Angiogenesis model for ultrasound contrast research: exploratory study.
ABSTRACT To optimize an angiogenesis model for imaging research that is stable and can be imaged several times over the angiogenic time course.
Mice and rats received two injections of 0.4 mL of extract of basement membrane matrix (Matrigel; Becton Dickinson Labware, Bedford, MA) in the subcutaneous spaces on either side of the spine. One of the two Matrigel plugs in each animal had either 0.1 microg/mL of basic fibroblast growth factor (bFGF) (11 mice), 1.0 microg/mL of bFGF (12 mice, 5 rats), or 1.0 microg/mL of bFGF and 60 U/mL of heparin (11 mice). Three to 12 days after implantation, animals were imaged before and after the administration of up to four injections of 0.1 mL AF0150. Phase inversion imaging was used on a Siemens Elegra (Siemens ultrasound, Issaquah, WA) equipped with a 13 MHz VFX transducer. Three observers subjectively assessed the pattern of enhancement using a four-point scale. The Matrigel plugs were then removed and two observers graded the angiogenic response on a four-point scale. Ten Matrigel plugs, five with 1.0 microg/mL bFGF and five without, were evaluated histologically following immunohistochemical staining with anti-CD31.
The angiogenic response was greater in Matrigel plugs with 1.0 than with 0.1 microg/mL of bFGF. Heparin did not increase the angiogenic response. Vessels were predominantly at the periphery of the plugs with variable central penetration. Plugs appeared anechoic and homogeneous on ultrasound. Contrast enhancement within the plug occurred in 44% of mice with an angiogenic response at or after day 6 and the enhancement increased with the angiogenic response. In the others, peripheral enhancement could not be distinguished from the enhancement of surrounding tissues that were also hyperemic. The thicker rat skin interfered with plug assessment.
A stable angiogenesis model without the complexity of tumors is described. This model offers the opportunity to image the development and/or inhibition of angiogenesis. Neovasculature in Matrigel was detectable using ultrasound contrast. Quantitative studies correlating the degree of enhancement to microvascular density will be determined in subsequent studies.
Article: Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery.[show abstract] [hide abstract]
ABSTRACT: This review offers a critical analysis of the state of the art of medical microbubbles and their application in therapeutic delivery and monitoring. When driven by an ultrasonic pulse, these small gas bubbles oscillate with a wall velocity on the order of tens to hundreds of meters per second and can be deflected to a vessel wall or fragmented into particles on the order of nanometers. While single-session molecular imaging of multiple targets is difficult with affinity-based strategies employed in some other imaging modalities, microbubble fragmentation facilitates such studies. Similarly, a focused ultrasound beam can be used to disrupt delivery vehicles and blood vessel walls, offering the opportunity to locally deliver a drug or gene. Clinical translation of these vehicles will require that current challenges be overcome, where these challenges include rapid clearance and low payload. The technology, early successes with drug and gene delivery, and potential clinical applications are reviewed.Annual Review of Biomedical Engineering 02/2007; 9:415-47. · 12.21 Impact Factor