iQ-solutions

K231929 · Sydney Neuroimaging Analysis Centre Pty, Ltd. · QIH · Dec 18, 2023 · Radiology

Device Facts

• Record ID: K231929
• Device Name: iQ-solutions
• Applicant: Sydney Neuroimaging Analysis Centre Pty, Ltd.
• Product Code: QIH · Radiology
• Decision Date: Dec 18, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 892.2050
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device

Intended Use

iQ-solutions™ is a software medical device intended for automatic annotation, visualization, and quantification of segmentable brain structures from a set of brain MRI scans. It is intended to accelerate and improve the quantification of brain structures that would otherwise require a manual process of identifying, and measuring regions of interest in brain MRI scans. iQ-solutions™ consists of both cross-sectional and longitudinal analysis pipelines. The cross-sectional pipeline is intended to conduct structure segmentation and volume analysis on brain MRI scans at a single time point. The longitudinal pipeline is intended to conduct volume change analysis on a single patient's MRI scans acquired on the same scanner, with consistent image acquisition protocol and with contrast at two different time points. The results of the cross-sectional pipeline cannot be compared with the results of the longitudinal pipeline.

Device Story

iQ-solutions™ is a standalone software device for processing brain MRI scans; inputs include pre-contrast T1-weighted, FLAIR, and post-contrast T1-weighted MRI scans. The device uses pre-trained convolutional neural networks (CNNs) to perform automatic segmentation, volume quantification, and longitudinal change analysis. It operates by integrating with a user's PACS system to receive images and return results. Outputs include PDF reports, dynamic web-based reports, and DICOM images with colored overlays of brain substructures and white matter hyperintensities. Used by trained professionals in hospitals, imaging centers, or image-processing labs. The device assists clinicians by automating manual measurement tasks; however, it is not a diagnostic tool, and final interpretation remains the responsibility of the physician. Benefits include accelerated quantification of brain structures and standardized volumetric analysis.

Clinical Evidence

No clinical data. Evidence consists of non-clinical bench testing using a dataset of >1500 patients and >2600 public scans. Performance metrics include: Sequence Classification (100% accuracy), Brain Extraction (DICE 0.982), White matter hyperintensity segmentation (DICE 0.789), Brain Tissue Segmentation (DICE 0.972), and Brain Volume Change Estimation (R² 0.869). All modules met pre-determined acceptance criteria.

Technological Characteristics

Standalone software operating on off-the-shelf hardware. Utilizes CNN-based supervised segmentation. DICOM compatible. Complies with ISO 13485, ISO 14971, IEC 62304, IEC 62366-1, and ISO 12052. Software architecture includes pre-processing (standardization of position/contrast), CNN-based segmentation, and post-processing for statistical calculation and report generation.

Indications for Use

Indicated for automatic annotation, visualization, and quantification of brain structures from MRI scans in patients requiring brain structure volume analysis. Used for cross-sectional segmentation/volume analysis or longitudinal volume change analysis on scans from the same scanner with consistent protocols.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• icobrain 5.0 (K192130)

Submission Summary (Full Text)

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December 18, 2023

Sydney Neuroimaging Analysis Centre Pty Ltd % Belinda Dowsett Associate Director, Medical Devices / IVD PharmaLex Pty Ltd Suite 10.04. 1 Chandos Street St Leonards, NSW 2064 Australia

Re: K231929

Trade/Device Name: iQ-solutions™ Regulation Number: 21 CFR 892.2050 Regulation Name: Medical image management and processing system Regulatory Class: Class II Product Code: QIH, LLZ Dated: September 19, 2023 Received: September 19, 2023

Dear Belinda Dowsett:

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 (the 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 available 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.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.

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For comprehensive regulatory information about mediation-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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Daniel M. Krainak, Ph.D. Assistant 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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### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

### Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2023 See PRA Statement below.

510(k) Number (if known) K231929

Device Name iO-solutionsTM

### Indications for Use (Describe)

iQ-solutions™ is a software medical device intended for automatic annotation, visualization, and quantification of segmentable brain structures from a set of brain MRI scans. It is intended to accelerate and improve the quantification of brain structures that would otherwise require a manual process of identifying, and measuring regions of interest in brain MRI scans.

iQ-solutions TM consists of both cross-sectional and longitudinal analysis pipelines.

