MREplus+ Software is an assisted ROI drawing tool for liver MRE and Fat/Water images and is used for receiving, display, ROI selection, and analysis generation. It displays to a trained reader MRE and Fat/Water images, preliminary ROIs that it calculates from these images, and statistical analysis calculated from the ROIs and images are presented in a way for review and, optionally, modification by the trained reader.

Device Description

The MREplus+ software is a tool for assisted Magnetic Resonance Elastography (MRE) and multipoint Dixon Fat/Water (FW) image analysis which calculates preliminary automated regions of interest (ROIs) and provides the environment for the trained readers to review the relevant MRE and FW information and approve or modify the ROIs. MREplus+ is intended to be used only with liver MRE and FW data. The inputs for MREplus+ are the MRE and FW images. In the case of MRE, this includes magnitude images (showing anatomy), wave images (showing wave propagation) with multiple time points across the wave cycle, and the elasticity and confidence images calculated by MRE's on-scanner MMDI algorithm or an offline MMDI packaged with MREplus+. In the case of FW, images include in-phase, out-of-phase, fat, water, fat fraction, and R2*. MREplus+ includes a DICOM receiver which can recognize and accept these images when sent from the MRI scanner or workstation using standard protocols. From these images, MREplus+ calculates automated ROIs. ROIs can be reviewed by an authorized trained reader for review, modification and approval. MREplus+ performs statistical calculations from the ROIs. MREplus+ outputs images, ROIs, and calculated results in an archive compatible report.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the MREplus+ Software:

Acceptance Criteria and Reported Device Performance

The FDA 510(k) summary does not explicitly list numerical "acceptance criteria" but rather describes the testing performed to demonstrate substantial equivalence to a predicate device. The performance is described qualitatively and in terms of failure rates and modification rates.

Acceptance Criteria Category (Derived from study descriptions)	Specific Criteria (Implicit)	Reported Device Performance
Functional Equivalence (MRE)	MREplus+ should accurately process MRE images, calculate preliminary automated ROIs, and allow for review, modification, and approval by a trained reader, achieving results comparable to the predicate device (GE Advantage Workstation).	MREplus+ demonstrated <1% processing failures and <20% ROI modifications in a study of 1347 patient cases. This indicates that the automated ROIs are largely accurate and require minimal human intervention, aligning with the "assisted ROI drawing tool" claim and demonstrating functional equivalence to manual drawing on the predicate. The overall conclusion states MREplus+ proved to be an "accurate software tool that facilitates liver MRE analysis with an accuracy of >99% compared to the standard predicate methodology," though the exact metric for this 99% accuracy is not quantified (e.g., consistency of stiffness values within a certain delta).
Functional Equivalence (Fat-Water)	MREplus+ should accurately calculate Fat Fraction from Fat-Water images, allowing for review, modification, and approval by a trained reader, achieving results comparable to the predicate device.	In all 92 Fat-Water cases, MREplus+ was able to accurately and reliably calculate Fat Fraction from Fat-Water images. This suggests complete success for this specific functionality.
Usability/Workflow (Implicit)	The software should function as an "assisted ROI drawing tool" where preliminary ROIs are provided, allowing for efficient review and optional modification by a trained reader, leading to the generation of an archive-compatible report. The workflow should be comparable to the predicate while potentially offering improvements in automation.	The "MRE study involving 1347 patient cases... MREplus+ demonstrated <1% processing failures and <20% ROI modifications" indicates a highly efficient workflow where automated ROIs are successful in the vast majority of cases, reducing manual effort compared to a fully manual system like the predicate. The "archive compatible report" output also matches the predicate's functionality.
Safety and Effectiveness	The device should be as safe and effective as the legally marketed predicate device and present no new concerns.	"The nonclinical and retrospective clinical validation tests conducted demonstrate that the device is as safe, as effective, and performs as well as or better than the legally marketed predicate device." The low processing failure and modification rates support this claim by showing it generates reliable results that require minimal correction by human users.

