The Emory Cardiac Toolbox™ 4.0 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™), for the 3D alignment of coronary artery models from CT coronary angiography onto the left ventricular 3D epicardial surface, 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.

The product is intended for use by trained nuclear technicians and nuclear medicine or nuclear cardiology physicians. The clinician remains ultimately responsible for the final interpretation and diagnosis based on standard practices and visual interpretation of all SPECT and PET data.

Device Description

The Emory Cardiac Toolbox™ 4.0 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. These parameters are: perfusion, ejection fraction, end-diastolic volume, end-systolic volume, myocardial mass, transient ischemic dilatation (TID), analysis of coronary blood flow and coronary flow reserve, and assessment of cardiac mechanic dyssynchrony. In addition, the program offers the capability of providing the following diagnostic information: computer assisted visual scoring, prognostic information, and expert system image interpretation. The program can also be used for the 3D alignment of coronary artery models from CT coronary angiography onto the left ventricular 3D epicardial surface and for generation of the short axis, vertical, and horizontal long axis tomograms from the SPECT raw data either filtered backprojection (FBP) or iterative reconstruction using (MLEM/OSEM). The Emory Cardiac Toolbox can be used with any of the following Myocardial SPECT Protocols: Same Day and Two Day Sestamibi, Dual-Isotope (Tc-99m/Tl-201), Tetrofosmin, and Thallium, Rubidium-82, Rubidium-82 with CTbased attenuation correction, N-13-ammonia, FDG protocols, and user defined normal databases. This program was developed to run in the .NET operating system environment which can be executed on any PC, any nuclear medicine computer system, or through a web browser. In addition, the program can be used for the decision support in interpretation and automatic structured reporting of the study. The program processes the studies automatically, however, user verification of output is required and manual processing capability is provided.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the Emory Cardiac Toolbox™ 4.0, extracted from the provided 510(k) summary:

Acceptance Criteria and Device Performance

The 510(k) summary for Emory Cardiac Toolbox™ 4.0 primarily focuses on demonstrating substantial equivalence to predicate devices and detailing the validation studies for its new features. It does not explicitly state pre-defined acceptance criteria in a quantitative format as one might find in a clinical trial protocol. Instead, it describes successful validations and accuracy against established methods or predicate devices.

However, based on the information provided, we can infer the performance goals for certain aspects of the device.

Feature/Parameter	Acceptance Criteria (Inferred)	Reported Device Performance
IDL to .NET Conversion Accuracy (for 14 perfusion, function, and dyssynchrony variables)	To demonstrate accuracy in deriving "similar values" when converting from the IDL to the .NET operating system.	Successfully achieved "accuracy greater than 99%."
Coronary Blood Flow Validation	Comparable performance to cleared predicate devices (INVIA's CORRIDOR 4DM V2010 and cfrQuant).	Validation conducted successfully in 44 patient studies, contributing to the claim of safety and effectiveness, and substantial equivalence to predicate devices.
Decision Support Validation (LVX)	Comparable performance to cleared predicate devices (Emory Cardiac Toolbox v2.0 K992450 (PERFEX) and Rcadia's COR Analyzer K110071).	Validation conducted successfully in 126 studies, contributing to the claim of safety and effectiveness, and substantial equivalence to predicate devices.

Study Details

2. Sample Sizes Used for the Test Set and Data Provenance

IDL to .NET Conversion: 301 patients. Data provenance is not explicitly stated (e.g., country, retrospective/prospective).
Coronary Blood Flow Validation: 44 patient studies. Data provenance is not explicitly stated.
Decision Support Validation (LVX): 126 studies. Data provenance is not explicitly stated.
Previous Versions Referenced (ECT 2.0, 2.1, 2.6, 3.1):
- ECT 2.0: 217 patients for LV functional parameter evaluation (in-house trials), 80 patients for a multicenter trial validation. Computer assisted visual scoring (20 patients), prognosis (504 patients), expert system (461 patients), and coronary fusion (9 patients).
- ECT 2.1: Rb-82 normal limits (n=176), PET tools for perfusion-metabolism match-mismatch (n=90).
- ECT 2.6: N-13-ammonia normal limits (n=144), alignment method for 3D CT coronary artery onto LV 3D epicardial surface (phantom and 8 patients).
- ECT 3.1: SPECT reconstruction (phantom, animal, and 4 patients for development; 10 patients for prospective validation); Phase analysis (90 normal patients for development; 75 additional patients for prospective validation).

