This work was supported by NIH grant R01ES029967.

This study was conducted with approval of the Mount Sinai Institutional Review Board (HS-20-01011), and all subjects gave written informed consent.
1. Preparation before starting the protocol
<ol>
	<li>Appropriate folder structure is necessary for this program. Start by creating a main folder for the project anywhere on the computer by right-clicking and selecting the New Folder option in the files directory. All input DICOM files and results will be stored ...

Improving Coronary Artery Calcification Assessment with the SWCS Tool

<ol>
	<li>O'Malley, P. G., Taylor, A. J., Jackson, J. L., Doherty, T. M., Detrano, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prognostic+value+of+coronary+electron-bean+computed+tomography+for+coronary+heart+disease+events+in+asymptomatic+populations.">Prognostic value of coronary electron-bean computed tomography for coronary heart disease events in asymptomatic populations.</a> The American Journal of Cardiology. 85 (8), 945-948 (2000).</li><li>Budoff, M. 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=Assessment+of+coronary+artery+disease+by+cardiac+computed+tomography.">Assessment of coronary artery disease by cardiac computed tomography.</a> Circulation. 114 (16), 1761-1791 (2006).</li><li>Rumberger, J. A., Simons, D. B., Fitzpatrick, L. A., Sheedy, P. F., Schwartz, R. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+artery+calcium+area+by+electron-beam+computed+tomography+and+coronary+atherosclerotic+plaque+area.">Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area.</a> Circulation. 92 (8), 2157-2162 (1995).</li><li>Mautner, G. 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=Coronary+artery+calcification:+assessment+with+electron+beam+CT+and+histomorphometric+correlation.">Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation.</a> Radiology. 192 (3), 619-623 (1994).</li><li>Agatston, A. 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=Quantification+of+coronary+artery+calcium+using+ultrafast+computed+tomography.">Quantification of coronary artery calcium using ultrafast computed tomography.</a> Journal of the American College of Cardiology. 15 (4), 827-832 (1990).</li><li>Shea, 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=Spatially+weighted+coronary+artery+calcium+score+and+coronary+heart+disease+events+in+the+multi-ethnic+study+of+atherosclerosis.">Spatially weighted coronary artery calcium score and coronary heart disease events in the multi-ethnic study of atherosclerosis.</a> Circulation: Cardiovascular Imaging. 14 (1), e011981 (2021).</li><li>Liang, C. J., Budoff, M. J., Kaufman, J. D., Kronmal, R. A., Brown, E. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+alternative+method+for+quantifying+coronary+artery+calcification:+the+multi-ethnic+study+of+atherosclerosis+(MESA).">An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).</a> BMC Medical Imaging. 12, 14 (2012).</li><li>McCollough, C. 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=Coronary+artery+calcium:+a+multi-institutional,+multimanufacturer+international+standard+for+quantification+at+cardiac+CT.">Coronary artery calcium: a multi-institutional, multimanufacturer international standard for quantification at cardiac CT.</a> Radiology. 243 (2), 527-538 (2007).</li><li>Detrano, 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=Coronary+calcium+as+a+predictor+of+coronary+events+in+four+racial+or+ethnic+groups.">Coronary calcium as a predictor of coronary events in four racial or ethnic groups.</a> The New England Journal of Medicine. 358 (13), 1336-1345 (2008).</li><li>Budoff, 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=Cardiovascular+events+with+absent+or+minimal+coronary+calcification:+The+Multi-Ethnic+Study+of+Atherosclerosis+(MESA).">Cardiovascular events with absent or minimal coronary calcification: The Multi-Ethnic Study of Atherosclerosis (MESA).</a> American Heart Journal. 158 (4), 554-561 (2009).</li><li>Hecht, H. 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=2016+SCCT/STR+guidelines+for+coronary+artery+calcium+scoring+of+noncontrast+noncardiac+chest+CT+scans:+A+report+of+the+Society+of+Cardiovascular+Computed+Tomography+and+Society+of+Thoracic+Radiology.">2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: A report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology.</a> Journal of Cardiovascular Computed Tomography. 11 (1), 74-84 (2017).</li><li>American College of Radiology. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ACR-NASCI-SPR+practice+parameter+for+the+performance+and+interpretation+of+cardiac+computed+tomography+(CT).">ACR-NASCI-SPR practice parameter for the performance and interpretation of cardiac computed tomography (CT).</a> American College of Radiology. , (2021).</li></ol>

While the protocol for this program is relatively easy to follow, there are a few critical steps that are necessary for successful use and reliable results. Before starting, it is important to make sure the patient data that will be used in this program is anonymized to ensure patient confidentiality. The initial formatting and naming of the project's main folder must be correct for the program to recognize where to pull and place data. Incorrect naming and/or placement of folders, especially the Meta_Data folder, leads ...

