CareMiBrain is dedicated brain PET scanner, and intended to obtain Position Emission Tomography (PET) inages of human brain to detect abnormal pattern of distribution of radioactivity after injection of a position emitting radiopharmaceutical. This device is to be used by trained healthcare professionals. This information can assist in research, diagnosis, therapeutic planning and therapeutic outcome assessment.

Device Description

CareMiBrain is a small aperture Positron Emission Tomography (PET) scanner to image the distribution of injected positron emitting radiopharmaceuticals in the head of live humans in seating/reclined position. CareMiBrain is a PET (Positron Emission Tomography) dedicated to brain imaging. All elements of the system are integrated into a compact volume, containing the detection system, acquisition and control electronics and software. All elements of the system are integrated into a compact volume, containing the detection system, acquisition and control electronics and software. The scanner consists of 48 monolithic Lutetium OrthoSilicate (LYSO) crystals arranged in 3 rings of 16 modules each. Physical ring diameter is 260mm, with an effective 220 mm transaxial and 152 mm axial FOV. Crystal dimensions are 50x50x15mm (width x height x thickness). Crystals are coupled to a photosensor array of 12x12 silicon photo-multiplier (SiPM), 3x3 mm each. The detectors of the equipment are integrated in a circular housing with the appropriate dimensions so that the patient can insert the head. The software that integrates the equipment allows the acquisition, reconstruction and export of tomographic images of the brain, as well as to make a diagnosis of the state of the detectors.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the studies proving the CareMiBrain device meets them, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Criteria (CareMiBrain - PET scanner)	Acceptance Criteria	Reported Device Performance
Spatial Resolution (NEMA NU 4-2008)
Transverse Resolution FWHM @5mm	2 mm	1.55 mm
Transverse Resolution FWHM @10mm	2 mm	1.45 mm
Transverse Resolution FWHM @15mm	2 mm	1.52 mm
Transverse Resolution FWHM @25mm	2 mm	1.59 mm
Axial Resolution FWHM @5mm	2 mm	1.45 mm
Axial Resolution FWHM @10mm	2 mm	1.40 mm
Axial Resolution FWHM @15mm	2 mm	1.58 mm
Axial Resolution FWHM @25mm	2 mm	1.41 mm
Radial Resolution FWHM @5mm	2 mm	1.51 mm
Radial Resolution FWHM @10mm	2 mm	1.58 mm
Radial Resolution FWHM @15mm	2 mm	1.64 mm
Radial Resolution FWHM @25mm	2 mm	1.52 mm
Extra Spatial Resolution (NEMA NU 4-2008)
Transverse Resolution FWHM @0 mm	2 mm	1.53 mm
Transverse Resolution FWHM @50 mm	2 mm	1.51 mm
Transverse Resolution FWHM @75 mm	2 mm	1.76 mm
Transverse Resolution FWHM @100mm	2 mm	1.66 mm
Axial Resolution FWHM @0 mm	2 mm	1.36 mm
Axial Resolution FWHM @50 mm	2 mm	1.44 mm
Axial Resolution FWHM @75 mm	2 mm	1.44 mm
Axial Resolution FWHM @100mm	2 mm	1.44 mm
Radial Resolution FWHM @0 mm	2 mm	1.57 mm
Radial Resolution FWHM @50 mm	2 mm	1.67 mm
Radial Resolution FWHM @75 mm	2 mm	1.64 mm
Radial Resolution FWHM @100mm	2 mm	1.64 mm
Spatial Resolution (NEMA NU 2-2012)
Transverse Resolution FWHM @10mm	2 mm	1.68 mm
Transverse Resolution FWHM @100mm	2 mm	1.86 mm
Axial Resolution FWHM @10 mm	2 mm	1.39 mm
Axial Resolution FWHM @100 mm	2 mm	1.40 mm
Radial Resolution FWHM @10 mm	2 mm	1.87 mm
Radial Resolution FWHM @100 mm	2 mm	1.86 mm
Count Rate Evaluation and Sensitivity (NEMA NU 2-2012)
Sensitivity along transverse center	15 cps/kBq	17.83 cps/kBq
Sensitivity off center	12 cps/kBq	13.82 cps/kBq
Count rate peak NECR	30 kcps	49 kcps
Count rate peak trues	160 kcps	193 kcps
Scatter fraction at peak NECR	9.25 MBq	7.4 MBq
Scatter fraction Mean	60 %	48 %
Image Quality - % contrast/background variability (NEMA NU 4-2008)
4.5 mm	0.65	0.73
6 mm	0.65	0.78
9 mm	0.65	1.14
12 mm	0.65	1.01

