing computational methods that have gained a pivotal role in microscopy-based research over the past decade. This Roadmap is written collectively by prominent researchers and encompasses selected aspects of how machine learning is applied to microscopy image data, with the aim of gaining scientific knowledge by improved image quality, automated detection, segmentation, classification and tracking of objects, and efficient merging of information from multiple imaging modalities. We aim to give the reader an overview of the key developments and an understanding of possibilities and limitations of machine learning for microscopy. It will be of interest to a wide cross-disciplinary audience in the physical sciences and life sciences.

Deep learning-based fusion of widefield diffuse optical tomography and micro-CT structural priors for accurate 3D reconstructions.

Widefield illumination and detection strategies leveraging structured light have enabled fast and robust probing of tissue properties over large surface areas and volumes. However, when applied to diffuse optical tomography (DOT) applications, they still require a time-consuming and expert-centric solving of an ill-posed inverse problem. Deep learning (DL) models have been recently proposed to facilitate this challenging step. Herein, we expand on a previously reported deep neural network (DNN) -based architecture (modified AUTOMAP - ModAM) for accurate and fast reconstructions of the absorption coefficient in 3D DOT based on a structured light illumination and detection scheme. Furthermore, we evaluate the improved performances when incorporating a micro-CT structural prior in the DNN-based workflow, named Z-AUTOMAP. This Z-AUTOMAP significantly improves the widefield imaging process's spatial resolution, especially in the transverse direction. The reported DL-based strategies are validated both in silico and in experimental phantom studies using spectral micro-CT priors. Overall, this is the first successful demonstration of micro-CT and DOT fusion using deep learning, greatly enhancing the prospect of rapid data-integration strategies, often demanded in challenging pre-clinical scenarios.

in vivo quantitative FRET small animal imaging: intensity versus lifetime-based FRET.

Förster Resonance Energy Transfer (FRET) microscopy is used in numerous biophysical and biomedical applications to monitor inter- and intramolecular interactions and conformational changes in the 2-10 nm range. FRET is currently being extended to in vivo optical imaging, its main application being in quantifying drug-target engagement or drug release in animal models of cancer using organic dye or nanoparticle-labeled probes. Herein, we compared FRET quantification using intensity-based FRET (sensitized emission FRET analysis with the 3-cube approach using an IVIS imager) and macroscopic fluorescence lifetime (MFLI) FRET using a custom system using a time-gated ICCD, for small animal optical in vivo imaging. The analytical expressions and experimental protocols required to quantify the product f D E of the FRET efficiency E and the fraction of donor molecules involved in FRET, f D , are described in detail for both methodologies. Dynamic in vivo FRET quantification of transferrin receptor-transferrin binding was acquired in live intact nude mice upon intravenous injection of near infrared-labeled transferrin FRET pair and benchmarked against in vitro FRET using hybridized oligonucleotides. Even though both in vivo imaging techniques provided similar dynamic trends for receptor-ligand engagement, we demonstrate that MFLI FRET has significant advantages. Whereas the sensitized emission FRET approach using the IVIS imager required 9 measurements (6 of which are used for calibration) acquired from three mice, MFLI FRET needed only one measurement collected from a single mouse, although a control mouse might be needed in a more general situation. Based on our study, MFLI therefore represents the method of choice for longitudinal preclinical FRET studies such as that of targeted drug delivery in intact, live mice.

Video-based formative and summative assessment of surgical tasks using deep learning.

To ensure satisfactory clinical outcomes, surgical skill assessment must be objective, time-efficient, and preferentially automated-none of which is currently achievable. Video-based assessment (VBA) is being deployed in intraoperative and simulation settings to evaluate technical skill execution. However, VBA is manual, time-intensive, and prone to subjective interpretation and poor inter-rater reliability. Herein, we propose a deep learning (DL) model that can automatically and objectively provide a high-stakes summative assessment of surgical skill execution based on video feeds and low-stakes formative assessment to guide surgical skill acquisition. Formative assessment is generated using heatmaps of visual features that correlate with surgical performance. Hence, the DL model paves the way for the quantitative and reproducible evaluation of surgical tasks from videos with the potential for broad dissemination in surgical training, certification, and credentialing.

Portable neuroimaging differentiates novices from those with experience for the Fundamentals of Laparoscopic Surgery (FLS) suturing with intracorporeal knot tying task.

