This research was supported in part by Shandong Province Medical Health Science and Technology Project (No. 202425020256, and 202403010254), National Natural Science Foundation of China grants 11972117 and 11802060, the Natural Science Foundation of Jiangsu Province under grant number BK20180352, and the Natural Science Foundation of Shandong Province under grant number ZR2024QA110.

De-identified clinical data, including in vivo IVUS images and blood pressure data, were acquired from a patient with CAD at Zhongda Hospital, Southeast University, with informed consent obtained. The sample patient was selected from the patient pool of a clinical study on intermediate coronary atherosclerotic lesions to demonstrate the method for quantifying the material properties of patient-specific coronary vessels14. The study was conducted following the protocol approved by the Clinical Research Ethics Committee of Zhongda Hospital, Southeast University (approval number: 2017ZDSYLL023-p01).
1. Data acquisition and processing
<ol>
	<li>Cine IVUS and VH-IVUS image acquisition
	<ol>
		<li>Place the IVUS catheter distal to the atherosclerotic lesion with the guidance of a coronary angiogram and pull it back to the proximal side. Generate grayscale IVUS images along the way to visualize the cross-section of the coronary vessel.</li>
		<li>Use the IVUS imaging system equipped with a high-performance 20 MHz, 2.9F platinum catheter to acquire IVUS images of the coronary arterial segment with atherosclerotic plaque from the patient with CAD (Figure 1).</li>
		<li>During the IVUS image acquisition, pause the catheter at the pre-selected lesion site for approximately 2 s to obtain a sequence of IVUS images called cine IVUS. The cine IVUS images clearly showed the dynamic cross-sectional changes at the given plaque site over the cardiac cycle.</li>
		<li>Generate VH-IVUS images based on IVUS frames acquired at the instant of R peak on electrocardiograms to visualize plaque components in color-coded form using the imaging system. 
		NOTE: VH-IVUS images provide an intuitive color map for four key plaque components in the atherosclerotic plaque: lipid-rich necrotic core (lipid) in red, calcification in white, fibrous tissue in dark green, and fibrous adipose tissue in light green.</li>
		<li>Save VH-IVUS and cine IVUS images in DICOM format for offline analysis.</li>
	</ol>
	</li>
	<li>Image segmentation and processing
	<ol>
		<li>Open DICOM files using the viewer, double-click the Corresponding Sequence Name to open the image and click Export &#62; Export Images to save each cine IVUS frame or VH-IVUS frame as an individual image in BMP format. Each BMP image contains 500 x 500 pixels, as indicated by the original DICOM file.</li>
		<li>Examine the cine IVUS image frame by frame to find the consecutive frames obtained at the pre-selected plaque site during one cardiac cycle. There were 26 cine IVUS frames generated during one cardiac cycle for this sample plaque site.</li>
		<li>Examine all the generated VH-IVUS images to find the VH-IVUS image obtained at the given plaque site. The VH-IVUS images used here were created using one IVUS frame from the cine IVUS frames in one cardiac cycle.</li>
		<li>Segment VH-IVUS and cine IVUS images using ImageJ software to obtain the contours of vessel boundaries and plaque component boundaries (See Figure 1C).
		<ol>
			<li>Select Straight &#62; Segmented Line tab and manually delineate the contours of the lumen, outer boundary of the coronary vessel, and plaque components on cine IVUS and VH-IVUS images. For the cine IVUS image, only segment the contours of the lumen and outer vessel boundary, while for the VH-IVUS image, segment the contours of the lumen, outer vessel boundary, and plaque component boundaries.</li>
			<li>For simplicity, keep only large lipid components for generating a finite element model and ignore small, isolated lipid components. Only one lipid was present in this plaque sample. Overlay the delineated contours onto the original images using Image &#62; Overlay &#62; Add Selection tab.</li>
			<li>Navigate to the To ROI Manager menu to manage contours, adjust properties, and set colors and line width to proper values for better visualization. Select the Properties tab, set the stroke color to a different color, and fill in the line width at width. Here, set the line colors as green, blue, and red for lumen, outer-boundary, and lipid contours, respectively, and the line width as 3.</li>
			<li>Smooth contours using Edit &#62; Selection &#62; Fit Spline from the command bar after selecting a specific contour to get a smooth contour. This operation utilizes spline curve fitting techniques to automatically smooth the contours.</li>
			<li>Click File &#62; Save As &#62; XY Coordinates tab to save point coordinates of each contour like lumen, outer-boundary, and plaque component in a separate txt file. This file contains the x and y coordinate values of the points constituting the contour, with pixels as the unit.</li>
		</ol>
		</li>
		<li>Record the real physical size of each pixel in cine IVUS and VH-IVUS images (denoted as pixel size) from the DICOM file. The real distance for one pixel in the IVUS data used here is 0.002 cm. This information would be used to convert the point coordinates with the pixel as the unit to real distance with cm as the unit.</li>
	</ol>
	</li>
	<li>Contour data processing
	<ol>
		<li>Cine IVUS contour data processing
		<ol>
			<li>Read txt files of lumen contours from all cine IVUS images in one cardiac cycle with MATLAB.</li>
			<li>Multiply all lumen contours by pixel size to get the actual size of the lumen contours.</li>
			<li>Calculate lumen circumferences for all lumen contours and identify the IVUS frames with maximum (Cmax) and minimum (Cmin) lumen circumferences, representing diastolic and systolic conditions, respectively.</li>
		</ol>
		</li>
		<li>VH-IVUS contour data processing
		<ol>
			<li>Read txt files of the contours of the lumen, outer-boundary, and plaque components from the VH-IVUS image with MATLAB.</li>
			<li>Multiply all contours by pixel size to get the actual size of all contours.</li>
			<li>Re-divide each contour into 100 equally spaced points and perform 2D smoothing to get new VH-IVUS contour data to replace the old ones.</li>
		</ol>
		</li>
	</ol>
	</li>
</ol>
2. Finite element model
<ol>
	<li>Coronary vessel geometry reconstruction
	<ol>
		<li>Create one layer of contours in three-dimensional space by adding z coordinate value for all points of VH-IVUS contours, including lumen, outer-boundary, and lipid, and set z = 0 for all points (Figure 2).</li>
		<li>Create another layer of contours by adding z coordinate value for all points of VH-IVUS contours and reset z = 0.05 cm for all points. 
		NOTE: These two layers of contours reconstruct the 3D coronary vessel geometry for the thin-layer structure-only model by adding a fixed 0.05 cm layer thickness to VH-IVUS contours (Figure 2).</li>
	</ol>
	</li>
	<li>Finite element mesh generation
	<ol>
		<li>Create two auxiliary contours by linearly interpolating lumen and outer-boundary contours with weights 1/3 and 2/3 (Figure 3A) for each layer.</li>
		<li>Divide vessel area into 8 circumferential parts and 3 radial parts (see Figure 3B) by connecting the lumen/outer boundary to the closest point on the lipid contour (e.g., points A and B in Figure 3B) or two auxiliary contours with radial lines.</li>
		<li>Connect all points between layers with straight lines, forming a 3D structure with 3 x 8 volumes (Figure 3B). Divide each volume using hexahedral elements to generate the finite element mesh (Figure 3C) and different material groups (Figure 3D).</li>
		<li>Perform a mesh analysis by refining mesh density by 10% until changes in solutions &#60; 5%.</li>
