CINA-ASPECTS is a computer-aided diagnosis (CADx) software device used to assist the clinician in the assessment and characterization of brain tissue abnormalities using CT image data.

The Software automatically reorients images, segments and analyzes ASPECTS Regions of Interest (ROIs). CINA-ASPECTS extracts image data for the ROI(s) to provide analysis and computer analytics based on morphological characteristics. The imaging features are then synthesized by an artificial intelligence algorithm into a single ASPECT (Alberta Stroke Program Early CT) Score.

CINA-ASPECTS is indicated for evaluation of patients presenting for diagnostic imaging workup with known MCA or ICA occlusion, for evaluation of extent of disease. Extent of disease refers to the number of ASPECTS regions affected which is reflected in the total score. This device provides information that may be useful in the characterization of early ischemic (acute) brain tissue injury during image interpretation.

CINA-ASPECTS provides a comparative analysis to the ASPECTS standard of care radiologist assessment using the ASPECTS region definitions and highlighting ROIs and numerical scoring.

Limitations:

CINA-ASPECT is not intended for primary interpretation of CT images. It is used to assist physician evaluation.
CINA-ASPECT has been validated in patients with known MCA or ICA unilateral occlusion prior to ASPECTS scoring.
CINA-ASPECTS is not suitable for use on brain scans displaying neurological pathologies other than acute stroke, such as tumors or abscesses, traumatic brain injuries, hemorrhagic transformation and hematoma.
Use of CINA-ASPECT in clinical settings other than brain ischemia within 12 hours from time last known well, caused by known ICA or MCA occlusions has not been tested.
CINA-ASPECTS has only been validated and is intended to be used in patient populations aged over 21.
CINA-ASPECTS has been validated and is intended to be used with images acquired with Canon Medical Systems Corporation, GE Healthcare, Philips Healthcare and Siemens Healthineers scanners.

Contraindications/Exclusions/Cautions:

Patient motion: Excessive patient motion leading to artifacts that make the scan technically inadequate.
Important streak artifacts and noisy images: Presence of important streak artifact and significant noise within the NCCT images that make the scan technically inadequate.
Hemorrhagic Transformation, Hematoma.

Device Description

CINA-ASPECTS is a standalone computer-aided diagnosis (CADx) software that processes noncontrast head CT (NCCT).

CINA-ASPECTS is a standalone executable program that may be run directly from the commandline or through integration, deployment and use with medical image communications devices. The software does not interface directly with any CT scanner or data collection equipment; instead, the software receives non-contrast head CT (NCCT) scans identified by medical image communications devices, processes them using algorithmic methods involving execution of multiple computational steps to provide an automatic ASPECT score based on the case input file for the physician.

The score includes which ASPECT regions are identified based on regional imaging features derived from non-contrast computed tomography (NCCT) brain image data and overlaid onto brain scan images. The results are generated based on the Alberta Stroke Program Early CT Score (ASPECTS) guidelines and provided to the clinician for review and verification. At the discretion of the clinician, the scores may be adjusted based on the clinician's judgment.

Series are processed by running the CINA-ASPECTS Image Processing Applications on noncontrast head CT images (NCCT) to perform the:

Reorientation, tilt-correction of the input imaging data;
Delineation of predefined regions of interest on the corrected input data and computing numerical values characterizing underlying voxel values within those regions;
Visualizing the voxels which have contributed to the ASPECTS score (also referred to as a 'heat map'); and
Labeling of these delineated regions and providing a summary score reflecting the number of regions with early ischemic change as per ASPECTS guidelines.

The CINA-ASPECTS User Interface Agent provides the ASPECTS information to the clinician to review and edit. It also requires the confirmation by a clinician that a Large Vessel Occlusion (LVO) is detected. This confirmation is used by the CINA-ASPECTS to limit the detection of areas of early ischemic changes to the infarcted brain hemisphere selected by the user. The final summary score together with the regions selected and underlying voxel values are then stored in DICOM format to be transferred by the medical image communications device for output to a Picture Archiving and Communication System (PACS) or workstation.

