The syngo. CT Neuro Perfusion software package is designed to evaluate areas of brain perfusion. The software processes images or volumes that were reconstructed from continuously acquired CT data after the injection of contrast media.

It generates the following result volumes:

. Cerebral blood flow (CBF)
Cerebral blood volume (CBV) .
Local bolus timing (time to start (TTS), time to peak (TTP), time to drain (TTD)) .
Mean transit time (MTT) .
o Transit time to the center of the IRF (TMax)
. Flow extraction product (permeability)
. Temporal MIP
. Temporal Average
. Baseline Volume
Modified dynamic input data .

The software allows the calculation of mirrored regions of interest and the visual inspection of time attenuation curves. One clinical application is to visualize the apparent blood perfusion and to calculate Hypoperfused Area and Mismatch Ratio in the brain tissue affected by acute stroke.

Areas of decreased perfusion appear as areas of changed signal intensity:

· Lower signal intensity for CBF and CBV
· Higher signal intensity for TTP, TTD, MTT, and TMax

A second application is to visualize blood brain barrier disturbances by modeling extra-vascular leakage of blood into the interstitial space. This additional capability may improve the differential diagnosis of brain tumors and may be helpful in therapy monitoring.

Device Description

The syngo. CT Neuro Perfusion software allows the quantitative evaluation of dynamic CT data of the brain acquired during the injection of a compact bolus of iodinated contrast material. It mainly aids in the early differential diagnosis of acute ischemic stroke. Blood-brain-barrier (BBB) imaging feature supports the diagnostic assessment of brain tumors.

By providing images of e.g. cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and Mean Transit Time (MTT) from one set of dynamic CT images or volumes, syngo.CT Neuro Perfusion allows a quick and reliable assessment of the type and extent of cerebral perfusion disturbances, including fast evaluation of the tissue at risk and non-viable tissue in the brain. The underlying approaches for this application were cleared as part of the predicate device and remain unchanged in comparison to the predicate device

syngo.CT Neuro Perfusion allows simultaneous multi-slice processing and supports the workflow requirements in a stroke workflow. The availability of flow extraction product imaging extends the option to the diagnosis of brain tumors. A listing of device modifications as part of the new software version VB50 of syngo.CT Neuro Perfusion is as follows:

Additional Parameters Hypoperfused Area and Mismatch Ratio:

These parameters are calculated based on NVT (non-viable tissue) and TAR (tissue at risk). Hypoperfused Area is calculated based on the sum of NVT and TAR while the Mismatch Ratio is calculated by dividing Hypoperfused Area by NVT.

AI/ML Overview

The provided text describes the Siemens syngo.CT Neuro Perfusion software, which evaluates brain perfusion from CT data. The new version (VB50) adds "Hypoperfused Area" and "Mismatch Ratio" parameters to aid in acute ischemic stroke assessment.

Here's a breakdown of the acceptance criteria and the study that supports the device, based on the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state quantitative "acceptance criteria" for the device's performance in a traditional sense (e.g., "sensitivity must be > X%" or "ICC must be > Y"). Instead, the study aims to demonstrate equivalence of the new parameters with a reference device and high concordance between existing and new parameters in clinical decision-making.

The key performance metrics reported are focused on the concordance of clinical decisions and correlation of volumes between the subject device (syngo.CT Neuro Perfusion VB50, referred to as Package A in the study) and a reference device (iSchemaView RAPID, referred to as Package B in the study).

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Concordance in "go vs. no-go" for MT (perfusion criteria alone)	High concordance	93.2% (110/118 cases)
Concordance in "go vs. no-go" for MT (perfusion + additional imaging criteria: ASPECTS, vessel occlusion)	Very high concordance	99.1% (117/118 cases)
Correlation of Hypoperfused Area (MT group)	Good correlation (e.g., ICC > 0.70)	ICC: 0.79 (between Package A and Package B)
Difference in Hypoperfused Area (NMT group)	Not explicitly quantified but implied to be non-significant	Mean difference ~12.75 mL (between Package A and Package B)
Difference in Hypoperfused Area (MT group)	Not explicitly quantified but implied to be non-significant	Mean difference ~17.3 mL (between Package A and Package B)
Overestimation in mean volume (MT group, Package B vs. Package A)	Not explicitly quantified but deemed acceptable for clinical decision	~11.6% (or 8.7% for median volumes)

Note: The document emphasizes that despite some volumetric differences, these did not "impact eligibility for MT" and "high agreement" was achieved in clinical decision-making.

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

Test Set Sample Size:
- Mechanical Thrombectomy (MT) group: 62 patients
- No Mechanical Thrombectomy (NMT) group: 56 patients
- Total: 118 patients (62 + 56)
Data Provenance: Retrospective. Patients presenting with Acute Ischemic Stroke (AIS) between January 2017 and December 2018 were screened. The study was conducted at a "single center." The country of origin is not explicitly stated in the provided text.

