HepaFatSmart (V2.0.0)

K231459 · Resonance Health Analysis Services Pty, Ltd. · LNH · Jun 20, 2023 · Radiology

Device Facts

• Record ID: K231459
• Device Name: HepaFatSmart (V2.0.0)
• Applicant: Resonance Health Analysis Services Pty, Ltd.
• Product Code: LNH · Radiology
• Decision Date: Jun 20, 2023
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 892.1000
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device

Intended Use

HepaFatSmart is intended for the quantitative measurement of volumetric liver fat fraction (VLFF), proton density fat fraction (PDFF) and steatosis grading. HepaFatSmart is an application that is used for the non-invasive evaluation of liver tissue by utilising magnetic resonance images to evaluate the difference in resonance frequencies between hydrogen nuclei in water and triglyceride fat. The quantitative triglyceride fat fraction is based on the measurement of a magnetic resonance parameter that reflects the ratio of the proton density signal of triglyceride fat to the total proton density signal in the liver.

Device Story

HepaFatSmart is an AI-assisted SaMD for quantitative liver fat assessment. It takes DICOM MRI datasets (Gradient Recalled Echo) as input via a secure portal (FAST). The device uses a convolutional neural network (CNN) to automatically predict a liver region of interest (ROI) and applies computer vision to remove artifacts and blood vessels. It calculates Alpha, VLFF, PDFF, and steatosis grade, and performs automated liver iron assessment to accept/reject analysis. Used by radiologists in clinical settings, it produces PDF and DICOM reports containing fat distribution maps and confidence intervals. The output supports clinical diagnosis, management of fatty liver/metabolic syndromes, and donor screening. By automating ROI selection, it minimizes human error and improves reproducibility compared to manual methods. It does not contact patients, control other devices, or deliver treatment; clinical judgment remains primary.

Clinical Evidence

Bench testing and validation study (n=300, 281 passed IQC). Repeatability study (n=42) showed 100% reproducibility. Validation study compared HepaFatSmart to reference standard HepaFat-Scan. Results showed high agreement: sensitivity and specificity for predicting VLFF thresholds (4.1%, 12.1%, 16.2%) were >98%. Bland-Altman analysis showed small bias (0.2%) and improved performance over predicate HepaFat-Al.

Technological Characteristics

SaMD; utilizes Gradient Recalled Echo (GRE) MRI data. Core technology: Convolutional Neural Network (CNN) for liver ROI prediction; computer vision for artifact/vessel removal. Algorithmic modules for Alpha, VLFF, PDFF, steatosis grade, and iron assessment. Cloud-based or onsite deployment via FAST portal. Software is 'locked' post-training. DICOM input/output.

Indications for Use

Indicated for individuals of all ages and genders with confirmed or suspected fatty liver disease; support clinical decision-making for patients with fatty liver-related disease or metabolic syndromes; aid in assessment and screening of living liver transplant donors.

Regulatory Classification

Identification

A magnetic resonance diagnostic device is intended for general diagnostic use to present images which reflect the spatial distribution and/or magnetic resonance spectra which reflect frequency and distribution of nuclei exhibiting nuclear magnetic resonance. Other physical parameters derived from the images and/or spectra may also be produced. The device includes hydrogen-1 (proton) imaging, sodium-23 imaging, hydrogen-1 spectroscopy, phosphorus-31 spectroscopy, and chemical shift imaging (preserving simultaneous frequency and spatial information).

Special Controls

*Classification.* Class II (special controls). A magnetic resonance imaging disposable kit intended for use with a magnetic resonance diagnostic device only is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.

Predicate Devices

• HepaFat-Scan (K122035)
• HepaFat-Al (K201039)

Submission Summary (Full Text)

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June 20, 2023

Resonance Health Analysis Services Pty Ltd % Mitchell Wells Managing Director 141 Burswood Road Burswood, Western Australia 6100 Australia

Re: K231459

Trade/Device Name: HepaFatSmart (V2.0.0) Regulation Number: 21 CFR 892.1000 Regulation Name: Magnetic resonance diagnostic device Regulatory Class: Class II Product Code: LNH Dated: May 19, 2023 Received: May 19, 2023

Dear Mitchell Wells:

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.

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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

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

Sincerely.