The CINA-ASPECTS device is made of two components:

The CINA-ASPECTS image processing application which reads the input file and generates an automatic ASPECT score and the applications outputs
A CINA-ASPECTS UI Agent which provides the ASPECTS information to the clinician to review and edit for final archiving.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the CINA-ASPECTS device, based on the provided FDA 510(k) summary:

CINA-ASPECTS Device Acceptance Criteria and Performance Study

1. Table of Acceptance Criteria and Reported Device Performance

The provided document details two main studies: a Standalone Performance Testing and a Clinical Multi-Reader Multi-Case (MRMC) Performance Study. The acceptance criteria aren't explicitly listed as a separate table with pass/fail metrics in the summary, but rather are demonstrated through the successful outcomes of these studies. The performance metrics reported are measures of the device's accuracy and utility.

Note: The FDA 510(k) summary typically presents a high-level overview. Specific numerical acceptance thresholds (e.g., "sensitivity must be > X%") are often detailed in the full submission but are not fully elaborated here. Instead, the document states that the device "met all design requirements and specifications" and "achieved its primary endpoint," implying successful adherence to pre-defined acceptance criteria.

Acceptance Criterion (Inferred from Study Goals)	Reported Device Performance (CINA-ASPECTS)
Standalone Performance
Accurate representation of key processing parameters under a range of clinical parameters.	Demonstrated accurate representation. "The Standalone Performance Testing demonstrated that the proposed device provides accurate representation of key processing parameters under a range of clinically relevant parameters." "The CINA-ASPECTS device performed properly and matched with the ground truth."
Generalizability across patient demographics, clinical parameters, ASPECTS regions, and image acquisition parameters.	Achieved primary endpoint and established generalizability. "The Standalone Performance Testing study demonstrated that CINA-ASPECTS achieved its primary endpoint and established that CINA-ASPECTS performances generalize to a range of typical patient demographics, Clinical parameters, ASPECTS regions, and image acquisition parameters encountered in multiple clinical sites and scanner makers and models."
Safety and effectiveness.	"The performance testing of the CINA-ASPECTS device establishes that the subject device is safe and effective, meets its intended use statement and is compatible with clinical use."
Clinical Performance (MRMC Study)
Improve agreement between readers (with AI assist) and reference standard for ASPECTS scoring.	Readers agreed with "almost ½ a region (4.1%, [95% Cl: 3.3% -4.9%]) more per scan with CINA-ASPECTS than without." "The clinical data demonstrates that CINA-ASPECTS shows a significant improvement in the agreement between the readers and a reference standard when using the CINA-ASPECTS software compared to routine clinical practice."
Improve overall reader ROC AUC.	Overall readers' ROC AUC improved significantly from 0.75 (Unaided arm) to 0.79 (Aided arm).
Reduce variation in performance between different readers.	The range in the ROC AUC between users was narrower when assisted by the software.
Reduce mean time spent per case.	The mean time spent per case among all readers was significantly reduced when using CINA-ASPECTS.
Substantial equivalence for improving reader accuracy compared to the predicate device.	"This study demonstrates substantial equivalence of the CINA-ASPECTS software for improving reader accuracy, compared to the predicate device. The results showed statistically significant improvement in the readers' accuracy when using the software compared to the conventional manual method used in routine clinical practice." "With CINA-ASPECTS the readers agreed, on average, with almost ½ a region (4.1%, [95% Cl: 3.3% -4.9%]) more per scan than without CINA-ASPECTS. These findings are similar to the results reported for the predicate device."

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 200 clinical anonymized NCCT cases.
Data Provenance: Retrospective, multinational, multi-vendor dataset from 5 clinical sites in two countries (US and France). Acquired by 4 different scanner makers (GE, Siemens, Canon, Philips) and 27 different scanner models.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The document mentions that the MRMC study evaluated the performance of "8 clinical readers" and that the "clinical data demonstrates that CINA-ASPECTS shows a significant improvement in the agreement between the readers and a reference standard." However, it does not explicitly state the number or qualifications of experts used to establish the ground truth specifically for the standalone performance test.

For the MRMC study readers, it states: "The panel of readers consisted of 4 expert neuroradiologists and 4 non-experts from different specialties (stroke neurologist, general radiologist, neurointensivist, vascular neurologist), representing the intended use population." While these readers contributed to the "aided" and "unaided" performance evaluation, they are not explicitly designated as the ground truth setters for the test set. The term "reference standard" is used, implying a separate, likely expert-derived, ground truth, but its specifics are not detailed here.