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

The document does not explicitly describe a separate ground truth establishment process involving a specific number of experts for the test set. The comparison is between the subject device's outputs and a reference device's outputs, as well as the observed clinical outcomes (MT vs. NMT) and adherence to a clinical standard (DEFUSE III criteria).

The "Methodology of the study" mentions evaluating "Individual patient triage between MT and NMT groups... to determine if the final clinical decision, based on a combination of factors, would remain the same regardless of eligibility determined based on perfusion imaging." This implies that actual clinical decisions by medical professionals (whose qualifications are not specified in this document) served as a benchmark in combination with the reference device's analysis.

4. Adjudication Method for the Test Set

The document does not describe an explicit "adjudication method" involving multiple experts resolving discrepancies for the test set results from the devices. Instead, it compares the outputs of two software packages (subject device and reference device) and then assesses the concordance of their outputs, particularly in the context of broader clinical guidelines (DEFUSE III). The focus is on how well the software outputs align with clinical decision-making criteria.

The "concordance" rates are reported based on direct comparison of the outputs and how they align with "go versus no-go" decisions for MT when perfusion criteria alone, and then additional clinical criteria, are considered.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not explicitly described in terms of human readers improving with AI vs. without AI assistance. The study described compares the outputs of two software packages (the subject device and a predicate device) and their alignment with clinical decision-making. It does not measure the improvement of human readers using these tools.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the study described is a standalone performance evaluation of the algorithm. It compares the output parameters (e.g., core infarct volume, hypoperfused area, mismatch ratio) generated by the "syngo.CT Neuro Perfusion" software (Package A) with those generated by the "iSchemaView RAPID" software (Package B). The evaluation focuses on the concordance of the software's outputs with each other and with established clinical guidelines, without directly assessing human-in-the-loop performance.

7. The Type of Ground Truth Used

The type of "ground truth" used is a combination of:

Reference Device Output: The outputs from the iSchemaView RAPID software (K182130) served as a key comparison point for the new parameters, as stated: "Equivalence of the parameters 'Hypoperfused Area' and 'Mismatch Ratio' with the reference device iSchemaView RAPID (K182130) was shown mainly by Bathla et al. 2020."
Clinical Decision-Making Criteria/Outcomes: The study assessed concordance with "go versus no-go" decisions for Mechanical Thrombectomy (MT) based on perfusion outputs alone, and then incorporating additional neuroimaging eligibility criteria as defined in DEFUSE III (e.g., ASPECTS, site of vessel occlusion). This implies that adherence to established clinical guidelines and actual patient triage decisions served as a form of "ground truth" for clinical utility.
Absence of Pathology/Direct Outcomes: There is no mention of pathology reports or direct patient outcomes data being used as ground truth for volumetric measurements or delineation of hypoperfused areas.

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size used for the training set for the syngo.CT Neuro Perfusion software. The study presented focuses on the validation of the new parameters (Hypoperfused Area and Mismatch Ratio) in comparison to a reference device and clinical criteria.

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

As no information is provided about a training set, the method for establishing its ground truth is also not described in the document. The text highlights that "The calculation of these values are from already existing parameters NVT (non-viable-tissue) and TAR (tissue at risk) within the commercially available syngo.CT Neuro Perfusion SOMARIS/8 VB20 release (K163284)," suggesting that the core algorithms for NVT and TAR were previously established and cleared, and the new parameters are derived from them.

Summary

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October 11, 2020

Image /page/0/Picture/1 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" and "ADMINISTRATION" in blue text.

Siemens Medical Solutions USA, Inc. % Ms. Veronica Padharia Regulatory Affairs Specialist 2501 N. Barrington Road HOFFMAN ESTATES IL 60192

Re: K202213

Trade/Device Name: syngo.CT Neuro Perfusion Regulation Number: 21 CFR 892.1750 Regulation Name: Computed tomography x-ray system Regulatory Class: Class II Product Code: JAK Dated: August 5, 2020 Received: August 6, 2020

Dear Ms. Padharia:

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/cfpmp/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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

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https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

For

Thalia T. Mills, Ph.D. Director Division of Radiological Health OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K202213

Device Name syngo.CT Neuro Perfusion

Indications for Use (Describe)

It generates the following result volumes:

. Cerebral blood flow (CBF)
Cerebral blood volume (CBV) .
Local bolus timing (time to start (TTS), time to peak (TTP), time to drain (TTD)) .
Mean transit time (MTT) .
o Transit time to the center of the IRF (TMax)
. Flow extraction product (permeability)
. Temporal MIP
. Temporal Average
. Baseline Volume
Modified dynamic input data .

