Assessment of optic nerve vascularity in healthy eyes using superb microvascular imaging: a preliminary study

Abstract

Background

Changes in optic nerve vascularity are observed in many diseases. Superb microvascular imaging (SMI) has the potential to become the method of choice for detecting microvasculature in the optic nerves.

Purpose

To evaluate optic nerve vascularity in healthy individuals through power Doppler sonography (PDUS) and SMI.

Material and Methods

Twenty-seven healthy patients with 54 eyes were prospectively evaluated. The duration of the examination for optic nerve vascularity lasted until the posterior ciliary artery blood supply was observed in PDUS and SMI. The visibility of vascularity, as well as the ratio of the vascular structures to the optic nerves (vascular index [VI]), was evaluated.

Results

Fifty-four eyes were evaluated from a total of 27 patients (mean age = 49.0 ± 19.42 years). The VI value for the right optic nerve was 29.58 ± 4.00 while for the left optic nerve, it was 31.21 ± 3.52. Vascularity was clearly observed in both eyes (n = 54) in all 27 cases in the evaluation performed with the SMI technique. However, with the power Doppler examination, vascular flow was not observed in 14 right eyes and in 10 left eyes within the specified timeframe.

Conclusion

The results indicate that imaging of vascular structures can be done faster and better with SMI than PDUS examination. The normal VI values may provide important information about the blood supply of the optic nerve, which is of relevance in orbital pathologies and many systemic conditions.

Keywords

Power Doppler superb microvascular imaging retinal vascularity

Introduction

The retinal blood vessels provide important information about the blood supply of the optic nerve and the general condition of vessels in the body, which are of relevance in orbital pathologies and many systemic conditions, such as diabetic retinopathy, thyroid-associated orbitopathy, ischemic optic neuritis, glaucoma, and retinal vein thrombosis. Optic nerve atrophy can also be seen in the diseases mentioned above, but the change in vascularity is observed earlier (1 –3). The pathogenesis for each disease is not yet fully understood, but recent studies indicate that changes in blood flow to the optic nerve could be of great importance (4). The ability to detect these changes at an early stage could offer the possibility of early detection and treatment of diseases that may otherwise cause blindness (5).

Various techniques, such as ultrasound color Doppler imaging, magnetic resonance imaging, laser Doppler flowmetry, and optical coherence tomography, have been developed to measure retinal artery blood flow. However, none of these techniques developed for the measurement of retinal artery blood flow have widespread clinical applications because of various limitations (2).

Superb microvascular imaging (SMI) is a new Doppler imaging method used to detect blood flow in microvascular structures. This new Doppler technique eliminates the signals of artifacts due to the movement of normal tissues and vascular pulsation; it only preserves signals from vascular structures, so that even very low-velocity blood flows can be detected (6). SMI provides detailed information about very slow and very thin vascular structures and allows the viewing of microvascular structures. There are two types of SMI: color SMI (cSMI) and monochrome SMI (mSMI) (7).

To our knowledge, the PubMed database does not contain any information about the application of this method in the imaging of ocular vessels, although there are numerous studies that have made use of conventional Doppler (studies about Color Doppler Vascular Index in colon cancer and stomach cancer have been reported, but not for the optic nerve) and other techniques (1,2,8,9). The aim of the present study was to evaluate optic nerve vascularity in healthy individuals through power Doppler (PD) and SMI. It can provide ease of use and rapid diagnostic advantage since it is a real-time and rapid method and has no known harmful effects such as radiation.

Material and Methods

Patients

The study was conducted from June to November 2019. It was approved by the Institutional Review Board and informed consent was obtained from all the participants. Based on their clinical history, patients who did not have any complaints in relation to ocular and optic nerve pathology or systemic diseases, such as diabetes or vasculopathies that may affect the optic nerve, were included in the study. Individuals were excluded if they were pregnant, smokers, had uncontrolled hypertension, or if any abnormality was found as part of the pretreatment screening, unless the investigators considered the abnormality to be clinically irrelevant. Finally, 27 healthy patients (18 women [66.6%], 9 men [33.3%]) with 54 eyes were prospectively evaluated. The cases were evaluated after they were categorized into two groups, namely, under the age of 45 years and older than 45 years.

