K Number
K182336
Device Name
SubtlePET
Date Cleared
2018-11-30

(94 days)

Product Code
Regulation Number
892.1200
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
SubtlePET is an image processing software intended for use by radiologists and nuclear medicine physicians for transfer, storage, and noise reduction of fluorodeoxyglucose (FDG) and amyloid PET images (including PET/CT and PET/MRI).
Device Description
The SubtlePET image processing software reduces noise to increase image quality using a deep neural network-based algorithm. The software employs a convolutional neural network-based method in a pixel's neighborhood to generate the value for each pixel. Using a residual learning approach, the software predicts the noise components and structural components. The software separates these components, which enhances the structure while simultaneously reducing the noise. The workflow of the product can be easily adapted to existing radiology departmental workflow. The product acts as a DICOM node that receives DICOM 3.0 digital medical image data from the modality or another DICOM source, processes the data and then forwards the enhanced study to the selected destination. This destination can be any DICOM node, typically either the PACS system or a specific workstation.
More Information

Not Found

Yes
The device description explicitly states the use of a "deep neural network-based algorithm" and a "convolutional neural network-based method," which are forms of artificial intelligence and machine learning.

No.
The device is described as image processing software intended for noise reduction of PET images to increase image quality for radiologists and nuclear medicine physicians, without any mention of directly treating or diagnosing medical conditions.

No

Explanation: The device is an image processing software designed to reduce noise and enhance the quality of PET images. It does not analyze images to diagnose or detect diseases; its sole function is to improve the visual quality of existing diagnostic images for interpretation by a physician.

Yes

The device is described as "image processing software" and its function is to process existing medical images (DICOM data) received from modalities or other sources. It does not include any hardware components for image acquisition or patient interaction. The description focuses solely on the software's algorithm and workflow within a digital environment.

No, this device is not an IVD (In Vitro Diagnostic).

Here's why:

  • IVDs are used to examine specimens from the human body. The definition of an IVD involves tests performed on samples like blood, urine, tissue, etc., to provide information about a person's health.
  • SubtlePET processes medical images. The device description clearly states that SubtlePET is "image processing software" that works with "fluorodeoxyglucose (FDG) and amyloid PET images." It receives, stores, and processes these images.
  • The intended use is for image enhancement and noise reduction. The purpose of SubtlePET is to improve the quality of existing medical images for interpretation by radiologists and nuclear medicine physicians. It does not perform any analysis on biological specimens.

The information provided consistently points to SubtlePET being a medical image processing software, not a device used for in vitro diagnostic testing.

No
The letter does not explicitly state that the FDA has reviewed and approved or cleared a PCCP for this specific device.

Intended Use / Indications for Use

SubtlePET is an image processing software intended for use by radiologists and nuclear medicine physicians for transfer, storage, and noise reduction of fluorodeoxyglucose (FDG) and amyloid PET images (including PET/CT and PET/MRI).

Product codes (comma separated list FDA assigned to the subject device)

LLZ, KPS

Device Description

The SubtlePET image processing software reduces noise to increase image quality using a deep neural network-based algorithm.

The software employs a convolutional neural network-based method in a pixel's neighborhood to generate the value for each pixel. Using a residual learning approach, the software predicts the noise components and structural components. The software separates these components, which enhances the structure while simultaneously reducing the noise.

The workflow of the product can be easily adapted to existing radiology departmental workflow. The product acts as a DICOM node that receives DICOM 3.0 digital medical image data from the modality or another DICOM source, processes the data and then forwards the enhanced study to the selected destination. This destination can be any DICOM node, typically either the PACS system or a specific workstation.

Mentions image processing

Yes

Mentions AI, DNN, or ML

Yes

Input Imaging Modality

PET, PET/CT, PET/MRI

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Radiologists and nuclear medicine physicians / Onsite on the facility VM and/or offsite on the cloud VM, depending on the site's configuration

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Subtle Medical conducted the following non-clinical performance tests:

  • Design traceability confirming all requirement tracing is complete from design inputs and verification/validation and that all risk controls are implemented
  • Design verification testing which included confirming all labeling complies with 21CFR801 and all software requirements work as expected
  • Design validation testing simulated intended use to confirm that the end-to-end functionality of the SubtlePET DICOM Dispatcher in conjunction with the SubtlePET algorithm meets the design requirements
  • Noise reduction bench test utilizing representative cases of human data already gathered under the auspices of IRB-approved clinical protocols. The study showed a significant average increase in quantitative metrics for all cases demonstrating that the software reduced noise in PET scans.
    Based upon the results of this testing, it was determined the SubtlePET performance was substantially equivalent to the predicate device.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K063391

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

§ 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.

0

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA) along with the Department of Health & Human Services. The FDA logo features a blue square with the letters 'FDA' in white, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue. To the left of the FDA logo is the Department of Health & Human Services seal, which includes an emblem with a caduceus-like symbol and the text 'DEPARTMENT OF HEALTH & HUMAN SERVICES-USA' arranged around it.

November 30, 2018

Subtle Medical, Inc. % Ms. Terese Bogucki Regulatory Consultant Decus Biomedical Inc. 2342 Shattuck Ave #333 BERKELEY CA 94704

Re: K182336

Trade/Device Name: SubtlePET Regulation Number: 21 CFR 892.2050 Regulation Name: Picture Archiving and Communications System Regulatory Class: Class II Product Code: LLZ Dated: August 27, 2018 Received: August 28, 2018

Dear Ms. Bogucki:

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 mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

1

requirements, including, but not limited to: registration and listing (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Michael D. O'Hara For

Robert A. Ochs, Ph.D. Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.