The provided text does not specify the country of origin for the data or if the studies were retrospective or prospective, except for two instances in ECT 3.1: "prospective validation in 10 patients" for SPECT reconstruction and "prospective validation in 75 additional patients" for phase analysis.

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

The document does not explicitly state the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") for establishing ground truth for the test sets described for version 4.0.

However, for the original Emory Cardiac Toolbox™ 2.0, it references an article "by Vansant et al Emory Cardiac Toolbox™ (CEquar®, EGS™) Version 2.0, Ref. 510(k) #: K992450 and Version 2.1, Ref. 510(k) #: K014033)" for initial program accuracy. The details of how ground truth was established in those studies would likely be found in those referenced 510(k)s or publications.

For the decision support system (LVX), given its intended use "to assist a trained physician to analyze nuclear cardiology images" and that the "physician should integrate all of the patients' clinical and diagnostic information... prior to making his final interpretation," it implies that the physicians using the system acted as the ultimate arbiters of truth, but how "ground truth" for the validation study itself was established for the 126 studies is not detailed.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method (like 2+1 or 3+1 consensus) for establishing ground truth for the test sets mentioned in the 4.0 validation or earlier versions.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

The document does not indicate that a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done to quantify how much human readers improve with AI vs. without AI assistance. The new features for version 4.0 (coronary blood flow, coronary flow reserve, and decision support) were primarily validated by demonstrating their derivation accuracy or by comparing their results to predicate devices, rather than through a comparative reader study with and without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, standalone performance was assessed for the new features. The validation of the "accuracy greater than 99%" for the IDL to .NET conversion, the "coronary blood flow validation" in 44 patients, and the "decision support validation" in 126 studies describe the algorithm's performance in generating specific measurements or interpretations. While user verification is required and manual processing is possible, the reported validations focus on the program's ability to process studies and produce results, which is a form of standalone evaluation. The device is intended to provide "decision support," meaning its output is fed to a human for final interpretation, but its internal validation steps would typically evaluate its standalone computational accuracy.

7. The Type of Ground Truth Used

IDL to .NET Conversion: The ground truth would likely be the values derived from the previous, established IDL version of the software. The goal was to show the new .NET version produced "similar values."
Coronary Blood Flow and Coronary Flow Reserve: The ground truth for these quantitative measurements would typically be established against other validated quantitative methods for measuring blood flow and reserve, implicitly by comparison/equivalence to the predicate devices (INVIA's CORRIDOR 4DM V2010 and cfrQuant).
Decision Support System (LVX): For decision support systems, ground truth is often clinical outcomes, invasive procedures (like angiography for coronary artery disease), or expert consensus on image interpretation. The text states equivalence to PERFEX and COR Analyzer, implying the ground truth methods used to validate those predicates (which are not detailed here) would be relevant. The phrasing "physician should integrate all of the patients' clinical and diagnostic information... prior to making his final interpretation" suggests that the ultimate "truth" is the comprehensive clinical diagnosis.

8. The Sample Size for the Training Set

The document does not explicitly provide a sample size for a training set directly associated with the new features of version 4.0. The studies described for version 4.0 (IDL to .NET conversion, coronary blood flow, decision support) are presented as validation studies, which typically use independent test sets, not training sets.

However, the text mentions "development" for earlier versions:

ECT 2.1: "development and validation of Rb-82 normal limits (n=176)"
ECT 2.6: "development and validation of N-13-ammonia normal limits (n=144)"
ECT 3.1: "development (phantom, animal, and patients n=4)" for SPECT reconstruction and "development in 90 normal patients" for phase analysis.

These "development" activities would involve data used to build or refine algorithms, akin to training data, but they are tied to earlier versions of the product.

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

As no specific training sets are described for the version 4.0 updates, the method for establishing ground truth for such sets is not mentioned. For the "development" phases of earlier versions (Rb-82 normal limits, N-13-ammonia normal limits, phase analysis in normal patients), the ground truth for "normal limits" would typically be derived from a healthy population cohort, likely using established clinical criteria to define "normal." For animal and phantom studies, the "ground truth" is typically the known physical properties or induced conditions.

