Thermal and Acoustic Stabilization Of Volatile Phase-Change Contrast Agents Via Layer-By-Layer Assembly.

OBJECTIVE: Phase-change contrast agents (PCCAs) are perfluorocarbon nanodroplets (NDs) that have been widely studied for ultrasound imaging in vitro, pre-clinical studies, and most recently incorporated a variant of PCCAs, namely a microbubble-conjugated microdroplet emulsion, into the first clinical studies. Their properties also make them attractive candidates for a variety of diagnostic and therapeutic applications including drug-delivery, diagnosis and treatment of cancerous and inflammatory diseases, as well as tumor-growth tracking. However, control over the thermal and acoustic stability of PCCAs both in vivo and in vitro has remained a challenge for expanding the potential utility of these agents in novel clinical applications. As such, our objective was to determine the stabilizing effects of layer-by-layer assemblies and its effect on both thermal and acoustic stability. METHODS: We utilized layer-by-layer (LBL) assemblies to coat the outer PCCA membrane and characterized layering by measuring zeta potential and particle size. Stability studies were conducted by; 1) incubating the LBL-PCCAs at atmospheric pressure at 37∘C and 45∘C followed by; 2) ultrasound-mediated activation at 7.24 MHz and peak-negative pressures ranging from 0.71 - 5.48 MPa to ascertain nanodroplet activation and resultant microbubble persistence. The thermal and acoustic properties of decafluorobutane gas-condensed nanodroplets (DFB-NDs) layered with 6 and 10 layers of charge-alternating biopolymers, (LBL6NDs and LBL10NDs) respectively, were studied and compared to non-layered DFB-NDs. Half-life determinations were conducted at both 37∘C and 45∘C with acoustic droplet vaporization (ADV) measurements occurring at 23∘C. DISCUSSION: Successful application of up to 10 layers of alternating positive and negatively charged biopolymers onto the surface membrane of DFB-NDs was demonstrated. Two major claims were substantiated in this study; namely, (1) biopolymeric layering of DFB-NDs imparts a thermal stability up to an extent; and, (2) both LBL6NDs and LBL10NDs did not appear to alter particle acoustic vaporization thresholds, suggesting that the thermal stability of the particle may not necessarily be coupled with particle acoustic vaporization thresholds. CONCLUSION: Results demonstrate that the layered PCCAs had higher thermal stability, where the half-lifes of the LBLxNDs are significantly increased after incubation at 37∘C and 45∘C. Furthermore, the acoustic vaporization profiles the DFB-NDs, LBL6NDs, and LBL10NDs show that there is no statistically significant difference between the acoustic vaporization energy required to initiate acoustic droplet vaporization.

Dispersion correction in the advanced volume holographic filter.

Thick volume Bragg gratings (VBG) have been used for wavefront selectivity in various applications such as data storage, endoscopy, or astronomic observation. However, a single thick grating is also selective in wavelength, severely limiting the spectral throughput of the system. Recently, our group introduced a two element Advanced Volume Holographic Filter (AVHF) where the first, dispersive Bragg grating is coupled to a thick VBG such that it dramatically improves the spectral bandwidth, and ultimately enhances the signal to noise ratio of polychromatic sources. Still, the two grating AVHF configuration introduced wavelength dispersion which prevents usage of the filter in imaging systems. Here, we present a solution to this problem by introducing a third diffraction grating that compensates for the dispersion of the two initial gratings. Using both simulation and experimental implementation of a visible-based, broadband AVHF system, the spectral dispersion was improved by a factor of up to 41 × compared to our previous system, re-collimating the output filtered beam. This new AVHF system can be utilized in imaging applications with noisy environments requiring filtration of a polychromatic source.

Advanced volume holographic filter to improve the SNR of polychromatic sources in a noisy environment.

We present a new type of filter that improves the SNR of systems where polychromatic signal and noise are located at different distances within the same line of sight. The filter is based on holographic technology that allows for the discrimination of wavefronts by range. In using a combination of two holographic elements, a pre-disperser and a thick volume hologram, we were able to significantly increase the spectral bandwidth of the filter, from 9nm without the pre-disperser to 70nm with both holographic elements. Laboratory proof of concept demonstrated that such a filter is capable of an SNR improvement of 15 dB for a monochromatic source, and up to 7.6 dB for a polychromatic source. This filter can find applications in astronomic observation, satellite or space debris tracking, and free-space optical communication.