· The cross-sectional pipeline is intended to conduct structure segmentation and volume analysis on brain MRI scans at a single time point.

· The longitudinal pipeline is intended to conduct volume change analysis on a single patient's MRI scans acquired on the same scanner, with consistent image acquisition protocol and with contrast at two different time points. The results of the cross-sectional pipeline cannot be compared with the results of the longitudinal pipeline.

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)

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### 510(k) Summary – iQ-solutions™ 5

#### General Information 5.1

| 510(k) Sponsor: | Sydney Neuroimaging Analysis Centre Pty Ltd (SNAC) |
|----------------------|-------------------------------------------------------------------------------------|
| Address: | Level 1, 94 Mallett Street<br>Camperdown NSW 2050<br>Australia |
| Contact Person: | Dr Tim (Chenyu) Wang<br>Director of Operations, Sydney Neuroimaging Analysis Centre |
| Contact Information: | Email: [e-mail]<br>Phone: + 61 2 9114 4187 |
| Date Prepared: | 16 Dec 2023 |

#### 5.2 Device Name and Classification

| Device Name: | iQ-solutions™ |
|-----------------------|----------------------------------------|
| Trade Name: | iQ-solutions™ |
| Common Name: | Medical Image Processing Software |
| Classification Name | System, Image processing, Radiological |
| Classification Panel: | Radiology |
| CFR Section: | 21 CFR §892.2050 |
| Device Class: | Class II |
| Product Code | QIH, LLZ |

#### 5.3 Predicate Device

| Product Name: | icobrain |
|-----------------------|----------------------------------------|
| Device Trade Name: | Icobrain |
| 510(k) Number | K192130 |
| Clearance Date: | December 13, 2019 |
| Manufacturer: | icometrix NV |
| Common Name | Medical Image Processing Software |
| Classification Name: | System, Image processing, Radiological |
| Classification Panel: | Radiology |
| CFR Section | 21 CFR §892.2050 |

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| Device Class | Class II |
|--------------|----------|
| Product Code | LLZ |

#### 5.4 Standards Applied

iQ-solutions™ software has been designed, developed, and tested by the following product and process standards:

- . ISO 13485:2016 Medical devices — Quality management systems — Requirements for regulatory purposes
- ISO 14971:2019 Medical devices – Application of risk management to medical devices
- IEC 62304:2006 + A1:2015 Medical device software software life cycle processes ●
- IEC 62366-1:2015 Medical devices – Part 1: Application of usability engineering to medical devices
- ISO 12052:2006 Digital Imaging and communication in Medicine (DICOM)
- CFR 21 Part 820 Quality System Regulation for Medical Devices

#### Device Description 5.5

The following flowchart describes the iQ-solutions™ process and analysis:

Image /page/5/Figure/13 description: The image is a flowchart that shows the steps involved in image processing. The first step is to input images in DICOM format. The next steps are pre-processing, image processing, and output generation. The final step is to generate a final report in PDF format, DICOM output images, and dynamic reports in a webpage format.

iQ-solutions™ is a standalone software device that processes brain MRI scans to outline and quantify the brain structures described in the intended use. The iQ-solutions™ software interacts with the user's picture archiving and communication system (PACS) to receive scans and returns the results to the same destination or other user-specified radiology software system or database.

iQ-solutions™ analysis module consists of pre-trained convolutional neural networks (CNN) that have been verified and validated to segment the specific brain structures and create binary masks accordingly using the incoming head MRI scans. Each convolutional neural network is coupled with a pre-processing component that transforms the MRI scans to the standard position and contrast; and a post-processing component that prepares for the output annotations, statistical calculation, and the input of the next analysis component in either analysis pipeline.

iQ-solutions™ operates together with a medical image routing software or an integration platform that can connect with iQ-solutions™ and a PACS system that can fulfill the requirements of iQsolutions™.

MRI scans are sent to iQ-solutions™ by means of transmission functions within the user's PACS system. Upon completion of processing, iQ-solutions™ returns results to the user's PACS or other userspecified radiology software system or database.

