RESUMEN
Contrast-enhanced diagnostic ultrasound (CEDUS) can lead to microvascular injury and petechial hemorrhage by the cavitational mechanism of ultrasonic bioeffects. Capillary hemorrhage has been noted in the heart and kidney, which are common targets of CEDUS examination. CEDUS has also become useful for monitoring intestinal inflammation. In the 1990s, the risk of intestinal microvascular hemorrhage was investigated both for incidental exposure by lithotripter shockwaves and for contrast agent microbubbles acting as cavitation nuclei with laboratory pulsed ultrasound systems. This study was initiated to update the risk assessment for intestine exposed to diagnostic imaging simulating CEDUS. The abdomens of anesthetized rats were scanned by a 1.6 MHz phased array probe during infusion of microbubble suspensions simulating Definity ultrasound contrast agent. Dual image frames were triggered intermittently, and the output power was varied to assess the exposure response. Petechiae counts in small intestine mucosa and muscle layers increased with increasing trigger interval from 2 s to 10 s, indicative of a slow refill after microbubble destruction. The counts increased with increasing output above a threshold of 1.4 MPa peak rarefactional pressure amplitude. Petechiae were also seen in Peyer's patches, and occult blood was detected in many affected segments of intestine. These results are consistent with early laboratory pulsed-ultrasound results.
Asunto(s)
Medios de Contraste , Fluorocarburos , Hemorragia/etiología , Aumento de la Imagen/métodos , Intestinos/irrigación sanguínea , Ultrasonografía/efectos adversos , Animales , Capilares/fisiopatología , Modelos Animales de Enfermedad , Hemorragia/fisiopatología , Intestinos/fisiopatología , Masculino , RatasRESUMEN
OBJECTIVES: Contrast-enhanced diagnostic ultrasound (US) has a potential to induce localized biological effects. The potential for contrast-enhanced diagnostic US bioeffects in liver were researched, with guidance from a report by Yang et al (Ultrasonics 2012; 52:1065-1071). METHODS: Contact and standoff scanning was performed for 10 minutes with a diagnostic US phased array at 1.6 MHz during bolus injection or infusion of a contrast agent at a high dose. The impact of the imaging on rat liver was investigated by measuring enzyme release, microvascular leakage, and staining of injured hepatocytes. RESULTS: The results showed liver enzyme release at 30 minutes, indicating liver injury, and elevated extraction of Evans blue dye, indicating microvascular leakage. In addition, Evans blue and trypan blue vital-staining methods revealed scattered stained cells within the US scan plane. For the Evans blue method, fluorescent cell counts in frozen sections were greatest for standoff exposure with contrast infusion. The count decreased strongly with depth for bolus injection, which was probably reflective of the high attenuation noted for this agent delivery method. CONCLUSIONS: The results qualitatively confirmed the report by Yang et al and additionally showed hepatocyte vital staining. Research is needed to determine the threshold for the effects and the contrast agent dose response.
Asunto(s)
Medios de Contraste/efectos adversos , Hepatocitos/efectos de los fármacos , Ultrasonografía , Animales , Azul de Evans , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Myocardial contrast echocardiography (MCE) for perfusion imaging can induce microscale bio-effects during intermittent high-Mechanical Index scans. The dependence of MCE-induced bio-effects on the ultrasonic frequency was examined in rats at 1.6, 2.5 and 3.5 MHz. Premature complexes were counted in the electrocardiogram, petechial hemorrhages with microvascular leakage on the heart surface were observed at the time of exposure, plasma troponin elevation was measured after 4 h and cardiomyocyte injury was detected at 24 h. Increasing response to exposure above an apparent threshold was observed for all endpoints at each frequency. The effects decreased with increasing ultrasonic frequency, and the thresholds increased. Linear regressions for frequency-dependent thresholds indicated coefficients and exponents of 0.6 and 1.07 for petechial hemorrhages, respectively, and 1.02 and 0.8 for cardiomyocyte death, compared with 1.9 and 0.5 (square root) for the guideline limit of the mechanical index. The results clarify the dependence of cardiac bio-effects on frequency, and should allow development of theoretical descriptions of the phenomena and improved safety guidance for MCE.
Asunto(s)
Muerte Celular , Medios de Contraste , Ecocardiografía/efectos adversos , Hemorragia/etiología , Miocitos Cardíacos/patología , Animales , Modelos Animales de Enfermedad , Masculino , Púrpura/etiología , Ratas , Ratas sin Pelo , Troponina/sangreRESUMEN
OBJECTIVES: Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. METHODS: In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. RESULTS: There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P < .001). However, the thresholds for the two anesthetic methods were virtually identical at 1.0 MPa, based on linear regression of the exposure response data. CONCLUSIONS: Thresholds for contrast-enhanced diagnostic US-induced injury of the microvasculature appear to be minimally affected by anesthetic methods.