4. Adjudication Method for the Test Set

The document does not explicitly state the adjudication method (e.g., 2+1, 3+1) used to establish the ground truth for the test set. It mentions agreement with a "reference standard" in the context of the MRMC study, but not how that reference standard was formed.

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

Was an MRMC study done? Yes, a retrospective, multinational, multi-vendor, and blinded Clinical Multi-Reader Multi-Case (MRMC) Performance study was conducted.
Effect size of how much human readers improve with AI vs without AI assistance:
- Agreement with reference standard: With CINA-ASPECTS, readers agreed, on average, with almost ½ a region (4.1%, [95% Cl: 3.3% -4.9%]) more per scan than without CINA-ASPECTS.
- Overall ROC AUC: Improved significantly from 0.75 (Unaided arm) to 0.79 (Aided arm).
- Reduced variation: The range in the ROC AUC between users was narrower when assisted by the software.
- Time spent: Mean time spent per case among all readers was significantly reduced when using CINA-ASPECTS.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)

Was a standalone study done? Yes. "Standalone performance testing was conducted to comply with special controls for this device type."

7. Type of Ground Truth Used

The document states that in the standalone performance testing, "The CINA-ASPECTS device performed properly and matched with the ground truth." For the MRMC study, it refers to improvement in "agreement between the readers and a reference standard."
However, the specific methodology for establishing this "ground truth" or "reference standard" (e.g., expert consensus of several independent radiologists, pathology results, outcomes data) is not explicitly detailed in the provided text. It is implied to be expert-derived, given the context of radiological assessment.

8. Sample Size for the Training Set

The document states, "The validation dataset was separated from the one used for the algorithm training/testing and has never been used in any way in the development of the software device." However, the sample size for the training set is not provided in this summary.

9. How the Ground Truth for the Training Set was Established

The document describes how the validation dataset was separated from the training/testing data but does not specify how the ground truth for the training set was established.

Summary

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Avicenna.AI % John Smith Partner Hogan Lovells US LLP 555 13th St. NW Washington, District of Columbia 20004

March 15, 2024

Re: K233342

Trade/Device Name: CINA-ASPECTS Regulation Number: 21 CFR 892.2060 Regulation Name: Radiological computer-assisted diagnostic software for lesions suspicious of cancer Regulatory Class: Class II Product Code: POK Dated: February 15, 2024 Received: February 15, 2024

Dear John Smith:

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.

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).

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Your device is also subject to, among other requirements, the Quality System (OS) 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.

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.

Jessica Lamb

Jessica Lamb, Ph.D. Assistant Director Imaging Software Team DHT 8B: Division of Radiological Imaging Devices and Electronic Products OHT 8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

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510(k) Number (if known) K233342

Device Name

CINA-ASPECTS

Indications for Use (Describe)

CINA-ASPECTS is a computer-aided diagnosis (CADx) software device used to assist the clinician in the assessment and characterization of brain tissue abnormalities using CT image data.

The Software automatically recrients images, segments and analyzes ASPECTS Regions of Interest (ROIs). CINA-ASPECTS extracts image data for the RO(s) to provide analysis and computer analytics based on morphological characteristics. The imaging features are then synthesized by an artificial intelligence algorithm into a single ASPECT (Alberta Stroke Program Early CT) Score.

CINA-ASPECTS is indicated for evaluation of patients presenting for diagnostic imaging with known MCA or ICA occlusion, for evaluation of extent of disease. Extent of disease refers to the number of ASPECTS regions affected which is reflected in the total score. This device provides information that may be useful in the characterization of early ischemic (acute) brain tissue iniurv during image interpretation.

CINA-ASPECTS provides a comparative analysis to the ASPECTS standard of care radiologist assessment using the ASPECTS region definitions and highlighting ROIs and numerical scoring.

