Research requiring the murine pancreatic duct to be imaged is often challenging due to the
difficulty in selectively cannulating the pancreatic duct. We have successfully catheterized the
pancreatic duct through the common bile duct in severe combined immune deficient (SCID)
mice and imaged the pancreatic duct with gas filled lipid microbubbles that increase ultrasound
imaging sensitivity due to exquisite scattering at the gas/liquid interface. A SCID mouse was
euthanized by CO<sub>2</sub>, a midline abdominal incision made, the common bile duct cut at its
midpoint, a 2 cm, 32 gauge tip catheter was inserted about 1 mm into the duct and tied with
suture. The duodenum and pancreas were excised, removed in toto, embedded in agar and an
infusion pump was used to instill normal saline or lipid-coated microbubbles (10 million / ml)
into the duct. B-mode images before and after infusion of the duct with microbubbles imaged the
entire pancreatic duct (~ 1 cm) with high contrast. The microbubbles were cavitated by high
mechanical index (HMI) ultrasound for imaging to be repeated. Our technique of catheterization
and using lipid microbubbles as a contrast agent may provide an effective, affordable technique
of imaging the murine pancreatic duct; cavitation with HMI ultrasound would enable repeated
imaging to be performed and clustering of targeted microbubbles to receptors on ductal cells
would allow pathology to be localized accurately. This research was supported by the
Experimental Mouse Shared Service of the AZ Cancer Center (Grant Number P30CA023074,
NIH/NCI and the GI SPORE (NIH/NCI P50 CA95060).
Most single element hydrophones depend on a piezoelectric material that converts pressure changes to electricity.
These devices, however, can be expensive, susceptible to damage at high pressure, and/or have limited bandwidth and
sensitivity. The acousto-electric (AE) hydrophone is based on the AE effect, an interaction between electrical current and
acoustic pressure generated when acoustic waves travel through a conducting material. As we have demonstrated
previously, an AE hydrophone requires only a conductive material and can be constructed out of common laboratory
supplies to generate images of an ultrasound beam pattern consistent with more expensive hydrophones. The sensitivity
is controlled by the injected bias current, hydrophone shape, thickness and width.
In this report we describe simulations aimed at optimizing the design of the AE hydrophone with experimental
validation using new devices composed of a resistive element of indium tin oxide (ITO). Several shapes (e.g., bowtie and
dumbbell) and resistivities were considered. The AE hydrophone with a dumbbell configuration achieved the best beam
pattern of a 2.25MHz ultrasound transducer with lateral and axial resolutions consistent with images generated from a
commercial hydrophone (Onda Inc.). The sensitivity of this device was ~2 nV/Pa. Our simulations and experimental
results both indicate that designs using a combination of ITO and gold (ratio of resistivities = ~18) produce the best
results. We hope that design optimization will lead to new devices for monitoring ultrasonic fields for biomedical
imaging and therapy, including lithotripsy and focused ultrasound surgery.
Clinical ultrasound (US) imaging and therapy require a precise knowledge of the intensity distribution of the
acoustic field. Although piezoelectric hydrophones are most common, these devices are limited in terms of, for example,
type of materials, cost, and performance at high frequency and pressure. As an alternative to conventional acoustic
detectors, we describe acoustoelectric hydrophones, developed using photolithographic fabrication techniques, where the
induced voltage (phase and amplitude) is proportional to both the US pressure and bias current injected through the
device. In this study a number of different hydrophone designs were created using indium tin oxide (ITO). A constriction
of the current path within the hydrophone created a localized "sensitivity zone" of high current density. The width of this
zone ranged from 30 to 1000 μm, with a thickness of 100 nm. A raster scan of the US transducer produced a map of the
acoustic field. Hydrophones were evaluated by mapping the pressure field of a 2.25 MHz single element transducer, and
their performance was compared to a commercial capsule hydrophone. Focal spot sizes at -6 dB were as low as 1.75 mm,
comparing well with the commercial hydrophone measurement of 1.80 mm. Maximum sensitivity was 2 nV/Pa and up to
the 2nd harmonic was detected. We expect improved performance with future devices as we optimize the design.
Acoustoelectric hydrophones are potentially cheaper and more robust than the piezoelectric models currently in clinical
use, potentially providing more choice of materials and designs for monitoring therapy or producing arrays for imaging.
Accurate three dimensional (3D) mapping of bioelectric sources in the body with high spatial resolution is important
for the diagnosis and treatment of a variety of cardiac and neurological disorders. Ultrasound current source density
imaging (UCSDI) is a new technique that maps electrical current flow in tissue. UCSDI is based on the acousto-electric
(AE) effect, an interaction between electrical current and acoustic pressure waves propagating through a conducting
material and has distinct advantages over conventional electrophysiology (i.e., without ultrasound). In this study, UCSDI
was used to simultaneously image current flow induced in two tissue phantoms positioned at different depths. Software
to simulate AE signal was developed in Matlab™ to complement the experimental model and further characterize the
relationship between the ultrasound beam and electrical properties of the tissue. Both experimental and simulated images
depended on the magnitude and direction of the current, as well as the geometry (shape and thickness) and location of
the current sources in the ultrasound field (2.25MHz transducer). The AE signal was proportional to pressure and current
with detection levels on the order of 1 mA/cm<sup>2</sup> at 258kPa. We have imaged simultaneously two separate current sources in tissue slabs using UCSDI and two bridge circuits to accurately monitor current flow through each source. These results are consistent with UCSDI simulations of multiple current sources. Real-time 3D UCSD images of current flow automatically co-registered with pulse echo ultrasound potentially facilitates corrective procedures for cardiac and neural abnormalities.
Photoacoustic (PA) imaging is a rapidly developing imaging modality that can detect optical contrast agents with high
sensitivity. While detectors in PA imaging have traditionally been single element ultrasound transducers, use of array
systems is desirable because they potentially provide high frame rates to capture dynamic events, such as injection and
distribution of contrast in clinical applications. We present preliminary data consisting of 40 second sequences of coregistered
pulse-echo (PE) and PA images acquired simultaneously in real time using a clinical ultrasonic machine.
Using a 7 MHz linear array, the scanner allowed simultaneous acquisition of inphase-quadrature (IQ) data on 64
elements at a rate limited by the illumination source (Q-switched laser at 20 Hz) with spatial resolution determined to be
0.6 mm (axial) and 0.4 mm (lateral). PA images had a signal-to-noise ratio of approximately 35 dB without averaging.
The sequences captured the injection and distribution of an infrared-absorbing contrast agent into a cadaver rat heart.
From these data, a perfusion time constant of 0.23 s<sup>-1</sup> was estimated. After further refinement, the system will be tested
in live animals. Ultimately, an integrated system in the clinic could facilitate inexpensive molecular screening for
coronary artery disease.
Semiconductor detector arrays made of CdTe/CdZnTe are expected to be the main components of future high-performance, clinical nuclear medicine imaging systems. Such systems will require small pixel-pitch and much larger numbers of pixels than are available in current semiconductor-detector cameras. We describe the motivation for developing a new readout integrated circuit, AEGIS, for use in hybrid semiconductor detector arrays, that may help spur the development of future cameras. A basic design for AEGIS is presented together with results of an HSPICE<sup>TM</sup> simulation of the performance of its unit cell. AEGIS will have a shaper-amplifier unit cell and neighbor pixel readout. Other features include the use of a single input power line with other biases generated on-board, a control register that allows digital control of all thresholds and chip configurations and an output approach that is compatible with list-mode data acquisition. An 8x8 prototype version of AEGIS is currently under development; the full AEGIS will be a 64x64 array with 300 μm pitch.