Necrotizing enterocolitis (NEC) is a gastrointestinal disease that affects 2% to 5% of premature infants and is responsible for almost 8% of all neonatal intensive care unit (NICU) admissions. NEC is caused by inflammation of the intestine, leading to an invasion of bacteria that can cause necrosis of the colon and intestine. Patients with NEC can suffer from a wide range of symptoms such as apnea, diarrhea and bloody stools, unstable body temperature, trouble feeding, discoloration of the abdominal region, and a swollen abdominal region. These symptoms of NEC often coincide with other gastrointestinal diseases, meaning that it can be difficult to definitively diagnose NEC without the use of radiographic imaging. Current diagnostic procedures utilize Bell’s staging system, which many believe is unreliable and inefficient practice. The progression of NEC occurs quickly and results in a mortality rate as high as 50%, yet the mortality rate can still increase when emergency surgical procedures are performed for more severe cases. Previous studies motivate our development of a noninvasive sensing and monitoring method that can be used in real-time. The proposed method utilizes both optical and thermal images to detect temperature differences in upper (thorax) and lower (abdomen) regions as an early indicator for NEC. We report on promising preliminary data from early studies at the Vanderbilt University Medical Center, Monroe Carell Jr. Children’s Hospital, under an approved IRB, investigating point-of-care NICU image-based thermographic trends of neonates at risk for NEC.
SignificanceSuccessful differentiation of carcinoma in situ (CIS) from inflammation in the bladder is key to preventing unnecessary biopsies and enabling accurate therapeutic decisions. Current standard-of-care diagnostic imaging techniques lack the specificity needed to differentiate these states, leading to false positives.AimWe introduce multiparameter interferometric polarization-enhanced (MultiPIPE) imaging as a promising technology to improve the specificity of detection for better biopsy guidance and clinical outcomes.ApproachIn this ex vivo study, we extract tissue attenuation-coefficient-based and birefringence-based parameters from MultiPIPE imaging data, collected with a bench-top system, to develop a classifier for the differentiation of benign and CIS tissues. We also analyze morphological features from second harmonic generation imaging and histology slides and perform imaging-to-morphology correlation analysis.ResultsMultiPIPE enhances specificity to differentiate CIS from benign tissues by nearly 20% and reduces the false-positive rate by more than four-fold over clinical standards. We also show that the MultiPIPE measurements correlate well with changes in morphological features in histological assessments.ConclusionsThe results of our study show the promise of MultiPIPE imaging to be used for better differentiation of bladder inflammation from flat tumors, leading to a fewer number of unnecessary procedures and shorter operating room (OR) time.
Eosinophilic esophagitis (EoE) is a clinicopathological condition requiring frequent upper endoscopy (EGD) with several biopsies and time-consuming histopathological diagnosis. We acquired in vivo fingerprint and high wavenumber Raman spectra from the esophageal mucosa of children undergoing EGD and assessed the efficacy of this non-obtrusive real-time approach for determining EoE activity. Spectral bands related to lipids (e.g., 1078, 1301, 1440, 2855cm-1), proteins (e.g., 935, 1003, 1342, 2931cm-1), and water (3075-3650cm-1) were found to differentiate between active, inactive, and non-EoE patients. The results from this study indicate that RS is a promising method for point-of-care assessment of EoE.
Inadvertent nerve injury is a common complication during many surgical procedures. Providing surgeons with a means to visualize nerves within a surgical field could reduce the risk of nerve injury and improve patient outcomes. Several wavelengths leveraging the intrinsic optical properties of nerves have been identified to enhance nerve contrast in an animal model. Here, we demonstrate the clinical feasibility of this technique in patients undergoing thyroidectomies. Spectral imaging successfully discriminated nerves from surrounding tissues within the surgical field. The results of this study demonstrate the clinical viability of spectral imaging for nerve visualization.
Iatrogenic nerve injuries often occur during surgical procedures yielding high morbidity. Numerous optical techniques are being investigated to provide nerve visualization and monitoring to both avoid and detect nerve injury. However, there is insufficient VIS-IR optical properties data for nerve and surrounding tissues, to facilitate needed advancements in the biophotonic approaches being developed for deployment. To fill this gap, we determined the absorption and reduced scattering coefficients of ex vivo nerve, muscle, tendon, and adipose tissues from four rats and human cadavers between 350-2500nm. The results provide valuable insights for optimizing the optical contrast of nerves for improved surgical guidance.
Low Cardiac Output Syndrome (LCOS) is a common complication of congenital heart disease corrective cardiopulmonary bypass surgery. Providing clinicians with realtime assessment of LCOS will facilitate early detection for implementation of more timely and effective interventions to reduce fatalities and improve infant outcomes. We demonstrate the realtime capture of relative temperature changes via an optical and thermographic imaging-based system that serve as an accurate measure of dynamic changes in peripheral blood perfusion. The results of this study show promise for the application of a realtime noninvasive optical and thermographic imaging-based system for LCOS detection.
