Photoacoustic tomography (PAT) is probably the fastest-growing area of biomedical imaging technology, owing to its capacity for high-resolution sensing of rich optical contrast in vivo at depths beyond the optical transport mean free path (~1 mm in human skin). Existing high-resolution optical imaging technologies, such as confocal microscopy and two-photon microscopy, have had a fundamental impact on biomedicine but cannot reach the penetration depths of PAT. By utilizing low ultrasonic scattering, PAT indirectly improves tissue transparency up to 1000-fold and consequently enables deeply penetrating functional and molecular imaging at high spatial resolution. Furthermore, PAT promises in vivo imaging at multiple length-scales; it can image subcellular organelles to organs with the same contrast origin — an important application in multiscale systems biology research.

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Multiscale photoacoustic microscopy and computed tomography.

The visualisation of living tissues at microscopic resolution is attracting attention in several fields. In medicine, the goals are to image healthy and diseased tissue with the aim of providing information previously only available from biopsy samples. In basic biology, the goal may be to image biological models of human disease or to conduct longitudinal studies of small-animal development. High-frequency ultrasonic imaging (ultrasound biomicroscopy) offers unique advantages for these applications. In this paper, the development of ultrasound biomicroscopy is reviewed. Aspects of transducer development, systems design and tissue properties are pre- sented to provide a foundation for medical and biological applications. The majority of applications appear to be developing in the 40 - 60-MHz frequency range, where resolution on the order of 50 mm can be achieved. Doppler processing in this frequency range is beginning to emerge and some examples of current achievements will be highlighted. The current state of the art is reviewed for medical applications in ophthalmology, intravascular ultrasound, dermatology, and cartilage imaging. Ultrasound biomicroscopic studies of mouse embryonic devel- opment and tumour biology are presented. Speculation on the continuing evolution of ultrasound biomicroscopy will be discussed. © 2000 World Federation for Ultrasound in Medicine & Biology.

Advances in ultrasound biomicroscopy

A multiwavelength backward-mode planar photoacoustic scanner for 3D imaging of soft tissues to depths of several millimeters with a spatial resolution in the tens to hundreds of micrometers range is described. The system comprises a tunable optical parametric oscillator laser system that provides nanosecond laser pulses between 600 and 1200 nm for generating the photoacoustic signals and an optical ultrasound mapping system based upon a Fabry-Perot polymer film sensor for detecting them. The system enables photoacoustic signals to be mapped in 2D over a 50 mm diameter aperture in steps of 10 microm with an optically defined element size of 64 microm. Two sensors were used, one with a 22 microm thick polymer film spacer and the other with a 38 mum thick spacer providing -3 dB acoustic bandwidths of 39 and 22 MHz, respectively. The measured noise equivalent pressure of the 38 microm sensor was 0.21 kPa over a 20 MHz measurement bandwidth. The instrument line-spread function (LSF) was measured as a function of position and the minimum lateral and vertical LSFs found to be 38 and 15 microm, respectively. To demonstrate the ability of the system to provide high-resolution 3D images, a range of absorbing objects were imaged. Among these was a blood vessel phantom that comprised a network of blood filled tubes of diameters ranging from 62 to 300 microm immersed in an optically scattering liquid. In addition, to demonstrate the applicability of the system to spectroscopic imaging, a phantom comprising tubes filled with dyes of different spectral characteristics was imaged at a range of wavelengths. It is considered that this type of instrument may provide a practicable alternative to piezoelectric-based photoacoustic systems for high-resolution structural and functional imaging of the skin microvasculature and other superficial structures.

Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues

This research develops a robust experimental procedure to track the evolution of fatigue damage in a nickel-base superalloy with the acoustic nonlinearity parameter, β, and demonstrates its effectiveness by making repeatable measurements of β in multiple specimens, subjected to both high- and low-cycle fatigue. The measurement procedure developed in this research is robust in that it is based on conventional piezoelectric contact transducers, which are readily available off the shelf, and it offers the potential for field applications. In addition, the measurement procedure enables the user to isolate sample nonlinearity from measurement system nonlinearity. The experimental results show that there is a significant increase in β linked to the high plasticity of low-cycle fatigue, and illustrate how these nonlinear ultrasonic measurements quantitatively characterize the damage state of a specimen in the early stages of fatigue. The high-cycle fatigue results are less definitive (the increase in β is not as...

Experimental characterization of fatigue damage in a nickel-base superalloy using nonlinear ultrasonic waves

The laser optoacoustic imaging system described herein utilizes time-resolved measurement of profiles of laser-induced transient pressure (acoustic) waves. The pressure waves are emitted by acoustic sources preferentially generated in absorbing tissues of diagnostic interest. This technique allows visualization of absorbed light distribution in turbid, layered and heterogeneous tissues irradiated by laser pulses in vivo. The laser optoacoustic tomography can be used for the characterization of structure and properties of normal tissue, and for the detection of tissue pathological changes. The optical heterogeneities that can be imaged with the laser optoacoustic imaging system include abnormal tissues such as tumors, injured tissues, blood vessels and other layered tissues. Further, three dimensional images of organs and portions of organs can be obtained.

