Tyler Harrison

Combined photoacoustic and ultrasound biomicroscopy

We report on the development of an imaging system capable of combined ultrasound and photoacoustic imaging based on a fast-scanning single-element 25-MHz ultrasound transducer and a unique light-delivery system. The system is capable of 20 ultrasound frames per second and slower photoacoustic frame rates limited by laser pulse-repetition rates. Laser and ultrasound pulses are interlaced for co-registration of photoacoustic and ultrasound images. In vivo imaging of a human finger permits ultrasonic visualization of vessel structures and speckle changes indicative of blood flow, while overlaid photoacoustic images highlight some small vessels that are not clear from the ultrasound scan. Photoacoustic images provide optical absorption contrast co-registered in the structural and blood-flow context of ultrasound with high-spatial resolution and may prove important for clinical diagnostics and basic science of the microvasculature.

Coregistered photoacoustic-ultrasound imaging applied to brachytherapy

Brachytherapy is a form of radiation therapy commonly used in the treatment of prostate cancer wherein sustained radiation doses can be precisely targeted to the tumor area by the implantation of small radioactive seeds around the treatment area. Ultrasound is a popular imaging mode for seed implantation, but the seeds are difficult to distinguish from the tissue structure. In this work, we demonstrate the feasibility of photoacoustic imaging for identifying brachytherapy seeds in a tissue phantom, comparing the received intensity to endogenous contrast. We have found that photoacoustic imaging at 1064 nm can identify brachytherapy seeds uniquely at laser penetration depths of 5 cm in biological tissue at the ANSI limit for human exposure with a contrast-to-noise ratio of 26.5 dB. Our realtime combined photoacoustic-ultrasound imaging approach may be suitable for brachytherapy seed placement and post-placement verification, potentially allowing for realtime dosimetry assessment during implantation.

Blood oxygen flux estimation with a combined photoacoustic and high-frequency ultrasound microscopy system: a phantom study

The metabolic rate of oxygen consumption, an important indicator of tissue metabolism, can be expressed as the change of net blood oxygen flux into and out of a tissue region per 100 g of tissue. In this work, we propose a photoacoustic and Doppler ultrasound method for imaging local blood oxygen flux of a single vessel. An imaging system for combined photoacoustic and high-frequency ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and Doppler ultrasound images are co-registered. Since the mean flow speed can be measured by color Doppler ultrasound, the vessel cross-sectional area can be measured by power Doppler or structural photoacoustic imaging, and multi-wavelength photoacoustic methods can be used to estimate oxygen saturation (sO(2)) and total concentration of haemoglobin (C(Hb)), all of the parameters necessary for oxygen flux estimation can be provided. The accuracy of the flow speed and sO(2) estimation has been investigated. In vitro sheep blood phantom experiments have been performed at different sO(2) levels and mean flow speeds. Blood oxygen flux has been estimated, and the uncertainty of the measurement has been quantified.

Double-SOI Wafer-Bonded CMUTs With Improved Electrical Safety and Minimal Roughness of Dielectric and Electrode Surfaces

Despite myriad potential advantages over piezoelectric ultrasound transducers, capacitive micromachined ultrasound transducers (CMUTs) have not yet seen widespread commercial implementation. The possible reasons for this may include key issues of the following: (1) long-term device reliability and (2) electrical safety issues associated with relatively high voltage electrodes on device surfaces which could present an electrical safety hazard to patients. A CMUT design presented here may mitigate some of these problems. Dielectric charging is one phenomenon which can lead to unpredictable performance and device failure. Using a previously published 1-D model of dielectric charging, we link minimal dielectric surface roughness with minimal dielectric charging. Previous studies of Fowler-Nordheim tunneling suggest that minimal-surface-roughness electrodes could lead to minimal transdielectric currents (and, hence, slower dielectric charging rates). These principles guided our device architecture, leading us to engineer near atomically smooth electrodes and dielectric surfaces to minimize dielectric charging. To provide maximum electrical safety to future patients, CMUT devices were engineered with the top membrane serving as a ground electrode. While multiple CMUT elements have not been individually addressable in most such designs to our knowledge, we introduce a fabrication method involving two silicon-on-insulator wafers with a step to define individually addressable electrodes. Our devices are modeled using a finite-element package. Measured deflections show excellent agreement with modeled performance. We test for charge effects by studying deflection hysteresis during snapdown and snapback cycles in the limit of long snapdown durations to simulate maximal-dielectric-charging conditions. Devices were also tested in long-term actuation tests and subjected to more than 3 × 1010 cycles without failure.

