Co-design of a Virtual Reality Cognitive Remediation Program for Depression (bWell-D) With Patient End Users and Clinicians: Qualitative Interview Study Among Patients and Clinicians.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of global disability; however, the existing treatments do not always address cognitive dysfunction-a core feature of MDD. Immersive virtual reality (VR) has emerged as a promising modality to enhance the real-world effectiveness of cognitive remediation. OBJECTIVE: This study aimed to develop the first prototype VR cognitive remediation program for MDD ("bWell-D"). This study gathered qualitative data from end users early in the design process to enhance its efficacy and feasibility in clinical settings. METHODS: Semistructured end-user interviews were conducted remotely (n=15 patients and n=12 clinicians), assessing the participants' perceptions and goals for a VR cognitive remediation program. Video samples of bWell-D were also shared to obtain feedback regarding the program. The interviews were transcribed, coded, and analyzed via thematic analysis. RESULTS: End users showed an optimistic outlook toward VR as a treatment modality, and perceived it as a novel approach with the potential of having multiple applications. The participants expressed a need for an engaging VR treatment that included realistic and multisensorial settings and activities, as well as customizable features. Some skepticism regarding its effectiveness was also reported, especially when the real-world applications of the practiced skills were not made explicit, as well as some concerns regarding equipment accessibility. A home-based or hybrid (ie, home and clinic) treatment modality was preferred. CONCLUSIONS: Patients and clinicians considered bWell-D interesting, acceptable, and potentially feasible, and provided suggestions to enhance its real-world applicability. The inclusion of end-user feedback is encouraged when developing future VR programs for clinical purposes.

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.

Fractal dimension and directional analysis of elastic and collagen fiber arrangement in unsectioned arterial tissues affected by atherosclerosis and aging.

Structural proteins like collagen and elastin are major constituents of the extracellular matrix (ECM). ECM degradation and remodeling in diseases significantly impact the microorganization of these structural proteins. Therefore, tracking the changes of collagen and elastin fiber morphological features within ECM impacted by disease progression could provide valuable insight into pathological processes such as tissue fibrosis and atherosclerosis. Benefiting from its intrinsic high-resolution imaging power and superior biochemical specificity, nonlinear optical microscopy (NLOM) is capable of providing information critical to the understanding of ECM remodeling. In this study, alterations of structural fibrillar proteins such as collagen and elastin in arteries excised from atherosclerotic rabbits were assessed by the combination of NLOM images and textural analysis methods such as fractal dimension (FD) and directional analysis (DA). FD and DA were tested for their performance in tracking the changes of extracellular elastin and fibrillar collagen remodeling resulting from atherosclerosis progression/aging. Although other methods of image analysis to study the organization of elastin and collagen structures have been reported, the simplified calculations of FD and DA presented in this work prove that they are viable strategies for extracting and analyzing fiber-related morphology from disease-impacted tissues. Furthermore, this study also demonstrates the potential utility of FD and DA in studying ECM remodeling caused by other pathological processes such as respiratory diseases, several skin conditions, or even cancer. NEW & NOTEWORTHY Textural analyses such as fractal dimension (FD) and directional analysis (DA) are straightforward and computationally viable strategies to extract fiber-related morphological data from optical images. Therefore, objective, quantitative, and automated characterization of protein fiber morphology in extracellular matrix can be realized by using these methods in combination with digital imaging techniques such as nonlinear optical microscopy (NLOM), a highly effective visualization tool for fibrillar collagen and elastic network. Combining FD and DA with NLOM is an innovative approach to track alterations of structural fibrillar proteins. The results illustrated in this study not only prove the effectiveness of FD and DA methods in extracellular protein characterization but also demonstrate their potential value in clinical and basic biomedical research where protein microstructure characterization is critical.

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.

Collagen morphology and texture analysis: from statistics to classification.

In this study we present an image analysis methodology capable of quantifying morphological changes in tissue collagen fibril organization caused by pathological conditions. Texture analysis based on first-order statistics (FOS) and second-order statistics such as gray level co-occurrence matrix (GLCM) was explored to extract second-harmonic generation (SHG) image features that are associated with the structural and biochemical changes of tissue collagen networks. Based on these extracted quantitative parameters, multi-group classification of SHG images was performed. With combined FOS and GLCM texture values, we achieved reliable classification of SHG collagen images acquired from atherosclerosis arteries with >90% accuracy, sensitivity and specificity. The proposed methodology can be applied to a wide range of conditions involving collagen re-modeling, such as in skin disorders, different types of fibrosis and muscular-skeletal diseases affecting ligaments and cartilage.

