Vascular Modeling & Hemodynamics Research OUTLINE. CLINICAL MOTIVATION: Stroke. BACKGROUND: Diagnosis

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1 Biomedical Ultrasonics Research Lab Vascular Modeling & Hemodynamics Research Tamie Poepping Biomedical Ultrasonics Research Laboratory Dept. of Physics & Astronomy The University of Western Ontario UWO: Tamie Poepping Sam Chippin Bushra Hussain Sarah Kefayati Janet Powell Anna Rozik Meghan Thorne Emily Wong Majid Yousif Collaborators: David Holdsworth (Robarts) Richard Rankin (Radiology) David Steinman (Toronto) Rose Thompson (Sydney) Funding: NSERC, Australian Research Council, Heart & Stroke Foundation, CFI & OMRI, UWO CIHR-STP Vascular Research OUTLINE CLINICAL MOTIVATION: Atherosclerosis INTRO CLINICAL MOTIVATION: Atherosclerosis & Stroke RISK FACTORS: stenosis severity, hemodynamics METHODS MULTI-MODALITY: PIV, DUS, CFD IN VITRO SYSTEM: vessel geometry, flow rate, plaque geometry & features, elasticity RESULTS HEMODYNAMIC EFFECTS due to: stenosis severity, plaque shape, plaque ulceration COMPARISON: between models & modalities Vessel thickening and hardening over decades. Can lead to heart attack and brain attack (stroke). Source: imagesmd.com CLINICAL MOTIVATION: Stroke BACKGROUND: Diagnosis Emboli (plaque or clot) Plaque ICA (to brain) ECA (to face & neck) X-ray angiogram Lateral (side) view D S Risk of stroke correlated to stenosis severity historical; reduced flow physically measurable Originally diagnosed using x-ray angiography to assess narrowing Being replaced by other modalities, mainly Doppler ultrasound CCA Source: American Heart Association %S = 100 (1 - S/D) S max stenosis D normal diameter US, MRI: composition, structure (ulcerations) DUS: flow (recirculation, turbulence)

2 Treatment & Prevention Drug therapy anti-clotting agents Surgery carotid endarterectomy BACKGROUND: Clinical Trials Clinical trials ( ): NASCET (North American Symptomatic Carotid Endarterectomy Trial) & ECST (European Carotid Surgery Trial) Carotid endarterectomy surgical removal of plaque significant benefit for symptomatic patients with a severe stenosis Led to an increased emphasis on determination of % stenosis, despite recognizing large role of other factors BACKGROUND: Risk Factors BACKGROUND: Risk Factors Risk of Ischemic Stroke FACTORS Vessel elasticity HEMODYNAMICS Windkessel effect EFFECTS blood pressure Hemodynamics vessel geometry plaque geometry - stenosis severity - stenosis eccentricity vessel elasticity Patient History diet exercise Vessel geometry Plaque geometry Flow patterns Wall shear stress - oscillating: low: high: Free (blood) shear Recirculation & turbulence atherosclerosis plaque build-up emboli platelet activation thrombo emboli Plaque Composition lipids ulcerations, ruptures compliance Genetic Disposition plaque development clot formation Plaque composition Plaque rupture athero & thrombo emboli Source: imagesmd.com OBJECTIVES BACKGROUND: Specificity Controlled studies using in vitro and numerical models: complex problem with confounding in vivo variables isolate variables and control each independently very difficult in vivo; easier in vitro (benchtop) and numerically Perform parallel synergistic studies using: Doppler ultrasound (DUS) Digital particle imaging (DPI) & velocimetry (PIV) Computational fluid dynamics (CFD) Gain improved understanding of carotid hemodynamics. Develop improved DUS methods, for in vivo studies, that better reflect hemodynamics and pathology Stroke risk with severe ( ) stenosis Symptomatic 26% Asymptomatic 4% Most symptomatic patients have < 50% stenosis Most asymptomatic patients with severe stenosis remain asymptomatic Stenosis severity alone is not a specific indicator of stroke risk

3 METHOD: Geometries ECA ICA METHOD: Plaque Ulcerations ECA 8 mm ICA 8 mm CCA Normal Eccentric Smith et al., Acad. Radiol CCA Eccentric 50% METHOD: Phantoms Acrylic or Silicone Tissue-mimicking material (TMM) and vessel-mimicking material (VMM) Normal Eccentric Flow Rate (ml/s) Silicone vessel Agar tissue Millable Teflon polymer Rapid production Patient specific geometry METHOD: Flow Flow model geometry Flow waveform Downstream resistance Model compliance Optically transparent Wong et al., European Radiol Smith et al., JMRI 1999 Poepping et al., UMB 2002 Wong et al., UMB 2008 Time (sec) Smith et al., Acad. Radiol Holdsworth et al., Physiol. Meas Poepping et al., UMB 2002 Digital Particle Imaging (DPI) Normal QT

