An Immersive and Interactive Platform for Cognitive Assessment and Rehabilitation (bWell): Design and Iterative Development Process.

BACKGROUND: Immersive technologies like virtual reality can enable clinical care that meaningfully aligns with real-world deficits in cognitive functioning. However, options in immersive 3D environments are limited, partly because of the unique challenges presented by the development of a clinical care platform. These challenges include selecting clinically relevant features, enabling tasks that capture the full breadth of deficits, ensuring longevity in a rapidly changing technology landscape, and performing the extensive technical and clinical validation required for digital interventions. Complicating development, is the need to integrate recommendations from domain experts at all stages. OBJECTIVE: The Cognitive Health Technologies team at the National Research Council Canada aims to overcome these challenges with an iterative process for the development of bWell, a cognitive care platform providing multisensory cognitive tasks for adoption by treatment providers. METHODS: The team harnessed the affordances of immersive technologies while taking an interdisciplinary research and developmental approach, obtaining active input from domain experts with iterative deliveries of the platform. The process made use of technology readiness levels, agile software development, and human-centered design to advance four main activities: identification of basic requirements and key differentiators, prototype design and foundational research to implement components, testing and validation in lab settings, and recruitment of external clinical partners. RESULTS: bWell was implemented according to the findings from the design process. The main features of bWell include multimodal (fully, semi, or nonimmersive) and multiplatform (extended reality, mobile, and PC) implementation, configurable exercises that pair standardized assessment with adaptive and gamified variants for therapy, a therapist-facing user interface for task administration and dosing, and automated activity data logging. bWell has been designed to serve as a broadly applicable toolkit, targeting general aspects of cognition that are commonly impacted across many disorders, rather than focusing on 1 disorder or a specific cognitive domain. It comprises 8 exercises targeting different domains: states of attention (Egg), visual working memory (Theater), relaxation (Tent), inhibition and cognitive control (Mole), multitasking (Lab), self-regulation (Butterfly), sustained attention (Stroll), and visual search (Cloud). The prototype was tested and validated with healthy adults in a laboratory environment. In addition, a cognitive care network (5 sites across Canada and 1 in Japan) was established, enabling access to domain expertise and providing iterative input throughout the development process. CONCLUSIONS: Implementing an interdisciplinary and iterative approach considering technology maturity brought important considerations for the development of bWell. Altogether, this harnesses the affordances of immersive technology and design for a broad range of applications, and for use in both cognitive assessment and rehabilitation. The technology has attained a maturity level of prototype implementation with preliminary validation carried out in laboratory settings, with next steps to perform the validation required for its eventual adoption as a clinical tool.

Quantitative nonlinear optical assessment of atherosclerosis progression in rabbits.

Quantification of atherosclerosis has been a challenging task owing to its complex pathology. In this study, we validated a quantitative approach for assessing atherosclerosis progression in a rabbit model using a numerical matrix, optical index for plaque burden, derived directly from the nonlinear optical microscopic images captured on the atherosclerosis-affected blood vessel. A positive correlation between this optical index and the severity of atherosclerotic lesions, represented by the age of the rabbits, was established based on data collected from 21 myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits with age ranging between new-born and 27 months old. The same optical index also accurately identified high-risk locations for atherosclerotic plaque formation along the entire aorta, which was validated by immunohistochemical fluorescence imaging.

Evaluation of texture parameters for the quantitative description of multimodal nonlinear optical images from atherosclerotic rabbit arteries.

The composition and structure of atherosclerotic lesions can be directly related to the risk they pose to the patient. Multimodal nonlinear optical (NLO) microscopy provides a powerful means to visualize the major extracellular components of the plaque that critically determine its structure. Textural features extracted from NLO images were investigated for their utility in providing quantitative descriptors of structural and compositional changes associated with plaque development. Ten texture parameters derived from the image histogram and gray level co-occurrence matrix were examined that highlight specific structural and compositional motifs that distinguish early and late stage plaques. Tonal-texture parameters could be linked to key histological features that characterize vulnerable plaque: the thickness and density of the fibrous cap, size of the atheroma, and the level of inflammation indicated through lipid deposition. Tonal and texture parameters from NLO images provide objective metrics that correspond to structural and biochemical changes that occur within the vessel wall in early and late stage atherosclerosis.

Assessment of local hemodynamics in periodontal inflammation using optical spectroscopy.