	</ol>
	</li>
	<li>Material property definition
	<ol>
		<li>Use a modified anisotropic Mooney-Rivlin material model to describe the material properties of the coronary vessel wall. Coronary vessels and plaque components were assumed to be hyperelastic, anisotropic, nearly incompressible, and homogeneous materials, and the strain energy density function of the modified anisotropic Mooney-Rivlin material model is: 
		<img alt="Equation 1" src="/files/ftp_upload/67573/67573eq01.jpg" style="margin: auto;" />&#160; &#160; &#160;(1) 
		<img alt="Equation 2" src="/files/ftp_upload/67573/67573eq02v2.jpg" style="margin: auto;" />&#160; &#160;(2) 
		<img alt="Equation 3" src="/files/ftp_upload/67573/67573eq03.jpg" style="margin: auto;" />&#160; &#160; (3) 
		where I1 and I2 are the first and second invariants of the right Cauchy-Green deformation tensor C defined as c = [cij] = XTX, X = [Xij] = [<img alt="Equation 6" src="/files/ftp_upload/67573/67573eq06.jpg" style="margin: auto;" />], (Xi) was the current position (aj) was the original position, I4 = cij(nc)i(nc)j, nc was the unit vector in the circumferential direction of the vessel. c1, c2, D1, D2, K1 and K2 were patient-specific material parameters.</li>
		<li>Assign the initial values of material parameters for a patient-specific coronary vessel according to the ex vivo biaxial testing results, that is, c1 = &#8722;1,312.9 kPa, c2 = 114.7 kPa, D1 = 629.7 kPa, D2 = 2.0, K1 = 35.9 kPa and K2 = 23.5 (Figure 4A-B)13,15.</li>
		<li>Assign the material parameters for the plaque component if present. More specifically, for lipids, c1=0.5 kPa, c2=0, D1=0.5 kPa, and D2=1.5; for calcification, we used c1=920 kPa, c2=0, D1=360 kPa, and D2=2.0 (Figure 4B)16. 
		NOTE: Plaque components (lipid and calcification) were assumed to be hyperelastic, isotropic, and nearly incompressible, and their mechanical properties were described by isotropic Mooney-Rivlin material model with the strain energy density functions given in formula (2).</li>
	</ol>
	</li>
	<li>Governing equations and boundary conditions setting
	<ol>
		<li>Define governing equations for the thin-layer structure-only model, which includes motion equation, nonlinear Cauchy-Green strain-displacement relation, and coronary vessel material model11.</li>
		<li>Prescribe patient-specific blood pressure waveforms on the lumen surface to simulate real physiological conditions (Figure 4C). To obtain patient-specific blood pressure waveforms, scale a typical aortic pressure waveform with systolic and diastolic pressure values measured by arm cuff (Figure 4D).</li>
	</ol>
	</li>
</ol>
3. Finite element model-based updating approach for patient-specific coronary artery material properties
NOTE: The iterative process to determine patient-specific coronary material properties is illustrated in Figure 5.
<ol>
	<li>Determine the no-load geometry corresponding to the zero-pressure condition as the initial geometry for the computational model by shrinking the coronary geometry reconstructed from the VH-IVUS image axially with a fixed shrinkage rate of 95% and circumferentially with circumferential shrinkage (denoted as S) initially set as 98%. 
	NOTE: Since the coronary geometry reconstructed from the VH-IVUS image was under in vivo conditions with blood pressure prescribed on the lumen and axial stretch from tethered distal and proximal coronary arterial segments, the in vivo coronary geometry should shrink circumferentially and axially to obtain the zero-pressure geometry.</li>
	<li>Fix the axial shrinkage rate at 95% and update the circumferential shrinkage during the following steps.</li>
	<li>Define the material ratio (denoted as k) to assign the patient-specific material properties of the coronary vessel as: that is, c1 = k*(&#8722;1,312.9) kPa, c2 = k*114.7 kPa, D1 = k*629.7 kPa, K1 = k*35.9 kPa, and fix D2 = 2.0 and K2 = 23.5. 
	NOTE: Since only two data points (minimum and maximum lumen circumferences corresponding to diastolic and systolic pressures) were obtained to determine the unknown parameters (circumferential shrinkage rate S and material parameters of Mooney-Rivlin model), we reduced the number of unknown parameters by assuming that the in vivo patient-specific material properties of coronary vessel were proportional to the initial guess with material ratio denoted as k: that is, c1 = k*(&#8722;1,312.9) kPa, c2 = k*114.7 kPa, D1 = k*629.7 kPa, K1 = k*35.9 kPa, while D2 = 2.0 and K2 = 23.5 were fixed.</li>
	<li>Update the k value set to an initial value k of 1 along with circumferential shrinkage rate S during the following iterative procedure.</li>
	<li>Run software to solve the computational model to obtain the numerical results.
	<ol>
		<li>Write all commands for creating the thin-layer structure-only model into a batch file (Supplementary File 1) using MATLAB.</li>
		<li>Load this batch file using the advanced user interface (AUI) to generate the model (Figure 6A). Solve the thin-layer structure-only model by clicking Data File/Solution and save it as a .dat file (Figure 6C). Simulate three cardiac cycles and adopt the solution in the last cycle to present numerical results.</li>
		<li>Export results of node coordinates to a txt file by navigating List &#62; Value List &#62; Zone and selecting X-POSITION, Y-POSITION, and Z-POSITION in Variables to List under Coordinate. Click Apply and Export to export the coordinate results.</li>
		<li>Save lumen contour data corresponding to diastolic and systolic pressure conditions to .txt files for lumen circumference calculations.</li>
	</ol>
	</li>
	<li>Compare lumen circumferences calculated by the FE model (thin-slice layer structure-only model) at diastolic pressure condition with in vivo cine IVUS data (Cmin) and check if the relative error was &#60;1%. If the condition was met, then go to the next step, or otherwise update the material ratio k using the secant method and go to step 3.3 to re-run again17,18. 
	NOTE: In the first iterative, the Newton method was used to update the material ratio instead of the secant method.</li>
	<li>Compare lumen circumferences calculated by the FE model at systolic pressure condition with in vivo cine IVUS data (Cmax) and check if the relative error was &#60;1%. If yes, then stop the iterative procedure, or otherwise update the circumferential shrinkage rate S and redirect to step 3.4 to re-run again. 
	NOTE: In the first iterative, the Newton method was used to update the circumferential shrinkage rate instead of the secant method.</li>
	<li>Record optimal S and k values and calculate the corresponding material parameters of the Mooney-Rivlin material model.</li>
	<li>Plot the circumferential and axial stress-stretch ratio curves of the coronary vessel (Figure 7), which can be derived as follows: 
	<img alt="Equation 4" src="/files/ftp_upload/67573/67573eq04.jpg" style="margin: auto;" />&#160; &#160; (4) 
	where&#160;&#963; represents Cauchy stress,&#160;&#955; represents stretch ratio, i = c, a&#160;represents the circumferential and axial directions.
	<ol>
		<li>To draw a material curve in a particular direction, fix the stretch ratio in the other direction to 1. Calculate effective Young&#39;s modulus in the circumferential and axial (labeled YMc and YMa, respectively) as the slope of the scale function of the material curve at the stretch ratio interval [1.0, 1.1] to reflect the general material stiffness of the coronary artery13: 
		<img alt="Equation 5" src="/files/ftp_upload/67573/67573eq05.jpg" style="margin: auto;" />&#160; &#160; (5)</li>
	</ol>
	</li>
	<li>Extract plaque stress/strain distributions at any time and record node distribution and maximum stress values during systolic and diastolic phases (Figure 8).</li>
</ol>

