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Test of a novel miniature blood pressure sensor in the coronary arteries of a swine model

Nan Wua, Kai Suna, Xiaotian Zoua, Kurt Barringhausb, Xingwei Wang*a

aDepartment of Electrical and Computer Engineering, University of Massachusetts Lowell, 1 University Avenue, Lowell, MA. 01854, USA;

bUniverisyt of Massachusetts Memorial Medical Center, University of Massachusetts Medical School, 55 Lake Avenue North Worcester, MA. 01655, USA

ABSTRACT

Fractional flow reserve (FFR) has proven to be very useful in diagnosis of narrowed coronary arteries. It is a technique that is used in coronary catheterization to measure blood pressure difference across a coronary artery stenosis in maximal flow. In-vivo blood pressure measurement is critical in FFR diagnosis. This paper presents a novel miniature all-optical fiber blood pressure sensor. It is based on Fabry-Perot (FP) interferometry principle. The FP cavity was fabricated by directly wet etching the fiber tip. Then, a diaphragm with well-controlled thickness was bonded to the end face of the fiber using the thermal bonding technique. Finally, the sensor was packaged with a bio-compatible and flexible coil for animal tests. A 25-50 kg Yorkshire swine model was introduced as the animal test target. The left anterior descending coronary artery (LAD) was exposed, and beyond the takeoff of the largest diagonal branch, a 3.0 mm vascular occluder was secured. Firstly, standard invasive manometry was used to obtain the blood pressure as baseline. Next, a guiding catheter was introduced into the ostium of the left main coronary artery, and the miniature blood pressure sensor was advanced into the LAD at a point beyond the vascular occlude. The blood pressure beyond the vascular occlude was recorded. The sensor successfully recorded the blood pressure at both near-end and far-end of the vascular occluder.

Keywords: Fiber optic sensor, Fabry-Perot, blood pressure sensor, fractional flow reserve.

1. INTRODUCTION Coronary artery disease (CAD), which is also called atherosclerotic heart disease, is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the oxygen and nutrients to the myocardium, which may cause angina pectoris, myocardial infarction, and sudden death1.CAD is the leading cause of the death; most patients with CAD show no evidence for decades as the disease progressing before the first onset of symptoms, often a "sudden" heart attack, finally arises. The disease is the most common cause of sudden death2, and is also the most common reason for the death of people over 20 years of age3. According to the present trends in the United States, There are at least 14 million patients. Moreover, half of healthy 40-year-old males will develop CAD in the future, and one in three healthy 40-year-old women3.

Recently, the angioplasty is commonly used to treat the CAD, which is initially described by interventional radiologist Charles Dotter in 19644. The angioplasty is the technique of mechanically widening the blockage and narrowed blood vessel caused by atherosclerosis. It inserts a guide wire from the groin to the coronary arteries, carrying on a catheter with a collapsed balloon into the narrowed locations and then inflated to a fixed size using water pressures some 75 to 500 times normal blood pressure (6 to 20 atmospheres). The balloon crushes the fatty deposits, hence opening up the blood vessel to improve the flow, and the balloon is then collapsed and withdrawn. The first use of transluminal balloon angioplasty for vasospasm is reported by the Russian neurosurgeon Zubkov and colleagues in 19835.

In order to locate blockages in a blood vessel and determine how severity they are, the angiogram is widely used for currently CAD treatment. Angiography or arteriography is a medical imaging acquisition technique which is used to visualize inside a blood vessel. It uses a guide wire to inject the radio-opaque contrast agent such as dyes to arteries, and then images by using X-ray based techniques such as fluoroscopy6. However, the 2-D X-ray imaging method sometimes is not sufficient to discover the obstacle. It may underestimate or overestimate the narrowing without considering the coronary collateral flow. Moreover, it is risky to some patients who may be allergic to dyes or who have kidney or liver

*[email protected]; phone 1 978 934-1981; fax 1 978 934-3027; http://faculty.uml.edu/xwang

Fiber Optic Sensors and Applications VIII, edited by Stephen J. Mihailov, Henry H. Du, Gary Pickrell, Anbo Wang, Alexis Mendez, Eric Udd, Proc. of SPIE Vol. 8028, 80280N · © 2011 SPIE

CCC code: 0277-786X/11/$18 · doi: 10.1117/12.884273

Proc. of SPIE Vol. 8028 80280N-1

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problems.