Summary

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K123646

FEB 2 2 2013

510(k) SUMMARY

Safety and Effectiveness

Medical Device Establishment:

Syntermed, Inc. Registration No. 1066019 Owner Operator I.D. 9041128 Device Requlation Number: 892.1200 Product Code: KPS Classification Panel: Radiology Voice: (888) 263-4446 ext 102, FAX: (714) 281-1290 Contact person: Kenneth F. Van Train Address: Syntermed, Inc. 130 Wieuca Road Suite 108 Atlanta, GA 30342 Date Summary Prepared: November 15, 2012

Medical Device:

Emory Cardiac Toolbox™ 4.0 - Display and Processing program for gated SPECT & PET myocardial perfusion studies executing on nuclear medicine computer systems and Windows PC's.

Classification Name - System, Tomography, Computed, Emission

Medical Device Equivalence:

vww.syntermed.com · Office: 888.263.4446 · Fax: 888.216.7511

Emory Cardiac Toolbox v3.1 K071503, Emory Cardiac Toolbox v2.0 K992450 (PERFEX), COR Analyzer developed by Rcadia K110071, CORRIDOR 4DM V2010 developed by INVIA K101279, and Coronary Flow Reserve (CFR) Quantification (cfrQuant) developed by University of Texas Medical School at Houston K113754.

Device Description:

Nuclear is evolving. We're evolving with you.

· 130 West Wieuca Road · Suite 108

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5. Intended Use and Potential Adverse Effect on Health:

The Emory Cardiac Toolbox™ 4.0 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™), for the 3D alignment of coronary artery models from CT coronary angiography onto the left ventricular 3D epicardial surface, 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 backproiection (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.

The interpretation provided by LVX is intended to assist a trained physician to analyze nuclear cardiology images. It was not meant to replace or eliminate the standard visual analysis of the gated SPECT & PET study. The physician should integrate all of the patients' clinical and diagnostic information, i.e. patients' history, stress and/or rest EKG, quality control images, visual interpretation of the gated tomographic images, and quantitative and decision support interpretative results, prior to making his final interpretation. This comprehensive processing technique (as with all diagnostic imaging) is not perfect, and will be associated with some false positive and false negative results. The expected accuracy of the initial program can be found in the multicenter trial results listed in the article by Vansant

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et al Emory Cardiac Toolbox™ (CEquar®, EGS™) Version 2.0, Ref. 510(k) #: K992450 and Version 2.1, Ref. 510(k) #: K014033). The accuracy for modifications in version 4.0 for analysis of coronary blood flow, coronary flow reserve and for evaluation of the decision support system (LVX) in comparison to PERFEX results can be found in Item H (Testing & Validation) of this 510(k) submission. The physician should be aware of the accuracy when integrating the quantitative results for his final interpretation. Therefore, this program has no direct adverse effect on health since the results represent only a part of the information which the physician will utilize for his final interpretation. The final responsibility for interpretation of the study lies with the physician.

6. Marketing History:

There have been several medical device gated SPECT programs marketed in the past which perform similar functions to those performed by the Emory Cardiac Tool Box™ 2.0, 2.1, 2.6 and 3.1. These programs are all used for the purpose of displaying wall motion and deriving functional parameters for the diagnostic interpretation by a physician. The Emory Cardiac Tool Box™ 4.0 provides additional features for the analysis of coronary blood flow, and for the decision support in interpretation (LVX) and automatic structured reporting of the SPECT and PET study and we believe is substantially equivalent to Emory Cardiac Toolbox v3.1 K071503 for conversion from IDL to NET; Emory Cardiac Toolbox v2.0 K992450 and COR Analyzer developed by Rcadia K110071 for decision support; and CORRIDOR 4DM V2010 developed by INVIA K101279 and Coronary Flow Reserve (CFR) Quantification (cfrQuant) developed by University of Texas Medical School at Houston K113754 for mvocardial blood flow and coronary flow reserve. To our knowledge there have been no safety problems with the COR Analyzer decision support system which has been in the marketplace since January 31, 2011 and with CORRIDOR which has been marketed since August 4, 2010 or Coronary Flow Reserve (CFR) Quantification (cfrQuant) marketed since July 19, 2012.

