aPROMISE X is intended to be used by healthcare professionals and researchers for acceptance, transfer, storage, image display, manipulation, quantification and reporting of digital medical images. The system is intended to be used with images acquired using nuclear medicine (NM) imaging. using PSMA PET/CT. The device provides general Picture Archiving and Communications System (PACS) tools as well as a clinical application for oncology including marking of regions of interest and quantitative analysis.

Device Description

aPROMISE (automated PROstate specific Membrane Antigen Imaging SEgmentation) X is an updated version of previously cleared device, aPROMISE v 1.2.1 (K211655), with a web interface where users can upload body scans of PSMA PET/CT image data in the form of DICOM files, review patient studies and share study assessments within a team. The software platform has two installation configurations: either deployed to a cloud infrastructure or to a local server at a clinical facility. The software platform can communicate via http-protocol as described in part 18 of the DICOM standard. This compatibility enables direct transmission of DICOM data from a PACS to aPROMISE X. Manual upload via aPROMISE X user interface is also supported. The software complies with the Digital Imaging and Communications in Medicine (DICOM) 3 standard.

Multiple scans can be uploaded for each patient and the system provides a separate review for each study. The review page display studies in a 4-panel view showing PET, CT, PET/CT fusion and maximum intensity projection (MIP) simultaneously and includes the option to display each view separately. The device is used to review entire patient studies, using image visualization and analysis tools for users to identify and mark regions of interest (ROIs). While reviewing image data, users can mark ROIs by selecting from pre-defined hotspots that are highlighted when hovering with the mouse pointer over the segmented region, or by manual drawing, i.e selecting individual voxels in the image slices to include as hotspots. Selected or drawn hotspots are subject to automatic quantitative analysis. The user can review the results of this quantitative analysis and determine which hotspots should be reported as suspicious lesions.

To create a report the signing user is required to confirm quality control, and electronically sign the report preview. Signed reports are saved in the device and can be exported as a JPG or DICOM file.

AI/ML Overview

The provided text, a 510(k) summary for the aPROMISE X device, details its comparison to a predicate device and includes information about performance testing. However, it does not contain specific acceptance criteria, reported device performance metrics (e.g., sensitivity, specificity, AUC), or a detailed description of a clinical study that proves the device meets specific acceptance criteria related to its diagnostic performance.

The document states that the Analytical Performance in Clinical Study "demonstrated that aPROMISE X enables the automated quantification of tracer uptake are more reproducible, and efficient than those obtained manually. The study demonstrated that aPROMISE X enables the reader to achieve a higher efficiency and quantitative consistency, while maintaining the diagnostic performance of the physicians." This implies some form of performance evaluation, but the specific metrics and methodology required to answer your detailed questions are not provided in this 510(k) summary.

Therefore, I cannot populate the table or answer most of your questions with the information available in the provided text.

Here is what I can infer or state based on the document:

1. A table of acceptance criteria and the reported device performance:

Acceptance Criteria	Reported Device Performance
Specific diagnostic performance metrics (e.g., sensitivity, specificity, AUC for lesion detection)	Not provided in this document. The document states that the Analytical Performance in Clinical Study demonstrated "maintaining the diagnostic performance of the physicians," but no specific metrics or associated acceptance criteria are listed.
Accuracy, linearity, and limit of detection of SUV and volume quantification (from Digital Phantom Validation Study)	"All SUV and volume quantification tests of aPROMISE X met their predetermined acceptance criteria." (Specific numerical criteria and results are not provided.)
Equivalent performance of aPROMISE X vs. predicate for standard functions in marking and quantitative assessments of user-defined ROI	"This study demonstrated the equivalent performance of aPROMISE X as compared to the previous version, predicate aPROMISE v1.2.1 (K211655) for standard functions in marking and quantitative assessments of user defined region of interest in PSMA PET/CT." (Specific metrics are not provided.)
Reproducibility and efficiency of automated quantification vs. manual quantification	"aPROMISE X enables the automated quantification of tracer uptake are more reproducible, and efficient than those obtained manually." (No numerical metrics provided.)
Reader efficiency and quantitative consistency with aPROMISE X vs. without	"aPROMISE X enables the reader to achieve a higher efficiency and quantitative consistency..." (No numerical metrics provided.)