Blood pressure (BP) measurement is an alternative method for evaluating the hemodynamic severity of single stenosis in coronary arteries by fractional flow reserve (FFR) 7-13. It is a technique that is used in coronary catheterization to measure blood pressure difference across a coronary artery stenosis in maximal flow. This method has been eventually accepted by doctors since 1990s. Accurate in-vivo blood pressure measurement is critical in FFR diagnosis. Several companies currently are working on developing intravascular blood pressure sensors and some of them are released in the market. PressureWire intravascular blood pressure measurement system which is developed by St. Jude Medical is one of them. The sensor is fabricated in a standard 0.014’’ guide wire with a length of up to 300 cm. The measurement range of the pressure is from -30 mmHg to +300 mmHg 14. Volcano Corp., another company which is also working in this area, released its intravascular blood pressure measurement system: Smart Map. The sensor configuration is similar to the one from St. Jude Medical which is fabricated in a standard medical guide wire. The performance of the instrument is similar to St. Jude Medical 15. Millar Instruments released its intravascular blood pressure measurement catheter of which the length is up to 140 cm and the French size can be as small as 2 16. Due to the increasing interests of applying intravascular blood pressure measurement technology in FFR, a lot of commercial blood pressure sensors have been used in the in-vivo experiments to collect clinical data 13, 17. Most of these sensors are electrical sensors which may generate electrical noise to interfere with other electrical equipments in the operating room and they are not immune to electro-magnetic interference (EMI).

On the other hand, fiber optic pressure sensor is a potential substitution to the current electrical pressure sensor. The fiber optic pressure sensor can be easily inserted into the coronary due to its compact size which is generally 125 µm in diameter. The sensor cannot interfere with other electrical equipments because there is no electrical signal in the sensor. Furthermore, the sensor is immune to EMI. However, there are few companies developing such fiber optic pressure sensor for in-vivo blood pressure measurement. Samba Sensors has released their fiber optic pressure sensor which is used for in-vivo blood pressure measurement. Their sensor features the compact size with 0.36 mm in diameter and the pressure range is from -37.5 mmHg to 262.5 mmHg 18. The sensor consists of a 0.36 mm – 0.42 mm diameter silicon sensor head attached to the tip of a 0.25 mm diameter optical fiber. The sensor’s bulky head prevents it from reducing the size further.

This paper reports a novel miniature all-optical fiber pressure sensor which is designed for the in-vivo blood pressure measurement. The sensor is based on Fabry-Perot interferometry principle. The FP cavity is fabricated by etching away the core of a fiber tip and then bonded with a silicon dioxide diaphragm. By interrogating the reflection interference spectrum shifts according to the deformation of the diaphragm caused by the ambient pressure change, the blood pressure can be determined. The sensor has the uniform size with the optical fiber which is generally 125 µm. The static experiments were performed in the lab in order to characterize the sensor’s performance. Then, an animal test was conducted in University of Massachusetts Medical School in Worchester, MA. The preliminary results indicate that the fiber optic sensor recorded the blood pressure waveforms and captured the pressure change before and after the artery occluder.

2. SENSOR DESIGN AND FABRICATION 2.1 Sensor design

The fiber optic blood pressure sensor is designed upon the FP structure, which is shown in Fig.1. The FP cavity is formed by attaching a silicon dioxide diaphragm on a piece of multimode fiber of which the core is wet etched away. The incident light reflects at two interfaces: the single mode fiber core/air interface and the diaphragm/air cavity interface. A pattern is generated by the interference of two reflection lights. The interference fringe would shift according to the deformation of the diaphragm. By interrogating the shift, the blood pressure change could be obtained.

