Quantib™ Brain is a non-invasive medical imaging processing application that is intended for automatic labeling, visualization, and volumetric quantification of segmentable brain structures from a set of magnetic resonance (MR) images. The Quantib™ Brain output consists of segmentations, visualizations and volumetric measurements of grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The output also visualizes and quantifies white matter hyperintensity (WMH) candidates. Users need to review and if necessary, edit WMH candidates using the provided tools, before validation of the WMHs. It is intended to provide the trained medical professional with complementary information for the evaluation and assessment of MR brain images and to aid the trained medical professional in quantitative reporting. Quantib™ Brain is a post-processing plugin for the GE Advantage Workstation (AW 4.7) or AW Server (AWS 3.2) platforms.

Device Description

Quantib™ Brain is post-processing analysis software for the GE Advantage Workstation (AW 4.7) and AW Server (AWS 3.2) platforms using Volume Viewer Apps. 13.0 Ext 4 (or higher). It is intended for automatic labeling, visualization, and volumetric quantification of identifiable brain structures from magnetic resonance images (a 3D T1-weighted MR image, with an additional T2-weighted FLAIR MR image for white matter hyperintensities (WMH) segmentation). The segmentation system relies on a number of atlases each consisting of a 3D T1-weighted MR image and a label map dividing the MR image into different tissue segments. Quantib™ Brain provides quantitative information on both the absolute and relative volume of the segmented regions. The automatic WMH segmentation is to be reviewed and if necessary, edited by the user before validation of the segmentation, after which volumetric information is accessible. Longitudinal analysis can be performed for the brain tissue segmentation and WMH seqmentation in order to compare multiple exams of an individual patient. Quantib Brain is intended to provide the trained medical professional with complementary information for the evaluation and assessment of MR brain images and to aid the radiology specialist in quantitative reporting.

AI/ML Overview

Here's an analysis of the acceptance criteria and study details for QuantibTM Brain 1.3 based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria (Implicit from Study)	Reported Device Performance
Brain Volumetry (GM, WM, CSF):
Dice index closer to 1 (perfect overlap)	CSF: 0.78 ± 0.05
	GM: 0.84 ± 0.02
	WM: 0.86 ± 0.02
Absolute difference of relative volumes	CSF: 1.8 ± 1.0 pp
(lower is better, implied target < ~5-10%)	GM: 2.7 ± 2.0 pp
	WM: 2.8 ± 1.9 pp
ICV:
Dice index closer to 1	0.97 ± 0.00
White Matter Hyperintensities (WMH):
Average Dice overlap (closer to 1)	0.61 ± 0.13
Absolute difference of relative volumes	0.5 ± 0.5 pp
(lower is better, implied target < ~5%)

Note: The document does not explicitly state numerical acceptance criteria prior to the study. The reported performance is the outcome, and it is presented as demonstrating substantial equivalence to the predicate device, implying these values were deemed acceptable.

2. Sample Size and Data Provenance for Test Set:

Brain Volumetry (GM, WM, CSF, ICV):
- Sample Size: 33 3DT1w MR images.
- Data Provenance: The set was "carefully selected to include data from multiple vendors and a series of representative scan settings." No specific countries of origin are mentioned, nor is it specified if the data was retrospective or prospective, though "carefully selected" and "representative" often point to a retrospective collection aimed at diversity.
White Matter Hyperintensities (WMH):
- Sample Size: 45 3DT1w images (7 contrast-enhanced, all with corresponding T2w FLAIR images).
- Data Provenance: This set also "represented various scan settings." Similar to the brain volumetry data, specific countries or retrospective/prospective nature are not detailed.

3. Number of Experts and Qualifications for Ground Truth:

The document states that "WMHs were manually segmented on the T2w FLAIR images" and "relative volumes ... were compared to relative volumes derived from manual segmentations and to manual segmentations".
It does not specify the number of experts involved in these manual segmentations or their qualifications (e.g., "radiologist with 10 years of experience").