Note: For Image Quality - % contrast/background variability, the reported values are higher than the acceptance criteria, which suggests better performance (lower variability is generally desired for image quality, but the metric here is contrast/background variability, implying a higher value reflects better contrast relative to background). The document claims these results "comply with its predetermined specification," indicating these values met the intended performance.

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

Test Set Sample Size: For the clinical effectiveness study, "Sample images from several clinical cases with different PET tracers using the CareMiBrain PET Scanner were provided." The exact number of clinical cases is not specified from this statement, but a previous mention notes that "More than 40 clinical images are provided from CareMiBrain to demonstrate the image capability". This suggests a test set of at least 40 clinical images.

Data Provenance:

Bench Performance Data: Independently tested by the "Institute for Instrumentation of Molecular Imaging (i3m)" according to NEMA NU 2-2012 and NEMA NU 4-2008 standards. The results were published in Scientific Reports Journal (DOI 10.1038/s41598-019-51898-z). This implies the testing was conducted in a laboratory setting.
Clinical Effectiveness Data: Tested by "independent hospitals" and the results published in the Spanish Journal of Nuclear Medicine and Molecular Imaging (DOI 10.1016/j.remn.2021.04.002). This indicates prospective data collection from real-world clinical use.

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

This information is not explicitly provided in the document. While clinical effectiveness was assessed and images were provided, there's no detail on how ground truth for these clinical cases was established (e.g., through a panel of qualified radiologists, comparing with other diagnostic methods, or follow-up).

4. Adjudication method for the test set

This information is not explicitly provided in the document.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done, or at least not described in this document. The purpose of the study was to demonstrate the device's inherent performance and clinical effectiveness for obtaining PET images, not its impact on human reader performance or AI assistance. The device is purely an imaging system, not an AI-powered diagnostic aid that assists human readers.

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

Yes, a standalone performance assessment was done. The entire bench performance testing, evaluated against NEMA standards, represents the standalone performance of the CareMiBrain device. The clinical images provided also demonstrate the device's output without human interpretation as part of the core performance metrics. The device itself is the "algorithm" in this context, producing images for human interpretation.

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

Bench Performance: Ground truth was established by adherence to recognized phantom-based testing protocols (NEMA NU 4-2008 and NEMA NU 2-2012) using phantoms with known properties.
Clinical Effectiveness: The document states "Sample images from several clinical cases with different PET tracers...were provided." While it mentions "clinical effectiveness," the specific type of ground truth for these clinical cases (e.g., confirmed diagnosis by pathology, follow-up outcomes, expert consensus on other imaging modalities) is not explicitly detailed.

8. The sample size for the training set

The document describes the device as a PET scanner (hardware and associated software for acquisition, reconstruction, and export of images), not an AI/Machine Learning model that would typically have a separate training set. Therefore, the concept of a "training set" in the context of an AI algorithm is not applicable to this device as described. The software's development would likely involve standard software engineering verification and validation processes, not machine learning training.

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

As the concept of a "training set" for an AI algorithm is not applicable to this device as described, this question is not relevant.