A comparison of methods using optical coherence tomography to detect demineralized regions in teeth.

Optical coherence tomography (OCT) is a three- dimensional optical imaging technique that can be used to identify areas of early caries formation in dental enamel. The OCT signal at 850 nm back-reflected from sound enamel is attenuated stronger than the signal back-reflected from demineralized regions. To quantify this observation, the OCT signal as a function of depth into the enamel (also known as the A-scan intensity), the histogram of the A-scan intensities and three summary parameters derived from the A-scan are defined and their diagnostic potential compared. A total of 754 OCT A-scans were analyzed. The three summary parameters derived from the A-scans, the OCT attenuation coefficient as well as the mean and standard deviation of the lognormal fit to the histogram of the A-scan ensemble show statistically significant differences (p < 0.01) when comparing parameters from sound enamel and caries. Furthermore, these parameters only show a modest correlation. Based on the area under the curve (AUC) of the receiver operating characteristics (ROC) plot, the OCT attenuation coefficient shows higher discriminatory capacity (AUC = 0.98) compared to the parameters derived from the lognormal fit to the histogram of the A-scan. However, direct analysis of the A-scans or the histogram of A-scan intensities using linear support vector machine classification shows diagnostic discrimination (AUC = 0.96) comparable to that achieved using the attenuation coefficient. These findings suggest that either direct analysis of the A-scan, its intensity histogram or the attenuation coefficient derived from the descending slope of the OCT A-scan have high capacity to discriminate between regions of caries and sound enamel.

Intravascular optical coherence tomography on a beating heart model.

The advantages and limitations of using a beating heart model in the development of intravascular optical coherence tomography are discussed. The model fills the gap between bench experiments, performed on phantoms and excised arteries, and whole animal in-vivo preparations. The beating heart model is stable for many hours, allowing for extended measurement times and multiple imaging sessions under in-vivo conditions without the complications of maintaining whole-animal preparation. The perfusate supplying the heart with nutrients can be switched between light scattering blood to a nonscattering perfusate to allow the optical system to be optimized without the need of an efficient blood displacement strategy. Direct access to the coronary vessels means that there is no need for x-ray fluoroscopic guidance of the catheter to the heart, as is the case in whole animal preparation. The model proves to be a valuable asset in the development of our intravascular optical coherence tomography technology.

Determining the effect of calculus, hypocalcification, and stain on using optical coherence tomography and polarized Raman spectroscopy for detecting white spot lesions.

Optical coherence tomography (OCT) and polarized Raman spectroscopy (PRS) have been shown as useful methods for distinguishing sound enamel from carious lesions ex vivo. However, factors in the oral environment such as calculus, hypocalcification, and stain could lead to false-positive results. OCT and PRS were used to investigate extracted human teeth clinically examined for sound enamel, white spot lesion (WSL), calculus, hypocalcification, and stain to determine whether these factors would confound WSL detection with these optical methods. Results indicate that OCT allowed differentiating caries from sound enamel, hypocalcification, and stain, with calculus deposits recognizable on OCT images. ANOVA and post-hoc unequal N HSD analyses to compare the mean Raman depolarization ratios from the various groups showed that the mean values were statistically significant at P < .05, except for several comparison pairs. With the current PRS analysis method, the mean depolarization ratios of stained enamel and caries are not significantly different due to the sloping background in the stained enamel spectra. Overall, calculus and hypocalcification are not confounding factors affecting WSL detection using OCT and PRS. Stain does not influence WSL detection with OCT. Improved PRS analysis methods are needed to differentiate carious from stained enamel.

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.

An update on novel non-invasive approaches for periodontal diagnosis.

For decades there has been an ongoing search for clinically acceptable methods for the accurate, non-invasive diagnosis and prognosis of periodontitis. There are several well-known inherent drawbacks with current clinical procedures. The purpose of this review is to summarize some of the newly emerging diagnostic approaches, namely, infrared spectroscopy, optical coherence tomography (OCT), and ultrasound. The history and attractive features of these new approaches are briefly illustrated, and the interesting and significant inventions related to dental applications are discussed. The particularly attractive aspects for the dental community are that some of these methods are totally non-invasive, do not impose any discomforts to the patients during the procedure, and require no tissue to be extracted. For instance, multiple inflammatory indices withdrawn from near infrared spectra have the potential to identify early signs of inflammation leading to tissue breakdown. Morphologically, some other non-invasive imaging modalities, such as OCT and ultrasound, could be employed to accurately measure probing depths and assess the status of periodontal attachment, the front-line of disease progression. Given that these methods reflect a completely different assessment of periodontal inflammation, if clinically validated, these methods could either replace traditional clinical examinations for the diagnosis of periodontitis or at least serve as attractive complementary diagnostic tools. However, the potential of these techniques should be interpreted more cautiously given the multifactorial character of periodontal disease. In addition to these novel tools in the field of periodontal inflammatory diseases, other alternative modalities like microbiologic and genetic approaches are only briefly mentioned in this review because they have been thoroughly discussed in other comprehensive reviews.

