syngo. CT Neuro Perfusion by SIEMENS MEDICAL SOLUTIONS USA, INC.

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
· Temporal average
· Baseline volume
Modified dynamic input data

The software also allows the calculation of mirrored regions or volumes of interest and the visual inspection of time attenuation curves. One clinical application is to visualize the apparent blood perfusion and the parameter mismatch in 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 extravascular leakage of blood into the interstitial space. This additional capability may improve the differential diagnosis of brain tumors and 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. The Blood-brain-barrier (BBB) imaging feature supports the diagnostic assessment of brain tumors.

By providing images of e.q. 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 VB20 of syngo.CT Neuro Perfusion is as follows:

· Auto Stroke Workflow
(Calculation and display of the stroke results without user input)
. Rapid Results Technology (Calculates stroke results and quality control images without user input and sends all images to other DICOM nodes)
Additional Parameters for Penumbra and Core Infarct Calculation

This software is designed to operate on at least the syngo.via VB20 hardware/software platform, and should be used with reconstructed images that meet the following minimum requirements:

Images should be reconstructed with the high sampling frequency. Scan modes ● are e. g. adaptive 4D spiral, Dynamic sequence and dynamic multi-scan modes of Siemens CT scanners.
A standard reconstruction kernel should be used
. Images should be reconstructed with an increment smaller than the slice thickness to achieve good resolution

AI/ML Overview

The provided text describes the syngo.CT Neuro Perfusion software, but it does not include a table of acceptance criteria with reported device performance or details of a specific comparative study. Instead, it focuses on demonstrating substantial equivalence to a predicate device through shared technological characteristics and general software verification and validation.

Here's a breakdown of the requested information based on the provided text, highlighting what is present and what is missing:

1. Table of Acceptance Criteria and Reported Device Performance

Not provided. The document states that "The testing results support that all the software specifications have met the acceptance criteria" and "The results of these tests demonstrate that the subject device performs as intended." However, specific quantitative acceptance criteria or corresponding reported performance metrics are not given.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Not provided. The document mentions "non-clinical tests" and "verification/validation testing" but does not specify the sample size of the test set (e.g., number of cases or patients) or the provenance (country of origin, retrospective/prospective nature) of any data used for testing.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not provided. There is no mention of experts being used to establish a ground truth for any test set. The document focuses on performance testing related to software functionality and specifications.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not provided. Since no expert review or ground truth establishment based on human readers is described, there is no mention of an adjudication method.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No such study described. The document does not describe an MRMC comparative effectiveness study involving human readers or any effect size related to AI assistance. The focus is on the device's technical performance and its substantial equivalence to a predicate.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Implied standalone testing, but not explicitly detailed. The "Non-Clinical Testing Summary" mentions "Performance tests were conducted to test the functionality of the syngo.CT Neuro Perfusion" and that "The results of these tests demonstrate that the subject device performs as intended." This suggests standalone testing of the algorithm's functionality, but the specifics of how this was measured (e.g., against what gold standard) for clinical parameters are not elaborated. The claims are focused on the software's ability to generate specific result volumes (CBF, CBV, TTP, etc.).

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

Not explicitly stated for clinical ground truth. The document does not specify a type of clinical ground truth (like pathology or outcomes data) used for comparing the device's generated parameters to a reference. The testing described appears to be primarily focused on verifying that the software's outputs are consistent with its design specifications and computational models, rather than an external clinical gold standard.

8. The sample size for the training set

Not provided. The document describes performance testing in support of substantial equivalence and software verification/validation. It does not mention a training set or its sample size, indicating that this submission is not primarily based on a new AI model requiring training data. The underlying approaches are stated to be "unchanged in comparison to the predicate device."

9. How the ground truth for the training set was established

Not applicable. As no training set is mentioned or implied for a new AI model, the method for establishing its ground truth is not discussed.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

March 1, 2017

Siemens Medical Solutions USA, Inc. % Ms. Kimberly Mangum Regulatory Affairs Specialist 40 Liberty Boulevard Mail Code 65-1A MALVERN PA 19355

Re: K163284

Trade/Device Name: syngo.CT Neuro Perfusion Regulation Number: 21 CFR 892.1750 Regulation Name: Computed tomography x-ray system Regulatory Class: II Product Code: JAK Dated: February 14, 2017 Received: February 16, 2017

Dear Ms. Mangum:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Michael D.'Hara

For

Robert Ochs, Ph.D. Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K163284

Device Name syngo.CT Neuro Perfusion

Indications for Use (Describe)

· 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
· 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

Submitted by: Siemens Medical Solutions USA, Inc. 40 Liberty Boulevard Malvern, PA 19355

Date Prepared: January 20, 2017

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.

l. Submitter

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

Contact Person

Kimberly Mangum Regulatory Affairs Specialist Siemens Medical Solutions, Inc. USA 40 Liberty Boulevard Malvern, PA 19355 Phone: (610) 448 - 6477 Fax: (610) 640 - 4481 Email: kimberly.mangum@siemens.com

