(83 days)
Yes
The device name "AI-Rad Companion Brain MR" and the description of "Automated segmentation and quantitative analysis" strongly suggest the use of AI/ML, despite later statements claiming specific follow-up algorithms do not include these components. The overall product branding and core functionality point towards AI/ML being integral to the initial segmentation and analysis.
No
This device is a post-processing image analysis software that assists clinicians in viewing, analyzing, and evaluating MR brain images. It does not directly treat or diagnose a disease.
Yes
This device is a diagnostic device because its intended use is to assist clinicians in viewing, analyzing, and evaluating MR brain images, providing automated segmentation and quantitative analysis of brain structures, and comparing them with normative data. This information aids in the diagnosis and assessment of brain conditions.
Yes
The device is described as "post-processing image analysis software" and its functionalities are purely software-based (segmentation, analysis, comparison, reporting). There is no mention of accompanying hardware components required for its primary function beyond the input MR images.
Based on the provided information, AI-Rad Companion Brain MR is not an In Vitro Diagnostic (IVD) device.
Here's why:
- IVD Definition: In Vitro Diagnostic devices are used to examine specimens taken from the human body, such as blood, urine, or tissue, to provide information about a person's health. This testing is performed outside of the body (in vitro).
- AI-Rad Companion Brain MR Function: This device analyzes medical images (MR brain images) that are acquired from the patient's body. It performs post-processing and analysis of these images to assist clinicians in evaluating the brain structures and white matter hyperintensities. This process does not involve the analysis of biological specimens taken from the body.
Therefore, AI-Rad Companion Brain MR falls under the category of medical image analysis software, not an In Vitro Diagnostic device.
No
The letter does not state that the FDA has reviewed and cleared a PCCP for this specific device.
Intended Use / Indications for Use
AI-Rad Companion Brain MR is a post-processing image analysis software that assists clinicians in viewing, analyzing, and evaluating MR brain images.
AI-Rad Companion Brain MR provides the following functionalities:
- Automated segmentation and quantitative analysis of individual brain structures and white matter hyperintensities
- Quantitative comparison of brain structure with normative data from a healthy population
- Presentation of results of reporting that includes all numerical values as well as visualization of these results
Product codes (comma separated list FDA assigned to the subject device)
QIH
Device Description
AI-Rad Companion Brain MR VA50 is an enhancement to the predicate, AI-Rad Companion Brain MR VA40 (K213706). Just as in the predicate, the brain morphometry feature of AIRad Companion Brain MR addresses the automatic quantification and visual assessment of the volumetric properties of various brain structures based on T1 MPRAGE datasets. From a predefined list of brain structures (e.g. Hippocampus, Caudate, Left Frontal Gray Matter, etc.) volumetric properties are calculated as absolute and normalized volumes with respect to the total intracranial volume. The normalized values are compared against age-matched mean and standard deviations obtained from a population of healthy reference subjects. The deviation from this reference population can be visualized as 3D overlay map or out-of-range flag next to the quantitative values.
Additionally, identical to the predicate, the white matter hyperintensities feature addresses the automatic quantification and visual assessment of white matter hyperintensities on the basis of T1 MPRAGE and T2 weighted FLAIR datasets. The detected WMH can be visualized as a 3D overlay map and the quantification in count and volume as per 4 brain regions in the report.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Yes
Input Imaging Modality
MR brain images, T1 MPRAGE, T2 weighted FLAIR
Anatomical Site
Brain
Indicated Patient Age Range
Not Found. The test set description for the WMH Follow-Up Feature mentions an age range of 25-88.
Intended User / Care Setting
healthcare professionals familiar with the post processing of magnetic resonance images.
Description of the training set, sample size, data source, and annotation protocol
The training data used for the fine tuning the hyper parameters of WMH follow-up algorithm is independent of the data used to test the white matter hyperintensity algorithm follow up algorithm.
