Stefan Preisser

Vapor bubble generation around gold nano-particles and its application to damaging of cells

We investigated vapor bubbles generated upon irradiation of gold nanoparticles with nanosecond laser pulses. Bubble formation was studied both with optical and acoustic means on supported single gold nanoparticles and single nanoparticles in suspension. Formation thresholds determined at different wavelengths indicate a bubble formation efficiency increasing with the irradiation wavelength. Vapor bubble generation in Bac-1 cells containing accumulations of the same particles was also investigated at different wavelengths. Similarly, they showed an increasing cell damage efficiency for longer wavelengths. Vapor bubbles generated by single laser pulses were about half the cell size when inducing acute damage.

Improved contrast deep optoacoustic imaging using displacement-compensated averaging: breast tumour phantom studies.

For real-time optoacoustic (OA) imaging of the human body, a linear array transducer and reflection mode optical irradiation is usually preferred. Such a setup, however, results in significant image background, which prevents imaging structures at the ultimate depth determined by the light distribution and the signal noise level. Therefore, we previously proposed a method for image background reduction, based on displacement-compensated averaging (DCA) of image series obtained when the tissue sample under investigation is gradually deformed. OA signals and background signals are differently affected by the deformation and can thus be distinguished. The proposed method is now experimentally applied to image artificial tumours embedded inside breast phantoms. OA images are acquired alternately with pulse-echo images using a combined OA/echo-ultrasound device. Tissue deformation is accessed via speckle tracking in pulse echo images, and used to compensate in the OA images for the local tissue displacement. In that way, OA sources are highly correlated between subsequent images, while background is decorrelated and can therefore be reduced by averaging. We show that image contrast in breast phantoms is strongly improved and detectability of embedded tumours significantly increased, using the DCA method.

Effect of irradiation distance on image contrast in epi-optoacoustic imaging of human volunteers

In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.

Mechanisms of nanoparticle-mediated photomechanical cell damage

Laser-assisted killing of gold nanoparticle targeted macrophages was investigated. Using pressure transient detection, flash photography and transmission electron microscopy (TEM) imaging, we studied the mechanism of single cell damage by vapor bubble formation around gold nanospheres induced by nanosecond laser pulses. The influence of the number of irradiating laser pulses and of particle size and concentration on the threshold for acute cell damage was determined. While the single pulse damage threshold is independent of the particle size, the threshold decreases with increasing particle size when using trains of pulses. The dependence of the cell damage threshold on the nanoparticle concentration during incubation reveals that particle accumulation and distribution inside the cell plays a key role in tissue imaging or cell damaging.

Computed Ultrasound Tomography in Echo Mode for Imaging Speed of Sound Using Pulse-Echo Sonography: Proof of Principle

The limitations of diagnostic echo ultrasound have motivated research into novel modalities that complement ultrasound in a multimodal device. One promising candidate is speed of sound imaging, which has been found to reveal structural changes in diseased tissue. Transmission ultrasound tomography shows speed of sound spatially resolved, but is limited to the acoustically transparent breast. We present a novel method by which speed-of-sound imaging is possible using classic pulse-echo equipment, facilitating new clinical applications and the combination with state-of-the art diagnostic ultrasound. Pulse-echo images are reconstructed while scanning the tissue under various angles using transmit beam steering. Differences in average sound speed along different transmit directions are reflected in the local echo phase, which allows a 2-D reconstruction of the sound speed. In the present proof-of-principle study, we describe a contrast resolution of 0.6% of average sound speed and a spatial resolution of 1 mm (laterally) × 3 mm (axially), suitable for diagnostic applications.

Vessel orientation-dependent sensitivity of optoacoustic imaging using a linear array transducer

Abstract. For clinical optoacoustic imaging, linear probes are preferably used because they allow versatile imaging of the human body with real-time display and free-hand probe guidance. The two-dimensional (2-D) optoacoustic image obtained with this type of probe is generally interpreted as a 2-D cross-section of the tissue just as is common in echo ultrasound. We demonstrate in three-dimensional simulations, phantom experiments, and in vivo mouse experiments that for vascular imaging this interpretation is often inaccurate. The cylindrical blood vessels emit anisotropic acoustic transients, which can be sensitively detected only if the direction of acoustic radiation coincides with the probe aperture. Our results reveal for this reason that the signal amplitude of different blood vessels may differ even if the vessels have the same diameter and initial pressure distribution but different orientation relative to the imaging plane. This has important implications for the image interpretation, for the probe guidance technique, and especially in cases when a quantitative reconstruction of the optical tissue properties is required.

