Page 40 - Spring 2018

Floyd Dunn and Biomedical Ultrasound
Because mice within 24 hours of birth are essentially poiki- lothermic, that is, able to function without ill effects over a wide range of body temperatures (including down to almost 0°C), they are well suited for testing a thermal mechanism. Accordingly, Floyd comprehensively investigated the ultra- sound-induced functional outcome of hind limb motor pa- ralysis in these animals. For these experiments, ultrasound was focused in the region of the third lumbar vertebra of the anesthetized day-old mouse. If the spinal cord was dam- aged in that region, then hind limb paralysis resulted and was easily detected.
Figure 3 shows the 50% threshold of paralysis, that is, one- half of the mice were paralyzed for the specific exposure time-intensity values that defined the centerline. The ex- posure conditions were such that, for each animal, a single ultrasonic pulse of known duration and intensity was inci- dent on the mouse’s spinal cord. For the experiment shown in Figure 3, the ultrasonic frequency of the single pulse was 982 kHz and the animal’s temperature was 10°C. Figure 3 compares the reciprocal of the ultrasonic pulse duration (t−1) with the square root of the ultrasonic intensity \[there are a few listed ultrasonic intensity values along the x-axis; note that the square root of 121 W/cm2 is 11 (W/cm2)1⁄2\]. Recipro- cal time is along the left y-axis and time is along the right y-axis. The solid diagonal lines that almost track the 50% threshold diagonal centerline are the 10% (above the cen- terline) and 90% (below the centerline) paralysis thresholds. The solid vertical and solid dashed horizontal lines provide visual guidance to the axes. Thermocouples were imbedded in the spinal cord to measure temperature; the open circles denote temperature increases of the indicated time-intensity coordinate.
Plotting the mouse paralysis data on a graph that related the pulse duration reciprocal (t−1) with the square root of inten- sity (I1⁄2) yielded a straight line for the 50% threshold. The slope of the straight line \[(t−1)/(I1⁄2) = 1/(I1⁄2 t)\] was an early indicator for an important ultrasonic dosage quantity, I t1⁄2 (Dunn et al., 1975), noting that the square root of I t1⁄2 is I1⁄2 t, the denominator of the threshold slope term.
Floyd then expanded the mouse paralysis studies to include body temperatures of 2°C, 10°C, and 20°C (Dunn, 1958) and then later expanded to the normal body temperature of 37°C (discussed in Determining Thresholds: Functional and Structural Outcomes). The mouse spinal cords were also evaluated histologically, which led to an interesting ob- servation: the lesions appeared histologically about 10-15
Figure 3. “Floyd Dunn 1956 Thesis Graph” by Elsa Dunn, 1977. Needlepoint in wool and acrylic fibers. See text for ex- planation of the data shown. See Dunn, 1956, Figure 13; 1958, Figure 4. © 2017 Dunn Living Trust. All rights reserved.
minutes after the loss of function occurred and the paralysis occurred almost immediately after the ultrasonic exposure, thus strongly suggesting that the histologically observed changes were associated with secondary processes of tissue damage. The care with which the experiments were conduct- ed (later verified with repeatability) showed that cavitation and thermal processes were not the principal mechanisms of action and that there was insufficient information to define a dose quantity. Later, however, these early studies would pro- vide the foundation for significant dose-effect observations because of the care and detail with which the experiments were performed.
Determining Thresholds:
Functional and Structural Outcomes These ultrasonically induced functional outcomes origi- nally observed by Floyd were further investigated by a host of graduate students and colleagues for decades to come, as were the earlier Fry brothers’ histological (structural) out- comes from the brain lesion project. Both structure and
38 | Acoustics Today | Spring 2018