The results from iQ-solutions™ are not intended to be used as a diagnostic tool, and the interpretation of measurements contained in the iQ-solutions™ report remains entirely the responsibility of the qualified radiologists or physicians managing the individual patient's care.

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iQ-solutions™ takes as input brain MRI scans. During image processing, cross-sectional and longitudinal segmentation is performed, and measurements of the segmented brain structures are provided. The resulting outputs are generated and provided in the form of quantitative reports and the annotation masks of specific segmentations in DICOM format. The reports are in PDF format which are returned to the PACS, together with DICOM images that display colored overlays of specific brain substructures and, where relevant, white matter hyperintensities superimposed on duplicates of the original DICOM images (with watermarks to inform users that these images are not to be used for diagnostic purposes). iQ-solutions™ also provide dynamic reports in a webpage format in which the scan overview panel becomes scrollable, allowing the user to browse through different slices of the scan in the sagittal, coronal, and axial planes.

In this release of iQ-solutions™, the two types of analysis pipelines (cross-sectional study and longitudinal study) are conducted, and different reports are generated together with the generated masks, including:

### iQ-MS™ PDF report:

- Normalized volume and volume change of the whole brain (sum of white matter and gray matter)
- Normalized volume and volume change of gray matter
- Normalized volume and volume change of the thalami
- Unnormalized volume and volume changes of FLAIR white matter hyperintensities (if any)
- Unnormalized volume of T1 post-contrast white matter hyperintensities
- Brain and brain substructure volumes compared with a healthy cohort.

### iQ-COG™ PDF report:

- Normalized volume and volume change of the whole brain (sum of white matter and gray matter)
- Normalized volume and volume change of cortical gray matter
- Normalized volume of the cortex in brain lobes (frontal, parietal, temporal, occipital)
- . Normalized volume and volume change of the hippocampi
- Asymmetry index of left and right cortex in lobes and left and right hippocampi
- Unnormalized volume and volume changes of FLAIR white matter hyperintensities (if any)
- . Brain and brain substructure volumes compared with a healthy cohort.

#### 5.6 Indications for Use

iQ-solutions™ is a software medical device intended for automatic annotation, visualization, and quantification of segmentable brain structures from a set of brain MRI scans. It is intended to accelerate and improve the quantification of brain structures that would otherwise require a manual process of identifying, annotating, and measuring regions of interest in brain MRI scans.

iQ-solutions™ consists of both cross-sectional and longitudinal analysis pipelines.

- . The cross-sectional pipeline is intended to conduct structure segmentation and volume analysis on brain MRI scans at a single time point.
- . The longitudinal pipeline is intended to conduct volume change analysis on a single patient's MRI scans acquired on the same scanner, with consistent image acquisition protocol and with consistent contrast at two different time points.

The results of the cross-sectional pipeline cannot be compared with the results of the longitudinal pipeline.

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#### 5.7 Comparison with Predicate Device

iQ-solutions™ (subject device) has the same intended use as icobrain 5.0 (K192130) (predicate device) as both are intended for automatic labelling, visualization and volumetric quantification of segmentable brain structures based on three-dimensional medical images. The devices both take 3D images of the brain as input and generate an electronic report with similar quantitative information. The principal difference between the devices is that, in addition to MRI images, the predicate icobrain 5.0 (K192130) is able to process non-contrast CT (NCCT) images (for 'icobrain cross'). This difference does not result in a new intended use; and does not impact the safety or effectiveness of the subject device.

The subject device and the predicate device have different technological characteristics with respect to software features, functionalities and core algorithms. These different technological characteristics do not impact the safety or effectiveness of the subject device: specifically, performance data confirms that the subject device is as safe and effective as the predicate device.

Table 2 shows the comparison between the subject device and its predicate and no major technological differences were found between the two systems that raise new issues of safety and/or effectiveness. Thus, the iQ-solutions™ is substantially equivalent to the predicate device.

