The cfrQuant coronary flow reserve (CFR) quantification software quantifies blood flow in the myocardial wall of the heart's left ventricle based on positron emission tomography (PET) images of radionuclide tracer distribution.

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

The software accepts cardiac PET images of either N-13 ammonia or Rb-82 tracer uptake during two physiologic states: baseline (rest) and increased blood flow (stress). A mathematical model computes absolute myocardial perfusion (flow per mass of tissue, or cc/min/gm) at rest and stress. The ratio of stress-to-rest flow is termed the coronary flow reserve (CFR). Visual displays of absolute flow and CFR as well as their numeric quantification are presented to aid diagnostic interpretation of myocardial PET images.

Device Description

The coronary flow reserve (CFR) quantification (cfrQuant) system is a software package intended for use by nuclear medicine and nuclear cardiology physicians and technologists to perform clinical quantitative analysis on cardiac positron emission tomography (PET) image data. Archiving of output data will be supported for clinical diagnostics, quality control, and research.

cfrQuant calculates absolute myocardial blood flow in cc/min/g using a twodimensional topographical map of PET tracer uptake and an integrated arterial input value. Absolute myocardial flow is calculated from a mathematical flow model validated using microspheres in animals (see Yoshida, Mullani and Gould in J Nuc Med 37:1701, 1996).

To compute CFR, three inputs are required: integrated arterial activity in the early part after bolus injection, average myocardial activity in the late part after bolus injection, and correction factors for partial volume effects of the PET scanner. The first number comes from a region of interest (ROI) drawn in the thoracic aorta or left atrium on images taken soon after radionuclide bolus administration. The second number comes from the topographic maps of myocardial uptake produced by the Positron CARDIAC software. The third number varies by PET camera and will be initialized in a user preference file.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the cfrQuant device, based on the provided text. Unfortunately, the provided document is a 510(k) summary and FDA letter, which primarily focuses on regulatory approval and substantial equivalence to predicate devices, rather than detailed performance studies and acceptance criteria as one might find in a full clinical study report. Therefore, some information is not explicitly stated or is inferred.

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary does not explicitly state quantitative acceptance criteria or a formal table of reported device performance metrics against those criteria. The device is cleared based on demonstrating substantial equivalence to predicate devices. The core "performance" is its ability to quantify absolute myocardial blood flow and coronary flow reserve (CFR) using established mathematical models.

However, the technology's validation is mentioned:

Acceptance Criteria (Inferred from description): The software should accurately calculate absolute myocardial blood flow in cc/min/g and coronary flow reserve (CFR) based on PET tracer uptake and arterial input, using a mathematical flow model validated with microspheres.
Reported Device Performance:
- "cfrQuant calculates absolute myocardial blood flow in cc/min/g using a two-dimensional topographical map of PET tracer uptake and an integrated arterial input value."
- "Absolute myocardial flow is calculated from a mathematical flow model validated using microspheres in animals (see Yoshida, Mullani and Gould in J Nuc Med 37:1701, 1996)."
- "The ratio of stress-to-rest flow is termed the coronary flow reserve (CFR). Visual displays of absolute flow and CFR as well as their numeric quantification are presented to aid diagnostic interpretation of myocardial PET images."

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

The provided document does not specify a distinct "test set" sample size or data provenance (country, retrospective/prospective) for a performance validation study of cfrQuant itself.

The primary evidence referenced for the underlying mathematical model's validity is a publication: "Yoshida, Mullani and Gould in J Nuc Med 37:1701, 1996." This publication describes validation using microspheres in animals, not human test sets for the cfrQuant software.

For 510(k) submissions, the focus is often on demonstrating equivalency to existing cleared devices rather than extensive new clinical performance studies, especially for software that implements a known scientific model.

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

Given the lack of a specific "test set" described for cfrQuant's performance validation, this information is not applicable or not provided. The ground truth for the underlying mathematical model's validation was established in animals using microspheres, which is a direct physiological measurement, rather than human expert consensus.

4. Adjudication Method for the Test Set

Not applicable as no specific human-read test set and adjudication process are described for cfrQuant's performance validation.

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

No, the document does not mention an MRMC comparative effectiveness study where human readers' performance with and without AI assistance was evaluated for cfrQuant.

