(67 days)
Hepatica (Hepatica v1) is a post-processing medical device software that presents quantified metrics which may contribute to the assessment of a patient's liver health.
Hepatica (Hepatica v1) uses image visualisation and analysis tools to process DICOM 3.0 compliant magnetic resonance image datasets to produce semi-automatic segmented 3D models of the work of Couinaud and the Brisbane 2000 terminology. For each identified Couinaud segment, volumetric data is determined and reported.
Hepatica v1) may also report iron corrected-T1 (cT1) and PDFF calculated using the IDEAL method from multi-slice acquisitions, on a per segment basis, over the whole liver. Both metrical values of different fundamental liver tissue characteristics that can be used as measures of liver tissue health.
Hepatica (Hepatica v1) provides trained clinicians with additional information to evaluate the volume and health of a patient's liver on a segmental basis. It is not intended to replace the established procedures for the assessment of a patient's liver health. However, information gathered through existing diagnostic tests, clinical evaluation of the patient, as well Hepatica (Hepatica v1), may support surgical decision making.
Hepatica v1 is a standalone software device that imports MR datasets encompassing the abdomen, including the liver. Visualisation and display of T1-weighted MR data which can be analysed, and quantitative metrics of tissue characteristics and liver volume are then reported. Datasets imported into Hepatica are DICOM 3.0 compliant and reported metrics are independent of the MRI equipment vendor. It allows for the 3D visualisation of the liver and quantification of metrics (cT1, PDFF and volumetry) from liver tissue and exportation of results and images to a deliverable report. Hepatica v1 supports semi-automatic liver segmentation of T1-weighted volumetric data. Liver segmentation in Hepatica v1 requires the placement of anatomical landmarks to define the outer contours of the liver and can be adjusted by the operator, where necessary. Where available, whole liver and segmental cT1 and PDFF quantitative metrics derived from the predicate device may be presented in the final report. Hepatica uses volumetric datasets to create 2D anatomical views from all supported scanners. Where available, cT1 and PDFF parametric maps are derived from the predicate device. Quantified metrics and images derived from the analysis of liver volume and tissue characteristics are collated into a report for evaluation and interpretation by a clinician.
Here's a breakdown of the acceptance criteria and study information for the Hepatica (Hepatica v1) device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state acceptance criteria in a quantitative format (e.g., "accuracy must be >X%"). Instead, it states that the performance testing "demonstrates that Hepatica v1 is at least as safe and effective as the predicate device and does not introduce any new risks."
However, it provides "Upper and Lower Limits of Agreement" from a Bland-Altman analysis, which can be interpreted as the range within which the device's measurements agree with the gold standard. A tighter range indicates higher accuracy. The precision results are also presented as "Upper and Lower limits of Agreement" for repeatability and reproducibility.
The table below summarizes the reported device performance, which implies that these values met the internal acceptance parameters for demonstrating substantial equivalence:
| Metric | Type of Measurement | Reported Device Performance (Upper and Lower Limits of Agreement) |
|---|---|---|
| Volume (% of total liver volume) | ||
| Segment 1 | Accuracy | -0.49% to 0.95% |
| Segment 2 | Accuracy | -3.09% to 5.06% |
| Segment 3 | Accuracy | -5.01% to 3.9% |
| Segment 4a | Accuracy | -4.60% to 4.26% |
| Segment 4b | Accuracy | -5.50% to 2.56% |
| Segment 5 | Accuracy | -1.54% to 3.38% |
| Segment 6 | Accuracy | -4.34% to 4.29% |
| Segment 7 | Accuracy | -3.30% to 1.79% |
| Segment 8 | Accuracy | -3.86% to 5.54% |
| Whole liver | Accuracy | -4.16% to 0.54% |
| Segment 1 | Repeatability | -0.72% to 0.65% |
| Segment 2 | Repeatability | -3.06% to 3.24% |
| Segment 3 | Repeatability | -2.67% to 3.13% |
| Segment 4a | Repeatability | -2.48% to 2.43% |
| Segment 4b | Repeatability | -1.82% to 1.96% |
| Segment 5 | Repeatability | -4.45% to 4.45% |
| Segment 6 | Repeatability | -3.60% to 4.10% |
| Segment 7 | Repeatability | -3.32% to 3.33% |
| Segment 8 | Repeatability | -4.99% to 3.81% |
