This software program should be used to guantitatively analyze the myocardial perfusion of patients' who have been injected with Cardiolite® (Technetium Tc99m Sestamibi) for a rest/stress same-day Single Photon Emission Computerized Tomography (SPECT) acquisition protocol. Cardiolite®, Kit for the Preparation of Technetium Tc99m Sestamibi is a myocardial perfusion agent that is useful in the evaluation of ischemic heart disease. Cardiolite®, Kit for the Preparation of Technetium Tc99m Sestamibi is useful in distinguishing normal from abnormal myocardium and in the localization of the abnormality, in patients with suspected myocardial infarction, ischemic heart disease or Evaluation of ischemic heart disease or coronary artery disease. coronary artery disease is accomplished using rest and stress techniques.

Cardiolite®, Kit for the Preparation of Technetium Tc99m Sestamibi is also useful in the evaluation of myocardial function using the first pass technique.

Rest-exercise imaging with Tc99m Sestamibi in conjunction with other diagnostic information may be used to evaluate ischemic heart disease and its localization.

In clinical trials, using a template consisting of the anterior wall, inferior-posterior wall and isolated apex, localization in the anterior or inferior-posterior wall in patients with suspected angina pectoris or coronary artery disease was shown. Disease localization isolated to the apex has not been established. Tc99m Sestamibi has not been studied or evaluated in other cardiac diseases.

It is usually not possible to differentiate recent from old myocardial infarction or to differentiate recent myocardial infarction from ischemia.

To detect or image the distribution of radionuclides in the body or organ, using the following technique(s). Tomographic imaging (SPECT) for non Positron emitter.

Device Description

This medical device (CEqual®) is a diagnostic software program that quantitatively analyzes the myocardial perfusion of patients' injected with Cardiolite® (99mTc Sestamibi) following a rest/stress same-day SPECT acquisition protocol. The algorithm automatically determines the processing parameters and, following operator verification of these parameters, samples the myocardium using maximum count profiles. These stress and rest profiles are then used to generate relative count "raw data" polar maps. In addition, the profiles are compared to a normal data base and the results of this comparison are used to generate quantitative stress and rest polar maps which indicate defect extent, severity, and reversibility for all abnormal perfusion areas of the patients' study. The final results are presented in the form of polar maps as well as a table indicating the % abnormal pixels in territories supplied by the left anterior descending, left circumflex, and right coronary arteries.

AI/ML Overview

The provided text describes the CEqual® software, a diagnostic program that quantitatively analyzes myocardial perfusion from SPECT acquisitions using Cardiolite® (Technetium Tc99m Sestamibi). The software generates polar maps indicating defect extent, severity, and reversibility, and a table showing the percentage of abnormal pixels in territories supplied by major coronary arteries.

Here is an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal acceptance criteria with specific threshold values for performance metrics (e.g., sensitivity, specificity, accuracy). Instead, it states that "The accuracy results obtained with this program are similar to those obtained with previous quantitative analysis programs of the TI-201 myocardial perfusion agent (1,2) and Cardiolite® (3,4)." This implies that the acceptance criterion was likely non-inferiority or comparable performance to existing, legally marketed predicate devices rather than meeting a specific numerical target.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Accuracy	Comparable to established quantitative analysis programs for Tl-201 and Cardiolite® myocardial perfusion agents.	"The accuracy results obtained with this program are similar to those obtained with previous quantitative analysis programs of the TI-201 myocardial perfusion agent (1,2) and Cardiolite® (3,4)."

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

Test Set Sample Size: 35 patients.
Data Provenance: The study was a "prospective validation which included 35 patients acquired and processed at another institution." This indicates the data was prospective and collected from an institution different from the developers. The country of origin is not specified, but the references suggest it was likely within the United States, given the authors and journals.

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

The document does not specify the number of experts used or their qualifications for establishing the ground truth for the test set.

4. Adjudication Method for the Test Set

The adjudication method for the test set is not specified in the provided text.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly stated as part of this device's validation. The focus was on the software's performance itself rather than human reader improvement with AI assistance. The text mentions the program is an "adjunctive diagnostic tool" and not meant to replace visual analysis, suggesting it's for human-in-the-loop use but doesn't quantify reader improvement.