Summary

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September 21, 2023

General Equipment for Medical Imaging, S.A. % Dave Yungvirt Chief Executive Officer Third Party Review Group, LLC 25 Independence Blvd Warren, New Jersey 07059

Re: K232569

Trade/Device Name: CareMiBrain Regulation Number: 21 CFR 892.1200 Regulation Name: Emission computed tomography system Regulatory Class: Class II Product Code: KPS Dated: August 21, 2023 Received: August 24, 2023

Dear Dave Yungvirt:

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

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

Sincerely,

D. Rayfield

Daniel M. Krainak, Ph.D. Assistant Director Magnetic Resonance and Nuclear Medicine Team 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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known)

K232569

Device Name CAREMIBR AIN

Indications for Use (Describe)

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of

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Image /page/3/Picture/0 description: The image contains the logo for OncoVision. The logo consists of a blue sphere on the left and the text "ONCO VISION" on the right. The word "ONCO" is in blue, and the word "VISION" is in green.

510(K) SUMMARY K232569

[As required by 21 CFR 807.92]

This 510(k) summary of safety and effectiveness information is prepared in accordance with 21 CFR 807.92

SUBMITTER´S INFORMATION l.

Submitter	General Equipment for Medical Imaging, S. A.
	(Oncovision Gem-Imaging S.A.)
	Calle de Jeroni de Montsoriu, 92 – BJ IZ
	46022 Valencia
	+34 96 372 24 72
	info@oncovision.com
510(K) Contact person	María Climent Vicedo
	Quality and Regulatory Affairs Manager
	General Equipment for Medical Imaging, S.A.
	Phone: (+34) 653 76 32 68
	Email: calidad@oncovision.com
Date	13 Sep 2023

II. DEVICE

Trade / Device Name	CareMiBrain
Common Name	Dedicated brain Positron Emission Tomography system
Classification Name	Emission Computed Tomography System
21 CFR Reference	892.1200
Classification	Class II
Panel	Radiology
Product Code	KPS

INNOVATIVE MEDICAL IMAGING

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Image /page/4/Picture/0 description: The image contains the logo for OncoVision. The logo consists of a blue sphere on the left and the word "ONCO" in blue on the right, stacked on top of the word "VISION" in green. The sphere has a swirling pattern of blue and white lines, giving it a three-dimensional appearance.

lll. IDENTIFICATION OF PREDICATE DEVICE

Predicate Trade/Device Name	BBX™-PET Scanner
510(k) Number	K210450
Common Name	PET Scanner
21 CFR Reference	892.1200
Regulation Name	Emission Computed Tomography System
Classification	Class II
Panel	Radiology
Product Code	KPS
Applicant	Prescient Imaging LLC.

IV. APPLICABLE FDA GUIDANCES

This document has been prepared according to the required content described in the FDA Guidance "The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k). Guidance for Industry and FDA", and "Classification of Products as Drugs and Devices & Additional Product Classification Issues: Guidance for Industry and FDA Staff".

V. DEVICE DESCRIPTION

The use of the device is limited only to patients whose height is higher than 140cm (55.2 inches).

INNOVATIVE MEDICAL IMAGING

ONCOVISON | General Equipment for Medical Inaging S.A | C/ Jerónimo de Monsoriu, 92 Bajo Lzq, 4002, Valencia, Spain | +34 963 722 472 | info@onovisio.com www.oncovision.com

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VI. INDICATIONS FOR USE

CareMiBrain is dedicated brain PET scanner, and intended to obtain Positron Emission Tomography (PET) images of human brain to detect abnormal pattern of distribution of radioactivity after injection of a positron emitting radiopharmaceutical. This device is to be used by trained healthcare professionals. This information can assist in research, diagnosis, therapeutic planning and therapeutic outcome assessment.