| Whole liver | Repeatability | -6.15% to 3.78% |
| Segment 1 | Reproducibility | -1.39% to 0.90% |
| Segment 2 | Reproducibility | -3.10% to 3.15% |
| Segment 3 | Reproducibility | -2.41% to 2.06% |
| Segment 4a | Reproducibility | -2.54% to 2.58% |
| Segment 4b | Reproducibility | -1.70% to 1.74% |
| Segment 5 | Reproducibility | -4.97% to 5.94% |
| Segment 6 | Reproducibility | -3.69% to 5.40% |
| Segment 7 | Reproducibility | -4.39% to 3.59% |
| Segment 8 | Reproducibility | -6.23% to 5.04% |
| Whole liver | Reproducibility | -16.6% to 6.95% |
| cT1 | ||
| Segment 1 | Accuracy | -1.13% to 0.61% |
| Segment 2 | Accuracy | -2.38% to 1.56% |
| Segment 3 | Accuracy | -1.51% to 1.31% |
| Segment 4a | Accuracy | -0.77% to 1.10% |
| Segment 4b | Accuracy | -1.32% to 1.13% |
| Segment 5 | Accuracy | -1.11% to 0.87% |
| Segment 6 | Accuracy | -1.00% to 0.83% |
| Segment 7 | Accuracy | -0.88% to 0.64% |
| Segment 8 | Accuracy | -0.91% to 1.09% |
| Whole liver | Accuracy | 0.00% to 0.00% (This suggests perfect agreement or rounding issues) |
| PDFF | ||
| Segment 1 | Accuracy | -0.26% to 0.21% |
| Segment 2 | Accuracy | -0.33% to 0.38% |
| Segment 3 | Accuracy | -0.16% to 0.17% |
| Segment 4a | Accuracy | -0.30% to 0.23% |
| Segment 4b | Accuracy | -0.16% to 0.14% |
| Segment 5 | Accuracy | -0.16% to 0.18% |
| Segment 6 | Accuracy | -0.16% to 0.26% |
| Segment 7 | Accuracy | -0.12% to 0.18% |
| Segment 8 | Accuracy | -0.24% to 0.32% |
| Whole liver | Accuracy | -0.02% to 0.02% |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The document states that the performance testing used "previously acquired in-vivo data from healthy and non-healthy volunteers." It also mentions "Volunteers participating in the performance testing were representative of the intended patient population." However, a specific number for the sample size (N) of these volunteers or images in the test set is not provided.
- Data Provenance: "Previously acquired in-vivo data." The country of origin is not explicitly stated. It can be inferred that the data is likely from the UK, given the submitter's address (Oxford, UK). The data is retrospective, as it was "previously acquired."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Number of Experts: The document refers to the gold standard as "radiologists." It does not specify the number of radiologists involved in establishing the ground truth.
- Qualifications of Experts: The qualification is "radiologists." No further details on their years of experience or sub-specialty are provided.
4. Adjudication Method for the Test Set
The document states that the "gold standard" is "radiologists." It does not describe any specific adjudication method (e.g., 2+1, 3+1 consensus) used to establish this ground truth. It implies that the radiologists' readings were considered the definitive truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The study compared the device's measurements to a "gold standard" (radiologists' assessments), not the performance of human readers with vs. without AI assistance. Therefore, there is no effect size reported for human readers improving with AI assistance.
6. If a Standalone Study Was Done
Yes, a standalone (algorithm only without human-in-the-loop performance) study was done. The performance testing section directly reports on the "Accuracy" and "Precision" of Hepatica v1's measurements (cT1, PDFF, and volumetry) when compared to the gold standard. The device operators are "trained Perspectum internal operators," but the reported metrics are explicitly from the device's output. The statement "The variation introduced by operator measurements are well within the acceptance criteria" also suggests an understanding of the device's standalone performance separate from human interpretation of the reports.
7. The Type of Ground Truth Used
The primary ground truth used for accuracy comparison is expert consensus/interpretation, specifically "radiologists." For cT1 and PDFF, these are quantitative measurements derived from imaging, which radiologists would interpret or measure. For volumetry, it's also based on radiological assessment.
8. The Sample Size for the Training Set
The document does not provide the sample size for the training set. It only mentions the "previously acquired in-vivo data from healthy and non-healthy volunteers" used for performance testing.
9. How the Ground Truth for the Training Set Was Established
Since the training set sample size and its specifics are not mentioned, how its ground truth was established is not described in the provided document.