 IVUS-Based Computational Method to Quantify Coronary Mechanical Properties

<ol>
	<li>Roth, G. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+burden+of+cardiovascular+diseases+and+risk+factors,+1990-2019:+update+from+the+GBD+2019+study.">Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study.</a> J Am Coll Cardiol. 76 (25), 2982-3021 (2020).</li><li>Kanwar, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+coronary+syndromes+without+coronary+plaque+rupture.">Acute coronary syndromes without coronary plaque rupture.</a> Nat Rev Cardiol. 13 (5), 257-265 (2016).</li><li>Milzi, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+plaque+composition+influences+biomechanical+stress+and+predicts+plaque+rupture+in+a+morpho-mechanic+OCT+analysis.">Coronary plaque composition influences biomechanical stress and predicts plaque rupture in a morpho-mechanic OCT analysis.</a> Elife. 10, e64020 (2021).</li><li>Stefanati, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+variability+of+mechanical+properties+on+the+predictive+capabilities+of+vulnerable+coronary+plaques.">Effect of variability of mechanical properties on the predictive capabilities of vulnerable coronary plaques.</a> Comput Methods Programs Biomed. 254, 108271 (2024).</li><li>Laurent, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expert+consensus+document+on+arterial+stiffness:+methodological+issues+and+clinical+applications.">Expert consensus document on arterial stiffness: methodological issues and clinical applications.</a> Eur Heart J. 27 (21), 2588-2605 (2006).</li><li>Daisuke, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+plaque+phenotype+associated+with+positive+remodeling.">Coronary plaque phenotype associated with positive remodeling.</a> J Cardiovasc Comput Tomogr. 18 (4), 401-407 (2024).</li><li>Macrae, R. A., Miller, K., Doyle, B. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methods+in+mechanical+testing+of+arterial+tissue:+A+review.">Methods in mechanical testing of arterial tissue: A review.</a> Strain. 52, 380-399 (2016).</li><li>Hayashi, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+approaches+on+measuring+the+mechanical+properties+and+constitutive+laws+of+arterial+walls.">Experimental approaches on measuring the mechanical properties and constitutive laws of arterial walls.</a> J Biomech Eng. 115 (4B), 481-488 (1993).</li><li>Sacks, M. S., Sun, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiaxial+mechanical+behavior+of+biological+materials.">Multiaxial mechanical behavior of biological materials.</a> Annu Rev Biomed Eng. 5, 251-284 (2003).</li><li>Charis, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+combined+plaque+structural+stress+and+wall+shear+stress+on+coronary+plaque+progression,+regression,+and+changes+in+composition.">Impact of combined plaque structural stress and wall shear stress on coronary plaque progression, regression, and changes in composition.</a> Eur Heart J. 40 (18), 1411-1422 (2019).</li><li>Wang, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantifying+patient-specific+in+vivo+coronary+plaque+material+properties+for+accurate+stress/strain+calculations:+An+IVUS-based+multi-patient+study.">Quantifying patient-specific in vivo coronary plaque material properties for accurate stress/strain calculations: An IVUS-based multi-patient study.</a> Front Physiol. 12, 721195 (2021).</li><li>Guo, X. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantify+patient-specific+coronary+material+property+and+its+impact+on+stress/strain+calculations+using+in+vivo+IVUS+data+and+3D+FSI+models:+a+pilot+study.">Quantify patient-specific coronary material property and its impact on stress/strain calculations using in vivo IVUS data and 3D FSI models: a pilot study.</a> Biomech Model Mechanobiol. 16 (1), 333-344 (2017).</li><li>Wang, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantification+of+patient-specific+coronary+material+properties+and+their+correlations+with+plaque+morphological+characteristics:+An+in+vivo+IVUS+study.">Quantification of patient-specific coronary material properties and their correlations with plaque morphological characteristics: An in vivo IVUS study.</a> Int J Cardiol. 371, 21-27 (2023).</li><li>Lu, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Accurate+identification+of+potential+critical+coronary+lesions+for+the+reduction+of+risk+of+cardiovascular+events:+study+protocol+for+a+randomized,+open-label,+active-controlled+multi-center+trial.">Accurate identification of potential critical coronary lesions for the reduction of risk of cardiovascular events: study protocol for a randomized, open-label, active-controlled multi-center trial.</a> Clin Trial Degenerat Dis. 3 (3), 106-110 (2018).</li><li>Lv, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Using+optical+coherence+tomography+and+intravascular+ultrasound+imaging+to+quantify+coronary+plaque+cap+stress/strain+and+progression:+A+follow-up+study+using+3D+thin-layer+models.">Using optical coherence tomography and intravascular ultrasound imaging to quantify coronary plaque cap stress/strain and progression: A follow-up study using 3D thin-layer models.</a> Front Bioeng Biotechnol. 9, 713525 (2021).</li><li>Camasao, D. B., Mantovani, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+mechanical+characterization+of+blood+vessels+and+their+substitutes+in+the+continuous+quest+for+physiological-relevant+performances.+A+critical+review.">The mechanical characterization of blood vessels and their substitutes in the continuous quest for physiological-relevant performances. A critical review.</a> Mater Today Bio. 10, 100106 (2021).</li><li>Holistic Numerical Methods Institute at University of South Florida. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Secant Method. , (2003).</li><li>Barnes, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+algorithm+for+solving+nonlinear+equations+based+on+the+secant+method.">An algorithm for solving nonlinear equations based on the secant method.</a> Comp J. 8 (8), 66-72 (1965).</li><li>Liu, M., Liang, L., Sun, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+inverse+method+for+estimation+of+in+vivo+mechanical+properties+of+the+aortic+wall.">A new inverse method for estimation of in vivo mechanical properties of the aortic wall.</a> J Mech Behav Biomed Mater. 72, 148-158 (2017).