Although lasers can effectively ablate atherosclerotic plaque, their clinical application is limited by difficulties in confining the effects of laser radiation to the plaque. Inadvertent irradiation of adjacent or underlying normal artery frequently causes perforations, dissections, spasm, pain and thrombosis. The goal of this proposal is to enhance the specificity of laser radiation for plaque by the use of naturally occurring chromophores: carotenoids. These compounds accumulate in plaque but not in normal artery and enhance selectivity by increasing the absorption of laser light by plaque in a spectral region where there is minimal absorption by normal artery. The optimal carotenoids for enhancing selectivity will be determined by first identifying the carotenoids that naturally accumulate in human plaque, and then determining which of these confers the greatest preferential absorption in the shortest period of time in an animal model of atherosclerosis. Characterizing the carotenoids found in human plaque will identify molecular structural features and physical-chemical properties which confer affinity for plaque. This may also help to explain the recently discovered association of beta carotene, a common carotenoid, with a significant reduction in myocardial infarction, stroke and vascular surgery. Once the optimal carotenoids are identified, their potential for enhancing the quality and selectivity of laser atherectomy will be assessed in an atherosclerotic animal model. Identifying those human plaques which accumulate the greatest amount of carotenoids will determine which types of atherosclerotic plaque have the greatest preferential absorption and thus, are best suited for removal by selective laser atherectomy. This research not only explores fundamental aspects of the interaction of carotenoids with atherosclerotic plaque but is successful, may result in a safer, more effective method for removing atherosclerotic arterial obstructions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL046384-02
Application #
3365521
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1992-02-01
Project End
1993-10-31
Budget Start
1993-02-01
Budget End
1993-10-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Cloft, H J; Murphy, K J; Prince, M R et al. (1996) 3D gadolinium-enhanced MR angiography of the carotid arteries. Magn Reson Imaging 14:593-600
Prince, M R; Narasimham, D L; Jacoby, W T et al. (1996) Three-dimensional gadolinium-enhanced MR angiography of the thoracic aorta. AJR Am J Roentgenol 166:1387-97
Levy, R A; Prince, M R (1996) Arterial-phase three-dimensional contrast-enhanced MR angiography of the carotid arteries. AJR Am J Roentgenol 167:211-5
Prince, M R; Narasimham, D L; Stanley, J C et al. (1995) Breath-hold gadolinium-enhanced MR angiography of the abdominal aorta and its major branches. Radiology 197:785-92
Prince, M R; Narasimham, D L; Stanley, J C et al. (1995) Gadolinium-enhanced magnetic resonance angiography of abdominal aortic aneurysms. J Vasc Surg 21:656-69
Prince, M R (1994) Gadolinium-enhanced MR aortography. Radiology 191:155-64
Prince, M R; Frisoli, J K (1993) Beta-carotene accumulation in serum and skin. Am J Clin Nutr 57:175-81
Frisoli, J K; Tudor, E G; Flotte, T J et al. (1993) Pharmacokinetics of a fluorescent drug using laser-induced fluorescence. Cancer Res 53:5954-61
Mitchell, D C; Prince, M R; Frisoli, J K et al. (1993) Beta carotene uptake into atherosclerotic plaque: enhanced staining and preferential ablation with the pulsed dye laser. Lasers Surg Med 13:149-57
Prince, M R; Yucel, E K; Kaufman, J A et al. (1993) Dynamic gadolinium-enhanced three-dimensional abdominal MR arteriography. J Magn Reson Imaging 3:877-81