KEYWORDS: Monte Carlo methods, Photoacoustic imaging, Optical simulations, Tissues, Tissue optics, Near infrared, Signal generators, Signal attenuation, Photoacoustic spectroscopy, Natural surfaces
Translation of photoacoustic (PA) imaging for abdominal imaging requires an optimized optical illumination for deep tissue light delivery. Simulations-based optimization of laser beam size has not been tested for deep imaging depths (< 0.5 cm). Additionally, while conventional PA imaging uses wavelengths in the first near infrared (NIR) window, tissue attenuation is minimized in the NIR-2 window, allowing for greater fluence penetration. In this study, Monte-Carlo simulated fluence maps were validated using PA images acquired of a lead-polystyrene phantom with lead positioned at multiple depths (1-4 cm) and illuminated with a 750 nm beam of varying widths (0.8-2.0 cm). At imaging depths of 4 cm, a 2× increase in fluence deposition when increasing beam diameter by a factor of 1.5, was consistently observed between MC simulations and experimental imaging. Using an optimized 1064 nm beam with a 1.6 cm beam, an 8× increase in deposited fluence at similar depths is observed.
The altered placental function which is characteristic of preeclampsia is challenging to characterize with existing imaging techniques. We have developed ultrasound-guided spectral photoacoustic imaging of placental function in an in vivo rat model of preeclampsia, and investigated the impact of therapy on preeclampsia and placental function. Additionally, we have studied the acute vascular response during pregnancy – determining vascular selectivity and response time to vasoactive compounds — using photoacoustic tomography. We integrate our photoacoustic imaging methods with contrast-enhanced ultrasound to provide measures of placental vascular flow. By combining these hybrid optical-acoustic imaging techniques, we characterize placental pathologies and their responses to treatment.
Transabdominal imaging using photoacoustics (PA) is limited by optical attenuation of tissue due to high scattering and absorption in the near infrared (NIR) window. Tissue attenuation is lowered when imaging with longer wavelengths in the NIR window (> 950 nm). However, intrinsic optical contrast is limited in this range and exogenous agents such as gold nanorods (AuNRs) prove popular alternatives. AuNRs have unique optical absorption peaks, due to localized surface plasmon resonance (LSPR), which allow tuning to wavelengths with minimal tissue attenuation. However, AuNRs tend to be bulky (> 50 nm) when adjusting peak LSPR to deep NIR wavelengths leading to poor clearance. In this study, we explored PA signal generation of a biodegradable and biocompatible semiconductor contrast agent – Cu-Fe (bornite) nanocrystals. The semiconductor nature of the nanocrystals allows for particles to be small (3-8 nm) facilitating excretion through kidneys. Here, PA signal generation of bornite was compared to two conventional photoacoustic contrast agents – AuNRs and indocyanine green dye. We found that at similar mass concentrations, bornite generated PA signal 5× greater than AuNRs. In-vivo imaging of bornite showed a 2x increase in sensitivity compared to AuNRs at similar volume concentrations.
Integrating spheres (IS) facilitate accurate measurements of the total reflectance and transmittance of turbid media, which can be used to determine optical properties of the sample measured. Translation of measurements into optical properties are achieved using theoretical photon migration models. A widely used approach with IS measurements is to use the inverse adding-doubling (IAD) method that utilizes the forward adding-doubling method, which is a rigorous numerical forward solver of the 1-D radiative transport equation. In order to experimentally satisfy the 1-D nature of the theoretical model, samples must be large enough to be modeled as infinite in extent along axes normal to incident beam. Here, we explore constraint on the required sample dimensions by comparing errors in modeled reflectance and transmittance between the adding-doubling and Monte Carlo simulations. We compare both the forward predictions and the inverse extraction of the optical properties for samples with varying dimensions, sample optical properties and beam profiles. Lateral losses (loss of light from sides of the sample) were observed to be significant when illumination beam diameters become comparable to sample length. Errors of 2-3% were noted between MC predictions vs. the adding-doubling estimates for reflectance and transmittance and these translated to 5-30% errors in IAD estimated optical absorption while the extracted scattering coefficients remained unaffected and had errors < 2%, relative to simulated values. We find that when the incident beam had diameter less than 80% of the sample length, the estimated optical properties of the medium were well extracted using the IAD.
In tissue optics, it is important to measure the wavelength-dependent scattering, absorption and anisotropy coefficients of tissues to describe interactions of light with such turbid media. Here, we use the inverse adding-doubling (IAD) technique coupled to measurements acquired using an integrating sphere (IS). The IS system provides a method to acquire highly accurate measurements for the total reflectance and transmittance for thin turbid samples. The IAD is an iterative technique that uses a numerical solver to radiative transport capable of fitting a set of measured reflectance and transmittance values and thereby yield optical absorption and reduced scattering coefficients of thin samples. We test the validity and performance of the IS/IAD system by obtaining measurements on a set of liquid phantoms prepared with controlled absorption and scattering properties. We explore sources of errors and discuss how the the accuracy these techniques may be improved. We demonstrate that the IAD/IS technique allows the accurate recovery of chromophore spectral properties.
Video Photoplethysmography (VPPG) is a numerical technique to process standard RGB video data of exposed human skin and extracting the heart-rate (HR) from the skin areas. Being a non-contact technique, VPPG has the potential to provide estimates of subject’s heart-rate, respiratory rate, and even the heart rate variability of human subjects with potential applications ranging from infant monitors, remote healthcare and psychological experiments, particularly given the non-contact and sensor-free nature of the technique. Though several previous studies have reported successful correlations in HR obtained using VPPG algorithms to HR measured using the gold-standard electrocardiograph, others have reported that these correlations are dependent on controlling for duration of the video-data analyzed, subject motion, and ambient lighting. Here, we investigate the ability of two commonly used VPPG-algorithms in extraction of human heart-rates under three different laboratory conditions. We compare the VPPG HR values extracted across these three sets of experiments to the gold-standard values acquired by using an electrocardiogram or a commercially available pulseoximeter. The two VPPG-algorithms were applied with and without KLT-facial feature tracking and detection algorithms from the Computer Vision MATLAB® toolbox. Results indicate that VPPG based numerical approaches have the ability to provide robust estimates of subject HR values and are relatively insensitive to the devices used to record the video data. However, they are highly sensitive to conditions of video acquisition including subject motion, the location, size and averaging techniques applied to regions-of-interest as well as to the number of video frames used for data processing.
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