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The feasibility of air-coupled ultrasound transducers to detect laser-induced ultrasound from artificial blood vessels embedded in an optically scattering phantom is demonstrated. These air-coupled transducers allow new applications in biomedical photoacoustic imaging where contact with tissue is not preferred. One promising application of such transducers is the addition of photoacoustic imaging to the regular x-ray mammographic screening procedure.

Photoacoustic imaging is a hybrid imaging modality based on the detection of acoustic waves generated by the absorption of short laser pulses in biological tissue. It combines the advantages of excellent contrast achieved in optical techniques with the high resolution of ultrasound imaging. In this article we present a review of the work done at the University of Twente to image tumor angiogenesis in vivo using this technique. We start with a description and the technical details of the different photoacoustic systems developed in our laboratory, with their validation on phantoms. We then discuss small-animal studies with results of serial imaging of angiogenesis over a 10-day period at the site of tumor induction in a rat. Further, we present clinical results using a photoacoustic mammoscope of breast cancer imaging based on angiogenesis-driven optical absorption contrast.

A real-time photoacoustic imaging system is designed and built. This system is based on a commercially available ultrasound imaging system. It can achieve a frame rate of 8 frames/sec. Vasculature in the hand of a human volunteer is imaged, and the resulting photoacoustic image is combined with the ultrasound image. The real-time photo acoustic imaging system with a hybrid ultrasound probe is demonstrated by imaging the branching of subcutaneous blood vessels in the hand.

Background and Objective: To optimize laser therapy of port-wine stains (PWSs), information about the vasculature as well as lesion depth is valuable. In this study we investigated the use of photoacoustic imaging (PAI) to obtain this information., Study Design/materials and Methods: PAI uses pulsed light to generate ultrasound upon absorption of short light pulses by blood. In this study we used PAI to image vasculature in PWSs in three human volunteers. Two-dimensional imaging (scan direction vs. depth) was carried out by scanning a double-ring photoacoustic sensor over the tissue surface., Results: In the photoacoustic images we observed an increased photoacoustic signal intensity at the locations of the PWS that is associated with increased vascularization. From the obtained images we measured the thickness of the vascular layer and estimated lesion depth. In some cases single vessels could be observed at the position of the PWS whereas in other cases the PWS appeared as a region with large photoacoustic signal intensity., Conclusions: PAI has the potential to reveal information about the lesion depth as well as thickness of the vascular layer., ((c) 2008 Wiley-Liss, Inc.)

We present a method to determine the speed of sound in tissue using a double-ring photoacoustic sensor working in reflection mode. This method uses the cross-correlation between the laser-induced ultrasound waves detected by two concentric ring shaped sensors, while a priori information about the depth-position of the photoacoustic source is not required. We demonstrate the concept by estimating the speed of sound in water as a function of temperature. Comparison of the estimated speed with values reported in literature shows an average systematic error of 0.1% and a standard deviation of 0.1%. Furthermore, we demonstrate that the method can be applied to layered media. The method has application in the correction of photoacoustic and ultrasound images afflicted by local speed variations in tissue. Additionally, the concept shows promise in monitoring temperature changes which are reflected in speed of sound changes in tissue.

Photoacoustic imaging is a hybrid imaging modality that is based on the detection of acoustic waves generated by absorption of pulsed light by tissue chromophores such as hemoglobin in blood. For this technique, usually large and costly Q-switched Nd:YAG lasers are used. These lasers provide a pulse energy of at least several milliJoules. In search of alternative light sources, we investigated the use of a small and compact pulsed laser diode to image blood vessels. We proved that a pulsed laser diode can be applied for imaging blood vessels in vivo.

Background and Objectives: In intravenous access to veins there is a risk of puncturing venous valves or blocking of the catheter by the valves. Therefore, we have investigated whether and how photoacoustic imaging (PAI), which visualizes the lumen of blood vessels, can be used to detect these valves., Study Design/materials and Methods: Venous valves in superficial veins on the dorsal side of the hand of human volunteers were located by palpation and visual inspection. Next, this location was imaged using PAI., Results: In 16 of 21 human volunteers venous valves that were found by palpation could be observed by PAI as local discontinuities in the imaged vessel. From these images, four characteristic features by which venous valves can be recognized in photoacoustic images were identified., Conclusions: PAI has the potential to be applied in the detection of venous valves., ((c) 2006 Wiley-Liss, Inc.)

