Speech acoustic indices for differential diagnosis between Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

While speech disorder represents an early and prominent clinical feature of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), little is known about the sensitivity of speech assessment as a potential diagnostic tool. Speech samples were acquired from 215 subjects, including 25 MSA, 20 PSP, 20 Parkinson's disease participants, and 150 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 26 speech dimensions related to phonation, articulation, prosody, and timing. A semi-supervised weighting-based approach was then applied to find the best feature combinations for separation between PSP and MSA. Dysarthria was perceptible in all PSP and MSA patients and consisted of a combination of hypokinetic, spastic, and ataxic components. Speech features related to respiratory dysfunction, imprecise consonants, monopitch, slow speaking rate, and subharmonics contributed to worse performance in PSP than MSA, whereas phonatory instability, timing abnormalities, and articulatory decay were more distinctive for MSA compared to PSP. The combination of distinct speech patterns via objective acoustic evaluation was able to discriminate between PSP and MSA with very high accuracy of up to 89% as well as between PSP/MSA and PD with up to 87%. Dysarthria severity in MSA/PSP was related to overall disease severity. Speech disorders reflect the differing underlying pathophysiology of tauopathy in PSP and α-synucleinopathy in MSA. Vocal assessment may provide a low-cost alternative screening method to existing subjective clinical assessment and imaging diagnostic approaches.

Photoacoustic and high-frequency ultrasound imaging of systemic sclerosis patients.

INTRODUCTION: Systemic sclerosis starts with an early phase characterized by Raynaud's phenomenon, puffy fingers/hands, autoantibodies, and a scleroderma nailfold microscopic pattern. Alterations in the nailfold microscopic pattern are not evident in all early SSc patients. Photoacoustics (PA) and high-frequency ultrasound (HFUS) could fulfill this need. The former can measure oxygen saturation while the latter can measure skin thickening. We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud's phenomenon (PRP) by measuring oxygenation of the fingertip and skin thickening. METHODS: We compared measurements of oxygenation and skin thickness of the third finger between (early) SSc patients and PRP individuals and healthy controls. The spearman rank correlation was used to analyze an association between capillary density and oxygen saturation of the fingers. RESULTS: Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR, and 9 healthy controls. We found a significant difference in oxygen saturation between (early) SSc patients (80.8% ± 8.1 and 77.9% ± 10.5) and individuals with PRP (93.9% ± 1.1). Measurements of skin thickening showed a significant difference in (early) SSc patients compared to individuals with PRP (0.48 ± 0.06 mm and 0.51 ± 0.16 mm vs. 0.27 ± 0.01 mm). There was no significant difference between healthy and PRP individuals in oxygenation or skin thickening. CONCLUSION: Photoacoustic and high-frequency ultrasound could help to distinguish between (early) SSc, PRP, and healthy individuals in both oxygenation and skin thickening.

A Fourier approach to Lagrangian vortex detection.

We study the transport properties of coherent vortices over a finite-time duration. Here, we reveal that such vortices can be identified based on the frequency-domain representation of Lagrangian trajectories. We use Fourier analysis to convert particles' trajectories from their time domain to a presentation in the frequency domain. We then identify and extract coherent vortices as material surfaces along which particles' trajectories share similar frequencies. Our method identifies all coherent vortices in an automatic manner, showing high vortices' monitoring capacity. We illustrate our new method by identifying and extracting Lagrangian coherent vortices in different two- and three-dimensional flows.

Surface mixing and biological activity in the North-West African upwelling.

Near-shore water along the North-West African margin is one of the world's major upwelling regions. It is associated with physical structures of oceanic fronts which influence the biological productivity. The study of these coherent structures in connection with chlorophyll concentration data is of fundamental importance for understanding the spatial distributions of the plankton. In this work, we study the horizontal stirring and mixing in different upwelling areas using Lagrangian coherent structures (LCSs). These LCSs are calculated using the recent geodesic theory of LCSs. We use these LCSs to study the link between the chlorophyll fronts concentrations and surface mixing, based on 10 years of satellite data. These LCSs move with the flow as material lines, thus the horizontal mixing is calculated from the intersection of these LCSs with the finite time Lyapunov exponent maps. We compare our results with those of a recent study conducted over the same area, but based on finite size Lyapunov exponents (FSLEs), whose output is a plot of scalar distributions. We discuss the differences between FSLE and geodesic theory of LCS. The latter yields analytical solutions of LCSs, while FSLEs can only provide LCSs for sharp enough ridges of nearly constant height.

