Large Scale Optical Projection Tomography without the Use of Refractive-Index-Matching Liquid.

The practical, rapid, and accurate optical 3D reconstruction of transparent objects with contemporary non-contact optical techniques, has been an open challenge in the field of optical metrology. The combination of refraction, reflection, and transmission in transparent objects makes it very hard to use common off-the-shelf 3D reconstruction solutions to accurately reconstruct transparent objects in three dimensions without completely coating the object with an opaque material. We demonstrate in this work that a specific class of transparent objects can indeed be reconstructed without the use of opaque spray coatings, via Optical Projection Tomography (OPT). Particularly, the 3D reconstruction of large thin-walled hollow transparent objects can be achieved via OPT, without the use of refractive-index-matching liquid, accurately enough for use in both cultural heritage and beverage packaging industry applications. We compare 3D reconstructions of our proposed OPT method to those achieved by an industrial-grade 3D scanner and report average shape differences of ±0.34 mm for 'shelled' hollow objects and ±0.92 mm for 'non-shelled' hollow objects. A disadvantage of using OPT, which was noticed on the thicker 'non-shelled' hollow objects, as opposed to the 'shelled' hollow objects, was that it induced partial filling of hollow areas and the deformation of embossed features.

Monitoring Health Parameters of Elders to Support Independent Living and Improve Their Quality of Life.

Improving the well-being and quality of life of the elderly population is closely related to assisting them to effectively manage age-related conditions such as chronic illnesses and anxiety, and to maintain their independence and self-sufficiency as much as possible. This paper presents the design, architecture and implementation structure of an adaptive system for monitoring the health and well-being of the elderly. The system was designed following best practices of the Human-Centred Design approach involving representative end-users from the early stages.

Urinary albumin excretion in rheumatoid arthritis is not associated with markers of vasculopathy in distal microvascular beds.

OBJECTIVE: Increased UAE is a marker of generalized vascular damage in high-cardiovascular risk patients. However, it remains unknown whether it corresponds to a state of diffuse vasculopathy in high-risk patients with RA. METHODS: UAE was estimated in 24-hour urine samples in RA and non-RA individuals. Retinal arteriolar and venular diameters were calculated from retinal images with computerized software. SEVR was estimated as an index of microvascular coronary perfusion with applanation tonometry. Dermal capillary density was measured from images obtained with nailfold capillaroscopy, using specifically designed software. RESULTS: In a total of 111 individuals, neither UAE (5.1 [2.8-10.8] vs 6.5 [3.0-11.7] mg/24 h) nor prevalence of microalbuminuria (11.0% vs 8.1%) significantly differed between patients (n = 74) and controls (n = 37). In the RA group, UAE was not significantly associated with inflammation, nor with any of the studied microvascular indices of the retinal microvasculature, the coronary microcirculation, and the dermal capillary network. CONCLUSION: Among RA patients, UAE was not associated with markers of vasculopathy in distal microvascular beds. Increased UAE in RA might be primarily considered as a manifestation of localized, compromised function of the renal microvasculature, rather than a marker of generalized microvascular impairment.

Dermal capillary rarefaction as a marker of microvascular damage in patients with rheumatoid arthritis: Association with inflammation and disorders of the macrocirculation.

OBJECTIVE: Capillary rarefaction is observed in various cardiovascular diseases, yet it remains understudied in RA, a chronic inflammatory disease accompanied by excess cardiovascular risk. We quantified capillary density in RA patients and explored potential associations with macrocirculatory disorders, inflammation, and cardiovascular risk. METHODS: Dermal capillary density was assessed with nailfold capillaroscopy in RA and non-RA individuals, using specifically designed semiautomated software. Macrocirculation assessments included large artery stiffening, evaluated with PWV, and myocardial blood flow, calculated as cardiac index from impedance cardiography. Cardiovascular risk score was estimated from the Framingham Heart Study. RESULTS: The number of capillaries per visual field was lower in patients (n = 99) compared to controls (n = 35) (132.6 ± 30.3 vs 152.9 ± 25.2, P = .001). In the RA group, capillary density negatively correlated with CRP and PWV, and positively with HDL and cardiac index. In the multivariate analysis, CRP independently predicted capillary rarefaction (P = .044). Capillary density significantly correlated with cardiovascular risk, even after adjustment for inflammation (P = .030). CONCLUSION: Capillary rarefaction appears pronounced in RA and correlates with lower cardiac output, increased arterial stiffness, and cardiovascular risk. However, the associations with macrocirculatory disorders may be obscured by inflammation, which appears as the major contributor to capillary rarefaction in RA.

