Cognitive screening test for rehabilitation using spatiotemporal data extracted from a digital trail making test part-A.

We investigated a newly developed digitized Trail Making Test using an iPad (iTMT) as a brief cognitive function screening test. We found that the iTMT part-A (iTMT-A) can estimate generalized cognitive function in rehabilitation inpatients examined using the Mini-Mental State Examination (MMSE). Forty-two hospitalized participants undergoing rehabilitation (rehab participants), 30 of whom had cerebral infarction/hemorrhage (stroke participants), performed the iTMT five times (first three times: iTMT-A; fourth: paper version of TMT-A; fifth: the inverse version of iTMT-A) and the MMSE once. Each iTMT-A trial's completion time was divided into the move and dwell times. A linear mixed model following post-hoc tests revealed that the completion time of the third and fourth iTMT-A was faster compared to that of the first iTMT-A, suggesting the presence of a learning effect. In the partial least squares (PLS) regression analysis, the coefficient of determination for estimating the MMSE score was increased by using the dwell and move times extracted from the repeated iTMT-A and the availability of TMT-B, even for subjects with low MMSE scores. These findings indicate that the dwell time of iTMT-A may be important for estimating cognitive function. The iTMT-A extracts significant factors temporally and spatially, and by incorporating the learning effect of repeated trials, it may be possible to screen cognitive and physical functions for rehabilitation patients.

Low-intensity pulsed ultrasound improves symptoms in patients with Buerger disease: a double-blinded, randomized, and placebo-controlled study.

Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease.

Correlation Analysis Between Echinocytosis Stages and Blood Viscosity During Oxygenator Perfusion: An In Vitro Study.

The study aimed to investigate the effect of red blood cell (RBC) morphology on oxygenator perfusion, focusing on stages of echinocytosis and their correlation with blood viscosity. A test circuit with an oxygenator and human RBC mixtures was used to induce changes in RBC shape by increasing sodium salicylate concentrations (0, 10, 20, 30, 60, and 120 mmol/L), while hematocrit, blood temperature, and anticoagulation were maintained. Blood viscosity was measured using a continuous blood viscosity monitoring system based on pressure-flow characteristics. Under a scanning electron microscope, the percentages of discocytes, echinocytes I-III, spheroechinocytes, and spherocytes were determined from approximately 400 cells per RBC sample. Early echinocytes, mainly discocytes and echinocytes I and II in the range of 0-30 mmol/L were predominant, resulting in a gradual increase in blood viscosity from 1.78 ± 0.12 to 1.94 ± 0.12 mPa s. At 60 mmol/L spherocytes emerged, and at 120 mmol/L, spheroidal RBCs constituted 50% of the population, and blood viscosity sharply rose to 2.50 ± 0.15 mPa s, indicating a 40% overall increase. In conclusion, the presence of spherocytes significantly increases blood viscosity, which may affect oxygenator perfusion.

The Number of Microbubbles Generated During Cardiopulmonary Bypass Can Be Estimated Using Machine Learning From Suction Flow Rate, Venous Reservoir Level, Perfusion Flow Rate, Hematocrit Level, and Blood Temperature.

GOAL: Microbubbles (MBs) are known to occur within the circuits of cardiopulmonary bypass (CPB) systems, and higher-order dysfunction after cardiac surgery may be caused by MBs as well as atheroma dispersal associated with cannula insertion. As complete MB elimination is not possible, monitoring MB count rates is critical. We propose an online detection system with a neural network-based model to estimate MB count rate using five parameters: suction flow rate, venous reservoir level, perfusion flow rate, hematocrit level, and blood temperature. METHODS: Perfusion experiments were performed using an actual CPB circuit, and MB count rates were measured using the five varying parameters. RESULTS: Bland-Altman analysis indicated a high estimation accuracy (R2 > 0.95, p < 0.001) with no significant systematic error. In clinical practice, although the inclusion of clinical procedures slightly decreased the estimation accuracy, a high coefficient of determination for 30 clinical cases (R2 = 0.8576) was achieved between measured and estimated MB count rates. CONCLUSIONS: Our results highlight the potential of this system to improve patient outcomes and reduce MB-associated complication risk.

