Sim&Size enables visualization of cerebral blood vessels for preoperational planning and sizing for neurovascular interventions and surgery. Sim&Size also allows for the ability to computationally model the placement of neurointerventional devices.

General functionalities are provided such as:

Segmentation of neurovascular structures
Automatic centerline detection
Visualization of X-Ray based images for 2D review and 3D reconstruction
Placing and sizing tools
Reporting tools

Information provided by the software is not intended in any way to eliminate, replace or substitute for, in whole or in part, the healthcare provider's judgment and analysis of the patient's condition.

Device Description

The Sim&Size software is a medical device intended to provide a 3D view of the final placement of implants. It uses an image of the patient produced by 3D rotational angiography. It offers clinicians the possibility of computationally model neurovascular implantable medical devices (IMD) in the artery or in the aneurysm to be treated through endovascular surgery. IMD such as the flow-diverters (FD) and the intrasaccular devices (ISD).

Sim&Size is a software designed with three modules. FDsize is the module that allows to pre-operationally plan the choice of size of flow-diverter devices. IDsize is the module that allows to pre-operationally plan the choice of size of intrasaccular devices. STsize is the module that allows to pre-operationally plan the choice of stent devices.

Associated to these three module is intended to import DICOM and to provide a 3D reconstruction of the vascular tree in the surgical area.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Sim&Size device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA submission details a type of "performance testing - bench" for the computational modeling of neurovascular devices. This includes verification tests (checking mathematical definitions) and validation tests (experimental bench tests, in vitro datasets). The document states that "All performance testing has been performed and passed. The Sim&Size software version 1.1.2 has met the required specifications for the completed tests."

While specific numerical acceptance criteria (e.g., tolerance ranges for length or apposition) are not explicitly stated in the provided text, the successful completion of these tests serves as the reported performance, meeting the implicit acceptance criteria of conforming to mathematical definitions, validity for new IMD devices, proper calibration, and predictability.

Acceptance Criteria Category	Specific Criteria (Implicit/Derived)	Reported Device Performance
Software Functionality	DICOM image import successful	Tests passed (continuous, supervised, acceptance)
	Patient manager functions correctly	Tests passed (continuous, supervised, acceptance)
	Image display & processing correct	Tests passed (continuous, supervised, acceptance)
	Anatomic reconstruction visualization correct	Tests passed (continuous, supervised, acceptance)
	Report creation and visualization correct	Tests passed (continuous, supervised, acceptance)
	Fusion correction (auto/manual) correct	Tests passed (continuous, supervised, acceptance)
	Cybersecurity requirements met	Tests passed (continuous, supervised, acceptance)
	No regression from predicate device	No regression identified between predicate and 1.1.2
FDsize Module Performance	Flow Diverter final length conforms to mathematical definition	Verification tests passed
	Flow Diverter apposition conforms to mathematical definition	Verification tests passed
	Simulation model valid for new IMDs	Validation tests passed
	Proper calibration with device geometrical parameters	Validation tests passed
	Predictability of Sim&Size output for new IMDs	Validation tests passed
STsize Module Performance	Laser cut stents verification via numerical solver	Verification tests passed (for in-house numerical solver)
	IMD final length (braided stents) conforms to mathematical definition	Verification tests passed
	IMD apposition (braided stents) conforms to mathematical definition	Verification tests passed
	Simulation model valid for new stent IMDs	Validation tests passed
	Proper calibration with device geometrical parameters	Validation tests passed
	Predictability of Sim&Size output for new IMDs	Validation tests passed

2. Sample Size for Test Set and Data Provenance

Sample Size for Test Set:
- For the FDsize and STsize modules' validation tests, the text mentions:
  - "Experimental bench tests using optical imaging of new IMD devices samples in both unconstrained and constrained configurations." (The exact number of samples is not specified.)
  - "In vitro (silicon model) datasets in which the predictability of the simulation model is assessed comparing in-vitro and virtual Flow Diverter devices implanted in silicone phantom based on anatomy of patients presenting with intracranial aneurysms." (The exact number of datasets/phantoms/patients is not specified.)
Data Provenance: The phrasing implies the use of in-vitro (silicon model) datasets and experimental bench tests rather than patient data directly for the validation of the modeling. The silicon models are "based on anatomy of patients presenting with intracranial aneurysms," suggesting a derivation from real patient data but not direct use of patient images for this specific performance validation. There is no explicit mention of country of origin for the underlying anatomical data. The study is retrospective in the sense that existing anatomical data or models derived from them are used.