4. Adjudication Method for Test Set:

The document does not provide any information on the adjudication method used for establishing ground truth manual segmentations (e.g., 2+1, 3+1, none). It simply states "manual segmentations."

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not reported.
The study focuses on the comparison of the algorithm's performance against manual segmentations, not on how human readers' performance might improve with or without AI assistance.

6. Standalone Performance Study:

Yes, a standalone performance study was performed. The reported Dice indices and absolute differences in relative volumes directly measure the algorithm's performance (segmentation and quantification) against ground truth manual segmentations, without human-in-the-loop interaction for the reported metrics.

7. Type of Ground Truth Used:

The ground truth used was expert manual segmentation.
- For brain volumetry (GM, WM, CSF, ICV), the automated segmentations and relative volumes were compared to manual segmentations.
- For WMH, the algorithm's output was compared to WMHs "manually segmented on the T2w FLAIR images."

8. Sample Size for the Training Set:

The document does not provide information on the sample size used for the training set. It only describes the test sets.

9. How Ground Truth for Training Set Was Established:

The document does not provide information on how the ground truth for the training set was established. It only refers to the "segmentation system relies on a number of atlases" but doesn't detail their origin or how their ground truth labels were created for training purposes.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains two logos. The logo on the left is the Department of Health & Human Services - USA logo. The logo on the right is the FDA U.S. Food & Drug Administration logo. The FDA logo is in blue.

Quantib B.V. % Floor van Leeuwen Quality & Regulatory Manager Westblaak 106 3012 KM Rotterdam NETHERLANDS

March 9, 2018

Re: K173939

Trade/Device Name: QuantibTM Brain 1.3 Regulation Number: 21 CFR 892.2050 Regulation Name: Picture archiving and communications system Regulatory Class: Class II Product Code: LLZ Dated: December 22, 2017 Received: December 26, 2017

Dear Floor van Leeuwen:

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. 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); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820);

{1}------------------------------------------------

Page 2 - Floor Leeuwen

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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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/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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K173939

Device Name QuantibTM Brain 1.3

Indications for Use (Describe)

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.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

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

The burden time for this collection of information is estimated to average 79 hours per response, including the 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:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"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."

{3}------------------------------------------------

Quantib™ Brain 1.3 510(k) Summary

Image /page/3/Picture/1 description: The image shows the logo for Quantib. The logo consists of a blue and light blue icon on the left and the word "Quantib" in dark blue on the right. The icon is made up of circles connected by lines, forming a network-like structure.

SUBMITTER 1

Quantib B.V. Westblaak 106 3012 KM Rotterdam Phone: (+31) 108 41 17 49 Contact Person: Floor van Leeuwen Date Prepared: December 20, 2017

Device 2

Name of Device: Quantib™ Brain 1.3 Common or Usual Name: Quantib™ Brain Classification Name: System, image processing, radiology (892.2050) Regulatory Class: II Product Code: Picture archiving and communication system (LLZ)

Predicate device 3

Device: Quantib™ Brain 1.2 Manufacturer: Quantib BV 510(k) Reg. No: K163013 This predicate has not been subject to a design-related recall Requlatory Class: II Product Code: Picture archiving and communication system (LLZ)

Device Description 4

{4}------------------------------------------------

Longitudinal analysis can be performed for the brain tissue segmentation and WMH seqmentation in order to compare multiple exams of an individual patient. Quantib Brain is intended to provide the trained medical professional with complementary information for the evaluation and assessment of MR brain images and to aid the radiology specialist in quantitative reporting.

5 Indications for Use

Indications for use Quantib™ Brain 1.3

Indications for use comparison with predicate device

The intended use of the modified device is equal to the intended use of the previously cleared predicate device [K163013].

6 DEVICE MODIFICATIONS

Quantib™ Brain 1.3 is an update of Quantib™ Brain 1.2 (the predicate device). The differences are the following:

6.1 BRAIN VOLUMETRY ALGORITHM

To improve the ICV results, a different voting mechanism is applied.