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January 12, 2021
Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
Perspectum Ltd. % Ioan Wigley Chief Compliance Officer 5520 John Smith Drive Oxford, Oxfordshire OX4 2LL UNITED KINGDOM
Re: K203280
Trade/Device Name: Hepatica (Hepatica v1) Regulation Number: 21 CFR 892.1000 Regulation Name: Magnetic resonance diagnostic device Regulatory Class: Class II Product Code: LNH Dated: October 1, 2020 Received: November 16, 2020
Dear Ioan Wigley:
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) K203280
Device Name Hepatica (Hepatica v1)
Indications for Use (Describe)
Hepatica (Hepatica v1) is a post-processing medical device software that presents quantified metrics which may contribute to the assessment of a patient's liver health.
Hepatica (Hepatica v1) uses image visualisation and analysis tools to process DICOM 3.0 compliant magnetic resonance image datasets to produce semi-automatic segmented 3D models of the work of Couinaud and the Brisbane 2000 terminology. For each identified Couinaud segment, volumetric data is determined and reported.
Hepatica v1) may also report iron corrected-T1 (cT1) and PDFF calculated using the IDEAL method from multi-slice acquisitions, on a per segment basis, over the whole liver. Both metrical values of different fundamental liver tissue characteristics that can be used as measures of liver tissue health.
Hepatica (Hepatica v1) provides trained clinicians with additional information to evaluate the volume and health of a patient's liver on a segmental basis. It is not intended to replace the established procedures for the assessment of a patient's liver health. However, information gathered through existing diagnostic tests, clinical evaluation of the patient, as well Hepatica (Hepatica v1), may support surgical decision making.
| 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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Date Prepared:
28th October 2020
1. Submitter Details
| Owner Address: | Perspectum LtdGemini One,5520 John Smith Drive,Oxford Business Park,Oxford,OX4 2LL |
|---|---|
| Owner/Operator Number: | 10056574 |
| Establishment Registration Number: | 3014232555 |
| Contact Person: | Ioan Wigley |
ioan.wigley@perspectum.com +44 (0) 1865 655329
2. Subject and Predicate Device
| Subject Device | Predicate Device | |
|---|---|---|
| 510(k) number | K203280 | K202170 |
| Legal Manufacturer | Perspectum Ltd. | Perspectum Ltd. |
| Owner/Owner Operator | 10056574 | 10056574 |
| Device Name | Hepatica (Hepatica v1) | LiverMultiScan (LMSv4) |
| Proprietary/Common | Hepatica | LiverMultiScan |
| Panel | Radiology | Radiology |
| Regulation | 892.1000 | 892.1000 |
| Risk Class | Class II | Class II |
| Product Class code | LNH | LNH |
| Classification | System, Nuclear MagneticResonance Imaging | System, Nuclear MagneticResonance Imaging |
3. Subject Device Description
3.1. Intended Use
Hepatica (Hepatica v1) is a post-processing medical device software that presents quantified metrics which may contribute to the assessment of a patient's liver health.
Hepatica (Hepatica v1) uses image visualisation and analysis tools to process DICOM 3.0 compliant magnetic resonance image datasets to produce semi-automatic segmented 3D models of the liver based on the work of Couinaud and the Brisbane 2000 terminology. For each identified Couinaud segment, volumetric data is determined and reported.
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Hepatica (Hepatica v1) may also report iron corrected-T1 (cT1) and PDFF calculated using the IDEAL method from multi-slice acquisitions, on a per segment basis, over the whole liver. Both metrical values of different fundamental liver tissue characteristics that can be used as measures of liver tissue health.
Hepatica (Hepatica v1) provides trained clinicians with additional information to evaluate the volume and health of a patient's liver on a segmental basis. It is not intended to replace the established procedures for the assessment of a patient's liver health. However, information gathered through existing diagnostic tests, clinical evaluation of the patient, as well Hepatica (Hepatica v1), may support surgical decision making.
3.2. Sterilization and Shelf Life
Hepatica v1 is a standalone software device thus it is non-contact, non-invasive and non-sterile. The shelf life of Hepatica v1 is indefinite as long as the manufacturer continues to support the device. Both sterilization and shelf life characteristics are equivalent of the predicate device.
