Desmond Hirson

A new 15-50 MHz array-based micro-ultrasound scanner for preclinical imaging.

Most institutions now have a suite of imaging tools to follow mouse models of human disease. Micro-ultrasound is one of these tools and is second after whole-mouse fluorescence or bioluminescent imaging, in terms of installed systems. We report in this paper the first commercially available array transducer-based ultrasound imaging system that enables micro-ultrasound imaging at center frequencies between 15 and 50 MHz. At the heart of the new scanner is a laser-machined high-frequency 256 element, linear transducer array capable of forming dynamic diffraction limited beams. The power of the linear array approach is embodied in the uniform high resolution maintained over the full field of view. This leads to greatly expanded scope for real-time functional imaging that is demonstrated in this paper. The unprecedented images made with the new imaging system will enable many new applications not previously possible. These include real-time visualization of flow in the mouse placenta, visualization of flow development in the embryo, studies of embryonic to adult cardiac development/disease, and studies of real-time blood flow in mouse models of tumour angiogenesis.

Development of a combined photoacoustic micro-ultrasound system for estimating blood oxygenation

Photoacoustic (PA) imaging can estimate the spatial distribution of oxygen saturation (sO2) in blood, and be co-registered with B-Mode images of the surrounding anatomy. This study will focus on the development of a PA imaging mode on a commercially available array based micro-ultrasound (μUS) system that is capable of creating such images. The system will then be validated in vivo against a complementary technique for measuring partial pressure of oxygen in blood (pO2). The pO2 estimates are converted to sO2 values based on a standard dissociation curve found in the literature. Beamforming techniques and signal processing will also be described, along with in vivo PA images of subcutaneous murine tumours.

Hybrid dual frequency transducer and Scanhead for micro-ultrasound imaging

We report on the design, assembly and evaluation of a dual frequency mechanically scanned transducer for ultrasound bubble manipulation and real time high frequency imaging applications. A low frequency 2 MHz annulus was designed to fit on the outside of a commercially available 30 MHz, 100% bandwidth single element fixed focus transducer such that the axial axes of each transducer would be substantially aligned. The acoustic pressure and beam characteristics of the low frequency transducer were characterized as a function of transmit center frequency and drive voltage. The focal depths of the low and high frequencies were measured to be 11.8–12.1mm and 12.7mm for transmit pulses of 2–3MHz and 30 MHz respectively. The probe was integrated into a commercially available Visualsonics RMV Scanhead and could achieve a frame rate of 20 fps. The dual frequency probe provided an average of ≫ 12dB enhancement of contrast to tissue ratios in rat kidney and rat xenograft Fibrosarcoma models.

Photoacoustic imaging with rotational compounding for improved signal detection

Photoacoustic microscopy with linear array transducers enables fast two-dimensional, cross-sectional photoacoustic imaging. Unfortunately, most ultrasound transducers are only sensitive to a very narrow angular acceptance range and preferentially detect signals along the main axis of the transducer. This often limits photoacoustic microscopy from detecting blood vessels which can extend in any direction. Rotational compounded photoacoustic imaging is introduced to overcome the angular-dependency of detecting acoustic signals with linear array transducers. An integrate system is designed to control the image acquisition using a linear array transducer, a motorized rotational stage, and a motorized lateral stage. Images acquired at multiple angular positions are combined to form a rotational compounded image. We found that the signal-to-noise ratio improved, while the sidelobe and reverberation artifacts were substantially reduced. Furthermore, the rotational compounded images of excised kidneys and hindlimb tumors of mice showed more structural information compared with any single image collected.

Modification of a commercially available photoacoustic imaging system for the use of 1064nm and 532nm wavelengthsto assess photoacoustic contrast agents

The use of near-infrared wavelengths for photoacoustic (PA) imaging takes advantage of the relatively low inherent absorption of tissues and has encouraged the development of agents which show high contrast in this range. Here, we describe the modification of a commercially available PA imaging system (Vevo LAZR, VisualSonics, Toronto) to take advantage of the 532nm and 1064nm wavelengths inherent in the generation of the currently tuneable range of 680 to 970nm and in the use of these two wavelengths to assess contrast agents. The photoacoustic imaging system generated light from a Nd/YAG laser modified to extract the 532 and 1064nm wavelengths in addition to its OPO-derived tuneable range (680 - 970 nm) and deliver this light through a fiber integrated into a linear array transducer (LZ400, VisualSonics). Gold nanorods (UT Austin), carbon nanotubes (Stanford U), DyLight 550 (Thermo Fisher) and blood were imaged in a phantom (PE20 tubing) and in a hindlimb subcutaneous tumor in vivo to determine their photoacoustic signal intensity at all wavelengths. In the phantom and in vivo, all agents caused an enhancement of the photoacoustic signal at their respective peak absorbance wavelengths. These results show that the 532nm and 1064nm wavelengths could prove useful in biomedical imaging due to the contrast agents customized for them. The 1064nm wavelength in particular has the advantage of having very low generation of endogenous signal in vivo, making agents tuned to this wavelength ideal for targeted contrast imaging.

Development and validation of a combined photoacoustic micro-ultrasound system for in vivo oxygen saturation estimation

Photoacoustic (PA) Imaging can estimate the spatial distribution of oxygen saturation (sO2) and total hemoglobin concentration (HbT) in blood, and be co-registered with B-Mode ultrasound images of the surrounding anatomy. This study will focus on the development of a PA imaging mode on a commercially available array based micro-ultrasound (μUS) system that is capable of creating such images. The system will then be validated in vivo against a complementary technique for measuring partial pressure of oxygen in blood (pO2). The pO2 estimates are converted to sO2 values based on a standard dissociation curve found in the literature. Finally, the system will be used for assessing oxygenation in a murine model of ischemia, both during injury and recovery.