Description of the test set, sample size, data source, and annotation protocol
Performance testing for AI-Rad Companion Brain MR WMH follow-up was performed on Siemens Healthineers test data from 75 subjects, which included Multiple Sclerosis patients (MS) and Alzheimer's patients (AD). Testing data had more female subjects as Multiple Sclerosis occurs in females more as compare to male subjects. and a balanced distribution with respect to age of the patient according to target patient population and field strength of the MR scanner used. For each dataset, three sets of ground truth of white matter hyperintensity changes between two time points are annotated manually. Each set is annotated by a disjoin group of annotator, reviewer and clinical expert, with the expert randomly assigned per case. For each test dataset, the three initial annotations are annotated by three different in-house annotators, then each initial annotation is reviewed by the in-house reviewer. Afterwards, each initial annotation is reviewed by the referred clinical expert.
Testing Cohort:
Subjects: 75
Studies: 150 (2 scans per subject)
of Females: 56
of Males: 19
Age Range: 25-88
Medical Indication: MS: 60, Alzheimer's: 15
Scan Protocol: T1w MPRAGE, T2w FLAIR
Field Strength: 3.0T
Manufacturer: Siemens
Data Origin: UPenn: (US): 15, ADNI (US): 15, Lausanne (EU): 22, Prague (EU): 23
Standard Annotation Process:
For each dataset, three sets of ground truth of white matter hyperintensity changes between two time points are annotated manually. Each set is annotated by a disjoint group of annotator, reviewer, and clinical expert, with the expert randomly assigned per case to minimize annotation bias. For each test dataset, the three initial annotations are annotated by three different in-house annotators. Then, each initial annotation is reviewed by the in-house reviewer. Afterwards, each initial annotation is reviewed by the referred clinical expert. The clinical expert reviews and corrects the initial annotation of the changed WMH areas according to the annotation protocol. If the corrections are significant and time-consuming, the corrections are communicated to the annotator for correction and then re-reviewed.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The white matter hyperintensities follow-up feature underwent a scientific evaluation. The results of clinical data-based software validation for the subject device AI-Rad Companion Brain demonstrated equivalent performance in comparison to the reference device and literature.
Study Type: Software validation / Performance testing for WMH follow-up
Sample Size: 75 subjects (150 scans)
Key Metrics:
Volumetric Segmentation Accuracy: PCC >= 0.77 (Accepted); AVG PCC = 0.94, 95% CI [0.83, 0.98]
Voxel-wise Segmentation Accuracy: Mean Dice score >= 0.47 (Accepted); AVG Dice = 0.50, 95% CI [0.42, 0.57]
WMH Change Region-wise Segmentation Accuracy: Median F1-score >= 0.69 (Accepted); AVG F1-score = 0.69, 95% CI [0.633, 0.733]
Key results: The performance data demonstrates continued conformance with special controls for medical devices containing software. The subject device AI-Rad Companion demonstrated equivalent performance in comparison to the reference device and literature. The nonclinical data and verification and validation results supports the safety and effectiveness of the subject device in that it should performs comparable to the predicate device that is currently marketed.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Volumetric Segmentation Accuracy: PCC (Average 0.94, 95% CI [0.83, 0.98])
Voxel-wise Segmentation Accuracy: Dice (Average 0.50, 95% CI [0.42, 0.57])
WMH Change Region-wise Segmentation Accuracy: F1-score (Average 0.69, 95% CI [0.633, 0.733])
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 892.2050 Medical image management and processing system.
(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).
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October 23, 2023
Siemens Medical Solutions U.S.A. % Kira Morales Regulatory Affairs Manager 40 Liberty Blvd. Malvern, PA 19355
Re: K232305
Trade/Device Name: AI-Rad Companion Brain MR Regulation Number: 21 CFR 892.2050 Regulation Name: Medical image management and processing system Regulatory Class: Class II Product Code: QIH Dated: July 31, 2023 Received: August 1, 2023
Dear Kira Morales:
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/cdrb/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.
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Page 2
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).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products): good manufacturing practice requirements as set forth in the quality systems (OS) 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.
2
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,
Signature
Daniel M. Krainak, Ph.D. Assistant Director DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K232305
Device Name AI-RAD Companion Brain MR
Indications for Use (Describe)
AI-Rad Companion Brain MR is a post-processing image analysis software that assists clinicians in viewing, analyzing, and evaluating MR brain images.
