The Emory Cardiac Toolbox™ 3.2 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 gated Tc-99m 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 mechanic 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), and for the quantitative analysis and display of SPECT AdreView™ (133)-mlBG) data sets used for evaluation of patients with congestive heart failure.

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™ 3.2 is used to display gated wall motion and for quantifying parameters of left-ventricular perfusion and function from gated SPECT & PET myocardial perfusion studies. These parameters are: perfusion, ejection fraction, end-diastolic volume, end-systolic volume, myocardial mass, transient ischemic dilatation (TID), and cardiac mechanic dyssynchrony. In addition, the program offers the capability of providing the following diagnostic information: computer assisted visual scoring, prognostic information, expert system image interpretation, and patient specific 3D coronary overlay. 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 using either filtered backprojection (FBP) or iterative reconstruction (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, N-13-ammonia, FDG protocols, and user defined normal databases. The program can also be used for the quantitative analysis and display of SPECT Adre\View™ (123)-mlBG) data sets. This program was developed to run in the IDL operating system environment which can be executed on any nuclear medicine computer systems which supports IDL and the Aladdin (General Electric) software development environment. 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 provided text to extract the acceptance criteria and study details:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a quantitative, pass/fail format for the new features of Emory Cardiac Toolbox™ 3.2. Instead, it relies on substantial equivalence to previous versions and validates the new AdreView™ analysis through its ability to differentiate abnormal and normal uptake.

Feature/Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Visual Scoring, Prognosis, Expert System, Coronary Fusion Algorithms	Successfully evaluated in their respective patient populations.	Successfully evaluated in 20, 504, 461, and 9 patients respectively.
Rb-82 Normal Limits	Development and validation successful.	Developed and validated in 176 patients.
PET tools for perfusion-metabolism match-mismatch	Successful evaluation.	Successfully completed in 90 patients.
N-13ammonia normal limits	Development and validation successful.	Developed and validated in 144 patients.
Alignment method for 3D CT coronary artery onto LV 3D epicardial surface	Successful validation using phantom and patient studies.	Validated using phantom and patient studies (n=8).
SPECT Reconstruction	Prospective validation.	Validated in 10 patients.
Phase analysis (SyncTool™)	Development and prospective validation.	Developed in 90 normal patients and prospectively validated in 75 additional patients.
SPECT AdreView™ (¹²³I-mIBG) Data Analysis (New in v3.2)	Capability to differentiate subjects with abnormal and normal AdreView™ uptake using the H/M ratio index.	Demonstrated the capability to differentiate subjects with abnormal and normal AdreView™ uptake using the H/M ratio index in a validation group of 1,016 patients.

2. Sample Size and Data Provenance for the Test Set

Sample Size for AdreView™ Validation: 1,016 patients
Data Provenance for AdreView™ Validation: The document does not explicitly state the country of origin or whether cases were retrospective or prospective for the AdreView™ validation group. It only mentions "two groups of patients used in this study, a pilot group consisting of 67 patients... and a validation group consisting of 1,016 patients." The pilot group was "used to develop the heart volume regions of interest," implying a development set, while the 1,016 patients were specifically for validation.
Other Sample Sizes Mentioned (for previous versions or other features):
- Initial program (v2.0) LV functional parameters: 217 patients (in-house), 80 patients (multicenter trial).
- Visual scoring: 20 patients
- Prognosis: 504 patients
- Expert system: 461 patients
- Coronary fusion algorithms: 9 patients
- Rb-82 normal limits: 176 patients
- PET tools (perfusion-metabolism): 90 patients
- N-13ammonia normal limits: 144 patients
- 3D CT coronary artery alignment: 8 patients
- SPECT reconstruction: 10 patients (prospective)
- Phase analysis (SyncTool™): 90 normal patients (development), 75 additional patients (prospective validation).

