Neurophet SCALE PET is a software for the registration, fusion, display and analysis of medical images from multiple modalities including MRI and PET. The software aids clinician in the assessment and quantification of pathologies from PET Amyloid/FDG scans of the human brain. It enables automatic analysis and visualization of amyloid protein concentration through the calculation of standard uptake volume ratios (SUVR) within target regions of interest and comparison to those within the reference regions.

The software is deployed via medical imaging workplaces and is organized as a series of workflows which are specific to use with radio-tracer and disease combinations.

Device Description

Neurophet SCALE PET is a standalone software product that automatically calculates standardized uptake value ratios (SUVR) and provides quantified calculation results for quantitative analysis of FDG and Amyloid PET images. The calculation results are intended to aid clinicians in diagnosing patients' pathologies. Furthermore, the function provided to visualize the results of the analysis of the image is designed to help clinicians perform accurate visual interpretation.

Functions and workflow supported by the product are as follows: The user may set specified region as reference region, however, in order to achieve reliable constant count in the reference region, FDA recommends the selection of the pons or cerebellar white matter as reference region for assessment of SUVR in FDG PET imaging.

Because this product complies with the standard DICOM medical imaging protocol, it can be used by being linked with picture archive and communications systems (PACS).

AI/ML Overview

Here's an analysis of the acceptance criteria and study details for the Neurophet SCALE PET device, based on the provided document:

Acceptance Criteria and Device Performance

Acceptance Criteria	Reported Device Performance
Segmentation Accuracy	Dice Similarity Coefficient (DSC) of 86.39 ± 3.12% on major subcortical brain structures.
SUVR Calculation Reliability	Intraclass Correlation Coefficient (ICC) > 0.6 for all Regions of Interest (ROI).

Study Details

2. Sample size used for the test set and the data provenance

The document does not explicitly state the sample size used for the test set in the performance studies. It also does not specify the provenance of the data (e.g., country of origin, retrospective or prospective).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document states that "manual segmentation done by experts" was used for the segmentation accuracy evaluation. However, it does not specify the number of experts involved or their qualifications (e.g., "radiologist with 10 years of experience").

4. Adjudication method for the test set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1, none) for establishing the ground truth for the test set. It only mentions "manual segmentation done by experts."

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

No, a multi-reader, multi-case (MRMC) comparative effectiveness study comparing human readers with AI assistance versus without AI assistance was not reported in this document. The studies focus on the standalone performance of the device.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, a standalone performance study was done. The Segmentation Accuracy and SUVR Calculation Reliability tests evaluate the algorithm's performance in comparison to expert manual segmentations and conventional PET processing tools, respectively. This assesses the device's capabilities without a human-in-the-loop directly interpreting the results or making a diagnosis.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for:

Segmentation Accuracy: "Manual segmentation done by experts." This indicates expert consensus-based ground truth.
SUVR Calculation Reliability: Comparison against "conventional PET processing tools." While not explicitly "ground truth" in the clinical sense, it serves as a reference standard for reliability.

8. The sample size for the training set

The document does not provide any information regarding the sample size used for the training set.

9. How the ground truth for the training set was established

The document does not provide any information on how the ground truth for the training set was established.

Summary

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August 5, 2022

NEUROPHET, Inc. % Priscilla Chung Regulatory Affairs Consultant LK Consulting Group USA, Inc. 18881 Von Karman Ave., STE 160 IRVINE CA 92612

Re: K221405

Trade/Device Name: Neurophet SCALE PET Regulation Number: 21 CFR 892.2050 Regulation Name: Medical image management and processing system Regulatory Class: Class II Product Code: LLZ Dated: May 4, 2022 Received: May 16, 2022

Dear Priscilla Chung:

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. Although this letter refers to your product as a device, please be aware 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

for

Michael D. O'Hara, Ph.D. Deputy Director DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K221405

Device Name Neurophet SCALE PET

Indications for Use (Describe)

Neurophet SCALE PET is a software for the registration, display and analysis of medical images from multiple modalities including MRI and PET. The software aids clinician in the assessment and quantification of pathologies from PET Amyloid/FDG scans of the human brain. It enables automatic analysis and visualization of amyloid protein concentration through the calculation of standard uptake volume ratios (SUVR) within target regions of interest and comparison to those within the reference regions.

The software is deployed via medical imaging workplaces and is organized as a series of workflows which are specific to use with radio-tracer and disease combinations.