We present photoacoustic images of tumor neovascularization obtained over a 10-day period after subcutaneous inoculation of pancreatic tumor cells in a rat. The images were obtained from ultrasound generated by absorption in hemoglobin of short laser pulses at a wavelength of 1064 nm. The ultrasound signals were measured in reflection mode using a single scanning piezodetector, and images were reconstructed with a weighted delay-and-sum algorithm. Three-dimensional data visualize the development and quantify the extent of individual blood vessels around the growing tumor, blood concentration changes inside the tumor and growth in depth of the neovascularized region.

A photoacoustic double-ring sensor, featuring a narrow angular aperture, is developed for laser-induced photoacoustic imaging of blood vessels. An integrated optical fiber enables reflection-mode detection of ultrasonic waves. By using the cross-correlation between the signals detected by the two rings, the angular aperture of the sensor is reduced by a factor of 1.9, from 1.5 to 0.8 deg. Consequently, photoacoustic images could be obtained in a manner analogous to the ultrasound B-scan mode. Next, the cross section of artificial blood vessels is visualized by reconstruction of the absorbed energy distribution. Finally, in vivo imaging and the subsequent reconstruction of the absorbed energy distribution is demonstrated for superficial blood vessels in the human wrist., (Copyright 2004 Society of Photo-Optical Instrumentation Engineers.)

A double-ring sensor was applied in photoacoustic tomographic imaging of artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to-peak time (tau(pp)) of the laser (1064 nm) induced pressure transient was used to estimate the axial vessel diameter. Comparison with the actual vessel diameter showed that the diameter could be approximated by 2ctau(pp), with c the speed of sound in blood. Using this relation, the lateral diameter could also precisely be determined. In vivo imaging and monitoring of changes in vessel diameters was feasible. Finally, acoustic time traces were recorded while flushing a vessel in the rabbit ear with saline, which proved that the main contribution to the laser-induced pressure transient is caused by blood inside the vessel and that the vessel wall gives only a minor contribution.

Background and Objectives: The ability to correctly visualize the architectural arrangement of microvasculature is valuable to many diverse fields in medicine. In this study, we applied photoacoustics (PA) to obtain high-resolution images of submillimeter blood vessels., Study Design/materials and Methods: Short laser pulses are used to generate ultrasound from superficial blood vessels in several animal models. From these ultrasound waves the interior of blood vessels can be reconstructed., Results: We present results from a novel approach based on the PA principle that allows specific in vivo visualization of dermal blood vessels without the use of contrast agents or ionizing radiation., Conclusions: We show PA images of externalized blood vessels and demonstrate in vivo PA imaging of vasculature through layers of skin varying in thickness., ((c) 2004 Wiley-Liss, Inc.)

This paper describes the simultaneous use of two, noninvasive, near-infrared techniques near-infrared spectroscopy (NIRS) and a continuous wave NIR laser Doppler flow system (LDF) to measure changes in the blood oxygenation, blood concentration and blood flow velocity in the brain. A piglet was used as animal model. A controlled change in the arterial CO2 pressure (PaCO2) was applied for achieving changes in the listed cerebrovascular parameters. The time courses of blood concentration parameters (NIRS) and RMS blood flow velocity (LDF) were found to correspond closely with those of carotid blood flow and arterial carbon dioxide pressure (PaCO2). This result shows the additional value of LDF when combined with NIRS, preferably in one instrument. Development of pulsed LDF for regional blood flow measurement is indicated.

Materials for solid photoacoustic breast phantoms, based on poly(vinyl alcohol) hydrogels, are presented. Phantoms intended for use in photoacoustics must possess both optical and acoustic properties of tissue. To realize the optical properties of tissue, one approach was to optimize the number of freezing and thawing cycles of aqueous poly(vinyl alcohol) solutions, a procedure which increases the turbidity of the gel while rigidifying it. The second approach concentrated on forming a clear matrix of the rigid poly(vinyl alcohol) gel without any scattering, so that appropriate amounts of optical scatterers could be added at the time of formation, to tune the optical properties as per requirement. The relevant optical and acoustic properties of such samples were measured to be close to the average properties of human breast tissue. Tumour simulating gel samples of suitable absorption coefficient were created by adding appropriate quantities of dye at the time of formation; the samples were then cut into spheres. A breast phantom embedded with such 'tumours' was developed for studying the applicability of photoacoustics in mammography.