VII. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

CareMiBrain and the predicate device are both Positron Emission Tomography systems used to image and measure the distribution of injected positron emitting radiopharmaceuticals in human beings. Main technological elements of CareMiBrain and predicate device are the same:

PET detectors are arranged in a cylindrical shape.
Detectors are composed of scintillator crystals and Silicon photomultipliers, that detect gamma rays emitted by radioactivity located inside the cylinder.
Single and coincidence events are captured on detector electronics and acquired and processed by software, that generates image using iterative reconstruction methods.
. Attenuation correction method is in both cases Calculated Attenuation Correction.

Main differences between predicate device and CareMiBrain are:

. Patient is in seated/reclined position in CareMiBrain, while in predicate device is lying on a bed.
Cylinder diameter is 26 cm in CareMiBrain, while in predicate device is 29cm.
Crystals are monolithic Lutetium Yttrium OrthoSilicate (LYSO) in CareMiBrain, while in predicate pixelated lutetium fine-silicate (LFS) crystals are used.

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VIII. COMPARISON TABLE

Attributes	Predicate device	Subject device	Justification of equivalence
	BBX™-PET Scanner	CareMiBrain
Device	Image: BBX™-PET Scanner	Image: CareMiBrain
Intended use	Dedicated Positron Emission Tomography	Dedicated Positron Emission Tomography	Same as predicate
Indications for use	BBX™-PET scanner is intended to obtain Positron Emission Tomography (PET) images of parts of the human body that fit in the patient aperture (e.g., head) to detect abnormal pattern of distribution of radioactivity after injection of a positron emitting radiopharmaceutical. This information can assist in research, diagnosis, therapeutic planning and therapeutic outcome assessment.	CareMiBrain is dedicated brain PET scanner, and intended to obtain Positron Emission Tomography (PET) images of human brain to detect abnormal pattern of distribution of radioactivity after injection of a positron emitting radiopharmaceutical. This device is to be used by trained healthcare professionals. This information can assist in research, diagnosis, therapeutic planning and therapeutic outcome assessment.	Same as predicate
Principle of detection	Positron Emission Tomography (PET) system to image the distribution of injected positron emitting radiopharmaceuticals into live humans or animals. The BBX-PET Scanner produces images that represent the	CareMiBrain is a small aperture Positron Emission Tomography (PET) scanner to image the distribution of injected positron emitting radiopharmaceuticals in the head of live humans, as defined in 21 CFR 892.1200.	Same as predicate
	internal distribution ofradioactivity in the head.	CareMiBrain generatestomographic images thatrepresent the internaldistribution of radioactivityin the patient's head andbrain.
Scintillatorconfiguration /Scanner	Double-layer staggeredLutetium Fine Silicatepixelated crystals (13 × 13and 14 × 14 arrays, 1.76-mmpitch) coupled to lightdetector solid state siliconphotomultiplier.One hundred twenty-eightblocks positioned in acircular shape make up thegantry, with bore diameterof 288mm, and 250mm and100mm transaxial and axialFOVs.	Monolithic Lutetium-basedscintillator (LYSO) coupledto solid state siliconphotomultiplier. Crystalsare 50x50x15mm. 3 rings of16 detectors positioned incircular shao.Bore diameter (openingdetector) is 260mm anduseful FOV is 220mmtransaxial and 150mm axial.	Both use scintillatorcrystals coupled to solidstate siliconphotomultipliers incircular shape. Borediameter is similar. AxialFOV is bigger forCareMiBrain.The most importantinnovation in the designof CareMiBrain PETscanner is the use ofcontinuous crystals incontrast to standardpixelated crystals.CareMiBrain usescontinuous crystalswhich make it possibleto measure multiplelayers of depth ofinteraction (DOI) of thegamma rays in thecrystals. This allows thesystem to minimize theparallax error whichdegrades the finalspatial resolution.These differences do notaffect the indications,only the performance
Targetpopulation	Adults, young adults	Adults and adolescent >140cm height	Same as predicate
Anatomical site	Parts of the human bodythat fit in the patientaperture	Parts of the human bodythat fit in the patientaperture	Same as predicate
Where used	Hospital	Hospital	Same as predicate
Energy usedand/ordelivered	Detects distribution ofradioactivity after injectionof a positron emittingradiopharmaceutical. Noenergy delivered	Detects distribution ofradioactivity after injectionof a positron emittingradiopharmaceutical. Noenergy delivered	Same as predicate