BACKGROUND: The goal of this study was to compare the brain activation patterns of experienced and novice individuals when performing the Fundamentals of Laparoscopic Surgery (FLS) suture with intracorporeal knot tying task, which requires bimanual motor control. METHODS: Twelve experienced and fourteen novice participants completed this cross-sectional observational study. Participants performed three repetitions of the FLS suture with intracorporeal knot tying task in a standard box trainer. Functional near infrared spectroscopy (fNIRS) data was recorded using an optode montage that covered the prefrontal and sensorimotor brain areas throughout the task. Data processing was conducted using the HOMER3 and AtlasViewer toolboxes to determine the oxy-hemoglobin (HbO) and deoxyhemoglobin (HbR) concentrations. The hemodynamic response function based on HbO changes during the task relative to the resting state was averaged for each repetition and by participant. Group-level differences were evaluated using a general linear model of the HbO changes with significance set at p < 0.05. RESULTS: The average performance score for the experienced group was significantly higher than the novice group (p < 0.01). There were significant cortical activations (p < 0.05) in the prefrontal and sensorimotor areas for the experienced and novice groups. Areas of statistically significant differences in activation included the right dorsolateral prefrontal cortex (PFC), the right precentral gyrus, and the right postcentral gyrus. CONCLUSIONS: Portable neuroimaging allowed for the differentiation of brain regions activated by experienced and novice participants for a complex surgical motor task. This information can be used to support the objective evaluation of expertise during surgical skills training and assessment.

Brain-behavior analysis of transcranial direct current stimulation effects on a complex surgical motor task.

Transcranial Direct Current Stimulation (tDCS) has demonstrated its potential in enhancing surgical training and performance compared to sham tDCS. However, optimizing its efficacy requires the selection of appropriate brain targets informed by neuroimaging and mechanistic understanding. Previous studies have established the feasibility of using portable brain imaging, combining functional near-infrared spectroscopy (fNIRS) with tDCS during Fundamentals of Laparoscopic Surgery (FLS) tasks. This allows concurrent monitoring of cortical activations. Building on these foundations, our study aimed to explore the multi-modal imaging of the brain response using fNIRS and electroencephalogram (EEG) to tDCS targeting the right cerebellar (CER) and left ventrolateral prefrontal cortex (PFC) during a challenging FLS suturing with intracorporeal knot tying task. Involving twelve novices with a medical/premedical background (age: 22-28 years, two males, 10 females with one female with left-hand dominance), our investigation sought mechanistic insights into tDCS effects on brain areas related to error-based learning, a fundamental skill acquisition mechanism. The results revealed that right CER tDCS applied to the posterior lobe elicited a statistically significant (q < 0.05) brain response in bilateral prefrontal areas at the onset of the FLS task, surpassing the response seen with sham tDCS. Additionally, right CER tDCS led to a significant (p < 0.05) improvement in FLS scores compared to sham tDCS. Conversely, the left PFC tDCS did not yield a statistically significant brain response or improvement in FLS performance. In conclusion, right CER tDCS demonstrated the activation of bilateral prefrontal brain areas, providing valuable mechanistic insights into the effects of CER tDCS on FLS peformance. These insights motivate future investigations into the effects of CER tDCS on error-related perception-action coupling through directed functional connectivity studies.

Error-related brain state analysis using electroencephalography in conjunction with functional near-infrared spectroscopy during a complex surgical motor task.

Error-based learning is one of the basic skill acquisition mechanisms that can be modeled as a perception-action system and investigated based on brain-behavior analysis during skill training. Here, the error-related chain of mental processes is postulated to depend on the skill level leading to a difference in the contextual switching of the brain states on error commission. Therefore, the objective of this paper was to compare error-related brain states, measured with multi-modal portable brain imaging, between experts and novices during the Fundamentals of Laparoscopic Surgery (FLS) "suturing and intracorporeal knot-tying" task (FLS complex task)-the most difficult among the five psychomotor FLS tasks. The multi-modal portable brain imaging combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) for brain-behavior analysis in thirteen right-handed novice medical students and nine expert surgeons. The brain state changes were defined by quasi-stable EEG scalp topography (called microstates) changes using 32-channel EEG data acquired at 250 Hz. Six microstate prototypes were identified from the combined EEG data from experts and novices during the FLS complex task that explained 77.14% of the global variance. Analysis of variance (ANOVA) found that the proportion of the total time spent in different microstates during the 10-s error epoch was significantly affected by the skill level (p < 0.01), the microstate type (p < 0.01), and the interaction between the skill level and the microstate type (p < 0.01). Brain activation based on the slower oxyhemoglobin (HbO) changes corresponding to the EEG band power (1-40 Hz) changes were found using the regularized temporally embedded Canonical Correlation Analysis of the simultaneously acquired fNIRS-EEG signals. The HbO signal from the overlying the left inferior frontal gyrus-opercular part, left superior frontal gyrus-medial orbital, left postcentral gyrus, left superior temporal gyrus, right superior frontal gyrus-medial orbital cortical areas showed significant (p < 0.05) difference between experts and novices in the 10-s error epoch. We conclude that the difference in the error-related chain of mental processes was the activation of cognitive top-down attention-related brain areas, including left dorsolateral prefrontal/frontal eye field and left frontopolar brain regions, along with a 'focusing' effect of global suppression of hemodynamic activation in the experts, while the novices had a widespread stimulus(error)-driven hemodynamic activation without the 'focusing' effect.