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.

Speckle reduction and lesion segmentation of OCT tooth images for early caries detection.

The significance of identifying early non-cavitated carious lesions and monitoring the lesion extent has led to increasing prospects for prevention, early diagnosis, and implementation of conservative treatments. This paper emphasizes the importance of speckle reduction and possible lesion segmentation options of optical coherence tomography (OCT) images prior to caries detection. First, a comparison of popular speckle reduction filters is presented. These filtering algorithms were evaluated to measure the ability of different methods for reducing background noise from raw images. Both qualitative and quantitative results (signal-to-noise ratio, contrast-to-noise ratio) are reported. Image segmentation is then applied to multiple tooth images. With proper thresholding, high intensity response regions are outlined with the possibility of assessing caries and monitoring its regression. Our results show that a rotating kernel transformation (RKT) filter with 9x9 kernel size provides a good compromise between noise reduction yet preserving the pathological features of interest as required for subsequent feature segmentation analyses.

Assessment of early demineralization in teeth using the signal attenuation in optical coherence tomography images.

Optical coherence tomography imaging is used to improve the detection of incipient carious lesions in dental enamel. Measurements of signal attenuation in images acquired with an 850-nm light source were performed on 21 extracted molars from eight human volunteers. Stronger attenuation was observed for the optical coherence tomography (OCT) signal in healthy enamel than in carious lesions. The measured attenuation coefficients from the two groups form distinct statistical populations. The coefficients obtained from sound enamel fall within the range of 0.70 to 2.14 mm(-1) with a mean value of 1.35 mm(-1), while those in carious regions range from 0.47 to 1.88 mm(-1), with a mean value of 0.77 mm(-1). Three values are selected as the lower threshold for signal attenuation in sound enamel: 0.99, 0.94, and 0.88 mm(-1). These thresholds were selected to provide detection of sound enamel with fixed specificities of 90%, 95%, and 97.5%, respectively. The corresponding sensitivities for the detection of carious lesions are 92.8%, 90.4%, and 87%, respectively, for the sample population used in this study. These findings suggest that attenuation of OCT signal at 850 nm could be an indicator of tooth demineralization and could be used as a marker for early caries detection.

Early dental caries detection using a fibre-optic coupled polarization-resolved Raman spectroscopic system.

A new fibre-optic coupled polarization-resolved Raman spectroscopic system was developed for simultaneous collection of orthogonally polarized Raman spectra in a single measurement. An application of detecting incipient dental caries based on changes observed in Raman polarization anisotropy was also demonstrated using the developed fibre-optic Raman spectroscopic system. The predicted reduction of polarization anisotropy in the Raman spectra of caries lesions was observed and the results were consistent with those reported previously with Raman microspectroscopy. The capability of simultaneous collection of parallel- and cross-polarized Raman spectra of tooth enamel in a single measurement and the improved laser excitation delivery through fibre-optics demonstrated in this new design illustrates its future clinical potential.

Shedding new light on early caries detection.

Dental caries continues to be a common chronic disease among various population groups. Patient care can be improved with detection at the earliest stage. However, current techniques do not have sufficient sensitivity and specificity. We discuss 2 new methods - optical coherence tomography (OCT) and polarized Raman spectroscopy (PRS) - that are potentially useful for early caries detection and monitoring. OCT produces morphologic depth images of near-surface tissue structures with a resolution that is an order of magnitude greater than ultrasound imaging. Based on measurement of back-scattered near infrared light, OCT shows that sound enamel causes high-intensity back-scattering at the tooth surface that decreases rapidly with depth. In contrast, incipient lesions cause higher light back-scattering at the tooth surface and subsurface scattering indicative of porosity caused by demineralization. The scatter region within the enamel correlates well with the classical triangular shape of subsurface lesions observed in histologic sections. OCT imaging not only allows identification of incipient lesions, but also provides information on surface integrity and lesion depth. PRS furnishes biochemical information about the tooth"s composition, mineral content and crystallinity. The depolarization ratio derived from the dominant phosphate peak of hydroxyapatite in sound teeth is consistently lower than that from incipient caries. This difference is attributed to the change in enamel crystallite morphology or orientation that occurs with acid demineralization. Thus, PRS can be used to confirm suspect lesions determined by OCT and rule out false-positive signals from non-carious anomalies. The combination of OCT and PRS provides a new detection method with high sensitivity and specificity that will improve caries management and patient care. Future studies are aimed at developing intraoral probes to validate the findings in vivo.