Determining the optical properties of a gelatin-TiO2 phantom at 780 nm

Tissue phantoms play a central role in validating biomedical imaging techniques. Here we employ a series of methods that aim to fully determine the optical properties, i.e., the refractive index n, absorption coefficient μa, transport mean free path ℓ * , and scattering coefficient μs of a TiO2 in gelatin phantom intended for use in optoacoustic imaging. For the determination of the key parameters μa and ℓ * , we employ a variant of time of flight measurements, where fiber optodes are immersed into the phantom to minimize the influence of boundaries. The robustness of the method was verified with Monte Carlo simulations, where the experimentally obtained values served as input parameters for the simulations. The excellent agreement between simulations and experiments confirmed the reliability of the results. The parameters determined at 780 nm are n = 1.359 ( ± 0.002 ) , μ ′ s = 1 / ℓ * = 0.22 ( ± 0.02 )   mm -1 , μ a = 0.0053(+0.0006-0.0003)  mm -1 , and μ s = 2.86 ( ± 0.04)  mm -1 . The asymmetry parameter g obtained from the parameters ℓ * and μ ′ s is 0.93, which indicates that the scattering entities are not bare TiO2 particles but large sparse clusters. The interaction between the scattering particles and the gelatin matrix should be taken into account when developing such phantoms.

Real-time clinical clutter reduction in combined epi-optoacoustic and ultrasound imaging

Abstract Flexible imaging of the human body, a requirement for broad clinical application, is obtained by direct integration of optoacoustic (OA) imaging with echo ultrasound (US) in a multimodal epi-illumination system. Up to date, successful deep epi-OA imaging is difficult to achieve owing to clutter. Clutter signals arise from optical absorption in the region of tissue irradiation and strongly reduce contrast and imaging depth. Recently, we developed a displacement-compensated averaging (DCA) technique for clutter reduction based on the clutter decorrelation that occurs when palpating the tissue. To gain first clinical experience on the practical value of DCA, we implemented this technique in a combined clinical OA and US imaging system. Our experience with freehand scanning of human volunteers reveals that real-time feedback on the clutter-reduction outcome is a key factor for achieving superior contrast and imaging depth.

Study of clutter origin in in-vivo epi-optoacoustic imaging of human forearms

Epi-optoacoustic (OA) imaging offers flexible clinical diagnostics of the human body when the irradiation optic is attached to or directly integrated into the acoustic probe. Epi-OA images, however, encounter clutter that deteriorates contrast and significantly limits imaging depth. This study elaborates clutter origin in clinical epi-optoacoustic imaging using a linear array probe for scanning the human forearm. We demonstrate that the clutter strength strongly varies with the imaging location but stays stable over time, indicating that clutter is caused by anatomical structures. OA transients which are generated by strong optical absorbers located at the irradiation spot were identified to be the main source of clutter. These transients obscure deep in-plane OA signals when detected by the transducer either directly or after being acoustically scattered in the imaging plane. In addition, OA transients generated in the skin below the probe result in acoustic reverberations, which cause problems in image interpretation and limit imaging depth. Understanding clutter origin allows a better interpretation of clinical OA imaging, helps to design clutter compensation techniques and raises the prospect of contrast optimization via the design of the irradiation geometry.

All-optical highly sensitive akinetic sensor for ultrasound detection and photoacoustic imaging

A novel all-optical akinetic ultrasound sensor, consisting of a rigid, fiber-coupled Fabry-Pérot etalon with a transparent central opening is presented. The sensing principle relies exclusively on the detection of pressure-induced changes of the refractive index in the fluid filling the Fabry-Pérot cavity. This enables resonance-free, inherently linear signal detection over a broad bandwidth. We demonstrate that the sensor achieves a exceptionally low peak noise equivalent pressure (NEP) values of 2 Pa over a 20 MHz measurement bandwidth (without signal averaging), while maintaining a flat frequency response, and a detection bandwidth up to 22.5 MHz (-6 dB). The measured large full field of view of the sensor is 2.7 mm × 1.3 mm and the dynamic range is [Formula: see text] or 63 dB at 20 MHz bandwidth. For different required amplitude ranges the upper amplitude detection limit can be customized from at least 2 kPa to 2 MPa by using cavity mirrors with a lower optical reflectivity. Imaging tests on a resolution target and on biological tissue show the excellent suitability of the akinetic sensor for optical resolution photoacoustic microscopy (OR-PAM) applications.