Wavelength-dependent Optical Attenuation Research Articles

Customized Enhancement of Thermal Sensitivity of Tumors at Different Subcutaneous Depths by Multichannel Lanthanide Nanocomposites.

The photothermal therapeutic effect on tumors located at different subcutaneous depths varies due to the attenuation of light by tissue. Here, based on the wavelength-dependent optical attenuation properties of tissues, the tumor depth is assessed using a multichannel lanthanide nanocomposite. A zeolitic imidazolate framework (ZIF-8)-coated nanocomposite is able to deliver high amounts of the hydrophilic heat shock protein 90 inhibitor epigallocatechin gallate through a hydrogen-bonding network formed by the encapsulated highly polarized polyoxometalate guest. It is superior to both bare and PEGylated ZIF-8 for drug delivery. With the assessment of tumor depth and accumulated amount of nanocomposite by fluorescence, an irradiation prescription can be customized to release sufficient HSP90 inhibitor and generate heat for sensitized photothermal treatment of tumors, which not only ensured therapeutic efficacy but also minimized damage to the surrounding tissues.

Multiscale photoacoustic tomography using reversibly switchable thermochromics.

Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep tissues, mainly due to wavelength-dependent optical attenuation and inaccurate acoustic inversion. Previous work has demonstrated that reversible color-shifting can drastically improve the detection sensitivity of PAT by suppressing nonswitching background signals. We aim to develop a new color switching-based PAT method using reversibly switchable thermochromics (ReST). We developed a family of ReST with excellent water dispersion, biostability, and temperature-controlled color changes by surface modification of commercial thermochromic microcapsules with the hydrophilic polysaccharide alginate. The optical absorbance of the ReST was switched on and off repeatedly by modulating the surrounding temperature, allowing differential photoacoustic detection that effectively suppressed the nonswitching background signal and substantially improved image contrast and detection sensitivity. We demonstrate reversible thermal-switching imaging of ReST in vitro and in vivo using three PAT modes at different length scales. ReST-enabled PAT is a promising technology for high-sensitivity deep tissue imaging of molecular activity in temperature-related biomedical applications, such as cancer thermotherapy.

Normalization of optical fluence distribution for three-dimensional functional optoacoustic tomography of the breast.

.Significance: In three-dimensional (3D) functional optoacoustic tomography (OAT), wavelength-dependent optical attenuation and nonuniform incident optical fluence limit imaging depth and field of view and can hinder accurate estimation of functional quantities, such as the vascular blood oxygenation. These limitations hinder OAT of large objects, such as a human female breast.Aim: We aim to develop a measurement-data-driven method for normalization of the optical fluence distribution and to investigate blood vasculature detectability and accuracy for estimating vascular blood oxygenation.Approach: The proposed method is based on reasonable assumptions regarding breast anatomy and optical properties. The nonuniform incident optical fluence is estimated based on the illumination geometry in the OAT system, and the depth-dependent optical attenuation is approximated using Beer–Lambert law.Results: Numerical studies demonstrated that the proposed method significantly enhanced blood vessel detectability and improved estimation accuracy of the vascular blood oxygenation from multiwavelength OAT measurements, compared with direct application of spectral linear unmixing without optical fluence compensation. Experimental results showed that the proposed method revealed previously invisible structures in regions deeper than 15 mm and/or near the chest wall.Conclusions: The proposed method provides a straightforward and computationally inexpensive approximation of wavelength-dependent effective optical attenuation and, thus, enables mitigation of the spectral coloring effect in functional 3D OAT imaging.

Self-Fluence-Compensated Functional Photoacoustic Microscopy.