Type of Use (Select one or both, as applicable)
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X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary (K221405)

This summary of 510(k) information is being submitted in accordance with requirements of 21 CFR Part 807.92.

1. Date: 7/20/2022

2. Applicant / Submitter

NEUROPHET, Inc. 12F, 124, Teheran-ro, Gangnam-gu Seoul, Republic of Korea Tel : +82-2-6954-7971 Fax : +82-2-6954-7972

3. U.S. Designated Agent

Priscilla Chung LK Consulting Group USA, Inc. 18881 Von Karman Ave. STE 160 Irvine, CA 92612 Fax: 714.409.3357 Tel: 714.202.5789 Email: juhee.c@LKconsultingGroup.com

4. Trade/Proprietary Name:

Neurophet SCALE PET

5. Common Name:

Medical Image Processing Software

6. Classification:

Medical Image Management and Processing System (21CFR 892.2050, Product code LLZ, Class 2, Radiology)

7. Device Description:

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visualize the results of the analysis of the image is designed to help clinicians perform accurate visual interpretation.

Because this product complies with the standard DICOM medical imaging protocol, it can be used by being linked with picture archive and communications systems (PACS).

8. Indication for use:

The software is deployed via medical imaging workplaces and is organized as a series of workflows which are specific to use with radio-tracer and disease combinations.

9. Predicate Device:

Primary Predicate: . Veuron-Brain-pAb (K203142) by HEURON CO., LTD.
. Reference Device: Scenium 2.0 (K121074) by Siemens Medical Solutions USA, Inc

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10. Substantial Equivalence:

	Subject Device	Primary predicate Device	Reference Device
Device name	Neurophet SCALE PET	Veuron-Brain-pAb	Scenium 2.0
510(k)	K221405	K203142	K121074
Manufacturer	NEUROPHET, Inc.	HEURON CO., LTD.	Siemens Medical SolutionsUSA, Inc
Product Code	LLZ	LLZ	LLZ
Indications forUse	Neurophet SCALE PET isa software for theregistration, fusion, displayand analysis of medicalimages from multiplemodalities including MRIand PET. The software aidsclinician in the assessmentand quantification ofpathologies from PETAmyloid/FDG scans of thehuman brain. It enablesautomatic analysis andvisualization of amyloidprotein concentrationthrough the calculation ofstandard uptake volumeratios (SUVR) within targetregions of interest andcomparison to those withinthe reference regions. Thesoftware is deployed viamedical imagingworkplaces and isorganized as a series ofworkflows which arespecific to use with radio-tracer and diseasecombinations.	The Veuron-Brain-pAb is asoftware for the registration,fusion, display and analysis ofmedical images from multiplemodalities including MRI andPET.The software aids clinician inthe assessment andquantification of pathologiesfrom PET Amyloid scans ofthe human brain. It enablesautomatic analysis andvisualization of amyloidprotein concentration throughthe calculation of standarduptake volume ratios (SUVR)within target regions ofinterest and comparison tothose within the referenceregions. The software isdeployed via medical imagingworkplaces and is organized asa series of workflows whichare specific to use with radio-tracer and diseasecombinations.	The Scenium display andanalysis software has beendeveloped to aid theClinician in the assessmentand quantification ofpathologies taken from PETand SPECT scans.The software is deploted viamedical imaging workplacesand is organized as a series ofworkflows which are specificto use with particular drugand disease combinations.The software aids in theassessment of human brainscans enabling automatedanalysis throughquantification of mean pixelvalues located withinstandard regions of interest. Itfacilitates comparison withexisting scans derived fromFDG-PET, amyloid PET, andSPECT studies andcalculation of uptake ratiosbetween regions of interest.
TargetAnatomical Sites	Brain	Brain	Brain
Where Used	Hospital	Hospital	Hospital
Design Features	• Import DICOM dataPerform automatic post-processing• Provide the userconfirmation• Export the resulting datathrough data network orUSB	• Import DICOM data Performautomatic post-processing• Provide the user confirmation• Export the resulting data onlythrough USB	• Import DICOM dataPerform automatic post-processing• Provide the userconfirmation• Export the resulting dataonly through data network
Physicalcharacteristics	• Software package• Operates on off-the-shelfhardware (multiplevendors)	• Software package• Operates on off-the-shelfhardware (multiple vendors)	No software required• Operates in a serverlesscloud environment• User interface throughPACS (multiple vendors)
OperatingSystem	Windows 10, 64-bit	Windows 10, 64-bit	Windows 7, 64-bit
Standards	• ISO 14971	• ISO 14971	• ISO 14971
	• IEC 62304	• IEC 62304	• IEC 62304
	• IEC 62366	• IEC 62366	• IEC 62366
Softwareverification andvalidation	Tested in accordance withverification and validationprocesses and planning.The testing results supportthat all the systemrequirements have met theiracceptance criteria and areadequate for its intendeduse.	Tested in accordance withverification and validationprocesses and planning. Thetesting results support that allthe system requirements havemet their acceptance criteriaand are adequate for itsintended use.	Tested in accordance withverification and validationprocesses and planning. Thetesting results support that allthe system requirements havemet their acceptance criteriaand are adequate for itsintended use.
CompatibleInput DataFormat andModality	DICOM & NiFTIPET, MRI	DICOM & NiFTIPET, MRI	DICOMPET, SPECT, MRI, CT
Input PatientData	Manual throughkeyboard/mouse	Manual throughkeyboard/mouse	Manual throughkeyboard/mouse
Output PatientData	Pictures: nii.gzReport: .csv, pdf	Pictures: PNGReport: .csv	Pictures: JPEGReport: DICOM
Study listfunctionality	Search, Importing,Exporting	Search, Importing, Exporting	Search, Importing, Exporting,Deleting