Measuring the amount of calcium within arteries using computed tomography (CT) is an established way to assess the severity of coronary atherosclerosis. Knowing and quantifying the extent of atherosclerosis is key to determining the risk of future coronary heart disease1,2,3,4. The most common way of measuring calcium in the coronary arteries is using the Agatston score5. However, part of the Agatston score calculation relies on the intensity of the chosen pixels, measured in Hounsfield Units (HU). Any pixels less than 130 HU are not accounted for in the calculation. Similarly, calcifications with an area less than 1 mm2 are not considered. Due to these thresholds, the Agatston score is not sensitive to small, weakly attenuating foci of calcification, which may still be important in revealing the presence of subclinical disease6.
A previously described metric called the spatially weighted calcium score (SWCS) was proposed to assess the risk of atherosclerotic plaque in patients with low levels of calcification7. Unlike the Agatston score, the SWCS does not use signal thresholding to reduce the impact of image noise. Instead, it makes use of a phantom-an object with known concentrations of calcium hydroxyapatite (CHA) placed on the participant such that it is in the scan&#39;s field of view. Here, a phantom with 0 mg/mL, 50 mg/mL, 100 mg/mL, and 200 mg/mL CHA was used during development; however, in the current implementation of the graphical tool, only the 0 mg/mL and 100 mg/mL sections are required. The phantom is used to create a scan-specific weighting function, which is then used to weigh each of the user-selected pixels as well as its neighbors. Pixels with neighboring pixels that have a high attenuation level are given more weight than ones surrounded by pixels with lower attenuation levels. This process makes the SWCS tolerant to noise and comparable from scan to scan8. The SWCS is continuous and produces a score even when there are low levels of calcification, allowing for quantification of the extent of atherosclerosis when the Agatston score is zero. By allowing the evaluation of micro-calcification even when the Agatston score is zero, the SWCS may be important in revealing the presence of subclinical disease. This may allow a better understanding of the genetic, environmental, and other risk factors in atherosclerosis9,10. A previous study, which examined individuals with an Agatston score of zero at baseline and non-zero at a follow-up approximately 15 years later, observed that those with a higher SWCS at baseline had a higher coronary heart disease (CHD) event rate. The predictive power of the SWCS is especially important in younger populations, where the detection and monitoring of residual risk over a long term may be helpful6.
Presented here is a semi-automatic tool for calculating the SWCS along with the Agatston score. The tool utilizes a graphical user interface running on a compatible programming language. The user is able to interact with the images to generate a final series of reports, which include the two calcium scores. To start, the user selects a case, or a series of Digital Imaging and Communications in Medicine (DICOM) files, to input into the program. These images must be breath-held, electrocardiogram-gated CT scans, acquired only during diastole to avoid respiratory and cardiac motion. While the program is operational with any cardiac CT images, to produce meaningful results, the source images should meet the minimum clinical calcium scoring guidelines11,12. For reference, a slice thickness of 3 mm, peak tube voltage of 100 kVp, average CT dose index-vol of 1.19 mGy, and image resolution of 512 x 512 pixels are used in the study here. Any images that are not 512 x 512 pixels are resampled in the program automatically to ensure adequate and consistent resolution of small areas of calcification. Once the images are loaded, the user is able to see them in the axial, sagittal, and coronal views. One may then adjust the brightness and contrast of the images for better visualization before selecting the 0 mg/mL and 100 mg/mL sections of the phantom. Next, the user can trace each of the four coronary arteries-left anterior descending (LAD), left coronary artery (LCA), left circumflex (LCX), and right coronary artery (RCA)-by placing either a point, a region of interest (ROI), or a combination of both to allow for a thorough selection of an artery&#39;s pixels regardless of how the artery appears in the axial plane. The user may delete and replace or redraw points and ROIs as needed. Clicking the SWCS button generates the final reports. Cases are auto-saved so that images, along with the points and ROIs, can be reloaded at a later time. Written instructions are also available at every point while using the program, making the program easy to use.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Calcium Hydroxyapatite</td>
			<td>Sigma-Aldrich</td>
			<td>289396-100G</td>
			<td>Suspended in EpoxAcast 690 resin for phantom creation</td>
		</tr>
		<tr>
			<td>Clinical Cardiac CT Scanner</td>
			<td>Siemens</td>
			<td>SOMATOM Force Dual Source CT</td>
			<td>Used for the source images; Any cardiac CT will be sufficient</td>
		</tr>
		<tr>
			<td>EpoxAcast 690</td>
			<td>Smooth-On</td>
			<td>03641</td>
			<td>Used for phantom creation</td>
		</tr>
		<tr>
			<td>MATLAB</td>
			<td>Mathworks</td>
			<td>R2019a</td>
			<td>Requires Image Processing Toolbox and Statistics and Machine Learning Toolbox; Any version compatible with and able to run version R2019a scripts is sufficient</td>
		</tr>
		<tr>
			<td>Standard Computer</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>macOS or Windows operating system</td>
		</tr>
		<tr>
			<td>syngo.via</td>
			<td>Siemens</td>
			<td>VB60A_HF04</td>
			<td>Commercial software used for computing Agatston score for validation study</td>
		</tr>
	</tbody>
</table>