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Table 2: Comparison table for iQ-solutions™ as the subject device and icobrain 5.0 (K192130) as the Predicate Device.

| Characteristic | Subject device:<br>iQ-solutions™ | Predicate Device:<br>icobrain 5.0 (K192130) | Summary |
|-------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | iQ-solutions™ is a software medical device<br>intended for automatic annotation,<br>visualization, and quantification of<br>segmentable brain structures from a set of<br>brain MRI scans. It is intended to accelerate<br>and improve the quantification of brain<br>structures that would otherwise require a<br>manual process of identifying, annotating, and<br>measuring regions of interest in brain MRI<br>scans.<br>iQ-solutions™ consists of both cross-sectional<br>and longitudinal analysis pipelines.<br>The cross-sectional pipeline is intended to<br>conduct structure segmentation and<br>volume analysis on brain MRI scans at a<br>single time point. The longitudinal pipeline is intended to<br>conduct volume change analysis on a single<br>patient's MRI scans acquired on the same<br>scanner, with a consistent image<br>acquisition protocol and with consistent<br>contrast at two different time points. The results of the cross-sectional pipeline<br>cannot be compared with the results of the<br>longitudinal pipeline. | icobrain 5.0 is intended for automatic labelling,<br>visualization and volumetric quantification of<br>segmentable brain structures from a set of<br>MRI or Non-Contrast CT (NCCT) images. This<br>software is intended to automate the current<br>manual process of identifying, labelling and<br>quantifying the volume of segmentable brain<br>structures identified on MRI or NCCT images.<br>icobrain 5.0 consists of two distinct image<br>processing pipelines: icobrain 5.0 cross and<br>icobrain 5.0 long.<br>icobrain 5.0 cross is intended to provide<br>volumes from MRI or NCCT images acquired<br>at a single brain time point. icobrain 5.0 long is intended to provide<br>changes in volumes between two MRI<br>images that were brain acquired on the<br>same scanner, with the same image<br>acquisition protocol and with the same<br>contrast at two different time points. The results of the icobrain 5.0 cross cannot be<br>compared with the results of icobrain 5.0 long. | Intended use is the same.<br>There is a difference in functionality that does<br>not constitute a major difference.<br>Both devices are intended for automatic<br>labelling, visualization and quantification of<br>segmentable brain structures.<br>Both devices have two pipelines that are<br>intended for cross-sectional analysis and<br>longitudinal analysis, which are intended for<br>images from a single time point and different<br>time points respectively. The results from the<br>pipelines cannot be compared.<br>iQ-solutions™ works with MRI images only,<br>while icobrain 5.0 works with both MRI<br>images and NCCT images (only for icobrain 5.0<br>cross). This difference does not result in a new<br>intended use; rather, use with NCCT only<br>broadens the application to scenarios in which<br>NCCT is the preferred input. This difference<br>does not affect the safety or effectiveness of<br>the subject device. |
| Technological<br>Characteristics | Software package, with off-the-shelf<br>software<br>Operates on off-the-shelf hardware<br>(multiple vendors) | Software package, with off-the-shelf<br>software<br>Operates on off-the-shelf hardware<br>(multiple vendors)<br>DICOM compatible | Same. |
| Characteristic | Subject device:<br>iQ-solutions™ | Predicate Device:<br>icobrain 5.0 (K192130) | Summary |
| | DICOM compatible Segmentation by machine learning and<br>deep learning algorithms (supervised<br>segmentation with Convolutional Neural<br>Networks) Image pre-processing components Measurement calculation Report generation techniques | Segmentation by classical machine learning<br>and deep learning (supervised voxel<br>classification with Convolutional Neural<br>Networks) Image pre-processing components Measurement calculation Report generation techniques | |
| Anatomical Region<br>of Interest | Head | Head | Same |
| Product Input<br>(Data Acquisition<br>Protocol) | Pre-contrast T1-weighted MRI scans from<br>single or multiple time points, Fluid-attenuated inversion recovery (FLAIR)<br>MRI scans from single or multiple time<br>points, and Post-contrast T1-weighted MRI scans from<br>a single time point. | T1-weighted and fluid-attenuated inversion<br>recovery (FLAIR) MRI images from a single<br>or multiple time points Non-contrast CT (NCCT) from a single time<br>point. | Similar.<br>Both the subject device and the predicate<br>device process T1 and FLAIR MRI images from<br>single or multiple time points.<br>NCCT may be used with icobrain 5.0 but not the<br>subject device; lack of this additional input<br>compatibility does not impact the safety or<br>clinical function of the subject device. |