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

Submission Number (if known)

K231459

Device Name

HepaFatSmart (V2.0.0)

#### Indications for Use (Describe)

Intended use:

HepaFatSmart is intended for the quantitative measurement of volumetric liver fat fraction (VLFF), proton density fat fraction (PDFF) and steatosis grading.

HepaFatSmart is an application that is used for the non-invasive evaluation of liver tissue by utilising magnetic resonance images to evaluate the difference in resonance frequencies between hydrogen nuclei in water and triglyceride fat. The quantitative triglyceride fat fraction is based on the measurement of a magnetic resonance parameter that reflects the ratio of the proton density signal of triglyceride fat to the total proton density signal in the liver.

Indications for use:

Support clinical diagnoses in individuals with confirmed or suspected fatty liver disease;

Support the subsequent clinical decision making processes for patients under management for fatty liver related disease or metabolic syndromes;

Aid in the assessment and screening of living donors for liver transplant.

Results, when interpreted by a trained physician can be used to support clinical diagnoses about the status of liver fat content, the subsequent clinical decision making processes for the management of fatty liver related diseases, metabolic syndromes, liver donor screening and lifestyle change. HepaFatSmart can be used to analyse the MRI images of patients of all populations independent of age and gender, with suspected clinical conditions related to the level of liver fat.

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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# 510(K) SUMMARY

This Summary has been prepared in accordance with 21 CFR 807.92.

# General Information

| Date Prepared | 07 June 2023 |
|-----------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Submitted by | Resonance Health Analysis Service Pty Ltd<br>141 Burswood Rd<br>Burswood 6100<br>AUSTRALIA |
| Main Contact | Mitchell Wells<br>Managing Director,<br>Resonance Health Analysis Services Pty Ltd<br>[e-mail]<br>Tel: [phone]<br>Fax: [phone] |
| US Contact (US Agent) | Michael van der Woude<br>Director & GM<br>Emergo Global Representation LLC<br>2500 Bee Cave Road, Building 1, Suite 300<br>Austin, TX 78746<br>Phone: [phone]<br>Fax : [phone]<br>Email : [e-mail] |

# Device Information

| Name of Device | HepaFatSmart |
|------------------------|-----------------------------------------------|
| Trade/proprietary Name | HepaFatSmart (V2.0.0) |
| Classification | Class II |
| Product Code | LNH |
| CFR Section | 892.1000 Magnetic Resonance Diagnostic Device |
| Panel | Radiology |

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# Description of the Device

HepaFatSmart is an SaMD designed to automatically analyse magnetic resonance imaging (MRI) datasets for quantitative assessment of a patient's liver fat, in form of volumetric liver fat fraction (VLFF), proton density fat fraction (PDFF), and steatosis grade. It is an Al assisted, automated version of HepaFat-Scan (another SaMD of Resonance Health). To carry out an analysis, the user simply uploads DICOM images to FAST, Resonance Health's secured user portal and job management system. No other user input is required for the analysis thereby minimising the impact of human error on obtained results. HepaFatSmart requires DICOM images as input data that have been acquired according to the HepaFatSmart (same as HepaFat-Scan) protocol.

The key components for the HepaFatSmart are:

- . MRI Protocol: A specific MRI protocol for acquisition of the raw image data. The MRI protocol is critical to ensure the quality of the end results. Its adherence is verified by the HepaFatSmart IQC module, an automated algorithm that checks the correctness of each parameter in the protocol.
- . HepaFatSmart: An image analysis software predicting a suitable liver region of interest (ROI) utilizing Al-assisted SaMD technology then performing the Alpha measurement and anomaly (excessive iron) detection. It is composed of one (1) convolutional neural network (CNN) performing liver ROI detection with undesired components (artefacts and major blood vessels) considered/removed using a computer vision technique with machine learning technology. Background noise correction is not considered as there is no or very minimal impact on the analysis outcome. Following the training of the Al assisted device, the system is completely 'locked down' for final validation prior to release in commercial use to ensure reproducibility of the results. In principle, the HepaFatSmart v2.0.0 uses the same MRI data analysis approach as HepaFat-Scan.
- . Volumetric Liver Fat Fraction Measurement (VLFF): A software module (algorithmic) that incorporates a conversion lookup table relating Alpha to VLFF is added to allow production of a VLFF report.
- . Proton Density Fat Fraction Measurement (PDFF): A software module (algorithmic) that incorporates a conversion lookup table relating VLFF to PDFF is added to allow production of a PDFF report.
- . Steatosis Grade Measurement: A software module (algorithmic) that incorporates a conversion lookup table relating VLFF to a steatosis grade.
- . Excessive liver iron assessment: An additional software module (algorithmic) that estimates the impact of liver iron content as per the inclusion criteria based on an algorithm to determine the analysis outcome (accept or reject).

