SignificancePreterm birth is defined as a birth before 37 weeks of gestation and is one of the leading contributors to infant mortality rates globally. Premature birth can lead to life-long developmental impairment for the child. Unfortunately, there is a significant lack of tools to diagnose preterm birth risk, which limits patient care and the development of new therapies.AimTo develop a speculum-free, portable preterm imaging system (PPRIM) for cervical imaging; testing of the PPRIM system to resolve polarization properties of birefringent samples; and testing of the PPRIM under an IRB on healthy, non-pregnant volunteers for visualization and polarization analysis of cervical images.ApproachThe PPRIM can perform 4×3 Mueller-matrix imaging to characterize the remodeling of the uterine cervix during pregnancy. The PPRIM is built with a polarized imaging probe and a flexible insertable sheath made with a compatible flexible rubber-like material to maximize comfort and ease of use.ResultsThe PPRIM device is developed to meet specific design specifications as a speculum-free, portable, and comfortable imaging system with polarized imaging capabilities. This system comprises a main imaging component and a flexible silicone inserter. The inserter is designed to maximize comfort and usability for the patient. The PPRIM shows high-resolution imaging capabilities at the 20 mm working distance and 25 mm circular field of view. The PPRIM demonstrates the ability to resolve birefringent sample orientation and full field capture of a healthy, non-pregnant cervix.ConclusionThe development of the PPRIM aims to improve access to the standard of care for women’s reproductive health using polarized Mueller-matrix imaging of the cervix and reduce infant and maternal mortality rates and better quality of life.
Preterm birth, defined as delivery at less than 37 weeks of gestation, is the leading cause of newborns mortality. The survivors may have life-long problems including neurological, hearing, respiratory and vision disorders. Preterm birth is often linked to the premature remodeling of the extracellular matrix of cervical collagen resulting from structural defects, infection or often unknown causes. The process of cervical remodeling, namely, the transformation of uterine cervix from a closed rigid structure to a compliant one for safe passage of the fetus, is a crucial stage of normal parturition, but this process can be drastically accelerated in preterm birth.
We explore the potential of Mueller polarimetry to detect these alterations of the extracellular matrix of cervical collagen early enough in order to provide the quantitative assessment of the preterm birth risk by polarimetric scoring of collagen. Unstained thin sections of the whole uterine cervices from both non-pregnant and pregnant mice were studied with the custom-built transmission Mueller matrix microscope. The results of statistical analysis and multi-Gaussian fit of the distributions of depolarization and linear retardance parameters of cervical tissue sections demonstrated that imaging Mueller polarimetry in the visible wavelength range is very sensitive to the changes of extracellular matrix of cervical collagen with pregnancy.
The circular arrangement of cervical collagen fibers around cervical os (that was observed for all non-pregnant mice) is lost through the whole length of mouse cervix one day before delivery. It suggests that the remodeling of cervical collagen may be evaluated in the direct observations with polarized light during the colposcopy test in late pregnancy. Thus, imaging Mueller polarimetry may serve as a fast and non-contact optical modality for the collagen scoring in pregnancy and the quantitative assessment of the preterm birth risk.
Significance: Obesity is a worldwide epidemic contributing directly to several cardiovascular risk factors including hypertension and type 2 diabetes. Wearable devices are becoming better at quantifying biomarkers relevant for the management of health and fitness. Unfortunately, both anecdotal evidence and recent studies indicate that some wearables have higher levels of error when utilized by populations with darker skin tones and high body mass index (BMI). There is an urgent need for a better evaluation of the limits of wearable health technologies when used by obese individuals.
Aims: (1) To review the current know-how on changes due to obesity in the skin epidermis, dermis, and subcutis that could affect the skin optical properties; (2) for the green wavelength range, to evaluate the difference in absorption and scattering coefficients from the abdominal skin between individuals with and without elevated BMI. The changes include alterations in layer thickness and cell size, as well as significant differences in chromophores and scatterer content, e.g., water, hemoglobin, collagen, and lipids.
Approach: We have summarized literature pertaining to changes in skin and its components in obesity and report the results of our search using articles published between years 1971 and 2020. A linear model was used to demonstrate the absorption and reduced scattering coefficient of the abdominal skin of individuals with and without elevated BMI in the green wavelength range (530 to 550 nm) that is typically found in most wearables.
