Photoplethysmography is a technique widely used in monitoring perfusion and blood oxygen saturation based on the amplitude of the pulsatile signal at one or multiple wavelengths. However, the pulsatile signal carries in its waveform a substantial amount of information about the mechanical properties of the tissue and vasculature under investigation that is still yet to be utilized to its full potential. In this work, we present the feasibility of pulse wave analysis for the application of monitoring hepatic implants and diagnosing graft complications. In particular, we demonstrate the utility of computing the slope of the pulse during the diastole phase to assess compliance changes in tissue. This hypothesis was tested in a series of in vitro experiments using a polydimethylsiloxane based phantom mimicking the optical and mechanical properties of the portal vein. The emptying time decreased from 148.1 ms for phantoms with compliance of 12 KPa to 97.5 ms for phantoms with compliance of 61 KPa. These compliance levels mimic those seen for normal and fibrotic hepatic tissue respectively.
In abdominal trauma patients, monitoring intestinal perfusion and oxygen consumption is essential during the resuscitation period. Photoplethysmography is an optical technique potentially capable of monitoring these changes in real time to provide the medical staff with a timely and quantitative measure of the adequacy of resuscitation. The challenges for using optical techniques in monitoring hemodynamics in intestinal tissue are discussed, and the solutions to these challenges are presented using a combination of Monte Carlo modeling and theoretical analysis of light propagation in tissue. In particular, it is shown that by using visible wavelengths (i.e., 470 and 525 nm), the perfusion signal is enhanced and the background contribution is decreased compared with using traditional near-infrared wavelengths leading to an order of magnitude enhancement in the signal-to-background ratio. It was further shown that, using the visible wavelengths, similar sensitivity to oxygenation changes could be obtained (over 50% compared with that of near-infrared wavelengths). This is mainly due to the increased contrast between tissue and blood in that spectral region and the confinement of the photons to the thickness of the small intestine. Moreover, the modeling results show that the source to detector separation should be limited to roughly 6 mm while using traditional near-infrared light, with a few centimeters source to detector separation leads to poor signal-to-background ratio. Finally, a visible wavelength system is tested in an in vivo porcine study, and the possibility of monitoring intestinal perfusion changes is showed.
Trauma is the number one cause of death for people between the ages 1 and 44 years in the United States. In
addition, according to the Centers of Disease Control and Prevention, injury results in over 31 million emergency
department visits annually. Minimizing the resuscitation period in major abdominal injuries increases survival rates by
correcting impaired tissue oxygen delivery. Optimization of resuscitation requires a monitoring method to determine
sufficient tissue oxygenation. Oxygenation can be assessed by determining the adequacy of tissue perfusion. In this
work, we present the design of a wireless perfusion and oxygenation sensor based on photoplethysmography. Through
optical modeling, the benefit of using the visible wavelengths 470, 525 and 590nm (around the 525nm hemoglobin
isobestic point) for intestinal perfusion monitoring is compared to the typical near infrared (NIR) wavelengths (805nm
isobestic point) used in such sensors. Specifically, NIR wavelengths penetrate through the thin intestinal wall (~4mm)
leading to high background signals. However, these visible wavelengths have two times shorter penetration depth that
the NIR wavelengths. Monte-Carlo simulations show that the transmittance of the three selected wavelengths is lower by
5 orders of magnitude depending on the perfusion state. Due to the high absorbance of hemoglobin in the visible range,
the perfusion signal carried by diffusely reflected light is also enhanced by an order of magnitude while oxygenation
signal levels are maintained. In addition, short source-detector separations proved to be beneficial for limiting the
probing depth to the thickness of the intestinal wall.
An implantable, optical oxygenation and perfusion sensor to monitor liver transplants during the two-week period following the transplant procedure is currently being developed. In order to minimize the number of animal experiments required for this research, a phantom that mimics the optical, anatomical, and physiologic flow properties of liver parenchyma is being developed as well. In this work, the suitability of this phantom for liver parenchyma perfusion research was evaluated by direct comparison of phantom perfusion data with data collected from in vivo porcine studies, both using the same prototype perfusion sensor. In vitro perfusion and occlusion experiments were performed on a single-layer and on a three-layer phantom perfused with a dye solution possessing the absorption properties of oxygenated hemoglobin. While both phantoms exhibited response patterns similar to the liver parenchyma, the signal measured from the multilayer phantom was three times higher than the single layer phantom and approximately 21 percent more sensitive to in vitro changes in perfusion. Although the multilayer phantom replicated the in vivo flow patterns more closely, the data suggests that both phantoms can be used in vitro to facilitate sensor design.
Between the years 1999 and 2008, on average 2,052 people died per year on the waiting list for liver transplants.
Monitoring perfusion and oxygenation in transplanted organs in the 7 to 14 days period post-transplant can enhance graft
and patient survival rates, and resultantly increase the availability of organs. In this work, we present in vitro results
using a unique liver phantom that support the ability of our sensor to detect perfusion changes in the portal vein at low
levels (50 mL/min . 4.5% of normal level). Our sensor measures diffuse reflection from three wavelengths (735, 805
and 940 nm) around the hemoglobin isobestic point (805 nm) to determine perfusion and oxygenation separately. To
assess the sensitivity of our sensor to flow changes in the low range, we used two peristaltic pumps to pump a dye
solution mimicking the optical properties of oxygenated blood, at various rates, through a PDMS based phantom
mimicking the optical properties of liver tissue. The collected pulsatile signal increased by 120% (2.2X) for every 100
mL/min flow rise for all three wavelengths in the range 50 to 500 mL/min. In addition, we used different dye mixtures to
mimic oxygenation changes at constant perfusion/flow levels. The optical properties of the dye mixtures mimic oxygen
saturations ranging between 0 and 100%. The sensor was shown to be sensitive to changes in oxygen saturations above 50%.
An implanted system is being developed to monitor transplanted liver health during the critical 7-10 day period posttransplantation.
The unit will monitor organ perfusion and oxygen consumption using optically-based probes placed on
both the inflow and outflow blood vessels, and on the liver parenchymal surface. Sensing probes are based on a 3-
wavelength LED source and a photodiode detector. Sample diffuse reflectance is measured at 735, 805, and 940 nm. To
ascertain optimal source-to-photodetector spacing for perfusion measurement in blood vessels, an ex vivo study was
conducted. In this work, a dye mixture simulating 80% blood oxygen saturation was developed and perfused through
excised porcine arteries while collecting data for various preset probe source-to-photodetector spacings. The results from
this study demonstrate a decrease in the optical signal with decreasing LED drive current and a reduction in perfusion
index signal with increasing probe spacing. They also reveal a 2- to 4-mm optimal range for blood vessel perfusion probe
source-to-photodetector spacing that allows for sufficient perfusion signal modulation depth with maximized signal to
noise ratio (SNR). These findings are currently being applied to guide electronic configuration and probe placement for in
vivo liver perfusion porcine model studies.
Each year thousands of patients are added to the waiting list for liver transplants. The first 7-10 days after transplant
have proven to be the most critical in patient recovery and it is hypothesized that monitoring organ vital signals in this
period can increase patient and graft survival rates. An implantable sensor to monitor the organ perfusion and
oxygenation signals following surgery is being developed by our group. The sensor operates based on measuring diffuse
reflection from three light emitting diodes (735, 805 and 940 nm). In this work the optimal source detector spacing to
maximize oxygenation signal level is investigated for a portal vein model. Monte Carlo simulations provided signal
levels and corresponding penetration depths as a function of separation between a point optical source and detector. The
modeling results indicated a rapid decay in the optical signal with increasing distance. Through further analysis, it was
found that there exists an optimal range of point source to detector spacing, between roughly 1 and 2 mm, in which the
blood signal from the simulated portal vein was maximized. Overall, these results are being used to guide the placement
and configuration of our probe for in vivo animal studies.
Previous studies have shown the ability of many lymphatic vessels to contract phasically to pump lymph. Every lymphangion can act like a heart with pacemaker sites that initiate the phasic contractions. The contractile wave propagates along the vessel to synchronize the contraction. However, determining the location of the pacemaker sites within these vessels has proven to be very difficult. A high speed video microscopy system with an automated algorithm to detect pacemaker location and calculate the propagation velocity, speed, duration, and frequency of the contractions is presented in this paper. Previous methods for determining the contractile wave propagation velocity manually were time consuming and subject to errors and potential bias. The presented algorithm is semiautomated giving objective results based on predefined criteria with the option of user intervention. The system was first tested on simulation images and then on images acquired from isolated microlymphatic mesenteric vessels. We recorded contraction propagation velocities around 10 mm/s with a shortening speed of 20.4 to 27.1 μm/s on average and a contraction frequency of 7.4 to 21.6 contractions/min. The simulation results showed that the algorithm has no systematic error when compared to manual tracking. The system was used to determine the pacemaker location with a precision of 28 μm when using a frame rate of 300 frames per second.
Proc. SPIE. 7572, Optical Diagnostics and Sensing X: Toward Point-of-Care Diagnostics
KEYWORDS: Detection and tracking algorithms, Imaging systems, Image processing, Optical microscopy, Data acquisition, Digital imaging, High speed cameras, Video microscopy, Velocity measurements, Lymphatic system
The lymphatic system is not well understood and tools to quantify aspects of its behavior are needed. A technique to
monitor lymph velocity that can lead to flow, the main determinant of transport, in a near real time manner can be
extremely valuable. We recently built a new system that measures lymph velocity, vessel diameter and contractions
using optical microscopy digital imaging with a high speed camera (500fps) and a complex processing algorithm.
The processing time for a typical data period was significantly reduced to less than 3 minutes in comparison to our
previous system in which readings were available 30 minutes after the vessels were imaged. The processing was
based on a correlation algorithm in the frequency domain, which, along with new triggering methods, reduced the
processing and acquisition time significantly. In addition, the use of a new data filtering technique allowed us to
acquire results from recordings that were irresolvable by the previous algorithm due to their high noise level. The
algorithm was tested by measuring velocities and diameter changes in rat mesenteric micro-lymphatics. We recorded
velocities of 0.25mm/s on average in vessels of diameter ranging from 54um to 140um with phasic contraction
strengths of about 6 to 40%. In the future, this system will be used to monitor acute effects that are too fast for
previous systems and will also increase the statistical power when dealing with chronic changes. Furthermore, we
plan on expanding its functionality to measure the propagation of the contractile activity.