Myocardial Strain Software Application by Circle Cardiovascular Imaging

The Myocardial Strain Software Application is intended for qualitative and quantitative evaluation of cardiovascular magnetic resonance (CMR) images. It provides measurements of 2D LV myocardial function (displacement, velocity, strain rate, time to peak, and torsion); these measurements are used by qualified medical professionals, experienced in examining and evaluating CMR images, for the purpose of obtaining diagnostic information for patients with suspected heart disease as part of a comprehensive diagnostic decision-making process.

Device Description

Circle's Myocardial Strain Software Application (Strain Module) is a software device that enables the analysis of CMR images acquired using SSFP cine imaging. It is designed to support physicians in the visualization, evaluation, and analysis of myocardial tissue deformation through CMR feature tracking. The device is intended to be used as an aid to the existing standard of care and does not replace existing software applications that physicians use. The Strain Module can be integrated into an image viewing software intended for visualization of cardiac images, such as Circle's FDA-cleared cvi42 software. The Strain Module does not interface directly with any data collection equipment, and its functionality is independent of the type of vendor acquisition equipment. The analysis results are available on-screen or can be saved for future review.

The Strain Module implements an algorithm for deformations modeling of topologies that relies on a two-dimensional (2D) version of the nearly incompressible deformable model. The deformation of the model is assumed to be completely determined by a set of control points placed on the middle curve of the myocardial wall; these points are first defined by the end-user in a reference phase, and then detected in all other phases based on the feature tracked boundaries and incompressibility constraint of the model. Once this feature tracking is complete, the Strain Module computes and reports various global and regional deformation quantities such as strains (including Global Longitudinal Strain (GLS) and Global Circumferential Strain (GCS)), strain rates, displacements, velocities, and torsion. These measurements of myocardial deformation can be made, as appropriate, in the radial, circumferential, or longitudinal directions.

AI/ML Overview

The provided text describes the Myocardial Strain Software Application (Strain Module) and its performance data, particularly in the context of its 510(k) submission to the FDA. However, it does not contain a specific table of acceptance criteria or a detailed breakdown of the study results that would allow for direct comparison for each criterion. It mentions that performance testing was conducted and references a Master Software Test Plan, but the actual, quantifiable acceptance criteria and the device's reported performance against them are not explicitly stated in the provided document.

Despite the lack of a direct table, I can extract and infer information about the validation and testing performed:

1. Table of Acceptance Criteria and Reported Device Performance:

As noted above, a specific table of acceptance criteria with corresponding performance metrics is not provided in the document. The text indicates that "Performance testing was conducted to verify compliance with specified design requirements" and that "The tracking performance and the clinically relevant Global Longitudinal and Global Circumferential strains were validated." It also mentions evaluation using "simple analytical phantoms" and "realistic phantoms with artificially imposed known deformation field and perturbations." This suggests that acceptance criteria would involve accuracy and precision for tracking performance and strain measurements, but the quantitative thresholds are not given.

The document states: "The computation of the deformation metrics from the tracked deformations were evaluated analytically." This implies that for certain computations, the device's output was compared to known mathematical solutions, and presumably met these.

2. Sample Size Used for the Test Set and Data Provenance:

Test Set Sample Size: Not explicitly stated as a number of cases or images. The text mentions "a combination of simple and realistic phantoms, real MRI data, and analytical solutions." It highlights that "the performance of the constrained tissue tracking algorithm was also compared to manual tracking in ES phase by three expert readers." This implies that at least some "real MRI data" was used.
Data Provenance: Not specified in terms of country of origin. The document mentions "real MRI data," which could be retrospective or prospective, but this detail is not provided.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:

Number of Experts: "three expert readers."
Qualifications: "expert readers" – specific qualifications (e.g., years of experience, subspecialty) are not detailed in the provided text.

4. Adjudication Method for the Test Set:

The document states that the algorithm's performance "was also compared to manual tracking in ES phase by three expert readers." This suggests a comparison against individual expert readings rather than a consensus ground truth that required an adjudication method like 2+1 or 3+1. It doesn't describe a formal adjudication process for establishing a single ground truth from the three experts, but rather a comparison for validation.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No MRMC comparative effectiveness study was mentioned. The study described focuses on technical performance validation rather than human-in-the-loop performance improvement. The document explicitly states: "No clinical studies were necessary to support substantial equivalence."