Optoacoustic imaging for medical diagnosis

Two-dimensional phased arrays for high frequency (>30 MHz) ultrasonic imaging are difficult to construct using conventional piezoelectric technology. A promising alternative involves optical detection of ultrasound, where the array element size is defined by the focal spot of a laser beam. Element size and spacing on the order of a few microns are easily achieved, suitable for imaging at frequencies exceeding 100 MHz. We have previously shown images made from a receive-only, two-dimensional optoacoustic array operating at 10 to 50 MHz. The main drawback of optical detection has been poor sensitivity when compared with piezoelectric detection. In this paper, we explore a different form of optical detection demonstrating improved sensitivity and offering a potentially simple method for constructing two-dimensional arrays. Results from a simple experiment using an etalon sensor confirm that the sensitivity of etalon detection is comparable with piezoelectric detection. This paper concludes with a proposal for a high frequency optoacoustic array system using an etalon.

High frequency optoacoustic arrays using etalon detection

Dynamically focused and steered high frequency ultrasound imaging systems require arrays with fine element spacing, wide bandwidths, and large apertures. However, these characteristics are difficult to achieve at frequencies greater than 30 MHz using conventional array construction methods. Optical schemes offer a solution. Focused laser beams incident on a suitable surface can generate and detect acoustic radiation. Precisely controlling the position and size of the beams defines points of transmission and detection, making it possible for pulse-echo image formation by synthetic aperture methods. An optical detection array was built, relying on a conventional piezoelectric transducer as an ultrasound source. The detection system, with near optimal resolution over a wide depth of field, demonstrates the potential for high frequency array implementation using optical techniques. A possible application is in pathology, where 2-D or 3-D fine resolution pulse-echo imaging can be performed in situ without the need for biopsies.

High frequency ultrasound imaging with optical arrays

A method and system for 3-D acoustic microscopy using short pulse laser excitation comprising a sample or object under investigation (12) is optometric acoustically coupled to a transducer (14) which includes optically absorbing and reflecting materials. Optical detection is utilized by way of a focused excitation beam (19) scanned by an acoustically optometric scanning device (23) across an absorbing layer of an optometric acoustic transducer (14) coupled to an object under investigation to create spherical ultrasonic waves within the object which may be living tissue. The reflected spherical ultrasonic waves are detected through the use of an unfocused probe beam and an optical detector array or a focused probe beam (21) and a single photo-detector (20) which receive the probe beam from a reflecting surface of the optometric acoustic transducer.

Method and system for 3-d acoustic microscopy using short pulse excitation and 3-d acoustic microscope for use therein

Contrast agents, such as bubbles, are used in ultrasound to enhance backscatter from blood. To increase contrast between these agents and tissue, nonlinear methods such as harmonic imaging can be used. Contrast is limited, however, by tissue second harmonic signals. We show that a major source of this signal is nonlinear propagation through tissue. In addition, we present methods to suppress this second harmonic generation. One simple approach is to decrease the f/number of the imaging system. Simulations show that doubling the size of the array, while keeping total power output constant, decreases propagating second harmonic generation. A second approach uses active noise cancellation to suppress second harmonic generation. A specific method, the harmonic cancellation system (HCS), is developed and presented as an example. In simulations, HCS decreased second harmonic generation by over 30 dB. Using such methods, contrast can be improved between tissue and bubbles in harmonic imaging.

Suppression of propagating second harmonic in ultrasound contrast imaging

Optical detection of ultrasound has numerous advantages over traditional piezoelectric methods. These systems offer noncontact inspection, rapid scanning capabilities, fine spatial sampling, and large bandwidths. In addition, difficulties associated with conventional ultrasound imaging systems such as cross-talk between elements, electrical connections, and electromechanical resonances are greatly reduced or even eliminated. Because of this, high frequency phased arrays for ultrasound detection can be emulated by accurately positioning and focusing optical beams on a suitable surface, which defines array elements. However, optical systems have lower sensitivity than their piezoelectric counterparts, limiting their widespread use in ultrasound imaging. Active optical detection offers a solution. An active ultrasound detector consisting of a neodymium-doped glass waveguide laser with an optical demodulation system, was built demonstrating enhanced sensitivity while preserving the benefits of traditional passive optical detection.

James D. Hamilton

Papers

High frequency optoacoustic arrays using etalon detection

High frequency ultrasound imaging with optical arrays

Method and system for 3-d acoustic microscopy using short pulse excitation and 3-d acoustic microscope for use therein

Suppression of propagating second harmonic in ultrasound contrast imaging

High frequency ultrasound imaging using an active optical detector