Traditional means to identify the physiological severity of arterial disease are hampered by their inability to identify atheroma extent and composition. New techniques that identify atheroma in vivo are being developed, however, accurate methodologies for atheroma characterization are hampered, due to the heterogeneous nature of the disease process. Novel acoustic targeting and highlighting agents, such as liposomes, may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. We have developed a unique methodology that, by process and composition, provides acoustic characteristics of liposomes. This formulation allows modification for antibody conjugation and therapeutic drug incorporation. Preliminary work by this group has been centered on the optimization of formulation, optimization of conjugation, and development of in vitro and in vivo quantitation techniques. This proposal describes a series of protocols to optimize highlighting and enhancing We plan to investigate the potential of these formulations to aid other imaging modalities as atheroma enhancement agents. Our long term goals are to determine, quantitate, and characterize the stage, extent, and physiologic severity of atherosclerosis and allow directed therapy to improve physiologic flow following intervention.

Public Health Relevance

This proposal seeks to develop a stable formulation (echogenic immunoliposomes) that has the ability to highlight, characterize, and quantify the progression of atherosclerosis.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Danthi, Narasimhan
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University of Texas Health Science Center Houston
Internal Medicine/Medicine
Schools of Medicine
United States
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Haworth, Kevin J; Bader, Kenneth B; Rich, Kyle T et al. (2017) Quantitative Frequency-Domain Passive Cavitation Imaging. IEEE Trans Ultrason Ferroelectr Freq Control 64:177-191
Klegerman, Melvin E; Moody, Melanie R; Hurling, Jermaine R et al. (2017) Gas chromatography/mass spectrometry measurement of xenon in gas-loaded liposomes for neuroprotective applications. Rapid Commun Mass Spectrom 31:1-8
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Radhakrishnan, Kirthi; Haworth, Kevin J; Peng, Tao et al. (2015) Loss of echogenicity and onset of cavitation from echogenic liposomes: pulse repetition frequency independence. Ultrasound Med Biol 41:208-21
Kim, Hyunggun; Kee, Patrick H; Rim, Yonghoon et al. (2015) Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule 1-Targeted Echogenic Immunoliposomes. Ultrasound Med Biol 41:1701-10
Klegerman, Melvin E; Zou, Yuejiao; Golunski, Eva et al. (2014) Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity. J Liposome Res 24:216-22
Raymond, Jason L; Haworth, Kevin J; Bader, Kenneth B et al. (2014) Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents. Ultrasound Med Biol 40:410-21

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