4 Normal Eccentric QT PIV: 3-D Stereoscopic Overlap area with interrogation grid Resulting 3D vector map Eccentric Left 2D vector map Computational Fluid Dynamics CFD uses numerical methods to solve equations for the motion of fluids within a defined geometry Compute time-varying 3-D velocity fields with high spatial and temporal resolution Use the velocity-field maps to track virtual particles or calculate shear stresses Right 2D vector map CFD: Particle tracking Shear stress experienced by particle Grad student: Emily Wong

5 CFD: Wall shear stress Ultrasound Primer PSV EDV B-Mode image Doppler velocity spectrum Grad student: Emily Wong Why Ultrasound? Doppler US B-mode image Tissue Doppler image Colour Doppler Sound waves at speed c = 1540 m/s f t Transducer (Transmits & Receives Ultrasound) f r Plaque volume Wall motion Moving RBC in vessel v cosθ v Spectral Doppler Doppler shift in frequency, f d = f r - f t = f t * 2 v cosθ / c Scatterer velocity, v = f d c / (2 cosθ) f t BACKGROUND: Doppler US BACKGROUND: Doppler US Single greyscale encoded spectrum # v Peak v Mean v Doppler Spectral Display Distribution of moving RBCs in vessel Distribution of velocities (velocity spectrum) Intensity Intensity Time (s)

6 BACKGROUND: Colour Doppler In-vitro Facility 2 m 1 m flow resistors ATL Ultramark 8 Peak Mean Flowmeter signal from transducer in-phase & quadrature signals mode control ECG pulse turnaround status UHDC Flow System reset signal acquisition computer Poepping et al., UMB 2002 ECA ICA METHOD: 3-D Stage METHOD: Doppler Analysis Doppler spectrum PSV EDV t1 t2 CCA Power v mean v peak Doppler frequency (velocity) t1 t3 t2 Time (s) Doppler Analysis Ensemble average Power v peak v mean Time (s) Ensemble standard deviation Doppler shift frequency (Blood velocity) SBI = 1 - v mean / v peak Integrated power Time (s)

7 Colour Doppler Emulation Colour Doppler Emulation concentric eccentric concentric eccentric concentric eccentric 260 (cm/s) 180 concentric eccentric 260 (cm/s) DPI: vs. Eccentric concentric eccentric DUS: Spectral Broadening Index 4 concentric eccentric Eccentric DUS: Spectral Broadening Index DUS: Turbulence Intensity concentric eccentric Eccentric concentric eccentric 112 (cm/s)

8 Turbulence Intensity Volume Comparisons: cross modality Fraction of total volume with TI > 20 cm/s DPI Fraction of total bifurcation volume DUS: v mean SBI TI Time (s) Grad student: Janet Powell Poepping et al., CAAJ 2007 Comparisons: effects of stents & ulcerations DUS: Turbulence Intensity Grad students: Emily Wong and Meghan Thorne Poepping, Thorne, Wong, Rankin, Holdsworth, CAAJ 2007 Wong et al., European Radiol DUS: Turbulence Intensity Comparisons: expt & numerical Digital Particle Imaging Computational Fluid Dynamics Turbulence Intensity (cm/s) Eccentric Wong et al., European Radiol Steinman, et al., Annals Biomed. Engineering 2000

9 Comparisons: numerical & expt Comparisons: expt & numerical Simulated DUS (from CFD) Measured DUS v peak v mean SBI Khoshniat et al., UMB 2005 Experimental DUS Numerical CFD Grad student: Emily Wong Spatial resolution Temporal resolution Vector info Dimensionality Limitations Comparison of Modalities PIV 0.5 mm x 2 mm 5-20 ms 2 for std PIV 3 for stereoscopic assemble multiple 2-D in vitro only poor z resolution CFD 0.25 mm 4 ms 3 3-D theoretical turbulence DUS mm 12 ms 1 for std DUS 3 for vector DUS assemble 1000s s.v. in vitro (3-D) in vivo (1-D) TOOLS Models Doppler ultrasound 3-D vector Doppler US 3-D ultrasound Particle imaging/velocimetry Computational fluid dynamics FACTORS Vessel elasticity Vessel geometry Plaque geometry Plaque composition SUMMARY STROKE RISK & THE CAROTID ARTERY BIFURCATION EFFECTS Flow patterns Wall shear stress Blood shear stress Turbulence Wall elasticity Plaque rupture SUMMARY Multi-disciplinary & multi-modality Physical models & in vitro system In vitro & in vivo (clinical) modalities Controlled investigation of independent factors Vessel geometry, flow rate, plaque geometry & features, elasticity Development of diagnostic DUS Translation to in vivo When, where, & how to best utilize DUS? Derive more specific indicators of stroke risk Tamie L. Poepping Assistant Professor Dept. of Physics & Astronomy University of Western Ontario London, Ontario N6A 3K7 Canada poepping@uwo.ca

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