3. Number of Experts and their Qualifications for Ground Truth (Test Set)

The provided text does not specify the number of experts used to establish ground truth for the test set, nor their specific qualifications. The validation tests rely on physical measurements from "optical imaging of new IMD devices samples" and "in vitro (silicon model) datasets" comparing "in-vitro and virtual" results. This suggests the ground truth for these performance tests is derived from direct physical and mathematical conformity, rather than expert consensus on imaging interpretation for the test set performance.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method (like 2+1 or 3+1) for the test set. The performance validation seems to rely on the comparison of the software's computational model outputs with physical measurements from bench tests and in-vitro models, rather than human interpretation.

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

No, an MRMC comparative effectiveness study was not explicitly mentioned or described. The focus of the performance data is on the standalone accuracy and predictability of the computational modeling, not on how the software improves human reader performance compared to a baseline without AI assistance.
The device explicitly states in its Indications for Use: "Information provided by the software is not intended in any way to eliminate, replace or substitute for, in whole or in part, the healthcare provider's judgment and analysis of the patient's condition." This reinforces that it's an assistive tool, but the study described does not quantify its impact on human readers.

6. Standalone (Algorithm Only) Performance Study

Yes, standalone performance (algorithm only) was done and is the primary focus of the performance testing. The "Performance Testing - Bench" section describes verification and validation tests for the "computational modeling of neurovascular devices" in both the FDsize and STsize modules. These tests assess the software's ability to accurately predict IMD length, apposition, conform to mathematical definitions, and be predictive in in-vitro models. This is an assessment of the algorithm's performance in isolation from clinical human-in-the-loop use.

7. Type of Ground Truth Used

The ground truth used for the performance testing (FDsize and STsize modules) includes:

Mathematical definitions: For verifying that computed lengths and appositions conform.
Experimental bench tests: Using "optical imaging of new IMD devices samples" providing physical measurements.
In-vitro (silicon model) datasets: Where the software's predictions are compared against physical implantations in phantoms.

Essentially, the ground truth is a combination of physical measurements, mathematical conformity, and in-vitro experimental results.

8. Sample Size for the Training Set

The document does not provide any information regarding a specific training set size. The description of performance testing focuses on verification and validation of the algorithms without detailing a machine learning training phase or associated dataset. Given the context, it's possible the computational models are based on established biomechanical principles and manufacturer device specifications, rather than being "trained" on a large image dataset in the context of deep learning.

9. How Ground Truth for the Training Set Was Established

As no explicit training set is mentioned in the context of typical machine learning, the question of how its ground truth was established is not addressed. The "simulation model" for the IMD devices is established via "device geometrical parameters that were provided by each of the IMD device manufacturers," and the "in-house numerical solver" for the STsize module, suggesting a rules-based or physics-based modeling approach rather than a data-driven machine learning approach requiring a separate training ground truth.

Summary

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January 27, 2022

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out to the right of the square.

Sim&Cure Lucile Azéma Quality Assurance and Regulatory Affairs Engineer 95 rue Pierre Flourens, Bâtiment H Montpellier, 34090 France

Re: K212373

Trade/Device Name: Sim&Size Regulation Number: 21 CFR 892.2050 Regulation Name: Medical Image Management and Processing System Regulatory Class: Class II Product Code: PZO Dated: December 24, 2021 Received: December 30, 2021

Dear Lucile Azéma:

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

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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/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 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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Naira Muradyan, Ph.D. Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices 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) K212373

Device Name Sim&Size

Indications for Use (Describe)

General functionalities are provided such as:

· Segmentation of neurovascular structures
· Automatic centerline detection
Visualization of X-Ray based images for 2D review and 3D reconstruction
· Placing and sizing tools
· Reporting tools

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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K212373 510(k) Summary

1. Submitter

Submitter's Name: Sim&Cure Address: 95 rue Pierre Flourens, Bâtiment H 34090 Montpellier FRANCE Phone: +33 953 43 88 09

Contact Person: Lucile AZEMA Quality Assurance and Regulatory Affairs Engineer Sim&Cure

Date of Preparation: January 26th, 2022

2. Device Information

Trade Name: Sim&Size Device Classification Name: Software for Visualization of Vascular Anatomy and Intravascular Devices Common Name: Radiological Image Processing Software Regulation Number: 892.2050 Class: II Product Code: PZO

3. Predicate Device

K202322 - Sim&Size, Sim&Cure.

4. Device Description

Associated to these three module is intended to import DICOM and to provide a 3D reconstruction of the vascular tree in the surgical area.