510(k) Number (if known)

K182336

Device Name SubtlePET

Indications for Use (Describe)

SubtlePET is an image processing software intended for use by radiologists and nuclear medicine physicians for transfer, storage, and noise reduction of fluorodeoxyglucose (FDG) and amyloid PET images (including PET/CT and PET/MRI).

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)☐ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

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time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
of this information collection, including suggestions for reducing this burden, to:

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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB number."

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5 510(k) Summary

Table 5-1. Subject Device Overview.
Submitter's Name:Subtle Medical, Inc.
Address:880 Santa Cruz Ave, Suite 200
Menlo Park, CA 94025
Contact Person:Terese Bogucki
Title:Regulatory Consultant
Telephone Number:650-488-7799
Fax Number:650-227-2264
Email:terri@decusbiomedical.com
Date Summary Prepared:5-NOV-2018
Device Proprietary Name:SubtlePET
Model Number:V 1.0.0
Common Name:SubtlePET
Regulation Number:21 CFR 892.2050
Regulation Name:Picture archiving and communications system
Primary Product Code:LLZ
Secondary Product Code:KPS
Device Class:Class II
Predicate Device:Trade name: Sapheneia Clarity
Manufacturer: Sapheneia Commercial Products AB
Address: Teknikringen 8
SE-583 30 Linkoping, Sweden
Regulation Number: 21 CFR 892.2050
Regulation Name: Picture Archiving and
Communications System
Device Class: Class II
Product Code: LLZ
510(k) Number: K063391
510(k) Clearance Date: April 26, 2007
Table 5-1. Subiect Device Overview

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5.1 Device Description

The SubtlePET image processing software reduces noise to increase image quality using a deep neural network-based algorithm.

The software employs a convolutional neural network-based method in a pixel's neighborhood to generate the value for each pixel. Using a residual learning approach, the software predicts the noise components and structural components. The software separates these components, which enhances the structure while simultaneously reducing the noise.

The workflow of the product can be easily adapted to existing radiology departmental workflow. The product acts as a DICOM node that receives DICOM 3.0 digital medical image data from the modality or another DICOM source, processes the data and then forwards the enhanced study to the selected destination. This destination can be any DICOM node, typically either the PACS system or a specific workstation.

5.2 Indications for Use

SubtlePET is an image processing software intended for use by radiologists and nuclear medicine physicians for transfer, storage, and noise reduction of fluorodeoxyglucose (FDG) and amyloid PET images (including PET/CT and PET/MRI).

5.3 Summary of Technological Characteristics Comparison

Table 5-2 shows the similarities and differences between the technological characteristics of the two products. The key difference is the imaging modality type. Testing demonstrates that the differences do not raise new questions of safety or effectiveness.

TopicPredicate DeviceSubject Device
Physical
CharacteristicsSoftware package that operates on
off-the-shelf hardwareSoftware package that operates
on a virtual machine (VM)
ComputerPC CompatibleVirtual machine host-
compatible system
Image
Processing
Enhancement
LocationOnsite on the desktop computer
serverOnsite on the facility VM
and/or offsite on the cloud VM,
depending on the site's
configuration
DICOM
Standard
ComplianceThe software processes DICOM
compliant image dataSame
Operating
SystemWindowsCentOS 7 Linux

Table 5-2. Summary of Technological Characteristics Comparison

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TopicPredicate DeviceSubject Device
ModalitiesMulti-modalityMulti-modality; specifically
processes PET, PET/CT and
PET/MR images
User InterfaceThe software is designed for use
on a radiology workstation. It is
unknown whether there is a user
interface.None - enhanced images are
viewed on existing PACS
workstations
ProtocolsCustom low dose protocolsStandard scanner protocols
Image
Enhancement
Algorithm
DescriptionSapheneia Clarity™ employs a
sophisticated statistical analysis
of the image structure in the
neighborhood of each pixel.
Using robust estimation methods
the dominant structures are
separated from the embedding
noise. Once the structure has been
determined, it is possible to
strengthen the interesting parts
while simultaneously reducing the
noise.The software employs a
convolutional neural network-
based method in a pixel's
neighborhood to generate the
value for each pixel.
Using a residual learning
approach, the software predicts
the noise components and
structural components. The
software separates these
components, which enhances
the structure while
simultaneously reducing the
noise.
Image
AcquisitionThe acquisition remains the same,
i.e. the image processing can be
generated from multiple
modalities and with predefined or
specific acquisition protocol
settings.The acquisition remains the
same.

5.4 Performance Data

Subtle Medical conducted the following non-clinical performance tests:

  • . Design traceability confirming all requirement tracing is complete from design inputs and verification/validation and that all risk controls are implemented
  • Design verification testing which included confirming all labeling complies . with 21CFR801 and all software requirements work as expected
  • Design validation testing simulated intended use to confirm that the end-to-. end functionality of the SubtlePET DICOM Dispatcher in conjunction with the SubtlePET algorithm meets the design requirements

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  • . Noise reduction bench test utilizing representative cases of human data already gathered under the auspices of IRB-approved clinical protocols. The study showed a significant average increase in quantitative metrics for all cases demonstrating that the software reduced noise in PET scans.
    Based upon the results of this testing, it was determined the SubtlePET performance was substantially equivalent to the predicate device.

5.5 Substantial Equivalence Conclusion

SubtlePET is an image enhancement software which has similar intended use and indications for use statement as the predicate device. The main difference in indications for use is that the predicate and subject devices apply enhancement to different multimodality image types. The two devices have similar technological characteristics: both algorithms are fixed image-domain nonlinear filtering that uses neighborhood information, and both methods have optimized parameters to ensure robustness and adaption to variable structures, tissues, noises and scales. This 510(k) submission includes information on the SubtlePET technological characteristics, as well as performance data and verification and validation activities demonstrating that SubtlePET is as safe and effective as the predicate, and does not raise different questions of safety and effectiveness.