Neuroimaging-based evidence for sympathetic correlation between brain activity and peripheral vasomotion during pain anticipation.

Anticipation of pain engenders anxiety and fear, potentially shaping pain perception and governing bodily responses such as peripheral vasomotion through the sympathetic nervous system (SNS). Sympathetic innervation of vascular tone during pain perception has been quantified using a peripheral arterial stiffness index; however, its innervation role during pain anticipation remains unclear. This paper reports on a neuroimaging-based study designed to investigate the responsivity and attribution of the index at different levels of anticipatory anxiety and pain perception. The index was measured in a functional magnetic resonance imaging experiment that randomly combined three visual anticipation cues and painful stimuli of two intensities. The peripheral and cerebral responses to pain anticipation and perception were quantified to corroborate bodily responsivity, and their temporal correlation was also assessed to identify the response attribution of the index. Contrasting with the high responsivity across levels of pain sensation, a low responsivity of the index across levels of anticipatory anxiety revealed its specificity across pain experiences. Discrepancies between the effects of perception and anticipation were validated across regions and levels of brain activity, providing a brain basis for peripheral response specificity. The index was also characterized by a 1-s lag in both anticipation and perception of pain, implying top-down innervation of the periphery. Our findings suggest that the SNS responds to pain in an emotion-specific and sensation-unbiased manner, thus enabling an early assessment of individual pain perception using this index. This study integrates peripheral and cerebral hemodynamic responses toward a comprehensive understanding of bodily responses to pain.

Sound-based cough peak flow estimation in patients with neuromuscular disorders.

INTRODUCTION/AIMS: Cough impairment is common in individuals with neuromuscular disorders and is associated with respiratory infections and shorter survival. Cough strength is assessed by measuring cough peak flow (CPF) using a flow meter, but this method requires a complex device setup and trained staff. The aim of the study is to evaluate the reliability of a smartphone app to estimate CPF based on cough sounds in a cohort of individuals with neuromuscular disorders. METHODS: Individuals with neuromuscular disorders underwent CPF measurement with a flow meter and a smartphone app. A CPF <270 L/min was considered abnormal. RESULTS: Of the 50 patients studied, 26 had amyotrophic lateral sclerosis (52%), 15 had hereditary myopathies (30%), and 9 had myasthenia gravis (18%). The intraclass correlation coefficient (ICC) between the CPF measured with a flow meter and CPF estimated with cough sounds was 0.774 (p < .001) even if the patients had orofacial weakness (ICC = 0.806, p < .001). The smartphone app had 94.4% sensitivity and 100% specificity to detect patients with CPF of less than 270 L/min. DISCUSSION: Our findings suggest that sounds measured with a smartphone app provide a reliable estimate of CPF in patients with neuromuscular disorders, even in the presence of with orofacial weakness. This may be a convenient way to monitor respiratory involvement in patients with neuromuscular disorders, but larger studies of more diverse patient cohorts are needed.

Repetitive pain experiences modulate feedforward control of hemodynamics and modification by nitrous oxide/oxygen inhalation in humans.

Background: Repetitive experiences of certain stresses evoke feedforward cardiovascular responses via central command (CC)--central signals from the higher brain. However, it is unclear whether the anticipatory cardiovascular responses before pain stimulation occur after repetitive pain experiences and how nitrous oxide/oxygen inhalation (N2O), a sedative widely used in dentistry, affects the responses. We tested the hypothesis that the repetitive cold pressor test (CPT) alters the anticipatory cardiovascular responses, which are attenuated by N2O. Materials and methods: Beat-to-beat systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and finger arterial stiffness (ß-stiffness) were measured during the 5-min rest, 30-s countdown (CD) before CPT, 2-min CPT, and 3-min recovery (CPT[1st]) in 15 young adults [age, 28 ± 4 years]. The same protocols were repeated randomly with the second CPT (CPT + CC) or placebo test (PLCB + CC). Results: SBP and DBP increased from baseline in CPT[1st] and CPT + CC under room air (RA) and 40 % N2O, while SBP was lower under N2O than under RA in CPT[1st]. HR in CPT[1st] was lower under N2O than under RA. The change (Δ) in HR was smaller during CPT[1st] than during CPT + CC under N2O, and a similar trend was observed under RA. ΔSBP by CD was lower under N2O than under RA in CPT[1st] but not in CPT + CC. HR increased with CD in CPT + CC but not in CPT[1st] under both RA and N2O. ß-stiffness increased by CD regardless of the pain experience, while it was lower under N2O. Conclusion: Repetitive pain experiences induce a feedforward HR increase. 40 % N2O decreases vascular stiffness, which may attenuate the anticipatory pressor response only when the feedforward HR increase does not exist.