Human factors	PET detection system in amovable cart. its gantry canmove up to allow brainimaging while the patient isseated. It can also movedown to image the breastwithout compression, whilea patient is lying on a biopsytable or rotate and allowimaging the breast, hand, orleg in a seated position.	PET detection system isfixed and includes a chair.Gantry can move up, down,horizontally and with tiltadjust to properly fit theheight of the patients forimaging the brain while thepatient is seated.	Only brain imaging inseating position ispossible. This position isthe same in predicate.Main difference is thatthe chair is integrated inthe system, as explainedin the discussion section.Imaging in lying positionis not possible.
Design	The BBX-PET Scanner iscomprised of two parts; theGantry containing detectorsand electronics, and theUniversal Console thatcontains the computerworkstation. These twoparts are connected to eachother using optical fiber andan USB cable.	CareMiBrain is comprised oftwo parts; the PET scanner,that includes the patient'schair for acquisition inseated position andcontains the electronics anddetectors; and the controlstation, including the PC andthe software for controllingthe data acquisition andperforming thereconstruction.Scanner and control stationare connected through adedicated network. Controlstation is connected tohospital's network withDICOM Worklist supportand PACS connectivity.	Same as predicate,except that theconnection is standardethernet cable insteadof a fiber optics cableand USB
PerformanceData¹(Specifications	Spatial Resolution: 2.2 mmFWHMSpatial resolution in FWHMat the center: 2.2mmSpatial resolution in FWHMat 10 cm: Not publishedEnergy resolution: NotpublishedTransverse resolution:2.2mmAxial resolution: 2.2mmSpatial linearity: NotpublishedFlood field uniformity: NotpublishedSystem sensitivity: 1.1%Coincidence timing window:Not publishedCoincidence dead time: Notpublished	Spatial Resolution: 1.9 mmFWHMSpatial resolution in FWHMat the center: 1.55mmSpatial resolution in FWHMat 10cm: 1.66mmEnergy resolution: < 20%Transverse resolution:1.55mmAxial resolution; 1.45mmSpatial linearity: ±0,12mmFlood field uniformity:10%System sensitivity: >7% with358-664 Kev window, >9%with 255-767 KeV window.Coincidence timing window:5nsCoincidence dead time:700ns	Performance is same orbetter than publishedpredicate data. Based onthe available, publishedperformance of thepredicate, the non-published predicateperformance valuescannot be better thanCareMiBrain measuredvalues, as they are highlyrelated. A change inperformance does notaffect indications, as it isin all cases improvingthe images.
Scatter fraction:	Not published	Scatter fraction: 48%
Scatter correction method:	Not published	Scatter correction method: dual energy window
Slice thickness:	Depends on reconstruction (2mm/4mm)	Slice thickness: Depends on reconstruction (0.5/1/2mm)
Count rate sensitivity:	10 cps/kBq	13.82 cps/kBq with 255-767 KeV window, 11.05 cps/kBq with 358-664 Kev window.
Isolation of the detector from background:	Not applicable for PET	Isolation of the detector from background: Not applicable for PET
Intrinsic spatial resolution:	Not applicable for PET	Intrinsic spatial resolution: Not applicable for PET
Attenuation:	Calculated method	Attenuation: Calculated method
Depth of Interaction:	Double-layer	Depth of interaction: < 4mm
Computer:	GPU	Computer: GPU
Materials andbiocompatibility	Standard electronic and medical grade materials	Standard electronic and medical grade materials	Same as predicate
Compatibility with theenvironment and otherdevices	Complies with standard IEC 60601-1-2 ed 4.0 (2014-02) Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic	Complies with standard ANSI/AAMI IEC 60601-1-2:2014. Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral standard: Electromagnetic	Same as predicate
	disturbances–Requirements and tests forEMC.	compatibility–Requirements and tests.
Sterility	The product is not sterileand has not to be sterilizedby the user.Cleaning standardprocedure of medicaldevices.	The product is not sterileand has not to be sterilizedby the user.Cleaning standardprocedure of medicaldevices.	Same as predicate
Mechanical andelectrical safety	Complies with standard IEC60601-1: 2005 (ThirdEdition) + COOR.1:2006 +CORR.2:2007 + A1:2012Medical electricalequipment – Part 1:General requirements forbasic safety and essentialperformance for electricalsafety	Complies with standardANSI/AAMI ES 60601-1:2005 (Third Edition)/(R)2012 and A1:2012,C1:2009/(R)2012 andA2:2010/(R)2012. Medicalelectrical equipment - Part1: General requirements forbasic safety and essentialperformance.	Same as predicate
Clinicalefectiveness2	3 clinical images areprovided from PrescientBBX-PET to demonstrate theimage capability and thefulfillment with itspredeterminedspecification.	More than 40 clinicalimages are provided fromCareMiBrain todemonstrate the imagecapability and thefulfillment with itspredeterminedspecification.	Same or better aspredicate