The output of HepaFatSmart is the automatically generated reports in both PDF and DICOM (secondary captured) formats. Visually, the PDF and DICOM reports are identical except that the DICOM report also contains relevant header information. The HepaFatSmart report is populated with information stored in the DICOM header of the MRI images, the analysis result, where an Alpha value is converted into a VLFF value, a PDFF value, and a steatosis grade, and the associated confidence interval and normal range.

The HepaFatSmart report also contains pictures of two (2) echo times (TEs) (1st Out-of-Phase, 1st OP, and In-Phase, IP) of the analysed slice, a predicted liver ROI superimposed with one (IP) of the two TE images, and a fat distribution map. This is essential for the radiologist to check if the image

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analysed is a liver image, the Al predicted ROI is placed correctly within the liver region, and the result provided is valid and consistent with other relevant clinical considerations.

HepaFatSmart SaMD can be accessed through a cloud-based or onsite platform. Resonance Health has developed its own cloud-based platform, called 'FAST'. Alternatively, HepaFatSmart can be offered on third parties' (channel partner) platforms.

It is important to note that HepaFatSmart as a medical device does not:

- come into direct contact with patients or end-users;
- . control any other device used on the patient;
- . deliver any treatment or energy to the patient; or
- . provide diagnostic information upon which inappropriate (or lack of) treatment likely to result in serious adverse events is based; as clinical judgment would be used in the patient's clinical management, based upon a range of other factors relating to the patient.

# INTENDED USE

The intended use of HepaFatSmart is:

HepaFatSmart is intended for the quantitative measurement of volumetric liver fat fraction (VLFF), proton density fat fraction (PDFF) and steatosis grading.

HepaFatSmart is an application that is used for the non-invasive evaluation of liver tissue by utilising magnetic resonance images to evaluate the difference in resonance frequencies between hydrogen nuclei in water and triglyceride fat. The quantitative triglyceride fat fraction is based on the measurement of a magnetic resonance parameter that reflects the ratio of the proton density signal of triglyceride fat to the total proton density signal in the liver.

# INDICATIONS FOR USE

- Support clinical diagnoses in individuals with confirmed or suspected fatty liver disease;
- Support the subsequent clinical decision-making processes for patients under management for fatty liver related disease or metabolic syndromes;
- Aid in the assessment and screening of living donors for liver transplant.
- . Results, when interpreted by a trained physician can be used to support clinical diagnoses about the status of liver fat content, the subsequent clinical decision-making processes for the management of fatty liver related diseases, metabolic syndromes, liver donor screening and lifestyle change.

HepaFatSmart can be used to analyse the MRI images of patients of all population independent of age and gender, with suspected clinical conditions related to the level of liver fat.

# PREDICATE INFORMATION

HepaFatSmart is substantially equivalent to the predicate device HepaFat-Scan (Resonance Health Analysis Services- K122035) and better than HepaFat-Al (Resonance Health Services - K201039).

# SUBSTANTIAL EQUIVALENCE INFORMATION

The table below summarizes the main similarities and differences between HepaFat-Al and the predicate.