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The subject device (Neurophet SCALE PET) and the predicate device are the image analysis software for PET images scanned the Human Brain.

Both devices have the same intended purpose to support clinicians in the assessment and quantification of pathology through PET scan images.
Both devices automatically calculate the Standardized Uptake Value Ratio (SUVR) value using brain MRI and PET images and provide quantitative analysis results as a report.
Both devices are DICOM compatible and operate on off-the-shelf hardware. Both devices are used by physicians skilled in brain MR imaging.
The compatible input data format and modality are also the same.

Therefore, Neurophet SCALE PET is functionally similar and improved from a previous 510(k) market-cleared Veuron-Brain-pAb software device (K203142).

Following are the differences between Neurophet SCALE PET and the predicate device:

ltem	Neurophet SCALE PET	Veuron-Brain-pAb	Scenium 2.0
SupportedPET imagetypes	Amyloid PETFDG PET	Amyloid PET	Amyloid PETFDG PETSPECT
Output	Pictures: nii.gz	Pictures: PNG	Pictures: JPEG

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Patient Data	Report: .csv, pdf	Report: .csv	Report: DICOM
DesignFeatures	Export the resulting datanetwork or user PC	Export the resulting dataonly through USB	Export the resultingdata only throughdata network

Although both are technically similar, there is a difference in the supported PET image type. The subject device supports Amyloid PET and FDG PET analysis, while the predicate device, Veuron-Brain-pAb(K203142). supports only Amyloid PET analysis. So, we additionally identified a reference device that covered the scope of supported PET image type for the subject device. The reference device, Scenium 2.0(K121074), is an image analysis software that has a similar purpose to the subject device and can support Amyloid PET, FDG PET, SPECT image analysis.

Also, there is a difference in output patient data between the subject device and the predicate device. However, this is only a difference in file format, and the types of output data that users can obtain are the same.

In the data export path, the predicate device can export the data only through a USB. So, we additionally identified a reference device that can export resulting data through data network. Therefore. it is possible to cover this difference by considering both the predicate device and the reference device.

11. Performance Data:

SW verification/validation and the measurement accuracy test were conducted to establish the performance, functionality and reliability characteristics of the subject devices. The device passed all of the tests based on pre-determined Pass/Fail criteria.

The result of the performance test is as follows.

1) Segmentation Accuracy

The performance of the Segmentation function was evaluated by comparing the Dice similarity coefficient (DSC) between Neurophet SCALE PET-produced segmentation and manual segmentation done by experts. For the DSC evaluation, the subject device performed a DSC of 86.39±3.12% on major subcortical brain structures.

2) SUVR Calculation Reliability

The reliability of the SUVR results was evaluated by statistical test using intraclass correlation coefficient between Neurophet SCALE PET-and conventional PET processing tools. For the ICC, the subject device was shown the good reliability (all ROI ICC scores > 0.6).

12. Conclusion:

The subject device is substantially equivalent in the areas of technical characteristics, general

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function, application, and indications for use. The new device does not introduce a fundamentally new scientific technology, and the device has been validated through system level test. Therefore, we conclude that the subject device described in this submission is substantially equivalent to the predicate device.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).