Study Details Proving Device Meets Acceptance Criteria:

Sample Sizes Used for the Test Set and Data Provenance:
- MRE Study (Test Set): 1347 patient cases.
- Fat-Water Study (Test Set): 92 patient cases.
- Data Provenance: The document states "retrospective clinical data bases." The country of origin is not explicitly stated, but the submission is to the U.S. FDA, and the submitter's address is in Minnesota, USA, implying the data is likely from the U.S. or at least acceptable for submission to the FDA.
Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts:
- The document implies that "standard expert reviewer readings using the predicate device" were used as the gold standard for comparison (ground truth). However, it does not specify the exact number of experts who established this ground truth or their specific qualifications (e.g., "radiologist with 10 years of experience"). It broadly refers to "trained readers" and "technician or radiologist."
Adjudication Method for the Test Set:
- The document states that the MREplus+ calculates "preliminary automated regions of interest (ROIs)" which are then "reviewed by an authorized trained reader for review, modification and approval." For the MRE study, it reports "<20% ROI modifications." This implies a human-in-the-loop (HITL) review and optional modification process. The ground truth was established by comparing to "standard expert reviewer readings using the predicate device," which would inherently involve human review and drawing of ROIs. There is no mention of a multi-reader adjudication method like 2+1 or 3+1 for resolving discrepancies amongst multiple human readers if such were used to establish the "standard expert reviewer readings."
If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:
- The document describes a comparison to human expert readings using a predicate device, which is a form of comparative effectiveness study. However, it is not explicitly framed as a Multi-Reader Multi-Case (MRMC) comparative effectiveness study in the standard sense of comparing multiple human readers with and without AI assistance to measure a statistically significant improvement.
- The study does not report an effect size of how much human readers improve with AI vs. without AI assistance in a quantified statistical manner (e.g., increase in AUC, sensitivity, or specificity with AI). Instead, it focuses on the accuracy of the AI's preliminary output (low modification rate) and the overall accuracy compared to the predicate method. The claim of "accuracy of >99% compared to the standard predicate methodology" serves as the primary performance metric, implicitly suggesting that if the AI's output closely matches the expert's, the human reader's task becomes one of verification rather than creation, thereby improving efficiency and consistency.
If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- The description of the MREplus+ as an "assisted ROI drawing tool" and the detail about "preliminary automated ROIs" followed by human review and optional modification suggest that the device is not intended for standalone (algorithm-only) use in a clinical setting for diagnosis.
- The reported performance metrics, like "<20% ROI modifications," inherently reflect the performance of the algorithm before human intervention. While these are algorithm-generated performances, the device's intended use is with a human-in-the-loop. The statement "MREplus+ proved to be an accurate software tool that facilitates liver MRE analysis with an accuracy of >99% compared to the standard predicate methodology" likely refers to the accuracy of the MREplus+ suggested ROIs' derived values when compared to the predicate's values, rather than a standalone diagnostic performance metric.
The Type of Ground Truth Used:
- The ground truth for the test sets was established by "standard expert reviewer readings using the predicate device." This is a form of expert consensus or expert-derived ground truth, where the "standard" implies an accepted clinical practice for deriving measurements from MRE and Fat/Water images. It's not pathology or outcomes data.
The Sample Size for the Training Set:
- The document does not specify the sample size used for the training set for the MREplus+ software. It only provides details about the validation (test) sets.
How the Ground Truth for the Training Set Was Established:
- The document does not provide information on how the ground truth for the training set was established. Since it is an AI-assisted tool, it would presumably require a large, annotated dataset for training, but these details are not present in the provided summary.

Summary

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Resoundant, Inc. % Mr. Bernard Horwath Regulatory Consultant HRG 4486 Timberline Ct VADNAIS HEIGHT MN 55127 August 1, 2019

Re: K183193

Trade/Device Name: MREplus+ Software Regulation Number: 21 CFR 892.2050 Regulation Name: Picture archiving and communications system Regulatory Class: Class II Product Code: LLZ Dated: June 28, 2019 Received: July 2, 2019

Dear Mr. Horwath:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for

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

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

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

Sincerely.

