Changes of brain parenchyma free water fraction reflect tissue damage and impaired processing speed in multiple sclerosis.

Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.

Atrophy of hippocampal subfields and amygdala nuclei in subjects with mild cognitive impairment progressing to Alzheimer's disease.

The hippocampus and amygdala are the first brain regions to show early signs of Alzheimer's Disease (AD) pathology. AD is preceded by a prodromal stage known as Mild Cognitive Impairment (MCI), a crucial crossroad in the clinical progression of the disease. The topographical development of AD has been the subject of extended investigation. However, it is still largely unknown how the transition from MCI to AD affects specific hippocampal and amygdala subregions. The present study is set to answer that question. We analyzed data from 223 subjects: 75 healthy controls, 52 individuals with MCI, and 96 AD patients obtained from the ADNI. The MCI group was further divided into two subgroups depending on whether individuals in the 48 months following the diagnosis either remained stable (N = 21) or progressed to AD (N = 31). A MANCOVA test evaluated group differences in the volume of distinct amygdala and hippocampal subregions obtained from magnetic resonance images. Subsequently, a stepwise linear discriminant analysis (LDA) determined which combination of magnetic resonance imaging parameters was most effective in predicting the conversion from MCI to AD. The predictive performance was assessed through a Receiver Operating Characteristic analysis. AD patients displayed widespread subregional atrophy. MCI individuals who progressed to AD showed selective atrophy of the hippocampal subiculum and tail compared to stable MCI individuals, who were undistinguishable from healthy controls. Converter MCI showed atrophy of the amygdala's accessory basal, central, and cortical nuclei. The LDA identified the hippocampal subiculum and the amygdala's lateral and accessory basal nuclei as significant predictors of MCI conversion to AD. The analysis returned a sensitivity value of 0.78 and a specificity value of 0.62. These findings highlight the importance of targeted assessments of distinct amygdala and hippocampus subregions to help dissect the clinical and pathophysiological development of the MCI to AD transition.

Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study.

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10-4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10-3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10-3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.

Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data.

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.

Fast Optical Signals for Real-Time Retinotopy and Brain Computer Interface.

A brain-computer interface (BCI) allows users to control external devices through brain activity. Portable neuroimaging techniques, such as near-infrared (NIR) imaging, are suitable for this goal. NIR imaging has been used to measure rapid changes in brain optical properties associated with neuronal activation, namely fast optical signals (FOS) with good spatiotemporal resolution. However, FOS have a low signal-to-noise ratio, limiting their BCI application. Here FOS were acquired with a frequency-domain optical system from the visual cortex during visual stimulation consisting of a rotating checkerboard wedge, flickering at 5 Hz. We used measures of photon count (Direct Current, DC light intensity) and time of flight (phase) at two NIR wavelengths (690 nm and 830 nm) combined with a machine learning approach for fast estimation of visual-field quadrant stimulation. The input features of a cross-validated support vector machine classifier were computed as the average modulus of the wavelet coherence between each channel and the average response among all channels in 512 ms time windows. An above chance performance was obtained when differentiating visual stimulation quadrants (left vs. right or top vs. bottom) with the best classification accuracy of ~63% (information transfer rate of ~6 bits/min) when classifying the superior and inferior stimulation quadrants using DC at 830 nm. The method is the first attempt to provide generalizable retinotopy classification relying on FOS, paving the way for the use of FOS in real-time BCI.

MRI-Based Radiomics Approach Predicts Tumor Recurrence in ER + /HER2 - Early Breast Cancer Patients.