3.3. Biocompatibility
Hepatica v1 is a standalone software device thus it is non-contact and non-invasive. No biocompatibility testing was deemed necessary to demonstrate the safety and effectiveness of Hepatica v1 does not consist of materials that differ from the predicate device.
3.4. Software
Hepatica v1 was successfully validated and verified against the requirements specification and its intended use. The results from the validation and verification activities, documented in this submission, corroborate that Hepatica v1 meets the product requirement specifications and intended use, which is deemed to be substantially equivalent to the predicate (see section below).
Validation and verification activities were conducted in a controlled environment and in compliance with IEC 62304:2006, ISO 13485:2016 and 21 CFR 820. Hepatica v1 is also in compliance with the DICOM standard.
3.5. Electromagnetic and Electrical Safety
Hepatica v1 is a standalone software device- there are no electrical safety risks associated with the direct use of the Hepatica v1 device. No electromagnetic or electrical safety testing was deemed necessary to demonstrate the safety and effectiveness of Hepatica v1.
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Perspectu
4. Subject and Predicate Comparison
Subject and Predicate Device Comparison 4.1.
The following characteristics were compared between the subject device and the predicate device in order to demonstrate substantial equivalence.
| Comparison of Subject and Predicate Device | ||
|---|---|---|
| Characteristic | Hepatica v1 (Subject device) | LMSv4 (Predicate device) |
| Intended Use andIndications for Use | "Hepatica (Hepatica v1) is a post-processingmedical device software that presentsquantified metrics which may contribute tothe assessment of a patient's liver health. | "LiverMultiScan (LMSv4) is indicated for useas a magnetic resonance diagnostic devicesoftware application for non-invasive liverevaluation that enables the generation,display and review of 2D magnetic resonancemedical image data and pixel maps for MRrelaxation times. |
| Hepatica (Hepatica v1) uses imagevisualisation and analysis tools to processDICOM 3.0 compliant magnetic resonanceimage datasets to produce semi-automaticsegmented 3D models of the liver based onthe work of Couinaud and the Brisbane 2000terminology. For each identified Couinaudsegment, volumetric data is determined andreported. | LiverMultiScan (LMSv4) is designed to utilizeDICOM 3.0 compliant magnetic resonanceimage datasets, acquired from compatibleMR systems, to display the internal structureof the abdomen including the liver. Otherphysical parameters derived from the imagesmay also be produced. | |
| Hepatica (Hepatica v1) may also report ironcorrected-T1 (cT1) and PDFF calculated usingthe IDEAL method from multi-sliceacquisitions, on a per segment basis, overthe whole liver. Both metrics presentnumerical values of different fundamentalliver tissue characteristics that can be usedas measures of liver tissue health. | LiverMultiScan (LMSv4) provides a number oftools, such as automated liver segmentationand region of interest (ROI) placements, tobe used for the assessment of selectedregions of an image. Quantitativeassessments of selected regions include thedetermination of triglyceride fat fraction inthe liver (PDFF), T2* and iron-corrected T1(cT1) measurements. T2* may be optionallycomputed using the DIXON or LMS MOSTmethods. | |
| Hepatica (Hepatica v1) provides trainedclinicians with additional information toevaluate the volume and health of a patient'sliver on a segmental basis. It is not intendedto replace the established procedures for theassessment of a patient's liver health.However, information gathered throughexisting diagnostic tests, clinical evaluation ofthe patient, as well Hepatica (Hepatica v1),may support surgical decision making." | These images and the physical parametersderived from the images, when interpretedby a trained clinician, yield information thatmay assist in diagnosis." | |
| Target Population | Patients who are suitable to undergo an MRIscan and not contra-indicated for MRI.Hepatica may benefit the clinicalmanagement of patients who are beingconsidered for liver resection(s). | Patients suitable to undergo an MRI scan andnot contra-indicated for MRI |
| Comparison of Subject and Predicate Device | ||
| Characteristic | Hepatica v1 (Subject device) | LMSv4 (Predicate device) |
| Device User | Trained Perspectum internal operator | Trained Perspectum internal operator |