</li><li>Yu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-specific+in+vivo+right+ventricle+material+parameter+estimation+for+patients+with+tetralogy+of+Fallot+using+MRI-based+models+with+different+zero-load+diastole+and+systole+morphologies.">Patient-specific in vivo right ventricle material parameter estimation for patients with tetralogy of Fallot using MRI-based models with different zero-load diastole and systole morphologies.</a> Int J Cardiol. 276, 93-99 (2019).</li><li>Meuwissen, M. H. H., Oomens, C. W. J., Baaijens, F. P. T., Petterson, R., Janssen, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+the+elasto-plastic+properties+of+aluminium+using+a+mixed+numerical-experimental+method.">Determination of the elasto-plastic properties of aluminium using a mixed numerical-experimental method.</a> J Mater Process Technol. 75, 204-211 (1998).</li><li>Davis, F. M., Luo, Y., Avril, S., Duprey, A., Lu, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Local+mechanical+properties+of+human+ascending+thoracic+aneurysms.">Local mechanical properties of human ascending thoracic aneurysms.</a> J Mech Behav Biomed Mater. 61, 235-249 (2016).</li><li>Fan, L., Wang, H., Kassab, G. S., Lee, L. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review+of+cardiac-coronary+interaction+and+insights+from+mathematical+modeling.">Review of cardiac-coronary interaction and insights from mathematical modeling.</a> WIREs Mech Dis. 16 (3), e1642 (2024).</li><li>Andreas, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+finite+element+updating+approach+for+identification+of+the+anisotropic+hyperelastic+properties+of+normal+and+diseased+aortic+walls+from+4D+ultrasound+strain+imaging.">A finite element updating approach for identification of the anisotropic hyperelastic properties of normal and diseased aortic walls from 4D ultrasound strain imaging.</a> J Mech Behav Biomed Mater. 58, 122-138 (2016).</li><li>Liu, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+in+vivo+nonlinear+anisotropic+mechanical+properties+of+ascending+thoracic+aortic+aneurysm+from+patient-specific+CT+scans.">Identification of in vivo nonlinear anisotropic mechanical properties of ascending thoracic aortic aneurysm from patient-specific CT scans.</a> Sci Rep. 9, 12983 (2019).</li><li>Trabelsi, O., Duprey, A., Favre, J. P., Avril, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Predictive+models+with+patient+specific+material+properties+for+the+biomechanical+behavior+of+ascending+thoracic+aneurysms.">Predictive models with patient specific material properties for the biomechanical behavior of ascending thoracic aneurysms.</a> Ann Biomed Eng. 44, 84-98 (2016).</li><li>Cosentino, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=On+the+role+of+material+properties+in+ascending+thoracic+aortic+aneurysms.">On the role of material properties in ascending thoracic aortic aneurysms.</a> Comput Biol Med. 109, 70-78 (2019).</li><li>Krauz, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+epicardial+adipose+tissue+in+acute+coronary+syndromes,+post-infarct+remodeling+and+cardiac+regeneration.">The role of epicardial adipose tissue in acute coronary syndromes, post-infarct remodeling and cardiac regeneration.</a> Int J Mol Sci. 25 (7), 3583 (2024).</li><li>McCracken, I. R., Smart, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Control+of+coronary+vascular+cell+fate+in+development+and+regeneration.">Control of coronary vascular cell fate in development and regeneration.</a> Semin Cell Dev Biol. 155 (Pt C), 50-61 (2024).</li><li>Holzapfel, G. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+layer-specific+mechanical+properties+of+human+coronary+arteries+with+nonatherosclerotic+intimal+thickening+and+related+constitutive+modeling.">Determination of layer-specific mechanical properties of human coronary arteries with nonatherosclerotic intimal thickening and related constitutive modeling.</a> Am J Physiol Heart Circ Physiol. 289 (5), H2048-H2058 (2005).</li><li>Han, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ventricle+stress/strain+comparisons+between+Tertalogy+of+Fallot+patients+and+healthy+using+models+with+different+zero-load+diastole+and+systole+morphologies.">Ventricle stress/strain comparisons between Tertalogy of Fallot patients and healthy using models with different zero-load diastole and systole morphologies.</a> PLoS One. 14 (8), e0220328 (2019).</li><li>Ryo, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+the+low-density+lipoprotein-cholesterol/high-density+lipoprotein-cholesterol+ratio+in+predicting+serial+changes+in+the+lipid+component+of+coronary+plaque.">Role of the low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio in predicting serial changes in the lipid component of coronary plaque.</a> Circ J. 81 (10), 1439-1446 (2017).</li><li>Thomas, T. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+characterization+and+quantification+of+atherosclerotic+carotid+plaque+components+with+multidetector+computed+tomography+and+histopathological+correlation.">In vivo characterization and quantification of atherosclerotic carotid plaque components with multidetector computed tomography and histopathological correlation.</a> Arterioscler Thromb Vasc Biol. 26 (10), 2366-2372 (2006).</li><li>Masanori, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+quantitative+tissue+characterization+of+human+coronary+arterial+plaques+by+use+of+integrated+backscatter+intravascular+ultrasound+and+comparison+with+angioscopic+findings.">In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings.</a> Circulation. 105 (21), 2487-2492 (2002).</li><li>Roach, M. R., Burton, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+reason+for+the+shape+of+the+distensibility+curves+of+arteries.">The reason for the shape of the distensibility curves of arteries.</a> Can J Biochem Physiol. 35, 681-690 (1957).</li><li>Fung, Y. C., Liu, S. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strain+distribution+in+small+blood+vessel+with+zero-stress+state+taken+into+consideration.">Strain distribution in small blood vessel with zero-stress state taken into consideration.</a> Am J Physiol. 262, 544-552 (1992).</li><li>Ohayon, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+residual+stress/strain+on+the+biomechanical+stability+of+vulnerable+coronary+plaques:+Potential+impact+for+evaluating+the+risk+of+plaque+rupture.">Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: Potential impact for evaluating the risk of plaque rupture.</a> Am J Physiol Heart Circ Physiol. 293, 1987-1996 (2007).</li></ol>

The authors declare no conflict of interest.