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts used to establish ground truth for the AdreView™ validation. For previous versions and other features, it refers to "standard visual analysis," "physician interpretation," and "expert system interpretation" but does not detail the number or specific qualifications of these experts.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for establishing ground truth in the validation studies. The statement "The physician should integrate all of the patients' clinical and diagnostic information...prior to making his final interpretation" implies a physician-led decision process, but not a specific adjudication protocol involving multiple experts.

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

No MRMC comparative effectiveness study demonstrating how much human readers improve with AI vs. without AI assistance is explicitly described for the new features in v3.2. The document focuses on the performance of the algorithm itself in differentiating normal/abnormal AdreView™ uptake, rather than the AI's assistance to human readers. The general statement about the program serving "merely as a display and processing program to aid in the diagnostic interpretation" suggests it's an assistive tool, but no study quantifies this assistance.

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance evaluation was done for the new AdreView™ analysis. The study focused on the "capability to differentiate subjects with abnormal and normal AdreView™ uptake using the H/M ratio index" from the algorithm's output. This is a direct evaluation of the algorithm's performance on its own. Similarly, many of the performance evaluations for previous versions (e.g., calculation of LV functional parameters, Rb-82 normal limits, PET tools) appear to be standalone evaluations of the algorithm's output.

7. Type of Ground Truth Used

For the AdreView™ validation, the ground truth was implicitly derived from the clinical classification of patients into "abnormal and normal AdreView™ uptake." The document does not specify the exact methods for this classification (e.g., based on clinical diagnosis, follow-up, or a single expert's visual assessment). For earlier features, "standard visual analysis of the gated SPECT & PET study" and "physician interpretation" are mentioned, suggesting expert consensus or clinical diagnosis as the implicit ground truth.

8. Sample Size for the Training Set

Pilot Group for AdreView™: 67 patients were used "to develop the heart volume regions of interest on the SPECT reconstructions." This functions as a development/training set for establishing parts of the algorithm.
Other Development Sets:
- Phase analysis (SyncTool™): Developed in 90 normal patients.
- SPECT reconstruction: "development (phantom, animal, and patients n=4)".
- Rb-82 normal limits: 176 patients used for "development and validation."
- N-13ammonia normal limits: 144 patients used for "development and validation."

9. How Ground Truth for the Training Set Was Established

For the 67-patient pilot group for AdreView™ to "develop the heart volume regions of interest," the method for establishing ground truth is not specified. It likely involved expert input or established anatomical guidelines for defining these regions.

For the "development" portions of other features (e.g., 90 normal patients for SyncTool™ phase analysis, 4 patients/phantoms/animals for SPECT reconstruction development), the document doesn't detail how ground truth was explicitly established, but it would typically involve expert interpretation, phantoms with known properties, or histological/pathological correlation where applicable, though none are specifically stated here beyond the nature of the data itself (e.g., "normal patients" for SyncTool).

Summary

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K130902

ITEM I

JUN 1 4 2013

510(k) SUMMARY

Safety and Effectiveness

1. 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 Syntermed, Inc. Address: 130 Wieuca Road Suite 108 Atlanta, GA 30342

Email: vantrain@syntermed.com

Date Summary Prepared: March 29, 2013

Medical Device:

Emory Cardiac Toolbox™ 3.2 - 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:

Emory Cardiac Toolbox v3.1, Reference#: K071503.

4. Device Description:

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program offers the capability of providing the following diagnostic information: computer assisted visual scoring, prognostic information, expert system image interpretation, and patient specific 3D coronary overlay. 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 using either filtered backprojection (FBP) or iterative reconstruction (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, N-13-ammonia, FDG protocols, and user defined normal databases. The program can also be used for the quantitative analysis and display of SPECT Adre\View™ (123)-mlBG) data sets. This program was developed to run in the IDL operating system environment which can be executed on any nuclear medicine computer systems which supports IDL and the Aladdin (General Electric) software development environment. The program processes the studies automatically, however, user verification of output is required and manual processing capability is provided.

