The influence of shear stress metrics on plaque progression in an - - PowerPoint PPT Presentation

The influence of shear stress metrics on plaque progression in an adult hypercholesterolemic pig model:

• Multimodality imaging, biomechanics and histology

Ayla Hoogendoorn

PhD candidate

Erasmus MC, The Netherlands

Biomechanics in atherosclerosis

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Shear stress

Wall shear stress

Low shear stress Endothelial dysfunction

Plaque initiation Plaque progression

Plaque formation

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Shear stress metrics:

Time-averaged wall shear stress, oscillatory shear index, relative residence time, transWSS and cross-flow index

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The porcine study: timeline

Observed plaque size (IVUS)

* p<0.05 compared to T1 # p<0.05 compared to fast responder

Range plaque burden (%):

0-80%

Histology: plaque types (n=20 arteries)

Lipids (red) Lipids (red)

Histology: plaque components

N=5 Lipids (red) Endothelial cells (brown) H&E staining Collagen staining

From imaging to wall shear stress CFD

Flow 1 Flow 2 Flow 3 Flow 4 Flow 5

Wall shear stress

Pa

Shear stress metrics

• Time-averaged wall shear stress (TAWSS)
• Oscillatory shear index (OSI)
• Cross-flow index (CFI)
• Transverse wall shear stress (transWSS)
• Relative residence time (RRT)

Pro-atherogenic

Low High

OSI ≈

Plaque growth vs. baseline shear stress metrics

Relationship between lipid-rich plaque and shear stress

NIRS 2D map at T3

Longitudinal direction Circumferential direction

Conclusion

• We presented:
• An adult, hypercholesterolemic pig model
• Plaque development imaged at 3 time point over 1 year
• Detailed, individually tailored, shear stress analysis
• The pig model showed:
• Large plaques with unstable features and, uniquely, 5 cases of old ruptures
• Difference between fast and slow responders
• All 5 shear stress metrics showed a significant relationship with plaque growth in the fast responding animals

Acknowledgements

Erasmus MC, biomedical engineering

Annette Kok Eline Hartman Kim van Gaalen Kim van der Heiden Frank Gijsen Ton van der Steen Jolanda Wentzel

Erasmus MC, experimental cardiology

Ilona Peters Maaike Visser – te Lintel Hekkert Dirk-Jan Duncker

Erasmus MC, interventional cardiology

Karen Witberg Jurgen Ligthart

AMC, biomedical engineering, Amsterdam

Lorena Casadonte Maria Siebes

Erasmus MC, radiology

Marcel Dijkshoorn Adriaan Coenen Koen Nieman

Erasmus MC, animal facilities

Vincent Vaes Dennis Akkermans

Slow and fast responders

Histology: plaque components

Collagen CD68 (macrophages)

Influence of PA on PA growth

TAWSS/OSI TAWSS/CFI

Predictive value for plaque at T3

Fast responders

Positive predictive value Sensitivity TAWSS (low) 49.4% 43.1% OSI (high) 48.0% 40.3% RRT (high) 49.3% 42.5% CFI (high) 47.0% 40.6% transWSS (high) 42.7% 36.8% * Plaque = Wall Thickness >0.5mm

Predictive value for plaque* at T3

• * Plaque = Wall Thickness >0.2mm

Fast responders

Positive predictive value Sensitivity TAWSS (low) 88.5% 36.9% OSI (high) 88.9% 35.6% RRT (high) 88.2% 36.4% CFI (high) 86.8% 35.8% transWSS (high) 84.5% 34.8%

Slow responders

Positive predictive value Sensitivity TAWSS (low) 64.3% 45.0% OSI (high) 58.7% 40.9% RRT (high) 64.1% 44.6% CFI (high) 56.3% 39.2% transWSS (high) 48.7% 33.9%

TransWSS

Transverse WSS

Near-infrared spectroscopy vs. TAWSS

Porcine models of atherosclerosis: the main challenges

• Many interventions needed to get plaque development
• (High-fat diet, diabetes, hypertension, etc.)
• Unstable plaques/plaque rupture is rare
• Only young, growing animals are used
• Less comparable to human situation
• Influence of vascular growth on changes in shear stress cannot be ruled out