Al-Rad Companion Brain MR provides the following functionalities:
- Automated segmentation and quantitative analysis of individual brain structures and white matter hyperintensities
- Quantitative comparison of brain structure with normative data from a healthy population
- Presentation of results of reporting that includes all numerical values as well as visualization of these results
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/4/Picture/1 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words are a series of orange dots arranged in a circular pattern.
510(k) SUMMARY FOR AI-Rad Companion Brain MR
Submitted by: Siemens Medical Solutions USA, Inc. 40 Liberty Boulevard Malvern, PA 19355 Date Prepared: July 31, 2023
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR §807.92.
1. Submitter
| Importer/Distributor | Siemens Medical Solutions USA, Inc.
40 Liberty Boulevard
Malvern, PA 193552
Registration Number: 2240869 |
|----------------------|-------------------------------------------------------------------------------------------------------------------|
| Manufacturing Site | Siemens Healthcare GmbH
Henkestrasse 127
Erlangen, Germany 91052
Registration Number: 3002808157 |
2. Contact Person
Kira Morales Regulatory Affairs Manager Siemens Medical Solutions USA, Inc. 40 Liberty Boulevard Malvern, PA 19335 Phone: +1 (484) 901 - 9471 Email: kira.morales@siemens-healthineers.com
3. Device Name and Classification
| Product Name: | AI-Rad Companion Brain MR |
|---|---|
| Trade Name: | AI-Rad Companion Brain MR |
| Classification Name: | Medical Image Management and Processing System |
| Classification Panel: | Radiology |
| CFR Section: | 21 CFR §892.2050 |
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| Device Class: | Class II |
|---|---|
| Product Code: | QIH |
4. Predicate Device
| Product Name: | AI-Rad Companion Brain MR |
|---|---|
| Propriety Trade Name: | AI-Rad Companion Brain MR |
| 510(k) Number: | K213706 |
| Clearance Date: | April 15, 2022 |
| Classification Name: | Picture Archiving and Communication System |
| Classification Panel: | Radiology |
| CFR Section: | 21 CFR §892.2050 |
| Secondary CFR Section: | 21 CFR §892.1000 |
| Device Class: | Class II |
| Primary Product Code: | QIH |
| Recall Information: | N/A |
5. Reference Device
| Product Name: | icobrain |
|---|---|
| 510(k) Number: | K192130 |
| Clearance Date: | December 13, 2019 |
| Classification Name: | Picture Archiving and Communication System |
| Classification Panel: | Radiology |
| CFR Section: | 21 CFR §892.2050 |
| Device Class: | Class II |
| Primary Product Code: | LLZ |
| Recall Information: | N/A |
6. Indications for Use
AI-Rad Companion Brain MR is a post-processing image analysis software that assists clinicians in viewing, analyzing, and evaluating MR brain images.
AI-Rad Companion Brain MR provides the following functionalities.
- . Automated segmentation and quantitative analysis of individual brain structures and white matter hyperintensities
- . Quantitative comparison of each brain structure with normative data from a healthy population
- Presentation of results for reporting that includes all numerical values as well as . visualization of these results
7. Device Description
AI-Rad Companion Brain MR VA50 is an enhancement to the predicate, AI-Rad Companion Brain MR VA40 (K213706). Just as in the predicate, the brain morphometry feature of AI-Rad
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Image /page/6/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words is a graphic of orange dots.
Companion Brain MR addresses the automatic quantification and visual assessment of the volumetric properties of various brain structures based on T1 MPRAGE datasets. From a predefined list of brain structures (e.g. Hippocampus, Caudate, Left Frontal Gray Matter, etc.) volumetric properties are calculated as absolute and normalized volumes with respect to the total intracranial volume. The normalized values are compared against age-matched mean and standard deviations obtained from a population of healthy reference subjects. The deviation from this reference population can be visualized as 3D overlay map or out-of-range flag next to the quantitative values.
Additionally, identical to the predicate, the white matter hyperintensities feature addresses the automatic quantification and visual assessment of white matter hyperintensities on the basis of T1 MPRAGE and T2 weighted FLAIR datasets. The detected WMH can be visualized as a 3D overlay map and the quantification in count and volume as per 4 brain regions in the report.