Retinal vessel morphology in rheumatoid arthritis: Association with systemic inflammation, subclinical atherosclerosis, and cardiovascular risk.

OBJECTIVE: Quantification of retinal vessel morphology has emerged as a marker of cardiovascular health. We examined retinal microvascular diameters in RA, particularly in regard to systemic inflammation, subclinical atherosclerosis, and cardiovascular risk. METHODS: Retinal images from RA patients and controls were processed using computerized software, to obtain CRAE and CRVE and AVR. Subclinical atherosclerosis was assessed with cIMT, and 10-year risk of general cardiovascular disease was calculated. RESULTS: Both CRAE (78.8 ± 8.9 vs 90.2 ± 9.9 µm, P < .001) and AVR (0.69 ± 0.09 vs 0.81 ± 0.09, P < .001) were decreased in RA patients (n = 87) compared to controls (n = 46), whereas CRVE did not differ. Among RA patients, CRAE and AVR were inversely associated with both cIMT and CRP, whereas CRVE positively correlated with CRP (P < .05 for all). CRAE additionally correlated with cardiovascular risk score (r = -.396, P = .001). In the multivariate analysis, cardiovascular risk was associated with CRAE; age with CRVE, while CRP independently predicted AVR. CONCLUSIONS: Our study shows altered retinal microvascular morphology in RA patients. Inflammation appears as the biological link for the observed association between retinal microvascular abnormalities and subclinical atherosclerosis. Retinal arteriolar narrowing might play its own role in cardiovascular risk prediction in RA.

In vivo analysis of the time and spatial activation pattern of microglia in the retina following laser-induced choroidal neovascularization.

Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach the immune response in the retina in vivo.

Relationship of 24-h ambulatory blood pressure variability with micro and macrovascular parameters and hypertension status.

OBJECTIVES: Increased blood pressure variability (BPV) has been associated with an increased risk of subclinical organ damage and cardiovascular events, independently of elevated average BP values. We aimed to investigate the association of BPV indices with micro- and macrovascular parameters, some of them not previously studied. METHODS: We evaluated 344 individuals (233 never-treated/newly diagnosed hypertensive and 111 normotensive individuals). BPV was assessed using average real variability (ARV) during 24-h, daytime and night-time ambulatory blood pressure monitoring, and systolic weighted standard deviation (wSD). Retinal microvascular diameter was assessed by nonmydriatic retinal photography. Arterial stiffness was assessed by pulse wave velocity (PWV) and aortic augmentation index (AIx); subendocardial variability ratio (SEVR) was used as an index of myocardial perfusion. Carotid intima-media thickness (cIMT) was measured by ultrasound. Data were analyzed using multiple regression analysis. RESULTS: After adjusting for potential confounders, PWV and cIMT were independently associated with ARV components in the total sample (P < 0.023 and P < 0.014, respectively). Within hypertensives only PWV and cIMT were independently associated with ARV components (P < 0.002 for PWV and P < 0.003 for cIMT). In contrast, within normotensives, only retinal parameters and AIx were associated with ARV components (P < 0.017 and P = 0.013, respectively). None of the univariate correlations between vascular parameters and wSD remained significant after adjustment for potential confounders. CONCLUSION: Short-term BPV as assessed by ARV is independently associated with macrovascular parameters in untreated hypertensive patients, and with microvascular parameters in normotensive individuals.