| Report User | An interpreting clinician or healthcarepractitioner | An interpreting clinician or healthcarepractitioner |
| Device UseEnvironment | Installation of Hepatica v1 is controlled and isinstalled on general purpose workstationsthat meet the minimum technicalrequirements at Perspectum's image analysiscentre by specialist members of staff | Installation of LMSv4 is controlled and isinstalled on general purpose workstationsthat meet the minimum technicalrequirements at Perspectum's image analysiscentre by specialist members of staff. |
| Clinical Setting | Hepatica v1 is a standalone software devicethat is intended to be installed on generaluse workstations at Perspectum's imageanalysis centres. The intended device userswill log on to the workstations, access thedevice, and use the device on general-useHD monitors.Hepatica v1 is a post-processing softwareand the intended device users are trained | LMSv4 is a standalone software device that isintended to be installed on general useworkstations at Perspectum's image analysiscentres. The intended device users will logon to the workstations, access the device,and use the device on general-use HDmonitors.LMSv4 is a post-processing software and theintended device users are trained |
| Perspectum internal operators.Operators use Hepatica v1 to conductquantitative analysis of liver tissuecharacteristics to produce a report.The end-users for the output from the | Perspectum internal operators.Operators use LMS to conduct quantitativeanalysis of liver tissue characteristics toproduce a report.The end-users for the output from the | |
| device, the report, are clinicians who receiveand interpret Hepatica v1 reports. | device, the report, are clinicians who receiveand interpret LMSv4 reports. | |
| AnatomicalLocation | Abdomen, including the Liver | Abdomen, including the Liver |
| EnergyConsiderations | Hepatica is a standalone softwareapplication. It does not deliver, monitor ordepend on energy delivered to or frompatients. | LMS is a standalone software application. Itdoes not deliver, monitor or depend onenergy delivered to or from patients. |
| Design: Purpose | Hepatica is a standalone software applicationthat imports MR datasets encompassing theabdomen, including the liver. Visualisationand display of T1-weighted MR data whichcan be analysed, and quantitative metrics oftissue characteristics and liver volume arethen reported.Datasets imported into Hepatica are DICOM3.0 compliant and reported metrics areindependent of the MRI equipment vendor. | LMS is a standalone software application thatimports MR data sets encompassing theabdomen, including the liver. Visualisationand display of 2D multi-slice, spin-echo MRdata can be analysed, and quantitativemetrics of tissue characteristics are thenreported.Datasets imported into LMS are DICOM 3.0compliant, reported metrics are independentof the MRI equipment vendor. |
| Design: Tools | Allows for the 3D visualisation of the liverand quantification of metrics (cT1, PDFF andvolumetry) from liver tissue and exportationof results and images to a deliverable report. | Allows for the visualisation via parametricmaps and quantification of metrics (cT1, T2*and PDFF) from liver tissue and exportationof results and images to a deliverable report. |
| Comparison of Subject and Predicate Device | ||
| Characteristic | Hepatica v1 (Subject device) | LMSv4 (Predicate device) |
| Hepatica v1 allows for: | LMSv4 allows for: | |
| Volumetry Reporting of whole liver and segmental volume Semi-automatic segmentation of the outer contour of the liver Semi-automatic segmentation of the liver into Couinaud segments via placed landmarks of anatomical areas of interest | cT1 Full segmentation of the outer liver contour and liver vasculature of the cT1 parametric map. IQR and median metrics are reported from the segmentation. ROI placed method on the cT1 map with IQR and median metrics from the placed ROI's potentially across multiple acquired slices. | |
| cT1 and PDFF metrics may be quantified and loaded from LMS when analysis has been conducted on the same patient. Datasets imported from LMS contain all image analysis warnings and cautions associated with the individual analysis and are included in the hepatica report. | T2* ROI placed method on the T2* map with IQR and median metrics from the placed ROI's potentially across multiple acquired slices. T2* parametric maps are calculated from the MOST method or the three-point DIXON method (1) | |