2. Sample size used for the test set and the data provenance:

Sample Size: Not specified for the "Analytical Performance in Clinical Study."
Data Provenance: Not specified (e.g., country of origin, retrospective or prospective).

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

Not specified. The study compared performance to "clinicians" and "physicians" but did not detail their role in ground truth establishment or their qualifications.

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

Not specified.

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

A study comparing performance was done ("compared the performance of aPROMISE X to that of clinicians"), and it suggested improvement in "efficiency and quantitative consistency" while "maintaining diagnostic performance." However, it's not explicitly stated as a formal MRMC study, and no specific effect sizes or quantitative improvements in diagnostic performance (e.g., AUC increase, sensitivity/specificity changes) with AI assistance versus without are provided.

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

The phrasing "aPROMISE X enables the automated quantification of tracer uptake" suggests the algorithm performs quantification. However, the study description focuses on comparing "aPROMISE X" (which is a system used by "healthcare professionals") "to that of clinicians," implying it might be evaluating the system as a whole rather than a purely standalone algorithm's diagnostic capability. The section primarily highlights where the AI assists the user, such as in hotspot detection for user selection: "Pre-definition of Hotspot: Algorithm, using a machine-learning model to detect high local intensity regions of interest in the PET series."

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

Not specified. The study is described as comparing to "clinicians" and "physicians," which implies clinical judgment, but the gold standard (e.g., biopsy results, long-term follow-up) for determining the true presence or absence of a clinically significant lesion is not mentioned.

8. The sample size for the training set:

Not specified. The document mentions a "machine-learning model" for hotspot detection, implying a training set was used, but its size is not disclosed.

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

Not specified.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & 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 blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

EXINI Diagnostics AB % Donna-Bea Tillman, Ph.D. Senior Consultant Biologics Consulting Group, Inc. 1555 King Street. Suite 300 ALEXANDRIA VA 22314

Re: K220590

Trade/Device Name: aPROMISE X Regulation Number: 21 CFR 892.2050 Regulation Name: Medical image management and processing system Regulatory Class: Class II Product Code: LLZ Dated: February 28, 2022 Received: March 1, 2022

Dear Donna-Bea Tillman:

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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Julie Sullivan, Ph.D. Assistant Director Nuclear Medicine and Radiation Therapy Branch 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) K220590

Device Name aPROMISE X

Indications for Use (Describe)

aPROMISE X is intended to be used by healthcare professionals and researchers for acceptance, image display, manipulation, quantification and reporting of digital medical images. The system is intended to be used with images acquired using nuclear medicine (NM) imaging, using PSMA PET/CT. The device provides general Picture Archiving and Communications System (PACS) tools as well as a clinical application for oncology including marking of regions of interest and quantitative analysis.

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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In accordance with 21 CFR 807.87(h) and 21 CFR 807.92 the 510(k) Summary for aPROMISE X is provided below.

1. SUBMITTER

K220590

Applicant:	EXINI Diagnostics ABIdeon Science ParkScheelevägen 27223 70 LundSweden
Contact:	Aseem Anand, Ph.D.Vice PresidentEXINI Diagnostics ABIdeon Science Park, Scheelevägen 27, SE-223 70Lund, SwedenTel: +46706604084aseem.anand@exini.com
Submission Correspondent:	Donna-Bea Tillman, Ph.D.Senior ConsultantBiologics Consulting1555 King Street, Suite 300Alexandria, Virginia 22314(410) 531-6542dtillman@biologicsconsulting.com
Date Prepared:	February 28, 2022

2. DEVICE

Device Trade Name:	aPROMISE X
Device Common Name:	Picture Archiving and Communication System
Classification Name:	21 CFR 892.2050 Medical Image Management andProcessing System
Regulatory Class:	II
Product Code:	LLZ

3. PREDICATE DEVICE

Predicate Device:

Exini aPROMISE (K211655)

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DEVICE DESCRIPTION 4.

INTENDED USE/INDICATIONS FOR USE 5.

SUBSTANTIAL EQUIVALENCE 6.

Comparison of Indications

aPROMISE X and the predicate aPROMISE have identical Indication for Use statements.

Technological Comparisons

The table below compares the key technological feature of the subject device aPROMISE X to the predicate devices, Exini aPromise (K211655).

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Table 1: Technological Comparison

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7. PERFORMANCE DATA

Sterilization and Shelf Life

aPROMISE X consists entirely of software; accordingly, there are no sterilization concerns. As a software only device, shelf-life (including performance date) is also not applicable because of low likelihood of time-dependent product degradation.