Sim&Size has been simplified as much as possible to guide the user in an intuitive way in order to reduce the total number of actions required and thus to optimize the time taken to obtain the desired results. They are currently seven steps required to choose the optimal size of IMD to be placed:

1- Importing the images: the 3D rotational angiography DICOM files are imported.
2- Selecting of the region of interest (ROI): the user positions and focuses a sphere in the placement zone.
3- Threshold validation: the user checks the accuracy of the automatically extracted arterial wall. The threshold can be adjusted if needed.
4- Choosing the entry point: the user clicks on the entry point to the arterial network in order to retrieve the vessel centerlines.

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Correct automatically or manually the centerline if needed: the user corrects the centerline going 5through a vessel fusion with the automatic tool or manually.
6- Initializing the implant: the user selects an IMD reference and the ideal placement zone.
7- Sizing the implant: IMD apposition is shown by a color chart in the 3D view. The user can change the IMD reference and placement zone to complete the planning for the intervention.

Patient images can be imported into Sim&Size in two wavs: the user can transfer images using an external storage device (i.e.. USB stick) or to retrieve images directly from PACS connectivity if the option is enabled (only the retrieve function is possible).

The Sim&Size software is compatible with the operating systems MS Windows and Mac OS, when it is first installed a check is done to verify if the user's computer meets the minimum requirements for the use of the software. When a new version of the software is available, the update can be done by the user through a link send by Sim&Cure, the user then follows the instructions indicated in the user manual or using the updater tool SacUpdates that notifies the user, then assists the download and the installation of the last version.

The computational modeling of the following devices is supported by the software:

In the FDsize module:
- Medtronic Pipeline Flex Embolization Device (PED P100018/S015); o
- Medtronic Pipeline Flex Embolization Device with Shield Technology (P100018/S026); O
- Stryker Surpass Evolve Flow Diverter System (P170024/S003); O
- MicroVention Flow Re-Direction Endoluminal Device System (FRED P180027); O
- MicroVention Flow Re-Direction Endoluminal Device X System (FRED X P180027/S002). O In the IDsize module:
  - MicroVention Woven EndoBridge Aneurysm Embolization System (WEB P170032). O
In the STsize module:

●

Stryker Neuroform Atlas Stent System (P180031): O
MicroVention Low-Profile Visualized Intraluminal Support (LVIS) and LVIS Jr (LVIS and o LVIS Jr - P170013).

The devices referenced here are FDA-approved neurointerventional devices.

5. Intended Use / Indications for Use

General functionalities are provided such as:

· Segmentation of neurovascular structures
Automatic centerline detection
Visualization of X-ray based images for 2D review and 3D reconstruction
Placing and sizing tools
Reporting tools

6. Comparison of Technological Characteristics with the predicate device

The predicate device for the new version of Sim&Size software is the last version of Sim&Size, cleared per premarket notification K202322. Both versions of Sim&Size have the same indications for use for preoperational planning of neurovascular procedures using existing image data. A summary comparison of technological characteristics is provided below:

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Characteristics	Predicate deviceSim&Size v 1.0.6K202322	Subject deviceSim&Size v 1.1.2This submission K212373
Indications for Use	Sim&Size enables visualization of cerebral blood vessels for preoperational planning and sizing for neurovascular interventions and surgery. Sim&Size also allows for the ability to computationally model the placement of neurointerventional devices. General functionalities are provided such as:• Segmentation of neurovascular structures• Automatic centerline detection• Visualization of X-ray based images for 2D review and 3D reconstruction• Placing and sizing tools• Reporting toolsInformation provided by the software is not intended in any way to eliminate, replace or substitute for, in whole or in part, the healthcare provider's judgment and analysis of the patient's condition.	Same
Interface to Image Sources	DICOM Image Data.	Same
Import of Patient Data	Manual through keyboard/mouse, automatic import with image file, study creation list.	Same
List Image Functionality	Deleting, anonymizing, search.	Same
Image Processing	Segmentation by user and comment.	Same
3D Assessment	3D assessment based on 3D model of the simulated device inside the vessels.	Same
Image and 3D Display	Orthogonal, color volume rendering, 2D slide review, active presets, 3D view of assemblies of devices.	Same
DICOM Support	Read DICOM images from 3D rotational angiography stations.	Same
Computer OS Compatibility	MS Windows and Mac OS.	Same
Data Interchange/ Transfer Method	Transfer by physical media; i.e. USB memory stick and PACS connectivity (retrieve function only).	Same
Output File Format	Local openGL rendering	Same
Preoperational Planning	Yes	Yes
Patient Contact	No	No
Human Intervention for Interpretation of Images	Yes	Yes
Characteristics	Predicate deviceSim&Size v 1.0.6K202322	Subject deviceSim&Size v 1.1.2This submission K212373
STSize Module	No.	YesThe computational model is based onthe FDsize module for the braidedstents and on the IDsize module forthe laser cut stents.
ImplantableMedical Device(IMD) Database	IMDs included:- Pipeline™ Flex Embolization Device (MicroTherapeutics, Inc. d/b/a ev3 Neurovascular,P100018/S015).- Woven EndoBridge (WEB) AneurysmEmbolization System (MicroVention, Inc.,P170032).- Surpass Evolve Flow Diverter System (StrykerNeurovascular, P170024/S003).	Addition of the following IMDs:In the FDsize module:- Pipeline™ Flex Embolization Devicewith Shield Technology (MicroTherapeutics, Inc. d/b/a ev3Neurovascular, P100018/S026).- Flow Re-Direction EndoluminalDevice System (MicroVention, Inc.,P180027).- Flow Re-Direction EndoluminalDevice X System (MicroVention, Inc.,P180027/S002).In the STsize module:- Neuroform Atlas Stent System(Stryker Neurovascular, P180031).- Low-Profile Visualized IntraluminalSupport (LVIS) and LVIS Jr(MicroVention, Inc., P170013).
Numerical solver	Sim&Cure Finite-Element (sacFE) solver(in-house solver)	Same
Fusion	Automatic and manual	Same