Retinal image registration as a tool for supporting clinical applications.

BACKGROUND AND OBJECTIVE: The study of small vessels allows for the analysis and diagnosis of diseases with strong vasculopathy. This type of vessels can be observed non-invasively in the retina via fundoscopy. The analysis of these vessels can be facilitated by applications built upon Retinal Image Registration (RIR), such as mosaicing, Super Resolution (SR) or eye shape estimation. RIR is challenging due to possible changes in the retina across time, the utilization of diverse acquisition devices with varying properties, or the curved shape of the retina. METHODS: We employ the Retinal Image Registration through Eye Modelling and Pose Estimation (REMPE) framework, which simultaneously estimates the cameras' relative poses, as well as eye shape and orientation to develop RIR applications and to study their effectiveness. RESULTS: We assess quantitatively the suitability of the REMPE framework towards achieving SR and eye shape estimation. Additionally, we provide indicative results demonstrating qualitatively its usefulness in the context of longitudinal studies, mosaicing, and multiple image registration. Besides the improvement over registration accuracy, demonstrated via registration applications, the most important novelty presented in this work is the eye shape estimation and the generation of 3D point meshes. This has the potential for allowing clinicians to perform measurements on 3D representations of the eye, instead of doing so in 2D images that contain distortions induced because of the projection on the image space. CONCLUSIONS: RIR is very effective in supporting applications such as SR, eye shape estimation, longitudinal studies, mosaicing and multiple image registration. Its improved registration accuracy compared to the state of the art translates directly in improved performance when supporting the aforementioned applications.

REMPE: Registration of Retinal Images Through Eye Modelling and Pose Estimation.

OBJECTIVE: In-vivo assessment of small vessels can promote accurate diagnosis and monitoring of diseases related to vasculopathy, such as hypertension and diabetes. The eye provides a unique, open, and accessible window for directly imaging small vessels in the retina with non-invasive techniques, such as fundoscopy. In this context, accurate registration of retinal images is of paramount importance in the comparison of vessel measurements from original and follow-up examinations, which is required for monitoring the disease and its treatment. At the same time, retinal registration exhibits a range of challenges due to the curved shape of the retina and the modification of imaged tissue across examinations. Thereby, the objective is to improve the state-of-the-art in the accuracy of retinal image registration. METHOD: In this work, a registration framework that simultaneously estimates eye pose and shape is proposed. Corresponding points in the retinal images are utilized to solve the registration as a 3D pose estimation. RESULTS: The proposed framework is evaluated quantitatively and shown to outperform state-of-the-art methods in retinal image registration for fundoscopy images. CONCLUSION: Retinal image registration methods based on eye modelling allow to perform more accurate registration than conventional methods. SIGNIFICANCE: This is the first method to perform retinal image registration combined with eye modelling. The method improves the state-of-the-art in accuracy of retinal registration for fundoscopy images, quantitatively evaluated in benchmark datasets annotated with ground truth. The implementation of registration method has been made publicly available.

Association of Urinary Sodium Excretion with Vascular Damage: A Local Kidney Effect, Rather Than a Marker of Generalized Vascular Impairment.

Evidence suggests that increased salt consumption induces blood pressure- (BP) mediated organ damage, yet it remains unclear whether it reflects a generalized micro- and macrovascular malfunction independent of BP. We studied 197 newly diagnosed and never-treated individuals with hypertension, intermediate hypertensive phenotypes, and normal BP, classified by use of 24-hour ambulatory BP monitoring. Sodium excretion and microalbuminuria were estimated in 24-hour urine samples, dermal capillary density was estimated from capillaroscopy, and arterial stiffness was estimated with pulse wave velocity (PWV) and augmentation index (AIx). Sodium excretion correlated with microalbuminuria (p<0.001) and 24-hour and day- and nighttime systolic BP, but not with office blood pressure, arterial stiffness, or capillary density. In the multivariate analysis, the association with microalbuminuria was maintained (p=0.007). In a population free from the long-standing effects of hypertension, increased salt intake appears to be associated with early signs of vascular kidney damage, rather than a diffuse micro- and macrovascular impairment.

