Ultrasonic Backscatter Microscope Research Articles

In vivovalidation of a bimodal technique combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy for diagnosis of oral carcinoma

Tissue diagnostic features generated by a bimodal technique integrating scanning time-resolved fluorescence spectroscopy (TRFS) and ultrasonic backscatter microscopy (UBM) are investigated in an in vivo hamster oral carcinoma model. Tissue fluorescence is excited by a pulsed nitrogen laser and spectrally and temporally resolved using a set of filters/dichroic mirrors and a fast digitizer, respectively. A 41-MHz focused transducer (37-μm axial, 65-μm lateral resolution) is used for UBM scanning. Representative lesions of the different stages of carcinogenesis show that fluorescence characteristics complement ultrasonic features, and both correlate with histological findings. These results demonstrate that TRFS-UBM provide a wealth of co-registered, complementary data concerning tissue composition and structure as it relates to disease status. The direct co-registration of the TRFS data (sensitive to surface molecular changes) with the UBM data (sensitive to cross-sectional structural changes and depth of tumor invasion) is expected to play an important role in pre-operative diagnosis and intra-operative determination of tumor margins.

Multimodal characterization of compositional, structural and functional features of human atherosclerotic plaques

Detection of atherosclerotic plaque vulnerability has critical clinical implications for avoiding sudden death in patients with high risk of plaque rupture. We report on multimodality imaging of ex-vivo human carotid plaque samples using a system that integrates fluorescence lifetime imaging (FLIM), ultrasonic backscatter microscopy (UBM), and photoacoustic imaging (PAI). Biochemical composition is differentiated with a high temporal resolution and sensitivity at the surface of the plaque by the FLIM subsystem. 3D microanatomy of the whole plaque is reconstructed by the UBM. Functional imaging associated with optical absorption contrast is evaluated from the PAI component. Simultaneous recordings of the optical, ultrasonic, and photoacoustic data present a wealth of complementary information concerning the plaque composition, structure, and function that are related to plaque vulnerability. This approach is expected to improve our ability to study atherosclerotic plaques. The multimodal system presented here can be translated into a catheter based intraluminal system for future clinical studies.

Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy.

We report a tissue diagnostic system which combines two complementary techniques of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and ultrasonic backscatter microscopy (UBM). TR-LIFS evaluates the biochemical composition of tissue, while UBM provides tissue microanatomy and enables localization of the region of diagnostic interest. The TR-LIFS component consists of an optical fiber-based time-domain apparatus including a spectrometer, gated multichannel plate photomultiplier, and fast digitizer. It records the fluorescence with high sensitivity (nM concentration range) and time resolution as low as 300 ps. The UBM system consists of a transducer, pulser, receiving circuit, and positioning stage. The transducer used here is 45 MHz, unfocused, with axial and lateral resolutions 38 and 200 microm. Validation of the hybrid system and ultrasonic and spectroscopic data coregistration were conducted both in vitro (tissue phantom) and ex vivo (atherosclerotic tissue specimens of human aorta). Standard histopathological analysis of tissue samples was used to validate the UBM-TRLIFS data. Current results have demonstrated that spatially correlated UBM and TR-LIFS data provide complementary characterization of both morphology (necrotic core and calcium deposits) and biochemistry (collagen, elastin, and lipid features) of the atherosclerotic plaques at the same location. Thus, a combination of fluorescence spectroscopy with ultrasound imaging would allow for better identification of features associated with tissue pathologies. Current design and performance of the hybrid system suggests potential applications in clinical diagnosis of atherosclerotic plaque.