6. If a Standalone Study Was Done

Yes, a standalone study was done. The description "The effectiveness of the program has been established in a prospective validation which included 35 patients acquired and processed at another institution" refers to the algorithm's performance as a standalone tool, comparing its quantitative results against some form of ground truth (or established accuracy benchmarks of predicate devices as per the acceptance criteria).

7. The Type of Ground Truth Used

The specific type of ground truth used to evaluate the 35 patients in the prospective validation is not explicitly stated. However, given the context of myocardial perfusion imaging for "evaluation of ischemic heart disease or coronary artery disease" and localization of abnormalities, common ground truth types in such studies include:

Expert Consensus: Visual interpretation by experienced cardiologists or nuclear medicine physicians.
Coronary Angiography: An invasive procedure considered the gold standard for anatomical assessment of coronary artery disease.
Clinical Outcomes: Follow-up data on patient events (e.g., myocardial infarction, revascularization).

The reference to "previous quantitative analysis programs" suggests the ground truth was comparable to what was used in those studies, which often involves a combination of expert visual assessment and, for more definitive studies, angiography.

8. The Sample Size for the Training Set

The document does not specify the sample size used for the training set. It mentions "a normal data base" used to generate quantitative stress and rest polar maps, implying a training or reference set was used, but the size is not provided.

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

The document states that the software compares patient profiles "to a normal data base." This "normal data base" serves as a reference for quantifying abnormalities. How the ground truth for this normal data base was established is not explicitly detailed. It can be inferred that this database would consist of studies from individuals confirmed to have normal myocardial perfusion, likely established through:

Absence of clinical symptoms of cardiac disease.
Normal findings on other diagnostic tests (e.g., EKG, echocardiogram).
Possibly, follow-up to ensure no cardiac events.
Expert interpretation confirming normalcy.

The references provided (1, 2, 3, 4) might contain more details about the methodology for creating such "normal databases" in studies of similar quantitative myocardial perfusion agents. For example, Van Train et al. (1993, Ref 3) specifically mentions "definition and validation of stress normal limits," which would involve establishing the ground truth for a normal cohort.

Summary

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972500

ITEM I

SUMMARY OF SAFETY AND EFFECTIVENESS

SEP - 8 1997

1. Indications for use:

Cardiolite®, Kit for the Preparation of Technetium Tc99m Sestamibi is also useful in the evaluation of myocardial function using the first pass technique.

Rest-exercise imaging with Tc99m Sestamibi in conjunction with other diagnostic information may be used to evaluate ischemic heart disease and its localization.

It is usually not possible to differentiate recent from old myocardial infarction or to differentiate recent myocardial infarction from ischemia.

2. Device Description:

୍ୟୁ

This medical device (CEqual®) is a diagnostic software program that quantitatively analyzes the myocardial perfusion of patients' injected

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with Cardiolite® (99mTc Sestamibi) following a rest/stress same-day SPECT acquisition protocol. The algorithm automatically determines the processing parameters and, following operator verification of these parameters, samples the myocardium using maximum count profiles. These stress and rest profiles are then used to generate relative count "raw data" polar maps. In addition, the profiles are compared to a normal data base and the results of this comparison are used to generate quantitative stress and rest polar maps which indicate defect extent, severity, and reversibility for all abnormal perfusion areas of the patients' study. The final results are presented in the form of polar maps as well as a table indicating the % abnormal pixels in territories supplied by the left anterior descending, left circumflex, and right coronary arteries.

3. Marketing History:

There have been other diagnostic programs marketed in the past which perform similar functions to those performed by CEqual®. These programs were used to quantitatively analyze the myocardial perfusion of patients' injected with T1201, another myocardial perfusion agent. The most widely utilized T1201 quantitative programs are the Cedars-Sinai and General Electric's "Bullseye" methods. To our knowledge there have been no safety problems with either of these two methods which have been in the marketplace for over the past five years. In addition, the CEqual® program executing on the Siemens and General Electric computer systems have been in the marketplace since October 1992 with no safety problems reported.

