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INTRODUCTION: We tested associations between two retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer [pRNFL] thickness) and four magnetic resonance imaging markers of cerebral small vessel disease (SVD; lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces [ePVSs]). METHODS: We used PallorMetrics to quantify optic disc pallor from fundus photographs, and pRNFL thickness from optical coherence tomography scans. Linear and logistic regression assessed relationships between retinal measures and SVD markers. Participants (N = 108, mean age 51.6) were from the PREVENT Dementia study. RESULTS: Global optic disc pallor was linked to ePVSs in the basal ganglia in both left (ß = 0.12, standard error [SE] = 0.05, P < 0.05) and right eyes (ß = 0.13, SE = 0.05, P < 0.05). Associations were also noted in different disc sectors. No pRNFL associations with SVD markers were found. DISCUSSION: Optic disc pallor correlated with ePVSs in the basal ganglia, suggesting retinal examination may be a useful method to study brain health changes related to SVD. Highlights: Optic disc pallor is linked to enlarged perivascular spaces in basal ganglia.There is no association between peripapillary retinal nerve fiber layer thickness and cerebral small vessel disease markers.Optic disc examination could provide insights into brain health.The sample included 108 midlife adults from the PREVENT Dementia study.
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Purpose: We sough to develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fiber layer (pRNFL) thickness. Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants. Separately, we used images diagnosed by clinical inspection as pale (n = 45) and assessed how measurements compared with healthy controls (n = 46). We also developed automatic rejection thresholds and tested the software for robustness to camera type, image format, and resolution. Results: We developed software that automatically quantified disc pallor across several zones in fundus photographs. Pallor was associated with pRNFL thickness globally (ß = -9.81; standard error [SE] = 3.16; P < 0.05), in the temporal inferior zone (ß = -29.78; SE = 8.32; P < 0.01), with the nasal/temporal ratio (ß = 0.88; SE = 0.34; P < 0.05), and in the whole disc (ß = -8.22; SE = 2.92; P < 0.05). Furthermore, pallor was significantly higher in the patient group. Last, we demonstrate the analysis to be robust to camera type, image format, and resolution. Conclusions: We developed software that automatically locates and quantifies disc pallor in fundus photographs and found associations between pallor measurements and pRNFL thickness. Translational Relevance: We think our method will be useful for the identification, monitoring, and progression of diseases characterized by disc pallor and optic atrophy, including glaucoma, compression, and potentially in neurodegenerative disorders.
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Aprendizaje Profundo , Fibras Nerviosas , Disco Óptico , Fotograbar , Programas Informáticos , Tomografía de Coherencia Óptica , Humanos , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Tomografía de Coherencia Óptica/métodos , Masculino , Femenino , Persona de Mediana Edad , Fibras Nerviosas/patología , Fotograbar/métodos , Adulto , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/citología , Anciano , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/patología , Fondo de OjoRESUMEN
Purpose: To evaluate the performance of an automated choroid segmentation algorithm in optical coherence tomography (OCT) data using a longitudinal kidney donor and recipient cohort. Methods: We assessed 22 donors and 23 patients requiring renal transplantation over up to 1 year posttransplant. We measured choroidal thickness (CT) and area and compared our automated CT measurements to manual ones at the same locations. We estimated associations between choroidal measurements and markers of renal function (estimated glomerular filtration rate [eGFR], serum creatinine, and urea) using correlation and linear mixed-effects (LME) modeling. Results: There was good agreement between manual and automated CT. Automated measures were more precise because of smaller measurement error over time. External adjudication of major discrepancies was in favor of automated measures. Significant differences were observed in the choroid pre- and posttransplant in both cohorts, and LME modeling revealed significant linear associations observed between choroidal measures and renal function in recipients. Significant associations were mostly stronger with automated CT (eGFR, P < 0.001; creatinine, P = 0.004; urea, P = 0.04) compared to manual CT (eGFR, P = 0.002; creatinine, P = 0.01; urea, P = 0.03). Conclusions: Our automated approach has greater precision than human-performed manual measurements, which may explain stronger associations with renal function compared to manual measurements. To improve detection of meaningful associations with clinical endpoints in longitudinal studies of OCT, reducing measurement error should be a priority, and automated measurements help achieve this. Translational Relevance: We introduce a novel choroid segmentation algorithm that can replace manual grading for studying the choroid in renal disease and other clinical conditions.