Optical-resolution photoacoustic microscopy (OR-PAM) can image blood oxygen saturation (sO2) in vivo with high resolution and excellent sensitivity and offers a great tool for neurovascular study and early cancer diagnosis. OR-PAM ignores the wavelength-dependent optical attenuation in superficial tissue, which cause errors in sO2 imaging. Monte Carlo simulation shows that variations in imaging depth, vessel diameter, and focal position can cause up to ∼60 % decrease in sO2 imaging. Here, we develop a self-fluence-compensated OR-PAM to compensate for the wavelength-dependent fluence attenuation. We propose a linearized model to estimate the fluence attenuations and use three optical wavelengths to compensate for them in sO2 calculation. We validate the model in both numerical and physical phantoms and show that the compensation method can effectively reduce the sO2 errors. In functional brain imaging, we demonstrate that the compensation method can effectively improve sO2 accuracy, especially in small vessels. Compared with uncompensated ones, the sO2 values are improved by 10~30% in the brain. We monitor ischemic-stroke-induced brain injury which demonstrates great potential for the pre-clinical study of vascular diseases.

Modeling combined ultrasound and photoacoustic imaging: Simulations aiding device development and artificial intelligence

Combined ultrasound and photoacoustic (USPA) imaging has attracted several pre-clinical and clinical applications due to its ability to simultaneously display structural, functional, and molecular information of deep biological tissue in real time. However, the depth and wavelength dependent optical attenuation and the unknown optical and acoustic heterogeneities limit the USPA imaging performance in deep tissue regions. Novel instrumentation, image reconstruction, and artificial intelligence (AI) methods are currently being investigated to overcome these limitations and improve the USPA image quality. Effective implementation of these approaches requires a reliable USPA simulation tool capable of generating US based anatomical and PA based molecular contrasts of deep biological tissue. Here, we developed a hybrid USPA simulation platform by integrating finite element models of light (NIRFast) and ultrasound (k-Wave) propagations for co-simulation of B-mode US and PA images. The platform allows optimization of different design parameters for USPA devices, such as the aperture size and frequency of both light and ultrasound detector arrays. For designing tissue-realistic digital phantoms, a dictionary-based function has been added to k-Wave to generate various levels of ultrasound speckle contrast. The feasibility of modeling US imaging combined with optical fluence dependent multispectral PA imaging is demonstrated using homogeneous as well as heterogeneous tissue phantoms mimicking human organs (e.g., prostate and finger). In addition, we also demonstrate the potential of the simulation platform to generate large scale application-specific training and test datasets for AI enhanced USPA imaging. The complete USPA simulation codes together with the supplementary user guides have been posted to an open-source repository (https://github.com/KothapalliLabPSU/US-PA_simulation_codes).

Preparation and performance study of a novel liquid scintillator with mixed solvent as the matrix

A novel liquid scintillator with the mixed solvent as the matrix was prepared for obtaining a good comprehensive performance. In this ternary liquid scintillator, the combination of 20% pseudocumene (PC) and 80% linear-alkyl benzene (LAB) by volume was chosen as the mixed solvent, and 2,5-diphenyloxazole (PPO) and 1,4-bis(2-Methylstyryl) benzene (bis-MSB) were as the primary fluor and wavelength shifter, respectively. The optimum prescription was obtained with regard to the light yield. Some characterizations based on the optimal formulation were conducted. The fluorescence emission spectra and wavelength-dependent optical attenuation length of the sample were measured by the fluorescence spectrophotometer and an UV–Vis spectrometer, respectively. The light yield was characterized by adopting the home-made optical platform device. The decay time was tested by adopting the time-correlated single photon counting (TCSPC) technique featured in high dynamic range of several orders of magnitude in light intensity. The experimental test results showed that the sample had a fairly good comprehensive performance.

Multiple irradiation sensing of the optical effective attenuation coefficient for spectral correction in handheld OA imaging

Spectral optoacoustic (OA) imaging enables spatially-resolved measurement of blood oxygenation levels, based on the distinct optical absorption spectra of oxygenated and de-oxygenated blood. Wavelength-dependent optical attenuation in the bulk tissue, however, distorts the acquired OA spectrum and thus makes quantitative oxygenation measurements challenging. We demonstrate a correction for this spectral distortion without requiring a priori knowledge of the tissue optical properties, using the concept of multiple irradiation sensing: recording the OA signal amplitude of an absorbing structure (e.g. blood vessel), which serves as an intrinsic fluence detector, as function of irradiation position. This permits the reconstruction of the bulk effective optical attenuation coefficient μeff,λ. If performed at various irradiation wavelengths, a correction for the wavelength-dependent fluence attenuation is achieved, revealing accurate spectral information on the absorbing structures. Phantom studies were performed to show the potential of this technique for handheld clinical combined OA and ultrasound imaging.