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| | HepaFatSmart | HepaFat-Al | HepaFat-Scan |
|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulatory Class | ll | ll | ll |
| 510(k) number | K231459 | K201039 | K122035 |
| Classification Name | System, Nuclear<br>Magnetic Resonance<br>Imaging, System, Image<br>Processing Radiological | System, Nuclear Magnetic<br>Resonance Imaging,<br>System, Image Processing<br>Radiological | System, Nuclear Magnetic<br>Resonance Imaging,<br>System, Image Processing<br>Radiological |
| CFR Section | 892.1000 | 892.1000 | 892.1000 |
| Product Code and<br>Classification Panel | LNH | LNH | LNH |
| Device Name | HepaFatSmart | HepaFat-Al | HepaFat-Scan |
| Trade/Common<br>Name | HepaFatSmart | HepaFat-Al | HepaFat-Scan |
| Description | Standalone software<br>platform designed to<br>automatically analyse<br>within seconds magnetic<br>resonance imaging (MRI)<br>datasets using the<br>method of HepaFat-Scan<br>with the liver ROI<br>predicted to generate an<br>estimate of the patient's<br>volumetric liver fat<br>fraction (VLFF),<br>converted into proton<br>density fat fraction<br>(PDFF) and steatosis<br>grade. No user input is<br>required for the analysis<br>thus minimising the<br>impact of human error<br>on obtained results. | Standalone software<br>platform designed to<br>automatically analyse<br>within seconds magnetic<br>resonance imaging (MRI)<br>datasets to generate an<br>estimate of the patient's<br>volumetric liver fat fraction<br>(VLFF), converted into<br>proton density fat fraction<br>(PDFF) and steatosis grade.<br>No user input is required<br>for the analysis thus<br>minimising the impact of<br>human error on obtained<br>results. | Standalone software<br>application to facilitate the<br>import and visualization of<br>multi-slice, gradient-echo<br>MRI data sets<br>encompassing the<br>abdomen, with<br>functionality independent<br>of the MRI equipment, to<br>provide objective and<br>reproducible<br>determination of the<br>triglyceride fat fraction in<br>magnetic resonance<br>images of the liver. It<br>utilises magnetic<br>resonance images that<br>exploit the difference in<br>resonance frequencies<br>between hydrogen nuclei<br>in water and triglyceride<br>fat. The quantitative<br>triglyceride fat fraction is<br>based on the<br>measurement of a<br>magnetic resonance<br>parameter that reflects<br>the ratio of the proton<br>density signal of<br>triglyceride fat to the total<br>proton density signal in<br>the liver. |
| | HepaFatSmart | HepaFat-Al | HepaFat-Scan |
| Technology | Convolutional neural<br>networks for the<br>prediction of the liver<br>region of interest (ROI).<br>Algorithmic for the<br>image quality checking<br>and calculated Alpha<br>conversion into VLFF,<br>PDFF and Steatosis<br>grade.<br>Algorithms for the<br>measurement and<br>calculation of Alpha<br>VLFF, PDFF and Steatosis<br>grade. | Convolutional neural<br>networks for the image<br>analysis.<br>Algorithmic for the image<br>quality checking and Alpha<br>conversion into VLFF. | Algorithmic, with human<br>interaction for Region of<br>Interest (ROI) selection. |
| Intended Use | HepaFatSmart is<br>intended for the<br>quantitative<br>measurement of<br>volumetric liver fat<br>fraction (VLFF), proton<br>density fat fraction<br>(PDFF) and steatosis<br>grading.<br>HepaFatSmart is an<br>application that is used<br>for the non-invasive<br>evaluation of liver tissue<br>by utilising magnetic<br>resonance images to<br>evaluate the difference<br>in resonance frequencies<br>between hydrogen<br>nuclei in water and<br>triglyceride fat. The<br>quantitative triglyceride<br>fat fraction is based on<br>the measurement of a<br>magnetic resonance<br>parameter that reflects<br>the ratio of the proton<br>density signal of<br>triglyceride fat to the<br>total proton density<br>signal in the liver. | HepaFat-Al is intended for<br>quantitative measurement<br>of the triglyceride fat<br>fraction in magnetic<br>resonance images of the<br>liver, also known as<br>volumetric liver fat fraction<br>(VLFF).<br>It utilises magnetic<br>resonance images that<br>exploit the difference in<br>resonance frequencies<br>between hydrogen nuclei<br>in water and triglyceride<br>fat. The quantitative<br>triglyceride fat fraction is<br>based on the<br>measurement of a<br>magnetic resonance<br>parameter that reflects the<br>ratio of the proton density<br>signal of triglyceride fat to<br>the total proton density<br>signal in the liver.