8. Substantially Equivalent (SE) and Technological Characteristics
The intended use of the predicate device and the subject device are equivalent. The main difference is that AI-Rad Companion Brain MR VA50 adds the additional features of the Brain Morphometry follow-up feature and White Matter Hyperintensities Follow-up as compared to the predicate, AI-Rad Companion Brain MR VA40.
The subject device. AI-Rad Companion Brain MR VA50 is substantially equivalent with regard to the intended use and technical characteristics compared to the predicate device, AI-Rad Companion Brain MR VA50 (K213706) with respect to the software features, functionalities, and core algorithms. The additional features, enhancements and improvements provided in AI-Rad Companion Brain MR VA50 increase the usability and reduce the complexity of the imaging workflow for the clinical user.
Icobrain serves as a reference device within this submission and a dedicated comparison of technological characteristics is provided. Siemens Healthineers has determined that AI-Rad Companion Brain MR VA50 is comparable to icobrain (K192130) as it has similar technological and performance characteristics with respect to the white matter hyperintensities feature (cleared in predicate K213706) and white matter hyperintensities follow-up feature. Comparable to the subject device, icobrain produces reports for the segmentation and volumetric analysis of FLAIR white matter hyperintensities in the peri-ventricular, juxta-cortical, infra-tentorial, and deep white matter hyperintensity regions. Comparable to the white matter hyperintensities follow-up feature, Icobrain identifies volume changes (new or enlarging) of white matter hyperintensities between two images at two different time points within the 4 brain regions and produces a progression map indicating the location of the new or enlarged area, a total count of new or enlarged areas and a total volume of new or enlarged areas. AI-Rad Companion Brain MR VA50 used equivalent validation methodology to analyze the performance of the white matter hyperintensities follow-up feature compared to icobrain (K192130).
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Image /page/7/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words is a graphic of orange dots.
The risk analysis and non-clinical data support that both devices perform equivalently and do not raise different questions of the safety and effectiveness.
| | Subject Device:
AI-Rad Companion
Brain MR VA50A | Predicate Device:
AI-Rad Companion
Brain MR VA40
(K213706) | Reference Device:
icobrain (K192130) |
|-------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | AI-Rad Companion
Brain MR is a post-
processing image
analysis software that
assists clinicians in
viewing, analyzing, and
evaluating MR brain
images.
AI-Rad Companion
Brain MR provides the
following
functionalities:
• Automatic
segmentation and
quantitative analysis
of individual brain
structures and
white matter
hyperintensities
• Quantitative
comparison of each
brain structure with
normative data from
a healthy
population
• Presentation of
results for reporting
that includes all
numerical values as
well as visualization
of these results | AI-Rad Companion
Brain MR is a post-
processing image
analysis software that
assists clinicians in
viewing, analyzing, and
evaluating MR brain
images.
AI-Rad Companion
Brain MR provides the
following
functionalities:
• Automatic
segmentation and
quantitative analysis
of individual brain
structures and white
matter
hyperintensities
• Quantitative
comparison of each
brain structure with
normative data from
a healthy population
• Presentation of
results for reporting
that includes all
numerical values as
well as visualization
of these results | icobrain is intended
for automatic
labeling,
visualization and
volumetric
quantification of
segmentable brain
structures
from a set of MR or
NCCT images. This
software is intended
to automate the
current manual
process of
identifying,
labeling and
quantifying the
volume of
segmentable brain
structures identified
on MR or NCCT
images. icobrain
consists of two
distinct image
processing pipelines:
icobrain cross and
icobrain long.
icobrain cross is
intended to provide
volumes from MR or
NCCT images
acquired at a single
time point. icobrain
long is intended to
provide changes in
volumes between two
MR images that were
acquired on the same
scanner |
| | | | with the same image
acquisition protocol
and with same
contrast at two
different timepoints.