Results: The general trends indicate a decrease in absorption for both dermis and subcutis and an increase in reduced scattering for both epidermis and dermis. At 544-nm wavelength, a typical wavelength used for photoplethysmography (PPG), the absorption coefficient’s relative percentage difference between high and low BMI skin, was 49% in the subcutis, 19% in the dermis, and negligible in the epidermis, whereas the reduced scattering coefficient relative difference was 21%, 29%, and 165% respectively.
Conclusions: These findings suggest that there could be significant errors in the output of optical devices used for monitoring health and fitness if changes due to obesity are not accounted for in their design.
Thin sections of uterine cervices from pregnant mice at day 6 and 18 of 19-days gestation period at different spatial locations along the cervices were studied with imaging Mueller polarimetry (IMP) combined with statistical analysis and multi-curve fit. The results suggest using depolarization and linear retardance images for collagen scoring and identification of cervical collagen changes during pregnancy. One day before delivery the remodeling of extracellular matrix of cervical collagen was detectable at the external cervical os, thus, proving that IMP modality may serve for the preterm birth risk assessment associated with the accelerated remodeling of cervical collagen.
There are 15 million infants born prematurely each year worldwide. Of these, about 1 million will die of complications from reduced gestation (37 weeks and less) before the age of five. Cervical remodeling, which is the transformation of the cervix from a firm structure to a soft one, is essential for both term and preterm birth (PTB). Monitoring the uterine cervix remodeling and particularly the arrangement of the cervix primary structural components (elastin and collagen) is of great interest to researchers studying PTB. We have utilized a Self-validating Mueller Matrix Micro-Mesoscope (SAMMM) with convolutional neural networks (CNN) and K-nearest neighbor (K-NN) for classification of elastin and collagen fibers in the mouse cervix. In this work, we proposed that an independent polarized microscope can be used for collagen and elastin classification leveraging the previously developed classifier. The Mueller matrix and decomposition parameters of depolarization, retardance and diattenuation obtained with this system are fed to the previously developed classifier. Excised cervical tissues (50 μm thickness) were used in this study including samples obtained at different gestation days.
Preterm birth (PTB) is defined as any birth prior to 37 weeks of gestation. Preterm birth contributes to 35% of 3.1 million neonatal deaths annually. There is a critical absence of clinical tools for diagnosis of preterm birth risk. We have proposed the use of Mueller Matrix Imaging (MMI) as a sensitive tool to monitor the atypical remodeling of collagen occurring in PTB. Here we expand our previous work to demonstrate that a Portable PReterm IMaging System capable of 3x4 MMI can be used at the point of care. It consists of a sheath insertable in the vaginal canal combined with a polarized imaging system. The main PPRIM body consists of a camera with integrated polarizers combined with a custom-made LED ring illuminator. The optical layout consists of a reverse telephoto lens suitable for imaging at long front working distance. Angle of incidence of the optical elements are minimized to reduce the sensitivity to misalignment and polarization aberrations. The system has a field of view of approximately 25 x 25 mm2 at 20 mm working distance. PPRIM is controlled by a laptop computer and custom software. To demonstrate the feasibility of the device, imaging tests were performed on a Gynecologic Skills Trainer as well as healthy volunteers.
Obesity is a widespread chronic illness which affects over 40% of the US adult population and its world-wide prevalence has increased over the years impacting both low and high-income countries. Obesity has been linked to higher risk of non-communicable diseases such as cardiovascular disease, type-2 diabetes, dyslipidemia, hypertension, among others. Currently the mostly prescribed regimes to combat chronic illness associated with obesity are efforts to change diet, behavior, and physical activity. Wearable devices have the potential of helping users reduce their obesity levels as these devices can easily acquire and communicate biometric data with users and clinicians. However, these technologies depend on optical sensors that are sensitive to molecular skin composition. We hypothesize that individuals with high BMI levels will present changes in skin optical properties when compared to their non-obese counterparts. Our objective is to capture skin optical properties at the wrist among a diverse cohort using a commercial optical system for research use. To meet an appropriate power, the human study, composed of males and females, is conducted with 100 adult participants. Statistical methods, including linear regression and t-tests, are used to determine interactions between measured data and participant demographics. We believe these results can improve design of optical wearables for the obese.