| PDFF Full liver segmentation of the PDFF parametric map where IQR and median metrics are reported from the segmentation. ROI placed method on the PDFF map with IQR and median metrics from the placed ROI's potentially across multiple acquired slices PDFF parametric maps are calculated using the LMS IDEAL method (2) | ||
| Design: MRRelaxometry | Hepatica v1 does not support quantification of metrics from MR relaxometry. If cT1 results are imported from LMS, cT1 may be reported for all individual Couinaud segments and for whole-liver analysis. Median T2* values are given from the cT1 quantification. | T1, iron- and fat- corrected T1 (cT1) and T2* mapping |
| Design: Liver FatQuantification | Liver fat quantification data is imported from the predicate device (LMSv4), where available. If PDFF results are imported from LMS, PDFF may be reported for all individual Couinaud segments as well as Whole-liver | Utilizes MR images that exploit the difference in resonance frequencies between hydrogen nuclei in water and triglyceride fat using the LMS IDEAL method (2). |
| Comparison of Subject and Predicate Device | ||
| Characteristic | Hepatica v1 (Subject device) | LMSv4 (Predicate device) |
| contour. PDFF parametric maps arecalculated using the LMS IDEAL method (2). | ||
| Design: LiverSegmentation | Hepatica v1 supports semi-automatic liversegmentation of T1-weighted volumetricdata.Liver segmentation in Hepatica v1 requiresthe placement of anatomical landmarks todefine the outer contours of the liver andcan be adjusted by the operator, wherenecessary.Where available, whole liver and segmentalcT1 and PDFF quantitative metrics derivedfrom the predicate device may be presentedin the final report. | LMSv4 supports automatic multi-slice fullliver segmentation of the cT1 and PDFFparametric maps. Use of this functionality isat the discretion of the operator, instead orin combination, with the ROI based method.The cT1 segmented liver is presented incolour level window, while the rest of thecT1 image is presented in greyscale levelwindow with liver vasculature excluded fromthe segmented volume. |
| Design: Regions ofInterest (ROI) | Does not support ROI functionality. | Median and interquartile rangemeasurements created from a crosssectional slice of liver tissue. For eachparametric map, statistics from multipleRegions of Interest (ROIs) - potentiallyplaced across multiple slices - aresummarised.Also supports the display of 'Live' ROIstatistics when moving the ROI across theparametric map. |
| Design: ParametricMaps | Hepatica uses volumetric datasets to create2D anatomical views from all supportedscanners.Where available, cT1 and PDFF parametricmaps are derived from the predicate device. | Iron corrected T1 (cT1), T2* and ProtonDensity Fat Fraction (PDFF) parametric mapscan be created from all supported scanners.It is possible to use the T2* and PDFF mapsand knowledge of the T2* and PDFFmeasurements and the scanner fieldstrength to correct for signal changes relatedto iron deposits, producing a cT1 map. ThecT1 map eliminates the effects of elevatediron from the T1 measurement (3) andstandardizes for the fat signal across scannermanufacturers.PDFF is quantified using the LMS IDEALmethod. Parametric maps of T2* may beoptionally be computed using either thethree-point DIXON method or the LMS MOSTmethod. |
| Comparison of Subject and Predicate Device | ||
| Characteristic | Hepatica v1 (Subject device) | LMSv4 (Predicate device) |
| Design:Visualisation | Numerous views in the Hepatica v1 interfacecan be used to assist analysis.Operators are able to see live views ofcrosshair placements during landmarkingacross multiple image planes simultaneouslyand adjust contrast where required.Lesion segmentation will be performed bynavigating through the axial slices using thecrosshair tool and "painting in" the segmenton each slice.Operators will be required to navigatethrough the axial, sagittal and coronal planesusing the crosshair tool to confirm that thedelineation carried out by the device isaccurate. The borders can be adjustedaccordingly.Views of the segmented liver and lesions areupdated in real-time and can be rotated in a3D space. Paint, eraser and zoomingfunctionalities are also available to theoperator.Where available, operators can review theposition of cT1 and PDFF slices (derived fromLMSv4) within the 3D view of the liver. | Numerous views within the LMSv4 interfacecan be used to assist in analysis, Iron-corrected T1 (cT1), T2* and triglyceride fat(also known as Proton Density Fat Fraction(PDFF)) parametric maps can be createdfrom all supported scanners. R² maps canalso be utilised to assess the quality of themap fitting.Iron- corrected T1 (cT1) displayed usingLMSv4 colourmap, designed to havemaximum contrast on liver parenchymaltissue. |