Prediction of blood pressure changes during surgical incision using the minimum evoked current of vascular stiffness value under sevoflurane anesthesia.

Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = - 0.735 (P < 0.01), similar to that in a previous study with propofol (R = - 0.723). Thus, a high correlation was observed. The slope of the linear regression equation was - 0.27, similar to that obtained in the study on propofol (- 0.28). These results suggest that, as with propofol anesthesia, MECK can be used as a predictive index for ROCBP under 0.7 MAC sevoflurane anesthesia.Clinical trial registration: Registry, University hospital Medical Information Network; registration number, UMIN000047425; principal investigator's name, Noboru Saeki; date of registration, April 8, 2022.

Vertical dynamic visual acuity is significantly lower than horizontal dynamic visual acuity.

Dynamic visual acuity (DVA) is crucial for the perception of moving objects. While traditional DVA assessment tools predominantly focus on horizontal movements, the evaluation of vertical DVA remains unstandardized. Consequently, the disparities between vertical and horizontal DVAs are yet to be thoroughly investigated. Therefore, we designed a system capable of conducting multidirectional DVA tests and eye movement measurements. During the experiments, the participants identified the gap direction of the Landolt-C ring moving either horizontally or vertically. The speed of movement decelerated from its maximum as a high-speed infrared camera captured the pupil movements of the left eye at 500 fps. We conducted tests on 15 healthy university students (aged [Formula: see text] years) and measured vertical and horizontal DVAs five times each. DVA was deduced from the Landolt-C ring speed with accurate gap direction responses, and eye movement was assessed based on the total gaze movement distance. The results revealed superior DVA and eye movement in the horizontal direction compared with the vertical direction ([Formula: see text]). This highlights the anisotropic characteristics of DVA and eye movement. The proposed system has the potential for multidirectional dynamic vision evaluation and training in clinical scenarios.

Motor-cognitive functions required for driving in post-stroke individuals identified via machine-learning analysis.

BACKGROUND: People who were previously hospitalised with stroke may have difficulty operating a motor vehicle, and their driving aptitude needs to be evaluated to prevent traffic accidents in today's car-based society. Although the association between motor-cognitive functions and driving aptitude has been extensively studied, motor-cognitive functions required for driving have not been elucidated. METHODS: In this paper, we propose a machine-learning algorithm that introduces sparse regularization to automatically select driving aptitude-related indices from 65 input indices obtained from 10 tests of motor-cognitive function conducted on 55 participants with stroke. Indices related to driving aptitude and their required tests can be identified based on the output probability of the presence or absence of driving aptitude to provide evidence for identifying subjects who must undergo the on-road driving test. We also analyzed the importance of the indices of motor-cognitive function tests in evaluating driving aptitude to further clarify the relationship between motor-cognitive function and driving aptitude. RESULTS: The experimental results showed that the proposed method achieved predictive evaluation of the presence or absence of driving aptitude with high accuracy (area under curve 0.946) and identified a group of indices of motor-cognitive function tests that are strongly related to driving aptitude. CONCLUSIONS: The proposed method is able to effectively and accurately unravel driving-related motor-cognitive functions from a panoply of test results, allowing for autonomous evaluation of driving aptitude in post-stroke individuals. This has the potential to reduce the number of screening tests required and the corresponding clinical workload, further improving personal and public safety and the quality of life of individuals with stroke.

