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Drug delivery monitoring by photoacoustic tomography with an ICG encapsulated double emulsion

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Abstract

The absorption spectrum of indocyanine green (ICG), a nontoxic dye used for medical diagnostics, depends upon its concentration as well as the nature of its environment, i.e., the solvent medium into which it is dissolved. In blood, ICG binds with plasma proteins, thus causing changes in its photoacoustic spectrum. We successfully encapsulated ICG in an ultrasound-triggerable perfluorocarbon double emulsion that prevents ICG from binding with plasma proteins. Photoacoustic spectral measurements on point target as well as 2-D photoacoustic images of blood vessels revealed that the photoacoustic spectrum changes significantly in blood when the ICG-loaded emulsion undergoes acoustic droplet vaporization (ADV), which is the conversion of liquid droplets into gas bubbles using ultrasound. We propose that these changes in the photoacoustic spectrum of the ICG emulsion in blood, coupled with photoacoustic tomography, could be used to spatially and quantitatively monitor ultrasound initiated drug delivery. In addition, we suggest that the photoacoustic spectral change induced by ultrasound exposure could also be used as contrast in photoacoustic imaging to obtain a background free image.

©2011 Optical Society of America

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Figures (9)

Fig. 1
Fig. 1 The size distribution of the ICG-loaded double emulsion. The mean droplet diameter is 4.4 μm.
Fig. 2
Fig. 2 A visible micrograph displaying the double emulsion. The dark green color shows that the ICG is encapsulated within the droplets.
Fig. 3
Fig. 3 Schematic of the photoacoustic experimental setup used: (a) for single point measurement and (b) for 2-D imaging. NDF - neutral density filters, FG - function generator.
Fig. 4
Fig. 4 The photoacoustic spectra of free ICG in saline (■) and in plasma(▲). The concentration of the emulsion was 3 μL/mL of saline or plasma. Each data point is the average from eight independent measurements. Error bars reflect the standard deviation at each point determined as described in the text.
Fig. 5
Fig. 5 The photoacoustic spectra of the ICG-loaded emulsion in plasma (■) and in saline (●). The green, dotted line represents the photoacoustic spectrum of free ICG in saline.
Fig. 6
Fig. 6 The PA spectrum of the ICG-loaded emulsion in plasma before (■) and after (▲) ADV. The green, dashed line represents the spectrum of free ICG in plasma.
Fig. 7
Fig. 7 The PA spectra of the ICG emulsion in canine blood before (■) and after (▲) ADV. The red dashed line represents the linear combination of the spectrum of whole blood and the spectrum of ICG emulsion in plasma. The green dashed line represents spectrum of whole blood and the spectrum of free ICG in plasma.
Fig. 8
Fig. 8 2-D, photoacoustic images of two vessels containing oxygenated canine blood at 860 nm before (a) and after (b) exposure to ultrasound (no emulsion present). Only vessel 1 was exposed to ultrasound pulses used to generate ADV.
Fig. 9
Fig. 9 2-D, photoacoustic images two vessels containing oxygenated canine blood and ICG-loaded double emulsion before (a) and after (b) ADV. Only vessel 1 was exposed to ultrasound pulses used to generate ADV. The concentration of the emulsion was 3 μL/mL of blood.

Equations (5)

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y i , j = a j f ( λ )
y i , 2 = a 2 y i , 1
a 2 i = 1 i = n ( y i , 2 a 2 y i , 1 ) 2 = 0
a 2 = i = 1 i = n y i , 2 y i , 1 i = 1 i = n y i , 1 2
a j = i = 1 i = n y i , j y i , 1 i = 1 i = n y i , 1 2 , j = 2 , .. n
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