Areas of decreased perfusion appear as areas of changed signal intensity:

· Lower signal intensity for CBF and CBV
· Higher signal intensity for TTP, TTD, MTT, and TMax

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(K) SUMMARY FOR SYNGO.CT NEURO PERFUSION

Identification of the Submitter I.

Importer/Distributor

Siemens Medical Solutions USA, Inc. 40 Liberty Boulevard Malvern, PA 19355 Establishment Registration Number 2240869

Manufacturing Site

Siemens Healthcare GmbH Siemensstr 1 D-91301 Forchheim, Germany

Establishment Registration Number 3004977335

Submitter Contact Person:

Veronica Padharia Regulatory Affairs Specialist, CNMT Siemens Medical Solutions USA, Inc. TEL: (630) 877-5761 FAX: (847) 304-6023 veronica.padharia@siemens-healthineers.com

Device Name and Classification II.

Product Name:	syngo.CT Neuro Perfusion
Propriety Trade Name:	syngo.CT Neuro Perfusion
Classification Name:	Computed Tomography X-ray System
Classification Panel:	Radiology
CFR Section:	21 CFR §892.1750
Device Class:	Class II
Product Code:	JAK

III. Predicate Device

Predicate Device

Trade Name:	syngo.CT Neuro Perfusion
510(k) Number:	K163284
Clearance Date:	03/01/2017
Classification Name:	Computed Tomography X-ray System
Classification Panel:	Radiology
CFR Section:	21 CFR §892.1750

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Device Class:	Class II
Product Code:	JAK

Reference Device

Trade Name:	iSchemaView RAPID
510(k) Number:	K182130
Clearance Date:	12/27/2018
Classification Name:	System, Image Processing, Radiological
Classification Panel:	Radiology
CFR Section:	21 CFR § 892.2050
Device Class:	Class II
Product Code:	LLZ

IV. Device Description

Additional Parameters Hypoperfused Area and Mismatch Ratio:

V. Indications for Use

The syngo.CT Neuro Perfusion software package is designed to evaluate areas of brain perfusion. The software processes images or volumes that were reconstructed from continuously acquired CT data after the injection of contrast media.

It generates the following result volumes:

Cerebral blood flow (CBF)
Cerebral blood volume (CBV) ●
Local bolus timing (time to start (TTS), time to peak (TTP), time to drain (TTD)) ●
Mean transit time (MTT)
Transit time to the center of the IRF (TMax)
Flow extraction product (permeability) ●
. Temporal MIP

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Temporal Average
Baseline Volume
Modified dynamic input data

Areas of decreased perfusion appear as areas of changed signal intensity:

Lower signal intensity for CBF and CBV .
Higher signal intensity for TTP, TTD, MTT, and TMax

Comparison of the IFU Statement and Technological Characteristics with the VI. Predicate Device

This section compares the IFU statement as well as the technological characteristics with the predicate device, syngo.CT Neuro Perfusion (K163284), and the reference device, iSchemaView RAPID (K182130).