Limitations:

CINA-ASPECT is not intended for primary interpretation of CT images. It is used to assist physician evaluation. 2. CINA-ASPECT has been validated in patients with known MCA or ICA unilateral occlusion prior to ASPECTS scoring.
CINA-ASPECTS is not suitable for use on brain scans displaying neurological pathologies other than acute stroke, such as tumors or abscesses, traumatic brain injuries, hemorrhagic transformation and hematoma.
Use of CINA-ASPECT in clinical settings other than brain ischemia within 12 hours from time last known well, caused by known ICA or MCA occlusions has not been tested.
CINA-ASPECTS has only been validated and is intended to be used in patient populations aged over 21.
CINA-ASPECTS has been validated and is intended to be used with images acquired with Canon Medical Systems Corporation, GE Healthcare, Philips Healthcare and Siemens Healthineers scanners.

Contraindications/Exclusions/Cautions:

. Patient motion: Excessive patient motion leading to artifacts that make the scan technically inadequate.
lmportant streak artifacts and noisy images: Presence of important streak artifact and significant noise within the . NCCT images that make the scan technically inadequate.

Hemorrhagic Transformation, Hematoma. .

Type of Use (Select one or both, as applicable)

区 Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) SUMMARY

AVICENNA.AI's CINA-ASPECTS

Submitter

Applicant:

AVICENNA.AI ZI Athelia, 297 Av. du Mistral Bât. A, 13600 La Ciotat France

Contact Person: Stephane Berger Regulatory Manager Phone: +33 6 12 12 28 13 E-mail: stephane.berger@avicenna.ai

Date prepared: February 15, 2024

Device Identification

Name of Device:	CINA-ASPECTS
Classification Name:	Radiological computer-assisted diagnostic software for lesions suspicious of cancer
Regulation No:	21 CFR § 892.2060
Product Code:	POK
Regulatory Class:	Class II
Classification Panel:	Radiology devices

Predicate Device

The CINA-ASPECTS device is substantially equivalent to the following predicate device with regard to indications for use, performance, and technological characteristics:

510(k):	K200760
Trade Name:	Rapid ASPECTS
Manufacturer:	ISchemaView Inc.
Classification Name:	Radiological computer-assisted diagnostic software for
	lesions suspicious of cancer
Regulation No:	21 CFR § 892.2060
Product Code:	POK
Regulatory Class:	Class II

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Device Description

CINA-ASPECTS is a standalone computer-aided diagnosis (CADx) software that processes noncontrast head CT (NCCT).

The score includes which ASPECT regions are identified based on regional imaging features derived from non-contrast computed tomography (NCCT) brain image data and overlaid onto brain scan images. The results are generated based on the Alberta Stroke Program Early CT Score (ASPECTS) quidelines and provided to the clinician for review and verification. At the discretion of the clinician, the scores may be adjusted based on the clinician's judgment.

Series are processed by running the CINA-ASPECTS Image Processing Applications on noncontrast head CT images (NCCT) to perform the:

Reorientation, tilt-correction of the input imaging data; .
. Delineation of predefined regions of interest on the corrected input data and computing numerical values characterizing underlying voxel values within those reqions;
. Visualizing the voxels which have contributed to the ASPECTS score (also referred to as a 'heat map'); and
. Labeling of these delineated regions and providing a summary score reflecting the number of regions with early ischemic change as per ASPECTS guidelines.

The CINA-ASPECTS device is made of two components:

-The CINA-ASPECTS image processing application which reads the input file and generates an automatic ASPECT score and the applications outputs
A CINA-ASPECTS UI Agent which provides the ASPECTS information to the clinician to review and edit for final archiving.

Intended Use / Indications for Use

CINA-ASPECTS is a computer-aided diagnosis (CADx) software device used to assist the clinician in the assessment and characterization of brain tissue abnormalities using CT image data.

The Software automatically reorients images, segments and analyzes ASPECTS Regions of Interest (ROIs). CINA-ASPECTS extracts image data for the ROI(s) to provide analysis and

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computer analytics based on morphological characteristics. The imaging features are then synthesized by an artificial intelligence algorithm into a single ASPECT (Alberta Stroke Program Early CT) Score.

CINA-ASPECTS provides a comparative analysis to the ASPECTS standard of care radiologist assessment using the ASPECTS region definitions and highlighting ROIs and numerical scoring.

