Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice

McLenachan, Samuel; Magno, Aaron L.; Ramos, David; Catita, Joana; McMenamin, Paul G.; Chen, Fred K.; Rakoczy, Elizabeth; Ruberte, Jesús

doi:10.1016/j.exer.2015.06.023

Cited by 60 publications

(61 citation statements)

References 36 publications

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“…For instance, in diabetic mice the vessel density was decreased in the deep vascular network but not in the superficial network. 28 Some previous histologic findings also revealed that vascular abnormalities were more pronounced in the deep retinal capillarylayer. 29,30 As expected, the ROC curve analysis revealed that fractal dimensions in the deep retinal capillary layer had higher discriminating powers than the superficial retinal capillary layer to detect the earlier microvascular network loss.…”

Section: Discussionmentioning

confidence: 78%

“…The density of the smaller vessels in the deep retinal capillary layer is greater than in the superficial layer. 12,28 To compensate for the lower blood flow and the resulting hypoxia and ischemia in macula at the early stage of DM, we speculate that capillary vasoconstriction in the deep retinal capillary layer occurs earlier or more frequently than that in the superficial layer. Evidence from previous studies supports our hypothesis, FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

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Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients

Chen

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Chen Q, Ma Q, Wu C, et al. Macular vascular fractal dimension in the deep capillary layer as an early indicator of microvascular loss for retinopathy in type 2 diabetic patients. Invest Ophthalmol Vis Sci. 2017;58:3785-3794. DOI:10.1167/ iovs.17-21461 PURPOSE. To determine the ability of fractal dimension to detect early changes in the retinal microvascular network imaged by optical coherence tomography angiography (OCT-A) in type 2 diabetic patients. METHODS.Sixty-seven patients with type 2 diabetic mellitus (DM) (48 with no diabetic retinopathy [DR], 19 with minimal DR) and 40 control subjects. Macular OCT-A images of the superficial and deep retinal capillary layers in a 2.5-mm diameter concentric annular zone (excluding the foveal avascular zone) were subdivided into six annular rings and four quadrants. A custom automated algorithm was developed to quantify the complexity and density of the two retinal capillary layers by fractal analysis.RESULTS. Compared to controls, the fractal dimensional parameter (D box ) of the two retinal capillary layers in most regions was significantly lower in diabetic patients with minimal DR (P < 0.05). The D box of the diabetic patients with no DR was also decreased in most regions of the deep retinal capillary layer (P < 0.05), but not in the superficial retinal capillary layer (P > 0.05). Based on the receiver operating characteristic curve analysis, the D box values for the deep retinal capillary layer had the highest index to discriminate diabetic patients with and without minimal DR from controls. CONCLUSIONS.Fractal dimension based on OCT-A has the potential to quantitatively characterize retinal microvascular changes in the early stage of DM. Changes in the fractal dimension in the deep retinal capillary layer could be an early indicator of microvasculature changes associated with retinopathy in type 2 diabetic patients.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients

Chen

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…19 In the mouse, it has been shown that the superficial plexus consists mostly of arterioles, which branch into three to four precapillary arterioles. 20 In contrast, the DVP is predominantly venous and consists of mostly capillaries. 12 Recent studies have differentiated three different vascular planes within the mouse retina, the intermediate layer (within the IPL) being the connection between the superficial and the DVP with mostly perpendicular divisions of the vessels, and thus being the less distinct one.…”

Section: Discussionmentioning

confidence: 99%

Optical Coherence Tomography Angiography in Mice: Comparison with Confocal Scanning Laser Microscopy and Fluorescein Angiography

Giannakaki-Zimmermann

Kokona

Wolf

et al. 2016

Trans. Vis. Sci. Tech.

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PurposeOptical coherence tomography angiography (OCT-A) allows noninvasive visualization of retinal vessels in vivo. OCT-A was used to characterize the vascular network of the mouse retina and was compared with fluorescein angiography (FA) and histology.MethodsIn the present study, OCT-A based on a Heidelberg Engineering Spectralis system was used to investigate the vascular network in mice. Data was compared with FA and confocal microscopy of flat-mount histology stained with isolectin IB4. For quantitative analysis the National Cancer Institute's AngioTool software was used. Vessel density, the number of vessel junctions, and endpoints were measured and compared between the imaging modalities.ResultsThe configuration of the superficial capillary network was comparable with OCT-A and flat-mount histology in BALBc mice. However, vessel density and the number of vessel junctions per region of interest (P = 0.0161 and P = 0.0015, respectively) in the deep vascular network of BALBc mice measured by OCT-A was significantly higher than with flat-mount histology. In C3A.Cg-Pde6b+Prph2Rd2/J mice, where the deep capillary plexus is absent, analysis of the superficial network provided similar results for all three imaging modalities.ConclusionOCT-A is a helpful imaging tool for noninvasive, in vivo imaging of the vascular plexus in mice. It may offer advantages over FA and confocal microscopy especially for imaging the deep vascular plexus.Translational RelevanceThe present study shows that OCT-A can be employed for small animal imaging to assess the vascular network and offers advantages over flat-mount histology and FA.

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“…These results will help us better understand the cellular and molecular basis of disease progression via longitudinal studies. OCT has been recently used in conjunction with imaging techniques such as scanning laser ophthalmoscopy, [32][33][34] fundus autofluorescence, 35 fluorescein angiography, 32,36,37 ultrasound, 38 and Indocyanine Green angiography, 39 helping in better diagnosis of diseased tissue. Multiphoton imaging has also been used to study fluorescent cells in the mouse retina.…”

Section: Discussionmentioning

confidence: 99%

High-resolution contrast-enhanced optical coherence tomography in mice retinae

et al. 2016

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Abstract. Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ∼0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.

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Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice

Cited by 60 publications

References 36 publications

Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients

Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients

Optical Coherence Tomography Angiography in Mice: Comparison with Confocal Scanning Laser Microscopy and Fluorescein Angiography

High-resolution contrast-enhanced optical coherence tomography in mice retinae

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