The Emory Cardiac Toolbox™ (CEqual®, EGS™) 3.1 software program should be used for the quantification of myocardial perfusion (CEqual®), for the display of wall motion and guantification of left-ventricular function parameters from gated Tc99m 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 anaylsys, 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).

Device Description

The Emory Cardiac Toolbox™ 3.1 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. 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

The information provided in the 510(k) summary (K071503) focuses on demonstrating substantial equivalence to predicate devices and detailing the validation studies conducted for different versions and features of the Emory Cardiac Toolbox. However, it does not explicitly state specific acceptance criteria in a quantitative manner or present a table comparing reported device performance against such criteria for the entire Emory Cardiac Toolbox 3.1.

Instead, the document describes the types of validation performed and the sample sizes used for various features. It asserts the software's safety and effectiveness based on these studies and its similarity to predicate devices.

Based on the provided text, here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

As noted, the document explicitly states the "expected accuracy of the initial program can be found in the multicenter trial results listed in the article by Vansant et al Emoy Cardinc Toolbox™ (CEqual®, EGS™) Version 2.0, Ref. 510(k) #: K992450 and Version 2.1, Ref. 510(k) #: K014033)". However, the specific quantitative acceptance criteria for the Emory Cardiac Toolbox 3.1 (or even 2.0/2.1 in detail within this document) are not defined within the provided text immediately, nor is a table directly presenting performance against such criteria. The document discusses "accuracy" in general terms for previous versions, and then "development and prospective validation" for new features in 3.1.

Therefore, a table cannot be fully constructed for explicit acceptance criteria as they are not explicitly detailed in this document. The document refers to external 510(k)s (K992450 and K014033) for baseline accuracy. For version 3.1 features, it describes validation studies conducted.

Summary of Device Performance/Validation Studies (as described within the document):

Feature/Version	Study Type/Description	Sample Size	Outcome (Descriptive, specific metrics not provided in this document)
Emory Cardiac Toolbox™ 2.0	Phantom and computer simulations	N/A	Established effectiveness
	In-house trial (LV functional parameters)	217 patients	Established effectiveness
	Multicenter trial (general effectiveness)	80 patients	Established effectiveness ("expected accuracy" referred to other 510(k)s)
	Computer assisted visual scoring	20 patients	Successfully evaluated
	Prognosis algorithms	504 patients	Successfully evaluated
	Expert system algorithms	461 patients	Successfully evaluated
	Coronary fusion algorithms	9 patients	Successfully evaluated
Emory Cardiac Toolbox™ 2.1	Rb-82 normal limits development & validation	176 patients	Successfully completed
	PET tools for perfusion-metabolism match-mismatch	90 patients	Successfully completed
Emory Cardiac Toolbox™ 2.6	N-13 ammonia normal limits development & validation	144 patients	Successfully completed
	3D CT coronary artery alignment (phantom & patient)	8 patients	Successfully completed
Emory Cardiac Toolbox™ 3.1	SPECT reconstruction validation	10 patients (prospective)	Successfully validated
	Phase analysis development (cardiac mechanic dyssynchrony)	90 normal patients	Successfully developed
	Phase analysis validation (cardiac mechanic dyssynchrony)	75 additional patients (prospective)	Successfully validated

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

The document describes several test sets for different features and versions of the software.

Emory Cardiac Toolbox 2.0 (initial program):
- "In-house trial validations which included an evaluation of left ventricular functional parameter calculations": 217 patients. (Provenance not specified, but "in-house" suggests internal data, likely US based, retrospective or mixed).
- "Multicenter trial validation": 80 patients. (Provenance not specified, typically implies multiple centers, often US, could be retrospective or prospective).
- Computer assisted visual scoring: 20 patients. (Provenance not specified).
- Prognosis: 504 patients. (Provenance not specified).
- Expert system: 461 patients. (Provenance not specified).
- Coronary fusion: 9 patients. (Provenance not specified).
Emory Cardiac Toolbox 2.1:
- Rb-82 normal limits validation: 176 patients. (Provenance not specified).
- PET tools for match-mismatch validation: 90 patients. (Provenance not specified).
Emory Cardiac Toolbox 2.6:
- N-13 ammonia normal limits validation: 144 patients. (Provenance not specified).
- 3D CT coronary artery alignment validation (patient studies): 8 patients. (Provenance not specified).
Emory Cardiac Toolbox 3.1 (new features):
- SPECT reconstruction validation: 10 patients. This was a prospective validation. (Provenance not specified).
- Phase analysis validation: 75 patients. This was a prospective validation. (Provenance not specified).

Overall Data Provenance (General): The document does not explicitly state the country of origin for the data for most studies, but the company (Syntermed, Inc.) and the submission location (Atlanta, GA) suggest a US context for clinical trials. Many studies involve "patients," implying retrospective or prospective clinical data. Multiple "validation" studies are mentioned as "prospective" for the 3.1 version's new features.