PMN-PT single crystal, high-frequency ultrasonic needle transducers for pulsed-wave Doppler application

High-frequency needle ultrasound transducers with an aperture size of 0.4 mm were fabricated using lead magnesium niobate-lead titanate (PMN-33% PT) as the active piezoelectric material. The active element was bonded to a conductive silver particle matching layer and a conductive epoxy backing through direct contact curing. An outer matching layer of parylene was formed by vapor deposition. The active element was housed within a polyimide tube and a 20-gauge needle housing. The magnitude and phase of the electrical impedance of the transducer were 47 omega and -38 degrees, respectively. The measured center frequency and -6 dB fractional bandwidth of the PMN-PT needle transducer were 44 MHz and 45%, respectively. The two-way insertion loss was approximately 15 dB. In vivo high-frequency, pulsed-wave Doppler patterns of blood flow in the posterior portion and in vitro ultrasonic backscatter microscope (UBM) images of the rabbit eye were obtained with the 44-MHz needle transducer.

High-frequency ultrasound annular array imaging. Part II: digital beamformer design and imaging

This is the second part of a two-paper series reporting a recent effort in the development of a high-frequency annular array ultrasound imaging system. In this paper an imaging system composed of a six-element, 43 MHz annular array transducer, a six-channel analog front-end, a field programmable gate array (FPGA)-based beamformer, and a digital signal processor (DSP) microprocessor-based scan converter will be described. A computer is used as the interface for image display. The beamformer that applies delays to the echoes for each channel is implemented with the strategy of combining the coarse and fine delays. The coarse delays that are integer multiples of the clock periods are achieved by using a first-in-first-out (FIFO) structure, and the fine delays are obtained with a fractional delay (FD) filter. Using this principle, dynamic receiving focusing is achieved. The image from a wire phantom obtained with the imaging system was compared to that from a prototype ultrasonic backscatter microscope with a 45 MHz single-element transducer. The improved lateral resolution and depth of field from the wire phantom image were observed. Images from an excised rabbit eye sample also were obtained, and fine anatomical structures were discerned.

Current and future innovations in high-frequency ultrasonic transducers and arrays

High-frequency ultrasonic imaging is considered the next frontier in ultrasonic imaging. Commercial high-frequency scanners often termed ultrasonic backscatter microscope (UBM) all use scanned single element transducers at frequencies higher than 30 MHz with a frame rate lower than 30 frames/s. The engineering of single element transducers and linear arrays at these frequencies has been problematic and may be addressed from the end of developing better piezoelectric materials and from the end of developing novel fabrication methodologies. The further improvement of UBM can be benefited greatly by the availability of superior single element transducers of wider bandwidth and higher sensitivity. Various novel piezoelectric materials, including 2-2 composites, fine grain materials, high or low dielectric constant materials, and fabrication methods that utilize conventional dice and fill, thick film, and MEMS have been explored to fulfill this need. Prototype linear arrays higher than 30 MHz have been developed and tested and preliminary images obtained. These recent developments will be discussed in this talk. [Work supported by NIH.]

Design, fabrication, and evaluation of high frequency, single-element transducers incorporating different materials.

The performance of high frequency, single-element transducers depends greatly on the mechanical and electrical properties of the piezoelectric materials used. This study compares the design and performance of transducers incorporating different materials. The materials investigated include 1-3 lead zirconate titanate (PZT) fiber composite, lead titanate (PbTiO3) ceramic, poly(vinylidene fluoride) (PVDF) film, and lithium niobate (LiNbO3) single crystal. All transducers were constructed with a 3-mm aperture size and an f-number between 2 and 3. Backing and matching materials were selected based on design goals and fabrication limitations. A simplified coaxial cable tuning method was employed to match the transducer impedance to 50 ohms for the PZT fiber composite and PbTiO3 ceramic transducers. Transducers were tested for two-way loss and -6 dB bandwidth using the pulse/echo response from a flat quartz target. Two-way loss varied from 21 to 46 dB, and bandwidths measured were in the range from 47 to 118%. In vitro ultrasonic backscatter microscope (UBM) images of an excised human eye were obtained for each device and used to compare imaging performance. Both press-focusing and application of a lens proved to be useful beam focusing methods for high frequency. Under equal gain schemes, the LiNbO3 and PbTiO3 transducers provided better image contrast than the other materials.