| Product Output | Multiple electronic reports with volumetric<br>information on brain structures and white<br>matter hyperintensities (if any) Automatically compares results to<br>reference percentile data and to prior scans<br>when available Annotated DICOM images that can be<br>displayed on DICOM workstations and<br>Picture Archive and Communications<br>Systems (PACS) | Multiple electronic reports with volumetric<br>information on brain structures and<br>hyperintensities and midline shift (for NCCT<br>only) Automatically compares results to a<br>reference healthy population data and to<br>prior scans when available Annotated DICOM images that can be<br>displayed on DICOM workstations and<br>Picture Archive and Communications<br>Systems (PACS) | Similar.<br>icobrain 5.0 additionally outputs the degree of<br>'midline shift' but this is calculated on NCCT<br>(relevant to specific clinical scenarios only). As<br>iQ-solutions™ does not analyze NCCT, this<br>difference does not impact the safety of the<br>subject device and is not clinically significant |
| Characteristic | Subject device:<br>iQ-solutions™ | Predicate Device:<br>icobrain 5.0 (K192130) | Summary |
| Findings Covered | MR:<br>Normalized volume and volume changes of the whole brain Normalized volume and volume changes of gray matter Normalized volume and volume changes of cortical gray matter Normalized cortical volumes of cortex in brain lobes (frontal, temporal, parietal and occipital) Normalized volume and volume changes in the hippocampi Normalized volume and volume changes of the thalamus Asymmetry index of structures, including cortex in lobes and hippocampus Unnormalized volume and volume changes of FLAIR white matter hyperintensities Unnormalized volume and volume changes of T1-w white matter hyperintensities (in post-contrast T1-w only) | MR:<br>Normalized volume and volume changes of the whole brain Normalized volume and volume changes of gray matter Normalized volume and volume changes of cortical gray matter Normalized volume and volume changes of cortex in frontal, temporal, parietal and occipital lobes Normalized volume and volume changes in the hippocampi Normalized volume and volume change of left and right hippocampus Asymmetry index of structures, including cortex in lobes and hippocampus Unnormalized volume and volume changes of FLAIR white matter hyperintensities FLAIR white matter hyperintensities in different regions (juxtacortical, periventricular, deep white matter and infratentorial). Unnormalized volume and volume changes of T1-w white matter hyperintensities and hypointensities CT: Normalized volumes of the whole brain Normalized volumes of the lateral ventricles Normalized volumes of basal cisterns | Similar.<br>iQ-solutions™ does not process NCCT images and therefore does not report findings for CT images.<br>For head MRI analysis, iQ-solutions™ is similar to icobrain 5.0, except that the subject device iQ-solutions™ does not report statistics related to regional (lobar) cortical volume change or T1-w image-derived hypo-intensities. iQ-<br>solutions™ additionally reports volume analysis of the thalamus.<br>These differences are not expected to affect the safety or effectiveness of the subject device or to be clinically significant in the proposed intended use. |
| Characteristic | Subject device:<br>iQ-solutions™ | Predicate Device:<br>icobrain 5.0 (K192130) | Summary |
| | | Measurement of midline shift<br>Volume of hyperintensities | |
| Removal of Cases<br>from the Worklist<br>Queue | No | No | Same |
| Performance<br>measurement<br>testing | Accuracy (for MRI only)<br>Brain segmentable structure<br>volumes/volume changes compared to FSL<br>generated and manually verified ground<br>truth. Reproducibility (for MRI only) Brain segmentable structure<br>volumes/volume changes compared to test-<br>retest images | Accuracy for MRI measurement Brain segmentable structure volumes/volume changes compared to simulated and/or manually labelled ground truth. Accuracy for CT measurement lesions and midline shift compared to manually labelled ground truth lateral ventricles and the whole brain: MRI images segmented by cleared icobrain 3.0 software taken as ground truth Reproducibility for MRI measurement Brain segmentable structure volumes/volume changes compared to test- retest images. Reproducibility for CT measurements Simulation study | Same for MRI measurements.<br>As iQ-solutions™ is not designed to analyze CT<br>images, the measurements for CT input are not<br>applicable in the subject device. |
| Environment of<br>Use | iQ-solutions™ is used by trained professionals<br>in hospitals, imaging centers or in image-<br>processing labs | icobrain 5.0 is used by trained professionals in<br>hospitals, imaging centers or image-processing<br>labs | Same |
| Tested Items | Product Risk Assessment<br>Software verification tests<br>Software validation tests | Product Risk Assessment<br>Software verification tests<br>Software validation tests | Same |