Oncotype Dx Recurrence Score (RS) has been validated in patients with ER + /HER2 - invasive breast carcinoma to estimate patient risk of recurrence and guide the use of adjuvant chemotherapy. We investigated the role of MRI-based radiomics features extracted from the tumor and the peritumoral tissues to predict the risk of tumor recurrence. A total of 62 patients with biopsy-proved ER + /HER2 - breast cancer who underwent pre-treatment MRI and Oncotype Dx were included. An RS > 25 was considered discriminant between low-intermediate and high risk of tumor recurrence. Two readers segmented each tumor. Radiomics features were extracted from the tumor and the peritumoral tissues. Partial least square (PLS) regression was used as the multivariate machine learning algorithm. PLS ß-weights of radiomics features included the 5% features with the largest ß-weights in magnitude (top 5%). Leave-one-out nested cross-validation (nCV) was used to achieve hyperparameter optimization and evaluate the generalizable performance of the procedure. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The exploratory analysis for the complete dataset revealed an average absolute correlation among features of 0.51. The nCV framework delivered an AUC of 0.76 (p = 1.1∙10-3). When combining "early" and "peak" DCE images of only T or TST, a tendency toward statistical significance was obtained for TST with an AUC of 0.61 (p = 0.05). The 47 features included in the top 5% were balanced between T and TST (23 and 24, respectively). Moreover, 33/47 (70%) were texture-related, and 25/47 (53%) were derived from high-resolution images (1 mm). A radiomics-based machine learning approach shows the potential to accurately predict the recurrence risk in early ER + /HER2 - breast cancer patients.

Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation.

Cerebrovascular reactivity (CVR) reflects the capacity of the brain's vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain's blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = - 0.58, p = 0.005; WM: r = - 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = - 0.48, p = 0.02, WM: r = - 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring.

Interaction of the salience network, ventral attention network, dorsal attention network and default mode network in neonates and early development of the bottom-up attention system.

The salience network (SN), ventral attention network (VAN), dorsal attention network (DAN) and default mode network (DMN) have shown significant interactions and overlapping functions in bottom-up and top-down mechanisms of attention. In the present study, we tested if the SN, VAN, DAN and DMN connectivity can infer the gestational age (GA) at birth in a study group of 88 healthy neonates, scanned at 40 weeks of post-menstrual age, and with GA at birth ranging from 28 to 40 weeks. We also ascertained whether the connectivity within each of the SN, VAN, DAN and DMN was able to infer the average functional connectivity of the others. The ability to infer GA at birth or another network's connectivity was evaluated using a multivariate data-driven framework. The VAN, DAN and the DMN inferred the GA at birth (p < 0.05). The SN, DMN and VAN were able to infer the average connectivity of the other networks (p < 0.05). Mediation analysis between VAN's and DAN's inference on GA at birth found reciprocal transmittance of change with GA at birth of VAN's and DAN's connectivity (p < 0.05). Our findings suggest that the VAN has a prominent role in bottom-up salience detection in early infancy and that the role of the VAN and the SN may overlap in the bottom-up control of attention.

Study of nonperfusion area changes after ranibizumab intravitreal injection for diabetic macular edema by means of widefield OCT angiography.

INTRODUCTION: To evaluate changes of retinal capillary non-perfusion areas (RCNPA) and the retinal capillary vessel density (RCVD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using widefield optical coherence tomography angiography (WFOCTA) in patients with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with intravitreal ranibizumab injection (IRI). MATERIALS AND METHODS: 24 eyes of 24 patients with DR and DME candidates to a loading dose of IRI were enrolled. All patients underwent WFOCTA with the PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline (T0) and 1 month after each intravitreal injection at 30 days (T1), 60 days (T2), and 90 days (T3). In all patients, the variation of RCNPA and the RCVD of the of the SCP and DCP were calculated using automatic software written in Matlab (MathWorks, Natick, MA). RESULTS: The SCP showed a significant longitudinal variation of RCNPA (p = 0.04). Post-hoc analysis revealed a statistically significant reduction of RCNPA at T1 (p = 0.04) and a not significant reduction at T2 (p=0.18) and T3 (p=0.96). The DCP showed longitudinal changes of the RCNPA that tended to statistical significance (p = 0.09). Post-hoc analysis revealed a trend towards a statistically significant reduction of RCNPA at T3 (p = 0.09) not statistically significant, at T1 (p=0.17) and T2 (p=0.75). The RCVD of SCP and DCP showed no significant changes in any of the time points. CONCLUSIONS: Widefield OCT angiography showed a decrease of RCNPA after IRI, probably related to the reperfusion of retinal capillaries.