The applicability of ultrasound dynamic receive beamformers to photoacoustic imaging

Ultrasound array transducers offer several advantages over mechanically-scanned transducers for photoacoustic imaging, including high imaging frame rates and dynamic focusing. Development of a photoacoustic array system can be accelerated by adapting existing commercial ultrasound systems and harnessing their performance-enhancing aspects such as parallel beamforming. One challenge faced when adapting commercial ultrasound systems for photoacoustic imaging is that the dynamic delay sequences required for focusing must account for one-way rather than two-way ultrasound wave propagation. Modifying the hardware may be difficult for developers and impossible for users, but some ultrasound systems provide a parameter, c: the speed of sound used to calculate these delays. A linear-array based ultrasound platform with parallel channel acquisition is used to compare experimental point-spread functions produced using an ultrasound beamformer with a scaled value of c to those produced by a photoacoustic beamformer. Scaling c by a factor of √2 provides the best image quality compared with adjustments by 1 and 2, but requires image rescaling, which can be done postacquisition or by modification of the rendering software. Although optimal focusing is achieved for linear scanning, this is not the case for sector scanning, which requires angular and depth rescaling.

Iterative algorithm for multiple illumination photoacoustic tomography (MIPAT) using ultrasound channel data

Photoacoustic tomography is a promising imaging modality offering high ultrasonic resolution with intrinsic optical contrast. However, quantification in photoacoustic imaging is challenging. We present an algorithm for quantitative photoacoustic estimation of optical absorption and diffusion coefficients based on minimizing an error function between measured photoacoustic channel data and a calculated forward model with a multiple-illumination pattern. Unlike many other algorithms, the proposed method does not require the erroneous assumption of ideal tomographic reconstruction of initial pressures and to our knowledge is the first demonstration of the efficacy of multiple-illumination photoacoustic tomography requiring only transducer channel data. Simulations show promise for numerically robust optical property estimation as illustrated by well-conditioned Hessian singular values in 2D examples.

A least-squares fixed-point iterative algorithm for multiple illumination photoacoustic tomography

The optical absorption of tissues provides important information for clinical and pre-clinical studies. The challenge in recovering optical absorption from photoacoustic images is that the measured pressure depends on absorption and local fluence. One reconstruction approach uses a fixed-point iterative technique based on minimizing the mean-squared error combined with modeling of the light source to determine optical absorption. With this technique, convergence is not guaranteed even with an accurate measure of optical scattering. In this work we demonstrate using simulations that a new multiple illumination least squares fixed-point iteration algorithm improves convergence - even with poor estimates of optical scattering.

S-sequence encoded synthetic aperture B-scan ultrasound imaging

Traditional synthetic aperture ultrasound scanning involves firing on one element and receiving on all elements of an array, then firing another transmit element and receiving on all elements until all transmit-receive element pairs have been sampled. It offers excellent resolution but at the expense of signal-to-noise. To remedy this difficulty we propose an aperture encoding scheme that involves firing on multiple elements sampled from a Hadamard S-matrix, then applying matrix inversion methods to decouple signals to recover the effective synthetic aperture imaging set for subsequent image reconstruction. Because more than one elements are fired at a time, signal-to-noise is improved.

Photoacoustic and high-frequency power Doppler ultrasound biomicroscopy: a comparative study

Both photoacoustic imaging and power Doppler ultrasound are capable of producing images of the vasculature of living subjects, however, the contrast mechanisms of the two modalities are very different. We present a quantitative and objective comparison of the two methods using phantom data, highlighting relative merits and shortcomings. An imaging system for combined photoacoustic and high-frequency power Doppler ultrasound microscopy is presented. This system uses a swept-scan 25-MHz ultrasound transducer with confocal dark-field laser illumination optics. A pulse-sequencer enables ultrasonic and laser pulses to be interlaced so that photoacoustic and power Doppler ultrasound images can be coregistered. Experiments are performed on flow phantoms with various combinations of vessel size, flow velocity, and optical wavelength. For the task of blood volume detection, power Doppler is seen to be advantageous for large vessels and high flow speeds. For small vessels with low flow speeds, photoacoustic imaging is seen to be more effective than power Doppler at the detection of blood as quantified by receiver operating characteristic analysis. A combination of the two modes could provide improved estimates of fractional blood volume in comparison with either mode used alone.

Optical resolution photoacoustic microendoscopy with ultrasound-guided insertion and array system detection

Abstract. Using a 0.8-mm-diameter image guide fiber bundle consisting of 30,000 single-mode fibers and an external linear array transducer, we demonstrate a dual-mode photoacoustic system capable of ultrasound-guided microendoscope insertion and photoacoustic imaging. The array optical resolution photoacoustic microendoscopy (AOR-PAME) system is designed to visualize the placement of the distal end of an endoscopy probe several centimeters into tissue, transmit scanning focused laser pulses into tissues via the fiber bundle, and acquire the generated photoacoustic signals. A ytterbium-doped fiber laser is tightly focused and is scanned across the proximal tip of the image guide fiber bundle using a two-dimensional galvanometer scanning mirror system. The end of the fiber bundle is used in contact mode with the object. The capabilities of AOR-PAME are demonstrated by imaging carbon fiber networks embedded in tissue-mimicking phantoms and the ears of a 60-g rat. The lateral resolution and signal-to-noise ratio are measured as 9 μm and 40 dB, respectively.