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Trasplante de Riñón , Humanos , Creatinina , Coroides/diagnóstico por imagen , Algoritmos , UreaRESUMEN
We aimed to compare measurements from three of the most widely used software packages in the literature and to generate conversion algorithms for measurement of the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) between SIVA and IVAN and between SIVA and VAMPIRE. We analyzed 223 retinal photographs from 133 human participants using both SIVA, VAMPIRE and IVAN independently for computing CRAE and CRVE. Agreement between measurements was assessed using Bland-Altman plots and intra-class correlation coefficients. A conversion algorithm between measurements was carried out using linear regression, and validated using bootstrapping and root-mean-square error. The agreement between VAMPIRE and IVAN was poor to moderate: The mean difference was 20.2 µm (95% limits of agreement, LOA, -12.2-52.6 µm) for CRAE and 21.0 µm (95% LOA, -17.5-59.5 µm) for CRVE. The agreement between VAMPIRE and SIVA was also poor to moderate: the mean difference was 36.6 µm (95% LOA, -12.8-60.4 µm) for CRAE, and 40.3 µm (95% LOA, 5.6-75.0 µm) for CRVE. The agreement between IVAN and SIVA was good to excellent: the mean difference was 16.4 µm (95% LOA, -4.25-37.0 µm) for CRAE, and 19.3 µm (95% LOA, 0.09-38.6 µm) for CRVE. We propose an algorithm converting IVAN and VAMPIRE measurements into SIVA-estimated measurements, which could be used to homogenize sets of vessel measurements obtained with different software packages.
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AIMS/HYPOTHESIS: Our aim was to determine whether quantitative retinal traits in people with type 2 diabetes are independently associated with incident major cardiovascular events including CHD and stroke. METHODS: A total of 1066 men and women with type 2 diabetes, aged 65-74 years, were followed up over 8 years in the population-based Edinburgh Type 2 Diabetes Study. Using retinal photographs taken at baseline and specialist software, a number of quantitative retinal traits were measured, including arteriolar and venular widths and tortuosity as well as fractal dimension (a measure of the branching pattern complexity of the retinal vasculature network). Incident CHD events occurring during follow-up included fatal and non-fatal myocardial infarction, first episodes of angina and coronary interventions for CHD. Incident cerebrovascular events included fatal and non-fatal stroke or transient ischaemic attack. Cox proportional hazard regression analyses were performed to identify the association of the retinal traits with cardiovascular events in the population with retinal data available (n = 1028). RESULTS: A total of 200 participants had an incident cardiovascular event (139 CHD and 61 cerebrovascular events). Following adjustment for age and sex, arteriolar tortuosity and fractal dimension were associated with cerebrovascular events (HR 1.27 [95% CI 1.02, 1.58] and HR 0.74 [95% CI 0.57, 0.95], respectively), including with stroke alone (HR 1.30 [95% CI 1.01, 1.66] and HR 0.73 [95% CI 0.56, 0.97], respectively). These associations persisted after further adjustment for established cardiovascular risk factors (HR 1.26 [95% CI 1.01, 1.58] and HR 0.73 [95% CI 0.56, 0.94], respectively). Associations generally reduced in strength after a final adjustment for the presence of diabetic retinopathy, but the association of fractal dimension with incident cerebrovascular events and stroke retained statistical significance (HR 0.73 [95% CI 0.57, 0.95] and HR 0.72 [95% CI 0.54, 0.97], respectively). Associations of retinal traits with CHD were generally weak and showed no evidence of statistical significance. CONCLUSIONS/INTERPRETATION: Arteriolar tortuosity and fractal dimension were associated with incident cerebrovascular events, independent of a wide range of traditional cardiovascular risk factors including diabetic retinopathy. These findings suggest potential for measurements of early retinal vasculature change to aid in the identification of people with type 2 diabetes who are at increased risk from stroke.