Spatiotemporal patterns of spontaneous movement in neonates are significantly linked to risk of autism spectrum disorders at 18 months old.

Infants make spontaneous movements from the prenatal period. Several studies indicate that an atypical pattern of body motion during infancy could be utilized as an early biomarker of autism spectrum disorders (ASD). However, to date, little is known about whether the body motion pattern in neonates is associated with ASD risk. The present study sought to clarify this point by examining, in a longitudinal design, the link between features of spontaneous movement at about two days after birth and ASD risk evaluated using the Modified Checklist for Autism in Toddlers by their caregivers at 18 months old. The body movement features were quantified by a recently developed markerless system of infant body motion analysis. Logistic regression analysis revealed that ASD risk at 18 months old is associated with the pattern of spontaneous movement at the neonatal stage. Further, logistic regression based on body movement features during sleep shows better performance in classifying high- and low-risk infants than during the awake state. These findings raise the possibility that early signs of ASD risk may emerge at a developmental stage far earlier than previously thought.

Simultaneous Control of Venous Reservoir Level and Arterial Flow Rate in Cardiopulmonary Bypass With a Centrifugal Pump.

Cardiopulmonary bypass (CPB) is an indispensable technique in cardiac surgery, providing the ability to temporarily replace cardiopulmonary function and create a bloodless surgical field. Traditionally, the operation of CPB systems has depended on the expertise and experience of skilled perfusionists. In particular, simultaneously controlling the arterial and venous occluders is difficult because the blood flow rate and reservoir level both change, and failure may put the patient's life at risk. This study proposes an automatic control system with a two-degree-of-freedom model matching controller nested in an I-PD feedback controller to simultaneously regulate the blood flow rate and reservoir level. CPB operations were performed using glycerin and bovine blood as perfusate to simulate flow-up and flow-down phases. The results confirmed that the arterial blood flow rate followed the manually adjusted target venous blood flow rate, with an error of less than 5.32%, and the reservoir level was maintained, with an error of less than 3.44% from the target reservoir level. Then, we assessed the robustness of the control system against disturbances caused by venting/suction of blood. The resulting flow rate error was 5.95%, and the reservoir level error 2.02%. The accuracy of the proposed system is clinically satisfactory and within the allowable error range of 10% or less, meeting the standards set for perfusionists. Moreover, because of the system's simple configuration, consisting of a camera and notebook PC, the system can easily be integrated with general CPB equipment. This practical design enables seamless adoption in clinical settings. With these advancements, the proposed system represents a significant step towards the automation of CPB.

Cough sound-based estimation of vital capacity via cough peak flow using artificial neural network analysis.

This study presents a novel approach for estimating vital capacity using cough sounds and proposes a neural network-based model that utilizes the reference vital capacity computed using the lambda-mu-sigma method, a conventional approach, and the cough peak flow computed based on the cough sound pressure level as inputs. Additionally, a simplified cough sound input model is developed, with the cough sound pressure level used directly as the input instead of the computed cough peak flow. A total of 56 samples of cough sounds and vital capacities were collected from 31 young and 25 elderly participants. Model performance was evaluated using squared errors, and statistical tests including the Friedman and Holm tests were conducted to compare the squared errors of the different models. The proposed model achieved a significantly smaller squared error (0.052 L2, p < 0.001) than the other models. Subsequently, the proposed model and the cough sound-based estimation model were used to detect whether a participant's vital capacity was lower than the typical lower limit. The proposed model demonstrated a significantly higher area under the receiver operating characteristic curve (0.831, p < 0.001) than the other models. These results highlight the effectiveness of the proposed model for screening decreased vital capacity.

Noninvasive characterization of peripheral sympathetic activation across sensory stimuli using a peripheral arterial stiffness index.