II. Device Name and Classification

510(k) Number: K163284 Product Name: syngo.CT Neuro Perfusion Propriety Trade Name: syngo.CT Neuro Perfusion Classification Name: Computed Tomography X-ray System Classification Panel: Radiology 21 CFR §892.1750 CFR Section: Device Class: Class II 90JAK Product Code:

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III. Predicate Device

Predicate Device:

Trade Name:	syngo.CT Neuro Perfusion
510(k) Number:	K123541
Clearance Date:	04/02/2013
Classification Name:	Computed Tomography X-ray System
Classification Panel:	Radiology
CFR Section:	21 CFR §892.1750
Device Class:	Class II
Product Code:	90JAK

Reference Device:

Trade Name:
510(k) Number:
Clearance Date:
Classification Name:
Classification Panel:
CFR Section:
Device Class:
Product Code:

RAPID K121447 10/04/2013 Picture archiving and communications system Radiologv 21 CFR § 892.2050 Class II LLZ

IV. Device Description

· Auto Stroke Workflow
(Calculation and display of the stroke results without user input)
. Rapid Results Technology (Calculates stroke results and quality control images without user input and sends all images to other DICOM nodes)
Additional Parameters for Penumbra and Core Infarct Calculation

This software is designed to operate on at least the syngo.via VB20 hardware/software platform, and should be used with reconstructed images that meet the following minimum requirements:

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Images should be reconstructed with the high sampling frequency. Scan modes ● are e. g. adaptive 4D spiral, Dynamic sequence and dynamic multi-scan modes of Siemens CT scanners.
A standard reconstruction kernel should be used
. Images should be reconstructed with an increment smaller than the slice thickness to achieve good resolution

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
Temporal Average
o Baseline Volume
Modified dvnamic input data

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

VI. Comparison of Technological Characteristics with the Predicate Device

The evaluation of tissue perfusion is the technological principle for both the subject and predicate devices. Both devices have the same Intended Use, same Indications for Use and similar visualization and evaluation technological characteristics. At a high-level, the subject and predicate device are based on the following same/similar technological characteristics:

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VII. Performance Data

The following performance data were provided in support of the substantial equivalence determination. This submission contains performance data to demonstrate continued conformance with special controls for medical devices containing software. Non-clinical tests (integration and functional) were conducted for syngo.CT Neuro Perfusion during product development. The modifications described in this Premarket Notification were supported with verification/validation testing.

Risk Analysis

The risk analysis was completed and risk control 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

Software Verification and Validation

Software Documentation for a Moderate Level of Concern software per FDA's Guidance Document "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" issued on May 11, 2005 is also included as part of this submission.

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Non-Clinical Testing Summary

Performance tests were conducted to test the functionality of the syngo.CT Neuro Perfusion. These tests have been performed to test the ability of the included features of the subject device. The results of these tests demonstrate that the subject device performs as intended. The result of all conducted testing was found acceptable to support the claim of substantial equivalence.

General Safety and Effectiveness Concerns

The device labeling contains instructions for use and any necessary cautions and warnings to provide for safe and effective use of the device. Risk management is ensured via a hazard analysis, which is used to identify potential hazards. These potential hazards are controlled during development, verification and validation testing. syngo.CT Neuro Perfusion is designed to fulfill the requirements of the following safety and performance standards:

RecognitionNumber	ProductArea	Title of Standard	PublicationDate	StandardsDevelopmentOrganization
12-300	Radiology	Digital Imaging and Communications inMedicine (DICOM) Set; PS 3.1 – 3.20	06/27/2016	NEMA
13-32	Software	Medical Device Software -Software LifeCycle Processes; 62304:2006 (1stEdition)	08/20/2012	AAMI, ANSI,IEC
5-40	Software/Informatics	Medical devices - Application of riskmanagement to medical devices; 14971Second Edition 2007-03-01	08/20/2012	ISO
5-95	General I(QS/RM)	Medical devices - Part 1: Application ofusability engineering to medical devicesIEC 62366-1:2015	06/27/2016	IEC
19-4	General II(ES/EMC)	AAMI / ANSI ES60601-1:2005/(R)2012and A1:2012, Medical electricalequipment - part 1: generalrequirements for basic safety andessential performance (IEC 60601-1:2005, mod)	07/09/2014	AAMI, ANSI

VIII. Conclusions

syngo.CT Neuro Perfusion has the same intended use and indication for use as the predicate device. The technological characteristics such as image visualization and image manipulation are the same as the predicate device. The result of all testing conducted was found acceptable to support the claim of substantial equivalence. The predicate devices were cleared based on non-clinical supportive information. The results of these tests demonstrate that the predicate devices are adequate for the intended use. The comparison of technological characteristics, non-clinical performance data, and software validation demonstrates that the subject device is as safe and effective when compared to the predicate device that is currently marketed for the same intended use. For the subject device, syngo.CT Neuro Perfusion, Siemens used the same testing with the same workflows as used to clear the predicate device. Since both devices were tested using the same methods, Siemens believes that the data generated from the syngo.CT Neuro Perfusion testing supports a finding of substantial equivalence.