Limitations:

CINA-ASPECT is not intended for primary interpretation of CT images. It is used to assist physician evaluation.
CINA-ASPECT has been validated in patients with known MCA or ICA unilateral occlusion prior to ASPECTS scoring.
CINA-ASPECTS is not suitable for use on brain scans displaying neurological pathologies other than acute stroke, such as tumors or abscesses, traumatic brain injuries, hemorrhagic transformation and hematoma.
Use of CINA-ASPECT in clinical settings other than brain ischemia within 12 hours from time last known well, caused by known ICA or MCA occlusions has not been tested.
CINA-ASPECTS has only been validated and is intended to be used in patient populations aged over 21.
CINA-ASPECTS has been validated and is intended to be used with images acquired with Canon Medical Systems Corporation, GE Healthcare, Philips Healthcare and Siemens Healthineers scanners.

Contraindications/Exclusions/Cautions:

Patient motion: Excessive patient motion leading to artifacts that make the scan technically ■ inadequate.
Important streak artifacts and noisy images: Presence of important streak artifact and significant noise within the NCCT images that make the scan technically inadequate.
Hemorrhagic Transformation, Hematoma.

Summary of Performance Data

The following performance data were provided in support of the substantial equivalence determination.

Software Verification and Validation Testing

CINA-ASPECTS complies with DICOM (Digital Imaging and Communications in Medicine) -Developed by the American College of Radiology and the National Electrical Manufacturers Association. NEMA PS 3.1 - 3.20.

Avicenna.Al conducted extensive performance validation testing and software verification and validation testing of the CINA-ASPECTS device as standalone software. CINA-ASPECTS is tested against its user needs and intended use by the successful execution of planned software

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verification and validation testing included in this submission.

Software performance, validation and verification testing demonstrated that the CINA-ASPECTS met all design requirements and specifications associated with the intended use of the software.

Standalone Performance Testing

Standalone performance testing was conducted to comply with special controls for this device type.

Avicenna.Al conducted a retrospective, multinational, multi-vendor and blinded Pivotal Standalone Testing Performance study of CINA-ASPECTS v1.5 software used to assist the clinicians in the assessment and characterization of brain tissues' abnormalities using CT image data.

The Standalone Performance Testing demonstrated that the proposed device provides accurate representation of key processing parameters under a range of clinically relevant parameters.

The Standalone Performance Testing dataset included 200 clinical anonymized NCCT cases from 5 clinical sites, distributed in two countries: US and France. It was acquired by 4 different scanner makers (GE, Siemens, Canon and Philips) and 27 different scanner models. The validation dataset was separated from the one used for the algorithm training/testing and has never been used in any way in the development of the software device.

The Standalone Performance Testing study demonstrated that CINA-ASPECTS achieved its primary endpoint and established that CINA-ASPECTS performances generalize to a range of typical patient demographics, Clinical parameters, ASPECTS regions, and image acquisition parameters encountered in multiple clinical sites and scanner makers and models.

The performance testing of the CINA-ASPECTS device establishes that the subject device is safe and effective, meets its intended use statement and is compatible with clinical use. The CINA-ASPECTS device performed properly and matched with the ground truth. Finally, the important heterogeneity of the dataset used for the device Pivotal Standalone Performance Testing and the good provided global and stratified performance results should quarantee enough robustness for generalization of its use for the intended population, ensuring the device reliability.

Clinical studies

Additionally. Avicenna.Al conducted a retrospective, multinational, multi-vendor and blinded Clinical Multi-Reader Multi-Case (MRMC) Performance study of CINA-ASPECTS v1.5 software used to assist the clinicians in the assessment and characterization of brain tissues' abnormalities using CT image data.

The MRMC study evaluated the performance of 8 clinical readers in the assessment of ASPECTS for NCCT retrospective scans with and without the aid of CINA-ASPECTS. The 8 readers scored each of the 10 ASPECTS regions of the 200 cases independently. The panel of readers consisted of 4 expert neuroradiologists and 4 non-experts from different specialties (stroke neurologist, general radiologist, neurointensivist, vascular neurologist), representing the intended use population.