| Design: SupportedModalities | DICOM 3.0 compliant MR data fromsupported MRI scanners. | DICOM 3.0 compliant MR data fromsupported MRI scanners. |
| Design: Report | Quantified metrics and images derived fromthe analysis of liver volume and tissuecharacteristics are collated into a report forevaluation and interpretation by a clinician.ImagesImages of the whole liver divided intoCouinaud segments are presented ingreyscale in the report.Where available, cT1 and PDFF slices are alsopresented from the imported LMSv4analysis.ValuesWhole and segmental liver volume metricscalculated during analysis are provided in thereport. | Quantified metrics and images derived fromthe analysis of liver tissue characteristic onparametric maps are collated into a reportfor evaluation and interpretation by aclinician.When segmentation analysis is used arepresentative pie- chart is provided basedon the confirmed segmentation contourfrom the PDFF map. The voxels within thesegmentation are separated into 5categories (<5% PDFF, 5-10% PDFF, 10-33% PDFF, 33-66% PDFF and >66%) to giveproportions based on PDFF. These categorieswere chosen based on the work of Kleiner etal (3) and Satkunasingham et al (4) on thegrading of histological features presented inNon-Alcoholic Fatty Liver Disease. |
| Comparison of Subject and Predicate Device | ||
| Characteristic | Hepatica v1 (Subject device) | LMSv4 (Predicate device) |
| Where available, whole liver segmental cT1and PDFF values are provided. For eachmetric, the median, IQR and a 'referencerange' are provided. | Based on the placed ROIs, for each metricthe median and IQR are given as well as a'reference range'. | |
| Compatibility withthe environment | Installation of Hepatica v1 is controlled and isinstalled on general purpose workstationsthat meet the minimum technicalrequirements at Perspectum's image analysiscentre by specialist members of staff. | Installation of LMSv4 is controlled and isinstalled on general purpose workstationsthat meet the minimum technicalrequirements at Perspectum's image analysiscentre by specialist members of staff. |
| Performance | Device performance was assessed withpreviously acquired in-vivo data from healthyand non-healthy volunteers. | Device performance was assessed withpurpose-built phantoms and in-vivo acquireddata from volunteers covering a range ofphysiological values for cT1, T2* and PDFF. |
| Human Factors | Assessed in accordance with IEC 62366 andFDA guidance document 'Applying HumanFactors and Usability Engineering to MedicalDevices.' | Assessed in accordance with IEC 62366 andFDA guidance document 'Applying HumanFactors and Usability Engineering to MedicalDevices.' |
| Supported MRISystems | Validated across all listed supportedmanufacturers and field strengths. | Validated across all listed supportedmanufacturers and field strengths. |
| Standards | IEC 62304, IEC 62366, DICOM 3.0, ISO 14971,ISO 13485 | IEC 62304, IEC 62366, DICOM 3.0, ISO 14971,ISO 13485 |
| System/OperatingSystem | Mac OS | Mac OS |
| Materials | Not applicable, standalone software | Not applicable, standalone software |
| Biocompatibility | Not applicable, standalone software | Not applicable, standalone software |
| Sterility | Not applicable, standalone software | Not applicable, standalone software |
| Electrical Safety | Not applicable, standalone software | Not applicable, standalone software |
| Mechanical Safety | Not applicable, standalone software | Not applicable, standalone software |
| Chemical Safety | Not applicable, standalone software | Not applicable, standalone software |
| Thermal Safety | Not applicable, standalone software | Not applicable, standalone software |
| Radiation Safety | Not applicable, standalone software | Not applicable, standalone software |
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Table 1. Comparison of similar characteristics between the subject and predicate device.
In conclusion, the subject device does not result in any new potential safety risk when compared to the chosen predicate device and performs in accordance with its use characteristics and intended use.
5. Performance Testing
Hepatica v1 underwent performance testing under controlled conditions to corroborate that it is safe and effective when used as intended. The performance testing conducted demonstrates that Hepatica v1 is at least as safe and effective as the predicate device and does not introduce any new risks.