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

The document does not specify the number of experts or their qualifications used to establish ground truth for any of the studies mentioned. It simply refers to "validation" or "evaluations" that likely rely on expert review or established methods.

4. Adjudication Method for the Test Set

The document does not specify any adjudication methods (e.g., 2+1, 3+1) for establishing ground truth in any of the described test sets.

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

The document does not describe a Multi-Reader Multi-Case (MRMC) comparative effectiveness study evaluating how much human readers improve with AI assistance vs. without it. The device is referred to as a "display and processing program to aid in the diagnostic interpretation," implying it assists physicians. However, it does not quantify this assistance in a comparative MRMC study. The "expert system interpretation" mentioned for version 2.0 suggests an AI component, but its impact on human reader performance is not detailed.

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

The device is explicitly described as serving "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." Furthermore, it states that "user verification of output is required." This strongly indicates that the device is not designed or evaluated as a standalone AI system without human-in-the-loop performance. Its role is assistive, and the physician retains final responsibility. Therefore, a standalone performance study as a replacement for human interpretation was likely not performed, nor would it be appropriate for its intended use.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The document refers to various types of "validation" but does not explicitly detail the specific type of ground truth used for each. However, based on the context of cardiac imaging and functional parameters, the ground truth likely involved a combination of:

Clinical outcomes/patient data: For prognostic information and normal limits.
Expert interpretation/consensus: For visual scoring, expert system interpretation, and possibly for validating quantitative measurements against a clinical standard.
Pathology: Not directly mentioned, but could be a component for definitive diagnoses if included in certain patient cohorts.
Phantom studies: Explicitly mentioned for version 2.0 (effectiveness) and version 2.6 (3D CT coronary artery alignment), which would use known, controlled configurations as ground truth.
Animal studies: Explicitly mentioned for version 3.1 (development for SPECT reconstruction and phase analysis), where ground truth could be established through invasive measurements or controlled conditions.

8. The Sample Size for the Training Set

The document mentions "development" for some features but doesn't explicitly refer to "training sets" in the modern machine learning sense with specific sample sizes. It mentions:

For Emory Cardiac Toolbox™ 2.1: "development and validation of Rb-82 normal limits (n=176)". This 176-patient cohort likely served as a development/training set for establishing these normal ranges.
For Emory Cardiac Toolbox™ 2.6: "development and validation of N-13ammonia normal limits (n=144)". This 144-patient cohort likely served as a development/training set.
For Emory Cardiac Toolbox™ 3.1: "development... in 90 normal patients" for phase analysis. This 90-patient cohort effectively served as a training/development set for the phase analysis algorithm.

Other studies are described as "evaluations" or "validations" rather than "development" directly tied to a specific cohort, suggesting pre-existing algorithms were tested on these patient populations.

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

Similar to the ground truth for the test set, the document is not specific on this point. For the "development" cohorts mentioned:

Normal limits (Rb-82, N-13 ammonia): Ground truth for "normal" would typically be established based on rigorous clinical criteria, including detailed patient history, lack of cardiac symptoms, clean EKG, and other physiological measurements, often confirmed by expert clinical review.
Phase analysis (90 normal patients): Ground truth for "normal" in phase analysis (assessing cardiac mechanic dyssynchrony) would involve established clinical criteria defining normal cardiac rhythm and function, likely based on expert cardiological assessment, EKG, echocardiography, and other standard diagnostic tests to confirm the absence of dyssynchrony.
Phantom and animal studies: As mentioned for other versions, these would use known physical properties or invasively measured physiological parameters to establish ground truth.

In general, it relies on conventional medical diagnostic methods and expert clinical assessment as the reference standard.

Summary

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K07/503

JUL 26 2007

ITEM I

510(k) SUMMARY

Safety and Effectiveness

1. Medical Device Establishment:

Syntermed. Inc. Registration No. 1066019 Owner Operator I.D. 9041128 Device Regulation Number: 892.1200 Product Code: KPS Classification Panel: Radiology Voice: (714) 281-1256, FAX: (714) 281-1290 Contact person: Kenneth F. Van Train Address: Syntermed, Inc. Tower Place Center 3340 Peachtree Road, NE Suite 1800 Atlanta, GA 30326 Date Summary Prepared: May 30, 2007

2. Medical Device:

Emory Cardiac Toolbox™ 3.1 - 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

3. Medical Device Equivalence:

AutoSPECT Plus developed by ADAC Laboratories K992317 for Emory Reconstruction Toolbox (ERTb™) and GE Vivid 7 Diagnostic Ultrasound System with TSI developed by GE Medical Systems K031663 for Phase Analysis.

