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A multi-element ultrasound hyperthermia system (Labthermics Technologies, Inc., Sonotherm 1000) was utilized to deliver energy to two relatively well-defined regions (3.8 X 3.8 cm) on the lateral aspect of the right rear leg of 22 dogs in 1, 2 and 3 weekly treatments to a target temperature of 42-43 degrees C, at a depth of 1 cm. The total treatment time was 30 min. One area heated on each dog was adjacent to the proximal femur and the other was 2-3 cm away from the distal aspect of the same bone. The system performed in an acceptably controlled manner and was able to deliver energy to a well-defined site. The mean temperature achieved, and rate of temperature rise in the heated regions, was independent of the region being treated. Little difference (0.12 degrees C) was noted between the mean temperatures of the heated regions, and the temperature bounds (42-43 degrees C) were exceeded by a small amount and for a relatively short period of time (out of range RMSE = 0.6 degrees C). Unheated regions showed much lower mean temperatures than did heated regions located 3.8 cm away, indicating that the energy was delivered in a well-defined manner. Superficial thermal injuries occurred in three of 22 dogs in the area heated 2-3 cm away from bone, and 11 of 22 dogs exhibited injuries in the tissue heated immediately adjacent to the femur.

A perfused tissue phantom, developed as a tool for analyzing the performance of ultrasound hyperthermia applicators, was investigated. The phantom, consisting of a fixed porcine kidney with thermocouples placed throughout the tissue, was perfused with degassed water by a variable flow rate pump. The phantom was insonated by an unfocused multielement ultrasound applicator and the temperatures in the phantom were recorded. The results indicate that for testing protocols where tissue phantoms are needed, the fixed kidney preparation offers an opportunity to use a more realistic phantom than has previously been available to assess the heating performance of ultrasound hyperthermia applicators.

High intensity focused ultrasound was employed to modify the permeability of the normal feline and canine blood-brain barrier (BBB) to a circulating vital dye--Evans blue (EB). The threshold doses (W sec/cm2) for focally increasing the permeability of the BBB in white matter (WM) and gray matter (GM) were as follows: internal capsule (WM)--340 to 680; thalamus (GM)--approximately 1326; and caudate nucleus (GM)--2284 to 2952. In the presence of supralesioning doses of ultrasound, the cross sectional area occupied by the EB was consistently greater than that of the attendant nonhemorrhagic lesion--thus suggesting that BBB changes may be inducible at sublesioning doses. These findings, in conjunction with those of others, suggest that high intensity focused ultrasound may have a role in the treatment of brain tumors based on cell destruction by two mechanisms: (a) direct, by the ultrasound and (b) indirect, by an antineoplastic agent which is delivered via an ultrasonically modified BBB.

Focused ultrasound has been used for focal modifications of brain tissue and in preliminary studies of the application of ultrasonic techniques for tissue modification in human stereotaxic neurosurgery; however, the technique has been seriously compromised by the necessity of removal of intervening skull. Such removal was necessary to avoid distortion and extremely large attenuation of the ultrasonic beam which resulted from passage through bone. Recent studies have shown that under proper conditions focal beams of ultrasound can be transmitted with tolerable and attenuation through skull, suggesting the possibility of transkull lesion production in brain. This report describes the acoustical parameters and histological features of focal brain lesions produced in 10 craniectomized cats with intense focal ultrasonic beams which first had passed through a formalin-fixed human skull overlay. The histological appearance of these lesions produced to date is similar to that produced previously without intervening skull.

Experimental results are presented demonstrating the application of pulse echo ultrasound to imaging the skin. A laboratory prototype B-mode mechanical scanner was employed to obtain images of human skin, both in vitro and in vivo, using broadband pulsed ultrasound at 25 MHz. Images were formed by processing digitized A-mode waveforms and displaying the resulting two-dimensional cross sections using a digital imaging system. Images obtained by rectifying the A-modes are compared to those derived using a software-based cross-correlation technique. Scans of test targets demonstrate that an axial resolution of 100 m can be achieved at 25 MHz when the digital correlation method is employed. Lateral resolution is limited by the 0.25 mm half-power focal beamwidth of the transducer. Seventeen in vitro ultrasonic scans of human skin were compared to frozen section histology. Average skin depth was well correlated between the two techniques ( = 0.99, p less than 0.001). Application of cross-correlated processing to 25 MHz in vivo images produced good delineation of epidermis, papillary, and reticular dermis. Conversion to a 50 MHz transducer did not delineate skin layers as well as the 25 MHz transducer due to inherent difficulties with transducer reverberations.