Clinically-Applicable Perfluorocarbon-Loaded Nanoparticles For In vivo Photoacoustic, 19F Magnetic Resonance And Fluorescent Imaging.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect. Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA, 19F MR, and fluorescence imaging in vitro and in vivo. Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x106 cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles. Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and 19F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use.

Feasibility of photoacoustic/ultrasound imaging of synovitis in finger joints using a point-of-care system.

We evaluate a portable ultrasound and photoacoustic imaging (PAI) system for the feasibility of a point-of-care assessment of clinically evident synovitis. Inflamed and non-inflamed proximal interphalangeal joints of 10 patients were examined and compared with joints from 7 healthy volunteers. PAI scans, ultrasound power Doppler (US-PD), and clinical examination were performed. We quantified the amount of photoacoustic (PA) signal using a region of interest (ROI) drawn over the hypertrophic joint space. PAI response was increased 4 to 10 fold when comparing inflamed with contralateral non-inflamed joints and with joints from healthy volunteers (p < 0.001 for both). US-PD and PAI were strongly correlated (Spearman's ρ = 0.64, with 95% CI: 0.42, 0.79). Hence, PAI using a compact handheld probe is capable of detecting clinically evident synovitis. This motivates further investigation into the predictive value of PAI, including multispectral PAI, with other established modalities such as US-PD or MRI.

In vivo photoacoustics and high frequency ultrasound imaging of mechanical high intensity focused ultrasound (HIFU) ablation.

The thermal effect of high intensity focused ultrasound (HIFU) has been clinically exploited over a decade, while the mechanical HIFU is still largely confined to laboratory investigations. This is in part due to the lack of adequate imaging techniques to better understand the in-vivo pathological and immunological effects caused by the mechanical treatment. In this work, we explore the use of high frequency ultrasound (US) and photoacoustics (PA) as a potential tool to evaluate the effect of mechanical ablation in-vivo, e.g. boiling histotripsy. Two mice bearing a neuroblastoma tumor in the right leg were ablated using an MRI-HIFU system conceived for small animals and monitored using MRI thermometry. High frequency US and PA imaging were performed before and after the HIFU treatment. Afterwards, the tumor was resected for further assessment and evaluation of the ablated region using histopathology. High frequency US imaging revealed the presence of liquefied regions in the treated area together with fragmentized tissue which appeared with different reflecting proprieties compared to the surrounding tissue. Photoacoustic imaging on the other hand revealed the presence of deoxygenated blood within the tumor after the ablation due to the destruction of blood vessel network while color Doppler imaging confirmed the blood vessel network destruction within the tumor. The treated area and the presence of red blood cells detected by photoacoustics were further confirmed by the histopathology. This feasibility study demonstrates the potential of high frequency US and PA approach for assessing in-vivo the effect of mechanical HIFU tumor ablation.

Preclinical detection of liver fibrosis using dual-modality photoacoustic/ultrasound system.

Liver fibrosis is a major cause for increasing mortality worldwide. Preclinical research using animal models is required for the discovery of new anti-fibrotic therapies, but currently relies on endpoint liver histology. In this study, we investigated a cost-effective and portable photoacoustic/ultrasound (PA/US) imaging system as a potential non-invasive alternative. Fibrosis was induced in mice using CCl4 followed by liver imaging and histological analysis. Imaging showed significantly increased PA features with higher frequency signals in fibrotic livers versus healthy livers. This corresponds to more heterogeneous liver structure resulting from collagen deposition and angiogenesis. Importantly, PA response and its frequency were highly correlated with histological parameters. These results demonstrate the preclinical feasibility of the PA imaging approach and applicability of dual PA/US system.

Opening the "White Box" in Tissue Engineering: Visualization of Cell Aggregates in Optically Scattering Scaffolds.