Subject Device	Predicate Device	Reference Device
Siemens syngo.CT NeuroPerfusionSOMARIS/8 VB50	Siemens syngo.CT NeuroPerfusionSOMARIS/8 VB20, K163284	iSchemaView RAPIDK182130
The syngo.CT Neuro Perfusionsoftware package is designed toevaluate areas of brain perfusion.The software processes images orvolumes that were reconstructedfrom continuously acquired CT dataafter the injection of contrast media.	The syngo.CT Neuro Perfusionsoftware package is designed toevaluate areas of brain perfusion.The software processes images orvolumes that were reconstructedfrom continuously acquired CT dataafter the injection of contrast media.	iSchemaView's RAPID is an imageprocessing software package to beused by trained professionals,including but not limited tophysicians and medical technicians.The software runs on a standard off-
It generates the following resultvolumes:• Cerebral blood flow (CBF)• Cerebral blood volume (CBV)• Local bolus timing (time to start(TTS), time to peak (TTP), time	It generates the following resultvolumes:• Cerebral blood flow (CBF)• Cerebral blood volume (CBV)• Local bolus timing (time to start(TTS), time to peak	the-shelf computer or a virtualplatform, such as VMware, and canbe used to perform image viewing,processing and analysis of images.Data and images are acquiredthrough DICOM compliant imagingdevices.
to drain (TTD))• Mean transit time (MTT)• Transit time to the center of theIRF (TMax)• Flow extraction product(permeability)• Temporal MIP• Temporal Average• Baseline Volume• Modified dynamic input data	• (TTP), time to drain (TTD))• Mean transit time (MTT)• Transit time to the center of theIRF (TMax)• Flow extraction product(permeability)• Temporal MIP• Temporal average• Baseline volume• Modified dynamic input data	The iSchemaView RAPID providesboth viewing and analysiscapabilities for functional anddynamic imaging datasets acquiredwith CT Perfusion (CT-P), CTAngiography (CTA), and MRIincluding a Diffusion Weighted MRI(DWI) Module and a DynamicAnalysis Module (dynamic contrast-enhanced imaging data for MRI andCT).
The software allows the calculationof mirrored regions of interest andthe visual inspection of timeattenuation curves. One clinical	The software also allows thecalculation of mirrored regions orvolumes of interest and the visual	The DWI Module is used to visualizelocal water diffusion properties from
application is to visualize theapparent blood perfusion and tocalculate Hypoperfused Area and	inspection of time attenuationcurves. One clinical application is tovisualize the apparent blood	the analysis of diffusion weightedMRI data.
Mismatch Ratio in the brain tissueaffected by acute stroke.	perfusion and the parametermismatch in brain tissue affected byacute stroke.	The Dynamic Analysis Module isused for visualization and analysis ofdynamic imaging data, showing
Areas of decreased perfusion appearas areas of changed signal intensity:• Lower signal intensity for CBFand CBV• Higher signal intensity for TTP,TTD, MTT, and TMax	Areas of decreased perfusion appearas areas of changed signal intensity:• Lower signal intensity for CBFand CBV• Higher signal intensity for TTP,TTD, MTT, and TMax	properties of changes in contrast overtime. This functionality includescalculation of parameters related totissue flow (perfusion) and tissueblood volume.
A second application is to visualizeblood brain barrier disturbances bymodeling extra-vascular leakage ofblood into the interstitial space. Thisadditional capability may improvethe differential diagnosis of braintumors and may be helpful in therapymonitoring.	A second application is to visualizeblood brain barrier disturbances bymodeling extravascular leakage ofblood into the interstitial space. Thisadditional capability may improvethe differential diagnosis of braintumors and be helpful in therapymonitoring.	RAPID CT-Perfusion and RAPIDMR-Perfusion can be used byphysicians to aid in the selection ofacute stroke patients (with knownocclusion of the intracranial internalcarotid artery or proximal middlecerebral artery) for endovascularthrombectomy.
		Instructions for use of contrast agentsfor this indication can be found inAppendix A of the User's Manual.Additional information for safe andeffective drug use is available inproductspecific iodinated CT andgadolinium-based MR contrast druglabeling.
		In addition to the RAPID imagingcriteria, patients must meet theclinical requirements forthrombectomy, as assessed by thephysician, and have none of thefollowing contraindications orexclusions.
		Contraindications/Exclusions:• Bolus Quality: absent orinadequate bolus.• Patient Motion: excessivemotion leading to artifacts thatmake the scan technicallyinadequate.• Presence of Hemorrhage.

IFU Comparison:

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Comparison of the IFU statement related to the Predicate Device syngo.CT Neuro Perfusion (K163284):

The IFU statement of the subject device includes both parameters Hypoperfused Area and Mismatch Ratio due to the significance in decision-making during the AIS clinical workflow. The sentence is as follows: "One clinical application is to visualize the apparent blood perfusion and to calculate Hypoperfused Area and Mismatch Ratio in the brain tissue affected by acute stroke". This is the relevant difference as compared to the predicate device.

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Comparison of the IFU statement related to the Reference Device iSchemaView RAPID (K182130)

The IFU Statement of the reference device is principally divided in eight sections. To simplify the comparison process, a comparison of each section of the reference device against the subject device's IFU statement is provided next:

The first two sections as listed in the table (right column) above describe the type of the medical device (image respectively post-processing software application), the target group ("trained professionals") as well as the system environment where the software runs on. We describe the target group and the system environment in our user manual but not in our IFU statement.

1. iSchemaView's RAPID is an image processing software package to be used by trained professionals, including but not limited to physicians and medical technicians.
1. The software runs on a standard off-the-shelf computer or a virtual platform, such as V Mware, and can be used to perform image viewing, processing and analysis of images. Data and images are acquired through DICOM compliant imaging devices.

The third and fourth section refer to the modality-specific feature "DWI Modules" which refers to the MR acquisition mode only. Our subject device conducts post-processing on CT data only as described in the second sentence of our IFU statement. The subject device is not intended to work on MR data.

1. The iSchemaView RAPID provides both viewing and analysis capabilities for functional and dynamic imaging datasets acquired with CT Perfusion (CT-P), CT Angiography (CTA), and MRI including a Diffusion Weighted MRI (DWI) Module and a Dynamic Analysis Module (dynamic contrast-enhanced imaging data for MRI and CT).
1. The DWI Module is used to visualize local water diffusion properties from the analysis of diffusion weighted MRI data.

