ABSTRACT
Microwave imaging is a low-cost imaging method that has shown promise for breast imaging and, in particular, neoadjuvant chemotherapy monitoring. The early studies of microwave imaging in the therapy monitoring setting are encouraging. For the neoadjuvant therapy application, it would be desirable to achieve the most accurate possible characterization of the tissue properties. One method to achieve increased resolution and specificity in microwave imaging reconstruction is the use of a soft prior regularization. The objective of this study is to develop a method to use magnetic resonance (MR) images, taken in a different imaging configuration, as this soft prior. To enable the use of the MR images as a soft prior, it is necessary to register the MR images to the microwave imaging space. Registration fiducials were placed around the breast that are visible in both the MRI and with an optical scanner integrated into the microwave system. Utilizing these common registration locations, numerical algorithms have been developed to warp the original breast MR images into a geometry closely resembling that in which the breast is pendant in the microwave system.
ABSTRACT
BACKGROUND: Low levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials. OBJECTIVE: We examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo. METHODS: Our novel site-specific gene delivery system was examined in naïve rat model and comprised the following steps: (1) intravenous co-administration of a solution containing acoustically active microspheres (Optison™, GE Healthcare, Princeton, New Jersey) and human ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres within the liver vasculature; (3) External application of locally-directed acoustic energy, (4) induction of microsphere disruption and in situ sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression of human ApoA-I protein; and (6) elevation of serum HDL-C. RESULTS: Co-administration of ApoA-I plasmids and acoustic microspheres, activated by external ultrasound energy, resulted in transcription and production of human ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05). CONCLUSIONS: HDL-C was increased in rats following ultrasound directed delivery of human ApoA-I plasmids by microsphere sonoporation. The present method provides a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation, potentially permitting the use of a minimally-invasive ultrasound-based, gene delivery system for treating individuals with low HDL-C.