Critical steps in the protocol 
The most critical step in the finite element model-based updating approach lies in the iterative procedure. In the approach, the finite element model should accurately recover the coronary vessel motion on the vascular cross-section from in vivo cine IVUS images. To this purpose, minimizing the lumen circumference difference between the finite element model and in vivo images was adopted in this study to find the proper material properties. There wer...

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity, accounting for more than 9.14 million deaths in 2019 globally1,2. The development of coronary artery diseases, such as atherosclerosis and stenosis, is often accompanied by alterations in mechanical forces and changes in vascular wall material properties3. The material properties of coronary arteries are not only the cornerstone to determine their mechanical response to the physiological loading but also the key elements to simulate the mechanical behavior of blood vessels, predict the development of atherosclerotic lesions, and evaluate the therapeutic effect of various medical devices4,5. Consequently, a profound understanding and accurate quantification of coronary material properties hold paramount value for early disease diagnosis, precision medicine, and prognosis assessment6.
Mechanical experiments of isolated coronary tissues, such as planar biaxial testing, indentation testing, inflation-extension, and uniaxial extension testing, are common approaches to quantify the mechanical properties of coronary vessel walls ex vivo7,8,9. From these approaches, coronary artery samples were obtained from patients or experimental animals. Mechanical testing was carried out to determine the strain responses of the vessel wall under different stress conditions, and then the material parameters were determined by fitting the experimental data10. Prior studies have shown that coronary properties are highly nonlinear and anisotropic11. Although ex vivo experiments can provide accurate material properties data, significant limitations also exist, which are as follows: First, the mechanical behavior of the sample after taking out from the living subjects would be different from that under in vivo conditions, which may affect the accuracy of testing results. Second, due to ethical and practical constraints, it is difficult to obtain a large collection of normal or pathological tissues of coronary arteries to perform the mechanical testing.
To overcome these limitations, researchers have explored novel techniques for in vivo, real-time, and patient-specific quantification of coronary material properties. Among them, the finite element model based updating approach (FEMBUA) based on medical image holds the promise to address these challenging issues. This approach makes use of advanced imaging techniques like intravascular ultrasound (IVUS) and virtual histology (VH)-IVUS to capture detailed coronary geometry, tissue compositions, and its movement12. By constructing 3D finite element (FE) models and incorporating patient-specific physiological blood pressure conditions, dynamic vascular behavior during cardiac cycles could be recovered by optimizing material parameters to match image data for rapid and accurate quantification of coronary material properties13. The advantages of the in vivo FE updating approach over ex vivo experiments include in vivo assessment without tissue excision, facilitating large-scale evaluations, and simulating vascular dynamics under complex conditions to aid the pathophysiology understanding of coronary diseases.
In this paper, key steps of the finite element model-based updating approach are introduced, which include a detailed segmentation and processing of cine IVUS and VH-IVUS image, reconstruction of computational thin-layer structure-only model, execution of the iterative scheme to search optimal material parameters for coronary arterial tissues. The aim of this protocol is to quantify the material properties of the coronary artery from a sample patient with CAD using the FEMBUA method as a demonstration, especially the illustration of step-by-step methods. We concluded by discussing the significance and other aspects of this in vivo method.
The selected participant is a 64-year-old female with no previous clinical history of coronary artery disease. This patient was diagnosed with coronary artery disease after having symptoms of chest pain. The coronary angiogram and IVUS scan were performed to confirm the diagnosis. A plaque lesion with 60% stenosis was found in the middle of the left anterior descending artery. After assessment, optimal medical therapy was adopted to treat the patient.

<table><tbody><tr><td>&amp;nbsp;Bee DICOM Viewer&amp;nbsp;</td><td>SinoUnion Healthcare Inc.</td><td>Version 3.5.1</td><td>A DICOM image reader software</td></tr><tr><td>ADINA&amp;nbsp;</td><td>Adina R &amp;amp; D</td><td>Version 9.0</td><td>Finite element solver</td></tr><tr><td>ImageJ&amp;nbsp;</td><td>National Institutes of Health</td><td></td><td>Segmented IVUS contours</td></tr><tr><td>MATLAB</td><td>MathWorks&amp;nbsp;</td><td>&amp;nbsp;Version R2018a</td><td>Commercial programming platform</td></tr><tr><td>Volcano s5 imaging system</td><td>Volcano Company</td><td></td><td>Intravascular ultrasound imaging system&amp;nbsp;</td></tr></tbody></table>

intravascular ultrasound image-based finite element modeling approach for quantifying in vivo mechanical properties of human coronary artery

Quantifying the mechanical properties of coronary arterial walls could provide meaningful information for the diagnosis, management, and treatment of coronary artery diseases. Since patient-specific coronary samples are not available for patients requiring continuous monitoring, direct experimental testing of vessel material properties becomes impossible. Current coronary models typically use material parameters from available literature, leading to significant mechanical stress/strain calculation errors. Here, we would introduce a finite element model-based updating approach (FEMBUA) to quantify patient-specific in vivo material properties of coronary arteries based on medical images. In vivo cine intravascular ultrasound (IVUS) and virtual histology (VH)-IVUS images of coronary arteries were acquired from a patient with coronary artery disease. Cine IVUS images showing the vascular movement over one cardiac cycle were segmented, and two IVUS frames with maximum and minimum lumen circumferences were selected to represent the coronary geometry under systolic and diastolic pressure conditions, respectively. VH-IVUS image was also segmented to obtain the vessel contours, and a layer thickness of 0.05 cm was added to the VH-IVUS contours to reconstruct the coronary geometry. A computational finite element model was created with an anisotropic Mooney-Rivlin material model used to describe the vessel's mechanical properties and pulsatile blood pressure conditions prescribed to the coronary luminal surface to make it contract and expand. Then, an iterative updating approach was employed to determine the material parameters of the anisotropic Mooney-Rivlin model by matching minimum and maximum lumen circumferences from the computational finite element model with those from cine IVUS images. This image-based finite element model-based updating approach could be successfully extended to determine the material properties of arterial walls in various vascular beds and holds the potential for risk assessment of cardiovascular diseases.

