? This research proposal is focusing on the development of ultrasound imaging methods to detect and characterize in vivo blood flow rheological disorders attributed to red blood cell (RBC) hyper-aggregation. It is known that the intensity of the ultrasound signal backscattered by blood is modulated by RBC aggregation. Theoretical models have further established the link between the ultrasound signal power and the volume of aggregates. In human and animal blood vessels, the aggregation and disaggregation of RBC aggregates are dynamically modulated by the flow condition, and the existence of pathologies affecting the protein content of the plasma. The rheological impacts of RBC aggregation in mammalian physiology are numerous and involve both the macro- and microcirculation. Among them may be cited its effect on the formation of sludge blood in microvessels, increased blood viscosity, occurrence of vascular thrombosis, and increased flow resistance. The ability of blood to perform its main function, i.e. to transport oxygen, carbon dioxide, nutrients and metabolic products can be affected by abnormally high levels of RBC aggregation. It is hypothesized that ultrasound can provide a tool to non-invasively measure RBC aggregation and blood flow disorders. The specific objectives are: 1) To measure, by ultrasonic means, the structural changes in RBC aggregation induced by copolymer coating, in either rat or mouse models; 2) To measure, by ultrasonic means, the endothelial vasoactive response following injection of vasoactive agents, 3) To measure, by ultrasonic means, the peripheral blood flow resistance in mouse models of sickle cell anemia and b-thalassemia, 4) To measure, by ultrasonic means, RBC perfusion disorders with an ultrasonic contrast agent, and 5) To follow-up the success of genetic therapies for sickle cell anemia and b-thalassemia by measuring either the RBC aggregation level with ultrasound, the endothelial vasoactive response with ultrasound, the peripheral blood flow resistance with ultrasound, and/or the RBC tissue perfusion disorders with an ultrasound contrast agent. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL078655-03
Application #
7112431
Study Section
Special Emphasis Panel (ZHL1-CSR-K (S1))
Program Officer
Pandit, Sunil
Project Start
2004-09-22
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2006
Total Cost
$95,025
Indirect Cost
Name
University of Montreal
Department
Type
DUNS #
207622838
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 3-J7
Janvier, Florence; Zhu, Julian X X; Armstrong, Jonathan et al. (2013) Effects of amphiphilic star-shaped poly(ethylene glycol) polymers with a cholic acid core on human red blood cell aggregation. J Mech Behav Biomed Mater 18:100-7
Stoyanova, Ekatherina; Trudel, Marie; Felfly, Hady et al. (2012) Vascular endothelial dysfunction in ?-thalassemia occurs despite increased eNOS expression and preserved vascular smooth muscle cell reactivity to NO. PLoS One 7:e38089
Yu, F T H; Armstrong, J K; Tripette, J et al. (2011) A local increase in red blood cell aggregation can trigger deep vein thrombosis: evidence based on quantitative cellular ultrasound imaging. J Thromb Haemost 9:481-8
Saha, Ratan K; Franceschini, Emilie; Cloutier, Guy (2011) Assessment of accuracy of the structure-factor-size-estimator method in determining red blood cell aggregate size from ultrasound spectral backscatter coefficient. J Acoust Soc Am 129:2269-77
Le Floc'h, Simon; Cloutier, Guy; Finet, Gérard et al. (2010) On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study. Phys Med Biol 55:5701-21
Franceschini, Emilie; Yu, François T H; Destrempes, François et al. (2010) Ultrasound characterization of red blood cell aggregation with intervening attenuating tissue-mimicking phantoms. J Acoust Soc Am 127:1104-15
Fenech, Marianne; Garcia, Damien; Meiselman, Herbert J et al. (2009) A particle dynamic model of red blood cell aggregation kinetics. Ann Biomed Eng 37:2299-309
Yu, Francois T H; Franceschini, Emilie; Chayer, Boris et al. (2009) Ultrasonic parametric imaging of erythrocyte aggregation using the structure factor size estimator. Biorheology 46:343-63
Saha, Ratan K; Cloutier, Guy (2008) Monte Carlo study on ultrasound backscattering by three-dimensional distributions of red blood cells. Phys Rev E Stat Nonlin Soft Matter Phys 78:061919
Franceschini, Emilie; Yu, Francois T H; Cloutier, Guy (2008) Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements. J Acoust Soc Am 123:EL85-91

Showing the most recent 10 out of 11 publications