ht. L Radiotim Oncology Bid. Phys., 1976, Vol. 1. pp. 377-378.
Pcrgamon Press.
Printed in the U.S.A.
TOXICITY AND POSSIBLE SYNERGISTIC EFFECTS OF ULTRASOUND PAUL L. CARSON,Ph.D. and WILLIAMR. HENDEE,Ph.D. Department of Radiology, University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, CO 80220,U.S.A. Extensive literature exists on the biological effects of ultrasound, and there are excellent summaries of much of this literature.47779 In addition, there have been a few attempts to extrapolate toxicity threshold data to clinically relevant exposure conditions.6*7 Based on it is fashionable to these extrapolations, conclude that risks are too high to perform diagnostic procedures at levels above the bioeffects threshold line, and to conclude that exposures below these thresholds are safe. As implied in Wells’ introduction,’ such generalizations are not adequate. Rather, for each individual case the exposed individual, in consultation with his physician, must weigh rather speculative estimates of hazard against possible benefits resulting from information delivered by the diagnostic procedure. Often this rather objective benefit risk evaluation is made by considering the case in the context of a class of procedures for which the evaluation has already been made. Currently, there is very little bioeffects threshold information for ultrasound applicable to the pulse regimes and exposure durations to which any particular location in the body may be subjected during pulsed ultrasound B-mode scanning. Additionally, there are only limited data bn exposures delivered by current diagnostic equipment.‘” Bioeffects data which is available is related primarily to continuous wave and single pulse, gated continuous wave ultrasound beams. Extrapolating from these data and from clinical experience, one may conclude with reasonable confidence that the probability of creating significant damage during common B-mode ultrasound examinations is relatively small.
In 1%5, Woeber described studies in which X-rays appeared to demonstrate an enhanced radiobiological effect when delivered in the presence of ultrasound radiation of 1 W/cm2.8 He attributed this relationship to nonthermal effects of ultrasound, implying that a synergistic relationship may exist between ionizing radiation and ultrasound at low average ultrasound intensity levels. In more recent experiments, Todd and Schroy’ and Martins (Ph.D. Thesis, University of CalifomiaBerkeley, LBL-37, 1973) observed that ultrasound exposure of certain cell cultures led to a reduction in the X-ray dose required to limit colony formation. In both these experiments free-field ultrasound intensity could not be determined. In spite of these reports, however, the assumption of a nonthermal synergism may be unfounded, because other experiments have shown that the X-ray response of at least certain tumors and cell cultures is not affected appreciably by sonication at over 100 times the usual average acoustic intensity encountered in diagnostic ultrasound.* In experiments yielding negative results, care was taken to minimize temperature changes, standing waves, and cavitation in the irradiated and sonicated cell cultures. At this time, there is little factual evidence to support the hypothesis that exposure to diagnostic ultrasound enhances the radiobiological effectiveness of X-radiation, including that delivered to patients undergoing therapy. Nevertheless, the possibility of a synergistic action of ionizing and ultrasound radiation should be explored further, both to obtain a better estimate of potential risks to patients undergoing diagnostic procedures, and to investigate possible therapeutic uses of 377
378
Vol. 1, No. 3-l
Radiation Oncology 0 Biology 0 Physics
ultrasound in combination with X-radiation. In light of the recent interest in hyperthermia, both as an autonomous biological stress and as an adjunct to radiation therapy, high intensity
ultrasound should be explored as well in terms of its capability to produce localized heating of a tumor region.
REFERENCES 1. Carson, P.L,, Hendee, W.R., Leung, S.S.: Performance evaluation and dosimetry in diagnostic ultrasound. Quart. Bull. of Am. Assoc. of Physicists in Med., Amer. Inst. of Phys., 7: 200-204,1973. 2. Clarke, P.R., Hill, C.R., Adams, K.: Synergysm between X-rays and ultrasound in tumor therapy. Br. I. Radial. 43: 9l-99, 1970. 3. Hill, CR.: Acoustic intensity measurements on ultrasonic diatptostic devices. In UZtrasono Graphia Media, Vol. 11, ed. by Bock, J. and Ossoinig, K. Verlag der Wiener Medizenishen Akademie, Vienna, 1971, pp. 21-27. 4. Taylor K.J.W.: Current status of toxicity invest&&ion. J. Clin. I&as. 2: 149-156, June, 1974. 5. Todd, P., Schroy, B.: X-ray inactivation of cultured m cells: enhancement by ultrasound. Radiology 113: 445-447, 1974.
6. Ulrich, W.: Ultrasound dosage for nontherapeutic use on human beings: extrapolations from a literature survey. Inst. Electric. Electron. Engrs, Trans. Biomed. Eng. 21: 48-51, 1974. 7. Wells P.N.T.: Possible Harmful effects in ultrasonic diagnosis. In: Cardiovascular Applications of Ultrasound, ed. by Reneman, R.S. American Elsevier, New York, 1974, pp. 1-17. 8. Woeber, K.: The effect of ultrasound in the treatment of cancer. In: Ultrasonic Energy, ed. by Kelly, E.. University of Illinois Press, Chicago, 1965. pp. 137-149. 9. Wotishop Proceedings-Zntemction of Ultrasound and Biological Tissues. ed. by Reid, J.M., Sikov, M.R.. Seattle, Wash&ton, Sep tember, 1972, Dept He&h, Education Welfare, pub. (FDA) 73-8008 BRII/DBE 73-l.