Central and Peripheral Thermal Signatures of Brain-Derived Fatigue during Unilateral Resistance Exercise: A Preliminary Study.

Infrared thermography (IRT) allows to evaluate the psychophysiological state associated with emotions from facial temperature modulations. As fatigue is a brain-derived emotion, it is possible to hypothesize that facial temperature could provide information regarding the fatigue related to exercise. The aim of this study was to investigate the capability of IRT to assess the central and peripheral physiological effect of fatigue by measuring facial skin and muscle temperature modulations in response to a unilateral knee extension exercise until exhaustion. Rate of perceived exertion (RPE) was recorded at the end of the exercise. Both time- (∆TROI: pre-post exercise temperature variation) and frequency-domain (∆PSD: pre-post exercise power spectral density variation of specific frequency bands) analyses were performed to extract features from regions of interest (ROIs) positioned on the exercised and nonexercised leg, nose tip, and corrugator. The ANOVA-RM revealed a significant difference between ∆TROI (F(1.41,9.81) = 15.14; p = 0.0018), and between ∆PSD of myogenic (F(1.34,9.39) = 15.20; p = 0.0021) and neurogenic bands (F(1.75,12.26) = 9.96; p = 0.0034) of different ROIs. Moreover, significant correlations between thermal features and RPE were found. These findings suggest that IRT could assess both peripheral and central responses to physical exercise. Its applicability in monitoring the psychophysiological responses to exercise should be further explored.

Contribution of Metabolomics to Multiple Sclerosis Diagnosis, Prognosis and Treatment.

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.

A Motion Artifact Correction Procedure for fNIRS Signals Based on Wavelet Transform and Infrared Thermography Video Tracking.

Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that allows to monitor the functional hemoglobin oscillations related to cortical activity. One of the main issues related to fNIRS applications is the motion artefact removal, since a corrupted physiological signal is not correctly indicative of the underlying biological process. A novel procedure for motion artifact correction for fNIRS signals based on wavelet transform and video tracking developed for infrared thermography (IRT) is presented. In detail, fNIRS and IRT were concurrently recorded and the optodes' movement was estimated employing a video tracking procedure developed for IRT recordings. The wavelet transform of the fNIRS signal and of the optodes' movement, together with their wavelet coherence, were computed. Then, the inverse wavelet transform was evaluated for the fNIRS signal excluding the frequency content corresponding to the optdes' movement and to the coherence in the epochs where they were higher with respect to an established threshold. The method was tested using simulated functional hemodynamic responses added to real resting-state fNIRS recordings corrupted by movement artifacts. The results demonstrated the effectiveness of the procedure in eliminating noise, producing results with higher signal to noise ratio with respect to another validated method.

Radiomics-based machine learning differentiates "ground-glass" opacities due to COVID-19 from acute non-COVID-19 lung disease.

Ground-glass opacities (GGOs) are a non-specific high-resolution computed tomography (HRCT) finding tipically observed in early Coronavirus disesase 19 (COVID-19) pneumonia. However, GGOs are also seen in other acute lung diseases, thus making challenging the differential diagnosis. To this aim, we investigated the performance of a radiomics-based machine learning method to discriminate GGOs due to COVID-19 from those due to other acute lung diseases. Two sets of patients were included: a first set of 28 patients (COVID) diagnosed with COVID-19 infection confirmed by real-time polymerase chain reaction (RT-PCR) between March and April 2020 having (a) baseline HRCT at hospital admission and (b) predominant GGOs pattern on HRCT; a second set of 30 patients (nCOVID) showing (a) predominant GGOs pattern on HRCT performed between August 2019 and April 2020 and (b) availability of final diagnosis. Two readers independently segmented GGOs on HRCTs using a semi-automated approach, and radiomics features were extracted using a standard open source software (PyRadiomics). Partial least square (PLS) regression was used as the multivariate machine-learning algorithm. A leave-one-out nested cross-validation was implemented. PLS ß-weights of radiomics features, including the 5% features with the largest ß-weights in magnitude (top 5%), were obtained. The diagnostic performance of the radiomics model was assessed through receiver operating characteristic (ROC) analysis. The Youden's test assessed sensitivity and specificity of the classification. A null hypothesis probability threshold of 5% was chosen (p < 0.05). The predictive model delivered an AUC of 0.868 (Youden's index = 0.68, sensitivity = 93%, specificity 75%, p = 4.2 × 10-7). Of the seven features included in the top 5% features, five were texture-related. A radiomics-based machine learning signature showed the potential to accurately differentiate GGOs due to COVID-19 pneumonia from those due to other acute lung diseases. Most of the discriminant radiomics features were texture-related. This approach may assist clinician to adopt the appropriate management early, while improving the triage of patients.