The results of
icobrain cross cannot
be compared with the
results of icobrain
long. |
| Brain
Morphometry | Pre-processing
functionality for
automatic segmentation
and volumetry of
MPRAGE data. | Pre-processing
functionality for
automatic segmentation
and volumetry of
MPRAGE data. | Image processing for
automatic
segmentation and
volumetry of
MPRAGE data. |
| Brain White
Matter
Hyperintensities
Segmentation | AI-Rad Companion
Brain MR White Matter
Hyperintensities
(WMH) includes
segmentation and
quantification of White
Matter Hyperintensities
on the basis of T1-
weighted
MPRAGE and T2-
weighted FLAIR
datasets as input. | Pre-processing
functionality for
automatic segmentation
and volumetry of
MPRAGE and FLAIR
data. | Image processing for
automatic
segmentation and
volumetry of FLAIR
data. |
| Brain White
Matter
Hyperintensities
Quantification | The WMH report
contains visualization of
WMH (3D overlay of
WMH map) and
numeric results of count
and volume of WMH as
per four brain regions
periventricular,
juxtacortial,
infratentorial and deep
white matter. | The WMH report
contains visualization of
WMH (3D overlay of
WMH map) and
numeric results of count
and volume of WMH as
per four brain regions
periventricular,
juxtacortial,
infratentorial and deep
white matter. | Unnormalized
volume and volume
changes of FLAIR
white matter
hyperintensities as
per 4 brain regions |
| Follow-up | The longitudinal
assessment of Brain MR
images from two
timepoints provides the
rate of change of
volumes of brain
structures and the count
and volume of new or
enlarged WMH. | The follow-up feature is
not available in the
equivalent device (AI-
Rad Companion Brain
MR VA40) | Assessment of
New/Enlarging lesion
count |
| Brain White
Matter
Hyperintensities
Map | Calculation of white
matter hyperintensities
map fused with the
processed FLAIR data
User customizable color
labels for the overlay
map. | Calculation of white
matter hyperintensities
map fused with the
processed FLAIR data
User customizable color
labels for the overlay
map. | Calculation of white
matter
hyperintensities map
overlaid with the
FLAIR data |
| Brain
Morphometry:
Quantification | Calculation of label
maps (display of brain
segmentation) and
partially combined label
maps (fused with the
processed MPRAGE
data). | Calculation of label
maps (display of brain
segmentation) and
partially combined label
maps (fused with the
processed MPRAGE
data). | Normalized and
unnormalized volume
and volume changes
of different brain
structures. |
| Brain
Morphometry:
Deviation Map
and Label map | • Deviation results
include deviation map,
which presents different
brain regions, color-
coded to indicate the
degree of deviation from
the average age- and
gender-matched
normative volume.
• Label results include
the label map, which
shows different brain
regions using different
colors. | • Deviation results
include deviation map,
which presents different
brain regions, color-
coded to indicate the
degree of deviation from
the average age- and
gender-matched
normative volume.
• Label results include
the label map, which
shows different brain
regions using different
colors. | Not available |
| Distribution &
Archiving | Creation of an image
series for morphometry
and WMH reports.
Automatic transfer of
generated maps and | Creation of an image
series for morphometry
and WMH reports.
Automatic transfer of
generated maps and | Automatic transfer of
generated image
series and report to a
PACS system. |
| | reports to a PACS
system. | reports to a PACS
system. | |
| Architecture | Cloud-based and on-edge deployment in the institution premise. For Edge deployment, the data processing is performed within the institution whereas logging, institution management, and audit logging are performed in the cloud. | Cloud-based and on-edge deployment in the institution premise. For Edge deployment, the data processing is performed within the institution whereas logging, institution management, and audit logging are performed in the cloud. | Cloud only solution with no components deployed on customer premise. |
| Communication | PACS (DICOM compatible) | PACS (DICOM compatible) | PACS (DICOM compatible) |
| User interface | Configuration UI
User can activate or deactivate the processing of brain MR cases in AI-Rad Companion Engine. If you activate AI-Rad Companion Brain MR, then the brain MR cases uploaded to AI-Rad Companion Engine are processed and is displayed in the Patient List. You can manually adjust the settings available in the General Settings screen. If you deactivate AI-Rad Companion Brain MR, then no brain MR cases are processed in AI-Rad Companion Engine. The settings available in the General Settings screen are not displayed. To activate or deactivate AI-Rad Companion Brain MR, see Configuring AI-Rad | Configuration UI
User can activate or deactivate the processing of brain MR cases in AI-Rad Companion Engine. If you activate AI-Rad Companion Brain MR, then the brain MR cases uploaded to AI-Rad Companion Engine are processed and is displayed in the Patient List. You can manually adjust the settings available in the General Settings screen. If you deactivate AI-Rad Companion Brain MR, then no brain MR cases are processed in AI-Rad Companion Engine. The settings available in the General Settings screen are not displayed. To activate or deactivate AI-Rad Companion Brain MR, see Configuring AI-Rad | Not available |
| | Companion in the AI-
Rad Companion Engine
Instructions for Use.