5. Intended Use:

The intended use of this program was to provide the physician with a program which would allow him to determine quantitative analysis of the myocardial perfusion, display wall motion and determine measurements of ejection fraction and ventricular volumes from his patients gated SPECT & PET myocardial perfusion study, obtain visual interpretation scores, prognostic information, expert system interpretation, for the 3D alignment of coronary artery models from CT coronary angiography onto the left ventricular 3D epicardial surface, for the assessment of cardiac mechanic 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), and for the quantitative analysis and display of SPECT AdreView™ (120-mlBG) data sets for evaluation of patients with congestive heart failure.

This program serves merely as a display and processing program to aid in the diagnostic interpretation of a patients' study. 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 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 et al Emory Cardiac Toolbox™ (CEqual®, EGS™) Version 2.0, Ref. 510(k) #: K992450 and Version 2.1, Ref. 510(k) #: K014033). The accuracy and reproducibility for modifications in version 3.2 for the quantitative analysis and display of SPECT AdreView™ (13)-

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mlBG) data sets 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. 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™ 3.2 provides additional features for the quantitative analysis and display of SPECT AdreView™ (123) mlBG) data sets and we believe is substantially equivalent to the T.I.D. and SyncTool™ analysis contained within our previous commercially released application Emory Cardiac Toolbox v3.1, K071503. To our knowledge there have been no safety problems with the T.I.D. or SyncTool™ applications in the Emory Cardiac Toolbox v3.1 which has been in the marketplace since July 26, 2007.

7. Performance Testing Summary

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 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 (SyncTool™) which included development in 90 normal patients and prospective validation in 75 additional patients. The validation results for the Emory Cardiac Toolbox™ 3.2 program are listed in Item H, Testing & Validation. In summary, there were two groups of patients used in this study, a pilot group consisting of 67 patients who were used to develop the heart volume regions of interest on the SPECT reconstructions and a validation group consisting of 1,016 patients that were used to validate the heart-to-mediastinum (H/M) ratio method. The results obtained in our validation for SPECT demonstrated the capability to differentiate subiects with abnormal and normal AdreView™ uptake using the H/M ratio index.

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8. Conclusions:

We contend that the method employed for the development and validation for the quantitative analysis and display of SPECT AdreView™ (1231-mIBG) data sets in Emory Cardiac Toolbox™ 3.2, have proven its safety and effectiveness. In our opinion the additional features in Emory Cardiac Toolbox™ 3.2 for generation of a ratio index (H/M ratio) for AdreView™ studies which is used to evaluate patients with congestive heart failure is substantially equivalent to the methods used to generate the T.I.D. ratio index and the SyncTool application for evaluation of congestive heart failure patients currently available in Emory Cardiac Toolbox™ 3.1. The Emory Cardiac Toolbox™ 3.2 is intended for the same purpose as Emory Cardiac Toolbox™ 3.1 and raises no new issues of safety or effectiveness.

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Image /page/4/Picture/0 description: The image is a black and white logo for the U.S. Department of Health and Human Services. The logo features a stylized abstract symbol that resembles a person with outstretched arms. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol. The text is in all capital letters and is evenly spaced around the circle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 14. 2013

Syntermed, Inc. % Kenneth Van Train, Ph.D. President 245 South Owens Drive ANAHEIM CA 92808

Re: K130902

Trade/Device Name: Emory Cardiac ToolboxTM 3.2 Regulation Number: 21 CFR 892.1200 Regulation Name: Emission Computed Tomography Regulatory Class: Class II Product Code: KPS Dated: March 29, 2013 Received: April 11, 2013

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. 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 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); 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. ·

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Page 2 - Kenneth Van Train, Ph.D.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Michael D. O'Hara

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

for

Enclosure

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Indications for Use

510(k) Number (if known)K130902

Device Name: Emory Cardiac Toolbox ™ 3.2

Indications for Use:

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

Over-The-Counter Use (21 CFR 801 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)

Michael D. O'Hara

(Division Sign-Off) Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health

510(k) K130902

Page 1 of 1

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.