6. Standalone (Algorithm-Only) Performance:

Yes, a standalone performance assessment was conducted. The validation section describes evaluating "tracking performance," deformation fields on phantoms, and comparing the algorithm's output to manual tracking performed by experts. This indicates an assessment of the algorithm's performance independent of real-time human assistance in a diagnostic workflow.

7. Type of Ground Truth Used:

For phantoms: "artificially imposed known deformation field" and "simple analytical phantoms generated with variable input parameters," and computations "evaluated analytically." This indicates a synthetic/mathematical ground truth.
For real MRI data: "manual tracking in ES phase by three expert readers." This implies an expert-derived or expert-consensus ground truth, though the consensus method among the three experts is not detailed as noted in point 4.

8. Sample Size for the Training Set:

The document explicitly states that the Strain Module "does not involve any artificial intelligence (AI) or machine learning (ML)." Therefore, there is no training set in the traditional sense of machine learning, as the algorithm relies on a "purely mathematical" model for feature tracking and deformation quantity computation.

9. How Ground Truth for the Training Set Was Established:

As there is no AI/ML component described, the concept of a training set and its associated ground truth establishment is not applicable to this device as per the provided information. The algorithm's basis is described as a "two-dimensional (2D) version of the nearly incompressible deformable model," which indicates a model-based, rather than data-driven (learning-based), approach.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath.

Circle Cardiovascular Imaging % Sydney Toutant Regulatory Affairs Manager Suite 110 - 800 5th Ave SW Calgary, AB T2P 3T6 Canada

Re: K232661

December 7, 2023

Trade/Device Name: Myocardial Strain Software Application Regulation Number: 21 CFR 892.2050 Regulation Name: Medical image management and processing system Regulatory Class: Class II Product Code: LLZ Dated: November 10, 2023 Received: November 13, 2023

Dear Sydney Toutant:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Jessica Lamb

Jessica Lamb. Ph.D. Assistant Director DHT8B: Division of Radiological Imaging Devices and Electronic Products OHT8: Office of Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

Submission Number (if known)

K232661

Device Name

Myocardial Strain Software Application

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/4/Picture/2 description: The image contains the logo for Circle Cardiovascular Imaging. The logo features a stylized green circle that is not fully closed, with a lighter green gradient towards the inside of the circle. Below the circle is the word "circle" in a gray, sans-serif font, and below that is the phrase "CARDIOVASCULAR IMAGING" in a smaller, sans-serif font, also in gray.

The following 510(k) summary of safety and effectiveness information is submitted in accordance with the requirements of the Safe Medical Device Act 1990 and 21 CFR 807.92(c).

l. SUBMITTER

Submitter's Name:	Circle Cardiovascular Imaging, Inc.
Address:	Suite 1100 – 800 5th Ave SW, Calgary, AB, Canada, T2P 3T6
Date Prepared:	August 31 2023
Telephone Number:	+1 587 747 4692
Contact Person :	Sydney Toutant
Email:	sydney.toutant@circlecvi.com

II. DEVICE

Name of the Device:	Myocardial Strain Software Application
Short Brand Name:	Strain Module
Common or Usual Name:	Radiological Image Processing System
Classification Name:	Medical image management and processing system
Proposed Classification:	Device Class: IIProduct Code: LLZRegulation Number: 21 CFR 892.2050

lll. PREDICATE DEVICE

The predicate device is 2D Cardiac Performance Analysis MR 1.0 (2D CPA MR) manufactured by TomTec Imaging Systems GmbH and cleared under K120135.

The predicate device has not been subject to a design-related recall.

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IV. DEVICE DESCRIPTION

The device allows users to perform the measurements listed in Table 1.