7. Conclusions:

The safety of this program has been determined through the various stages of software development which included the initial design, coding, debugging, testing, and validation. The effectiveness of the initial program, Emory Cardiac Toolbox™ 2.0. has been established in phantom and computer simulations studies, in-house trial validations which included an evaluation of left ventricular functional parameter calculations in 217 patients, and in a multicenter trial validation consisting of 80 patients. In addition, the computer assisted visual scoring, prognosis, expert system, and coronary fusion algorithms were successfully evaluated in 20, 504, 461, and 9 patients respectively. Additional validation of the Emory Cardiac Toolbox™ 2.1 program for development and validation of Rb-82 normal limits (n=176) and validation of PET tools for assessment of perfusion - metabolism match-mismatch (n=90) were successfully completed. Validation for the Emory Cardiac Toolbox™ 2.6 program included development and validation of N-13ammonia normal limits (n= 144) and validation of the alignment method for 3D CT coronary artery onto the left ventricular 3D epicardial surface using phantom and

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patient studies (n = 8). Validation for the Emory Cardiac Toolbox™ 3.1 program included development (phantom, animal, and patients n=4) and prospective validation of SPECT reconstruction in 10 patients and for phase analysis which included development in 90 normal patients and prospective validation in 75 additional patients. Validation for the Emory Cardiac Toolbox™ 4.0 program included 301 patients used to validate the accuracy in deriving similar values for 14 perfusion, function and dyssynchrony variables from IDL to .NET conversion which demonstrated an accuracy greater than 99%, the coronary blood flow validation was conducted in 44 patient studies, and the decision support validation was conducted in 126 studies and these results are listed in Item H, Testing & Validation. We contend that the method employed for the development and validation for the conversion from IDL to .NET operating system, the analysis of coronary blood flow and coronary flow reserve, and the decision support for interpretation of SPECT and PET data have proven its safety and effectiveness. In our opinion the additional features in Emory Cardiac Toolbox™ 4.0 for decision support for interpretation and coronary blood flow analysis are substantially equivalent to Emory Cardiac Toolbox v2.0 K992450 (PERFEX) and Rcadia's COR Analyzer K110071 for decision support (LVX) and INVIA's CORRIDOR 4DM V2010 K101279 and Coronary Flow Reserve (CFR) Quantification (cfrQuant) developed by University of Texas Medical School at Houston K113754 for coronary blood flow analysis which have all been cleared for marketing. The Emory Cardiac Toolbox™ 4.0 is intended for the same purpose as Emory Cardiac Toolbox™ 3.1 along with the additional purpose of decision support for interpretation, coronary blood flow, and coronary flow reserve analysis and raises no new issues of safety or effectiveness.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

February 22, 2013

Syntermed, Inc. Kenneth F. Van Train, Ph.D. President, 130 Wieuca Road Suite 108 Atlanta, GA 30342

Re: K123646

Emory Cardiac Toolbox 4.0 Regulation Number: 21 CFR 892.1200 Regulation Name: Emission Computerized Tomography Regulatory Class: Class II Product Code: KPS Dated: November 16, 2012 Received: November 27, 2012

Dear Dr. 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. 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.

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 requirements, including, but not limited to: registration and listing (21

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Page 2 - [Contact Person's Name]

CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Michael Hara

Janine M. Morris Director Division Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number: K123646

Device Name:_Emory Cardiac Toolbox™ 4.0

Indications For Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Michi FDA'Hara

(Division Sign C

Page 1 of

Division of Radiotogical Hea

Office of In Vitro Diagnostics and Radiological He

510(k) L.123646

Regulation Number and Section

§ 892.1200 Emission computed tomography system.

(a)
Identification. An emission computed tomography system is a device intended to detect the location and distribution of gamma ray- and positron-emitting radionuclides in the body and produce cross-sectional images through computer reconstruction of the data. This generic type of device may include signal analysis and display equipment, patient and equipment supports, radionuclide anatomical markers, component parts, and accessories.(b)
Classification. Class II.