We describe in detail the FEMBUA method, which enables rapid plaque material and stress analysis of coronary plaques after real-time IVUS imaging and can determine the in vivo material properties and biomechanical results of plaques. The in vivo material parameters of the Mooney-Rivlin material model for this coronary vessel are provided in Table 1. The simulation results of the finite element model, including the stress/strain distributions in the coronary vessel, are plotted in <stron...

Intravascular Ultrasound Image-Based Finite Element Modeling Approach for Quantifying In Vivo Mechanical Properties of Human Coronary Artery

In vivo cine intravascular ultrasound images show the coronary cross-sectional movement corresponding to different pressure loading conditions. Based on a finite element model, an iterative scheme was employed to determine the patient-specific mechanical properties of coronary arteries in vivo by matching coronary motion from the computational model and medical images.

Quantifying the mechanical properties of coronary arterial walls could provide meaningful information for the diagnosis, management, and treatment of ...

intravascular-ultrasound-image-based-finite-element-modeling-approach

Research

JoVE Journal

Engineering

434 Views.  Shandong Second Provincial General Hospital. In vivo cine intravasculaire echografiebeelden tonen de coronaire dwarsdoorsnedebeweging die overeenkomt met verschillende drukbelastingsomstandigheden. Op basis van een eindig-elementenmodel werd een iteratief schema gebruikt om de patiëntspecifieke mechanische eigenschappen van kransslagaders in vivo te bepalen door de kransslagader te matchen met het rekenmodel en medische beelden. 

Video: Intravasculaire echografie op beeldvorming gebaseerde eindige-elementenmodelleringsbenadering voor het kwantificeren van in vivo mechanische eigenschappen van mens

Synthesis of Phase-shift Nanoemulsions with Narrow Size Distributions for Acoustic Droplet Vaporization and Bubble-enhanced Ultrasound-mediated Ablation

High-intensity focused ultrasound (HIFU) is used clinically to thermally ablate tumors. To enhance localized heating and improve thermal ablation in tumors, lipid-coated perfluorocarbon droplets have been developed which can be vaporized by HIFU. The vasculature in many tumors is abnormally leaky due to their rapid growth, and nanoparticles are able to penetrate the fenestrations and passively accumulate within tumors. Thus, controlling the size of the droplets can result in better accumulation within tumors. In this report, the preparation of stable droplets in a phase-shift nanoemulsion (PSNE) with a narrow size distribution is described. PSNE were synthesized by sonicating a lipid solution in the presence of liquid perfluorocarbon. A narrow size distribution was obtained by extruding the PSNE multiple times using filters with pore sizes of 100 or 200 nm. The size distribution was measured over a 7-day period using dynamic light scattering. Polyacrylamide hydrogels containing PSNE were prepared for in vitro experiments. PSNE droplets in the hydrogels were vaporized with ultrasound and the resulting bubbles enhanced localized heating. Vaporized PSNE enables more rapid heating and also reduces the ultrasound intensity needed for thermal ablation. Thus, PSNE is expected to enhance thermal ablation in tumors, potentially improving therapeutic outcomes of HIFU-mediated thermal ablation treatments.

Phase-shift nanoemulsions (PSNE) can be vaporized using high intensity focused ultrasound to enhance localized heating and improve thermal ablation in tumors. In this report, the preparation of stable PSNE with a narrow size distribution is described. Furthermore, the impact of vaporized PSNE on ultrasound-mediated ablation is demonstrated in tissue-mimicking phantoms.

High-intensity  focused ultrasound (HIFU) is used clinically to thermally ablate tumors. To  enhance localized heating and improve thermal ablation in ...

Concurrent Quantitative Conductivity and Mechanical Properties Measurements of Organic Photovoltaic Materials using AFM

Organic photovoltaic (OPV) materials are inherently inhomogeneous at the nanometer scale. Nanoscale inhomogeneity of OPV materials affects performance of photovoltaic devices. Thus, understanding of spatial variations in composition as well as electrical properties of OPV materials is of paramount importance for moving PV technology forward.1,2 In this paper, we describe a protocol for quantitative measurements of electrical and mechanical properties of OPV materials with sub-100 nm resolution. Currently, materials properties measurements performed using commercially available AFM-based techniques (PeakForce, conductive AFM) generally provide only qualitative information. The values for resistance as well as Young's modulus measured using our method on the prototypical ITO/PEDOT:PSS/P3HT:PC61BM system correspond well with literature data. The P3HT:PC61BM blend separates onto PC61BM-rich and P3HT-rich domains. Mechanical properties of PC61BM-rich and P3HT-rich domains are different, which allows for domain attribution on the surface of the film. Importantly, combining mechanical and electrical data allows for correlation of the domain structure on the surface of the film with electrical properties variation measured through the thickness of the film.

Organic photovoltaic (OPV) materials are inherently inhomogeneous at the nanometer scale. Nanoscale inhomogeneity of OPV materials affects performance of photovoltaic devices. In this paper, we describe a protocol for quantitative measurements of electrical and mechanical properties of OPV materials with sub-100 nm resolution.

Organic photovoltaic  (OPV) materials are inherently inhomogeneous at the nanometer scale. Nanoscale  inhomogeneity of OPV materials affects performance ...

Ultrasound Velocity Measurement in a Liquid Metal Electrode

A growing number of electrochemical technologies depend on fluid flow, and often that fluid is opaque. Measuring the flow of an opaque fluid is inherently more difficult than measuring the flow of a transparent fluid, since optical methods are not applicable. Ultrasound can be used to measure the velocity of an opaque fluid, not only at isolated points, but at hundreds or thousands of points arrayed along lines, with good temporal resolution. When applied to a liquid metal electrode, ultrasound velocimetry involves additional challenges: high temperature, chemical activity, and electrical conductivity. Here we describe the experimental apparatus and methods that overcome these challenges and allow the measurement of flow in a liquid metal electrode, as it conducts current, at operating temperature. Temperature is regulated within &#177;2 &#176;C using a Proportional-Integral-Derivative (PID) controller that powers a custom-built furnace. Chemical activity is managed by choosing vessel materials carefully and enclosing the experimental setup in an argon-filled glovebox. Finally, unintended electrical paths are carefully prevented. An automated system logs control settings and experimental measurements, using hardware trigger signals to synchronize devices. This apparatus and these methods can produce measurements that are impossible with other techniques, and allow optimization and control of electrochemical technologies like liquid metal batteries.