The patients were examined while in the supine position. A coupling gel was used between the probe and the eyelids to obtain images. The probe was placed gently on the eyelids without any compression. They were instructed to keep their eyes closed and to refrain from moving their eyes during the examination. The duration of the examination for optic nerve vascularity lasted until the posterior ciliary artery blood supply was observed in all three of the PD imaging, mSMI, and cSMI (Fig. 1a–c). The posterior ciliary arteries were observed near the lateral or medial of the optic nerve. The visualization of flow in the ciliary artery was taken as reference in the present study. Since we conducted the study on healthy individuals, it was assumed that the vascular structures were normal. In cSMI, the visibility of vascularity as well as the ratio of the vascular structures to the optic nerves (vascular index [VI]) was evaluated. A region of interest (ROI), including the area where vascularization was continuously monitored, was manually drawn at the optic nerve boundary (Fig. 2). Within the ROI, the rate of color pixels in the whole area was automatically calculated by the device in percentages to obtain the VI values, including the arterial and venous total vascularity supply. The highest VI value was then evaluated.

Fig. 1.

(a) Power doppler imaging, (b) mSMI, and (c) cSMI demonstrating optic nerve vascularity. cSMI, color superb microvascular imaging; mSMI, monochrome superb microvascular imaging.

Fig. 2.

A ROI including the area, shown as the VI value on the bottom left, where vascularization is continuously monitored was manually drawn at the optic nerve boundary. The optic nerve vascularity measurement was done from 3 mm posterior to the papillae. ROI, region of interest; VI, vascular index.

Ultrasound and superb microvascular imaging

All lesions were detected using the US Aplio 500 (L14-5, Aplio 500; Toshiba Medical Systems, Tokyo, Japan). The PD, mSMI, and cSMI samples of the optic nerve vasculature were obtained with a high-frequency linear probe (frequency range = 5–14 MHz) and recorded. The mSMI and cSMI modes were used (SMI > 50 Hz frame rate vs. PD with 10–15 Hz frame rates). PD and SMI evaluations were performed using a pulse repetition frequency set at 870–966 Hz and 220–234 Hz, respectively. The color gain for SMI was automatically set to 40 dB, which adequately suppressed the background color. All ultrasound exams were performed by the same radiologist.

Statistical analysis

SPSS 21.0 (IBM Corp., Armonk, NY, USA) was used for the analysis of variables. The Kolmogorov–Smirnov and Shapiro–Wilk tests were used to assess the fit of data to a normal distribution. Group comparisons were made using an independent t test, as the data provided the assumption of normality. Quantitative variables are shown as mean ± SD. Variables were investigated at the 95% confidence interval, and P < 0.05 was accepted as significant.

Results

Vascular index values

In the present study, 54 eyes were evaluated from a total of 27 patients (mean age = 49.0 ± 19.42 years). The Shapiro–Wilk test, which is ideal for displaying the normal distribution of a small to medium-sized dataset, showed normal distribution. P values for the right eye and for the left eye were 0.108 and 0.415, respectively. The VI value for the right optic nerve was 29.58 ± 4.00 and that for the left optic nerve was 31.21 ± 3.52. Data showing differences between groups in terms of right and left VI values are presented in Table 1. Both the right and left optic nerve VI values of the male patients were lower than those of the female patients. The VI values in both eyes were slightly lower in patients aged < 45 years compared to those aged > 45 years. The VI value of the group with the power Doppler positive in the right eye was lower than that of the negative group. The VI value of the group with the power Doppler positive in the left eye was higher than that of the negative group. Although there were slight differences in the values stated above, no statistically significant difference was observed in any of them (P > 0.05).

Table 1.

Data showing differences between groups for right and left optic nerve VI values.

	Right VI	P	Left VI	P
Male	28.86 ± 3.48	0.523	30.98 ± 4.03	0.816
Female	29.93 ± 4.29	0.523	31.33 ± 3.36	0.816
Age < 45 years	28.29 ± 4.27	0.170	30.31 ± 3.81	0.280
Age > 45 years	30.46 ± 3.68	0.170	31.83 ± 3.29	0.280
Right ocular Doppler (+)	28.21 ± 3.93	0.064	30.79 ± 2.91	0.526
Right ocular Doppler (–)	31.05 ± 3.67	0.064	31.67 ± 4.16	0.526
Left ocular Doppler (+)	29.74 ± 4.58	0.786	31.78 ± 3.75	0.288
Left ocular Doppler (–)	29.30 ± 2.96	0.786	30.26 ± 3.04	0.288

Values are given as mean ± SD.

SD, standard deviation; VI, vascular index.

SMI and Doppler findings

Vascularity was clearly observed in both eyes (n = 54) in all 27 cases in the waiting period until the posterior ciliary artery blood supply was observed in the evaluations conducted using the mSMI and cSMI techniques. However, in the PD examination, vascular flow was not observed in 14 right eyes and in 10 left eyes within the specified timeframe (Fig. 3a–c) (Table 2). No flow was observed in both eyes in seven of those with no flow (n = 24) with Doppler. Therefore, in the waiting period, no vascularity was observed in at least one eye in 17 of 27 cases (62.96%) with PD.

Fig. 3.

In the waiting period until the posterior ciliary artery blood supply was observed. (a) Vascular flow was not observed with power Doppler examination, whereas optic nerve and more prominent ciliary vascularity was clearly observed in the evaluation made with (b) cSMI and (c) mSMI techniques. cSMI, color superb microvascular imaging; mSMI, monochrome superb microvascular imaging.

Table 2

Demographic information of patients.

Patient	Age (years)	Sex	Right PD	Left PD	Right eye VI (%)	Left eye VI (%)	Right mSMI	Left mSMI
1	72	M	–	–	29.1	30.0	+	+
2	76	F	+	+	36.9	38.2	+	+
3	23	F	–	–	29.9	34.4	+	+
4	34	M	–	+	24.2	27.5	+	+
5	69	M	+	+	29.0	34.9	+	+
6	62	F	–	–	28.8	31.6	+	+
7	22	F	+	+	28.7	27.3	+	+
8	15	F	+	–	25.9	25.3	+	+
9	28	F	+	+	32.9	31.6	+	+
10	70	M	–	+	28.6	34.5	+	+
11	71	M	–	+	28.9	25.6	+	+
12	21	F	+	+	28.0	23.8	+	+
13	33	M	+	+	32.0	35.6	+	+
14	44	F	–	+	18.1	32.7	+	+
15	73	M	+	+	32.1	34.5	+	+
16	49	F	–	–	30.3	29.4	+	+
17	44	F	–	–	30.7	30.4	+	+
18	60	F	+	+	25.9	31.8	+	+
19	18	F	–	+	29.0	32.6	+	+
20	47	F	–	+	31.4	33.3	+	+
21	45	F	+	–	31.4	30.6	+	+
22	63	F	+	–	31.0	34.6	+	+
23	42	F	+	+	31.8	32.3	+	+
24	68	M	–	–	22.8	25.8	+	+
25	52	M	–	–	33.1	30.5	+	+
26	70	F	–	+	30.1	32.8	+	+
27	52	F	+	+	38.1	31.3	+	+

Monitoring vascularity with PD and mSMI in both eyes in the waiting period until the posterior ciliary artery blood supply observation, and evaluation of VI with cSMI.

cSMI, color superb microvascular imaging; PD, power Doppler; mSMI, monochrome superb microvascular imaging; VI, vascular index.

Discussion

In the present study, we evaluated the retinal blood flow values in normal eyes. VI values in men were lower than those in women, which did not show statistical significance. mSMI and cSMI were better than color/power Doppler ultrasonography (CDUS/PDUS), as SMI detected the presence of blood flow in patients in whom CDUS/PDUS could not identify any blood flow in the waiting period until the posterior ciliary artery blood supply was observed. In cSMI, the VI that shows total retinal blood flow was similar in both eyes.

The measurement of optic nerve head blood flow is especially important in conditions where a blood flow change is believed to play an important role in the etiology of diseases, such as ischemic optic neuropathy, diabetic retinopathy, dystrophic optic neuropathy, and glaucoma, a topic that has attracted much research attention (2 –4,8,10).

Imaging methods including retinal function imager (RFI), optical coherence tomography angiography (OCTA), laser speckle flowgraphy (LSFG), and Doppler US (CDUS/PDUS) may be used for measuring optic nerve blood flow (5). The RFI is a direct method in which the hemoglobin in erythrocytes is visualized and blood flow velocities are calculated from a series of photos. It is highly suitable for research and clinical trials, but it is too time-consuming to integrate in daily practice (5,11,12). The OCTA is a technique wherein images are obtained using a swept source. It uses multiple scans that are conducted in the same area, and the images are evaluated for changes as an expression of motion and flow with good reproducibility; however, problems with artifacts are often encountered (5,13). LSFG uses a laser light that creates a light-scatter pattern in the tissue. Particles moving in the area cause changes in the speckle pattern from which a relative blood flow can be estimated (14). Only the evaluation of the vascular flow at the level of the retina and optic nerve head can be made with the techniques mentioned above, except Doppler US. It does not give information about the optic nerve structure and diameter or the adjacent retrobulbar area. However, the optic nerve, retinal and ophthalmic vessels, and other orbital structures can be evaluated with CDUS and/or SMI-US.

DUS was first introduced as an ophthalmological method of measuring blood flow in the early 1990s (15). It can be used to assess velocity and detect regional blood flow, as well as in patients for whom opacities make it impossible to examine the retina with an ophthalmoscope (16). However, flow velocity depends on the size of the vessel, insonation angle of the sound beam, depth of the examined object, scanner sensitivity, and the skills and experience of the operator (17).

The SMI is a novel Doppler method whose greatest advantage is that it more successfully shows very fine vascular structures compared with CDUS and PDUS (18 –20). In Doppler ultrasound, there are two sources for the signal: blood flow and tissue movement (clutter). During image processing in conventional Doppler US, the wall filter eliminates all clutter signals that superpose with slow-flow signal because the device cannot distinguish between them. SMI uses a developed filtering algorithm for isolating and eliminating clutter while preserving the slow-flow signals. It has higher frame rates and lower pulse repetition frequencies than color Doppler imaging (19,21,22).

As far as we know, there has been no study about SMI in retinal vascularity, so no comparisons can be made. However, in studies on the liver, breast, parotid gland, testis, musculoskeletal system, and carotid plaque, it has been reported that the imaging of vascular structures can be done faster and better with SMI than with Doppler examination (18,19,23,24). In the present study, similar to the literature, mSMI and cSMI depicted retinal blood flow more quickly and more responsively than CDUS/PDUS. Detecting the changes in optic nerve vascularity earlier and obtaining images faster and independent of technical limitations compared to power Doppler will contribute to diagnosis and early treatment.

The present study has some limitations. First and foremost, we had a relatively small sample size. Second, although it showed advantages in the detailed evaluation of microvascular structures, the data on SMI have not been standardized. Third, lack of inter-observer variability constitutes the limitations of the study.

In conclusion, this preliminary study determined the reference VI values for retinal vascularity. The ability to detect the changes in optic nerve vascularity at an early stage could offer the possibility of early detection and treatment of diseases that may otherwise cause blindness. Our results indicate that SMI has the potential to become the method of choice for detecting microvasculature in the optic nerves.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Abdussamet Batur

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