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) K183193

Device Name

MREplus+ Software

Indications for Use (Describe)

MREplus+ Software is an assisted ROI drawing tool for liver MRE and Fat/Water images and is used for receiving, display, ROI selection, and analysis generation. It displays to a trained reader MRE and Fat Water images, preliminary ROIs that it calculates from these images, and statistical analysis calculated from the ROIs and images are presented in a way for review and, optionally, modification by the trained reader.

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

Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
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K183193

510(k) Summary Resoundant MREplus+ Software

Date Prepared:	25 June 2019
Submitter:	Resoundant Inc.421 First Ave SWSuite 204WRochester, MN 55902Telephone: 507-322-0011
Contact:	Mr. Bernard HorwathRegulatory Affairs Consultant4486 Timberline CtVadnais Heights, MN 55127Telephone: 651- 231-1761
Proprietary Name:	MREplus+ Software

Common/Usual Name: System, Image Processing, Radiological

Regulation Name: Picture Archiving and Communications System 21 CFR 892.2050, Class II Product Code - LLZ System, Image Processing, Radiological

Description:

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Indications for Use: MREplus+ Software is an assisted ROI drawing tool for liver MRE and Fat/Water images and is used for receiving, display, ROI selection, and analysis generation. It displays to a trained reader MRE and Fat/Water images, preliminary ROIs that it calculates from these images, and statistical analysis calculated from the ROIs and images. ROIs and images are presented in a way for review and, optionally, modification by the trained reader.

Substantial Equivalence:

The MREplus+ Software is substantially equivalent to the following predicate device:

Primary Predicate: GE Advantage Workstation 4.1 510(k): K020483 GE Medical Systems This predicate has not been subject to a design related recall.

Comparison with Predicate:

Both MREplus+ and the predicate software tools display MRE and FW images, provide the tools for drawing a ROI, calculate average stiffness from the ROI area, and allow DICOM archivecompatible images to be generated for the clinical report. ROI selection on both stations must be performed by trained readers. The scope of the GE Advantage Workstation 4.1 is broader, as it allows for display and analysis of images of multiple modalities, whereas MREplus+ works specifically with liver MRE and FW data.

The GE Advantage Workstation (GE AW) comes pre-installed on a dedicated workstation. It receives and stores medical DICOM images of multiple modalities transferred from a device with DICOM push capabilities (such as an MRI or CT scanner, or another GE AW). A trained user is able to select one of the stored image sets and display them using the system. Images from qualitative modalities may be used as an element in diagnosis directly. For quantitative modalities, such as MRE, the user uses the GE Advantage Workstation tools to select an ROI within the image and calculate values, such as size, mean value, or standard deviation, from it. The GE Advantage Workstation outputs the ROIs over the original images as DICOM images which are archived clinically as part of the report. The values calculated from the ROIs may be recorded by the user and entered into the report manually or be displayed as part of the output images. The clinical report is then used as an element in diagnosis.

MREplus+ is intended to be used only with liver MRE and FW data, so its scope is a subset of the scope of the GE Advantage Workstation. MREplus+ is installed on standard computers, servers, or workstations, which reside on the intranet of the institution and, similarly to the GE AW, have restricted login privileges. MREplus+ receives DICOM medical images transferred from MRI scanners or other sources and automatically pre-processes the received MRE images to generate automated ROIs. An authorized trained user, such as a technician or radiologist, can use MREplus+ to display an MRE or FW exam along with ROIs. The MREplus+ user reviews the ROIs in context of all acquired MRE or FW data, similarly to the fully-manual ROI drawing on the GE AW. The user may perform modifications or, if none are required, approves the ROIs. At this stage. MREplus+ generates and outputs an archive compatible report containing final ROIs overlaid on the input images and the calculated statistical values associated with ROI areas and underlying images.

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MREplus+ also supports direct generation of the archive compatible analysis report from the automated ROIs, for presentation to a radiologist in conjunction with other imaging data. This behavior can be enabled by the institution, and does not preclude subsequent review or modification of the ROIs and subsequent analysis.