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Enfermedad Coronaria/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Fractales , Arteria Retiniana/patología , Accidente Cerebrovascular/diagnóstico , Anciano , Arteriolas/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fotograbar , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
INTRODUCTION: Discovering non-invasive and easily acquired biomarkers that are conducive to the accurate diagnosis of dementia is an urgent area of ongoing clinical research. One promising approach is retinal imaging, as there is homology between retinal and cerebral vasculature. Recently, optical coherence tomography angiography (OCT-A) has emerged as a promising new technology for imaging the microvasculature of the retina. METHODS: A systematic review and meta-analysis was conducted to examine the application of OCT-A in dementia. RESULTS: Fourteen studies assessing OCT-A in preclinical Alzheimer's disease (AD), mild cognitive impairment, or AD were included. Exploratory meta-analyses revealed a significant increase in the foveal avascular zone area and a significant decrease in superficial parafoveal and whole vessel density in AD, although there was significant heterogeneity between studies. DISCUSSION: Although certain OCT-A metrics may have the potential to serve as biomarkers for AD, the field requires further standardization to allow conclusions to be reached regarding their clinical utility.
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BACKGROUND: Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. METHODS: Retinal microvascular parameters (fractal dimension [FD] - a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background. RESULTS: Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03-1.34 for arterioles and OR 1.24, CI 1.05-1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. CONCLUSIONS: This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria.
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Albuminuria/complicaciones , Insuficiencia Renal Crónica/complicaciones , Vasos Retinianos/anatomía & histología , Anciano , Bancos de Muestras Biológicas , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Microvasos , Persona de Mediana Edad , Tamaño de los Órganos , Reino UnidoRESUMEN
Objective: Changes to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status. Methods: We retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal-annular arteriole:venule ratio (NA-AVR), a novel combined parameter. Results: Left and right eyes were analysed from 440 participants (aged 50-59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020). Conclusions: Semiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.
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Hipertensión/complicaciones , Oftalmoscopía , Enfermedades de la Retina/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Automatización , Presión Sanguínea , Femenino , Fondo de Ojo , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Interpretación de Imagen Asistida por Computador , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Enfermedades de la Retina/etiología , Enfermedades de la Retina/fisiopatología , Estudios RetrospectivosRESUMEN
BACKGROUND: Tissue derived biomarkers may offer utility as indicators of accumulated damage. Reduced thickness of retinal neuronal tissue and the vascular choroid have previously been associated with vascular damage and diabetes. We evaluated associations between retinal thickness, retinal microvascular and choroidal measures, and renal function in a population with a high burden of comorbidity. METHODS: Participants were recruited from nuclear cardiology or renal medicine clinics. Retinal and choroidal thickness were measured from spectral-domain optical coherence tomograms. Retinal microvascular parameters were assessed from digital fundus photographs using a semi-automated software package. MAIN OUTCOME MEASURE: Chronic kidney disease (CKD) categorised as: CKD stages 1-2, eGFR ≥60 ml/min/1.73m2; CKD stage 3, eGFR 30-59 ml/min/1.73m2, and CKD stages 4-5, eGFR ≤29 ml/min/1.73m2. RESULTS: Participants (n = 241) had a mean age of 65 years and a mean eGFR of 66.9 ml/min/1.73m2. Thirty-nine % of the cohort had diabetes and 27% were using diuretics. Thinning of the inner retina and changes to its microvascular blood supply were associated with lower eGFR and CKD stages 4 and 5, while no associations were found between the outer retinal layers or their choroidal blood supply and CKD of any stage. These associations remained following adjustment for age, mean arterial blood pressure, diabetes status, low-density lipoprotein, body mass index, and sex. CONCLUSIONS: Inner retinal thinning and retinal microvascular variation is associated with advanced CKD (stages 4 & 5) independent of important confounding factors, but not with earlier stage CKD (stage 3) and, therefore, its utility as a biomarker for early CKD is not supported in this study.