Biocompatibility Testing

There are no direct or indirect patient-contacting components of the subject device. Therefore, patient contact information is not needed for this device.

Electrical safety and electromagnetic compatibility (EMC)

Not applicable. The subject device is a software-only device. It contains no electric components, generates no electrical emissions, and uses no electrical energy of any type.

Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered as a moderate level of concern.

Bench Testing

Exini performed the following studies verify and validate the performance of aPROMISE.

. Digital Phantom Validation Study. This study assessed the accuracy, linearity, and limit of detection of aPROMISE X against the known values of a digital reference object (NEMA phantom). All SUV and volume quantification tests of aPROMISE X met their predetermined acceptance criteria.
. Comparison to Predicate. This study demonstrated the equivalent performance of aPROMISE X as compared to the previous version, predicate aPROMISE v1.2.1 (K211655) for standard functions in marking and quantitative assessments of user defined region of interest in PSMA PET/CT.
Analytical Performance in Clinical Study. This study compared the performance of aPROMISE X to that of clinicians and demonstrated that aPROMISE X enables the automated quantification of tracer uptake are more reproducible, and efficient than those obtained manually. The study demonstrated that aPROMISE X enables the reader to achieve a higher efficiency and quantitative consistency, while maintaining the diagnostic performance of the physicians.

These results demonstrate that aPROMISE X performs in accordance with specifications and meets user needs and intended uses.

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Animal Testing

Not applicable. Animal studies are not necessary to establish the substantial equivalence of this device.

Clinical Data

Not applicable. Clinical studies are not necessary to establish the substantial equivalence of this device.

CONCLUSION 8.

Based on the detailed comparison, the differences between the subject and predicate devices do not raise new questions of safety and effectiveness. Software verification and performance testing demonstrate that the device performs according to the device requirements. Therefore, the aPROMISE X device can be found substantially equivalent to the 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).