Introduction: The peripheral arterial stiffness index has been proposed and validated as a noninvasive measure quantifying stimulus intensity based on amplitude changes induced by sympathetic innervation of vascular tone. However, its temporal response characteristics remain unclear, thus hindering continuous and accurate monitoring of the dynamic process of sympathetic activation. This paper presents a study aimed at modeling the transient response of the index across sensory stimuli to characterize the corresponding peripheral sympathetic activation. Methods: The index was measured using a continuous arterial pressure monitor and a pulse oximeter during experiments with local pain and local cooling stimuli designed to elicit different patterns of sympathetic activation. The corresponding response of the index was modeled to clarify its transient response characteristics across stimuli. Results: The constructed transfer function accurately depicted the transient response of the index to local pain and local cooling stimuli (Fit percentage: 78.4% ± 11.00% and 79.92% ± 8.79%). Differences in dead time (1.17 ± 0.67 and 0.99 ± 0.56 s, p = 0.082), peak time (2.89 ± 0.81 and 2.64 ± 0.68 s, p = 0.006), and rise time (1.81 ± 0.50 and 1.65 ± 0.48 s, p = 0.020) revealed different response patterns of the index across stimuli. The index also accurately characterized similar vasomotor velocities at different normalized peak amplitudes (0.19 ± 0.16 and 0.16 ± 0.19 a.u., p = 0.007). Discussion: Our findings flesh out the characterization of peripheral arterial stiffness index responses to different sensory stimuli and demonstrate its validity in characterizing peripheral sympathetic activation. This study valorizes a noninvasive method to characterize peripheral sympathetic activation, with the potential to use this index to continuously and accurately track sympathetic activators.

Prediction of autistic tendencies at 18 months of age via markerless video analysis of spontaneous body movements in 4-month-old infants.

Early intervention is now considered the core treatment strategy for autism spectrum disorders (ASD). Thus, it is of significant clinical importance to establish a screening tool for the early detection of ASD in infants. To achieve this goal, in a longitudinal design, we analyzed spontaneous bodily movements of 4-month-old infants from general population and assessed their ASD-like behaviors at 18 months of age. A total of 26 movement features were calculated from video-recorded bodily movements of infants at 4 months of age. Their risk of ASD was assessed at 18 months of age with the Modified Checklist for Autism in Toddlerhood, a widely used screening questionnaire. Infants at high risk for ASD at 18 months of age exhibited less rhythmic and weaker bodily movement patterns at 4 months of age than low-risk infants. When the observed bodily movement patterns were submitted to a machine learning-based analysis, linear and non-linear classifiers successfully predicted ASD-like behavior at 18 months of age based on the bodily movement patterns at 4 months of age, at the level acceptable for practical use. This study analyzed the relationship between spontaneous bodily movements at 4 months of age and the ASD risk at 18 months of age. Experimental results suggested the utility of the proposed method for the early screening of infants at risk for ASD. We revealed that the signs of ASD risk could be detected as early as 4 months after birth, by focusing on the infant's spontaneous bodily movements.

Pharmacological effects of caffeine on ventilation in adult zebrafish under free-swimming conditions.

The zebrafish is widely used as a model in biological studies. In particular, the heart rate and cortisol levels of zebrafish are commonly measured to elucidate the pharmacological effects of chemical substances. Meanwhile, although ventilation is also an important physiological index reflecting emotion-like states, few studies have evaluated the effects of chemicals on ventilation in adult zebrafish. In this study, we assessed whether it is possible to evaluate the pharmacological effects elicited by caffeine in adult zebrafish under free-swimming conditions. We measured the ventilation in adult zebrafish exposed to multiple concentrations of caffeine under restraint and free-swimming conditions and evaluated the pharmacological effects of caffeine using linear mixed model analysis. In addition, results of electrocardiogram analysis and swimming speeds were compared with those in previous reports to ensure that an appropriate dose of caffeine was administered. Under restraint conditions, caffeine significantly decreased heart rate and increased ventilation in a concentration-dependent manner. Under free-swimming conditions, the ventilation rate significantly increased with increasing caffeine concentration. These results indicate that the pharmacological effects elicited by chemicals on ventilation can be evaluated in free-swimming zebrafish.

Neural Network-based Estimation of Microbubbles Generated in Cardiopulmonary Bypass Circuit: A Clinical Application Study.