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Table 1. Measurements in the Strain Module
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Measurement [units]	Description	Workflow	Application
Strain [%]	In general, myocardial strain is a measure of the deformation inshape and dimension of the heart muscle during the cardiaccycle. Mathematically Circle uses the Lagrangian strain tensorand measures the deformation with respect to the reference (enddiastole) phase. The radial, circumferential and longitudinalstrains are defined as the strain tensor evaluated in the radial,circumferential and longitudinal directions on the appropriate SAXor LAX slices (in 2D), respectively.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• This measurement for the globalmyocardium, or specific regions ofmyocardium, can be represented overtime by Strain Curves.• Strain is also presented as an ImageOverlay.
Peak Strain [%]	The maximum of the strain in absolute value, over the wholecardiac cycle.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• This measurement, on a regional basis,can be visualized and reported in PolarMaps.Note: Global peak circumferential strainand global peak longitudinal strain canbe added by the user to the clinicalreport.
Time to Peak Strain [ms]	Trigger time elapsed from the first phase till the phase where thepeak strain has been reached.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Strain Rate [1/s]	Derivative of the strain with respect to time.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Strain Curves, as above.
Peak Systolic Strain Rate[1/s]	The maximum of the strain rate in absolute value over all phasesstarting from the end systole till the next diastole.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Peak Diastolic Strain Rate[1/s]	The maximum of the strain rate in absolute value over all phasesstarting from the end diastole till the next systole.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Displacement[mm or degree]	The displacement vector represents the position of a point withrespect to the position of that point in the reference (end diastole)phase. The radial (both SAX and LAX) and longitudinal (LAX)	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal	• Strain Curves, as above.Displacement is also presented as anImage Overlay.

	displacements are expressed in mm and the circumferential(SAX) displacement is presented in degree.	• LAX-Radial
Peak Displacement [mm ordegree]	The maximum of the displacement in absolute value, over thewhole cardiac cycle (expressed in mm for radial and longitudinal,and in degree for circumferential displacements).	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Time to Peak Displacement [ms]	Trigger time elapsed from the first phase till the phase where thepeak displacement has been reached.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Velocity [mm/s or degree/s]	Derivative of the displacement with respect to time (expressed inmm/s or degree/s, as appropriate). The circumferential velocityrepresents an angular velocity.	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Strain Curves, as above.
Peak Systolic Velocity [mm/s ordegree/s]	The maximum of the velocity in absolute value over all phasesstarting from the end diastole till the next systole (expressed inmm/s or degree/s, as appropriate).	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Peak Diastolic Velocity [mm/s ordegree/s]	The maximum of the velocity in absolute value over all phasesstarting from the end systole till the next end diastole (expressedin mm/s or degree/s, as appropriate).	• SAX-Circumferential• SAX-Radial• LAX-Longitudinal• LAX-Radial	• Polar Maps, as above.
Torsion [deg/cm]	The difference in rotation between the apical and basal slicesdivided by the distance between apical and basal slices. Note thatcircumferential displacement represents an angle.	• SAX-Circumferential	• Strain Curves, as above.
Torsion Rate [deg/(cm*s)]	The difference in rotational velocity between apical and basalslices divided by the distance between the apical and basalslices. Note that circumferential velocity represents an angularvelocity.	• SAX-Circumferential	• Strain Curves, as above.

Circle Cardiovascular Imaging Inc.

Non-Confidential

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V. INTENDED USE / INDICATIONS FOR USE

Intended Use

The Myocardial Strain Software Application is intended for qualitative and quantitative evaluation of cardiovascular MR images in a DICOM Standard format. As prerequisite, the user confirms endocardial and epicardial contours in a reference phase, and the software tracks features over the cardiac cycle and computes 2D myocardial deformation and movement (e.g., strain, displacement, velocity).

Indications for Use

The Myocardial Strain Software Application is intended for qualitative evaluation of cardiovascular magnetic resonance (CMR) images. It provides measurements of 2D LV myocardial function (displacement, velocity, strain rate, time to peak, and torsion); these measurements are used by qualified medical professionals, experienced in examining and evaluating CMR images, for the purpose of obtaining diagnostic information for patients with suspected heart disease as part of a comprehensive diagnostic decision-making process.

VI. COMPARISON WITH PREDICATE DEVICE

The detailed analysis of the subject device and the predicate device (shown in Table 2 and Table 3) demonstrates that the subject device is substantially equivalent in indications for use / intended use, technological characteristics, functionality, and operating principles with the predicate (K120135). Of the three characteristics (technical, biological, and clinical) required for the demonstration of equivalence, biological characteristics are not applicable since both the subject device and predicate device are software as a medical device applications with no tangible component interfacing with the body.

