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. 2023 Aug 8;13(8):1230.
doi: 10.3390/biom13081230.

Non-Invasive Retinal Blood Vessel Wall Measurements with Polarization-Sensitive Optical Coherence Tomography for Diabetes Assessment: A Quantitative Study

Hadi Afsharan  1 , Dilusha Silva  2 , Chulmin Joo  3 , Barry Cense  1   3
Affiliations

Non-Invasive Retinal Blood Vessel Wall Measurements with Polarization-Sensitive Optical Coherence Tomography for Diabetes Assessment: A Quantitative Study

Hadi Afsharan et al. Biomolecules. .

Abstract

Diabetes affects the structure of the blood vessel walls. Since the blood vessel walls are made of birefringent organized tissue, any change or damage to this organization can be evaluated using polarization-sensitive optical coherence tomography (PS-OCT). In this paper, we used PS-OCT along with the blood vessel wall birefringence index (BBI = thickness/birefringence2) to non-invasively assess the structural integrity of the human retinal blood vessel walls in patients with diabetes and compared the results to those of healthy subjects. PS-OCT measurements revealed that blood vessel walls of diabetic patients exhibit a much higher birefringence while having the same wall thickness and therefore lower BBI values. Applying BBI to diagnose diabetes demonstrated high accuracy (93%), sensitivity (93%) and specificity (93%). PS-OCT measurements can quantify small changes in the polarization properties of retinal vessel walls associated with diabetes, which provides researchers with a new imaging tool to determine the effects of exercise, medication, and alternative diets on the development of diabetes.

Keywords: PS-OCT; blood vessel wall birefringence index (BBI); diabetes; retinal blood vessels; retinal imaging.

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Conflict of interest statement

The other authors declare that they have no competition interest related to this article.

Figures

Figure 1
Figure 1
Intensity (gray-scaled) and retardation cross-sectional images of the right eye of a diabetic subject. (a,b) are the cross-sectional images of an area near the ONH imaged with different scanning sizes (a) 4.5 mm by 1.5 mm, (b) ~1.0 mm by 1.5 mm). (c–e) are magnified regions of blood vessels 1 to 3 indicated in (b). In intensity images, darker areas represent a higher intensity. In retardation images, blue to red represent lower (0°) to higher (180°) retardation.
Figure 2
Figure 2
Diagram showing different steps taken to extract blood vessel wall polarization properties and corresponding BBI. Blue, red and purple arrows indicate steps taken based on the intensity, retardation and flow images, respectively. Black arrows show analysis based on blood vessel edge detection.
Figure 3
Figure 3
(a) Blood vessel diameters of five different blood vessels recorded from five healthy and five diabetic subjects plotted against corresponding wall thickness values. These data were averaged over four adjacent B-scans. There is a linear relationship between blood vessel diameter and corresponding wall thickness within all groups with R2 values ranging from 0.91 to 0.95. Error bars show SD. (b) Variations of BBI’ (i.e., normalized BBI) versus BBI follows a linear relationship with an R2 value of 0.95.
Figure 4
Figure 4
Birefringence of the blood vessel wall plotted against SNR of the area containing the blood vessel wall. While all the healthy blood vessels have higher SNRs, the birefringence values of the diabetic blood vessels are consistent and do not vary as a function of SNR. SNR and birefringence values are averaged over four adjacent B-scans. Error bars indicate SD.
Figure 5
Figure 5
Thickness and DPPR/UD measurements of diabetic and normal vessel walls. Realigned intensity (top panel) and corresponding color-Doppler flow (bottom panel) cross-sectional images with respect to the retinal surface recorded from (a) a diabetic patient and (c) a healthy individual. In the intensity images, a darker color indicates a lower intensity. The areas between two red lines mark the isolated blood vessels for analysis. (b) Associated DPPR and intensity images obtained by averaging A-lines within the isolated blood vessel area in (a). (d) Associated DPPR and intensity images generated by averaging A-lines within the isolated blood vessel area in (c). The DPPR is the product of DPPR/UD (birefringence) and optical path length. A least-squares fit was used to calculate DPPR/UD and to determine the boundary and therefore thickness of the blood vessel wall. In (b), the fit has a steep slope meaning that the diabetic blood vessel wall induced higher birefringence compared to the relatively moderate slope of the healthy blood vessel wall in (d). Blue-highlighted areas indicate blood vessel wall tissue.
Figure 6
Figure 6
BBI data obtained from normal and diabetic artery and vein walls. (a) Distribution of the BBI in healthy and diabetic subjects in different retinal arteries and veins. In diabetic patients, the BBI experienced a reduction in comparison to normal tissue. This reduction was higher in veins. The boxplots were generated based on the median, lower and upper quartiles. Bulletpoints show the distribution of the data and whiskers indicate the minimum and maximum values. No outlier points were identified in the plots. The difference between normal and diabetic BBIs are also statistically significant (p < 0.001). (b) Plots showing the BBI values of arteries and veins extracted from normal and diabetic subjects. Data are represented as mean ± SD (averaged over four adjacent B-scans). Arrows show the thresholds obtained by determining the 5th and 95th percentiles. Green and red backgrounds mark the normal and diabetic values. Statistical analyses were performed using one-way ANOVA.
Figure 7
Figure 7
Thresholds used to discriminate healthy and diabetic subjects for artery and vein walls. Histogram representation of the extracted BBI values for the analyzed (a) arteries and (b) veins of healthy (blue) and diabetic (red) subjects. The 5th and 95th percentiles were used to find the thresholds to distinguish between blood vessels of healthy subjects and from patients with diabetes (red and blue arrows). For arteries, BBI values smaller than 15.6 m are considered diabetic, while BBIs higher than 15.8 m are normal. For veins, the threshold is at 13.8 m.
Figure 8
Figure 8
Variation of the BBI values along different blood vessels. Cropped intensity en face images of the right eyes of (a) a healthy subject and (b) a diabetic patient. The arrows indicate the blood vessels where BBI was obtained. (c) BBI variation along the indicated blood vessels. Each value is the average of measurements obtained from four adjacent B-scans. Error bars show SD. NM: normal, DB: diabetic.
Figure 9
Figure 9
Repeatability of the thickness, DPPR/UD and BBI measurements. A blood vessel from the right eye of a diabetic subject was imaged four times and used to evaluate repeatability. Error bars are the SD of four adjacent B-scans. Based on ANOVA analysis, PRV for DPPR/UD, thickness and BBI were 0.12%, 0% and 6.3%, with p-values of 0.88, ~1 and 0.86, respectively, meaning that the measurements are repeatable.
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