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Ophthalmic Artery as a Sensor for Non-invasive Intracranial Pressure Measurement Electronic System

L. Bartusis, R. Zakelis, G. Daubaris, A. Ragauskas Telematics Science Laboratory, Kaunas University of Technology, Studentu str. 50, LT-51368 Kaunas, Lithuania, phone: +370 686 200 84, e-mail: telematics@ktu.lt S. Rutkauskas Department of Radiology, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Eiveniu str. 2, LT-50009 Kaunas, Lithuania V. Matijosaitis Department of Neurology, Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Eiveniu str. 2, LT-50009 Kaunas, Lithuania A. Preiksaitis Department of Neurology and Neurosurgery, Vilnius University Faculty of Medicine, Siltnamiu str. 29, LT-04130 Vilnius, Lithuania


Introduction
More than one hundred and seventy years ago, Magendie discovered a small foramen in the floor of the fourth ventricle and pointed out the connection between the cerebrospinal fluid (CSF) in the ventricular system and in the subarachnoid spaces of the brain and cord. By this significant discovery, he paved the way to understanding the circulation of CSF and to problems associated with increased CSF pressure. In the late 19 th century, Quinke suggested the technique of lumbar puncture to measure the pressure of the CSF. This was the earliest clinical method of an assessment of intracranial pressure (ICP) [1].
Although these two pioneering scientists realized the importance of ICP measurement, they couldn't suspect that in the modern 21 st century this fundamental physiological parameter would be monitoring so routinely in clinical practice, especially in intensive care units (ICU). The main reason of this phenomenon -traumatic brain injury (TBI).
Data are critical to understand TBI as an important public health problem. For example, each year an estimated 1,7 million people sustain a TBI annually in the USA alone. Of them: 52 thousand die, 275 thousand are hospitalized [2].
Continuous monitoring of various physiological parameters, including ICP is necessary in order to minimize mortality rate of such patients. Physicians could apply adequate treatment only if they know physiological parameters such as arterial blood pressure (ABP), intracranial pressure, autoregulation condition of brain blood flow and others.
Unfortunately, measuring ICP using invasive technology is the only way currently available in clinical practice [3]. The reason of this current situation is because scientists were focused on searching correlations between biophysical parameters, which could be measured noninvasively, and ICP. Indeed, ICP affects a lot of biophysical parameters: diameter of cranium [4], stress level of skull bones [5], otoacoustic emission signal [6], etc. However, such correlations between biophysical parameters and ICP are individual for every single human being and varies in time because of the influence of other physiological parameters. Correlation based non-invasive absolute ICP (aICP) measurement systems must be individually calibrated for every single patient. Unfortunately, non-invasive "gold standard" aICP measurement system which is needed for calibration does not exist.
In order to solve the problem of calibration, it is necessary to find measurement method which works perfectly without any calibration and to find the way of applying this principle for a non-invasive aICP meter.