semi-automatic graphical tool for measuring coronary artery spatially weighted calcium score from gated cardiac computed tomography images

The current standard for measuring coronary artery calcification to determine the extent of atherosclerosis is by calculating the Agatston score from computed tomography (CT). However, the Agatston score disregards pixel values less than 130 Hounsfield Units (HU) and calcium regions less than 1 mm2. Due to this thresholding, the score is not sensitive to small, weakly attenuating regions of calcium deposition and may not detect nascent micro-calcification. A recently proposed metric called the spatially weighted calcium score (SWCS) also utilizes CT but does not include a threshold for HU and does not require elevated signals in contiguous pixels. Thus, the SWCS is sensitive to weakly attenuating, smaller calcium deposits and may improve the measurement of coronary heart disease risk. Currently, the SWCS is underutilized owing to the added computational complexity. To promote translation of the SWCS into clinical research and reliable, repeatable computation of the score, the aim of this study was to develop a semi-automatic graphical tool that calculates both the SWCS and the Agatston score. The program requires gated cardiac CT scans with a calcium hydroxyapatite phantom in the field of view. The phantom allows for deriving a weighting function, from which each pixel&#39;s weight is adjusted, allowing for the mitigation of signal variations and variability between scans. With all three anatomical views visible simultaneously, the user traces the course of the four main coronary arteries by placing points or regions of interest. Features such as scroll-to-zoom, double-click to delete, and brightness/contrast adjustment, along with written guidance at every step, make the program user-friendly and easy to use. Once tracing the arteries is complete, the program generates reports, which include the scores and snapshots of any visible calcium. The SWCS may reveal the presence of subclinical disease, which may be used for early intervention and lifestyle changes.

Author Spotlight: Advancing Cardiovascular Imaging - Introducing the Spatially Weighted Calcium Score for Early Disease Detection 

Semi-Automatic Graphical Tool for Measuring Coronary Artery Spatially Weighted Calcium Score from Gated Cardiac Computed Tomography Images

The mission of the Biomedical Engineering and Imaging Institute is to create innovative biomedical engineering and imaging technologies that can be utilized in medical science and clinical practice. The goal is to identify and develop techniques for early and accurate diagnosis of diseases, which can then be useful in optimizing more effective treatments. Our cardiovascular imaging group concentrates on image acquisition and analysis techniques for MRI, PET, and CT imaging.CT imaging can be used to measure calcification and determine the severity of coronary artery disease without invasive procedures. The Agatston score is the most commonly used method for calcium scoring, but it relies on signal thresholds, which can cause early stages of the disease to be missed due to small lowly attenuating deposits not being detectable above image noise. Dr.Jason Liang and his colleagues at the University of Washington developed the idea of the spatially weighted calcium score.However, at present, there are no reliable and consistent tools to compute the score. We have created a program that offers researchers the ability to calculate it accurately and repeatedly. The spatially weighted calcium score is designed to be sensitive to detect micro-calcification, which occurs before advanced coronary calcification can be detected by traditional calcium scoring CT scans.That sensitivity is significant in identifying subclinical coronary artery disease and by providing quantitative data, which can be useful when assessing novel risk factors like metal exposure from e-cigarettes, evaluating modifiable risks in younger populations, and exploring the impact of interventions. The immediate application of this work is to examine the relationship between coronary artery calcification and exposure to toxic metals from use of e-cigarettes. This project is funded by NIH and led by Professor Ana Navas-Acien at Columbia University.