An experimental evaluation of the accuracy of keypoints-based retinal image registration.

This work regards an investigation of the accuracy of a state-of-the-art, keypoint-based retinal image registration approach, as to the type of keypoint features used to guide the registration process. The employed registration approach is a local method that incorporates the notion of a 3D retinal surface imaged from different viewpoints and has been shown, experimentally, to be more accurate than competing approaches. The correspondences obtained between SIFT, SURF, Harris-PIIFD and vessel bifurcations are studied, either individually or in combinations. The combination of SIFT features with vessel bifurcations was found to perform better than other combinations or any individual feature type, alone. The registration approach is also comparatively evaluated against representative methods of the state-of-the-art in retinal image registration, using a benchmark dataset that covers a broad range of cases regarding the overlap of the acquired images and the anatomical characteristics of the imaged retinas.

Retinal image registration under the assumption of a spherical eye.

We propose a method for registering a pair of retinal images. The proposed approach employs point correspondences and assumes that the human eye has a spherical shape. The image registration problem is formulated as a 3D pose estimation problem, solved by estimating the rigid transformation that relates the views from which the two images were acquired. Given this estimate, each image can be warped upon the other so that pixels with the same coordinates image the same retinal point. Extensive experimental evaluation shows improved accuracy over state of the art methods, as well as robustness to noise and spurious keypoint matches. Experiments also indicate the method's applicability to the comparative analysis of images from different examinations that may exhibit changes and its applicability to diagnostic support.

Retinal image registration through simultaneous camera pose and eye shape estimation.

In this paper, a retinal image registration method is proposed. The approach utilizes keypoint correspondences and assumes that the human eye has a spherical or ellipsoidal shape. The image registration problem amounts to solving a camera 3D pose estimation problem and, simultaneously, an eye 3D shape estimation problem. The camera pose estimation problem is solved by estimating the relative pose between the views from which the images were acquired. The eye shape estimation problem parameterizes the shape and orientation of an ellipsoidal model for the eye. Experimental evaluation shows 17.91% reduction of registration error and 47.52% reduction of the error standard deviation over state of the art methods.

Impaired metabolic profile is a predictor of capillary rarefaction in a population of hypertensive and normotensive individuals.

Capillary rarefaction is typically encountered in essential hypertension, yet identification of factors interfering with this phenomenon remains substantially underinvestigated. We examined whether components of metabolic profile (dyslipidemia, insulin resistance), inflammatory (high-sensitivity C-reactive protein, high-sensitivity C-reactive protein), and angiogenic (vascular endothelial growth factor) factors are implicated in this phenomenon in a population of newly diagnosed, never-treated hypertensive patients and normotensive controls. Nailfold capillary density was estimated with nailfold capillaroscopy using specifically designed software. A total of 159 individuals, 93 hypertensives, and 66 normotensives were included. Nailfold capillary density was lower among hypertensives compared to normotensives (146.4 ± 31.0 vs. 155.4 ± 26.9, respectively; P = .047). In the total population, capillary density significantly correlated with high-density lipoprotein (HDL) (r = 0.232; P = .003), HDL/low-density lipoprotein ratio (r = 0.175; P = .025), age (r = 0.236; P = .003), but neither with vascular endothelial growth factor or high-sensitivity C-reactive protein. An inverse association was found with body mass index (r = -0.174; P = .029), insulin levels (r = -0.200; P = .018), and homeostasis model assessment-insulin resistance (r = -0.223; P = .009). In the separate analysis for the hypertensive population, sex (P = .014) and homeostasis model assessment-insulin resistance (P = .011) were identified as significant predictors of capillary rarefaction after adjustment for other factors. On the contrary, only HDL levels (P = .036) predicted capillary density in the multiple regression model for the normotensive population. Different aspects of impaired metabolic profile, that is, insulin resistance and low HDL levels, but not angiogenic or inflammatory markers, appear to be independently associated with capillary rarefaction in hypertensive and normotensive individuals.