Single mode fiber Multimode fiber

DiaphragmCavityFiber core

Fig.1 Schematic diagram of the design of a fiber optic blood pressure sensor. The sensor consists of a single mode fiber , a multimode fiber of which the core is wet etched and a silicon dioxide diaphragm.



2.2 Sensor fabrication

Detailed fabrication method is published on somewhere else 19. The procedure of the fabrication is repeated briefly here. A piece of multimode fiber was spliced with a segment of single mode fiber. The multimode fiber was cleaved to left approximately 20 µm to 30 µm length attached to the single mode fiber. A 49% hydrofluoric acid (HF) was used to etch away the core of the multimode fiber. Because of the different etching rate between the fiber core and the fiber cladding due to the different doping level, the core is etched faster than the fiber, which guarantees that the core is removed while the cladding is remained. The fiber with the multimode fiber was placed in the HF for 3 min to etch away enough fiber core. The etched fiber was thermal bonded with a piece of silicon dioxide diaphragm. The procedure of the fabrication is illustrated in Fig.2.

(a) (b) (c) (d)

Fig.2. The procedure of sensor fabrication. (a) A piece of multimode fiber was spliced with a single mode fiber and then cleaved. (b) The core of the multimode fiber was etched away in 49% HF solution. (c) The etched fiber was thermally bonded with a piece of silicon dioxide diaphragm. (d) The sensor was fabricated.

The silicon dioxide diaphragm was prepared by etching away the silicon substrate with an oxide layer on top of it. A silicon wafer with a specific thickness of a silicon dioxide layer was purchased. Then, the silicon dioxide layer was released after back etching away the silicon by using deep reactive ion etching (RIE). Because of the MEMS technology, the diaphragm can be very flat and uniform.

3. EXPERIMENTS 3.1 Sensor characterization

In order to evaluate the static performance of the fiber optic blood pressure sensor, a static experiment was designed. The experiment was conducted in a sealed chamber with water, as shown in Fig.3. Our sensor was placed in the water side by side with an electrical reference sensor (PX303-030G5V, Omega). An optical sensing analyzer (OSA) (Si720, Micron Optics) was introduced to monitor the reflective interference fringe shift. A computer was used to collect data from OSA and the reference sensor and the corresponding data generated was compared.

Pressure chamber

CTS

PC

Optical fiber sensor

Reference sensor

Fig.3. The schematic diagram of the static experiment setup.

3.2 Animal experiment protocol

Briefly, 25-50 kg Yorkshire swine was premedicated with intramuscular Glycopirrolate B (0.01 mg/kg) and an anesthetic cocktail (5mg/kg Telazol; 2.5mg/kg Ketamine; 2.5mg/kg Xylazine) after which endotracheal intubation was performed. Anesthesia was maintained with inhalational 2-3% Isoflurane. Exposure of the left anterior descending coronary artery (LAD) was obtained via a median sternotomy, and a 3.0mm vascular occluder was secured beyond the takeoff of the largest diagonal branch. Next, femoral arterial access was obtained via cutdown, and a 6 French introducer



sheath was inserted. Heparin was administered intravenously (50 units/kg), and a 6 French JR-4 guide catheter (Medtronic; Minneapolis, MN) was guided to the aortic arch. Baseline blood pressure measurements were obtained with standard invasive manometry. Optical spectral measurements were similarly obtained for comparison offline.

Next, the guiding catheter was introduced into the ostium of the left main coronary artery, and angiography was performed in the LAO projection. The fiber optic blood pressure sensor was advanced into the LAD at a point beyond the vascular occluder. Pressure and spectral measurements were again obtained. The vascular occluder was deployed in order to create stenoses of various degrees as confirmed with repeat angiography. Spectral measurements were obtained beyond the stenosis to determine the correlation of stenosis severity with the anticipated shift in the optical spectrum.

4. RESULTS AND DISCUSSIONS 4.1 Sensor characterization

A typical reflection interference spectrum is shown in Fig.4 (a). The spectrum showed a blue shift when the ambient pressure increasing. By monitoring the wavelength of the notch, the pressure change can be interpreted.

