RESUMEN
The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6-8% of the injected dose to extravasate per gram muscle tissue 30 min after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor of 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs.
Asunto(s)
Permeabilidad Capilar , Microburbujas , Ultrasonido , Animales , Azul de Evans/farmacocinética , Femenino , Geles , Ratones , Ratones Endogámicos C57BL , Músculos/metabolismo , Tamaño de la PartículaRESUMEN
In vivo attenuation and backscatter coefficients of normal human forearm dermis and subcutaneous fat were determined in the ranges 14 to 50 MHz and 14 to 34 MHz, respectively. Data were collected using three different transducers to ensure that results were independent of the measurement system. Attenuation coefficient was obtained by computing spectral slopes vs. depth, with the transducers axially translated to minimize diffraction effects. Backscatter coefficient was obtained by compensating recorded backscatter spectra for system-dependent effects and, additionally, for one transducer using the reference phantom technique. Good agreement was seen between the computed attenuation and backscatter results from the different transducers/methods. The attenuation coefficient of the forearm dermis was well described by a linear dependence with a slope that ranged between 0.08 to 0.39 (median = 0.21) dB mm(-1) MHz(-1). The backscatter coefficient of the dermis was generally in the range 10(-3) to 10(-1) Sr(-1) mm(-1) and showed an increasing trend with frequency. No significant differences in attenuation coefficient slope between the forearm dermis and fat were noted. Within the range of 14 to 34 MHz, the ratio of integrated (average) backscatter of dermis to that of fat ranged from 1.03 to 87.1 (median = 6.45), indicating significantly higher backscatter for dermis than for fat. Data were also recorded at the fingertip where the attenuation coefficient slope of the dermis was seen to be higher than that at the forearm.