Longitudinal (Follow-
up) configurations and
Support for output in
different orientations are
added.
Conformation UI
On the Results Preview,
user can confirm or
decline the results and
send them to the PACS.
All changes are
temporarily saved until
the case is sent to the
PACS. | Companion in the AI-
Rad Companion Engine
Instructions for Use.
Conformation UI
On the Results Preview,
user can confirm or
decline the results and
send them to the PACS.
All changes are
temporarily saved until
the case is sent to the
PACS. | |
| Software
requirement/Op
erating system | AI-Rad Companion
Brain MR was tested on
Microsoft Windows 10.
AI-Rad Companion
Brain MR is not
validated on any other
operating system, for
example, MAC.
AI-Rad Companion
Brain MR is not
validated for use with
touch screen or mobile
devices.
AI-Rad Companion
Notifier requires a 64-bit
Windows Operating
System (Windows 10
recommended). It is
recommended to use
Google Chrome as a
preferred web browser
for use with AI-Rad
Companion Brain MR. | AI-Rad Companion
Brain MR was tested on
Microsoft Windows 10.
AI-Rad Companion
Brain MR is not
validated on any other
operating system, for
example, MAC.
AI-Rad Companion
Brain MR is not
validated for use with
touch screen or mobile
devices.
AI-Rad Companion
Notifier requires a 64-bit
Windows Operating
System (Windows 10
recommended). It is
recommended to use
Google Chrome as a
preferred web browser
for use with AI-Rad
Companion Brain MR. | Not available |
| System
deployment | Cloud based deployment
Edge deployment
Platform | Cloud based deployment
Edge deployment
Platform | Cloud Only Solution |
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Image /page/8/Picture/0 description: The image shows the Siemens Healthineers logo. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words is a graphic of orange dots.
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Image /page/9/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the word "Healthineers" is a graphic of orange dots.
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Image /page/10/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words is a graphic of orange dots.
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Image /page/11/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words are a series of orange dots arranged in a circular pattern.
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Image /page/12/Picture/0 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the words is a graphic of orange dots.
| DICOM
SR/SC/PDF | AI-Rad Companion
Brain MR exports the
numerical reports
(DICOM SR, DICOM
SC and PDF) in both
manual and automatic
confirmation. | Data transfer is handled
by the teamplay Images
infrastructure and uses
the DICOM standard.
The results are sent back
to a configurable target
node via the teamplay
digital health platform
infrastructure in
accordance with the
DICOM standards. | DICOM structured
report |
| -------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ---------------------------- |
|---|
Table 1: Comparison table for AI-Rad Companion Brain MR VA50, predicate device AI-Rad Companion Brain MR VA40 (K213706) and reference device icobrain (K192130)
The conclusions from all verification and validation data suggest that these enhancements are equivalent with respect to safety and effectiveness of the predicate device. These modifications do not change the intended use of the product. Siemens is of the opinion that AI-Rad Companion Brain MR VA50 is substantially equivalent to the currently marketed device, AI-Rad Companion Brain MR VA40
9. Nonclinical Tests
Non-clinical tests were conducted to test the functionality of AI-Rad Companion Brain MR. Software validation and bench testing have been conducted to assess the performance claims as well as the claim of substantial equivalence to the predicate device. Non-clinical performance testing demonstrates that AI-Rad Companion Brain MR complies with appropriate FDA guidance documents as well as with the following voluntary FDA recognized Consensus Standards (Table 2).
