Analysis of Total Retinal Blood Flow in Normal and Diabetic Rats with Ultrahigh-Speed Spectral / Fourier Domain OCT

Abstract

 

Purpose:

 

Assessing total retinal blood flow in vivo is an important research area because many ocular diseases, such as diabetic retinopathy and glaucoma are associated with changes in ocular blood flow. This study investigates the feasibility of total retinal blood flow measurement in a small animal model of diabetes using Doppler OCT.

 

Methods:

 

An ultrahigh-speed spectral OCT system at 840nm with a 244kHz A-scan rate was developed. At 244kHz, the maximum axial velocity measurable with Doppler OCT was 75.4mm/s. Animal procedures were performed under an approved protocol by the Committee on Animal Care at MIT. Diabetes was induced in three male Sprague Dawley rats with streptozotocin (STZ). The three diabetic rats and four age-matched control rats were imaged at baseline and once a week for three weeks after diabetes induction. By OCT scanning over 200μmx200μm centered at the central retinal artery repeatedly, a rapid volume acquisition rate of 55Hz was achieved. Total flow was measured by extracting Doppler images in the en face plane and integrating over the vessel cross section. This algorithm is simple and robust since it avoids the need to measure blood vessel angles as in other Doppler approaches.

 

Results:

 

Fig.1(A) shows an example of the pulsatile total blood flow measured in a normal rat at baseline. Fig.1(B) shows that pulsatility significantly modulates flow and therefore should be averaged for an accurate comparison of control and diabetic cohorts. Fig.1(C) summarizes the short-term repeatability evaluated from the nine cardiac cycles in (A). Fig.1(D) summarizes the measured total flow values. Because there was a significant variation in flow among individuals, reduction in flow compared to baseline was calculated separately in each animal. At week 3, total flow decreased by 28.2±9.0% in diabetic rats, while it decreased by 7.3±19.8% in the control rats. The p-value was <0.05. However, these preliminary results should be interpreted with caution because of the variation in flow. Future effort will involve reducing the sources of variation.

 

Conclusions:

 

These results demonstrate the ability of ultrahigh speed OCT to measure the pulsatile total retinal blood flow and the feasibility of longitudinal studies in small animal models of disease.  

 

Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • blood supply • diabetic retinopathy