4. Potential Adverse Effect On Health:

The intent of this program was to provide the physician with an adjunctive diagnostic tool to aid in the diagnostic interpretation of the patients' Cardiolite® same-day study. It was not meant to replace or eliminate the standard visual analysis of the Cardiolite® images. 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 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 accuracy of the program is listed in the operators manual and the physician should be aware of the accuracy when integrating the quantitative results for his final interpretation.

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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 integration and interpretation of the study lies with the physician. of the results

5. Conclusions:

The safety of this program has been determined through the various stages of software development which included the code translation, debugging, testing, and in-house validation. The effectiveness of the program has been established in a prospective validation which included 35 patients acquired and processed at another institution. The accuracy results obtained with this program are similar to those obtained with previous quantitative analysis programs of the TI-201 myocardial perfusion agent (1,2) and Cardiolite® (3,4). We contend that the method employed for the development and the final multicenter trial validation results of this quantitative software program (CEqual®) have proven its safety and effectiveness.

References

1 . Depasquale EE, Nody AC, DePuey EG, et al: Quantitative rotational thallium-201 tomography for identifying and localizing coronary artery Circulation 77:316-327, 1988. disease.

Van Train K, Maddahi J, Berman DS, et al: Quantitative Analysis of 2. Tomographic Stress Thallium-201 Myocardial Scintigrams: A Multicenter Trial. J Nucl Med 31:1168-1179, 1990.

Van Train KF, Areeda J, Garcia EV, et al: Quantitative same-day 3. rest-stress Technetium-99m sestamibi SPECT: definition and validation of stress normal limits and criteria for abnormality. J Nucl Med 1993; 34:1494-1502.

Van Train KF, Garcia EV, Maddahi J, et al: Multicenter Trial 4. Quantitative Analysis of Same-Day Validation for Rest-Stress Technetium-99m-Sestamibi Myocardial Tomograms. J Nucl Med 1994; 35:609-618.

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Image /page/3/Picture/0 description: The image shows a logo for the Department of Health. The logo features a stylized eagle with three lines representing its wings. The text "DEPARTMENT OF HEALTH &" is arranged in a circular fashion around the eagle. The logo is black and white and appears to be scanned from a document.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

SEP - 8 1997

Kenneth F. Van Train President NucCardiac Software, Inc. 21520-"G" Yorba Linda Blvd., Suite 420 Yorba Linda, CA 92887

Re: K972509

C Equal - Quantitative Analysis SPECT Software Dated: July 2, 1997 Received: July 3, 1997 Regulatory Class: II 21 CFR 892.1200/Procode: 90 KPS

Dear Mr. Van Train:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, subject to the general controls provisions of the general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under Radiation Control provisions, or other Federal laws or regulations.

This letter will allow you to begin marketing your 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 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4613. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsmamain.html".

Sincerely vours.

h7liau Yu
Lillian Yin, Ph.D.

Director, Division of Reproductive, Abdominal, Ear, Nose and Throat, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page ] of 1

510(k) Number (if known): K972509

Dovice Name: CEqual for Toshiba Corporation (Diagnostic Software)

Nuclear Medicine Device

Indication For Use: To detect or image the distribution of radionuclides in the body or organ, using the following technique(s).

		YES	NO	Energy Range (keV)
A.	Planar imaging		X
B.	Whole body imaging		X
C.	Tomographic imaging (SPECT) for non Positron emitter	X		140 keV
D.	Positron imaging by coincidence		X
E.	Positron imaging without coincidence		X
F.	Other indication(s) in the device label, but not included in above list	None

(Please do not write below this line - Continue on another page if needed)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use_ V (Per 21 CFR 801.109)

Over-the-Counter Use

(Optional Romar 1-2-96)

David le hopman

(Division Sign-Off) Division of Reproductive, Abdominal, ENT, and Radiological Devices 78507 510(k) Number _

P UNT

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.