Design and fabrication of ultrafine piezoelectric composites.

Making fine scale (< 20 microm) piezoelectric composites for high frequency (> 50 MHz) ultrasound transducers remains challenging. Interdigital phase bonding (IPhB), described in this paper, presents a new technique developed to make piezoelectric composites at the ultrafine scale using a conventional dicing saw. Using the IPhB technique, a composite structure with a pitch that is less than the dicing saw blade thickness can be created. The approach is flexible enough to make composites of different combination of pitch and volume ratio. Using a conventional dicing saw with a 50 microm thick blade, composite with a 25 microm pitch and a volume ratio of 61 percent are fabricated. Such a composite is suitable for fabrication of ultrasonic transducers and arrays with central frequencies of up to 85 MHz. Single element transducers working at central frequencies of 50-60 MHz were made of these composites as a mean to characterize the acoustic performance. Measurement results of the transducers show that the longitudinal electromechanical coupling coefficient is greater than 0.6 and that there are no noticeable lateral resonances in the frequency range of 55-150 MHz. Design criteria for fine scale elements are also discussed based on theoretical results from finite element analysis (FEA).

A new ultrasound instrument for in vivo microimaging of mice.

We report here on the design and evaluation of the first high-frequency ultrasound (US) imaging system specifically designed for microimaging of the mouse. High-frequency US or US biomicroscopy (UBM) has the advantage of low cost, rapid imaging speed, portability and high resolution. In combination with the ability to provide functional information on blood flow, UBM provides a powerful method for the investigation of development and disease models. The new UBM imaging system is demonstrated for mouse development from day 5.5 of embryogenesis through to the adult mouse. At a frequency of 40 MHz, the resolution voxel of the new mouse scanner measures 57 microm x 57 microm x 40 microm. Duplex Doppler provides blood velocity sensitivity to the mm per s range, consistent with flow in the microcirculation, and can readily detect blood flow in the embryonic mouse heart, aorta, liver and placenta. Noninvasive UBM assessment of development shows striking similarity to invasive atlases of mouse anatomy. The most detailed noninvasive in vivo images of mouse embryonic development achieved using any imaging method are presented.

Applications for multifrequency ultrasound biomicroscopy in mice from implantation to adulthood.

A new multifrequency (19-55 MHz) ultrasound biomicroscope with two-dimensional imaging and integrated Doppler ultrasound was evaluated using phantoms and isoflurane-anesthetized mice. Phantoms revealed the biomicroscope's lateral resolution was between 50 and 100 microm, whereas that of a conventional 13 MHz ultrasound system was 200-500 microm. This difference was apparent in the markedly higher resolution images achieved using the biomicroscope in vivo. Transcutaneous images of embryos in pregnant mice from approximately 2 days after implantation (7 days gestation) to near term (17.5 days) were obtained using frequencies from 25 to 40 MHz. The ectoplacental cone and early embryonic cavities were visible as were the placenta and embryonic organs throughout development to term. We also evaluated the ability of the biomicroscope to detect important features of heart development by examining embryos from 8.5 to 17.5 day gestation in exteriorized uteri using 55 MHz ultrasound. Cardiac looping, division of the outflow tract, and ventricular septation were visible. In postnatal imaging, we observed the heart and kidney of neonatal mice at 55 MHz, the carotid artery in juveniles (approximately 8 g body wt) and adults (approximately 25 g body wt) at 40 MHz, and the adult heart, aorta, and kidney at 19 MHz. The coefficient of variation of carotid and aortic diameter measurements was 1-3%. In addition, blisters in GRIP1 -/- embryos and aortic valvular stenosis in two adults were readily visualized. Using image-guided Doppler function, low blood velocities in vessels as small as 100 microm in diameter including the primitive heart tube at day 8.5 were measurable, but high blood velocities (>37.5 cm/s) such as in the heart and large arteries in late gestation and postnatal life were off-scale. Accurate cardiac dimension measurements were impeded by poor temporal resolution (4 frames/s). In summary, the multifrequency ultrasound biomicroscope is a versatile tool well suited to detailed study of the morphology of various organ systems throughout development in mice and for hemodynamic measurements in the low velocity range.

Interdigital pair bonding for high frequency (20-50 MHz) ultrasonic composite transducers.