Specification/Characteristic	aPROMISE X(proposed device)	aPROMISE 1.2.1(predicate device)	Comparison to predicate
General
Intended user	Health care professionalsand researchers	Health care professionalsand researchers	No difference
Intended useenvironment	Healthcare clinics	Healthcare clinics	No difference
Classification	21 CFR 892.2050System, ImageProcessing, Radiological(LLZ) Class II	21 CFR 892.2050System, ImageProcessing, Radiological(LLZ) Class II	No difference
Installation	Web-based serviceaccessed through cloudinfrastructure or localserver network withpersonal log-in.	Web-based serviceaccessed through cloudinfrastructure withpersonal log-in.	EquivalentThe difference involves anadditional option for productdeployment. The differencedoes not affect the clinical useof the device and does not raisedifferent questions of safety oreffectiveness.
Operating system	Windows or macOS withChrome browser	Windows or macOS withChrome browser	No difference
DICOMcompatibility andImagingModalities	DICOM 3:Whole body● PET● CT	DICOM 3:Whole body● PET● CT	No difference
Image upload	Via file selector or dragand drop from a localcomputer or network.Upload can handle zipfiles. Semiautomatictransfer via http-protocol enabling directtransmission of DICOMdata if integrated with aPACS.	Via file selector or dragand drop from a localcomputer or network.Upload can handle zipfiles.	EquivalentThe difference involves anadditional option for imageupload. The difference does notaffect the clinical use of thedevice and does not raisedifferent questions of safety oreffectiveness.
Support formultiple scans	Yes, multiple scans canbe analyzed one at a time.	Yes, multiple scans canbe analyzed one at a time.	No difference
Specification/Characteristic	aPROMISE X(proposed device)	aPROMISE 1.2.1(predicate device)	Comparison to predicate
Colormaps	A selection of commonlyused colormapssupported:For PET image:• Cool• Invertedgrayscale• Grayscale withoverflow• Hot Iron• Spectrum• WarmFor CT image:• Grayscale	A selection of commonlyused colormapssupported:For PET image:• Cool• Invertedgrayscale• Grayscale withoverflow• Hot Iron• Spectrum• WarmFor CT image:• Grayscale	No difference
Zoom	Automatically adjustedimage size.Manually adjustablezoom in planar views	Automatically adjustedimage size.Manually adjustablezoom in planar views	No difference
Windowing	Manual adjustment ofwindowing. Slider orselection form a drop-down menu for PET.Click'n'drag or selectionfrom a drop-down menufor CT	Manual adjustment ofwindowing. Slider orselection form a drop-down menu for PET.Click'n'drag or selectionfrom a drop-down menufor CT	No difference
Image layouts	4 panel view showingPET, CT, PET/CT fusionand MIP simultaneouslyand option to display eachview separately.Coronal, axial and sagittalviews can be displayed	4 panel view showingPET, CT, PET/CT fusionand MIP simultaneouslyand option to display eachview separately.Coronal, axial and sagittalviews can be displayed	No difference
Intensity display	Local intensity displayedin left corner of the imagewhen hovering overimage	Local intensity displayedin left corner of the imagewhen hovering overimage	No difference
Hotspot display	Segmented hotspots canbe displayed in planarviews if the user turns onthe hotspot segmentationdisplay option from thecontrol panel resulting in	Segmented hotspots canbe displayed in planarviews if the user turns onthe hotspot segmentationdisplay option from thecontrol panel resulting in	No difference
Specification/Characteristic	aPROMISE X(proposed device)	aPROMISE 1.2.1(predicate device)	Comparison to predicate
	visually presenting pre-defined hotspots in theviewer.	visually presenting pre-defined hotspots in theviewer.
OrganSegmentation	AI enabled automatedsegmentation of skeletonand soft tissue organs.	AI enabled automatedsegmentation of skeletonand soft tissue organs.	EquivalentThe option to segment theprostate is removed since it isno longer needed as a result ofthe new hotspot detectionmodel. The difference does notaffect the clinical use of thedevice and does not raisedifferent question of safety oreffectiveness.
Pre-definition ofHotspot	Algorithm, using amachine-learning modelto detect high localintensity regions ofinterest in the PET series.	Algorithm, using ananalytical model todetect high local intensityregions of interest in thePET series.	EquivalentSame feature but adjustedmethod for the detection of highlocal intensity regions tosegment as hotspots. Thedifference does not affect theclinical use of the device and donot raise different questions ofsafety or effectiveness.
Hotspot pre-selection	No hotspot pre-selectionoccurs. It is always theuser who needs to selecthotspots to include forquantification andreporting. All detectedhigh local intensity ROIscan be shown for reviewby the user.	No hotspot pre-selectionoccurs. It is always theuser who needs to selecthotspots to include forquantification andreporting. All detectedhigh local intensity ROIscan be shown for reviewby the user.	No difference
Hotspotverification	The user can select pre-defined segmentation ofhotspots or segment eachhotspot manually that areconsidered to be lesionsby the user.	The user can select pre-defined segmentation ofhotspots or segment eachhotspot manually that areconsidered to be lesionsby the user.	No difference
HotspotQuantification	Standard Uptake Values(SUV):-SUV-max	Standard Uptake Values(SUV):-SUV-max	No difference
Specification/Characteristic	aPROMISE X(proposed device)	aPROMISE 1.2.1(predicate device)	Comparison to predicate
	-SUV-mean-SUV-peak-Volume-Lesion Index (LI)-Intensity-weightedTissue Lesion Volume(ITLV)	-SUV-mean-SUV-peak-Volume-Lesion Index (LI)-Intensity-weightedTissue Lesion Volume(ITLV)
Quality Control	SW enforced requirementto verify the user reviewof- Image quality- PET/CT image- Patient study data- Reference values- Study is not a superscan	SW enforced requirementto verify the user reviewof- Image quality- PET/CT image- Patient study data- Reference values- Study is not a superscan	No difference
Userconfirmation forreport generation	User completion of theQuality Control andreport previewconfirmation byelectronic signature usinguser-ID and password isrequired for reportcreation	User completion of theQuality Control andreport previewconfirmation byelectronic signature usinguser-ID and password isrequired for reportcreation	No difference
Report (Summarypage export)	The user can export thereport with quantificationresults of a study to thehard drive (jpg orDICOM SecondaryCapture) or PACS(DICOM SecondaryCapture).	The user can export thereport with quantificationresults of a study to thehard drive (jpg orDICOM SecondaryCapture.	No difference
CSV export	Supports export of studyand quantification valuesas a CSV file for allcreated reports	Supports export of studyand quantification valuesas a CSV file for allcreated reports	No difference