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

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

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

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

A low-dimensional representation of arm movements and hand grip forces in post-stroke individuals

Characterizing post-stroke impairments in the sensorimotor control of arm and hand is essential to better understand altered mechanisms of movement generation. Herein, we used a decomposition algorithm to characterize impairments in end-effector velocity and hand grip force data collected from an instrumented functional task in 83 healthy control and 27 chronic post-stroke individuals with mild-to-moderate impairments. According to kinematic and kinetic raw data, post-stroke individuals showed reduced functional performance during all task phases. After applying the decomposition algorithm, we observed that the behavioural data from healthy controls relies on a low-dimensional representation and demonstrated that this representation is mostly preserved post-stroke. Further, it emerged that reduced functional performance post-stroke correlates to an abnormal variance distribution of the behavioural representation, except when reducing hand grip forces. This suggests that the behavioural repertoire in these post-stroke individuals is mostly preserved, thereby pointing towards therapeutic strategies that optimize movement quality and the reduction of grip forces to improve performance of daily life activities post-stroke

U-Limb: A multi-modal, multi-center database on arm motion control in healthy and post-stroke conditions

BACKGROUND: Shedding light on the neuroscientific mechanisms of human upper limb motor control, in both healthy and disease conditions (e.g., after a stroke), can help to devise effective tools for a quantitative evaluation of the impaired conditions, and to properly inform the rehabilitative process. Furthermore, the design and control of mechatronic devices can also benefit from such neuroscientific outcomes, with important implications for assistive and rehabilitation robotics and advanced human-machine interaction. To reach these goals, we believe that an exhaustive data collection on human behavior is a mandatory step. For this reason, we release U-Limb, a large, multi-modal, multi-center data collection on human upper limb movements, with the aim of fostering trans-disciplinary cross-fertilization. CONTRIBUTION: This collection of signals consists of data from 91 able-bodied and 65 post-stroke participants and is organized at 3 levels: (i) upper limb daily living activities, during which kinematic and physiological signals (electromyography, electro-encephalography, and electrocardiography) were recorded; (ii) force-kinematic behavior during precise manipulation tasks with a haptic device; and (iii) brain activity during hand control using functional magnetic resonance imaging

LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases--a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial

Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned. Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-2

Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

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Technology-aided assessment of functionally relevant sensorimotor impairments in arm and hand of post-stroke individuals

BACKGROUND Assessing arm and hand sensorimotor impairments that are functionally relevant is essential to optimize the impact of neurorehabilitation interventions. Technology-aided assessments should provide a sensitive and objective characterization of upper limb impairments, but often provide arm weight support and neglect the importance of the hand, thereby questioning their functional relevance. The Virtual Peg Insertion Test (VPIT) addresses these limitations by quantifying arm and hand movements as well as grip forces during a goal-directed manipulation task requiring active lifting of the upper limb against gravity. The aim of this work was to evaluate the ability of the VPIT metrics to characterize arm and hand sensorimotor impairments that are relevant for performing functional tasks. METHODS Arm and hand sensorimotor impairments were systematically characterized in 30 chronic stroke patients using conventional clinical scales and the VPIT. For the latter, ten previously established kinematic and kinetic core metrics were extracted. The validity and robustness of these metrics was investigated by analyzing their clinimetric properties (test-retest reliability, measurement error, learning effects, concurrent validity). RESULTS Twenty-three of the participants, the ones with mild to moderate sensorimotor impairments and without strong cognitive deficits, were able to successfully complete the VPIT protocol (duration 16.6 min). The VPIT metrics detected impairments in arm and hand in 90.0% of the participants, and were sensitive to increased muscle tone and pathological joint coupling. Most importantly, significant moderate to high correlations between conventional scales of activity limitations and the VPIT metrics were found, thereby indicating their functional relevance when grasping and transporting objects, and when performing dexterous finger manipulations. Lastly, the robustness of three out of the ten VPIT core metrics in post-stroke individuals was confirmed. CONCLUSIONS This work provides evidence that technology-aided assessments requiring goal-directed manipulations without arm weight support can provide an objective, robust, and clinically feasible way to assess functionally relevant sensorimotor impairments in arm and hand in chronic post-stroke individuals with mild to moderate deficits. This allows for a better identification of impairments with high functional relevance and can contribute to optimizing the functional benefits of neurorehabilitation interventions

Technology-aided assessment of functionally relevant sensorimotor impairments in arm and hand of post-stroke individuals

Background: Assessing arm and hand sensorimotor impairments that are functionally relevant is essential to optimize the impact of neurorehabilitation interventions. Technology-aided assessments should provide a sensitive and objective characterization of upper limb impairments, but often provide arm weight support and neglect the importance of the hand, thereby questioning their functional relevance. The Virtual Peg Insertion Test (VPIT) addresses these limitations by quantifying arm and hand movements as well as grip forces during a goal-directed manipulation task requiring active lifting of the upper limb against gravity. The aim of this work was to evaluate the ability of the VPIT metrics to characterize arm and hand sensorimotor impairments that are relevant for performing functional tasks. Methods: Arm and hand sensorimotor impairments were systematically characterized in 30 chronic stroke patients using conventional clinical scales and the VPIT. For the latter, ten previously established kinematic and kinetic core metrics were extracted. The validity and robustness of these metrics was investigated by analyzing their clinimetric properties (test-retest reliability, measurement error, learning effects, concurrent validity). Results: Twenty-three of the participants, the ones with mild to moderate sensorimotor impairments and without strong cognitive deficits, were able to successfully complete the VPIT protocol (duration 16.6 min). The VPIT metrics detected impairments in arm and hand in 90.0% of the participants, and were sensitive to increased muscle tone and pathological joint coupling. Most importantly, significant moderate to high correlations between conventional scales of activity limitations and the VPIT metrics were found, thereby indicating their functional relevance when grasping and transporting objects, and when performing dexterous finger manipulations. Lastly, the robustness of three out of the ten VPIT core metrics in post-stroke individuals was confirmed. Conclusions: This work provides evidence that technology-aided assessments requiring goal-directed manipulations without arm weight support can provide an objective, robust, and clinically feasible way to assess functionally relevant sensorimotor impairments in arm and hand in chronic post-stroke individuals with mild to moderate deficits. This allows for a better identification of impairments with high functional relevance and can contribute to optimizing the functional benefits of neurorehabilitation interventions