INNOVATIVE MEDICAL IMAGING

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INNOVATIVE MEDICAL IMAGING

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Image /page/8/Picture/0 description: The image contains the logo for OncoVision. The logo consists of a blue sphere on the left and the word "ONCO" in blue above the word "VISION" in green on the right. The sphere has a white design on it.

INNOVATIVE MEDICAL IMAGING

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1 Performance data for CareMiBrain published in Scientific Reports, (2019) 9:15484 | https://doi.org/10.1038/s41598-019-51898-z

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INNOVATIVE MEDICAL IMAGING

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Image /page/11/Picture/0 description: The image contains the logo for OncoVision. The logo consists of a blue sphere on the left and the word "ONCO" in blue above the word "VISION" in green on the right. The sphere has a gradient of blue colors, with the darker shades on the left and lighter shades on the right.

IX. PERFORMANCE DATA

CareMiBrain performance has been independently tested, and the following data is provided in support of substantial equivalence determination. See in section 18 the Summary testing for each non-clinical test performed following the guidance "Recommended Content and Format of Non-Clinical Bench Performance Testing Information in Premarket Submissions".

2 CareMiBrain clinical evaluation published in Rev Esp Med Nucl Imagen Mol., 2021. https://doi.org/10.1016/j.remn.2021.04.002

ONCOVISON | General Equipment for Medical Inaging S.A | Jerónimo de Monsoriu, 92 Bajo Lzq, 46022, Valencia, Spain | +34 963 722 472 | info@oncovison.com www.oncovision.com

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i. Electrical safety and electromagnetic compatibility (EMC)

Electrical safety and EMC testing were conducted on the CareMiBrain device and certified by independent certification company DEKRA and SGS. The system complies with the following standards:

. ANSI / AAMI ES 60601-1:2005 / ( R ) 2012 and A1:2012, C1:2009/ (R ) 2012 and A2:2010/( R) 2012. Medical electrical equipment - Part 1: General requirements for basic safety and essential performance.
ANSI / AAMI IEC 60601-1-2:2014. Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral standard: Electromagnetic compatibility - Requirements and tests.

ii. 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 (CDRH, 2005)."

According to the FDA regulations, the CareMiBrain Level of Concern is "Moderate". A software malfunction cannot directly cause any harm to the patient but might lead to an erroneous diagnosis or a delay in delivery of appropriate medical care that might lead to minor injury. But as the scope of the CareMiBrain Suite is to provide additional information to other techniques which are usually performed (pathologic analysis, etc.), the physician criteria would always prevail over it.

