Ocular Blood Flow Response to Applied Force: In Vivo Tests Toward Noninvasive Intracranial Pressure Monitoring1 (2015)

Cerebrospinal fluid (CSF) surrounds the optic nerve and central retinal artery in the intra-orbital space. The pressure of CSF in this area is referred to as intracranial pressure (ICP), and when elevated may cause swelling of the optic nerve and alter blood flow within the central retinal artery. In some cases, the posterior eye globe can eventually be flattened. Yang et al. [1] have suggested that elevated ICP can have a damaging effect on the optic nerve and visual acuity.There is a need for a noninvasive ICP measurement technique. A reliable, noninvasive tool for detecting relative changes in ICP would have a dramatic impact on neuro-intensive care, where only invasive measurement techniques (intracranial transducer, ventricular drain, or lumbar puncture) are currently available [2]. Specifically, such a device is needed for ICP monitoring in remote environments, such as spaceflight, where other equipment is unavailable. Vision impairments experienced during spaceflight are not fully understood. It is hypothesized that elevated ICP induced by microgravity is a significant factor in these changes. An in-flight ICP monitoring technique would offer valuable insight toward understanding the correlation between ICP and visual impairment [3].Transcranial Doppler ultrasonography can be used to detect changes in orbital and intracranial vascular flow patterns. The acoustic axis of the transducer can be aligned nearly parallel with the central retinal artery behind the globe near the anterior portion of the optic nerve head for maximum sensitivity. Bhatia and Grupta [4] have shown that these flow patterns are affected by ICP.Ragauskas et al. [5] have worked on a similar methodology. Similarly, their method is another variation of ophthalmodynamometry, which uses ophthalmic artery blood flow dynamics to determine ICP. Ragauskas et al. [5] illustrated an extracranial portion of the ophthalmic artery that travels in the extradural intraorbital space. This area is not surrounded by CSF and therefore is not exposed to ICP. Our proposed device differs by measuring flow at the optic nerve head, where CSF surrounds the blood vessel.Our proposed methodology to correlate changes in ocular blood flow velocity patterns in response to an applied force under different ICP levels has shown promise. By applying small forces to the front of the eye with a controlled actuator, we can observe changes in the blood flow velocity through the central retinal artery using transcranial Doppler ultrasound (Fig. 1).A single element, nonimaging ultrasound transducer is instrumented with a Futek load cell so that the amount of force applied to the eye with the ultrasound transducer is recorded. In addition, a Flexi-Force load cell is surgically implanted into the episcleral space near Tenon’s capsule and is used to measure in vivo force near the optic nerve head. Data from both load cells are recorded using an Arduino microprocessor.A porcine model is used to collect in vivo data and manipulate ICP. An elevated drip bag of normal saline is used to increase ICP via lumbar catheter (Fig. 2). The drip rate or height of the bag is used to slowly incrementally increase ICP from baseline (8–10 mm Hg) to 40 mm Hg. An ICP monitor is placed in the right frontal lobe (Fig. 2).The animal experiments are used to correlate in vivo central retinal artery blood flow properties such as resistivity and PI. A small force is applied to the cornea (front of the eye) while blood flow velocity is measured within the central retinal artery using Doppler ultrasound. A linear actuator is used to slowly apply force to the cornea with the ultrasound transducer and the implanted load cell measures the force response near the optic nerve head.A test begins as force is applied to the cornea with the ultrasound transducer, changing blood flow dynamics in the central retinal artery. After baseline (ICP of 8–10 mm Hg) tests are performed, ICP is incrementally increased until it reaches 40 mm Hg or until no reaction in blood flow dynamics is observed. Measurements are taken as ICP increases at approximately every 2 mm Hg. After baseline measurements are collected, the duration of the procedure is about 1 hr. Measurement of blood flow dynamics takes between 30 and 60 s at each increment of ICP.During each test, the blood flow velocity of the central retinal artery is monitored simultaneously at four depths (or gates) from the ultrasound transducer. The depths of 32, 38, 44, and 50 mm are monitored so that a strong blood velocity signal is maintained during the actuation of the transducer. The blood velocity profiles are matched up with the transducer load cell (Fig. 3). Specifically, the blood flow velocity profiles at the beginning and maximum applied force of the ultrasound transducers are compared.The (approximately) 1.5–2.5 N of force applied to the cornea is sufficient to produce significant changes in central retinal artery blood dynamics regardless of the ICP value. The surgically implanted load cell measured 0.4–0.6 N of force for both normal and elevated levels of ICP. The RI (difference in peak systolic velocity and minimum diastolic velocity divided by peak systolic velocity) and PI (difference in peak systolic velocity and minimum diastolic velocity divided by mean velocity) are calculated over the cardiac cycles. Preliminary results indicate that resistivity index (RI) and pulsatility index (PI) do not change as ICP is increased before the force is applied to the cornea (Fig. 4).Of particular interest is the change in RI and PI as force is applied to the cornea. In multiple animal experiments, the magnitude of percent change of RI and PI differed in response to differences in ICP (Fig. 5). Baseline ICP (8–10 mm Hg) results in a 15% increase in RI. Results indicate that as ICP increases, the percent difference in RI and PI decreases. ICP values between 25 and 30 mm Hg result in only a 0–7% increase in RI, and for ICP values between 35 and 40 mm Hg, a 5–10% decrease in RI is observed. A statistical fit of the RI data results in a 0.086 norm of residuals. Each in vivo test (period of applied force) took about 1 min to complete. Human subject testing was used to calibrate a comfortable tolerance of the amount of force applied to the cornea. Results indicate the human patients are comfortable with forces up to 3 N. Future work is currently aimed at increasing the number of in vivo experiments and validating the methodology toward developing a fast method for noninvasive monitoring of relative ICP changes.