BACKGROUND: Among the newly emerging diagnostic approaches for periodontitis, optical spectroscopy is a promising complementary diagnostic tool. The objective of this study is to verify the reproducibility of this method at a geographically distinct location (Suzhou, China) to a broader patient population using similar instrumentation to that in a previous report. METHODS: Using a portable optical near-infrared spectrometer, optical spectra were obtained, processed, and evaluated from healthy (n = 62), gingivitis (n = 98), and periodontitis (n = 47) sites from a total of 51 patients. A modified Beer-Lambert unmixing model that incorporates a non-parametric scattering loss function was used to determine the relative contribution of oxyhemoglobin and deoxyhemoglobin to the overall spectrum. The balance between tissue oxygen delivery and oxygen use in periodontal tissues was then assessed. RESULTS: Tissue oxygenation decreased significantly from healthy sites to sites with gingivitis (P <0.01) and between gingivitis and periodontitis (P = 0.015). This is largely caused by a significant increase in deoxyhemoglobin between normal and gingivitis (P <0.01) and a concomitant decrease in oxyhemoglobin between gingivitis and periodontitis (P = 0.02). CONCLUSION: This study supports previous findings that tissue oxygenation as measured by optical spectroscopy is significantly decreased in periodontitis and that optical spectroscopy can simultaneously determine multiple inflammatory indices related to periodontal disease directly in gingival tissues in vivo.

Multimodal nonlinear optical imaging of atherosclerotic plaque development in myocardial infarction-prone rabbits.

Label-free imaging of bulk arterial tissue is demonstrated using a multimodal nonlinear optical microscope based on a photonic crystal fiber and a single femtosecond oscillator operating at 800 nm. Colocalized imaging of extracellular elastin fibers, fibrillar collagen, and lipid-rich structures within aortic tissue obtained from atherosclerosis-prone myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits is demonstrated through two-photon excited fluorescence, second harmonic generation, and coherent anti-Stokes Raman scattering, respectively. These images are shown to differentiate healthy arterial wall, early atherosclerotic lesions, and advanced plaques. Clear pathological changes are observed in the extracellular matrix of the arterial wall and correlated with progression of atherosclerotic disease as represented by the age of the WHHLMI rabbits.

Differentiating atherosclerotic plaque burden in arterial tissues using femtosecond CARS-based multimodal nonlinear optical imaging.

A femtosecond CARS-based nonlinear optical microscope was used to simultaneously image extracellular structural proteins and lipid-rich structures within intact aortic tissue obtained from myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI). Clear differences in the NLO microscopic images were observed between healthy arterial tissue and regions dominated by atherosclerotic lesions. In the current ex-vivo study, we present a single parameter based on intensity changes derived from multi-channel NLO image to classify plaque burden within the vessel. Using this parameter we were able to differentiate between healthy regions of the vessel and regions with plaque, as well as distinguish plaques relative to the age of the WHHLMI rabbit.

Assessment of skin flaps using optically based methods for measuring blood flow and oxygenation.

The objective of this study was to compare two noninvasive techniques, laser Doppler and optical spectroscopy, for monitoring hemodynamic changes in skin flaps. Animal models for assessing these changes in microvascular free flaps and pedicle flaps were investigated. A 2 x 3-cm free flap model based on the epigastric vein-artery pair and a reversed MacFarlane 3 x 10-cm pedicle flap model were used in this study. Animals were divided into four groups, with groups 1 (n = 6) and 2 (n = 4) undergoing epigastric free flap surgery and groups 3 (n = 3) and 4 (n = 10) undergoing pedicle flap surgery. Groups 1 and 4 served as controls for each of the flap models. Groups 2 and 3 served as ischemia-reperfusion models. Optical spectroscopy provides a measure of hemoglobin oxygen saturation and blood volume, and the laser Doppler method measures blood flow. Optical spectroscopy proved to be consistently more reliable in detecting problems with arterial in flow compared with laser Doppler assessments. When spectroscopy was used in an imaging configuration, oxygen saturation images of the entire flap were generated, thus creating a visual picture of global flap health. In both single-point and imaging modes the technique was sensitive to vessel manipulation, with the immediate post operative images providing an accurate prediction of eventual outcome. This series of skin flap studies suggests a potential role for optical spectroscopy and spectroscopic imaging in the clinical assessment of skin flaps.