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With CINA-ASPECTS the readers agreed, on average, with almost ½ a region (4.1%, [95% Cl: 3.3% -4.9%]) more per scan than without CINA-ASPECTS. These findings are similar to the results reported for the predicate device.

In addition, the overall readers' ROC AUC also improved significantly from 0.75 (Unaided arm) to 0.79 (Aided arm). The range in the ROC AUC between users was also narrower when assisted by the software, indicating a reduction in the variation of performance between different readers when the device's outputs were available.

Finally, the mean time spent per case among all readers was significantly reduced when using CINA-ASPECTS, indicating that the end-users' were not only more accurate in the assessment of ASPECTS but also faster when the device outputs were available.

As the study used retrospective data, there were no specific safety endpoints in the reader study.

This study demonstrates substantial equivalence of the CINA-ASPECTS software for improving reader accuracy, compared to the predicate device. The results showed statistically significant improvement in the readers' accuracy when using the software compared to the conventional manual method used in routine clinical practice.

Substantial Equivalence

Both proposed and predicate devices have intended use. Both devices are computeraided diagnosis (CADx) software devices used to assist clinicians in the assessment and characterization of brain tissue abnormalities using CT image data.

Both devices segment and identify ASPECTS regions and use machine learning algorithms to analyze image data to facilitate the evaluation of extent of disease and to identify and count the affected ASPECTS regions to generate an ASPECTS score. Both devices display and highlight the affected ASPECTS regions along with the automatically generated ASPECTS score.

Both devices are not intended for primary interpretation of CT images and both require that cases processed meet prerequisite criteria such that a primary diagnosis of ICA or MCA occlusion has already been made by clinicians prior to accessing the processing results and the resulting ASPECTS score.

Both devices include a gating condition requiring users to confirm that the case in question is for a confirmed ICA or MCA occlusion before processing results are made available.

Both devices include pre-processing steps to normalize NCCT scan orientation in order to identify and segment ASPECTS regions on the subject NCCT scan.

In both cases, the algorithms identify signs indicative of ischemic damage and relate these to the segmented ASPECTS regions in order to determine whether or not individual ASPECTS regions are included as contributing to a reduced ASPECT score. In both cases, the segmented ASPECTS regions are labelled and presented to users in the software User Interface with the regions highlighted depending on whether they have been determined to affect the ASPECT score or not. In both cases, users can manually edit and override the automated result for one or more ASPECTS regions by selecting the regions.

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Both predicate and proposed devices use trained machine learning AI algorithms to analyze NCCT scans to identify signs indicative of ischemic damage.

The following principal difference exists between CINA-ASPECTS and the predicate device:

CINA-ASPECTS is indicated for cases within 12 hours from time last known well. -
CINA-ASPECTS uses machine learning algorithms based on deep learning techniques.
CINA-ASPECTS has only been validated and is intended to be used in patient populations aged over 21.
CINA-ASPECTS has been validated and is intended to be used on Canon Medical Systems -Corporation, GE Healthcare, Philips Healthcare and Siemens Healthineers scanners whereas Rapid ASPECTS has been validated and is intended to be used on GE Lightspeed VCT Scanners.

Table 1 compares the key features of the subject and the predicate devices.