The representative results shown in this section display what successful use of the program entails. Here, a patient with an Agatston score greater than zero is used as an example. As discussed earlier, the results within a patient&#39;s metadata folder will have spreadsheets in the form of CSV files, images in the form of PNG files, and reports in the form of PDF files, as shown in Figure 5. The number of PNG files differs from case to case, since only snapshots of selected pixels with noti...

Watch this Scientific Journal Video about Advancing Cardiovascular Imaging - Introducing the Spatially Weighted Calcium Score for Early Disease Detection at JoVE.com

This video demonstrates the use of a novel graphical tool for measuring the spatially weighted calcium score (SWCS), an alternative to the Agatston score, for quantifying coronary artery calcification. The graphical tool computes SWCS based on image data from gated cardiac computed tomography and user-defined paths of the coronary arteries.

The current standard for measuring coronary artery calcification to determine the extent of atherosclerosis is by calculating the Agatston score from ...

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Research

JoVE Journal

Bioengineering

Measuring Coronary Artery Spatially Weighted Calcium Score for Quantifying Coronary Artery Calcification

To begin, create the appropriate folder structure for the protocol. Navigate to the project's main folder and locate the program file. Double-click on the file to launch the software and display the program's code.To launch the program, click anywhere on the editor window and click the green Run button on the top ribbon of the Editor tab. Click the open DICOM button in the bottom left corner to access the files directory. Navigate to the main project folder and find the original data.Select the patient's folder to be analyzed and click Open. The images in axial, sagittal, and coronal views will appear on the screen. To examine the slices in a specific view, hover and scroll over them.Use the crosshairs to display the location of the pointer at that moment. Using the sliders found in the bottom right corner of the program, adjust the brightness and contrast of the image. To analyze the coronary artery calcification, click the zero milligrams per milliliter phantom button.Hover over the axial view and scroll until the zero milligrams per milliliter section of the phantom is visible. Position the cursor at the zero milligrams per milliliter phantom midpoint in the axial view. Observe the crosshairs in the sagittal and coronal views without moving the cursor.Scroll through several slices until the crosshairs in the three views are centered on the zero milligrams per milliliter phantom. To generate a red cluster of circles in the axial view and a column of three points in the sagittal and coronal views, place a 10 by 10 point grid on the current and adjacent slices. If a phantom is unavailable or of poor quality, select the No Phantom button to use an aggregation of 10 sample phantoms and their corresponding weighting functions.Then select an artery button to start tracing each of the four coronary arteries. Hover over the axial view. Scroll to navigate to either the proximal or distal end of the chosen artery and observe the shape of the artery in the slice.To mark a circular artery, click on its center in the axial view and a five millimeter diameter point will appear, which will also be visible in the sagittal and coronal views. If the artery is more visible in the sagittal or coronal views, place a point there ensuring it aligns with the artery's center in the axial view. Quickly double-click in any of the three views to delete the suboptimal placed points.Observe the bottom left area for a notification confirming the points deletion. If the shape of the artery is not circular in the axial plane, ensure the desired axial slice is in view and click the Draw ROI button. In the popup window, scroll to zoom in or out, and start tracing around the artery with single clicks.To delete the previous point in the artery tracing, use the Backspace key while the ROI is open and close the ROI by double-clicking on the last or first point placed. Refine the closed ROI by dragging its perimeter points or double-clicking on the perimeter to add a point. Then lock in and redraw the ROI will appear at the bottom of the popup window.Once satisfied with the current ROI, click the Lock-in button and close the pop-up window using the red button in the top left corner. To delete a locked-in ROI, double-click any perimeter points in the axial view of the main program window. Scroll through one slice in the axial view and repeat the procedure until the end of the chosen artery is reached.After completing the tracing, re-click on the Arteries button to ensure no accidental points were placed. After tracing all four arteries, click the SWCS button in the bottom right corner to generate results. The bottom left area will show the progress and display Done Processing when finished.Close the program window by clicking the red button. To access the results, open the files directory, navigate to the project's main folder and enter the metadata folder. Look for a folder with the same name as the original folder for the subject and find the file in the desired format.Review the PDFs to obtain the final SWCS and Agatston score for the case and the weighting function used. The percentage difference between the Agatston score obtained from the program versus the commercial software is presented using the Bland-Altman plot.

703 Views.  Icahn School of Medicine at Mount Sinai.  This video demonstrates the use of a novel graphical tool for measuring the spatially weighted calcium score (SWCS), an alternative to the Agatston score, for quantifying coronary artery calcification. The graphical tool computes SWCS based on image data from gated cardiac computed tomography and user-defined paths of the coronary arteries. 

Improving Coronary Artery Calcification Assessment with the SWCS Tool

Summary