A variational method for quantitative photoacoustic tomography with piecewise constant coefficients

In this article, we consider the inverse problem of determining spatially heterogeneous absorption and diffusion coefficients from a single measurement of the absorbed energy (in the steady-state diffusion approximation of light transfer). This problem, which is central in quantitative photoacoustic tomography, is in general ill-posed since it admits an infinite number of solution pairs. We show that when the coefficients are known to be piecewise constant functions, a unique solution can be obtained. For the numerical determination of the coefficients, we suggest a variational method based based on an Ambrosio-Tortorelli-approximation of a Mumford-Shah-like functional, which we implemented numerically and tested on simulated two-dimensional data

Multi-scale volumetric dynamic optoacoustic and laser ultrasound (OPLUS) imaging enabled by semi-transparent optical guidance

Major biological discoveries have been made by interrogating living organisms with light. However, the limited penetration of unscattered photons within biological tissues severely limits the depth range covered by optical methods. Deep-tissue imaging has been achieved by combining light and ultrasound. Optoacoustic imaging uniquely exploits optical generation of ultrasound to render high-resolution images at depths unattainable with optical microscopy. Recently, laser ultrasound has further been suggested as a means of generating broadband acoustic waves for high-resolution pulse-echo ultrasound imaging. Herein, we propose an approach to simultaneously interrogate biological tissues with light and ultrasound based on layer-by-layer coating of silica optical fibers with a controlled degree of transparency. We exploit the time separation between optoacoustic signals and ultrasound echoes collected with a custom-made spherical array transducer for simultaneous three-dimensional optoacoustic and laser ultrasound (OPLUS) imaging with a single laser pulse. OPLUS is shown to enable large-scale comprehensive anatomical characterization of tissues along with functional multi-spectral imaging of spectrally-distinctive chromophores and assessment of cardiac dynamics at ultrafast rates only limited by the pulse repetition frequency of the laser. The suggested approach provides a flexible and scalable means for developing a new generation of systems synergistically combining the powerful capabilities of optoacoustics and ultrasound imaging in biology and medicine.Comment: 21 pages, 4 figure

Image-guided optical spectroscopy in diagnosis of osteoarthritis: a clinical study

This goal of this study was to clinically evaluate the potential of a novel hybrid imaging techniques, called x-ray guided multispectral diffuse optical tomography, for identifying physiological parameters of joint tissues that can be used to distinguish between osteoarthritic and healthy joints in the hand. Between 2006 and 2009, the distal interphalangeal (DIP) finger joints from 40 subjects including 22 osteoarthritis patients and 18 healthy controls were examined clinically and scanned by the hybrid imaging platform that integrated a C-arm based x-ray tomosynthetic system with a mutlispectral diffuse optical imaging system. Based on the reconstructed results from the 40 subjects, it was observed that oxygen saturation and water content were two statistically most significant physiological discriminators for differentiation of the healthy joints from the osteoarthritic ones

A review of some recent developments in polarization-sensitive optical imaging techniques for the study of articular cartilage

This article reviews recent developments in the optical imaging of articular cartilage using polarized-light methods, with an emphasis on tools that could be of use in tissue engineering approaches to treatment. Both second-harmonic generation microscopy and polarization-sensitive optical coherence tomography are described and their potential role in the treatment of cartilage disorders such as osteoarthritis is suggested. Key results are reviewed and future developments are discussed