Retinal image registration based on keypoint correspondences, spherical eye modeling and camera pose estimation.

In this work, an image registration method for two retinal images is proposed. The proposed method utilizes keypoint correspondences and assumes a spherical model of the eye. Image registration is treated as a pose estimation problem, which requires estimation of the rigid transformation that relates the two images. Using this estimate, one image can be warped so that it is registered to the coordinate frame of the other. Experimental evaluation shows improved accuracy over state-of-the-art approaches as well as robustness to noise and spurious keypoint correspondences. Experiments also indicate the method's applicability to diagnostic image enhancement and comparative analysis of images from different examinations.

Super resolution for fundoscopy based on 3D image registration.

An approach to the generation of super-resolution (SR) images from fundoscopy images is proposed that is based on the 3D registration of the original fundoscopy images. The proposed approach utilizes a simple 3D registration method to enable the application of conventional SR techniques which, otherwise, employ 2D image registration. Qualitative and quantitative comparative evaluation shows that the obtained results improve image definition and alleviate noise.

Association between retinal vessel caliber and arterial stiffness in a population comprised of normotensive to early-stage hypertensive individuals.

BACKGROUND: Although impairment of the micro- and macrocirculation is considered inherent to sustained hypertension, there is a substantial lack of studies investigating whether an association exists between micro- and macrovascular damage, especially in early-stage hypertension. METHODS: We studied a meticulously selected population, free of diabetes and cardiovascular disease, of 223 individuals: 137 never-treated, newly diagnosed patients with recent onset of hypertension and 86 normotensive individuals. Nonmydriatic retinal photography was used to assess retinal microvascular diameters, including central retinal arteriolar (CRAE) and venular equivalent and arteriovenous ratio (AVR). Arterial stiffness was evaluated by measurement of pulse wave velocity (PWV) and aortic augmentation index (AIx). RESULTS: Compared with normotensive subjects, hypertensive patients exhibited significantly increased PWV (8.1 vs. 7.1 m/sec; P < 0.001) and AIx (23.86% vs. 18.8%; P = 0.01) and decreased CRAE (86.47 vs. 91.44 µm; P = 0.001) and AVR (0.74 vs. 0.78; P = 0.007). A significant inverse association was demonstrated between PWV and CRAE (r = -0.205; P = 0.002), which remained significant after multivariable analysis. Likewise, CRAE (P = 0.04) and AVR (P = 0.02) were independent predictors of AIx. CONCLUSIONS: This study shows for the first time an association between quantitatively assessed retinal abnormalities and increased arterial stiffness in a sample of early-stage hypertensive and normotensive individuals, suggesting that micro- and macrocirculation impairment in hypertension is a dynamic, mutual, interdependent process present from its very early stages. Given the predictive value of both retinal arteriolar narrowing and arterial stiffness in terms of cardiovascular mortality and morbidity, identification of combined micro- and macrovascular damage might be helpful in cardiovascular risk stratification of hypertensive patients.

Accumulation of microvascular target organ damage in newly diagnosed hypertensive patients.