A comparison of the devices is provided in the following table:

Device Parameter	MREplus+ Software	GE Advantage Workstation 4.1	Difference if any
510(k)		K020483	NA
Classification	21 CFR 892.2050, Class II	21 CFR 892.2050, Class II	Same
Product Code	Product Code - LLZSystem, Image Processing,Radiological	Product Code - LLZSystem, Image Processing,Radiological	Same
Indications forUse	MREplus+ is an assistedROI drawing tool for liverMRE and Fat/Water imagesand is used for receiving,display, ROI selection, andanalysis generation. Itdisplays to a trained readerMRE and Fat/Water images,preliminary ROIs that itcalculates from theseimages, and statisticalanalysis calculated from theROIs and images. ROIs andimages are presented in away for review and,optionally, modification bythe trained reader. Thesevalues can be used as anelement in diagnosis of liverdisease.	The Advantage Workstation4.1 is a review station, whichallows selection, review,processing, filming, andmedia interchange of multi-modality images from avariety of diagnosticimaging systems. Wheninterpreted by a trainedphysician, filmed imagesmay be used as an elementfor diagnosis.	Intended use issubstantiallyequivalent.MREplus+ isintended for usewith liver MREand Fat/Waterdata, which is asubset of thescope ofapplications forthe GEAdvantage
ProductConfiguration	Software	Workstation	MREplus+ is astand-aloneapplication,whereas GE AWcomes pre-installed ondedicatedworkstations
Operating system	Windows or Linux	Linux	MREplus+ asstand-aloneapplication can

Input format	MRE and FW Liver DICOMImages	Multi-modality DICOMImages	be configured fordifferent OS,whereas the GEdedicatedworkstation mustselect an OS.DICOM input isthe same, withthe MREplus+liver imagesbeing a subset ofGE multi-modality images
Output	MREplus+ report displaysDICOM images whichincludes the generated ROIsoverlaid on the input images,and the calculated liverstatistical values	Advantage Workstation 4.1allows for display ofDICOM images of user-drawn ROIs overlaid oninput DICOM images, andthe calculated liver statisticalvalues	The outputimages withoverlaid ROIsand calculatedliver statisticalvalues aresubstantiallyequivalent.
Intended User	MRE-trained reader (e.g.technician or radiologist)	MRE-trained reader (e.g.technician or radiologist)	Same

Feature and Technical Characteristic Comparison

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Software Information

The MREplus+ software has been developed in accordance with the "Guidance for the Content of Premarket Submission for Software Contained in Medical Devices" for moderate level of concern. The Risk Management and Hazard Analysis combined with the appropriate testing and labeling mitigation measures taken indicate that the device is safe and effective and presents no new concerns.

The main activities in the software development process are described as follows.

Software Description ●
Level of Concern ●
Hazard/Risk Analysis ●
Software Requirements Specification ●
Architecture Design Flow Chart
Software Design Specification
Traceability Analysis
Software Development Life Cycle Plan ●
Software Development Environment ●
Software Design Verification/Validation Test ●
Revision Level History ●
Unresolved Anomalies ●

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Verification and Validation:

MREplus+ has been extensively tested through the design verification and system validation phases of its development. Validation Testing has been conducted using retrospective clinical data bases to compare MREplus+ 's functional capabilities with the standard expert reviewer readings using the predicate device. Studies included the following:

. MRE study involving 1347 patient cases where the patient profile included liver disease or suspicion of liver disease, inclusive of all ages, weight, and races. Images were collected at both 1.5T and 3T. MREplus+ demonstrated <1% processing failures and <20% ROI modifications.
Fat-Water study involving 92 patient cases, where recruited patents were undergoing bariatric surgery and FW results indicated a full range of liver fat content. Images were collected at both 1.5T and 3T. In all cases MREplus+ was able to accurately and reliably calculate Fat Fraction from Fat-Water images.

MREplus+ has consistently proven to be an accurate software tool that facilitates liver MRE analysis with an accuracy of >99% compared to the standard predicate methodology.

Conclusion:

Through the data and information presented. Resoundant Inc considers the MREplus+ Software substantially equivalent to the predicate device already on the market (cleared by the 510(k) process) in terms of indications for use, scientific technology, design, and functional performance and presents no new concerns about safety and effectiveness. The nonclinical and retrospective clinical validation tests conducted demonstrate that the device is as safe, as effective, and performs as well as or better than the legally marketed predicate device.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).