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Coroides/patología , Microvasos/patología , Insuficiencia Renal Crónica/fisiopatología , Retina/patología , Vasos Retinianos/patología , Anciano , Biomarcadores , Coroides/diagnóstico por imagen , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Microvasos/diagnóstico por imagen , Persona de Mediana Edad , Oftalmoscopía , Tamaño de los Órganos , Fotograbar , Retina/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Tomografía de Coherencia ÓpticaRESUMEN
Objectives: Ultra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection. Methods: Ten volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Results: Ten patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43). Conclusion: Stable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection. Trial registration number: NCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24.
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INTRODUCTION: We test whether measures of the retinal vasculature are associated with cognitive functioning and cognitive change. METHODS: Retinal images from a narrow-age cohort were analyzed using Vessel Assessment and Measurement Platform for Images of the Retina, producing a comprehensive range of quantitative measurements of the retinal vasculature, at mean age 72.5 years (SD = 0.7). Cognitive ability and change were measured using a battery of multiple measures of memory, visuospatial, processing speed, and crystallized cognitive abilities at mean ages 73, 76, and 79 years. We applied multivariate growth curve models to test the association between retinal vascular measurements with cognitive abilities and their changes. RESULTS: Almost all associations were nonsignificant. In our most parsimonious model, venular asymmetry factor was associated with speed at age 73. DISCUSSION: Our null findings suggest that the quantitative retinal parameters applied in this study are not significantly associated with cognitive functioning or cognitive change.
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PURPOSE: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. METHODS: Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test. RESULTS: Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10-3 ± 2.865 × 10-3 vs. 6.375 × 10-3 ± 1.532 × 10-3, p = 0.008; entire image: 8.235 × 10-3 ± 2.839 × 10-3 vs. 6.050 × 10-3 ± 1.414 × 10-3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU. CONCLUSIONS: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.
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Enfermedad de Alzheimer/complicaciones , Drusas Retinianas , Vasos Retinianos , Anciano , Biomarcadores , Estudios de Casos y Controles , Femenino , Humanos , Degeneración Macular , Masculino , Microscopía Confocal/métodos , Persona de Mediana Edad , Oftalmoscopía/métodos , Proyectos Piloto , Drusas Retinianas/diagnóstico por imagen , Drusas Retinianas/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patologíaRESUMEN
Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31+/CD144+), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers. Cell tracking using MRI, PET, and qPCR in a murine model of limb ischemia demonstrated that hESC-ECP was detectable up to day 7 following injection. Efficacy in several murine models of limb ischemia (immunocompromised/immunocompetent mice and mice with either type I/II diabetes mellitus) demonstrated significantly increased blood perfusion and capillary density. Overall, we demonstrate a GMP-compatible hESC-ECP that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy.
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Células Endoteliales/citología , Miembro Posterior/citología , Isquemia/terapia , Neovascularización Fisiológica/fisiología , Animales , Biomarcadores/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Células Endoteliales/metabolismo , Miembro Posterior/metabolismo , Humanos , Isquemia/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Pericitos/citología , Pericitos/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Trasplante de Células Madre/métodosRESUMEN
PURPOSE: Semiautomated software applications derive quantitative retinal vascular parameters from fundus camera images. However, the extent of agreement between measurements from different applications is unclear. We evaluate the agreement between retinal measures from two software applications, the Singapore "I" Vessel Assessment (SIVA) and the Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE), and examine respective associations between retinal and systemic outcomes. METHOD: Fundus camera images from 665 Lothian Birth Cohort 1936 participants were analyzed with SIVA and VAMPIRE. Intraclass correlation coefficients (ICC) and Bland-Altman plots assessed agreement between retinal parameters: measurements of vessel width, fractal dimension, and tortuosity. Retinal-systemic variable associations were assessed with Pearson's correlation, and intersoftware correlation magnitude differences were examined with Williams's test. RESULTS: ICC values indicated poor to limited agreement for all retinal parameters (0.159-0.410). Bland-Altman plots revealed proportional bias in the majority, and systematic bias in all measurements. SIVA and VAMPIRE measurements were associated most consistently with systemic variables relating to blood pressure (SIVA r's from -0.122 to -0.183; VAMPIRE r's from -0.078 to -0.177). Williams's tests indicated significant differences in the magnitude of association between retinal and systemic variables for 7 of 77 comparisons (P < 0.05). CONCLUSIONS: Agreement between two common software applications was poor. Further studies are required to determine whether associations with systemic variables are software-dependent. TRANSLATIONAL RELEVANCE: Standardization of the measurement of retinal vascular parameters is warranted to ensure that they are reliable and application-independent. This would be an important step towards realizing the potential of the retina as a source of imaging-derived biomarkers that are clinically useful.