Interdigital pair bonding is a novel methodology that enables the fabrication of high frequency piezoelectric composites with high volume fractions of the ceramic phase. This enhancement in ceramic volume fraction significantly reduces the dimensional scale of the epoxy phase and increases the related effective physical parameters of the composite, such as dielectric constant and the longitudinal sound velocity, which are major concerns in the development of high frequency piezoelectric composites. In this paper, a method called interdigital pair bonding (IPB) is used to prepare 1-3 piezoelectric composite with a pitch of 40 microns, a kerf of 4 microns, and a ceramic volume fraction of 81%. The composites prepared in this fashion exhibited a very pure thickness-mode resonance up to a frequency of 50 MHz. Unlike the 2-2 piezoelectric composites with the same ceramic and epoxy scales developed earlier, the anticipated lateral modes between 50 to 100 MHz were not observed in the current 1-3 composites. The mechanisms for the elimination of the lateral modes at high frequency are discussed. The effective electromechanical coupling coefficient of the composite was 0.72 at a frequency of 50 MHz. The composites showed a high longitudinal sound velocity of 4300 m/s and a high clamped dielectric constant of 1111 epsilon 0, which will benefit the development of high frequency ultrasonic transducers and especially high frequency transducer arrays for medical imaging.

Advances in ultrasound biomicroscopy.

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 presented 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 microm 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 development and tumour biology are presented. Speculation on the continuing evolution of ultrasound biomicroscopy will be discussed.

A history of medical and biological imaging with polyvinylidene fluoride (PVDF) transducers.

Polyvinylidene fluoride (PVDF) is a ferroelectric polymer with unique properties suitable for use in a wide range of medical and biological imaging applications. Most notable among these is its low acoustic impedance, which matches that of the body reasonably well, and its flexible mechanical properties. This paper traces the exploitation of PVDF as a transducer material from its early beginnings for thyroid and breast imaging to its current well-established applications in ultrasound biomicroscopy. Although PVDF's electromechanical properties fall short of composite ceramic materials in the traditional diagnostic frequency range, it has significant advantages in the 25-to 100-MHz range. Design criteria for high frequency transducers are reviewed, and examples of relevant medical and biological images are used to illustrate the excellent image quality obtained with this remarkable material.

The use of high-frequency ultrasound as a method of assessing the severity of a plaque of psoriasis.

BACKGROUND AND DESIGN: Ultrasound imaging, while initially developed to visualize internal organs, is now being applied to image the skin. In this preliminary study, we used a high-frequency, 40-MHz ultrasound imaging system to provide high-resolution images in psoriasis and examined the relationship between clinical and ultrasound ratings in plaque-type psoriasis. The ultrasound image of a psoriatic plaque demonstrates a superficial echogenic band (band A), followed by a nonchogenic band (band B), and a deeper echogenic band (band C). RESULTS: In psoriatic plaques (N = 145), the severity of the psoriasis as assessed according to the degree of scaling, erythema, and thickness (SET score) correlated best with the width of band B (P < .001, r = 0.86) and less well with the width of bands A (P < .001, r = 0.59) and C (P < .001, r = 0.44). For the treated psoriatic plaques (n = 64), for which paired readings were available before and after therapy, changes in the SET scores correlated best with the change in the width of band B (P < .001, r = 0.96) and less well with the change in the width of bands A (P < .001, r = 0.61) and C (P < .001, r = 0.45). Ultrasound analyses and clinical evaluation were performed by independent raters. CONCLUSIONS: The data suggest that high-frequency ultrasound imaging may prove to be a noninvasive technique that can be used as an adjunct to the clinical evaluation of the lesional severity of psoriatic plaques.

High frequency 40-MHz ultrasound. A possible noninvasive method for the assessment of the boundary of basal cell carcinomas.

BACKGROUND: Ultrasound imaging systems operating close to 20 MHz in frequency have been used to image skin tumors. Ultrasound imaging at 20 MHz has been used to determine the boundaries of basal cell carcinomas (BCCs). An inherent shortcoming of imaging systems operating at these frequencies is their limited resolution. OBJECTIVE: We investigated whether 40-MHz ultrasound imaging could provide higher resolution compared with the lower frequency systems and thus be a superior, noninvasive method of assessing the boundaries of BCCs. METHODS: Nine BCCs from six individuals were examined clinically and ultrasonographically, and then biopsied to confirm diagnosis. The depth of BCCs measured on histological sections was compared with the corresponding value obtained using ultrasound. For this study we required a nonsurgical, nondestructive means of treating BCCs that would allow repeated ultrasound imaging, and therefore topical 5-flurouracil (5-FU) was chosen. Following 5-FU therapy a biopsy was obtained from the site of the treated BCC after ultrasound imaging had been performed. Clinical, ultrasonic and histopathologic evaluation of each BCC was carried out independently by different individuals. At the end of the study all the BCC sites were treated surgically be electrodesiccation and curettage or completely excised. RESULTS: High resolution ultrasound images of BCCs were obtained with agreement between histology and ultrasound findings in all none lesions prior to therapy and in eight of none lesions posttherapy. There was a significant correlation between the depth of BCCs measured histologically and using ultrasound (P = 0.0004, r = 0.92). CONCLUSIONS: This study suggests that 40-MHz ultrasound may provide an estimate of the boundary of a BCC in vivo. High frequency 40-MHz ultrasound imaging may be an adjunct to clinical and histologic evaluation but does not replace the need to obtain tissue for microscopic examination.