Key Feature	Subject device: CINA-ASPECTSSoftware	Predicate device: ISchemaView Inc.Rapid ASPECTS Software (K200760)
Intended Use /Indications forUse	CINA-ASPECTS is a computer-aideddiagnosis (CADx) software device usedto assist the clinician in the assessmentand characterization of brain tissueabnormalities using CT image data.	Rapid ASPECTS is a computer aideddiagnosis (CADx) software device usedto assist the clinician in the assessmentand characterization of brain tissueabnormalities using CT image data.
	The Software automatically reorientsimages, segments and analyzesASPECTS Regions of Interest (ROIs).CINA-ASPECTS extracts image datafor the ROI(s) to provide analysis andcomputer analytics basedonmorphological characteristics. Theimaging features are then synthesizedby an artificial intelligence algorithminto a single ASPECT (Alberta StrokeProgram Early CT) Score.	The Software automatically registersimages and segments and analyzesASPECTS Regions of Interest (ROIs).Rapid ASPECTS extracts image datafor the ROI(s) to provide analysis andcomputer analytics basedonmorphological characteristics. Theimaging features are then synthesizedby an artificial intelligence algorithminto a single ASPECT (Alberta StrokeProgram Early CT) Score.
	CINA-ASPECTS is indicatedforevaluation of patients presenting fordiagnostic imaging workup with knownMCA or ICA occlusion, for evaluation ofextent of disease. Extent of diseaserefers to the number of ASPECTSregions affected which is reflected inthe total score. This device providesinformation that may be useful in thecharacterization of early ischemic	Rapid ASPECTS is indicated forevaluation of patients presenting fordiagnostic imaging workup, orevaluation of extent of disease. Extentof disease refers to the number ofASPECTS regions affected which isreflected in the total score. This deviceprovides information that may be usefulin the characterization of early ischemicbrain tissue injury during image
Key Feature	Subject device: CINA-ASPECTSSoftware	Predicate device: ISchemaView Inc.Rapid ASPECTS Software (K200760)
	(acute) brain tissue injury during imageinterpretation.CINA-ASPECTS provides acomparative analysis to the ASPECTSstandard of care radiologistassessment using the ASPECTSregion definitions and highlighting ROIsand numerical scoring	interpretation.Rapid ASPECTS provides acomparative analysis to the ASPECTSstandard of care radiologistassessment using the ASPECTS atlasdefinitions and atlas display includinghighlighted ROIs and numericalscoring.
	Limitations:1. CINA-ASPECT is not intended forprimary interpretation of CT images. Itis used to assist physician evaluation.2. CINA-ASPECT has been validated inpatients with known MCA or ICAunilateral occlusion prior to ASPECTSscoring.3. CINA-ASPECTS is not suitable foruse on brain scans displayingneurological pathologies other thanacute stroke, such as tumors orabscesses, traumatic brain injuries,hemorrhagic transformation andhematoma.4. Use of CINA-ASPECT in clinicalsettings other than brain ischemiawithin 12 hours from time last knownwell, caused by known ICA or MCAocclusions has not been tested.5. CINA-ASPECTS has only beenvalidated and is intended to be used inpatient populations aged over 21.6. CINA-ASPECTS has been validatedand is intended to be used with imagesacquired with Canon Medical SystemsCorporation, GE Healthcare, PhilipsHealthcare and Siemens Healthineersscanners.	Limitations:1. Rapid ASPECTS is not intended forprimary interpretation of CT images. Itis used to assist physician evaluation.2. Rapid ASPECTS has been validatedin patients with known MCA or ICAocclusion prior to ASPECT scoring.3. Use of the Rapid ASPECTS Modulein clinical settings other than early brainischemia (within 6 hours) caused byknown ICA or MCA occlusions has notbeen tested.4. Rapid ASPECTS has been validatedand is intended to be used on GELightspeed VCT Scanners.Contraindications/Exclusions/Caution:• Patient Motion: excessive motionleading to artifacts that make the scantechnically inadequate.• Hemorrhagic Transformation,Hematoma
	Contraindications/Exclusions/Caution:• Patient motion: Excessivepatient motion leading toartifacts that make the scantechnically inadequate.• Important streak artifacts andnoisy images: Presence ofimportant streak artifact and	• Very thin or no Ventricles
Key Feature	Subject device: CINA-ASPECTSSoftware	Predicate device: ISchemaView Inc.Rapid ASPECTS Software (K200760)
	significant noise within theNCCT images that make thescan technically inadequate.- Hemorrhagic Transformation,Hematoma.
Environment ofuse	Clinical/Hospital environment	Clinical/Hospital environment
Primary Users	Neuroradiologist/Clinician	Neuroradiologist/Clinician
Anatomicalregionofinterest	Stroke/Head	Stroke/Head
Standard ofCareRepresentation	ASPECTS Scoring	ASPECTS Scoring
Dataacquisitionprotocol	Non-contrast head CT scans	Non-contrast head CT scans
TechnicalImplementation	AI/Deep Learning	ML/AI/Random Forest
Segmentationof region ofinterest	No; device does not mark, highlight, ordirect users' attention to a specificlocation in the original image	No; device does not mark, highlight, ordirect users' attention to a specificlocation in the original image
Image Overlay	ASPECTS regions, highlighted byalgorithms.	ASPECTS regions, highlighted byalgorithms.
GatingConditions	Users must confirm ICA or MCAocclusion prior to accessing CINA-ASPECTS results	Users must confirm LVO prior toaccessing Rapid ASPECTS results
Alteration oforiginal imagedata base	No	No
Key Feature	Subject device:Software	CINA-ASPECTS	Predicate device: ISchemaView Inc.Rapid ASPECTS Software (K200760)
AltersStandard ofCare Workflow	In parallel to		In parallel to