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	Subject Device	Predicate Device
	Strain Module	2D CPA MR (K120135)
	Manufactured by Circle	Manufactured by TomTec
IntendedUse	The Myocardial Strain Software Application is intendedfor qualitative and quantitative evaluation ofcardiovascular MR images in a DICOM Standardformat. As prerequisite, the user confirms endocardialand epicardial contours in a reference phase, and thesoftware tracks features over the cardiac cycle andcomputes 2D myocardial deformation and movement	2D CPA MR software is intended for quantification ofthe myocardial deformation (strain) and movement(displacement / velocity) for digital magneticresonance images. Possible quantification results arevelocity, displacement, strain, strain rate, time-to-peakand phase.
	(e.g., strain, displacement, velocity).	Prerequisite is to draw a contour (endocard orendocard and epicard) in a digital magnetic resonanceimage. Based on this manual drawn contour, the SWcalculates with a tracking algorithm the borders'displacement.
Indicationsfor Use	The Myocardial Strain Software Application is intendedfor qualitative and quantitative evaluation ofcardiovascular magnetic resonance (CMR) images. Itprovides measurements of 2D LV myocardial function(displacement, velocity, strain, strain rate, time topeak, and torsion); these measurements are used byqualified medical professionals, experienced inexamining and evaluating CMR images, for thepurpose of obtaining diagnostic information forpatients with suspected heart disease as part of acomprehensive diagnostic decision-making process.	2D Cardiac Performance Analysis is intended forcardiac quantification based on magnetic resonanceimages. It provides measurements of myocardialfunction (displacement, velocity, strain, strain rate) thatis used for diagnostic purposes of patients withsuspected heart disease.

Table 2. Intended use and indications comparison.

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Feature	Subject Device	Predicate Device
	Strain ModuleManufactured by Circle	2D CPA MR (K120135)Manufactured by TomTec
Device Class	II	II
Product Code	LLZ	LLZ
Regulation Name	Medical image management andprocessing system	Picture Archiving and CommunicationsSystem
Regulation Number	21 CFR 892.2050	21 CFR 892.2050
DICOM Compliant?	Yes	Yes
Input Data Type	cine MR images(vendor independent)	cine MR images(vendor independent)
Prerequisites	Endocardial and epicardial contours inreference phase(s).	Contours (endocardial, or endocardial andepicardial) in a digital magnetic resonanceimage
Myocardial deformationassessment technique	Feature tracking (FT)	Feature tracking (FT)
Comprehensive functionalassessment of myocardial function	Yes	Yes
2D functional analysis ofmyocardial deformation	Yes	Yes
Express parameters in theirspatial directions (e.g.,circumferential, longitudinal radial)	Yes	Yes
Overlay of tracked contour andgraphical displays for measuredparameters	Yes	Yes
Myocardial Function Global andRegional Measurements	Displacement Velocity Strain Strain Rate Time to Peak Torsion	Displacement Velocity Strain Strain Rate Time to Peak
Operating System	Microsoft WindowsApple macOS	Microsoft Windows

Table 3. Requlatory and technological features comparison

VII. PERFORMANCE DATA AND TESTING

Performance testing was conducted to verify compliance with specified design requirements in accordance with ISO 13485:2016, IEC 62304:2015, ISO 14971:2019, and DICOM standards.

Verification and validation testing were conducted to ensure specifications and performance of the device and were performed per the FDA Guidance "Technical Performance Assessment of Quantitative Imaging in Radiological Device Premarket Submission". No clinical studies were necessary to support substantial equivalence.

Strain Module has been tested according to the specifications that are documented in a Master Software Test Plan. Testing is an integral part of Circle Cardiovascular Imaging Inc.'s software development as described in the company's product development process.

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Validation of Outputs

The tracking performance and the clinically relevant Global Longitudinal and Global Circumferential strains were validated using a complination of simple and realistic phantoms, real MRI data, and analytical solutions. The tracking performance was evaluated with simple analytical phantoms generated with variable input parameters; the deformation field generated by the strain module was evaluated on realistic phantoms with artificially imposed known deformation field and perturbations; and the performance of the constrained tissue tracking algorithm was also compared to manual tracking in ES phase by three expert readers. The computation of the deformation metrics from the tracked deformations were evaluated analytically.

VIII. CONCLUSION

The information submitted in this premarket notification, including the performance testing and predicate device comparison, support the safety and effectiveness of Strain Module as compared to the predicate device when used for the defined intended use.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).