5.1. Performance Testing - Clinical
To assess the accuracy and precision of Hepatica v1 measurements across supported scanners, previously acquired invivo volunteer data was used. Volunteers participating in the performance testing were representative of the intended patient population. Inter and intra operator variability was also assessed. The results of which are summarized below:
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Accuracy
| Metric | Volume (% of total livervolume) | cT1 | PDFF |
|---|---|---|---|
| Liver Segment | Upper and Lower Limits ofAgreement | Upper and Lower Limitsof Agreement | Upper and Lower Limitsof Agreement |
| Segment 1 | -0.49% to 0.95% | -1.13% to 0.61% | -0.26% to 0.21% |
| Segment 2 | -3.09% to 5.06% | -2.38% to 1.56% | -0.33% to 0.38% |
| Segment 3 | -5.01% to 3.9% | -1.51% to 1.31% | -0.16% to 0.17% |
| Segment 4a | -4.60% to 4.26% | -0.77% to 1.10% | -0.30% to 0.23% |
| Segment 4b | -5.50% to 2.56% | -1.32% to 1.13% | -0.16% to 0.14% |
| Segment 5 | -1.54% to 3.38% | -1.11% to 0.87% | -0.16% to 0.18% |
| Segment 6 | -4.34% to 4.29% | -1.00% to 0.83% | -0.16% to 0.26% |
| Segment 7 | -3.30% to 1.79% | -0.88% to 0.64% | -0.12% to 0.18% |
| Segment 8 | -3.86% to 5.54% | -0.91% to 1.09% | -0.24% to 0.32% |
| Whole liver | -4.16% to 0.54% | 0.00% to 0.00% | -0.02% to 0.02% |
Table 2: Performance testing results for Hepatica v1 accuracy when compared to the gold standard (radiologists)
Precision
| Liver Segment (% of total livervolume) | Repeatability | Reproducibility |
|---|---|---|
| Upper and Lower limits of Agreement | Upper and Lower Limits of Agreement | |
| Segment 1 | -0.72% to 0.65% | -1.39% to 0.90% |
| Segment 2 | -3.06% to 3.24% | -3.10% to 3.15% |
| Segment 3 | -2.67% to 3.13% | -2.41% to 2.06% |
| Segment 4a | -2.48% to 2.43% | -2.54% to 2.58% |
| Segment 4b | -1.82% to 1.96% | -1.70% to 1.74% |
| Segment 5 | -4.45% to 4.45% | -4.97% to 5.94% |
| Segment 6 | -3.60% to 4.10% | -3.69% to 5.40% |
| Segment 7 | -3.32% to 3.33% | -4.39% to 3.59% |
| Segment 8 | -4.99% to 3.81% | -6.23% to 5.04% |
| Whole liver | -6.15% to 3.78% | -16.6% to 6.95% |
Table 3: Pooled performance testing results for Hepatica v1 precision
Performance testing of Hepatica v1 demonstrates that:
- . Metrics reported by Hepatica v1 (cT1, PDFF and volumetry in the whole liver and in each liver segment) are comparable to the gold standard (considered to be radiologists)
- Hepatica v1 measurements of volumetry are highly repeatable ●
- Hepatica v1 measurements of volumetry are highly reproducible
- The variation introduced by operator measurements are well within the acceptance criteria ●
- cT1 and PDFF measurements reported by Hepatica v1 are within the acceptance criteria set for the predicate device. ●
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Image /page/12/Picture/1 description: The image shows the logo for Perspectum. The word "Perspectum" is written in a bold, dark gray font. To the right of the word is a circular logo with four colored sections: yellow, blue, green, and pink.
5.2. Clinical Investigation
No clinical investigations or studies were conducted during performance testing of Hepatica v1.
6. Conclusion
The subject device is substantially equivalent to the predicate device, and is based on the following observations:
- The indications for use and intended use of the subject device fall within the general tool-type claims of the predicate device.
- The subject device and predicate device both support multi-slice MR data acquired using the specific acquisition protocols, from supported MR systems, to acquire the input data.
- The subject and predicate devices include software applications which utilise MR data to visualise and enable quantification of physiological characteristics in the liver to provide measurements which may be used to assess liver health.
- Both the subject device and the predicate device include applications to facilitate the import and visualization of ● MR data sets and include tools to enable the manipulation of the views and to enable the quantification and analysis of tissue characteristics in the liver from the MR data.
- The subject and predicate device are both standalone software applications to facilitate the import and visualization of MR data sets.
- The subject and predicate devices enable the quantification of analysis of tissue characteristics in the liver from the MR data.
- The subject and predicate device facilitate the creation of a medical report containing the images and analysis output derived from quantification of liver tissue parameters intended to be interpreted by a trained clinician.
- The subject and predicate device reports all include tabular display of quantification statistics, parametric map images and include normal range references.
- Both the subject and predicate devices are designed to run on general-purpose computing hardware. ●
- Both the subject and predicate device are intended to be used in the same use environment and by trained Perspectum operators.
- Performance testing demonstrates that the subject device performs at least as safely and effectively as the proposed predicate device.
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comparison of MOLLI, shMOLLI, 3'5-MOLLI and SASHA. J. Cardiovasc. Magn. Reson. 15, E18 (2013).
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§ 892.1000 Magnetic resonance diagnostic device.
(a)
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).(b)
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.