Computational macroscopic lifetime imaging and concentration unmixing of autofluorescence.

Single-pixel computational imaging can leverage highly sensitive detectors that concurrently acquire data across spectral and temporal domains. For molecular imaging, such methodology enables to collect rich intensity and lifetime multiplexed fluorescence datasets. Herein we report on the application of a single-pixel structured light-based platform for macroscopic imaging of tissue autofluorescence. The super-continuum visible excitation and hyperspectral single-pixel detection allow for parallel characterization of autofluorescence intensity and lifetime. Furthermore, we exploit a deep learning based data processing pipeline, to perform autofluorescence unmixing while yielding the autofluorophores' concentrations. The full scheme (setup and processing) is validated in silico and in vitro with clinically relevant autofluorophores flavin adenine dinucleotide, riboflavin, and protoporphyrin. The presented results demonstrate the potential of the methodology for macroscopically quantifying the intensity and lifetime of autofluorophores, with higher specificity for cases of mixed emissions, which are ubiquitous in autofluorescence and multiplexed in vivo imaging.

Design and characterization of a time-domain optical tomography platform for mesoscopic lifetime imaging.

We report on the system design and instrumental characteristics of a novel time-domain mesoscopic fluorescence molecular tomography (TD-MFMT) system for multiplexed molecular imaging in turbid media. The system is equipped with a supercontinuum pulsed laser for broad spectral excitation, based on a high-density descanned raster scanning intensity-based acquisition for 2D and 3D imaging and augmented with a high-dynamical range linear time-resolved single-photon avalanche diode (SPAD) array for lifetime quantification. We report on the system's spatio-temporal and spectral characteristics and its sensitivity and specificity in controlled experimental settings. Also, a phantom study is undertaken to test the performance of the system to image deeply-seated fluorescence inclusions in tissue-like media. In addition, ex vivo tumor xenograft imaging is performed to validate the system's applicability to the biological sample. The characterization results manifest the capability to sense small fluorescence concentrations (on the order of nanomolar) while quantifying fluorescence lifetimes and lifetime-based parameters at high resolution. The phantom results demonstrate the system's potential to perform 3D multiplexed imaging thanks to spectral and lifetime contrast in the mesoscopic range (at millimeters depth). The ex vivo imaging exhibits the prospect of TD-MFMT to resolve intra-tumoral heterogeneity in a depth-dependent manner.

Error related fNIRS-EEG microstate analysis during a complex surgical motor task.

Fundamentals of Laparoscopic Surgery (FLS) is a standard education and training module with a set of basic surgical skills. During surgical skill acquisition, novices need to learn from errors due to perturbations in their performance which is one of the basic principles of motor skill acquisition. This study on thirteen healthy novice medical students and nine expert surgeons aimed to capture the brain state during error epochs using multimodal brain imaging by combining functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). We performed error-related microstate analysis in the latent space that was found using regularized temporally embedded Canonical Correlation Analysis from fNIRS-EEG recordings during the performance of FLS "suturing and intracorporeal knot-tying" task - the most difficult among the five psychomotor FLS tasks. We found from two-way analysis of variance (ANDVA) with factors, skill level (expert, novice), and microstate type (1-6) that the proportion of the total time spent in microstates in the error epochs was significantly affected by the skill level ( ), microstate type ( ), and the interaction between the skill level and the microstate type ( ). Therefore, our study highlighted the relevance of portable brain imaging to capture error behavior when comparing the skill level during a complex surgical task. Clinical Relevance-This establishes the brain-behavior relationship for monitoring complex surgical motor task errors that differentiated experts from novices.