Development and Testing of an Implantable Perfusion and Oxygenation Sensor for Liver Transplant Monitoring

Since the first successful liver transplant in 1968 the surgery has become very common and 6,291 patients received liver transplants in 2010 in the United States. However, the monitoring methods used post-surgery, in the recovery phase, are still very basic and rely mainly on blood tests and looking for unusual symptoms. Complications are usually detected after the organ is substantially damaged which poses a risk to the patients’ life. This dissertation presents the development and testing of an implantable sensor that can potentially be used to monitor the transplant continuously and transmit the information wirelessly to the medical staff for timely intervention. Such a sensor could have a great effect on survival and reduction of retransplantation rates. The presented sensor employs near infrared spectroscopy to measure perfusion changes, arterial oxygenation and venous oxygenation in the parenchyma of the liver tissue and the supplying vessels. Light at three different wavelengths (735-, 805- and 940-nm) is shined on the tissue and the diffuse reflectance is collected via a photodetector. The collected signals can be transmitted wirelessly to an external unit for processing and display. In this dissertation, different perfusion and oxygenation monitoring techniques are reviewed and the instrumentation of an NIRS based wireless sensor is introduced. A phantom that mimics the anatomy of the liver and its optical and mechanical properties is presented. The processing methods to extract the information of interest from the diffuse reflectance are described in details. Finally, results from in vitro phantom experiments, ex vivo perfused livers and in vivo porcine studies are presented. The first in vivo wireless monitoring of hepatic perfusion and oxygenation levels is reported. The studies show that the sensor can track perfusion changes with a resolution of 0.1 mL/min/g of tissue. The possibility of tracking oxygen saturation changes is also shown as well as the ability to separate them from perfusion changes. Combining results from the pulsatile wave and DC levels, venous and arterial oxygen saturation changes were tracked with a resolution of 1.39% and 2.19% respectively. In conclusion, optical spectroscopy is shown to track perfusion, and arterial and venous oxygenation in tissue. In particular, the method was tested on hepatic and intestinal tissue

Wireless Monitoring of Liver Hemodynamics <i>In Vivo</i>

<div><p>Liver transplants have their highest technical failure rate in the first two weeks following surgery. Currently, there are limited devices for continuous, real-time monitoring of the graft. In this work, a three wavelengths system is presented that combines near-infrared spectroscopy and photoplethysmography with a processing method that can uniquely measure and separate the venous and arterial oxygen contributions. This strategy allows for the quantification of tissue oxygen consumption used to study hepatic metabolic activity and to relate it to tissue stress. The sensor is battery operated and communicates wirelessly with a data acquisition computer which provides the possibility of implantation provided sufficient miniaturization. In two <i>in vivo</i> porcine studies, the sensor tracked perfusion changes in hepatic tissue during vascular occlusions with a root mean square error (RMSE) of 0.135 mL/min/g of tissue. We show the possibility of using the pulsatile wave to measure the arterial oxygen saturation similar to pulse oximetry. The signal is also used to extract the venous oxygen saturation from the direct current (DC) levels. Arterial and venous oxygen saturation changes were measured with an RMSE of 2.19% and 1.39% respectively when no vascular occlusions were induced. This error increased to 2.82% and 3.83% when vascular occlusions were induced during hypoxia. These errors are similar to the resolution of a commercial oximetry catheter used as a reference. This work is the first realization of a wireless optical sensor for continuous monitoring of hepatic hemodynamics.</p></div

Venous oxygen saturation.

<p>Data from the telemetry sensor (black dots) and the central venous catheter (grey line) for study 1 (left) and 2 (right).</p

Heart rate measurements.

<p>Data from the arterial pressure catheter (grey) and the telemetry sensor (black).</p

Hepatic flow changes prior to the increase in blood pressure.

<p>(Left) Total hemoglobin concentration (ΔHbT) and flow changes. (Right) Scatter plot of measured hemoglobin concentration change (ΔHbT) vs. tissue perfusion (flow normalized by liver weight).</p

Hepatic flow changes.

<p>(Left) Changes in total hemoglobin concentration (ΔHbT, black dots) in hepatic tissue versus total hepatic flow measured by the addition of the HA and PV Transit-Time flowmeters' measurements (grey line). (Right) Total hepatic flow (grey) and mean arterial pressure (black) trends show that the increase in flow after t = 200 min is accompanied by an increase in the arterial pressure suggesting that a systemic response is responsible for that increase.</p

Scatter plot of the predicted vs. measured MOS for study 1 (black) and 2 (grey).

<p>Scatter plot of the predicted vs. measured MOS for study 1 (black) and 2 (grey).</p

Typical PPG signal.

<p>a- Schematic of the collected reflectance signal (Note that the various signal components are not drawn to scale to allow easy visualization). b- Spectrum of the reflectance signal collected with our sensor prior to amplification and with the DC signal omitted.</p