Dynamic Measurement Platform Of Pupillary Light Reflex And Correlation Of The Pupil Change And Intracranial Pressure

Background:Pupillary light reflex(PLR), which refers to the phenomenon of pupil diameter contraction, collaboratively dominated by the sympathetic and parasympathetic when the lighting conditions change. PLR, because of the particularity of its nerve reflex pathway, becomes an important part of nervous system examination. Clinical practice found that there was quite different in PLR of traumatic brain injury(TBI) patients between different injury conditions as well as the same injury condition at different times. If excluding the influence of nerve cranial damaged by the factors such as drugs, II and III, PLR difference of TBI patients may be related to abnormal electrophysiological activity in the central nervous system, which was closely associated with intracranial pressure(ICP). But no study reported about the correlation of PLR and ICP. Based on this, the issue, according to PLR dynamic precision digital measurement, investigated the correlation between PLR and ICP from the pupillary response data and proposed a method of based-PLR non-invasive intracranial pressure monitoring(n ICP).Objective:1. To provide a new way for clinical PLR examination by building a dynamic measurement platform that makes dynamic precise digital measurement of pupil change; 2. To explore the idea based on n ICP monitoring pupil change by finding number patterns of PLR changes and ICP.Method:The objective of our study conducted according to two part: the specific work was as follows:1. Set up a platform for automatically and dynamically measuring light reflex of pupil. We achieved the design of the pupillary light reflex dynamic measurement and finally set up the platform. Meanwhile we conducted the measurement of PLR on healthy adults.(1) Study the physiological anatomical characteristics and the existing detection means of pupil and establish methods of measurement pupil detection. We divided the automatically and dynamically measuring platform according to functions as follows: Image acquisition system, light control system, graphic calculation analysis system and computer platform. Each module was separately conducted screening of hardware elements, assembly, and software development. Visual Studio software was used to produce the software in the development environment of Windows operating system, resulting the camera equipment control, image acquisition, read, graphic calculation and light automatic control.(2) We applied this platform to automatically and dynamically measure the pupils of healthy adult, assessing the operation of platform: The experiment was conducted in three different scene respectively: dark environment, the natural light environment indoor, and the corridor outdoor in the afternoon. Six groups were included according to light intensity while controlled by PSo C(Programmable System-On-Chip).2. The correlation of the pupil change and intracranial pressure. We made a canine model of hyper-intracranial pressure and detect the PLR in the canine. After analyzing the correlation between PLR and ICP, we initially performed a n ICP design based on PLR.(1) The adjustable high cranial pressure animal model: Fourteen Beagle canines were divided into two groups. Ten canines in experiment group were buried capsule in the right frontal epidural and ICP in the left frontal. Four canines in control group were only buried ICP probe in left frontal. The balloon expansion in experimental group was conducted using trace pump, in a constant speed of 10ml/h. We recorded the change of the intracranial pressure in real time and sketch the experimental dogs’ intracranial volume- pressure curve. The two groups were compared on artificial feeding, the anima abnormality, infection, prognosis and initial intracranial pressure and intracranial pressure after buried capsule.(2) Apply of the pupil dynamic measurement platform, we measured the pupil PLR changes of the canines in different intracranial pressure. The experiment was conducted when the canine was sober and cooperate in the environmental light intensity of 80~120Lux by choosing white LED light source with an intensity of 600 Lux.With reference to the dog intracranial volume- pressure curve, we expanded the capsule and raised the intracranial pressure in a gradient of 5mm Hg, resulting 5 groups of pressure gradient. Finally, we record the pupil changes in following different intracranial pressure conditions: normal pressure、15mm Hg、20mm Hg、25mm Hg and 30 mm Hg.(3).Initially design the n ICP equipment based on n ICP according to the correlation of pupil changes and intracranial pressure.3. Statistical analysis in SPSS16.0. The counter variable was conducted using frequency and percentage. We performed statistical description using mean ±standard deviation. Because of the relative small sample in the part of making the model, we used Fisher’s exact test to compare two groups. We measured variable comparison between the two groups with group t test. Under the different condition of intracranial pressure, repeated measurement data analysis of variance was used to compare the pupil diameter. It is significant when the p value is below 0.05.Result:1. Set up a platform for automatically and dynamically measuring light reflex of pupil.(1)We choose the pupil image acquisition based on infrared imaging and graphics processing calculation method. The platform hardware configuration is as follows: Image acquisition system with WP U500 industrial camera and removal of infrared cut-off filter M3520- MPW2 optical lens, loading the FU- LGP025 visible deadline piece, composing infrared cameras; Use model for TS- 6030 LED lamp as auxiliary infrared light source; Choose 10 w white LED lamp as the stimulating light source, 20 cm distance provided on 1000- lux light intensity. Applying UT381 to light intensity detection and feedback control. Computer platforms equipped with start interface, more than 4 g of memory and above 1 t drive. Software is under the Windows system, using Visual Studio2010 environment creating MFC form and the c + + language was used. We built software interface In the MFC framework. Direct Show development kit was used to obtaining image and complete the settings of parameters of the camera. When we analyze the data, threshold segmentation, Hough transform, Otsu algorithm and algorithm filling method were all used to parse the pupil image. We can get 30 frame 1920×1080 images per second.(2) The operation of test platform for healthy adults PLR dynamic measurement: light intensity in dark environment, the natural light environment indoor, and the corridor of outdoor in the afternoon were 0.1Lux, 120 Lux and 350 Lux respectively. The stimulating light intensity was 40Lux、155Lux、270Lux、375Lux、490Lux and 600 Lux respectively. The infrared LED light source can stablely output background near infrared and continuously capture the pupil dynamically changing image in a speed of 30 frame 1920×1080 per second with the temporal resolution 33 millisecond. The result showed that the average diameter of pupil before stimulating was 5.61±0.15 mm,4.89±0.13 mm and 4.25±0.16 mm respectively. After removing light stimulation, the average diameter of pupil was 5.2±0.38 mm, 4.62±0.32 mm and 3.96±0.25 mm respectively revealing that the ambient light affect the pupil size. The mean maximum and minimum size after pupil contraction was 4.11±0.27 mm and 3.33±0.25 mm. The size decreased with light intensity of stimulation increasing, showing the size of pupil after contraction is related to the light intensity of stimulation. The size after contraction was similar when the light intensity was 490 Lux or 600 Lux. The difference of the speed of contraction and expansion among groups was not obvious. The result showed that pupil data resolution in theoretical state of is one over one thousand millimeter.2. The relationship between variation of pupil and intracranial pressure(1) We made the canine model of hyper-intracranial pressure and conducted the Fisher’s exact probability test. The experimental and control groups showed no statistical significance on artificial feeding, the animal abnormality, infection and prognosis(P>0.05). Using group t test, experimental group showed no statistical significance on initial intracranial pressure(10.9±1.2) comparing with control group(10.5±0.9, t=0.597, P=0.562). No statistical significance on initial intracranial pressure of experimental group before and after implanting capsule(11.5±1.4, t=1.029,P=0.317). We obtained the intracranial volume- pressure curve of canine after expanding capsule in a constant speed of 10ml/h. The average intracranial pressure before expanding, when expanding to 1ml and to 1.5ml were 10.8mm Hg, 13.2mm Hg, and 17.8mm Hg respectively. After that the intracranial pressure rapidly go up to 36.5mm Hg with the capsule volume being 2ml.The average volume of capsule is 2.8ml while the minimum and the maximum was 2.5ml and 4.0ml respectively.One of our canine experienced progressive consciousness and abnormal breathing when the capsule was expanded to 4ml and finally died in 24 hours. The other canines were all alive healthily.(2) We measured the pupil light reflex dynamically in the canine model of hyper-intracranial pressure and compared the difference of pupil diameter in different ICP conditions. The result showed that the difference of pupil diameter before contraction is not statistically significant.(Right eye: P=0.059, left eye P=0.994). However, the difference of pupil diameter after contraction is statistically significant(Right eye P<0.001,left eye P<0.001) while the variation of pupil diameter has no discipline with the increasing of ICP. The difference of the pupil contracting speed is statistically significant(right eye P=0.002, left eye P=0.023) and that speed gradually reduced with the increase of ICP. Finally, the difference of pupil diameter is not statistically significant after re-expansion(right eye P=0.069,left eye P=0.057).3. We realized a design for portablely and noninvasively detecting device of intracranial pressure based on pupil light reflex. The designing content included the controlling equipment for camera and light source, the coat used for installing camera and light source, and the camera to shoot the size of the pupil. The controlling equipment was used to save the pupil image to the memory card. Meanwhile the coat was connected to controlling equipment according to axis of rotation.Conclusion:1. We successfully set up a platform for automatically and dynamically measuring light reflex of pupil, providing the equipment and methods for detecting the pupil diameter and speed of change.2. We made an adjustable canine model of hyper-intracranial pressure under the condition that the function of nervous system in experimental animals was fully protected. The model is easy to operate and have a reliable ICP value, meeting the most pathophysiology demand of high cranial pressure. We verified that the contracting rate of pupil gradually reduced in light reflex with the intracranial pressure increasing beyond a certain gradient. The contracting rate of pupil in light reflex can be regarded as a good indicator for assessing the variation trend of intracranial pressure.3. We put forward a design method for the portable n ICP detecting equipment based on the newly set platform of automatically and dynamically measuring light reflex of pupil and the changing rule of the relationship between the pupil light reflex and ICP value. As long as it is successfully developed in the future, it will come true that physical examination of nervous system and detection of n ICP value can be combined together which will be widely applied in clinical practice.