The fifth section refers to the analysis of dynamic imaging data of the blood flow. The assessment of dynamic image data is realized by cerebral blood flow (CBF) and cerebral blood volume (CBV) as listed in our IFU statement.

The Dynamic Analysis Module is used for visualization and analysis of dynamic imaging data, 5. showing properties of changes in contrast over time. This functionality includes calculation of parameters related to tissue flow (perfusion) and tissue blood volume.
The sixth section describes which specific medical procedure (endovascular thrombectomy) can be applied using the reference device. Our IFU statement does not provide such specific information.
RAPID CT-Perfusion and RAPID MR-Perfusion can be used by physicians to aid in the 6. selection of acute stroke patients (with known occlusion of the intracranial internal carotid artery or proximal middle cerebral artery) for endovascular thrombectomy.
The seventh section provides specific information concerning the use of a contrast agent. Our IFU statement explains that the subject device processes images or volumes after the injection of contrast media. Specific information concerning the contrast agent are communicated to the end-user in the user manual.
1. Instructions for use of contrast agents for this indication can be found in Appendix A of the User's Manual. Additional information for safe and effective drug use is available in productspecific iodinated CT and gadolinium-based MR contrast drug labeling.

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The eighth section describes the contraindications. Such information is listed in the user manual of the subject device.

In addition to the RAPID imaging criteria, patients must meet the clinical requirements for 8. thrombectomy, as assessed by the physician, and have none of the following contraindications or exclusions.
Contraindications/Exclusions:
. Bolus Quality: absent or inadequate bolus.
. Patient Motion: excessive motion leading to artifacts that make the scan technically inadequate.
Presence of Hemorrhage. .

Additionally, the subject device is able to evaluate brain tumors while the reference device does not provide such functionality. This functionality, the evaluation of brain tumors, is already part of the predicate device (syngo.CT Neuro Perfusion, VB20) as listed in the IFU statement comparison table.

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Comparison of Technological Characteristics

The only modification made to syngo.CT Neuro Perfusion VB50 software is the addition of the Hypoperfused Area and Mismatch Ratio parameters. All remaining features are unchanged. Please refer to the table below for a high-level overview of features within Neuro Perfusion:

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As outlined in the table above, the change in the VB50 release of Neuro Perfusion is the addition of the Hypoperfused Area and Mismatch Ratio parameters.

The calculation of these values are from already existing parameters NVT (non-viable-tissue) and TAR (tissue at risk) within the commercially available syngo.CT Neuro Perfusion SOMARIS/8 VB20 release (K163284):

Hypoperfused Area is calculated based on the sum of NVT and TAR
Mismatch Ratio is calculated by dividing Hypoperfused Area by NVT

Equivalence of the parameters "Hypoperfused Area" and "Mismatch Ratio" with the reference device iSchemaView RAPID (K182130) was shown mainly by Bathla et al. 2020'. This study also contains all patients of Bathla 20192.

Testing population used in the study

Patients presenting with AIS between January 2017 and December 2018 were screened. For the MT group, consecutive patients were included who underwent MT (mechanical thrombectomy) and met the following criteria: AIS presenting between 6 and 24 hours since last known normal, presence of ICA or M1-MCA occlusion and availability of a CTP study. For the NMT group, the inclusion criteria were: AIS presenting between 6 and 24 hours of last known normal, no endovascular therapy and presence of a confirmed acute stroke on follow-up imaging. In total 74 patients were in the MT group, of these 9 did not have complete perfusion data, 3 patients had motion artifacts, 62 were included in the final analysis. 73 patients were in the NMT group, complete perfusion data was not available for 12 patients, 5 had motion artefact, so 56 patients were included.

1 Bathla et al. (2020): "Comparing the Outcomes of Two Independent CT Perfusion Softwares and Their Impact on Therapeutic Decisions in Acute Ischemic Stroke"

2 Bathla et al. (2019): "Achieving comparable perfusion results across vendors. The next step in standardizing stroke care: a technical report

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Methodology of the study

The values for core infarct and hypoperfused area were compared between the two groups using Bland-Altman plots and Wilcoxon signed rank test. Correlation between the core infarct and hypoperfused area was evaluated using intraclass correlation coefficient (ICC). Individual patient triage between MT and NMT groups were evaluated based on a combination of perfusion outputs alone, and after considering additional neuroimaging eligibility criteria as defined in DEFUSE III, to determine if the final clinical decision, based on a combination of factors, would remain the same regardless of eligibility determined based on perfusion imaging.