<br>When interpreted by a<br>trained physician, the<br>results provide information<br>that can aid in diagnosis. | HepaFat-Scan is a software<br>device intended for<br>quantitative measurement<br>of the triglyceride fat<br>fraction in magnetic<br>resonance images of the<br>liver. It utilises magnetic<br>resonance images that<br>exploit the difference in<br>resonance frequencies<br>between hydrogen nuclei<br>in water and triglyceride<br>fat. The quantitative<br>triglyceride fat fraction is<br>based on the<br>measurement of a<br>magnetic resonance<br>parameter that reflects<br>the ratio of the proton<br>density signal of<br>triglyceride fat to the total<br>proton density signal in<br>the liver.<br>When interpreted by a<br>trained physician, the<br>results provide<br>information that can aid in<br>diagnosis. |
| Indications | Support clinical<br>• diagnoses in<br>individuals with | HepaFat-Al is indicated to:<br>• Assess the volumetric<br>liver fat fraction | HepaFat-Scan is a software<br>device intended for<br>quantitative measurement |
| | HepaFatSmart | HepaFat-Al | HepaFat-Scan |
| | confirmed or suspected fatty liver disease;<br>Support the subsequent clinical decision-making processes for patients under management for fatty liver related disease or metabolic syndromes; Aid in the assessment and screening of living donors for liver transplant. Results, when interpreted by a trained physician can be used to support clinical diagnoses about the status of liver fat content, the subsequent clinical decision-making processes for the management of fatty liver related diseases, metabolic syndromes, liver donor screening and lifestyle change. HepaFatSmart can be used to analyse the MRI images of patients of all population independent of age and gender, with suspected clinical conditions related to the level of liver fat. | proton density fat fraction and steatosis grade in individuals with confirmed or suspected fatty liver disease;<br>Monitor liver fat content in patients undergoing weight loss management; Aid in the assessment and screening of living donors for liver transplant. | of the triglyceride fat fraction in magnetic resonance images of the liver. It utilises magnetic resonance images that exploit the difference in resonance frequencies between hydrogen nuclei in water and triglyceride fat. The quantitative triglyceride fat fraction is based on the measurement of a magnetic resonance parameter that reflects the ratio of the proton density signal of triglyceride fat to the total proton density signal in the liver.<br><br>When interpreted by a trained physician, the results provide information that can aid in diagnosis. |
| User | Radiologist | Radiologist | Resonance Health's trained analyst |
| Hosting platform | Cloud-based or onsite platform | Cloud-based or onsite platform | Resonance Health's internal server |
| Image-type utilized | Magnetic Resonance | Magnetic Resonance | Magnetic Resonance |
| Image format | DICOM | DICOM | DICOM |
| Data Acquisition method | Gradient Recalled Echo (GRE) | Gradient Recalled Echo (GRE) | Gradient Recalled Echo (GRE) |
| | HepaFatSmart | HepaFat-Al | HepaFat-Scan |
| Anatomical Sites | Liver | Liver | Liver |
| Result report<br>content | Unique Report ID Patient ID, patient name, and date of birth for full identification of the patient. Scan date, and analysis date. Referrer and MRI centre. Results displayed: VLFF (%), PDFF (%) and Steatosis grade, associated with confidence intervals and normal range. Pictures of the 2 TEs of the analysed slice and analysis liver ROI placed on 1 TE. Liver colour map (for illustration purpose only, not for diagnostic) | Unique Report ID Patient ID, patient name, and date of birth for full identification of the patient. Scan date, and analysis date. Referrer and MRI centre. Results displayed: VLFF (%), PDFF (%) and Steatosis grade, associated with confidence intervals and normal range. Pictures of the 3 TEs of the analysed slice. Liver colour map (for illustration purpose only, not for diagnostic) | Unique Report ID Patient ID, patient name, and date of birth for full identification of the patient. Scan date, and analysis date. Referrer and MRI centre. Results displayed: VLFF (%) associated with confidence intervals and normal range. Picture of the analysed slice. |
| Result report<br>format | PDF (encrypted) and<br>secondary capture<br>(DICOM) | HTML and PDF | PDF |