KEYWORDS: Arteries, Photoplethysmography, Blood pressure, Tissue optics, Signal attenuation, Monte Carlo methods, Instrument modeling, Geometrical optics, Finite element methods, Blood
Obesity is a significant risk factor for development and management of cardiovascular disease, one of the leading causes of death in the United States. Blood pressure (BP) is a key factor for monitoring cardiac health. In support of design and development of wearable health devices, we have developed a model to generate synthetic photoplethysmographic waveforms captured by a commercial device for the radial artery at the volar surface of the wrist. We focus on impacts to the PPG signal as a result of various changes attributed to obesity, epidermal melanin, and vascular layers.
Along with second harmonic generation and two-photon excited fluorescence measured with Non-Linear Microscopy, polarization properties measured with Mueller Matrix Polarimetry Microscopy can improve our understanding of the remodeling process in preterm pregnancy. This is critical to define therapeutic targets and to develop clinical tools for early and accurate detection of preterm risks. While manual analyzing and classifying individual cervical samples is time-consuming, automated algorithms can be advantageous when the number of samples is large. To such extent, we demonstrate the use of Convolutional Neural Networks (CNN) for feature extraction and K-Nearest Neighbor (KNN) for classification as an alternative to manual assessment.
Wearable devices, with Photoplethysmography (PPG)-based sensors, are helping patients to monitor chronic health conditions outside the clinic. The prime source of PPG signals is the blood volume change in the dermal vasculature. Here, we present a novel approach of using a skin model, containing double vascular layer within the dermis to investigate the pulsatile contribution from the region. Finite Element Method (FEM) is used to design vessels and PPG signals from the wrist are extracted by studying light transport through Monte Carlo simulations. By assessing PPG sensors in common wearables, the influence of obesity on the PPG signals are also investigated.
Glioma itself accounts for 80% of all malignant primary brain tumors, and glioblastoma multiforme (GBM) accounts for 55% of such tumors. Diffuse reflectance and fluorescence spectroscopy have the potential to discriminate healthy tissues from abnormal tissues and therefore are promising noninvasive methods for improving the accuracy of brain tissue resection. Optical properties were retrieved using an experimentally evaluated inverse solution. On average, the scattering coefficient is 2.4 times higher in GBM than in low grade glioma (LGG), and the absorption coefficient is 48% higher. In addition, the ratio of fluorescence to diffuse reflectance at the emission peak of 460 nm is 2.6 times higher for LGG while reflectance at 650 nm is 2.7 times higher for GBM. The results reported also show that the combination of diffuse reflectance and fluorescence spectroscopy could achieve sensitivity of 100% and specificity of 90% in discriminating GBM from LGG during ex vivo measurements of 22 sites from seven glioma specimens. Therefore, the current technique might be a promising tool for aiding neurosurgeons in determining the extent of surgical resection of glioma and, thus, improving intraoperative tumor identification for guiding surgical intervention.
The ability to recover the intrinsic fluorescence of biological fluorophores is crucial to accurately identify the fluorophores and quantify their concentrations in the media. Although some studies have successfully retrieved the fluorescence spectral shape of known fluorophores, the techniques usually came with heavy computation costs and did not apply for strongly absorptive media, and the intrinsic fluorescence intensity and fluorophore concentration were not recovered. In this communication, an experimental approach was presented to recover intrinsic fluorescence and concentration of fluorescein in the presence of hemoglobin (Hb). The results indicated that the method was efficient in recovering the intrinsic fluorescence peak and fluorophore concentration with an error of 3% and 10%, respectively. The results also suggested that chromophores with irregular absorption spectra (e.g., Hb) have more profound effects on fluorescence spectral shape than chromophores with monotonic absorption and scattering spectra (e.g., black India ink and polystyrene microspheres).
The emerging technique of three-dimensional (3D) printing provides a simple, fast, and flexible way to fabricate structures with arbitrary spatial features and may prove useful in the development of standardized, phantom-based performance test methods for biophotonic imaging. Acrylonitrile Butadiene Styrene (ABS) is commonly used in the printing process, given its low cost and strength. In this study, we evaluate 3D printing as an approach for fabricating biologically-relevant optical phantoms for hyperspectral reflectance imaging (HRI). The initial phase of this work involved characterization of absorption and scattering coefficients using spectrophotometry. The morphology of phantoms incorporating vessel-like channels with diameters on the order of hundreds of microns was examined by microscopy and OCT. A near-infrared absorbing dye was injected into channels located at a range of depths within the phantom and imaged with a near-infrared HRI system (650-1100 nm). ABS was found to have scattering coefficients comparable to biological tissue and low absorption throughout much of the visible and infrared range. Channels with dimensions on the order of the resolution limit of the 3D printer (~0.2 mm) exhibited pixelation effects as well as a degree of distortion along their edges. Furthermore, phantom porosity sometimes resulted in leakage from channel regions. Contrast-enhanced channel visualization with HRI was possible to a depth of nearly 1 mm – a level similar to that seen previously in biological tissue. Overall, our ABS phantoms demonstrated a high level of optical similarity to biological tissue. While limitations in printer resolution, matrix homogeneity and optical property tunability remain challenging, 3D printed phantoms have significant promise as samples for objective, quantitative evaluation of performance for biophotonic imaging modalities such as HRI.
