The Emory Cardiac Toolbox™ 4.0 – 4.3 software program should be used for the quantification of myocardial perfusion for the display of wall motion and quantification of left-ventricular function parameters from SPECT & PET myocardial perfusion studies (EGS™) including to quantitatively evaluate the wall motion and wall thickening of the heart using longitudinal, radial, and circumferential strain measurements, for the 3D alignment of coronary artery models from CT coronary angiography onto the left ventricular 3D epicardial surface and analysis of the CT data to evaluate calcified plaques in the coronary arteries, for the assessment of cardiac mechanical dyssynchrony using phase analysis, for generation of the short axis, vertical, and horizontal long axis tomograms from the SPECT raw data using either filtered back projection (FBP) or iterative reconstruction (MLEM/OSEM), for the quantification of myocardial blood flow and coronary flow reserve, and for the decision support in interpretation (LVX) and automatic structured reporting of the study.

Device Description

The Emory Cardiac Toolbox™ 4.3 is used to display gated wall motion and for quantifying parameters of left-ventricular perfusion and function from gated SPECT & PET myocardial perfusion studies and for the evaluation of dynamic PET studies.

AI/ML Overview

The Emory Cardiac Toolbox™ 4.3 device's performance validation is described in section 8 of the provided document. The device includes two main new features: Emory-CACS for calcium plaque evaluation and ECTb™ Strain for wall motion and thickening analysis using strain measurements.

Here's a breakdown of the acceptance criteria and study details for each feature:

1. Table of acceptance criteria and reported device performance:

Feature	Acceptance Criteria (Proxy)	Reported Device Performance
Emory-CACS	High correlation with the predicate device (Siemens SyngoVia™ toolbox) for both plaque volume and Agatston score. (Implied: r² > 0.99 for both based on predicate's performance)	Plaque Volume: Linear regression (m = 1.10; b = 0.46) produced an r² = 0.99. Agatston Score: Linear regression (m = 1.01; b = 1.06) produced an r² > 0.99. "The values obtained by the Emory-CACS module demonstrated excellent correlations with the Syngo.CT CaScoring developed by Siemens Medical Solutions."
ECTb™ Strain Analysis	Establish normal limits for longitudinal, radial, and circumferential strains from a low-risk cohort. Demonstrate strong correlation between PET MPI and TTE for longitudinal, radial, and circumferential strains at both stress and rest in a CAD cohort. (Implied: r > 0.5 for all correlations based on predicate's performance or clinical significance)	Normal Limits: Established using a low-risk cohort (n=22), defined as mean radial strain - 2SD, and mean circumferential/longitudinal strain + 2SD. Correlation (CAD Cohort, n=80): Longitudinal Strain: Stress (r=0.68, p<.001), Rest (r=0.58, p<.001) Radial Strain: Stress (r=-0.70, p<.001), Rest (r=-0.59, p<.001) Circumferential Strain: Stress (r=0.67, p<.001), Rest (r=0.69, p<.001) "The results demonstrate that all values between ECTb™ Strain and TTE correlated strongly and were found to be highly reproducible."

2. Sample size used for the test set and the data provenance:

Emory-CACS:
- Sample Size: 52 patients, 110 vessels with calcified plaques.
- Data Provenance: Retrospective, as the lesions had been "previously scored by Emory radiologists." The country of origin is not explicitly stated but can be inferred as the U.S. (Emory is in Atlanta, GA).
ECTb™ Strain Analysis:
- Sample Size:
  - Low-risk cohort (for establishing normal limits): n=22
  - High-risk / CAD cohort (for validation): n=80
- Data Provenance: Not explicitly stated whether retrospective or prospective, but clinical comparison tests are often retrospective utilizing existing patient data. Country of origin is not explicitly stated but can be inferred as the U.S. (Emory is in Atlanta, GA).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Emory-CACS:
- Number of experts: Not explicitly stated, but lesions were "previously scored by Emory radiologists." This implies at least one, and likely more, radiologists.
- Qualifications: "Emory radiologists." Specific experience level (e.g., "10 years of experience") is not provided.
ECTb™ Strain Analysis:
- Number of experts: Not applicable in the same way as Emory-CACS, as the ground truth was established by another accepted reference standard (TTE echo).
- Qualifications: Not applicable for establishing ground truth from experts, but rather from the TTE echo measurements.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Emory-CACS: Not explicitly described. The text states lesions were "previously scored by Emory radiologists," suggesting consensus or a single expert's reading, but no formal adjudication method like "2+1" is mentioned.
ECTb™ Strain Analysis: Not applicable, as the ground truth was established by an existing clinical measurement method (TTE echo), not by expert consensus on the device's output.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