Ophthalmic artery as gravimetric scales
Gravimetric scales are one of the earliest measurement device used in the history of mankind. This instrument works without calibration very accurately if it is preliminary balanced. If we want to measure the weight of a physical body, we put the physical body on one plate of the gravimetric scales ( Fig. 1, a) whereas on the other one we put a known values of weights till both plates balance each other perfectly ( Fig. 1, b). In case of balance the weights on both plates are equal because Earth's gravitational force affects both plates and physical bodies equally. In order to know the measured body weight we could simply look at the opposite plate of the gravimetric scales and count the values of the known weights.
In order to apply this measurement technique to the non-invasive aICP meter, instead of comparing weights it is necessary to compare absolute pressures. However, gravimetric scales must be replaces with something else.
One very particular blood vessel, which is called ophthalmic artery (OA) exists in human being head. OA arising from the anteriorly convex arch of the internal carotid artery inside human head, where aICP exists, passing under the optic nerve within the optic nerve canal into the orbit, where small intraorbital pressure affects this part of OA [7] (Fig. 1, c). It is proved, that various parameters of the blood flow equalize in both intracranial and extracranial parts of OA in case of equality of ICP and external pressure (Pe) applied to the tissues surrounding the eyeball [8] (Fig. 1, d). At this point instead of weights it is possible to compare pressures, whereas OA becomes aICP sensor. Fig. 1. Ophthalmic artery analogy with gravimetric scales: adisbalance of scales; b -balance of scales; c -ophthalmic artery, when Pe=0; d -ophthalmic artery, when Pe=ICP; e -pulsatility indexes, when Pe=0; f -pulsatility indexes, when Pe=ICP For the pressure balance Pe=ICP indication could be used insonation angle independent parameters of the blood flow measured by Doppler ultrasound. A pulsatility index which is invariant to ultrasonic insonation angle can be used in a simplest case here V syst -peak systolic blood flow velocity, V diastminimum diastolic blood flow velocity, V mean -mean blood flow velocity during the cardiac cycle. For example, pulsatility indexes measured in both OA segments are presented in Fig. 1: e) -without external pressure, f) -in the point of pressure balance.
Innovative equipment for the search of the OA segments and measurement of the blood flow parameters The first task before begining the non-invasive measurement of blood flow parameters is to find anatomical positions of both OA segments: intracranial (IOA) and extracranial (EOA). For this reason, an innovative hardware and software has been created in Telematics Scientific laboratory of Kaunas University of Technology. The core of this system is two-depth twelve channel transcranial Doppler (TCD) device [9]. The structure of a novel aICP meter is presented in Fig. 2. a) b) c) Fig. 2. Non-invasive measurement system of absolute ICP: ablock diagram (black arrows -electrical signals, white arrowpressure "signal"); b -photograph of the current version of aICP meter; c -head frame with pressure chamber and ultrasonic transducer puted on a head The combined electronic and mechanical scanning ultrasonic TCD transducer, which consists of array of twelve piezoelements is installed into mechanical head frame (Fig. 2, c). Central frequency of ultrasonic pulses is 2 MHz. Maximum emitted ultrasonic power of 50 mW/cm 2 is safe for ultrasonic Doppler measurements through the eye and meets the clinical safety requirements. Electronic scanning of single ultrasonic beam is used in order to locate IOA and EOA. In addition mechanical scanning is needed (using head frame which has six degrees of freedom) in order to find optimal transducer position on the orbit. Magnetic resonance image (MRI) of region of interest (ROI) together with schematic representation of ultrasonic transducer is presented in Fig. 3, a).
Using a specially created software it is possible to see two separate white spots simultaneously when ultrasonic TCD transducer is in optimal position on the orbit and ultrasonic beam is focused into the intracranial and extracranial segments of the OA. This software is also capable to visualize blood flow spectrograms from a different segments of the OA (Fig. 3, b).
aICP measurement process can be initiated when both spectrograms are stable in time. For this purpose a pressure cuff which surrounds the tissues of the eyeball is infliated till 4 mmHg of absolute pressure. This pressure is maintained an average of 1 minute while blood flow velocities are measured in both segments of the OA. This system is capable to measure blood flow velocities up to 90.5 cm/s. Absolute pressure in the pressure cuff is increased by 4 mmHg sampling steps and measurement of the blood flow velocities is conducted fully automatically. This measurement process continues until the pressure balance aICP=Pe is obtained [10,11]. Measured Pe value (mmHg) in the balance point which estimates aICP is displayed as a final measurement result.

Results of comparative clinical studies
According to definition ICP is a pressure of CSF. Intracranial segment of OA is surrounded by CSF. That means that aICP is measured non-invasively as a pressure in the CSF using OA as a pressure sensor. "Gold standard" invasive ICP meters with systematic error close to zero were used for CSF pressure measurements via lumbar puncture and ventriculostomy in comparative prospective clinical studies [12].
84 neurological patients (101 paired measurements) were included in the latest clinical studies. The average age of patiens was 46.4 years (from 18 to 78). Patients were selected with different diseases and a wide range of different physiological parameters. These studies were performed at the Department of Neurology at Kaunas Clinics of University and Department of Neurology and Neurosurgery at Vilnius University. The studies design was approved by the local research and ethics committee (registration number BE-2-26).
Measurement data analysis of the latest comparative clinical studies showed that an accuracy of non-invasive aICP meter expressed by the mean systematic error (bias) is 0.03 mmHg (CL=0.97). Precision of aICP meter expressed by standard deviation (SD) of random error is SD=2.3 mmHg (CL=0.97). That is statistically significant clinical evidence on high accuracy and precision of noninvasive ICP measurement which is based on application of ophthalmic artery as an intracranial pressure sensor.

Conclusions
Innovative non-invasive aICP meter was created, which measures ICP absolute value fully automatically. Location of IOA and EOA segments only is done with operator assistance.
Many influential physiological parameters: heart rate, arterial blood pressure, intraocular pressure etc., and individual patient specific factors such as anatomical and physiological differences of patients, can influence parameters of the OA blood flow including pulsatility indexes. However, these factors do not affect the value of negligible systematic error of proposed non-invasive aICP meter.
The standard deviation of random error across all patient records is SD=2.3 mmHg and it is even less then 4-5 mmHg error tolerance that is a worthwhile practical clinical goal [13].
In conclusion it is fair to say that OA is a proper sensor for electronic non-invasive aICP measurement system which is able to measure absolute ICP values accurately and precisely without patient specific calibration at the first time.