On the other hand, the software validation process has been designed following the ISO/IEC 62304 guidelines. According to ISO/IEC 62304, it must comply with level B in the security level, which equals to "Moderate Level of Concern" in FDA regulation.

iii. Performance Testing - Bench

Performance testing was conducted, and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff," Guidance for the Submission of Premarket Notifications for Emission Computed Tomography Devices and Accessories (SPECT and PET) and NuclearTomography Systems" Section IX.C.2. (CDRH, 1998).

Performance CareMiBrain PET Scanner has been tested by an independent institute for Instrumentation of Molecular Imaging, i3m) according to NEMA NU 2-2012 (for whole-body PETs) and the results published in Scientific Reports Journal (DOI 10.1038/s41598-019-51898-z). The measurements performed include:

Spatial Resolution
Scatter Fraction and count rate (NECR) ●

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Image /page/13/Picture/0 description: The image shows the logo for OncoVision. The logo consists of a blue sphere on the left and the word "ONCO" in blue on the right, stacked on top of the word "VISION" in green. The sphere has a white line running through it.

Sensitivity ●
Image Quality, accuracy of attenuation correction and scatter correction
Accuracy: corrections for count losses and randoms

Test results indicate that CareMiBrain PET Scanner complies with its predetermined specification and the applicable standards.

For a better understanding of the performed tests, these have been following the NEMA NU 4-2008, the standard on performance measurement of small animal Positron Emission Tomographs, and NEMA NU 2-2018, used for performance measurements of human Positron Emission Tomographs.

This is because in some test the length of the ring prevented the NEMA NU 2-2018 from being followed. However, the NEMA NU 4-2008 tests are more restrictive.

Therefore, to establish an acceptance tolerance we have relied on other PETs, because when these tests were performed there was no dedicated brain PET available, as we can see in Moliner, L., Rodríguez-Alvarez, M.J., Catret, J.V. et al. NEMA Performance Evaluation of CareMiBrain dedicated brain PET and Comparison with the whole-body and dedicated brain PET systems. Sci Rep 9, 15484 (2019). https://doi.org/10.1038/s41598-019-51898-z

Performance Criteria	Results	CareMiBrain - PET scannerAcceptance criteria
Spatial Resolution (NEMA NU 4-2008)
Transverse Resolution FWHM @5mm	1,55 mm	2 mm
Transverse Resolution FWHM @10mm	1,45 mm	2 mm
Transverse Resolution FWHM @15mm	1,52 mm	2 mm
Transverse Resolution FWHM @25mm	1,59 mm	2 mm
Axial Resolution FWHM @5mm	1,45 mm	2 mm
Axial Resolution FWHM @10mm	1,40 mm	2 mm
Axial Resolution FWHM @15mm	1,58 mm	2 mm
Axial Resolution FWHM @25mm	1,41 mm	2 mm
Radial Resolution FWHM @5mm	1,51 mm	2 mm
Radial Resolution FWHM @10mm	1,58 mm	2 mm
Radial Resolution FWHM @15mm	1,64 mm	2 mm
Radial Resolution FWHM @25mm	1,52 mm	2 mm
Extra spatial resolution values (NEMA NU 4-2008).
Transverse Resolution FWHM @0 mm	1,53 mm	2 mm
Transverse Resolution FWHM @50 mm	1,51 mm	2 mm
Transverse Resolution FWHM @75 mm	1,76 mm	2 mm
Transverse Resolution FWHM @100mm	1,66 mm	2 mm
Axial Resolution FWHM @0 mm	1,36 mm	2 mm
Axial Resolution FWHM @50 mm	1,44 mm	2 mm
Axial Resolution FWHM @75 mm	1,44 mm	2 mm

We provide a table with a summary of the bench test have been performed.