No, a multi-reader multi-case (MRMC) comparative effectiveness study focused on human reader improvement with AI assistance was not explicitly described for either new feature in this validation summary. The studies focused on comparing the device's performance directly against a predicate device or an accepted clinical reference standard.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Yes, for both features, the validation described appears to be a standalone (algorithm only) performance assessment.
- Emory-CACS: The module was compared directly against the SyngoVia™ module, analyzing the same lesions. This implies the device's output was generated and then compared to the predicate's output without human modification or interpretation of the device's results as part of the primary validation.
- ECTb™ Strain Analysis: The PET MPI measurements (presumably generated by the ECTb™ Strain algorithm) were correlated with TTE echo measurements, which is a comparison of two different measurement modalities.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

Emory-CACS: The ground truth for the reference lesions was established by the "previously scored by Emory radiologists" and the output of the predicate device (Siemens SyngoVia™ toolbox). In essence, the predicate device's output served as the reference standard against which Emory-CACS was compared.
ECTb™ Strain Analysis: The ground truth (reference standard) for strain measurements was established using Transthoracic Echocardiography (TTE echo), which is an accepted clinical reference standard for cardiac function assessment.

8. The sample size for the training set:

The document does not explicitly state the sample size for the training set for either the Emory-CACS or ECTb™ Strain analysis features. The described methodology focuses solely on the validation/test sets used for performance assessment.

9. How the ground truth for the training set was established:

Since the training set size and details are not provided, the method for establishing its ground truth is also not described in the document.

Summary

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March 30, 2023

Syntermed % Kenneth Van Train President 245 South Owens Drive ANAHEIM CA 92808

Re: K223422

Trade/Device Name: Emory Cardiac Toolbox™ 4.3 Regulation Number: 21 CFR 892.1200 Regulation Name: Emission computed tomography system Regulatory Class: Class II Product Code: KPS, JAK, LLZ Dated: February 24, 2023 Received: March 1, 2023

Dear Kenneth Van Train:

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 (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 located 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.

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

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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 803) for devices or postmarketing safety reporting (21 CFR 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 (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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.

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,

Dghk

Daniel M. Krainak, Ph.D. Assistant Director Magnetic Resonance and Nuclear Medicine Team DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K223422

Device Name

Emory Cardiac Toolbox 4.3

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)	XPrescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) SUMMARY K223422

1. Identification of the Submitter:

Kenneth Van Train President Syntermed. Inc. 333 Sandy Springs Circle Suite 107 Atlanta, GA 30328 Voice: (888) 263-4446 ext. 102, FAX: (714) 281-1290 Date of submission: January 3, 2022

2. Identification of the Product:

Device Proprietary Name: Emory Cardiac Toolbox™ 4.3 Common Name: Cardiac image processing software for SPECT and PET Classification Name: Emission Computed Tomography System Regulation Number: KPS: 21 CFR 892.1200, JAK: 21 CFR 892.1750, and LLZ: 21 CFR 892.2050 Product Code: KPS, JAK, and LLZ Classification Panel: Radiology Device Class: Class II

3. Medical Device Equivalence:

Emory Cardiac Toolbox™ 4.0 K123646
Syngo.CT Ca Scoring developed by Siemens Medical Solutions USA, Inc. ● K201034
TOMTEC-Arena (AutoStrain Suite) developed by TOMTEC Imaging Systems ● GmbH K201632.

4. Device Description:

5. New features in the current device

The new features added to the Emory Cardiac Toolbox™ are the analysis of the CT data to evaluate calcified plaques in the coronary arteries and analysis of wall motion and wall thickening of the heart using longitudinal, radial, and circumferential strain measurements.

6. Indication for Use

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The Emory Cardiac Toolbox™ 4.0 – 4.3 software program should be used for the quantification of myocardial perfusion for the display of wall motion and quantification of left-ventricular function parameters from SPECT & PET myocardial perfusion studies (EGS™) including to quantitatively evaluate the wall motion and wall thickening of the heart using longitudinal, radial, and circumferential strain measurements, for the 3D alignment of coronary artery models from CT coronary angiography onto the left ventricular 3D epicardial surface and analysis of the CT data to evaluate calcified plaques in the coronary arteries, for the assessment of cardiac mechanical dyssynchrony using phase analysis, for generation of the short axis, vertical, and horizontal long axis tomograms from the SPECT raw data using either filtered backprojection (FBP) or iterative reconstruction (MLEM/OSEM), for the quantification of myocardial blood flow and coronary flow reserve, and for the decision support in interpretation (LVX) and automatic structured reporting of the study.