Imaging of immature articular cartilage using ultrasound backscatter microscopy at 50 MHz.

A high frequency sonographic technique-ultrasound backscatter microscopy-was used to visualize the subsurface structure of immature porcine articular cartilage from the knee joint. In 20-week-old pigs, all parts that were scanned, except the weight-bearing regions of the femoral condyles, demonstrated heterogeneous ultrasound backscatter characteristics within the articular cartilage. A trilaminar pattern consisting of hypoechoic, hyperechoic, and anechoic layers ranging from superficial to deep generally was observed, except in the weight-bearing regions of the femoral condyles, where a homogeneous anechoic pattern was seen. In the younger pigs (6 and 10 weeks old), the trilaminar backscatter pattern was not observed. Small, highly echogenic structures that correlated with vascular channels in histologic assessment were observed frequently in the cartilage of younger pigs, but they were seldom present in the cartilage of 20-week-old pigs. Structural details, such as disruption of the subchondral bone and presence of a thickened fibrous layer on the articular surface at the chondrosynovial junction, also were detected with the ultrasound backscatter microscope. We concluded that high frequency ultrasound can be used to visualize the subsurface structure of immature articular cartilage and some of its developmental changes. Further research is required to explain the mechanism underlying the observed backscatter characteristics of immature articular cartilage and to study its potential for the imaging of pathologic changes.

Does high-frequency (40-60 MHz) ultrasound imaging play a role in the clinical management of cutaneous melanoma?

The assessment of cutaneous melanoma in the clinical setting is often difficult, and important features such as depth and width remain unknown until the pathology report is received. Access to prognostic features such as vertical height before excisional biopsy would offer a basis for guidance in defining surgical margins and early planning of treatment options. Recently developed high-frequency ultrasound imaging in the 40-to 60-MHz range is a noninvasive method that provides in vivo information about cutaneous lesions. Imaging at these frequencies provides high-resolution data within the range of the epidermis and dermis (3-4 mm in depth). Ten cutaneous melanomas and seven pigmented lesions were assessed in this fashion. Vertical height was documented and compared to histopathological findings. High-frequency ultrasound imaging determination of vertical height correlated well with the standard measurement of Breslow's thickness on histological sections only in midrange (1.0-3.0 mm) lesions. Inflammatory cells at the base of three melanomas provoked an overestimation of the depth measurement with ultrasonography. Thick keratin layers such as those found on the feet acted as a virtual block to the high-frequency scanner. The application of this new advance in noninvasive imaging technology to the clinical assessment of cutaneous melanoma provides interesting in vivo data but in its present state does not replace the need for the biopsy of pigmented lesions and histopathological diagnosis.

A 40-100 MHz B-scan ultrasound backscatter microscope for skin imaging.

There is a growing interest in high resolution, subsurface imaging of cutaneous tissues using higher frequency ultrasound, and several commercial systems have been developed recently which operate at 20 MHz. Some of the possible applications of higher frequency skin imaging include tumour staging, boundary definition, and studies of the response of tumours to therapy, investigations of inflammatory skin conditions such as psoriasis and eczema, and basic studies of skin aging, sun damage and the effects of irritants. Investigation of these areas is quite new, and the role of ultrasound skin imaging is continuing to evolve. Lateral resolution in the 20 MHz imaging systems ranges from 200 to 300 microns, which limits imaging applications to cutaneous structures which are relatively large in size. In this paper, a real-time ultrasound backscatter microscope (UBM) for skin imaging is described which operates in the 40-100 MHz range, providing axial resolution between 17 and 30 microns and lateral resolution between 33 and 94 microns. This improvement in resolution over current skin ultrasound systems should prove useful in determining the margins of small skin lesions, and in obtaining more precise, in vivo skin thickness measurements to characterize nonmalignant skin disease. Example images of normal skin, seborrhoeic keratosis and malignant melanoma illustrate the imaging potential of this system.

Principles and applications of ultrasound backscatter microscopy.

The development of ultrasound backscatter microscopy (UBM) is described together with initial clinical and biological applications. UBM is essentially an extension of the powerful B-mode backscatter methods developed for clinical imaging in the 3-10-MHz frequency range. The development of new high sensitivity transducers in the 40-100-MHz range now permits visualization of tissue structures with resolution approaching 20 mum and a maximum penetration of approximately 4 mm. The performance characteristics and trade-offs of these new polymer and ceramic devices are reviewed, and the implementation of high-frequency imaging systems is described. Initial clinical applications of UBM include ophthalmic, skin, and intravascular imaging. Examples of images and progress in these areas are presented. The biological application of UBM is illustrated by studies of drug uptake in living tumor spheroids. Significant increases in backscatter levels resulting from drugs targeting oxic and hypoxic cell populations are demonstrated.