The cardiopulmonary bypass system used in cardiac surgery can generate microbubbles (MBs) that may cause complications, such as neurocognitive dysfunction, when delivered into the blood vessel. Estimating the number of MBs generated, thus, is necessary to enable the surgeons to deal with it. To this end, we previously proposed a neural network-based model for estimating the number of MBs from four factors measurable from the cardiopulmonary bypass system: suction flow rate, venous reservoir level, blood viscosity, and perfusion flow rate. However, the model has not been adapted to the data collected from actual surgery cases. In this study, the accuracy of MBs estimated by the proposed model was examined in four clinical cases. The results showed that the coefficient of determination between estimated MBs and the measured MBs throughout the surgeries was R2=0.558 (p<0.001). We found that the surgical treatments, such as administration of drugs, fluids and blood transfusions, increased the number of measured MBs. The coefficient of determination increased to R2= 0.8762 (p<0.001) by excluding the duration of these treatments. This result indicates that the model can estimate the number of MBs with high accuracy under the clinical environment.

Projection of Damaged Visual and Language Regions on Low Trail Making Test Part-B Performance in Stroke Patients.

Background: The Trail Making Test Part-B (TMT-B) is an attention functional test to investigate cognitive dysfunction. It requires the ability to recognize not only numbers but also letters. We analyzed the relationship between brain lesions in stroke patients and their TMT-B performance. Methods: From the TMT-B, two parameters (score and completion time) were obtained. The subjects were classified into several relevant groups by their scores and completion times through a data-driven analysis (k-means clustering). The score-classified groups were characterized by low (≤10), moderate (10 < score < 25), and high (25) scores. In terms of the completion time, the subjects were classified into four groups. The lesion degree in the brain was calculated for each of the 116 regions classified by automated anatomical labeling (AAL). For each group, brain sites with a significant difference (corrected p < 0.1) between each of the 116 regions were determined by a Wilcoxon Rank-Sum significant difference test. Results: Lesions at the cuneus and the superior occipital gyrus, which are mostly involved in visual processing, were significant (corrected p < 0.1) in the low-score group. Furthermore, the moderate-score group showed more-severe lesion degrees (corrected p < 0.05) in the regions responsible for the linguistic functions, such as the superior temporal gyrus and the supramarginal gyrus. As for the completion times, lesions in the calcarine, the cuneus, and related regions were significant (corrected p < 0.1) in the fastest group as compared to the slowest group. These regions are also involved in visual processing. Conclusion: The TMT-B results revealed that the subjects in the low-score group or the slowest- group mainly had damage in the visual area, whereas the subjects in the moderate-score group mainly had damage in the language area. These results suggest the potential utility of TMT-B performance in the lesion site.

Artificially-reconstructed brain images with stroke lesions from non-imaging data: modeling in categorized patients based on lesion occurrence and sparsity.

Brain imaging is necessary for understanding disease symptoms, including stroke. However, frequent imaging procedures encounter practical limitations. Estimating the brain information (e.g., lesions) without imaging sessions is beneficial for this scenario. Prospective estimating variables are non-imaging data collected from standard tests. Therefore, the current study aims to examine the variable feasibility for modelling lesion locations. Heterogeneous variables were employed in the multivariate logistic regression. Furthermore, patients were categorized (i.e., unsupervised clustering through k-means method) by the charasteristics of lesion occurrence (i.e., ratio between the lesioned and total regions) and sparsity (i.e., density measure of lesion occurrences across regions). Considering those charasteristics in models improved estimation performances. Lesions (116 regions in Automated Anatomical Labeling) were adequately predicted (sensitivity: 80.0-87.5% in median). We confirmed that the usability of models was extendable to different resolution levels in the brain region of interest (e.g., lobes, hemispheres). Patients' charateristics (i.e., occurrence and sparsity) might also be explained by the non-imaging data as well. Advantages of the current approach can be experienced by any patients (i.e., with or without imaging sessions) in any clinical facilities (i.e., with or without imaging instrumentation).