Comparison Table with predicate device(s)

Submitted Device: Emory Cardiac Toolbox™ 4.3 (K223422) Predicate Devices:

Emory Cardiac Toolbox™ 4.0 (K123646) ●
Calcium Scoring: Syngo.CT Ca Scoring developed by Siemens Medical Solutions . USA, Inc. (K201034)
Strain Analysis: TOMTEC-Arena (AutoStrain Suite) developed by TOMTEC Imaging ● Systems GmbH (K201632)

Function or Parameter	ECTb™ 4.0	ECTb™ 4.3	Syngo.CT	TOMTEC-Arena
2D and 3D Display ofperfusion and left-ventricularfunction from gated SPECT &PET myocardial perfusionstudies	Yes	Yes	NA	NA
Quantitative analysis ofperfusion for extent, severity,reversibility, mass, andviability	Yes	Yes	NA	NA
Quantitative analysis offunction for ejection fraction,end-diastolic volume, end-systolic volume, myocardialmass volumes, wallthickening, and transientischemic dilation (TID)	Yes	Yes	NA	NA
Provides computer assistedvisual scoring and prognosticinformation	Yes	Yes	NA	NA
Decision support for imageinterpretation	Yes	Yes	NA	NA
3D alignment of coronary	Yes	Yes	NA	NA
artery models from CTcoronary angiography onto leftventricular 3D epicardialsurface
Can be used with the followingmyocardial protocols: SameDay and two Day Sestamibi,Dual-Isotope (Tc-99m/TI-201),Tetrofosmin, Thallium,Rubidium-82, N-13 Ammonia,and FDG	Yes	Yes	NA	NA
Provides automatic andmanual reorientation ofSPECT gated and non-gateddata sets.	Yes	Yes	NA	NA
Measurement of Leftventricular dyssyncrony	Yes	Yes	NA	NA
Provides a method foranalyzing Myocardial BloodFlow and Coronary FlowReserve	Yes	Yes	NA	NA
Automatic highlighting ofcoronary calcifications. Thecalcified plaques areassigned manually to theirrespective coronary artery bymouse click.	NA	Yes	Yes	NA
Automatic highlighting of metausing a default threshold of1000 HU.	NA	Yes	Yes	NA
Ability to calculate Agatstonscores and plaque volumes	NA	Yes	Yes	NA
Automatic evaluation oflesions by a 3D segmentationalgorithm	NA	Yes	Yes	NA
Ability to split a lesion into 2territories.	NA	Yes	Yes	NA
Ability to window the CalciumScoring CT	NA	Yes	Yes	NA
Ability to generate a reportrelated to the calciumscoring data.	NA	No	Yes	NA
Quantitatively evaluate thewall motion and wallthickening of the heart usinglongitudinal, radial, andcircumferential strainmeasurements.	NA	Yes	NA	Yes
Quantitative strain analysis	NA	No	NA	Yes
Regional strain (by wall andby 17-segment polar maps)	NA	Yes	NA	Yes
Comparison to a normal limit(with color-coding) for globaland 17-segment regionalanalysis	NA	Yes	NA	No

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8. Performance Validation

Emory-CACS: The CACS module was validated against the FDA approved Siemens SynqoVia™ toolbox (K201034). A clinical comparison test was the method used for validation. The test data was comprised a group of 52 patients using 110 vessels with calcified plaques that had been previously scored by Emory radiologists; the same lesions selected by the radiologist were analyzed by the Emory-CACS and SYngo.CT CaScoring modules. Regression analysis was performed between the SyngoVia™ and the Emory-CACS module. On a per patient basis, linear plaque volume regression (m = 1.10; b = 0.46) produced an r2 = 0.99 and Agatston score regression (m = 1.01; b = 1.06) produced an r2 > 0.99. The values obtained by the Emory-CACS module demonstrated excellent correlations with the Syngo.CT CaScoring developed by Siemens Medical Solutions.

ECTb™ Strain: MPI measurements were validated for resting global longitudinal strain vs. an accepted reference standard, TTE echo A clinical comparison test was the method used for validation. Longitudinal, radial, and circumferential strains from a low-risk cohort (n=22) were used to establish normal limits to evaluate against the results of a high-risk cohort (n=80). Positive strain, lower limits of normal were determined as the mean radial strain minus 2-standard deviations (SD). For circumferential and longitudinal strains, both negative in sign, lower limits of normal were determined as the mean strain plus 2-SDs. Validation of strain analysis for ECTb™ 4.3 was performed in 80 patients with variable coronary artery disease (CAD) and 22 patients with low-risk of CAD. In the CAD cohort, longitudinal strain assessed with PET MPI and TTE were strongly correlated at stress (r= 0.68, p <.001) and rest (r= 0.58, p<.001). PET MPI radial strain was also highly correlated with TTE at stress (r=-0.70, p<.001) and at rest (r=-0.59, p<.001). Similarly, PET MPI circumferential strain was highly correlated with TTE at stress (r=0.67, p<.001) and at rest (r=0.69.p<.001). The results de monstrate that all values between ECTb™ Strain and TTE correlated strongly and were found to be highly reproducible.

9: Conclusion

The current device has the same indication for use and has the same technological characteristics as the predicate device(s). The performance of the additional new features have been tested and the results have met the predefined acceptance criteria, and it has been determined to be substantially equivalent to predicate device(s).

Regulation Number and Section

N/A