Quantitative blood oxygen saturation imaging using combined photoacoustics and acousto-optics.

In photoacoustic spectroscopy (PAS), wavelength dependent optical attenuation of biological tissue presents a challenge to measure the absolute oxygen saturation of hemoglobin (sO2). Here, we employ the combination of photoacoustics and acousto-optics (AO) at two optical wavelengths to achieve quantification, where AO serves as a sensor for the relative local fluence. We demonstrate that our method enables compensation of spatial as well as wavelength dependent fluence variations in PAS without a priori knowledge about the optical properties of the medium. The fluence compensated photoacoustic images at two excitation wavelengths are used to estimate the absolute oxygen saturation of blood in a spatially and spectroscopically heterogeneous phantom.

An aircraft based three channel broadband cavity enhanced absorption spectrometer for simultaneous measurements of NO<sub>3</sub>, N<sub>2</sub>O<sub>5</sub> and NO<sub>2</sub>

Abstract. A three channel broadband cavity enhanced absorption spectroscopy (BBCEAS) instrument has been developed for airborne measurements of atmospheric trace gases involved in night-time oxidation chemistry and air quality. The instrument was deployed on board the Facility for Airborne Atmospheric Measurements BAe 146-301 atmospheric research aircraft during the Role of Nighttime Chemistry in Controlling the Oxidising Capacity of the Atmosphere (RONOCO) measurement campaigns between December 2009 and January 2011. In its present configuration (i.e. specifications of the cavity optics and spectrometers) the instrument is designed to measure NO3, N2O5 (by detection of NO3 after thermal dissociation of N2O5), H2O and NO2 by characterising the wavelength dependent optical attenuation within ambient samples by molecular absorption around 662 nm (NO3 and H2O) and 445 nm (NO2). This paper reports novel advancements in BBCEAS instrumentation including a refined method for performing BBCEAS mirror reflectivity calibrations using measurements of the phase delay introduced by the optical cavities to amplitude modulated radiation. Furthermore, a new methodology is introduced for fitting the strong but unresolved transitions of water vapour, which is required for accurate retrieval of water absorption features from the 662 nm absorption band used to measure NO3 concentrations. The paper also details the first example of airborne measurements of NO3, N2O5 and NO2 over Europe from a flight over the North Sea and Thames Estuary on the night of the 20 July 2010, one of the most polluted days of the RONOCO summertime flying period. As part of this analysis, the performance of the BBCEAS instrument is assessed by comparing airborne NO2 measurements to those reported concurrently by a photolytic chemiluminescence based detector.

Effects of wavelength-dependent fluence attenuation on the noninvasive photoacoustic imaging of hemoglobin oxygen saturation in subcutaneous vasculature in vivo

Quantitative measurements of the oxygen saturation of hemoglobin (sO2) in a blood vessel in vivo presents a challenge in photoacoustic imaging. As a result of wavelength-dependent optical attenuation in the skin, the local fluence at a subcutaneous vessel varies with the optical wavelength in spectral measurement and hence needs to be compensated for so that the intrinsic absorption coefficient can be recovered. Here, by employing a simplified double-layer skin model, we demonstrate that although the absolute value of sO2 in a vessel is seriously affected by the volume fraction of blood and the spatially averaged sO2 in the dermis, the difference of sO2 between neighboring vessels is minimally affected. Experimentally, we acquire compensational factors for the wavelength-dependent optical attenuation by measuring the PA spectrum of a subcutaneously inserted 25 µm thick black film using our PA microscope. We demonstrate in vivo that the difference in sO2 between a typical artery and a typical vein is conserved before and after spectral compensation. This conservation holds regardless of the animal's systemic physiological state.