Skin perfusion and oxygenation is easily disrupted by imposed pressure. Fiber optics probes, particularly those spectroscopy or Doppler based, may relay misleading information about tissue microcirculation dynamics depending on external forces on the sensor. Such forces could be caused by something as simple as tape used to secure the fiber probe to the test subject, or as in our studies by the full weight of a patient with spinal cord injury (SCI) sitting on the probe. We are conducting a study on patients with SCI conducting pressure relief maneuvers in their wheelchairs. This study aims to provide experimental evidence of the optimal timing between pressure relief maneuvers. We have devised a wireless pressure-controlling device; a pressure sensor positioned on a compression aluminum plate reads the imposed pressure in real time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the sample. This apparatus was used to monitor the effect of increasing values of pressure on spectroscopic fiber probes built to monitor tissue oxygenation and Doppler probes used to assess tissue perfusion.
Spectral variations in contrast enhancement of mucosal vasculature are a key feature of narrow band imaging (NBI) devices. In prior NBI studies, the enhanced visualization of larger, deeper vessels with green light (e.g., 540 nm) relative to violet light (e.g., 415 nm) has often been attributed to the well-known monotonic decrease in scattering coefficient with wavelength in biological tissues. We have developed and implemented numerical and experimental approaches to elucidate and quantify this and other light-tissue interaction effects relevant to NBI. A Monte Carlo model incorporating vessel-like inclusions with a range of diameters (20 to 400 microns) and depths (20 to 400 microns) was used to predict reflectance and fluence distributions in the tissue and calculate vessel contrast values. These results were compared to experimental measurements based on a liquid phantom with a hemoglobin-filled capillary. By comparing results for cases representing mucosa regions with and without blood, we were able to evaluate the relative significance of absorption and scattering on spectral variations in depth-selectivity. Results indicate that at 415 nm, detection of superficial vasculature with NBI was almost entirely dependent on the absorption coefficient of the blood in the vessel of interest. The enhanced visualization of deep vessels at 540 nm bands relative to 415 nm was due primarily to absorption by the superficial vasculature rather than a decrease in scattering coefficient. While computationally intensive, our numerical modeling approach provides unique insights into the light propagation mechanisms underlying this emerging clinical imaging technology.
Clinician’s recommendations on wheelchair pressure reliefs in the context of the high prevalence of pressure ulcers that
occur in people with spinal cord injury is not supported by strong experimental evidence. Some data indicates that
altered tissue perfusion and oxygenation occurring under pressure loads, such as during sitting, induce various
pathophysiologic changes that may lead to pressure ulcers.
Pressure causes a cascade of responses, including initial tissue hypoxia, which leads to ischemia, vascular
leakage, tissue acidification, compensatory angiogenesis, thrombosis, and hyperemia, all of which may lead to tissue
damage. We have developed an advanced skin sensor that allows measurement of oxygenation in addition to perfusion,
and can be safely used during sitting. The sensor consists of a set of fiber optics probes, spectroscopic and Laser Doppler
techniques that are used to obtain parameters of interest. The overriding goal of this project is to develop the evidence
base for clinical recommendations on pressure reliefs.
In this paper we will illustrate the experimental apparatus as well as some preliminary results of a small clinical
trial conducted at the National Rehabilitation Hospital.