Nanoparticle sensors and lubricants for degenerative articular cartilage

Articular cartilage is a highly organized, anisotropic tissue lining the ends of bones within synovial joints. Composed primarily of water, collagens, proteoglycans and chondrocytes which synergistically give rise to the tissue's mechanical and tribological properties. Fluid pressurization and resistance to fluid flow within the porous extracellular matrix of cartilage, coupled with the low hydraulic permeability of the tissue endow the tissue with a viscoelastic response to loading and aid to reduce the coefficient of friction between articulating surfaces, with the pressurized fluid supporting 95% of applied loads. Experiencing millions of articulations throughout an average lifetime, articular cartilage possesses distinct biotribological properties. These require effective lubrication, mediated by the synergistic interaction between fluid and boundary lubricants, to provide a low coefficient of friction and prevent wear at the cartilage surface. Osteoarthritis is the progressive deterioration of articular cartilage and synovial joint structure and function, leading to softer and wear prone tissue on account of altered biochemical composition of the extracellular matrix. Plain radiography remains the most accessible tool and the current standard of care to visualize musculoskeletal diseases and injuries (e.g., osteoarthritis), but cannot directly visualize soft tissues or cartilage, and diagnoses are based solely on boney changes, which occur in the later stages of the disease. Coupled with no way to quantitatively assess tissue health prior to irreversible deterioration, there remains no cure for osteoarthritis. Integral to OA pathology are concomitant changes in the biochemical composition of synovial fluid that result in deterioration of rheological properties, contributing to increased cartilage wear. To address both the lack of quantitative diagnosis methods and lack of chondroprotective therapies, this dissertation presents a dual faceted approach to quantitatively image articular cartilage health, coupled with lubrication strategies to improve cartilage lubrication, and preserve cartilage tissue. This dissertation describes the synthesis of tantalum oxide nanoparticles of varying surface charges for use as contrast agents for rapid, minimally invasive, non-destructive, and quantitative contrast-enhanced computed tomography to assess both the biochemical content and biomechanical integrity of articular cartilage. Ex vivo contrast enhanced computed tomography attenuation using the nanoparticle contrast agent reveals correlations between attenuation and the mechanical and biochemical properties of the tissue. The lubrication strategy described within this dissertation involves introducing a rolling ball element between two surfaces to reduce friction. In this strategy, either single, globular macromolecules or nanoparticles are employed as ball bearings between articulating surfaces to reduce friction when asperities on the surfaces are in direct contact. Rheological characterization and construction of classical Stribeck curves using the lubricant formulations reveal that introducing the rolling element reduces the coefficient of friction during boundary lubrication, while leaving the rheological properties of the base fluid intact. Ex vivo cartilage mechanical testing involving shear deformation under varying speeds and loads reveal improved biotribological performance compared to pure synovial fluid or saline

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease

Экспериментальные исследования оптоакустического воздействия на модель эритроцитов в присутствии углеродных наночастиц

Experimental model has been developed to study optoacoustic signal from model blood cells presented by polystyrene microspheres with nanoparticles. It was found out that nanoparticles due to their strong absorption of light significantly affect the coefficient of cellular optical absorption, while the thermophysical parameters, namely the coefficient of thermal expansion, compressibility and isobaric specific heat of cells remain unchanged, since nanoparticles occupy a small intracellular volume compared to the cell volume. Optoacoustic signals were obtained using model solutions at various concentrations of cells and nanoparticles using 1064 nm laser. The results of experimental measurements using LIMO 100–532/1064-U system based on Nd:YAG showed that the amplitude of the optoacoustic signal increased without increasing the temperature in the laser area.Разработана экспериментальная модель для изучения оптико-акустического сигнала от моделей клеток крови, представляющих собой полистирольные микросферы с наночастицами. Установлено, что наночастицы из-за их сильного поглощения света существенно влияют на коэффициент клеточного оптического поглощения, при этом теплофизические параметры, а именно коэффициент теплового расширения, сжимаемость и изобарическая удельная теплоемкость клеток остаются неизменными, так как наночастицы занимают незначительный внутриклеточный объем по сравнению с объемом самой клетки. Оптоакустические сигналы были получены с использованием модельных растворов при различных концентрациях клеток и наночастиц для воздействия лазером с длиной волны 1064 нм. Экспериментальные данные, полученные с помощью лазерной установки LIMO100–532/1064-U на основе Nd:YAG, показали, что амплитуда оптоакустического сигнала возрастала без увеличения температуры в зоне воздействия лазера