MRI-based clinical-radiomics model predicts tumor response before treatment in locally advanced rectal cancer.

Neoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the "tumor core" (TC) and the "tumor border" (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based "clinical-radiomic" machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10-5). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.

Prediction of state anxiety by machine learning applied to photoplethysmography data.

BACKGROUND: As the human behavior is influenced by both cognition and emotion, affective computing plays a central role in human-machine interaction. Algorithms for emotions recognition are usually based on behavioral analysis or on physiological measurements (e.g., heart rate, blood pressure). Among these physiological signals, pulse wave propagation in the circulatory tree can be assessed through photoplethysmography (PPG), a non-invasive optical technique. Since pulse wave characteristics are influenced by the cardiovascular status, which is affected by the autonomic nervous activity and hence by the psychophysiological state, PPG might encode information about emotional conditions. The capability of a multivariate data-driven approach to estimate state anxiety (SA) of healthy participants from PPG features acquired on the brachial and radial artery was investigated. METHODS: The machine learning method was based on General Linear Model and supervised learning. PPG was measured employing a custom-made system and SA of the participants was assessed through the State-Trait Anxiety Inventory (STAI-Y) test. RESULTS: A leave-one-out cross-validation framework showed a good correlation between STAI-Y score and the SA predicted by the machine learning algorithm (r = 0.81; p = 1.87∙10-9). The preliminary results suggested that PPG can be a promising tool for emotions recognition, convenient for human-machine interaction applications.

Mismatch between Tissue Partial Oxygen Pressure and Near-Infrared Spectroscopy Neuromonitoring of Tissue Respiration in Acute Brain Trauma: The Rationale for Implementing a Multimodal Monitoring Strategy.

The brain tissue partial oxygen pressure (PbtO2) and near-infrared spectroscopy (NIRS) neuromonitoring are frequently compared in the management of acute moderate and severe traumatic brain injury patients; however, the relationship between their respective output parameters flows from the complex pathogenesis of tissue respiration after brain trauma. NIRS neuromonitoring overcomes certain limitations related to the heterogeneity of the pathology across the brain that cannot be adequately addressed by local-sample invasive neuromonitoring (e.g., PbtO2 neuromonitoring, microdialysis), and it allows clinicians to assess parameters that cannot otherwise be scanned. The anatomical co-registration of an NIRS signal with axial imaging (e.g., computerized tomography scan) enhances the optical signal, which can be changed by the anatomy of the lesions and the significance of the radiological assessment. These arguments led us to conclude that rather than aiming to substitute PbtO2 with tissue saturation, multiple types of NIRS should be included via multimodal systemic- and neuro-monitoring, whose values then are incorporated into biosignatures linked to patient status and prognosis. Discussion on the abnormalities in tissue respiration due to brain trauma and how they affect the PbtO2 and NIRS neuromonitoring is given.

Working Memory Decline in Alzheimer's Disease Is Detected by Complexity Analysis of Multimodal EEG-fNIRS.