INNOVATIVE MEDICAL IMAGING

ONCOVISON | General Equipment for Medical Inaging S.A | C/ Jerónimo de Monsoni, 92 Bajo Iza, 40022, Valencia, Spain | +34 963 722 472 | info@oncovisor.om www.oncovision.com

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Image /page/14/Picture/0 description: The image contains the logo for OncoVision. The logo consists of a blue sphere on the left side, with the text "ONCO" in blue and "VISION" in green on the right side. The sphere has a design of intersecting lines, creating a sense of depth and dimension.

Axial Resolution FWHM @100mm	1,44 mm	2 mm
Radial Resolution FWHM @0 mm	1,57 mm	2 mm
Radial Resolution FWHM @50 mm	1,67 mm	2 mm
Radial Resolution FWHM @75 mm	1,64 mm	2 mm
Radial Resolution FWHM @100mm	1,64 mm	2 mm
Spatial resolution (NEMA NU 2-2012).
Transverse Resolution FWHM @10mm	1,68 mm	2 mm
Transverse Resolution FWHM @100mm	1,86 mm	2 mm
Axial Resolution FWHM @10 mm	1,39 mm	2 mm
Axial Resolution FWHM @100 mm	1,40 mm	2 mm
Radial Resolution FWHM @10 mm	1,87 mm	2 mm
Radial Resolution FWHM @100 mm	1,86 mm	2 mm
Count rate evaluation and sensitivity (NEMA NU 2-2012).
Sensitivity along transverse center	17,83 cps/kBq	15 cps/kBq
Sensitivity off center	13,82 cps/kBq	12cps/kBq
Count rate peak NECR	49 kcps	30 kcps
Count rate peak trues	193 kcps	160 kcps
Scatter fraction at peak NECR	7,4 MBq	9,25 MBq
Scatter fraction Mean	48 %	60 %
Image Quality - % contrast/ background variability (NEMA NU 4-2008).
4,5 mm	0,73	0,65
6mm	0,78	0,65
9mm	1,14	0,65
12mm	1,01	0,65

iv. Performance Testing - Animal

Not applicable

Performance Testing - Clinical V.

Clinical effectiveness was conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff," Guidance for the Submission of Premarket Notifications for Emission Computed Tomography Devices and Accessories (SPECT and PET) and Nuclear Tomography Systems" Section IX.F. (CDRH, 1998).

Clinical effectiveness has been tested by independent hospitals and the results published in Spanish Journal of Nuclear Medicine and Molecular imaging (DOI 10.1016/j.remn.2021.04.002)

Sample images from several clinical cases with different PET tracers using the CareMiBrain PET Scanner were provided.

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Image /page/15/Picture/0 description: The image contains the logo for OncoVision. On the left side of the logo is a blue sphere with white lines running across it. To the right of the sphere is the word "ONCO" in blue, stacked on top of the word "VISION" in green. The logo is simple and modern, and the colors are calming and professional.

CONCLUSION X.

The data support the safety of the device and the hardware and software verification and validation demonstrate that the CareMiBrain PET Scanner should perform as intended in the specified use conditions. The publications and sample images from the provided clinical cases supported the clinical effectiveness of the CareMiBrain PET Scanner. Based upon performance data, CareMiBrain PET Scanner is substantially equivalent to the predicate device.

INNOVATIVE MEDICAL IMAGING

ONCOVISION | Geneal Equipment for Medical Inaging S.A | C. Jerónim de Monsoriu, 92 Bajo Lzi, 46022, Valencia, Spain | +34 963 722 472 | info@onovisio.com www.oncovision.com

Regulation Number and Section

§ 892.1200 Emission computed tomography system.

(a)
Identification. An emission computed tomography system is a device intended to detect the location and distribution of gamma ray- and positron-emitting radionuclides in the body and produce cross-sectional images through computer reconstruction of the data. This generic type of device may include signal analysis and display equipment, patient and equipment supports, radionuclide anatomical markers, component parts, and accessories.(b)
Classification. Class II.