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	Comparison
Purpose of theapplication	visualization of tissue perfusionusing rapid sequences collectedafter the administration ofcontrast medium	visualization of tissue perfusionusing rapid sequences collectedafter the administration ofcontrast medium	Same
Acquisition	patient scan followingadministration of contrast media	patient scan followingadministration of contrast media	Same
Feature	Subject Device	Predicate Device	Comparison
CT Scanning Mode	Scanning at a single tableposition or using spirals with thesame scan range	Scanning at a single tableposition or using spirals with thesame scan range	Same
Motion Correction	Rigid motion correction whichcan be used in brain datasets	Rigid motion correction whichcan be used in brain datasets	Same
Time Point Removal	On user request time points andtime ranges (time point volumes)can be removed from the currentevaluation if they show strongpatient or organ movement.	On user request time points andtime ranges (time point volumes)can be removed from the currentevaluation if they show strongpatient or organ movement.	Same
4D Noise Reduction	Noise reduction withpreservation of time-attenuationinformation can be performed toimprove the image quality ofnoisy input images and to allowfor robust image evaluation	Noise reduction withpreservation of time-attenuationinformation can be performed toimprove the image quality ofnoisy input images and to allowfor robust image evaluation	Same
Brain Segmentation	The task can apply the brainsegmentation algorithm	The task can apply the brainsegmentation algorithm	Same
HU Segmentation	Removes all pixels that lieoutside the Min HU and Max HUthresholds	Removes all pixels that lieoutside the Min HU and Max HUthresholds	Same
Reference Vessel Definition	Automatic identification of thereference vessel with simpleinteractive override if the userdoes not accept automaticdetection	Automatic identification of thereference vessel with simpleinteractive override if the userdoes not accept automaticdetection	Same
Vessel and Arteries Definition	Automatic identification of thebrain vessels and arteries withsimple interactive overridepossibility	Automatic identification of thebrain vessels and arteries withsimple interactive overridepossibility	Same
Hemisphere Plane Definition	Automatic hemisphere planedefinition which can be manuallycorrected	Automatic hemisphere planedefinition which can be manuallycorrected	Same
Normalization	Normalization of CBF and CBVvalues based on a histogramanalysis of the non-ischemichemisphere	Normalization of CBF and CBVvalues based on a histogramanalysis of the non-ischemichemisphere	Same
Result Storage	Storage of all result images inthe database as DICOM CTgrayscale, color RGB, EnhancedCT	Storage of all result images inthe database as DICOM CTgrayscale, color RGB, EnhancedCT	Same
ROI (region of interest)evaluation	ROI (region of interest)measurements with calculationof mean value, standarddeviation and area for detailedanalysis of specific ischemicareas	ROI (region of interest)measurements with calculationof mean value, standarddeviation and area for detailedanalysis of specific ischemicareas	Same
ROI mirroring	Mirroring of the ROIs at thehemisphere plane and output ofstatistical parameters like meanvalue, standard deviation andarea	Mirroring of the ROIs at thehemisphere plane and output ofstatistical parameters like meanvalue, standard deviation andarea	Same
Feature	Subject Device	Predicate Device	Comparison
TAC display	Parallel display of several timeattenuation curves	Parallel display of several timeattenuation curves	Same
AutomaticStrokecalculation	Automatic calculation of allsteps, visualization of allintermediate results allowing afinal result check	Manual assessment of eachcalculation step including aresult check	Equivalent
Sending ofImages toPACS	Automatic sending of resultimages to PACS includingquality control images.Possibility to do the evaluationmanually.	Sending of images to PACSafter manual assessment of theresults	Equivalent
Tissue at riskand non-viabletissuevisualization	The flexible penumbra analysismode allows highlighting ofareas as Non-viable Tissue(NVT) and Tissue At Risk (TAR)according to certain user definedthresholds. Thresholds of twodifferent Perfusion maps, e.g.CBF, CBV, MTT, TTP can beused. Results can be smoothedto reduce artifacts. Relativethresholds can be used for CBVand CBF. The visualization isdone as color coded overlay ontemporal MIP. Additional TACand statistical values aredisplayed	The flexible penumbra analysismode allows highlighting ofareas as Non-viable Tissue(NVT) and Tissue At Risk (TAR)according to certain user definedthresholds. Thresholds of twodifferent Perfusion maps, e.g.CBF, CBV, MTT, TTP can beused. The visualization is doneas color coded overlay ontemporal MIP. Additional TACand statistical values aredisplayed	Modified
User Interface	syngo.via GUI	syngo.via GUI	Same
Archiving/Storing	CD-R, film, DVD, USB, Network	CD-R, film, DVD, USB, Network	Same
Hardware	As specified by syngo.via	As specified by syngo.via	Same
Communication	DICOM compatible	DICOM compatible	Same