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#### SUMMARY OF HEPAFATSMART PERFORMANCE - SUBSTANTIAL EQUIVALENCE

The device HepaFatSmart is in principle a new version of the predicate HepaFat-Al but with the name changed. As indicated in the Software Validation Report, three different technical analyses were performed to indicate the technical equivalency of HepaFatSmart compared with the reference standard HepaFat-Scan: Repeatability Study, Linear Regression Analysis and Bland Altman Analysis.

#### Repeatability Study (n = 42)

Repeatability study using a dataset with two different MRI scans for each subject to evaluate the device performance is a self-proven process as each paired data for a subject is supposed to produce the same analysis outcome. Briefly, the results are summarised as following:

Image /page/10/Figure/4 description: The image contains two scatter plots, labeled A and B, comparing two sets of measurements. Plot A compares 'HepaFat-Scan VLFF Scan 1 (%)' on the x-axis with 'HepaFat-Scan VLFF Scan 2 (%)' on the y-axis, showing a positive correlation. Plot B compares 'HepaFatSmart VLFF Scan 1 (%)' on the x-axis with 'HepaFatSmart VLFF Scan 2 (%)' on the y-axis, also showing a positive correlation. Both plots feature a diagonal line, indicating a perfect agreement between the two scans, and data points clustered closely around this line.

Figure 1. Plot A of HepaFat-Scan 2 against HepaFat-Scan VLFF measured at scan 1 for the 42 subjects in the repeatability study. Plot B is for HepaFatSmart (41 subjects). The solid line is the line of equivalence. Note, 41 instead of 42 subjects were used in the HepaFatSmart related analysis as a single case was identified as a high iron case with the newly introduced excessive iron assessment algorithm. All the results are closely scattered around the equivalency line, indicating good performance and substantial equivalence for both the predicate HepaFatSmart,

From the linear regression analysis shown in Figure 1 for both the reference standard HepaFat-Scan (plot A) and HepaFatSmart (plot B), all the results are closely scattered around the equivalency line and difficult to tell visually which one is better.

Image /page/10/Figure/7 description: The image contains two Bland-Altman plots comparing HepaFat-Scan and HepaFatSmart measurements. The left plot, labeled "A. HepaFat-Scan (reference standard)," displays the difference between two HepaFat-Scan measurements against their mean, with the y axis labeled as "HepaFat-Scan VLFF Scan 2 - HepaFat-Scan VLFF Scan 1" and the x axis labeled as "Mean HepaFat-Scan VLFF (%)". The right plot, labeled "B. HepaFatSmart," shows the difference between two HepaFatSmart measurements against their mean, with the y axis labeled as "HepaFatSmart VLFF Scan 2 - HepaFatSmart VLFF Scan 1" and the x axis labeled as "Mean HepaFatSmart VLFF (%)".

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Figure 2. Bland Altman analysis of the repeatability study: plot A - HepaFat-Scan VLFF measured scan 1 and 2 for the 42 subjects; plot B is for HepaFatSmart (41 subjects). Bias and both repeatability coefficients are slightly better for HepaFatSmart compared with the reference standard HepaFat-Scan.

From the Bland Altman analysis shown in Figure 2 for both the reference standard HepaFat-Scan (plot A) and HepaFatSmart (plot B), bias and both repeatability coefficients for the HepaFatSmart are slightly better than those obtained from the repeated scans of HepaFat-Scan, indicating the performance of the HepaFatSmart is comparable (no worse) than human for the repeatability data analysed. This does not suggest yet that the HepaFatSmart is better than human analyst as the original human analysis (HepaFat-Scan) historically used two small liver ROIs rather than a single large liver ROI used in the HepaFatSmart with potentially slightly larger sampling error in the original HepaFat-Scan analysis. From the repeatability data, there was no statistically significant bias and tight repeatability coefficients for the HepaFatSmart, indicating the substantial equivalence to the predicate HepaFat-Scan and a possibility that the results from HepaFatSmart and HepaFat-Scan could be interchangeable.

In addition, HepaFatSmart demonstrated 100% repeatable (reproducible) in the repeatability study using the same datasets analysed twice with zero VLFF difference between the first and second analyses, which is better than human analysis with HepaFat-Scan.

#### Validation Study (n=300)

Validation study using a dataset with two different MRI scans for each subject to evaluate the device performance is a self-proven process as each paired data for a subject is supposed to produce the same analysis outcome. Briefly, the results are summarised as following (note the study population size is smaller than 300 as per the IQC module in place):

Image /page/11/Figure/5 description: The image contains two scatter plots, labeled A and B, comparing HepaFatSmart VLF and HepaFat-Scan VLFF. Plot A shows a broader range of values, extending up to 45% on both axes, while plot B focuses on a smaller range, up to 10%. Both plots show a positive correlation between the two methods, with data points clustered around a diagonal line, indicating agreement between HepaFatSmart and HepaFat-Scan VLFF measurements.

Figure 3. Linear regression analysis of the validation study (n = 281) by comparing HepaFatSmart with the reference standard HepaFat-Scan: plot A shows the full VLFF range and plot B shows the VLFF range between 0 – 10%. The solid line is the line of equivalence. 281 da…