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. 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 and Potential Adverse Effect on Health:

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 cornary angiography onto the left ventricular 3D epicardial surface, for the assessment of cardiac mechanic dyssynchrony using phase analysis, 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 (MLFM/QSEM). 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 Emoy Cardinc Toolbox™ (CEqual®, EGS™) Version 2.0, Ref. 510(k) #: K992450 and Version 2.1, Ref. 510(k) #: K014033). The accuracy for modifications in version 3.1 for SPECT reconstruction and for evaluation of cardiac mechanic dyssynchrony by phase analysis can be found in Item H (Testing & Validation) of this 510(k) submission. The physician should be aware of the accuracy when integrating the quantistive 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

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physician will utilize for his final interpretation. interpretation of the study lies with the physician.

The final responsibility for

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, and 2.6. 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™ 3.1 provides additional features for the assessment of cardiac mechanic dvssynchrony using phase anaylsys, 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) which executes in the IDL operating system environment and we believe is substantially equivalent to AutoSPECT Plus developed by ADAC Laboratories K992317 for Emory Reconstruction Toolbox (ERTb™) and GE Vivid 7 Diagnostic Ultrasound System with TSI developed by GE Medical Systems K031663 for Phase Analysis. To our knowledge there have been no safety problems with the AutoSPECT Plus program which has been in the marketplace since October 1, 1999 and with GE Vivid 7 Diagnostic Ultrasound System with TSI which has been which has been in the marketplace since June 9. 2003.

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 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 and these results are listed in Item H. Testing & Validation. We contend that the method employed for the development and validation for the assessment of cardiac mechanic dyssynchrony using phase anaylsys, and for generation of the short axis, vertical, and horizontal long axis tomograms from the

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SPECT raw data using either filtered backprojection (FBP) or iterative SFLCT Taw data using oldior "Microa" Salac Toolbox™ 3.1, have proven its reconstraction (MELM/OOLM), Embly Other Statures in Emory Cardiac Salely and Cheoliverioos: The Spicition and phase analysis are substantially Toolbox - O.T TOP OF LOT Tor OF LOS Laboratories K992317 for Emory Reconstruction Toolbox (ERTb™) and GE Vivid 7 Diagnostic Ultrasound Emory Reconstrabiler Fronton (E Medical Systems K031663 for Phase Analysis Oystem with TOT doveloped a for marketing. The Emory Cardiac Toolbox™ 3.1 is intended for the same purpose along with the additional purpose of alignment Intended for the Same parpose analysis and raises no new issues of safety or effectiveness.

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Image /page/4/Picture/0 description: The image shows a logo with a circular border containing text. Inside the circle is a stylized graphic of three curved lines that resemble a bird in flight or abstract waves. The text around the circle reads "DEPARTMENT OF HEALTH & HUMAN SERVICES".

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 9200 Corporate Blvd. Rockville MD 20850

Mr. Kenneth F. Van Train President Syntermed, Inc. 245 Owens Drive ANAHEIM CA 92808

Re: K071503

Trade/Device Name: Emory Cardiac Toolbox 3.1 Regulation Number: 21 CFR 892.1200 Regulation Name: Emission computed tomography system Regulatory Class: II Product Code: KPS and LLZ Dated: May 30, 2007 Received: June 5, 2007

Dear Mr. 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 indiver 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 Concercular Act (Act) that do not require approval of a premarket approval application (PMA) and COSII. therefore, market the device, subject to the general controls provisions of the Art, Tho may, 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 (Spocial Controls) or class III (Premarket Approval), it may be subject to such 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.

Image /page/4/Picture/10 description: The image shows a circular logo with the text "1906-2006" at the top. The letters "PA" are prominently displayed in the center of the logo. Below the letters, the word "Centennial" is written in a cursive font. Three stars are arranged in a horizontal line at the bottom of the logo.

oting Publio Shalth lating and Prop

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Page 2 -

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); 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.

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at one of the following numbers, based on the regulation number at the top of this letter:

21 CFR 876.xxx	(Gastroenterology/Renal/Urology)	240-276-0115
21 CFR 884.xxx	(Obstetrics/Gynecology)	240-276-0115
21 CFR 894.xxx	(Radiology)	240-276-0120
Other		240-276-0100

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (240) 276-3150

or at its Internet address http://www.fda.gov/cdrl/industry/support/index.html

Sincerely yours.

Nancy C. Hogdon

Nancy C. Brogdon Director, Division of Reproductive. Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K071503 510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Emory Cardiac Toolbox 3.1 Executing on Nuclear Medicine Computers Device Name:

Indications For Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use √
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Formal 1-2-96)

Helent lemer
Division Sign Off

(Division Sign-Off) Division of Reproductive, Abdominal, and Radiological Device 510(k) Number _

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.