Ultrasound velocimetry is used to study mixing by fluid flow in liquid metal electrodes. The focus of this manuscript is to illustrate the methods used for making precise, spatially-resolved ultrasound measurements while limiting oxidation and controlling and monitoring temperature, applied current, and the heater power being supplied.

A growing number of electrochemical technologies depend on fluid flow, and often that fluid is opaque. Measuring the flow of an opaque fluid is inherently ...

Fabrication of High Contrast Gratings for the Spectrum Splitting Dispersive Element in a Concentrated Photovoltaic System

High contrast gratings are designed and fabricated and its application is proposed in a parallel spectrum splitting dispersive element that can improve the solar conversion efficiency of a concentrated photovoltaic system. The proposed system will also lower the solar cell cost in the concentrated photovoltaic system by replacing the expensive tandem solar cells with the cost-effective single junction solar cells. The structures and the parameters of high contrast gratings for the dispersive elements were numerically optimized. The large-area fabrication of high contrast gratings was experimentally demonstrated using nanoimprint lithography and dry etching. The quality of grating material and the performance of the fabricated device were both experimentally characterized. By analyzing the measurement results, the possible side effects from the fabrication processes are discussed and several methods that have the potential to improve the fabrication processes are proposed, which can help to increase the optical efficiency of the fabricated devices.

The fabrication of high contrast gratings as the parallel spectrum splitting dispersive element in a concentrated photovoltaic system is demonstrated. Fabrication processes including nanoimprint lithography, TiO2 sputtering and reactive ion etching are described. Reflectance measurement results are used to characterize the optical performance.

High contrast gratings are designed and fabricated and its application is proposed in a parallel spectrum splitting dispersive element that can improve ...

Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System

Phased arrays are increasingly used as high-intensity focused ultrasound (HIFU) transducers in the existing extracorporeal ultrasound-guided HIFU (USgHIFU) systems. The HIFU transducers in such systems are usually spherical in shape with a central hole where a US imaging probe is mounted and can be rotated. The image on the plane of treatment can be reconstructed through the image sequence acquired during the rotation of the probe. Therefore, the treatment plan can be made on the reconstructed images. In order to evaluate the targeting accuracy in the focal plane of such systems, the protocol of a method using a bovine muscle and marker-embedded phantom is described. In the phantom, four solid balls at the corners of a square resin model serve as the reference markers in the reconstructed image. The target should be moved so that both its center and the center of the square model can coincide according to their relative positions in the reconstructed image. Swine muscle with a thickness of about 30 mm is placed above the phantom to mimic the beam path in clinical settings. After sonication, the treatment plane in the phantom is scanned and the boundary of the associated lesion is extracted from the scanned image. The targeting accuracy can be evaluated by measuring the distance between the centers of target and lesion, as well as three derivative parameters. This method cannot only evaluate the targeting accuracy of the target consisting of multiple focal spots rather than a single focal spot in a clinically relevant beam path of the USgHIFU phased-array system, but it can be also used in the preclinical evaluation or regular maintenance of USgHIFU systems configured with phased-array or self-focused HIFU transducer.

This study describes a protocol to evaluate the targeting accuracy in the focal plane of an ultrasound-guided high-intensity focused ultrasound phased-array system.

Phased arrays are increasingly used as high-intensity focused ultrasound (HIFU) transducers in the existing extracorporeal ultrasound-guided HIFU ...

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction

Scientific efforts in the field of computational modeling of cardiovascular diseases have largely focused on heart failure with reduced ejection fraction (HFrEF), broadly overlooking heart failure with preserved ejection fraction (HFpEF), which has more recently become a dominant form of heart failure worldwide. Motivated by the paucity of HFpEF in silico representations, two distinct computational models are presented in this paper to simulate the hemodynamics of HFpEF resulting from left ventricular pressure overload. First, an object-oriented lumped-parameter model was developed using a numerical solver. This model is based on a zero-dimensional (0D) Windkessel-like network, which depends on the geometrical and mechanical properties of the constitutive elements and offers the advantage of low computational costs. Second, a finite element analysis (FEA) software package was utilized for the implementation of a multidimensional simulation. The FEA model combines three-dimensional (3D) multiphysics models of the electro-mechanical cardiac response, structural deformations, and fluid cavity-based hemodynamics and utilizes a simplified lumped-parameter model to define the flow exchange profiles among different fluid cavities. Through each approach, both the acute and chronic hemodynamic changes in the left ventricle and proximal vasculature resulting from pressure overload were successfully simulated. Specifically, pressure overload was modeled by reducing the orifice area of the aortic valve, while chronic remodeling was simulated by reducing the compliance of the left ventricular wall. Consistent with the scientific and clinical literature of HFpEF, results from both models show (i) an acute elevation of transaortic pressure gradient between the left ventricle and the aorta and a reduction in the stroke volume and (ii) a chronic decrease in the end-diastolic left ventricular volume, indicative of diastolic dysfunction. Finally, the FEA model demonstrates that stress in the HFpEF myocardium is remarkably higher than in the healthy heart tissue throughout the cardiac cycle.

This work introduces two computational models of heart failure with preserved ejection fraction based on a lumped-parameter approach and finite element analysis. These models are used to evaluate the changes in the hemodynamics of the left ventricle and related vasculature induced by pressure overload and diminished ventricular compliance.

Scientific efforts in the field of computational modeling of cardiovascular diseases have largely focused on heart failure with reduced ejection fraction ...

Optical Coherence Tomography Based Biomechanical Fluid-Structure Interaction Analysis of Coronary Atherosclerosis Progression

In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis as one of the leading causes of global death, morbidity and economic burden, novel ways of analyzing and predicting its progression are needed. One such computational method is the use of fluid-structure interaction (FSI) to analyze the interaction between the blood flow and artery/plaque domains. Coupled with in vivo imaging, this approach could be tailored to each patient, assisting in differentiating between stable and unstable plaques. We outline the three-dimensional reconstruction process, making use of intravascular Optical Coherence Tomography (OCT) and invasive coronary angiography (ICA). The extraction of boundary conditions for the simulation, including replicating the three-dimensional motion of the artery, is discussed before the setup and analysis is conducted in a commercial finite element solver. The procedure for describing the highly nonlinear hyperelastic properties of the artery wall and the pulsatile blood velocity/pressure is outlined along with setting up the system coupling between the two domains. We demonstrate the procedure by analyzing a non-culprit, mildly stenotic, lipid-rich plaque in a patient following myocardial infarction. Established and emerging markers related to atherosclerotic plaque progression, such as wall shear stress and local normalized helicity, respectively, are discussed and related to the structural response in the artery wall and plaque. Finally, we translate the results to potential clinical relevance, discuss limitations, and outline areas for further development. The method described in this paper shows promise for aiding in the determination of sites at risk of atherosclerotic progression and, hence, could assist in managing the significant death, morbidity, and economic burden of atherosclerosis.