Early identification of hypertensive target organ damage (TOD) emerges as important for global cardiovascular risk assessment. Retinal vascular alterations, capillary rarefaction, and microalbuminuria represent different forms of microvascular TOD. However, data regarding their concomitant presence in the early stages of hypertension, the association of the number of affected organs with cardiovascular risk, and aldosterone effect on multiple TOD are lacking. We studied naïve, never-treated patients with recent duration of hypertension and healthy volunteers. Innovative software was developed to estimate retinal vascular diameters and capillary density. Biochemical parameters including microalbuminuria and serum aldosterone were derived. Framingham Risk Score was used to determine cardiovascular risk. In total 103 subjects, 66 hypertensives and 37 normotensives, were included. Hypertensive patients exhibited a greater number of affected target organs compared with normotensives (P = .014), with retinopathy and capillary rarefaction (40.9%) representing the most common TOD among hypertensives. The number of affected organs was linearly correlated with increased Framingham score and serum aldosterone, analyzed with univariate (P < .001 and P = .002) and multivariate analysis (P = .025 and P = .004), respectively. Physicians dealing with hypertensive patients should be aware of the possibility of diffuse microvascular impairment and seek multiple TOD even in the early stages of hypertension.

Development of a three-dimensional surface imaging system for melanocytic skin lesion evaluation.

Even though surface morphology is always taken into account when assessing clinically pigmented skin lesions, it is not captured by most modern imaging systems using digital imaging. Our aim is to develop a novel three-dimensional (3D) imaging technique to record detailed information of the surface anatomy of melanocytic lesions that will enable improved classification through digital imaging. The apparatus consists of three high-resolution cameras, a light source, and accompanying software. Volume measurements of specific phantoms using volumetric tubes render slightly lower values than those obtained by our 3D imaging system (mean%± SD, 3.8%± 0.98, P<0.05). To examine the reproducibility of the method, sequential imaging of melanocytic lesions is carried out. The mean%± SD differences of area, major axis length, volume, and maximum height are 2.1%± 1.1, 0.9%± 0.8, 3.8%± 2.9, and 2.5%± 3.5, respectively. Thirty melanocytic lesions are assessed, including common and dysplastic nevi and melanomas. There is a significant difference between nevi and melanomas in terms of variance in height and boundary asymmetry (P<0.001). Moreover, dysplastic nevi have significantly higher variances in pigment density values than common nevi (P<0.001). Preliminary data suggest that our instrument has great potential in the evaluation of the melanocytic lesions. However, these findings should be confirmed in larger-scale studies.

Divergent retinal vascular abnormalities in normotensive persons and patients with never-treated, masked, white coat hypertension.

BACKGROUND: Hypertensive patients with retinal arteriolar abnormalities are at increased risk for cardiovascular events. However, the extent of retinal microvascular changes in naïve, never-treated patients with hypertension of short duration has not been established. In addition to this, the lack of relevant data about other phenotypes of hypertension (masked and white-coat hypertension) determined by ambulatory blood-pressure measurement (ABPM) is notable, despite their relationship to increased cardiovascular risk mediated by underlying target-organ and vascular damage. METHODS: We conducted a study in which nonmydriatic retinal photography was used to assess central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters and the retinal arteriovenus ratio (AVR) in a group of 103 individuals with never-treated hypertension of recent (< 1 year) appearance, 28 individuals with masked and 20 with white-coat hypertension, and 50 normotensive individuals, as appropriately classified by ABPM. RESULTS: Patients with sustained and masked hypertension had narrower values of CRAE than did normotensive individuals (86.7±10.1 and 87.6±9.2 vs. 94.8±10.6, P < 0.001 and P = 0.02, respectively). The AVR was lower in patients with sustained hypertension (0.736±0.102), masked hypertension (0.716±0.123), and white-coat hypertension (0.739±0.127) than in normotensive subjects (0.820±0.095), P < 0.001, P < 0.001, and P = 0.03, respectively. Both AVR and CRAE were negatively associated with mean systolic and diastolic daytime, nighttime, and 24-hour blood pressures, even after adjustment for other factors. CONCLUSIONS: Subtle retinal microvascular signs of pathology are observed in hypertensive patients at early stages of hypertension and in patients with both masked and white coat hypertension. These changes may be indicative or may mediate the differences in cardiovascular mortality in persons with masked and white-coat hypertension, and relevant information about this can be easily accessed with retinal photography.