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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.

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 CCl_4 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.

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.

This paper presents a novel algorithm for automatic detection of Glottal Closure Instants (GCI) from the speech signal. Our approach is based on a novel multiscale method that relies on precise estimation of a multiscale parameter at each time instant in the signal domain. This parameter quantifies the degree of signal singularity at each sample from a multi-scale point of view and thus its value can be used to classify signal samples accordingly. We use this property to develop a simple algorithm for detection of GCIs and we show that for the case of clean speech, our algorithm performs almost as well as a recent state-of-the-art method. Next, by performing a comprehensive comparison in presence of 14 different types of noises, we show that our method is more accurate (particularly for very low SNRs). Our method has lower computational times compared to others and does not rely on an estimate of pitch period or any critical choice of parameters.

Quantitative measurements of the chromophores concentration in vivo present a challenge in photoacoustic imaging. The obtained signal depends on the absorbed optical density which is the product of absorption coefficient and local fluence. As a result of wavelength-dependent optical attenuation and scattering, the local fluence in biological media varies with depth and the optical wavelength. This fluence heterogeneity needs to be compensating in the order to recover the absolute absorption coefficient. In this paper we describe a new approach to recover the absolute optical absorption coefficient from measured PA signals based in combination between photoacoustic and acousto-optic signals. The present method is based on two principles, a given photon trajectory through a scattering medium can be travelled in two directions with equal probability and photons which traverse a certain volume can be labeled in that volume with the use of focused ultrasound. We give proof of the principle using Monte Carlo simulation and we demonstrate the experimental feasibility of the technique in tissue-mimicking phantom by correcting a fluence heterogeneity caused by the optical diffusion.

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. Conclusion: Photoacoustic and high-frequency ultrasound could help to distinguish between (early) SSc, PRP, and healthy individuals in both oxygenation and skin thickening.