The noninvasive and longitudinal imaging of cells or cell aggregates in large optically scattering scaffolds is still a largely unresolved problem in tissue engineering. In this work, we investigated the potential of near-infrared (NIR) photoacoustic (PA) tomography imaging to address this issue. We used clinically relevant sizes of highly light scattering polyethersulfone multibore(®) hollow fiber scaffolds seeded with cells. Since cells have little optical absorption at NIR wavelengths, we studied labeling of cells with absorbers. Four NIR labels were examined for their suitability based on absorption characteristics, resistance to bleaching, and influence on cell viability. On the basis of these criteria, carbon nanoparticles proved most suitable in a variety of cells. For PA imaging, we used a research setup, based on computed tomography geometry. As proof of principle, using this imager we monitored the distribution and clustering of labeled rat insulinoma beta cell aggregates in the scaffolds. This was performed for the duration of 1 week in a nondestructive manner. The results were validated using fluorescence imaging, histology, and light microscopy imaging. Based on our findings, we conclude that PA tomography is a powerful tool for the nondestructive imaging of cells in optically scattering tissue-engineered scaffolds.

Pulsed photoacoustic flow imaging with a handheld system.

Flow imaging is an important technique in a range of disease areas, but estimating low flow speeds, especially near the walls of blood vessels, remains challenging. Pulsed photoacoustic flow imaging can be an alternative since there is little signal contamination from background tissue with photoacoustic imaging. We propose flow imaging using a clinical photoacoustic system that is both handheld and portable. The system integrates a linear array with 7.5 MHz central frequency in combination with a high-repetition-rate diode laser to allow high-speed photoacoustic imaging--ideal for this application. This work shows the flow imaging performance of the system in vitro using microparticles. Both two-dimensional (2-D) flow images and quantitative flow velocities from 12 to 75 mm/s were obtained. In a transparent bulk medium, flow estimation showed standard errors of ∼7% the estimated speed; in the presence of tissue-realistic optical scattering, the error increased to 40% due to limited signal-to-noise ratio. In the future, photoacoustic flow imaging can potentially be performed in vivo using fluorophore-filled vesicles or with an improved setup on whole blood.

Mapping optical fluence variations in highly scattering media by measuring ultrasonically modulated backscattered light.

Knowledge of the local optical fluence in biological tissue is of fundamental importance for biomedical optical techniques to achieve quantification. We report a method to noninvasively measure the local optical fluence in optically inhomogeneous scattering media. The concept is based on two aspects: the local tagging of light using ultrasonic modulation and the photon path reversibility principle. Our method has advantages over known computational-based fluence mapping techniques, for its purely experimental nature and without the requirement of prior knowledge of the optical properties of the medium. We provide a theoretical formalism and validation of the method with experiments in tissue-like phantoms. Further, we combine our method with photoacoustic imaging and compensate the photoacoustic signals for fluence variations in optically inhomogeneous media.

Two-dimensional spatiotemporal monitoring of temperature in photothermal therapy using hybrid photoacoustic-ultrasound transmission tomography.

Recently, we presented an add-on to a photoacoustic (PA) computed tomography imager that permits the simultaneous imaging of ultrasound (US) transmission parameters such as the speed of sound (SOS), without additional measurements or instruments. This method uses strong absorbers positioned outside the object in the path of light for producing laser-induced US to interrogate the object in a conventional PA imager. Here, we investigate the feasibility of using this approach, first with PA to pin-point the location of photothermal therapeutic agents and then with serial SOS tomograms to image and monitor the resulting local temperature changes when the agents are excited with continuous wave (CW) light. As the object we used an agar-based tissue-mimicking cylinder carrying beads embedded with different concentrations of gold nanospheres. PA and SOS tomograms were simultaneously acquired as the gold nanospheres were photothermally heated using a 532-nm CW laser. In a first approximation, using the relation between SOS of water and temperature, the SOS tomograms were converted into temperature maps. The experimental results were verified using simulations: Monte Carlo modeling of light propagation through a turbid medium and using the obtained absorbed energy densities in heat diffusion modeling for spatial temperature distribution.