1520 1530 1540 1550 1560 1570-50

-45

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-35

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nsity

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)

Wavelength (nm) 0 2 4 6 8 10

-202468

1012141618

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Fig.4. (a) A typical reflection interference pattern which is obtained directly from OSA. (b) The processed data indicates the sensitivity and the hysteresis information of the sensor.

Fig.4 (b) shows the experimental data after being processed to find the relationship between the pressure change and the notch wavelength shift. The pressure in the water was increased from 0 psi to approximately 10 psi in the step of 1 psi and following by decreasing the pressure from 10 psi to 0 psi in the same step. Each cycle was repeated 3 times in order to obtain the sensor’s hysteresis. A linear fit (blue line in Fig.4 (b)) was performed to calculate the sensor’s linearity. After calculation, the correlation coefficient (R) was 0.9996 which demonstrate that the sensor exhibits high linearity. The sensitivity of the sensor was calculated as 1.93 nm/psi. The hysteresis was low because the measurement points match quite well for each experiment cycle. The maximum hysteresis was about 0.3%.

4.2 Animal test

Fig.5 (a) shows the pressure tracing obtained from the aorta demonstrating the baseline blood pressure (67 mmHg/39 mmHg). The heart rate is 64 beats per minute (bpm), reflecting a cardiac cycle time of 0.94 sec. Fig.5 (b) demonstrates the pressure waveform detected by our optical fiber blood pressure sensor. Compared with Fig.5 (a), the waveform obtained by our sensor is very similar. The fiber optic blood pressure sensor showed that the systolic pressure was 65 mmHg, the diastolic pressure was 38 mmHg, and heart rate was 64.4 bpm, which is consistent with the invasively measured blood pressure. However, due to the low sampling rate of the OSA (5 Hz), some details were lost. The waveform in Fig.5 (b) was not smooth. This problem can be solved by substituting the spectrum interrogation approach with light intensity interrogation approach.

(a) (b)



391 392 393 394 395 396

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sure

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Hg)

Time (s) Fig.5 (a) The blood pressure tracing in the aorta as the baseline blood pressure. (b) The blood pressure waveform obtained by fiber optic blood pressure sensor.

In order to determine whether the fiber optic pressure sensor is capable of detecting a decline in the blood pressure generated by coronary stenoses, the data from the optical sensor were obtained in the presence or absence of critical stenoses of the LAD utilizing the surgically placed vascular occluder. Fig.6 (a) shows the coronary angiography following the insertion of the fiber optic blood pressure sensor into the LAD. The circle identifies a 90% stenosis with markedly reduced flow at the site of the vascular occluder. Fig.6 (b) indicates that mean coronary blood pressure obtained distal to the stenosis decreased from 50 mmHg to 45 mmHg in 20 seconds upon complete occlusion of the porcine LAD.

1700 1720 1740 1760 1780

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Fig.6 (a) The coronary angiography showing that the insertion of the fiber optic blood pressure sensor into the LAD. (b) The blood pressure decreasing data obtained by the fiber optic blood pressure sensor after applying the occluder.

5. CONCLUSIONS A fiber optic blood pressure sensor was designed, fabricated and tested. The sensor consists of a single mode fiber which is utilized to transmit the incident light and collect the reflection lights, a multimode fiber on which the FP cavity is fabricated by etching away the core, and a silicon dioxide diaphragm that is sensitive to the ambient blood pressure change. The material of the sensor is all silicon dioxide which is biocompatible. A static experiment was performed to characterize the sensor’s performance. Typically, the sensor has the sensitivity of 1.93 nm/psi and high linearity with the correlation coefficient (R) of 0.9996. A 25-50 kg Yorkshire swine was used in the animal test as the target. The fiber optic blood pressure sensor showed the capability of obtaining the waveform the blood pressure. In addition, the sensor can sense the blood pressure difference between the presence and the absence of the coronary artery occluder.

(a) (b)



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