There is a need to determine which atherosclerotic lesions will progress in the coronary vasculature to guide intervention before myocardial infarction occurs. This article outlines the biomechanical modeling of arteries from Optical Coherence Tomography using fluid-structure interaction techniques in a commercial finite element solver to help predict this progression.

In this paper, we present a complete workflow for the biomechanical analysis of atherosclerotic plaque in the coronary vasculature. With atherosclerosis ...

Bioengineering

In Silico Clinical Trials for Cardiovascular Disease

The SILICOFCM project mainly aims to develop a computational platform for in silico clinical trials of familial cardiomyopathies (FCMs). The unique characteristic of the platform is the integration of patient-specific biological, genetic, and clinical imaging data. The platform allows the testing and optimization of medical treatment to maximize positive therapeutic outcomes. Thus, adverse effects and drug interactions can be avoided, sudden cardiac death can be prevented, and the time between the commencement of drug treatment and the desired result can be shortened. This article presents a parametric model of the left ventricle automatically generated from patient-specific ultrasound images by applying an electromechanical model of the heart. Drug effects were prescribed through specific boundary conditions for inlet and outlet flow, ECG measurements, and calcium function for heart muscle properties. Genetic data from patients were incorporated through the material property of the ventricle wall. Apical view analysis involves segmenting the left ventricle using a previously trained U-net framework and calculating the bordering rectangle based on the length of the left ventricle in the diastolic and systolic cycle. M-mode view analysis includes bordering of the characteristic areas of the left ventricle in the M-mode view. After extracting the dimensions of the left ventricle, a finite elements mesh was generated based on mesh options, and a finite element analysis simulation was run with user-provided inlet and outlet velocities. Users can directly visualize on the platform various simulation results such as pressure-volume, pressure-strain, and myocardial work-time diagrams, as well as animations of different fields such as displacements, pressures, velocity, and shear stresses.

In Silico Clinical Trials for Cardiovascular Disease

This protocol demonstrates the workflow of the SILICOFCM platform for automatically generating a parametric model of the left ventricle from patient-specific ultrasound images by applying a multi-scale electromechanical model of the heart. This platform enables in silico clinical trials intended to reduce real clinical trials and maximize positive therapeutic outcomes.

The SILICOFCM project mainly aims to develop a computational platform for in silico clinical trials of familial cardiomyopathies (FCMs). The unique ...

4D Ultrasound and MALDI Imaging for Cardiac and Vascular Analysis in Mice

Multimodal Study of Murine Cardiovascular Remodeling: Four-Dimensional Ultrasound and Mass Spectrometry Imaging

Cardiovascular disease (CVD) is the leading cause of death in the United States. Damage in&#160;the cardiovascular system can be due to environmental exposure, trauma, drug toxicity, or numerous other factors.&#160;As a result, cardiac tissue and vasculature undergo structural changes and display diminished function. The damage and the resulting remodeling can be detected and quantified with ultrasound (US) imaging at the organ level and mass spectrometry imaging (MSI) at the molecular level. This manuscript describes an innovative methodology for studying murine cardiac pathophysiology, coupling in vivo four-dimensional (4D) ultrasound imaging and analysis with ex vivo matrix-assisted laser desorption/ionization (MADLI) MSI of the heart. 4D ultrasound can provide dynamic volumetric measurements, including radial displacement, surface area strain, and longitudinal strain throughout an entire cardiac cycle. In the vasculature, MSI and ultrasound are used to assess vessel wall compositions, hemodynamics, and vessel wall dynamics. The methodology can be tailored to study a myriad of CV diseases by adjusting functional metrics of interest and/or varying MALDI MSI protocol to target specific molecules. MALDI MSI can be used to study lipids, small metabolites, peptides, and glycans. This protocol outlines the use of MALDI MSI for untargeted lipidomic analysis and the use of ultrasound imaging for cardiovascular hemodynamics and biomechanics.

Here, we describe a protocol to use in vivo four-dimensional ultrasound imaging and ex vivo mass spectrometry imaging to assess biomechanical and biomolecular alterations in the murine cardiovascular system. This technique is applied to analyze cardiac remodeling in surgically induced myocardial infarction and vascular changes in aging animals.

Cardiovascular disease (CVD) is the leading cause of death in the United States. Damage in&#160;the cardiovascular system can be due to environmental ...

Using Digital Image Correlation to Characterize Local Strains on Vascular Tissue Specimens

Characterization of the mechanical behavior of biological and engineered soft tissues is a central component of fundamental biomedical research and product development. Stress-strain relationships are typically obtained from mechanical testing data to enable comparative assessment among samples and in some cases identification of constitutive mechanical properties. However, errors may be introduced through the use of average strain measures, as significant heterogeneity in the strain field may result from geometrical non-uniformity of the sample and stress concentrations induced by mounting/gripping of soft tissues within the test system. When strain field heterogeneity is significant, accurate assessment of the sample mechanical response requires measurement of local strains. This study demonstrates a novel biomechanical testing protocol for calculating local surface strains using a mechanical testing device coupled with a high resolution camera and a digital image correlation technique. A series of sample surface images are acquired and then analyzed to quantify the local surface strain of a vascular tissue specimen subjected to ramped uniaxial loading. This approach can improve accuracy in experimental vascular biomechanics and has potential for broader use among other native soft tissues, engineered soft tissues, and soft hydrogel/polymeric materials. In the video, we demonstrate how to set up the system components and perform a complete experiment on native vascular tissue.

We describe the use of digital image correlation to characterize the local surface strain field on vascular tissue samples subjected to uniaxial tensile testing. These measurements facilitate precise quantification of the sample mechanical response and the generation of constitutive stress-strain relations.

Characterization of the mechanical behavior of biological and engineered soft tissues is a central component of fundamental biomedical research and ...

Intravascular Ultrasound Image-Based Finite Element Modeling Approach for Quantifying In Vivo Mechanical Properties of Human Coronary Artery

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