Light-tissue interactions that influence vascular contrast enhancement in narrow band imaging (NBI) have not been the subject of extensive theoretical study. In order to elucidate relevant mechanisms in a systematic and quantitative manner we have developed and validated a Monte Carlo model of NBI and used it to study the effect of device and tissue parameters, specifically, imaging wavelength (415 versus 540 nm) and vessel diameter and depth. Simulations provided quantitative predictions of contrast-including up to 125% improvement in small, superficial vessel contrast for 415 over 540 nm. Our findings indicated that absorption rather than scattering-the mechanism often cited in prior studies-was the dominant factor behind spectral variations in vessel depth-selectivity. Narrow-band images of a tissue-simulating phantom showed good agreement in terms of trends and quantitative values. Numerical modeling represents a powerful tool for elucidating the factors that affect the performance of spectral imaging approaches such as NBI.
Narrow-band imaging (NBI) is a spectrally-selective reflectance imaging technique for enhanced visualization of
superficial vasculature. Prior clinical studies have indicated NBI's potential for detection of vasculature abnormalities
associated with gastrointestinal mucosal neoplasia. While the basic mechanisms behind the increased vessel contrast - hemoglobin absorption and tissue scattering - are known, a quantitative understanding of the effect of tissue and device
parameters has not been achieved. In this investigation, we developed and implemented a numerical model of light
propagation that simulates NBI reflectance distributions. This was accomplished by incorporating mucosal tissue layers
and vessel-like structures in a voxel-based Monte Carlo algorithm. Epithelial and mucosal layers as well as blood vessels
were defined using wavelength-specific optical properties. The model was implemented to calculate reflectance
distributions and vessel contrast values as a function of vessel depth (0.05 to 0.50 mm) and diameter (0.01 to 0.10 mm).
These relationships were determined for NBI wavelengths of 410 nm and 540 nm, as well as broadband illumination
common to standard endoscopic imaging. The effects of illumination bandwidth on vessel contrast were also simulated.
Our results provide a quantitative analysis of the effect of absorption and scattering on vessel contrast. Additional
insights and potential approaches for improving NBI system contrast are discussed.
Narrow band imaging (NBI) is a spectrally-selective reflectance imaging technique that is used as an adjunctive
approach to endoscopic detection of mucosal abnormalities such as neoplastic lesions. While numerous clinical studies
in tissue sites such as the esophagus, oral cavity and lung indicate the efficacy of this approach, it is not well
theoretically understood. In this study, we performed Monte Carlo simulations to elucidate the factors that affect NBI
device performance. The model geometry involved a two-layer turbid medium based on mucosal tissue optical
properties and embedded cylindrical, blood-filled vessels at varying diameters and depths. Specifically, we studied the
effect of bandpass filters (415±15 nm, 540±10 nm versus white light), blood vessel diameter (20-400 μm) and depth (30
- 450 μm), wavelength, and bandwidth on vessel contrast. Our results provide a quantitative evaluation of the two
mechanisms that are commonly believed to be the primary components of NBI: (i) the increased contrast provided by
high hemoglobin absorption and (ii) increase in the penetration depth produced by the decrease in scattering with
increasing wavelength. Our MC model can provide novel, quantitative insight into NBI, may lead to improvements in its
performance.
Quantitative data on the fundamental optical properties (OPs) of biological tissue, including absorption and reduced
scattering coefficients are important for elucidating light propagation during optical spectroscopy and facilitating
diagnostic device design and optimization, and may enable rapid detection of early neoplasia. However, systems for in
situ broadband measurement of mucosal tissue OPs in the ultraviolet-visible range have not been realized. In this study,
we evaluated a fiberoptic-based reflectance system, coupled with neural network inverse models (trained with Monte
Carlo simulation data), for measuring OPs in highly attenuating, two-layer turbid media. The experimental system
incorporated a broadband light source, a fiberoptic probe and a CCD camera. The calibration method involved a set of
standard nigrosin-microsphere phantoms as well as a more permanent spectralon phantom for quality assurance testing
and recalibration. The system was experimentally evaluated using two-layer hydrogel phantoms with hemoglobin and
polystyrene microspheres. The effects of tissue top-layer thickness and fitting approaches based on known absorption
and scattering distributions were discussed. With our method, measurements with error less than 28% were obtained in
the wavelength range of 350-630 nm.
NON-SPIE: Medical Instrumentation: Application and Design
This is a course designed as an upper-level course which covers the basics of principles of medical instrumentation design. The course presents an insider's perspective on how medical instrumentation is designed, built, and functions. Since the cours
NON-SPIE: Medical Instrumentation: Application and Design
This is a course designed as an upper-level course which covers the basics of principles of medical instrumentation design. The course presents an insider's perspective on how medical instrumentation is designed, built, and functions. Since the cours
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