Summary of the findings and their clinical importance/implications

From the point of view of 'go versus no-go' for MT, the core infarct volume, mismatch ratio and hypoperfused area only were considered initially. This yielded concordance in 60/62 cases between the two packages in the MT group. When low ASPECTS (defined as <6 in DEFUSE III) was also considered, one additional patient (in retrospect) would not have qualified regardless of the discrepancy in perfusion outputs. The second patient would qualify based on package A (Subject Device), but not package B (Reference Device). In the NMT group, concordant results were noted in 49/56 patients when perfusion criteria alone were considered. Of the seven patients for whom the results differed, five patients would additionally qualify based on package A and two patients based on package B alone. Of these, however, three patients did not have any vascular occlusion on the angiogram images, while two patients had M2/M3-MCA occlusions. Two patients had low ASPECTS scores. Therefore, none of these patients would additionally qualify when all DEFUSE III criteria were considered. Overall, there was high concordance when perfusion outputs were considered in isolation (110/118, 93.2%), which improved even further when additional imaging criteria (site of vessel occlusion and ASPECTS) were also considered (117/118, 99.1%).

Discussion on the limitations of the use of the subject device

The discussion on the limitations is identical in content to Bathla et al. 2020. The results show that despite differences in perfusion post-processing techniques, high agreement between perfusion softwares in term of 'go versus no-go' for MT can be achieved in real-world settings when patients are triaged based on imaging inclusion and exclusion criteria as defined in DEFUSE III. Similarly, we did not find any significant differences in the core and hypoperfused area in the NMT group and between the core volumes in the MT group. Even though the hypoperfused area in the MT group showed good correlation between the two packages (ICC: 0.79), the difference in calculated volumes was significant as discussed below. The use of Tmax to reliably define hypoperfusion has been demonstrated. Hypoperfusion is defined as Tmax>6 s for both packages. However, we noted a mean difference in hypoperfused area to be about 12.75 mL for the NMT group and 17.3 mL for the MT group. For the MT group, this translated to a difference of about 11.6% overestimation in mean volume (8.7% for median volumes) using package B when compared with package A.

Appropriate criteria to achieve comparable results

Limitations of the study include the retrospective nature, a small sample size and a single center experience.

High concordance in terms of proceeding or not proceeding with MT in AIS patients is achievable between syngo.via and RAPID, and increases even further when additional neuroimaging criteria (ASPECTS and site of occlusion) are also considered. Both packages show similar core volume estimations in both the MT and NMT groups. The penumbral volumes in patients in the MT group may be overestimated with RAPID but do not appear to impact eligibility for MT.

Fundamental scientific technology

The fundamental scientific technology of syngo.CT Neuro Perfusion SOMARIS/8 VB50 is the same compared to the commercially available predicate device. The post-processing software functionality remains unchanged from the predicate device with the exception of the feature modifications listed

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above. Siemens believes that the feature modifications subject to this syngo.CT Neuro Perfusion application are substantially equivalent to the predicate device.

VII. Performance Data / Safety and Effectiveness

The following performance data has been provided in support of the substantial equivalence determination:

Bench Testing

Verification and Validation activities demonstrate continued conformance with special controls for medical devices containing software, including assurance that functions work as designed, performance requirements and specifications have been met, and that all hazard mitigations have been fully implemented. Integration and Functional testing were conducted for syngo.CT Neuro Perfusion during product development. In addition, testing was performed to ensure the feature modifications within this submission meet the predetermined acceptance values.

It is in Siemens' opinion that the results of these test activities demonstrate that the subject device performs as intended and the results were found acceptable to support the claim of substantial equivalence.

Traceability of requirement and functional specifications is ensured during component integration, software validation and system testing

Validation Summary of the Parameters (Hypoperfused Area and Mismatch Ratio)

Performance data was provided in the form of Verification to support the substantial equivalence determination. In addition to the V&V testing, both the Hypoperfused Area and Mismatch Ratio parameters have been evaluated in publications as described in both papers Bathla et el. 2019 and Bathla et al. 2020. The summary of these publication is shown above in section VI of the 510(k) Summary.

Risk Analysis

Risk Management has been ensured via the risk analysis in compliance with ISO 14971 to identify and provide mitigation to potential hazards beginning early in the design cycle and continuing throughout the development of the product.

For this submission, the risk analysis was performed to ensure the risk control was implemented to mitigate identified hazards. The testing results support that all the software specifications have met the acceptance criteria. Testing for verification and validation of the device was found acceptable to support the claims of substantial equivalence. Siemens adheres to recognized and established industry standards for development including ISO 13485 and IEC 62304.