6.2 WHITE MATTER HYPERINTENSITIES ALGORITHM

In the White Matter Hyperintensities segmentation algorithm of Quantib Brain 1.3 we have implemented a different type of classify the set of candidate lesions. To improve the algorithm performance, we have extended the set of features used in the classifier.

6.3 LONGITUDINAL REVIEW ALGORITHM

No changes are made to the longitudinal review algorithm.

{5}------------------------------------------------

7 Technological Characteristics

The following technological characteristics are the same for Quantib™ Brain 1.3 and its predicate device Quantib Brain 1.2:

. Intended use and Indications for use
. Target users, anatomical site and usage location
Design .
Compatibility with the environment and other devices .

The following technological characteristics are different:

. Performance: Assessment of the performance of the new WMH algorithm is added. The dataset used for validation has been extended with additional patient data.
. Reported measures: When a contrast-enhanced 3DT1w scan (in combination with a T2w FLAIR scan) are used as input data, the absolute and relative cross sectional volumes of the brain tissues, and therefore also the relative WMH volumes, are not reported. Absolute WMH measures and WMH longitudinal analysis are displayed.
. Required input: Contrast-enhanced 3DT1w scans are no longer excluded from processing of WMH. However, not all measures are reported to the user whenever a contrast-enhanced scan is used as input

8 PERFORMANCE DATA:

1. Quality and safety

Quantib™ Brain 1.3 was designed in compliance with the following process standards:

ISO 14971 - Medical devices - Application of risk management to medical devices
IEC 62304 - Medical device software - Software life cycle processes

The following quality assurance measures were applied to Quantib™ Brain 1.3 development:

Risk and hazard analysis ●
Design reviews
Unit level testing ●
Integration testing ●
System testing
Performance testing ●
. Usability engineering

2. Algorithm performance

To validate the quality of Quantib™ Brain volume measurements and segmentations, the relative volumes and the segmentations were compared to relative volumes derived from manual segmentations and to manual segmentations of the same scan. This analysis was performed for GM, WM, CSF, ICV, and WMHs.

For Brain Volumetry (segmentation and measures of GM, WM, CSF, and ICV) the test set included 33 3DT1w MR images. The set was carefully selected to include data from multiple vendors and a series of representative scan settings. For each scan we selected six (6) slices for comparison. The results are summarized below.

{6}------------------------------------------------

	Dice index	Absolute difference of the relativevolumes [pp]
CSF	0.78 ± 0.05	1.8 ± 1.0
GM	0.84 ± 0.02	2.7 ± 2.0
WM	0.86 ± 0.02	2.8 ± 1.9
ICV	0.97 ± 0.00

Results of comparison between manual and automatic brain tissue segmentation. Reported values are averages ± std. dev., computed over 6 segmented slices of 33 scans. The Dice index provides a measure for overlap of manual and automatic segmentations (1 = perfect overlap). The absolute differences of the relative volumes (of the brain tissues) are averages ± std. dev. in percentage points.

The test set for the White Matter Hyperintensities protocol included 45 3DT1w images, of which 7 contrast-enhanced, all with corresponding T2w FLAIR images. This set also represented various scan settings. WMHs were manually segmented on the T2w FLAIR images and compared to Quantib™ Brain automatic segmentation output. The average Dice overlap between the manual segmentations and Quantib™ Brain segmentations was 0.61 ± 0.13 (over all cases). The absolute difference of the relative volumes (for WMHs) was 0.5 ± 0.5 percentage points (over 38 cases without contrast-enhancement).

CONCLUSIONS ഗ

By virtue of its intended use and physical and technological characteristics, Quantib™ Brain 1.3 is substantially equivalent to a device that has been approved for marketing in the United States. The performance data shows that Quantib™ Brain 1.3 is as safe and effective as 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).