Alzheimer's disease (AD) is characterized by working memory (WM) failures that can be assessed at early stages through administering clinical tests. Ecological neuroimaging, such as Electroencephalography (EEG) and functional Near Infrared Spectroscopy (fNIRS), may be employed during these tests to support AD early diagnosis within clinical settings. Multimodal EEG-fNIRS could measure brain activity along with neurovascular coupling (NC) and detect their modifications associated with AD. Data analysis procedures based on signal complexity are suitable to estimate electrical and hemodynamic brain activity or their mutual information (NC) during non-structured experimental paradigms. In this study, sample entropy of whole-head EEG and frontal/prefrontal cortex fNIRS was evaluated to assess brain activity in early AD and healthy controls (HC) during WM tasks (i.e., Rey-Osterrieth complex figure and Raven's progressive matrices). Moreover, conditional entropy between EEG and fNIRS was evaluated as indicative of NC. The findings demonstrated the capability of complexity analysis of multimodal EEG-fNIRS to detect WM decline in AD. Furthermore, a multivariate data-driven analysis, performed on these entropy metrics and based on the General Linear Model, allowed classifying AD and HC with an AUC up to 0.88. EEG-fNIRS may represent a powerful tool for the clinical evaluation of WM decline in early AD.

Electroencephalography-Derived Prognosis of Functional Recovery in Acute Stroke Through Machine Learning Approaches.

Stroke, if not lethal, is a primary cause of disability. Early assessment of markers of recovery can allow personalized interventions; however, it is difficult to deliver indexes in the acute phase able to predict recovery. In this perspective, evaluation of electrical brain activity may provide useful information. A machine learning approach was explored here to predict post-stroke recovery relying on multi-channel electroencephalographic (EEG) recordings of few minutes performed at rest. A data-driven model, based on partial least square (PLS) regression, was trained on 19-channel EEG recordings performed within 10 days after mono-hemispheric stroke in 101 patients. The band-wise (delta: 1-4[Formula: see text]Hz, theta: 4-7[Formula: see text]Hz, alpha: 8-14[Formula: see text]Hz and beta: 15-30[Formula: see text]Hz) EEG effective powers were used as features to predict the recovery at 6 months (based on clinical status evaluated through the NIH Stroke Scale, NIHSS) in an optimized and cross-validated framework. In order to exploit the multimodal contribution to prognosis, the EEG-based prediction of recovery was combined with NIHSS scores in the acute phase and both were fed to a nonlinear support vector regressor (SVR). The prediction performance of EEG was at least as good as that of the acute clinical status scores. A posteriori evaluation of the features exploited by the analysis highlighted a lower delta and higher alpha activity in patients showing a positive outcome, independently of the affected hemisphere. The multimodal approach showed better prediction capabilities compared to the acute NIHSS scores alone ([Formula: see text] versus [Formula: see text], AUC = 0.80 versus AUC = 0.70, [Formula: see text]). The multimodal and multivariate model can be used in acute phase to infer recovery relying on standard EEG recordings of few minutes performed at rest together with clinical assessment, to be exploited for early and personalized therapies. The easiness of performing EEG may allow such an approach to become a standard-of-care and, thanks to the increasing number of labeled samples, further improving the model predictive power.

Dynamic contrast-enhanced near-infrared spectroscopy using indocyanine green on moderate and severe traumatic brain injury: a prospective observational study.

BACKGROUND: The care given to moderate and severe traumatic brain injury (TBI) patients may be hampered by the inability to tailor their treatments according to their neurological status. Contrast-enhanced near-infrared spectroscopy (NIRS) with indocyanine green (ICG) could be a suitable neuromonitoring tool. METHODS: Monitoring the effective attenuation coefficients (EAC), we compared the ICG kinetics between five TBI and five extracranial trauma patients, following a venous-injection of 5 mL of 1 mg/mL ICG, using two commercially available NIRS devices. RESULTS: A significantly slower passage of the dye through the brain of the TBI group was observed in two parameters related to the first ICG inflow into the brain (P=0.04; P=0.01). This is likely related to the reduction of cerebral perfusion following TBI. Significant changes in ICG optical properties minutes after injection (P=0.04) were registered. The acquisition of valid optical data in a clinical environment was challenging. CONCLUSIONS: Future research should analyze abnormalities in the ICG kinetic following brain trauma, test how these values can enhance care in TBI, and adapt the current optical devices to clinical settings. Also, studies on the pattern in changes of ICG optical properties after venous injection can improve the accuracy of the values detected.

Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.