FDA Recognized Standards

Siemens hereby certifies that syngo.CT Neuro Perfusion will meet the following voluntary standards covering electrical and mechanical safety listed below, prior to introduction into interstate commerce:

RecognitionNumber	ProductArea	Title of Standard	Date ofRecognition	StandardsDevelopmentOrganization
12-300	Radiology	Digital Imaging and Communications inMedicine (DICOM) Set; PS 3.1 - 3.20	06/27/2016	NEMA
13-79	Software	Medical Device Software - Software life-cycleprocesses [including Amendment 1 (2016)];62304:2006/A1: 2016	01/14/2019	AAMI, ANSI,IEC
5-40	Software/Informatics	Medical Devices - Applications of riskmanagement to medical devices;14971:2007/(R)2010	06/27/2016	ANSI, AAMI,ISO

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5-129	General I(QS/RM)	Medical devices - Part 1: Applications ofusability engineering to medical devices;62366-1 Edition 1.1 Consolidated Version	07-06-2020	IEC
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VIII. Conclusion

There are no differences in the Indications for Use or Fundamental Technology Characteristics of the syngo.CT Neuro Perfusion software as compared to the currently commercially available software (K163284).

The modifications made (in regard to the addition of the Hypoperfused Area and Mismatch Ratio parameters) in this submission were previously withdrawn (K192052).

The feature modifications made within the VB50 release of Neuro Perfusion do not raise any new issues of safety and effectiveness as compared to the predicate device. Modifications made fall within already existing fundamental scientific technology which remains within previously cleared specification. Based on this information-as well as documentation in support of modifications made-it is Siemens' opinion that the syngo.CT Neuro Perfusion software is substantially equivalent to the predicate device.

Regulation Number and Section

§ 892.1750 Computed tomography x-ray system.

(a)
Identification. A computed tomography x-ray system is a diagnostic x-ray system intended to produce cross-sectional images of the body by computer reconstruction of x-ray transmission data from the same axial plane taken at different angles. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.