Pcrgamon Press.
Printed in the U.S.A.
TOXICITY AND POSSIBLE SYNERGISTIC EFFECTS OF ULTRASOUND PAUL L. CARSON,Ph.D. and WILLIAMR. HENDEE,Ph.D. Department of Radiology, University of Colorado Medical Center, 4200 East Ninth Avenue, Denver, CO 80220,U.S.A. Extensive literature exists on the biological effects of ultrasound, and there are excellent summaries of much of this literature.47779 In addition, there have been a few attempts to extrapolate toxicity threshold data to clinically relevant exposure conditions.6*7 Based on it is fashionable to these extrapolations, conclude that risks are too high to perform diagnostic procedures at levels above the bioeffects threshold line, and to conclude that exposures below these thresholds are safe. As implied in Wells’ introduction,’ such generalizations are not adequate. Rather, for each individual case the exposed individual, in consultation with his physician, must weigh rather speculative estimates of hazard against possible benefits resulting from information delivered by the diagnostic procedure. Often this rather objective benefit risk evaluation is made by considering the case in the context of a class of procedures for which the evaluation has already been made. Currently, there is very little bioeffects threshold information for ultrasound applicable to the pulse regimes and exposure durations to which any particular location in the body may be subjected during pulsed ultrasound B-mode scanning. Additionally, there are only limited data bn exposures delivered by current diagnostic equipment.‘” Bioeffects data which is available is related primarily to continuous wave and single pulse, gated continuous wave ultrasound beams. Extrapolating from these data and from clinical experience, one may conclude with reasonable confidence that the probability of creating significant damage during common B-mode ultrasound examinations is relatively small.
In 1%5, Woeber described studies in which X-rays appeared to demonstrate an enhanced radiobiological effect when delivered in the presence of ultrasound radiation of 1 W/cm2.8 He attributed this relationship to nonthermal effects of ultrasound, implying that a synergistic relationship may exist between ionizing radiation and ultrasound at low average ultrasound intensity levels. In more recent experiments, Todd and Schroy’ and Martins (Ph.D. Thesis, University of CalifomiaBerkeley, LBL-37, 1973) observed that ultrasound exposure of certain cell cultures led to a reduction in the X-ray dose required to limit colony formation. In both these experiments free-field ultrasound intensity could not be determined. In spite of these reports, however, the assumption of a nonthermal synergism may be unfounded, because other experiments have shown that the X-ray response of at least certain tumors and cell cultures is not affected appreciably by sonication at over 100 times the usual average acoustic intensity encountered in diagnostic ultrasound.* In experiments yielding negative results, care was taken to minimize temperature changes, standing waves, and cavitation in the irradiated and sonicated cell cultures. At this time, there is little factual evidence to support the hypothesis that exposure to diagnostic ultrasound enhances the radiobiological effectiveness of X-radiation, including that delivered to patients undergoing therapy. Nevertheless, the possibility of a synergistic action of ionizing and ultrasound radiation should be explored further, both to obtain a better estimate of potential risks to patients undergoing diagnostic procedures, and to investigate possible therapeutic uses of 377
378
Vol. 1, No. 3-l
Radiation Oncology 0 Biology 0 Physics
ultrasound in combination with X-radiation. In light of the recent interest in hyperthermia, both as an autonomous biological stress and as an adjunct to radiation therapy, high intensity
ultrasound should be explored as well in terms of its capability to produce localized heating of a tumor region.
REFERENCES 1. Carson, P.L,, Hendee, W.R., Leung, S.S.: Performance evaluation and dosimetry in diagnostic ultrasound. Quart. Bull. of Am. Assoc. of Physicists in Med., Amer. Inst. of Phys., 7: 200-204,1973. 2. Clarke, P.R., Hill, C.R., Adams, K.: Synergysm between X-rays and ultrasound in tumor therapy. Br. I. Radial. 43: 9l-99, 1970. 3. Hill, CR.: Acoustic intensity measurements on ultrasonic diatptostic devices. In UZtrasono Graphia Media, Vol. 11, ed. by Bock, J. and Ossoinig, K. Verlag der Wiener Medizenishen Akademie, Vienna, 1971, pp. 21-27. 4. Taylor K.J.W.: Current status of toxicity invest&&ion. J. Clin. I&as. 2: 149-156, June, 1974. 5. Todd, P., Schroy, B.: X-ray inactivation of cultured m cells: enhancement by ultrasound. Radiology 113: 445-447, 1974.
6. Ulrich, W.: Ultrasound dosage for nontherapeutic use on human beings: extrapolations from a literature survey. Inst. Electric. Electron. Engrs, Trans. Biomed. Eng. 21: 48-51, 1974. 7. Wells P.N.T.: Possible Harmful effects in ultrasonic diagnosis. In: Cardiovascular Applications of Ultrasound, ed. by Reneman, R.S. American Elsevier, New York, 1974, pp. 1-17. 8. Woeber, K.: The effect of ultrasound in the treatment of cancer. In: Ultrasonic Energy, ed. by Kelly, E.. University of Illinois Press, Chicago, 1965. pp. 137-149. 9. Wotishop Proceedings-Zntemction of Ultrasound and Biological Tissues. ed. by Reid, J.M., Sikov, M.R.. Seattle, Wash&ton, Sep tember, 1972, Dept He&h, Education Welfare, pub. (FDA) 73-8008 BRII/DBE 73-l.