The ultrasonic absorption coefficient of freshly-excised rat liver is measured as a function of intensity in a 1 MHz focused field. The 7 cm diameter source has a geometric focus of 20 cm and a half-intensity linear focal beamwidth of 4.65 mm. Free-field harmonic content and radiation force measurements within the focal region indicate that quasilinear shock (sigma = 1) is attained in the intensity range of 225 W cm-2 to 275 W cm-2 SPTP intensity. Radiometric measurements of focal beamwidth and intensity response (focal intensity versus transducer input voltage squared) demonstrated beam narrowing up to 700 W cm-2 and focal intensities greater than would be expected from linear theory. This nonlinear acoustic field is employed to measure the absorption coefficient of liver at the beam focus. The pressure absorption coefficient, measured via the transient thermoelectric technique, was 0.038 Np cm-1 at low intensities (below 100 W cm-2 SPTP) and rose to approximately 0.117 Np cm-1 at 750 W cm-2 SPTP intensity. The absorption predicted using spherically converging beam theory is in agreement with the experimental data at the lower (below 200 W cm-2) and the higher (above 650 W cm-2) intensities. Gaussian theory provided a poor fit to the experimental data even after deficiencies in the model were considered.

Reported effects of ultrasound on sister chromatid exchange have been contradictory. These studies are discussed and their results, including ultrasonic dosimetry and biologic considerations, are compared. In the few studies showing positive effects, the magnitude was small, and the effects occurred as a result of in vitro exposure. Based on a review of these reports, there does not appear to be sufficient reason to alter presently held views on the safety of clinical ultrasound.

Ultrasonic absorption measurements in the range 0.5--56 MHz, and measurements of velocity at 8.87 MHz, were made in collagen suspensions in which molecular integrity was preserved, in a range of concentrations 0.07--0.7% by weight, at 10 and 20 degrees C. Absorption and velocity values, per unit concentration, exhibited by collagen are much greater in magnitude than those exhibited by globular proteins.

An unfocused multielement ultrasound applicator was developed for hyperthermia treatment of superficial tumors. The applicator contains sixteen 3.8-cm(2) individually controllable elements on a 15.2-cm(2) piezoelectric ceramic plate. The acoustical power output of each element can be independently applied to facilitate uniform heating throughout the treatment area while minimizing undesired heating in normal tissues. The performance of the applicator was examined by measuring acoustical power output and beam profiles. The results of this analysis indicated that the applicator is capable of producing required therapeutic output levels with excellent localization and control of the power deposition.

The compilation of the literature on ultrasonic propagation properties of mammalian tissues [J. Acoust. Soc. Am. 64, 423 (1978)] is continued with the addition of 45 papers yielding over 700 lines of parametric data.

An integrated ultrasonic system has been developed employing static gray scale imaging, digital image processing, and analyses of quantitative ultrasonic backscatter for interactive interrogation of brain through the adult human skull. Operating at 750 kHz, to avoid severe spatial and temporal pulse distortion which accompany ultrasonic transkull transmission at higher frequencies, storage and image processing of successive images taken at selected gain settings in the same image plane allow the reconstruction of a composite cross-section of the brain and skull and enable visualization of internal brain structure. Analyses of digitized backscatter data obtained with the visualization transducer over selectable interrogation paths referenced to the cross-sectional image permit quantitative classification of tissue type independent of qualitative visual image analysis, such that enhanced diagnostic potential is provided. A previous paper described in detail the modifications of the commercial ultrasound diagnostic unit which serves as the core of this system. The present paper presents the rationale for the integrated system design approach, as well as a description of graphics display and tissue classification features which have been incorporated into the instrumentation configuration and are deemed necessary for successful transkull ultrasonic imaging and diagnosis.

The earlier report that the frequency dependence of ultrasonic absorption of mammalian testis memicked a single relaxation process is explained as an effect of ultrasonic beam width upon the transient thermoelectric technique. More detailed measurements show that the frequency dependence of the ultrasonic absorption in testis is much the same as the attenuation in other soft tissues, viz., a proportional to f1.1. The earlier finding that testis exhibits an ultrasonic absorption coefficient significantly lower than reported for other tissues is confirmed.

A detailed review of the literature on ultrasonic propagation properties of mammalian tissues and organs has revealed 144 papers containing compilable data. Over 1300 lines of parametric data are listed, including the tissue, species, age, specimen preparation, anatomical structure, pathology, temperature, measurement method, frequency, velocity, attenuation, acoustic impedance, and density.