Feature	Subject Device	Predicate Device	Reference Device	Comments
	syngo.CT NeuroPerfusion(SOMARIS/8 VB50)	syngo.CT NeuroPerfusion(SOMARIS/8 VB20,K163284)	iSchemaView RAPID(K182130)
Tissue at riskand non-viable tissuevisualization	The flexible penumbraanalysis mode allowshighlighting of areas asNon-viable Tissue(NVT) and Tissue-At-Risk (TAR) accordingto certain user definedthresholds. Thresholdsof two differentPerfusion maps, e.g.CBF, CBV, MTT, TTPcan be used. Results canbe smoothed to reduceartefacts. Relativethresholds can be usedfor CBV and CBF. Thevisualization is done ascolor coded overlay ontemporal MIP.Additional TAC andstatistical values aredisplayed.Hypoperfused Area(sum of existingparameters TAR andNVT) and MismatchRatio parameters(division ofHypoperfused Area byNVT or(TAR+NVT)/NVT)have been added.	The flexible penumbraanalysis mode allowshighlighting of areas asNon-viable Tissue(NVT) and Tissue AtRisk (TAR) accordingto certain user definedthresholds. Thresholdsof two differentPerfusion maps, e.g.CBF, CBV, MTT, TTPcan be used. Results canbe smoothed to reduceartefacts. Relativethresholds can be usedfor CBV and CBF. Thevisualization is done ascolor coded overlay ontemporal MIP.Additional TAC andstatistical values aredisplayed	According to bothpublications Bathla etal. 2019 and Bathla etal. 2020 the definitionof the HypoperfusedArea and MismatchRatio parameters isconsideredsubstantiallyequivalent to howthese parameters areutilized within thereference device,iSchemaView RAPID(K182130).	ModifiedAddition ofHypoperfused Areaand Mismatch Ratioparameters.Both parameters derivefrom already clearedparameters NVT andTAR.The subject deviceprovides the additionalparametersHypoperfused Area(sum of TAR andNVT) and MismatchRatio (division ofHypoperfused Area byNVT or (TAR+NVT) /NVT).The reference device,iSchemaView RAPID(K182130) was used asa comparison marketedsoftware in order todetermine howmodifications to thethresholds of theseparameters resulted incomparablemeasurements.
Purpose oftheapplication	Visualization of tissueperfusion using rapidsequences collectedafter the administrationof contrast medium	Visualization of tissueperfusion using rapidsequences collectedafter the administrationof contrast medium	Visualization of tissueperfusion using rapidsequences collectedafter the administrationof contrast medium	Same; No changebetween the primarypredicate and devicesubject to this review.
Acquisition	Patient scan followingadministration ofcontrast media	Patient scan followingadministration ofcontrast media	N/A	No change between theprimary predicate anddevice subject to thisreview.
CT ScanningMode	Scanning at a singletable position or usingspirals with the samescan range	Scanning at a singletable position or usingspirals with the samescan range	N/A	No change between theprimary predicate anddevice subject to thisreview.
MotionCorrection	Rigid motion correctionwhich can be used inbrain datasets	Rigid motion correctionwhich can be used inbrain datasets	N/A	No change between theprimary predicate anddevice subject to thisreview.
Feature	Subject Device	Predicate Device	Reference Device	Comments
	syngo.CT NeuroPerfusion(SOMARIS/8 VB50)	syngo.CT NeuroPerfusion(SOMARIS/8 VB20,K163284)	iSchemaView RAPID(K182130)
Time PointRemoval	On user request timepoints and time ranges(time point volumes)can be removed fromthe current evaluation ifthey show strong patientor organ movement.	On user request timepoints and time ranges(time point volumes)can be removed fromthe current evaluation ifthey show strong patientor organ movement.	N/A	No change between theprimary predicate anddevice subject to thisreview.
4D NoiseReduction	Noise reduction withpreservation of time-attenuation informationcan be performed toimprove the imagequality of noisy inputimages and to allow forrobust image evaluation	Noise reduction withpreservation of time-attenuation informationcan be performed toimprove the imagequality of noisy inputimages and to allow forrobust image evaluation	N/A	No change between theprimary predicate anddevice subject to thisreview.
BrainSegmentation	The task can apply thebrain segmentationalgorithm	The task can apply thebrain segmentationalgorithm	N/A	No change between theprimary predicate anddevice subject to thisreview.
HUSegmentation	Removes all pixels thatlie outside the Min HUand Max HU thresholds	Removes all pixels thatlie outside the Min HUand Max HU thresholds	N/A	No change between theprimary predicate anddevice subject to thisreview.
ReferenceVesselDefinition	Automatic identificationof the reference vesselwith simple interactiveoverride if the user doesnot accept automaticdetection	Automatic identificationof the reference vesselwith simple interactiveoverride if the user doesnot accept automaticdetection	N/A	No change between theprimary predicate anddevice subject to thisreview.
Vessel andArteriesDefinition	Automatic identificationof the brain vessels andarteries with simpleinteractive overridepossibility	Automatic identificationof the brain vessels andarteries with simpleinteractive overridepossibility	N/A	No change between theprimary predicate anddevice subject to thisreview.
HemispherePlaneDefinition	Automatic hemisphereplane definition whichcan be manuallycorrected	Automatic hemisphereplane definition whichcan be manuallycorrected	N/A	No change between theprimary predicate anddevice subject to thisreview.
Normalization	Normalization of CBFand CBV values basedon a histogram analysisof the non-ischemichemisphere	Normalization of CBFand CBV values basedon a histogram analysisof the non-ischemichemisphere	N/A	No change between theprimary predicate anddevice subject to thisreview.
ResultStorage	Storage of all resultimages in the databaseas DICOM CTgrayscale, color RGB,Enhanced CT	Storage of all resultimages in the databaseas DICOM CTgrayscale, color RGB,Enhanced CT	N/A	No change between theprimary predicate anddevice subject to thisreview.
ROI (regionof interest)evaluation	ROI (region of interest)measurements withcalculation of meanvalue, standarddeviation and area fordetailed analysis ofspecific ischemic areas	ROI (region of interest)measurements withcalculation of meanvalue, standarddeviation and area fordetailed analysis ofspecific ischemic areas	N/A	No change between theprimary predicate anddevice subject to thisreview.
Feature	Subject Device	Predicate Device	Reference Device	Comments
syngo.CT NeuroPerfusion(SOMARIS/8 VB50)	syngo.CT NeuroPerfusion(SOMARIS/8 VB20,K163284)	iSchemaView RAPID(K182130)
ROImirroring	Mirroring of the ROIsat the hemisphere planeand output of statisticalparameters like meanvalue, standarddeviation and area	Mirroring of the ROIsat the hemisphere planeand output of statisticalparameters like meanvalue, standarddeviation and area	N/A	No change between theprimary predicate anddevice subject to thisreview.
TAC display	Parallel display ofseveral time attenuationcurves	Parallel display ofseveral time attenuationcurves	N/A	No change between theprimary predicate anddevice subject to thisreview.
AutomaticStrokecalculation	Automatic calculationof all steps,visualization of allintermediate resultsallowing a final resultcheck	Automatic calculationof all steps,visualization of allintermediate resultsallowing a final resultcheck	N/A	No change between theprimary predicate anddevice subject to thisreview.
Sending ofImages toPACS	Automatic sending ofresult images to PACSincluding qualitycontrol images.Possibility to do theevaluation manually.	Automatic sending ofresult images to PACSincluding qualitycontrol images.Possibility to do theevaluation manually.	N/A	No change between theprimary predicate anddevice subject to thisreview.