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The eye provides an opportunistic "window" to view the microcirculation. There is published evidence of an association between retinal microvascular calibre and renal function measured by estimated glomerular filtration rate (eGFR) in individuals with diabetes mellitus. Beyond vascular calibre, few studies have considered other microvascular geometrical features. Here we report novel null findings for measures of vascular spread (vessel fractal dimension), tortuosity, and branching patterns and their relationship with renal function in type 2 diabetes over a mean of 3 years. We performed a nested case-control comparison of multiple retinal vascular parameters between individuals with type 2 diabetes and stable (non-progressors) versus declining (progressors) eGFR across two time points within a subset of 1072 participants from the GoDARTS study cohort. Retinal microvascular were measured using VAMPIRE 3.1 software. In unadjusted analyses and following adjustment for age, gender, systolic blood pressure, HbA1C, and diabetic retinopathy, no associations between baseline retinal vascular parameters and risk of eGFR progression were observed. Cross-sectional analysis of follow-up data showed a significant association between retinal arteriolar diameter and eGFR, but this was not maintained following adjustment. These findings are consistent with a lack of predictive capacity for progressive loss of renal function in type 2 diabetes.
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Diabetes Mellitus Tipo 2/fisiopatología , Riñón/fisiopatología , Microvasos/patología , Vasos Retinianos/patología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/patología , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVES: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect tissue-resident macrophage activity and identify cellular inflammation within tissues. We hypothesised that USPIO-enhanced MRI would provide a non-invasive imaging technique that would improve the diagnosis and management of patients with acute myocarditis. METHODS: Ten volunteers and 14 patients with suspected acute myocarditis underwent T2, T2* and late gadolinium enhancement (LGE) 3T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Myocardial oedema and USPIO enhancement were determined within areas of LGE as well as throughout the myocardium. RESULTS: Myocarditis was confirmed in nine of the 14 suspected cases of myocarditis. There was greater myocardial oedema in regions of LGE in patients with myocarditis when compared with healthy volunteer myocardium (T2 value, 57.1±5.3 vs 46.7±1.6 ms, p<0.0001). There was no demonstrable difference in USPIO enhancement between patients and volunteers even within regions displaying LGE (change in R2*, 35.0±15.0 vs 37.2±9.6 s-1, p>0.05). Imaging after 3 months in patients with myocarditis revealed a reduction in volume of LGE, a reduction in oedema measures within regions displaying LGE and improvement in ejection fraction (mean -19.7 mL, 95% CI (-0.5 to -40.0)), -5.8 ms (-0.9 to -10.7) and +6% (0.5% to 11.5%), respectively, p<0.05 for all). CONCLUSION: In patients with acute myocarditis, USPIO-enhanced MRI does not provide additional clinically relevant information to LGE and T2 mapping MRI. This suggests that tissue-resident macrophages do not provide a substantial contribution to the myocardial inflammation in this condition.Clinical trial registration NCT02319278; Results.
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Dextranos/farmacología , Imagen por Resonancia Cinemagnética/métodos , Miocarditis , Miocardio/patología , Enfermedad Aguda , Adulto , Medios de Contraste/farmacología , Femenino , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Inflamación/diagnóstico por imagen , Activación de Macrófagos/inmunología , Nanopartículas de Magnetita , Masculino , Persona de Mediana Edad , Miocarditis/diagnóstico por imagen , Miocarditis/inmunología , Miocarditis/patología , Valor Predictivo de las PruebasRESUMEN
OBJECTIVES: Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI. METHODS: Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues. RESULTS: Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2-3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10-16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3-9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01). CONCLUSION: Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions. TRIAL REGISTRATION NUMBER: Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02319278?term=DECIFER&rank=2).