Table 1: Comparison of key features between CINA-ASPECTS and predicate device (ISchemaView Inc. Rapid ASPECTS)

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Conclusion

In conclusion, the predicate device has the same intended use and substantially similar indications for use and technological characteristics as CINA-ASPECTS. Performance data demonstrates that CINA-ASPECTS performs as intended within the same clinically relevant parameters for the intended use as the predicate device. The clinical data demonstrates that CINA-ASPECTS shows a significant improvement in the agreement between the readers and a reference standard when using the CINA-ASPECTS software compared to routine clinical practice. CINA-ASPECTS is intended to improve reader performance in estimating an overall ASPECTS score. However, some imaging and anatomical factors, such as important streak and motion artifacts, beam-hardening artifacts, noisy images, presence of tumors, etc., may impede the NCCT interpretation by the device. Therefore, a particular attention must be paid to these confounding factors. The risk/benefit profile of CINA-ASPECTS remains favorable based on the favorable impact on readers' overall aided performance in calculating an ASPECT score (as measured in the reader study), and the inherent inter-reader variability in identifying individual affected ASPECTS reqions.

The company believes that CINA-ASPECTS is substantially equivalent to the Rapid ASPECTS predicate.

Regulation Number and Section

§ 892.2060 Radiological computer-assisted diagnostic software for lesions suspicious of cancer.

(a)
Identification. A radiological computer-assisted diagnostic software for lesions suspicious of cancer is an image processing prescription device intended to aid in the characterization of lesions as suspicious for cancer identified on acquired medical images such as magnetic resonance, mammography, radiography, or computed tomography. The device characterizes lesions based on features or information extracted from the images and provides information about the lesion(s) to the user. Diagnostic and patient management decisions are made by the clinical user.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) A detailed description of the image analysis algorithms including, but not limited to, a detailed description of the algorithm inputs and outputs, each major component or block, and algorithm limitations.
(ii) A detailed description of pre-specified performance testing protocols and dataset(s) used to assess whether the device will improve reader performance as intended.
(iii) Results from performance testing protocols that demonstrate that the device improves reader performance in the intended use population when used in accordance with the instructions for use. The performance assessment must be based on appropriate diagnostic accuracy measures (
e.g., receiver operator characteristic plot, sensitivity, specificity, predictive value, and diagnostic likelihood ratio). The test dataset must contain sufficient numbers of cases from important cohorts (e.g., subsets defined by clinically relevant confounders, effect modifiers, concomitant diseases, and subsets defined by image acquisition characteristics) such that the performance estimates and confidence intervals of the device for these individual subsets can be characterized for the intended use population and imaging equipment.(iv) Standalone performance testing protocols and results of the device.
(v) Appropriate software documentation (
e.g., device hazard analysis; software requirements specification document; software design specification document; traceability analysis; and description of verification and validation activities including system level test protocol, pass/fail criteria, results, and cybersecurity).(2) Labeling must include:
(i) A detailed description of the patient population for which the device is indicated for use.
(ii) A detailed description of the intended reading protocol.
(iii) A detailed description of the intended user and recommended user training.
(iv) A detailed description of the device inputs and outputs.
(v) A detailed description of compatible imaging hardware and imaging protocols.
(vi) Warnings, precautions, and limitations, including situations in which the device may fail or may not operate at its expected performance level (
e.g., poor image quality or for certain subpopulations), as applicable.(vii) Detailed instructions for use.
(viii) A detailed summary of the performance testing, including: Test methods, dataset characteristics, results, and a summary of sub-analyses on case distributions stratified by relevant confounders (
e.g., lesion and organ characteristics, disease stages, and imaging equipment).