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7. Performance Data

The following performance data were performed on Sim&Size in support of the substantial equivalence determination.

Software Verification and Validation Testing

Software verification and validation testing were conducted, and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices."

The software for this device was considered as a "moderate" level of concern, since prior to mitigation of hazards, a failure of the software device could result in minor injury, either to a patient or to a user of the device.

The verification and validation tests included:

Tests of importation of DICOM images. ●
. Patient manager tests.
Tests of image display and processing. ●
. Functioning tests for visualization of anatomic reconstruction.
Report creation and visualization tests. ●
Fusion correction tests (automatic and manual). ●
. Cybersecurity tests.

All the new features described have been tested and the tests are passed.

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In addition, some non-regression testing is included in our continuous tests to check if the addition of new features has not involuntarily induced alteration between versions. There is no regression between the predicate device and the version 1.1.2.

All the continuous, supervised and acceptance tests are pass with the version 1.1.2.

The verification and validation tests demonstrate that the performance and the safety are maintained between the predicate and the subject device.

Performance Testing - Bench

The following performance is tested through the bench tests for computational modeling of neurovascular devices.

FDsize module

The verification testing checks that the Flow Diverter final length and apposition computed through ● the software conform to their mathematical definition.
. The validation tests included:
- Experimental bench tests using optical imaging of new IMD devices samples in both O unconstrained and constrained configurations.
- In vitro (silicon model) datasets in which the predictability of the simulation model is assessed O comparing in-vitro and virtual Flow Diverter devices implanted in silicone phantom based on anatomy of patients presenting with intracranial aneurysms.

This validation testing allows to:

Ensure that the simulation model originally implemented is also valid for the new IMD devices o added.
Verify the proper calibration of the simulation model with the device geometrical parameters O that were provided by each of the IMD device manufacturers.
Assess the predictability of the Sim&Size output for the new IMDs. O

IDsize module

No change in comparison with predicate device K202322.

STsize module

. The verification testing for laser cut stents is provided through the verification of the in-house numerical solver.
The verification testing for braided stents checks that the IMD final length and apposition computed through the software conform to their mathematical definition.
. The validation tests included:
- Experimental bench tests using optical imaging of new IMD devices samples in both o unconstrained and constrained configurations.
- In vitro (silicon model) datasets in which the predictability of the simulation model is assessed O comparing in-vitro and virtual Stent devices implanted in silicone phantom based on anatomy of patients presenting with intracranial aneurysms.

This validation testing allows to:

Ensure that the simulation model originally implemented is also valid for the new stent IMDs O added.
Verify the proper calibration of the simulation model with the device geometrical parameters O that were provided by each of the IMD device manufacturers.
Assess the predictability of the Sim&Size output for the new IMDs. O

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All performance testing has been performed and passed. The Sim&Size software version 1.1.2 has met the required specifications for the completed tests.

8. Summary

Sim&Cure has demonstrated that the Sim&Size software device is substantially equivalent to its listed predicate device. The results of the verification and validation tests demonstrate that the inclusion of the new implantable medical device databases in the Sim&Size software does not raise new questions of safety and effectiveness.

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).