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SNAC has determined that the predicate icobrain 5.0 (K192130) has similar technological and performance characteristics with respect to the segmentation and quantification of normalized volume and volume changes of different brain structures, including the whole brain, the gray matter, the cortical gray matter and the cortex in the brain lobes; the unnormalized volume and volume changes of FLAIR white matter hyperintensities; and the volume of contrast-enhancing T1 white matter hyperintensities. The differences between the subject device and the predicate device are not considered to be substantial or significant in the proposed intended use.

The conclusions from the verification and validation data support the assertion that the safety and effectiveness of the subject and predicate devices are equivalent; and that any differences in the technological characteristics and functionalities of the subject device do not alter/impact its intended use relative to the predicate product or have any additional implications with respect to safety or efficacy. We (SNAC) conclude that iQ-solutions™ is substantially equivalent to icobrain 5.0.

#### 5.8 Performance Data

Each algorithm was tested using the test dataset, which was further verified by trained neuroimaging analysts and expert radiologists. All algorithms within iQ-solutions™ were verified to have generated results/metrics for compatible scans that met the pre-determined acceptance level(s).

#### 5.9 Data Preparation and Demographics Info

The algorithms were developed based on SNAC in-house datasets collected from more than 1500 patients over a period of ten years, commencing July 2012, acquired from a wide range of clinical scanners, including 1.5T and 3T scanners from Siemens (1750 scans in total), GE (2214 scans in total) and Philips (1593 scans in total). Additionally, publicly available MRI datasets from healthy people were included for both training and testing, including 2629 scans obtained from 2159 subjects. The demographic information is included in Table 3.

| Datasets | Diagnosis<br>(subject/scans) | Number of<br>Subjects (F/M) | Age (mean ± std) | Number of Scans<br>(Vendor:1.5T/3T) |
|-----------------|--------------------------------------------|-----------------------------|-----------------------------|---------------------------------------------------------------------------------------------|
| Public<br>Data | Healthy (1823/2225),<br>Dementia (336/404) | 2159 (1146/1013) | 18y to 95y<br>(44.84±20.63) | 2629, including SIEMENS<br>(347/1449), Philips<br>(307/208), GE (79/221)<br>and others. |
| Private<br>Data | Multiple sclerosis<br>(1570/5664) | 1570 (1069/501) | 18y to 93y<br>(44.02±13.49) | 5664, including SIEMENS<br>(698/1052), Philips<br>(243/1350), GE<br>(1008/1206) and others. |

Table 3. Demographic Summary for Used Data

The in-house dataset contains patients diagnosed with multiple sclerosis, and the patients are also with brain atrophy and related cognitive dysfunctions. The scans of healthy people were also included in the training process to avoid bias. Table 4 summarizes the number of cases and involved subjects used in training and testing all the algorithms.

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| Analysis Modules/Datasets | Number of Cases<br>(Train/Validation) | Number of<br>Cases (Test) | Number of<br>Subjects (All) |
|----------------------------------------------------------|---------------------------------------|---------------------------|-----------------------------|
| Sequence Classification | 4862 | 1207 | 2784 |
| Brain Extraction | 1843 | 458 | 1454 |
| Scaling Factor Estimation | 2986 | 527 | 3513 |
| White matter hyperintensity Segmentation | 1858 | 464 | 1026 |
| Contrast-Enhancing Lesion Segmentation | 79 | 737 | 310 |
| Lesion Inpainting | 449 | 80 | 529 |
| Brain Tissue Segmentation | 4179 | 500 | 3313 |
| Brain Volume Change Estimation | 1487 | 166 | 1648 |
| WMH Lesion Activity | 116 | 64 | 180 |
| Cortical Lobar and Subcortical Structure<br>Segmentation | Not applicable ** | 1504 | 1436 |
| Test-ReTest Dataset | Not applicable ** | 120 | 3 |
| Comprehensive Test Set | Not applicable ** | 81 | 81 |