Photoacoustic tomography system for noninvasive real-time three-dimensional imaging of epilepsy

A real-time three-dimensional (3D) photoacoustic imaging system was developed for epilepsy imaging in small animals. The system is based on a spherical array containing 192 transducers with a 5 MHz central frequency. The signals from the 192 transducers are amplified by 16 homemade preamplifier boards with 26 dB and multiplexed into a 64 channel data acquisition system. It can record a complete set of 3D data at a frame rate of 3.3 f/s, and the spatial resolution is about 0.2 mm. Phantom experiments were conducted to demonstrate the high imaging quality and real time imaging ability of the system. Finally, we tested the system on an acute epilepsy rat model, and the induced seizure focus was successfully detected using this system

Multispectral imaging for preclinical assessment of rheumatoid arthritis models

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition affecting multiple body systems. Murine models of RA are vital in progressing understanding of the disease. The severity of arthritis symptoms is currently assessed in vivo by observations and subjective scoring which are time-consuming and prone to bias and inaccuracy. The main aim of this thesis is to determine whether multispectral imaging of murine arthritis models has the potential to assess the severity of arthritis symptoms in vivo in an objective manner. Given that pathology can influence the optical properties of a tissue, changes may be detectable in the spectral response. Monte Carlo modelling of reflectance and transmittance for varying levels of blood volume fraction, blood oxygen saturation, and water percentage in the mouse paw tissue demonstrated spectral changes consistent with the reported/published physiological markers of arthritis. Subsequent reflectance and transmittance in vivo spectroscopy of the hind paw successfully detected significant spectral differences between normal and arthritic mice. Using a novel non-contact imaging system, multispectral reflectance and transmittance images were simultaneously collected, enabling investigation of arthritis symptoms at different anatomical paw locations. In a blind experiment, Principal Component (PC) analysis of four regions of the paw was successful in identifying all 6 arthritic mice in a total sample of 10. The first PC scores for the TNF dARE arthritis model were found to correlate significantly with bone erosion ratio results from microCT, histology scoring, and the manual scoring method. In a longitudinal study at 5, 7 and 9 weeks the PC scores identified changes in spectral responses at an early stage in arthritis development for the TNF dARE model, before clinical signs were manifest. Comparison of the multispectral image data with the Monte Carlo simulations suggest that in this study decreased oxygen saturation is likely to be the most significant factor differentiating arthritic mice from their normal littermates. The results of the experiments are indicative that multispectral imaging performs well as an assessor of arthritis for RA models and may outperform existing techniques. This has implications for better assessment of preclinical arthritis and hence for better experimental outcomes and improvement of animal welfare

New insights in osteoarthritis diagnosis and treatment: Nano-strategies for an improved disease management

Osteoarthritis (OA) is a common chronic joint pathology that has become a predominant cause of disability worldwide. Even though the origin and evolution of OA rely on different factors that are not yet elucidated nor understood, the development of novel strategies to treat OA has emerged in the last years. Cartilage degradation is the main hallmark of the pathology though alterations in bone and synovial inflammation, among other comorbidities, are also involved during OA progression. From a molecular point of view, a vast amount of signaling pathways are implicated in the progression of the disease, opening up a wide plethora of targets to attenuate or even halt OA. The main purpose of this review is to shed light on the recent strategies published based on nanotechnology for the early diagnosis of the disease as well as the most promising nano-enabling therapeutic approaches validated in preclinical models. To address the clinical issue, the key pathways involved in OA initiation and progression are described as the main potential targets for OA prevention and early treatment. Furthermore, an overview of current therapeutic strategies is depicted. Finally, to solve the drawbacks of current treatments, nanobiomedicine has shown demonstrated benefits when using drug delivery systems compared with the administration of the equivalent doses of the free drugs and the potential of disease-modifying OA drugs when using nanosystems. We anticipate that the development of smart and specific bioresponsive and biocompatible nanosystems will provide a solid and promising basis for effective OA early diagnosis and treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacemen