Publication Highlight: Non-Invasive Real-Time Pulsed Doppler Assessment of Blood Flow in Mouse Ophthalmic Artery
Overview
It has been shown that even small disturbances in ocular vascular perfusion can lead to structural damage and visual impairment pathologies, such as glaucoma, age-related macular degeneration, and diabetic retinopathy1,2. Researchers recently verified a method in Cell Reports Methods to measure blood flow velocity in the ophthalmic artery of mice, the major artery that supplies blood to the eyes3. This method provides a simpler, lower-cost approach for longitudinally monitoring ocular perfusion, especially of importance for screening drugs that target the ophthalmic artery directly.
Using the Doppler Flow Velocity System (DFVS), the researchers scanned the surface of the eye with a high-frequency Doppler probe, near the temporal cantus of the eye and were able to reproducibly assess blood flow velocity of the ophthalmic artery, as shown in Figure 1. The researchers monitored Doppler indices like peak systolic velocity, end-diastolic velocity, and the resistivity and pulsatility indices that can further serve as quantitative biomarkers for ocular vascular health.
MicroCT imaging and 3D reconstruction of the ultrasound trajectory anatomically established this blood flow velocity as the ophthalmic artery as it emerged from the optic canal. To further confirm that this was the ophthalmic artery, the researchers ligated both of external carotid artery (ECA) and the internal carotid artery (ICA). The ophthalmic artery is a branch of the ICA. The researchers confirmed that when the ICA is ligated, subsequent downstream blood flow to the ophthalmic artery is reduced, as highlighted in Figure 2.
This technique offers a simple, non-invasive method to measure blood flow to the eye4. The ophthalmic artery is the primary blood supply to the eye and a major branch of the internal carotid artery, making it a key marker for both ocular and as a potential surrogate for cerebral circulation. Due to the method’s absolute blood flow velocity measurements, reproducibility, and real-time monitoring, this method offers a promising tool for preclinical vascular research.
Figure 1. Setup of non-invasive Doppler OphA blood flow velocity measurements at mouse orbital opening.
An anesthetized mouse is placed in a prone position on the ECG board. The Doppler probe sensor tip is at the temporal canthus. Doppler in-phase(I), quadrature (Q), and ECG signals are acquired, processed, displayed, and recorded in real-time (middle). Representative Doppler velocity signal waveforms with major parameters acquired for analysis (right). DVFS, Doppler flow velocity system; US, ultrasound; ECG, electrocardiogram; FV, flow velocity. *Figure and text adapted from Sharina, I. et al. Cell Reports Methods. 2025.
Figure 2. Targeted artery (Ophthalmic Artery) originates as a branch off the ICA.
(A) Experimental setup for sequential ECA and ICA branch occlusion. A surgically prepared mouse on the heated board with continuous ECG monitoring, the Doppler probe, and the dissected area are shown. (B) Magnified view of the neck region prepared for occlusion. CCA, common carotid artery; ICA, internal carotid artery; ECA, external carotid artery. (C) Schematic representation of anatomical features in close proximity to CCA and ICA/ECA branching site (adapted from Liu et al5). (D) Changes of the Doppler signal during sequential occlusion of the blood flow in left ECA and ICA. A representative of 6 independent sequential occlusions from 3 individual mice is shown. *Figure and text adapted from Sharina, I. et al. Cell Reports Methods. 2025.
Highlighted Findings
Here are a few important findings reported in this publication. For in-depth information on the methods, findings, and results, please check out the full-text publication linked to this article. Â
- The researchers successfully and noninvasively measured the blood flow velocity in the ophthalmic artery with high-temporal resolution
- The orbital opening in mice provides an acoustic window for pulsed Doppler access to the ophthalmic artery
- Confirmation of the ophthalmic artery was done by subsequent microCT imaging with vascular contrast agent, occlusion of the internal carotid artery and the subsequent reduced blood flow in the ophthalmic artery, and a vasodilator response using 1 mg/kg sodium nitroprusside.
Conclusion
The Doppler Flow Velocity system is used in this study primarily to quantify blood flow velocity in the ophthalmic artery. However, the DFVS can be used to measure the blood flow velocity in any vessels such as carotid, femoral, or renal arteries, making it a versatile system for systemic hemodynamic assessments. The DFVS is also commonly used for preliminary cardiac analysis, global arterial stiffness measurements, validation of surgical models such as Transverse Aortic Constriction models, and validation of specific ligation models.
References
D, M., A, H., D, W., N, K. & B, S. Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma? Clin Ophthalmol 2, 849 (2008).
Toda, N. & Nakanishi-Toda, M. Nitric oxide: Ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res 26, 205–238 (2007).
Sharina, I. et al. Non-invasive real-time pulsed Doppler assessment of blood flow in mouse ophthalmic artery. Cell Reports Methods 5, 100983 (2025).
Fantini, S., Sassaroli, A., Tgavalekos, K. T. & Kornbluth, J. Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophotonics 3, 031411 (2016).
- Liu, Z. et al. Improving orthotopic mouse models of patient-derived breast cancer brain metastases by a modified intracarotid injection method. Scientific Reports 2019 9:1 9, 1–7 (2019).