Precision of Raman depolarization and optical attenuation measurements of sound tooth enamel.

The demineralization of enamel that is associated with early caries formation affects the optical properties of the enamel. Polarized Raman spectroscopy and optical coherence tomography have been used to detect these changes and potentially offer a means to detect and monitor early caries development. The total optical attenuation coefficient as measured by optical coherence tomography and the polarization anisotropy of the Raman peak arising from the symmetric nu(1) vibration of PO4(3-) at approximately 959 cm(-1) have been demonstrated as being sensitive markers of early caries. This ex vivo study on extracted human teeth demonstrates that these measurements can be made with reasonable precision with concomitantly good repeatability and reproducibility in sound enamel. Such reliability is crucial for these techniques to have a practical clinical value.

Detection of early dental caries using polarized Raman spectroscopy.

A new technique based on polarized Raman spectroscopy is demonstrated for detecting early dental caries on extracted human teeth. Sound tooth enamel exhibited strong Raman polarization anisotropy whereas early caries consistently showed a lower degree of Raman polarization anisotropy. In particular, for sound enamel, the Raman peak arising from the symmetric nu1 vibration of PO(4) (3-) at 959 cm(-1) is strongly polarized. This is in contrast to the spectra of carious lesions that displayed weaker polarization dependence at 959 cm(-1). Such difference in the degree of Raman polarization anisotropy allows for discrimination between early dental caries and sound enamel.

Ex vivo detection and characterization of early dental caries by optical coherence tomography and Raman spectroscopy.

Early dental caries detection will facilitate implementation of nonsurgical methods for arresting caries progression and promoting tooth remineralization. We present a method that combines optical coherence tomography (OCT) and Raman spectroscopy to provide morphological information and biochemical specificity for detecting and characterizing incipient carious lesions found in extracted human teeth. OCT imaging of tooth samples demonstrated increased light backscattering intensity at sites of carious lesions as compared to the sound enamel. The observed lesion depth on an OCT image was approximately 290 microm matching those previously documented for incipient caries. Using Raman microspectroscopy and fiber-optic-based Raman spectroscopy to characterize the caries further, spectral changes were observed in PO4 (3-) vibrations arising from hydroxyapatite of mineralized tooth tissue. Examination of various ratios of PO4 (3-) nu2, nu3, nu4 vibrations against the nu1 vibration showed consistent increases in carious lesions compared to sound enamel. The changes were attributed to demineralization-induced alterations of enamel crystallite morphology and/or orientation. OCT imaging is useful for screening carious sites and determining lesion depth, with Raman spectroscopy providing biochemical confirmation of caries. The combination has potential for development into a new fiber-optic diagnostic tool enabling dentists to identify early caries lesions with greater sensitivity and specificity.

Regional variations in myocardial tissue oxygenation mapped by near-infrared spectroscopic imaging.

Near-infrared fibre-optic single point spectroscopy has been widely exploited to provide information regarding blood volume and oxygenation in vivo, but it does not provide any information on regional differences in perfusion. We have combined the chemical sensitivity of spectroscopy with the spatial sensitivity of imaging to generate maps of regional cardiac oxygenation. Spectroscopic images were acquired for isolated, arrested, blood-perfused porcine hearts (n=4) over the wavelength range 650 and 1050 nm. Spectroscopic images were acquired during normal perfusion, regional ischemia (occlusion of left anterior descending artery) global ischemia, and reperfusion. Hemoglobin (Hb) and myoglobin (Mb) content and oxygenation were determined by reconstructing the tissue spectra measured at each pixel as weighted sums of water, oxy- and deoxy-Hb (and -Mb) absorptivity spectra. The spectroscopic images acquired during regional ischemia clearly revealed increased deoxy-(Hb+Mb) levels and decreased oxy-(Hb+Mb) levels in the ischaemic regions relative to the normally-perfused regions. Global ischemia produced a dramatic decrease in oxy-(Hb+Mb) levels and a moderate increase in deoxy-(Hb+Mb). These images confirm that blood oxygenation can be mapped in cardiac tissue by near-infrared spectroscopic imaging.