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

The device is inherently an "algorithm only" tool for quantification. Its performance, as described, is the output of its calculations. The reference to the "mathematical flow model validated using microspheres in animals" (Yoshida, Mullani and Gould, 1996) serves as the standalone validation of the core algorithm's underlying principle.

The cfrQuant system is described as a "software package intended for use by nuclear medicine and nuclear cardiology physicians and technologists to perform clinical quantitative analysis." While physicians use the output, the calculation itself is standalone.

7. The Type of Ground Truth Used

For the underlying mathematical model that cfrQuant implements, the ground truth was microspheres in animals. This is a direct physiological measurement of blood flow, considered a gold standard in such preclinical studies.

8. The Sample Size for the Training Set

Not applicable or not provided. This device is based on a pre-established mathematical model, not a machine learning model that requires a "training set" in the conventional sense. The "training" of the model itself would have occurred during its initial development and validation, as referenced by the Yoshida et al. publication.

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

Not applicable in the typical machine learning sense. The ground truth for the validation of the mathematical model was established using microsphere injection in animals with subsequent direct physiological measurement of blood flow. This provides a direct, highly accurate "ground truth" for the flow calculations made by the model.

Summary

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5. 510(k) Summary

K 113754

JUL 19 2012

Owner/Contact:

K. Lance Gould. M.D. Professor of Cardiovascular Medicine University of Texas Medical School at Houston 6431 Fannin St., Suite MSB 4.256 Houston, TX 77030 Phone 713 500 6611 Fax 713 500 6615 Email K.Lance.Gould@uth.tmc.edu

Date of preparation: December 19, 2011

Device trade name: cfrQuant

Common name: Coronary Flow Reserve (CFR) Quantification

Classification names: emission computed tomography system (21 CFR 892.1200, Product Code KPS)

Devices claimed for equivalence:

K101279, Corridor4DM v2010 .
. K083327, syngoCirculation DynamicPET
K080770, ImagenMD with ImagenQ .

General description: The coronary flow reserve (CFR) quantification (cfrQuant) system is a software package intended for use by nuclear medicine and nuclear cardiology physicians and technologists to perform clinical quantitative analysis on cardiac positron emission tomography (PET) image data. Archiving of output data will be supported for clinical diagnostics, quality control, and research.

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Intended use: cfrQuant is intended for quantification of absolute myocardial blood flow and coronary flow reserve when applied to diagnostic cardiac PET imaging in patients with suspected or known coronary artery disease.

Technological characteristics: CFR is a software package that uses standard, industrial computing hardware and applications.

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Image /page/2/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread.

DEPARTMENT OF HEALTH & HUMAN SERVICES

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

K. Lance Gould, M.D. Professor of Cardiovascular Medicine University of Texas Medical School at Houston 6431 Fannin Street. Suite MSB 4.256 HOUSTON TX 77030

JUL 19 2012

Re: K113754

Trade/Device Name: cfrQuant (Coronary Flow Reserve Quantification) Regulation Number: 21 CFR 892.1200 Regulation Name: Emission computed tomography system Regulatory Class: II Product Code: KPS Dated: July 3, 2012 Received: July 6, 2012

Dear Dr. Gould:

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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parti807); labeling (21 CFR:Parts 801 and 809); medical device reporting (reporting of

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medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety 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,

Janine M. Morris

Acting Director Division of Radiological Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Comments of Children Comments

4. Indications for Use

510(k) Number: K113754

Device Name: cfrQuant (Coronary Flow Reserve Quantification)

Indications for Use:

The software accepts cardiac PET images of either N-13 ammonia or Rb-82 tracer uptake during two physiologic states: baseline (rest) and increased blood flow (stress). A mathematical model computes absolute myocardial perfusion (flow per mass of tissue, or cc/min/gm) at rest and stress. The ratio of stress-torest flow is termed the coronary flow reserve (CFR). Visual displays of absolute flow and CFR as well as their numeric quantification are presented to aid diagnostic interpretation of myocardial PET images.

Prescription Use YES (Part 21 CFR 801 Subpart D)

Over-The-Counter Use NO (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Arush D. Shah

(Division Sign-Off)
Division of Radiological Devices
Office of In Vitro Diagnostic Device Evaluation and Safety
510K
K113754

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.