| Recognition
Number | Product
Area | Title of Standard | Reference
Number and
Date | Standards
Development
Organization |
|-----------------------|--------------------------|---------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------|------------------------------------------|
| 5-129 | General | Medical Devices – Application
of usability engineering to
medical devices [including
Corrigendum 1 (2016)] | IEC 62366-1
Edition 1.1
2020-06
CONSOLIDATED
VERSION | IEC |
| 5-125 | General | Medical Devices – application
of risk management to
medical devices | ISO 14971 Third
Edition 2019-12 | ISO |
| 13-79 | Software/
Informatics | Medical device software –
software life cycle processes
[Including Amendment 1
(2016)] | IEC 62304
Edition 1.1
2015-06 | AAMI
ANSI
IEC |
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Image /page/13/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange. To the right of the word "Healthineers" is a graphic of orange dots arranged in a circular pattern.
| | | | CONSOLIDATED
VERSION | |
|--------|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------|------------|
| 12-349 | Radiology | Digital Imaging and
Communications in Medicine
(DICOM) Set | PS 3.1 - 3.20
2021e | NEMA |
| 5-134 | General | Medical devices – symbols to
be used with information to
be supplied by the
manufacturer – Part 1:
General Requirements | 15223-1
Fourth edition
2021-07 | ISO
IEC |
| 13-97 | Software/
Informatics | Health software - Part 1:
General requirements for
product safety | 82304-1
Edition 1.0
2016-10 | IEC |
Table 2: List of recognized standards
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. The performance data demonstrates continued conformance with special controls for medical devices containing software. Non-clinical tests were conducted on the subject device during product development.
Software "bench" testing in the form of Unit. System and Integration tests were performed to evaluate the performance and functionality of the new features and software updates. All testable requirements in the Requirement Specifications and the Risk Analysis have been successfully verified and traced in accordance with the Siemens Healthineers DH product development (lifecycle) process. Human factor usability validation is addressed in system testing and usability validation test records. Software verification and regression testing have been performed successfully to meet their previously determined acceptance criteria as stated in the test plans.
Siemens Healthineers adheres to the cybersecurity requirements as defined the FDA Guidance "Content of Premarket Submissions for Management for Cybersecurity in Medical Devices," issued October 2, 2014 by implementing a process of preventing unauthorized access, modifications, misuse or denial of use, or the unauthorized use of information that is stored, accessed, or transferred from a medical device to an external recipient.
10. Performance Software Validation
AI-Rad Companion Brain MR VA50A brain morphometry feature is identical to the predicate device AI-Rad Companion Brain MR VA20A.
AI-Rad Companion Brain MR VA50A White Matter Hyperintensities (WMH) segmentation feature is identical to the predicate device AI-Rad Companion Brain MR VA40A
In AI-Rad Companion Brain MR VA50A 2 features were added as below:
14
SIEME Healthineers
- The Brain Morphometry follow-up feature ●
- White Matter Hyperintensities Follow-up ●
Brain Morphometry Follow-Up Feature
The Brain Morphometry follow-up feature of the subject device automatically calculates the atrophy range in percentage for each segmented brain structure using the Brain Morphometry feature. The Brain Morphometry follow-up feature takes the two MPRAGE scans from two timepoints of the same patient as input and calculates atrophy rates between timepoints. Brain morphometry follow-up consists of atrophy rate calculation Morphometry follow-up does not include any machine learning or deep learning component therefore it is verified by V&V testing, and no additional evaluation is provided in this document.
White Matter Hyperintensities Follow-Up Feature
To validation AI-Rad Companion Brain MR software from a clinical perspective, the white matter hyperintensities follow-up feature underwent a scientific evaluation. The results of clinical data-based software validation for the subject device AI-Rad Companion Brain demonstrated equivalent performance in comparison to the reference device and literature. A complete scientific evaluation report is provided in support of the device modifications. The brain morphometry & white matter hyperintensities algorithms, unchanged from the predicate. did not undergo a new scientific evaluation.