Inadvertent nerve injury is a common complication during many surgical procedures. Intraoperative localization of nerves could reduce the risk of nerve injury and improve patients’ quality of life post-operation. To address this need, we combine diffuse reflectance and polarization imaging techniques into a single imaging system for in vivo nerve mapping. Both modalities successfully localize nerves within the field of view in an in vivo rat model and together provide enhanced contrast in relation to the surrounding tissues. The results of this study provide valuable insight into the future development of a real-time imaging system for clinical translation.
The modulation of the state of polarization of photons due to scatter generates associated geometric phase that is being investigated as a means for decreasing the degree of uncertainty in back-projecting the paths traversed by photons detected in backscattered geometry. In our previous work, we established that polarimetrically detected Berry phase correlates with the mean photon penetration depth of the backscattered photons collected for image formation. In this work, we report on the impact of state-of-linear-polarization (SOLP) filtering on both the magnitude and population distributions of image forming detected photons as a function of the absorption coefficient of the scattering sample. The results, based on Berry phase tracking implemented Polarized Monte Carlo Code, indicate that sample absorption plays a significant role in the mean depth attained by the image forming backscattered detected photons.
The propagation of light in turbid media is an active area of research with relevance to numerous investigational fields, e.g., biomedical diagnostics and therapeutics. The statistical random-walk nature of photon propagation through turbid media is ideal for computational based modeling and simulation. Ready access to super computing resources provide a means for attaining brute force solutions to stochastic light-matter interactions entailing scattering by facilitating timely propagation of sufficient (>107) photons while tracking characteristic parameters based on the incorporated physics of the problem. One such model that works well for isotropic but fails for anisotropic scatter, which is the case for many biomedical sample scattering problems, is the diffusion approximation. In this report, we address this by utilizing Berry phase (BP) evolution as a means for capturing anisotropic scattering characteristics of samples in the preceding depth where the diffusion approximation fails. We extend the polarization sensitive Monte Carlo method of Ramella-Roman, et al., to include the computationally intensive tracking of photon trajectory in addition to polarization state at every scattering event. To speed-up the computations, which entail the appropriate rotations of reference frames, the code was parallelized using OpenMP. The results presented reveal that BP is strongly correlated to the photon penetration depth, thus potentiating the possibility of polarimetric depth resolved characterization of highly scattering samples, e.g., biological tissues.
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.
KEYWORDS: Sensors, Blood, Signal detection, Veins, Monte Carlo methods, Surgery, Diffuse reflectance spectroscopy, Liver, Optical properties, In vivo imaging
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.
The use of small animal models to investigate human diseases is an integral part of the development of new diagnostic and treatment regimens. Consequently, functional imaging modalities such as single photon emission computed tomography (SPECT) are increasingly being utilized to streamline the screening of animal phenotypes and to monitor disease states, progressions, and therapies. This paper focuses on the utilization of polarization filtering to minimize specular reflection from a glass tube used for holding live human-tumor-mice during functional imaging in a dedicated small animal SPECT system. The system presented is potentially useful for the real-time non-invasive investigation of diseases, such as cancer, and drug therapies in small animals because it utilizes optical motion-registered functional imaging that minimizes the effects of motion artifacts.
The remodeling of cardiac tissues has been implicated in the development of congestive heart failure. Therefore, the current emphasis in cardiovascular research is geared toward understanding the underlying processes in order to facilitate the development of better prevention and treatment regimens by improving the early detection and diagnosis of this disease. This paper focuses on the application of polarized light to address a major drawback of cardiovascular biomechanics research, which is the utilization of toxic chemicals to prepare samples for histological examination. To accomplish this without the use of toxic chemicals, a polarization microscopy imaging technique was developed and applied to a non-stained rat septum sample. This imaging technique provided sufficient enhancement of collagenous structures to determine the myo-lamina sheet angle, β, without the need for caustic staining.
The Mueller matrix describes all the polarizing properties of a sample, and therefore the optical differences between cancerous and non-cancerous tissue should be present within the matrix elements. We present in this paper the Mueller matrices of three types of tissue; normal, benign mole, and malignant melanoma on a Sinclair swine model. Feature extraction is done on the Mueller matrix elements resulting in the retardance images, diattenuation images, and depolarization images. These images are analyzed in an attempt to determine the important factors for the identification of cancerous lesions from their benign counterparts. In addition, the extracted features are analyzed using statistical processing to develop an accurate classification scheme and to identify the importance of each parameter in the determination of cancerous versus non-cancerous tissue.
The effect of changing corneal birefringence, due to motion artifact, remains a major obstacle to the development of an accurate non-invasive polarimetric glucose sensor for patients with diabetes mellitus. Consequently, there is still a need to characterize fully, and to quantify the relative changes in corneal birefringence to facilitate the optimization of detection algorithms, enabling in vivo accuracy within 10mg/dl. In this paper, we present preliminary results, utilizing a Mueller matrix imaging technique, that demonstrates notable relative changes in the apparent retardance and in the apparent fast axis location of rabbit cornea.
Much work has been done to make the optical measurement of glucose concentrations in the aqueous humor a feasible, non- invasive, alternative for the blood finger stick, method currently used by people with diabetes mellitus. Recent work has demonstrated that the time lag between blood and aqueous humor glucose levels is within five minutes but there is still work to be done in overcoming the confounding effects of changing birefringence, due to motion artifact, on the detected glucose signal during in-vivo measurements. To address this issue, we designed and implemented a dual orthogonal polarization detection system. We present promising preliminary results that indicate that this method, with some slight modifications and optimization of our system, has the potential to extract glucose concentration information from a birefringent sample in the presence of motion artifact.
KEYWORDS: Polarization, Polarizers, Polarimetry, Signal detection, Sensors, Signal to noise ratio, Semiconductor lasers, Laser applications, Telecommunications, Linear polarizers
The ability to detect skin cancer accurately, quickly, and non-invasively has been the object of researchers for many years. This paper describes a novel Automated Mueller Matrix Polarimetric Imaging System that has the potential for non- invasive determination of cancerous lesions from their benign counterparts. Our system collects the 16 images used to calculate the 16 Mueller matrix elements in less than 70 seconds. To validate the system, we used known samples that show a maximum error of 1.41 percent in the Mueller matrix. Tissue-phantoms with varying concentrations of scatterers were used to determine the effects of changes in the sample scattering coefficient on the Mueller matrix. The system was also used to image a benign lesion on a human subject to show the ability to collect of polarization information from the skin.
In this paper, we describe the use of the full sixteen element Mueller matrix to differentiate between surface lesions on the skin, as an eventual noninvasive diagnostic technique for detection of certain types of skin cancers. A semi-automated system using a polarized light beam and a computer controlled CCD camera was developed to collect 16 polarization images of a sample and to calculate the complete Mueller matrix in near real time. The system was initially calibrated and the accuracy and precision were evaluated with a mirror and polarizer. This study also includes in vivo results from normal skin, a benign nevus, and a known cancerous lesion acquired from a single Sinclair swine. Differences were observed between the Mueller matrices of all three in vivo cases. These preliminary results demonstrate the potential for using an automated polarization imaging apparatus for eventual clinical cancer diagnostics.
The widespread occurrence of diabetes mellitus and the severity of its associated complications necessitate the development of non-invasive blood glucose measurement devices in an attempt to improve treatment regimens and curb the complications associated with this disease. One method showing promise in this endeavor utilizes optical polarimetry to monitor blood glucose levels indirectly by measuring glucose rotation of polarized light, which is a direct indication of glucose concentration, in the aqueous humor of the eye. The presence of other optically active (chiral) components in the aqueous humor of the eye have the potential to confound the glucose measurement of optical rotation when using a single wavelength polarimeter. Thus, this has led to the recent investigation of multispectral polarimetric systems which have the potential to enable the removal of confounder contributions to the net observed optical rotation, therefore, increasing glucose specificity and reducing glucose prediction errors. Such polarimetric systems take advantage of the uniqueness in the rotation of polarized light, as a function of wavelength, by the chiral molecule of interest. This is commonly referred to as the optical rotatory dispersion (ORD) spectra of the chiral molecule. ORD characterization of the chiral molecules within the aqueous humor is necessary for determining the optimum number of wavelengths needed to reduce glucose prediction errors; however, this information is often only given at the sodium-D line (589 nm) in the literature. This report describes the system we designed and built to measure ORD spectra for glucose and for albumin, the main optical confounder within the aqueous humor, as well as our investigation of the effects of temperature and pH on these ORD spectra.
The application of optical polarimetry, using the anterior chamber of the eye as the sensing site, is being investigated as a potential method to develop a noninvasive physiological glucose monitor. First, we present results characterizing the optical rotatory dispersion of the main optically active analytes found within the aqueous humor of the eye including, glucose, albumin, and ascorbic acid. This information is used in conjunction with multiple linear regression to demonstrate how multispectral polarimetry can be used to minimize glucose prediction error in samples containing varying physiological concentrations of glucose and albumin. For this multispectral study, a novel dual wavelength (532 nm and 635 nm) polarimeter was designed and constructed. This sensor is novel in that it provides simultaneous measurements using a 532 nm laser in an open- loop configuration and a 635 nm laser in a closed-loop configuration. In addition, we present in vivo results using New Zealand White rabbits that indicate the time delay between blood and aqueous human glucose levels is below ten minutes. Lastly, we provide preliminary in vivo polarimetric results and discuss the main issues currently hindering the measurement of glucose.
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