Table 4. Summary of Number of Cases used in Developing/Evaluating Analysis Modules

# 5.10 Data Annotation and Acceptance Criteria

All data used for development were manually labelled to form the ground truth. The labelled items included sequence types (pre-contrast or post-contrast, T1-weighted or FLAR, brainbased or spine-based), skull and scaling factor based on skulls, skull stripped head, brain tissues (white matter, gray matter and CSF), white matter hyperintensities in patients, contrast-enhancing lesions, white matter hyperintensity lesion changes (new lesions or enlarged lesions), cortical gray matter lobes, thalamus, hippocampus, brain volume change. Specifically, the annotations for skullstripping, brain tissues, cortical gray matter lobes, thalamus, hippocampus, and brain volume changes were originally generated using widely used software items such as FSL and FreeSurfer, and the annotations were manually reviewed and accepted by trained neuroimaging analysts. The annotations for white matter hyperintensities (including pre-contrast ones, contrast-enhancing ones, and lesion changes) were manually annotated by trained neuroimaging analysts. All the annotations are further reviewed by senior neuroimaging analysts according to SNAC SOP.

The Pass/Fail criteria are based on both the metrics and acceptable rate of the manual review. For classification modules, accuracy is higher than 0.9 to be accepted; for segmentation modules, DICE score is higher than 0.6 (for brains the DICE should be higher than 0.9) or R² is higher than 0.7 to be accepted. For modules that are lack of ground truths (scaling factor estimation, lesion inpainting, and substructure volume change estimation), the metrics are better than previously accepted results to be accepted. For all models, the manual acceptable rate should be higher than 80% to call it acceptable.

# 5.11 Data Split

When used for development, the data were split into training, validation, and test splits. For the training/validation/test splits of each task, the same subject was ensured to be included in only one of the three splits, therefore it is ensured the same subject was not used for training and evaluation. The splits of each analysis component have been reviewed before the development process.

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Besides the data used for development, 81 extra patients were reserved as the Comprehensive Test Set, which is used to evaluate the performance of all the analysis components.

# 5.12 Verification and Validation Result

The performance data demonstrates continued conformance with special controls for medical devices containing software. Non-clinical tests were conducted on the subject device during product development.

Software "bench" testing was performed to evaluate the performance and functionality of the technical characteristics of iQ-solutions™. All testable requirement Specifications and the Risk Analysis have been successfully verified and traced.

| Analysis Modules | Metric Result | Acceptable Rate | Pass/Fail |
|----------------------------------------------------------|-----------------|-----------------|-----------|
| Sequence Classification | Accuracy = 100% | 100% | Pass |
| Brain Extraction | DICE = 0.982 | 99.3% | Pass |
| Scaling Factor Estimation | STD = 0.0096 | 100% | Pass |
| White matter hyperintensity Segmentation | DICE = 0.789 | 98.8% | Pass |
| Contrast-Enhancing Lesion Segmentation | DICE = 0.790 | 92.1% | Pass |
| Lesion Inpainting | PSNR = 30.79dB | 97.5% | Pass |
| Brain Tissue Segmentation | DICE = 0.972 | 100% | Pass |
| Brain Volume Change Estimation | $R^2 = 0.869$ | 96.3% | Pass |
| WMH Lesion Activity | $R^2 = 0.833$ | 97.5% | Pass |
| Cortical Lobar and Subcortical Structure<br>Segmentation | $R^2 = 0.833$ | 96.0% | Pass |
| Substructure Volume Change Estimation | STD = 0.0102 | 98.8% | Pass |

Table 5: Summary of Performances of all the Analysis Modules

The conclusions from the verification and validation data support the assertion that the safety and effectiveness of the subject and predicate devices are equivalent; and that any differences in the technological characteristics and functionalities of the subject device do not alter/impact its intended use relative to the predicate product or have any additional implications with respect to safety or efficacy. SNAC concludes that iQ-solutions™ is substantially equivalent to icobrain 5.0 (K192130).

# 5.13 Non-Clinical Tests

Non-clinical tests were conducted to test the functionality of iQ-solutions™. Software validation and bench testing have been conducted to assess the performance claims as well as the claim of substantial equivalence to the predicate device. A summary of tests is pr…