Performance testing for AI-Rad Companion Brain MR WMH follow-up was performed on Siemens Healthineers test data from 75 subjects, which included Multiple Sclerosis patients (MS) and Alzheimer's patients (AD). Testing data had more female subjects as Multiple Sclerosis occurs in females more as compare to male subjects. and a balanced distribution with respect to age of the patient according to target patient population and field strength of the MR scanner used. For each dataset, three sets of ground truth of white matter hyperintensity changes between two time points are annotated manually. Each set is annotated by a disjoin group of annotator, reviewer and clinical expert, with the expert randomly assigned per case. For each test dataset, the three initial annotations are annotated by three different in-house annotators, then each initial annotation is reviewed by the in-house reviewer. Afterwards, each initial annotation is reviewed by the referred clinical expert.
| Validation Type | Acceptance Criteria |
|---|---|
| Volumetric Segmentation Accuracy | A PCC >= 0.77 is considered as a passed case |
| for volumetric segmentation accuracy | |
| Voxel-wise Segmentation Accuracy | A mean Dice score >=0.47 is considered as a |
| passed case for segmentation quality | |
| WMH Change Region-wise Segmentation | |
| Accuracy | A median F1-score >=0.69 is considered a |
| passed case |
Acceptance Criteria:
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Image /page/15/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the words is a graphic of orange dots.
Summary Performance data, Standard Deviations & CIs:
| | Volumetric
Segmentation | Voxel-wise Segmentation | WMH Lesion-wise
Segmentation |
|--------|----------------------------|-------------------------|---------------------------------|
| | PCC | Dice | F1-score |
| AVG | 0.94 | 0.50 | 0.69 |
| STD | n.a. | 0.22 | 0.13 |
| 95% CI | [0.83,0.98] | [0.42,0.57] | [0.633,0.733] |
Testing Data Information:
| Testing Cohort | |
|---|---|
| # Subjects | 75 |
| # Studies | 150 (2 scans per subject) |
| # of Females | 56 |
| # of Males | 19 |
| Age Range | 25-88 |
| Medical Indication | MS: 60 |
| Alzheimer's: 15 | |
| Scan Protocol | T1w MPRAGE |
| T2w FLAIR | |
| Field Strength | 3.0T |
| Manufacturer | Siemens |
| Data Origin | UPenn: (US): 15 |
| ADNI (US): 15 | |
| Lausanne (EU): 22 | |
| Prague (EU): 23 |
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Image /page/16/Picture/0 description: The image contains the logo for Siemens Healthineers. The word "SIEMENS" is written in teal, and the word "Healthineers" is written in orange below it. To the right of the word "Healthineers" is a graphic of orange dots.
Standard Annotation Process:
For each dataset, three sets of ground truth of white matter hyperintensity changes between two time points are annotated manually. Each set is annotated by a disjoint group of annotator, reviewer, and clinical expert, with the expert randomly assigned per case to minimize annotation bias. For each test dataset, the three initial annotations are annotated by three different in-house annotators. Then, each initial annotation is reviewed by the in-house reviewer. Afterwards, each initial annotation is reviewed by the referred clinical expert. The clinical expert reviews and corrects the initial annotation of the changed WMH areas according to the annotation protocol. If the corrections are significant and time-consuming, the corrections are communicated to the annotator for correction and then re-reviewed.
Testing & Training Data Independence:
WMH follow-up algorithm does not include any machine learning component. The training data used for the tine tuning the hyper parameters of WMH follow-up algorithm is independent of the data used to test the white matter hyperintensity algorithm follow up algorithm.
11. Summary of Nonclinical Tests
Based on the nonclinical performance documented within the Scientific Evaluation, AI-Rad Companion Brain MR VA50 was found to have a safety and effectiveness profile that is similar to the predicate. Since the predicate device was cleared based on the results of the prior conducted scientific evaluation, the same methodology was required to support the substantial equivalence. The nonclinical data and verification and validation results supports the safety and effectiveness of the subject device in that it should performs comparable to the predicate device that is currently marketed.
12. Summary of Clinical Tests
The predicate (K213706) was not validated using clinical tests and therefore no clinical tests were conducted to test the performance and functionality of the modifications introduced within AI-Rad Companion Brain MR. Verification and validation of the enhancements and improvements have been performed and these modifications have been validated for their intended use. No animal testing has been performed on the subject device.
13. Safety and Effectiveness
The device labeling contains instructions for use and any necessary cautions and warnings to ensure safe and effective use of the device.
Risk management is ensured via ISO 14971:2019 compliance to identify and provide mitigation of potential hazards in a risk analysis early in the design phase and continuously throughout the development of the product. These risks are controlled via measures realized during software development, testing and product labeling.
Furthermore, the device is intended for healthcare professionals familiar with the post processing of magnetic resonance images.