MIM software is used by trained medical professionals as a tool to aid in evaluation and information management of digital medical images. The medical image modalities include, but are not limited to, CT, MR, CR, DX, MG, US, SPECT, PET and XA as supported by ACR/NEMA DICOM 3.0. MIM assists in the following indications:

· Receive, transmit, store, retrieve, display, print, and process medical images and DICOM objects.

· Create, display, and print reports from medical images.

· Registration, fusion display, and review of medical images for diagnosis, treatment evaluation, and treatment planning.

· Evaluation of cardiac left ventricular function and perfusion, including left ventricular end-diastolic volume, end-systolic volume, and ejection fraction.

· Localization and definition of objects such as tumors and normal tissues in medical images.

· Creation, transformation, and modification of contours for applications including, but not limited to, quantitative analysis, aiding adaptive therapy, transferring contours to radiation therapy treatment planning systems, and archiving contours for patient follow-up and management.

· Quantitative and statistical analysis of PET/SPECT brain scans by comparing to other registered PET/SPECT brain scans.

· Planning and evaluation of permanent implant brachytherapy procedures (not including radioactive microspheres).

· Calculating absorbed radiation dose as a result of administering a radionuclide.

When using the device clinically, within the United States, the user should only use FDA approved radiopharmaceuticals. If used with unapproved ones, this device should only be used for research purposes.

Lossy compressed mammoaraphic images and digitized film screen images must not be reviewed for primary image interpretations. Images that are printed to film must be printed using an FDA-approved printer for the diagnosis of digital mammography images. Mammographic images must be viewed on a display system that has been cleared by the FDA for the diagnosis of digital mammography images. The software is not to be used for mammography CAD.

Device Description

MIM - Centiloid Scaling extends the features of MIM - Additional Tracers (K223800). It is designed for use in medical imaging and operates on Windows, Mac, and Linux computer systems. The intended use and indications for use in MIM - Centiloid Scaling are unchanged from the predicate device, MIM - Additional Tracers (K223800).

MIM - Centiloid Scaling is a standalone software application that extends the functionality of the predicate device by providing:

· Conversion of SUVr calculations to a standardized Centiloid scale for PET-based amyloid burden measurement with Florbetapir (Amvvid®), Florbetaben (Neuraceq®), and Flutemetamol (Vizamyl™)

AI/ML Overview

The MIM - Centiloid Scaling device is intended to convert SUVr (Standardized Uptake Value ratio) calculations to a standardized Centiloid scale for PET-based amyloid burden measurement using specific radiopharmaceuticals (Florbetapir (Amyvid®), Florbetaben (Neuraceq®), and Flutemetamol (Vizamyl™)).

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the validation methods and desired outcomes of the Centiloid Project and comparisons to expert visual reads.

Criterion	Reported Device Performance
SUVr Calculation Accuracy (against GAAIN-published values)
- Linear regression R² for GAAIN Regions (across all 3 tracers)	> 0.97
- Linear regression R² for Clark Regions (across all 3 tracers)	> 0.96
(Comparable to Navitsky et al.²: GAAIN R²=0.89, Clark R²=0.90)
Centiloid Conversion Equation Validation
- Linear regression R² for MIM-calculated SUVr (Clark regions) vs. GAAIN-published SUVr (PiB scans) (across all 3 tracers)	> 0.91 (Acceptance criterion: R² > 0.70)
Centiloid Calculation Accuracy (against GAAIN-published Centiloid values)
- Linear regression R² for Amyvid	0.97
- Linear regression R² for Neuraceq	0.98
- Linear regression R² for Vizamyl	0.96
- Bland-Altman bias	Minimal (< 1.51 Centiloids for all tracers), no trending differences
Accuracy against Consensus Expert Visual Reads (Binary Classification)
- Combined Overall Accuracy	95.1% (range 92.0-98.7%)
- Combined Kappa	0.90 (range 0.84-0.97)
- Specific Accuracy for Amyvid (Overall, Kappa, Neg, Pos)	Overall: 92.0%, Kappa: 0.84, Negative Read: 90.7%, Positive Read: 93.5%
- Specific Accuracy for Neuraceq (Overall, Kappa, Neg, Pos)	Overall: 95.4%, Kappa: 0.90, Negative Read: 92.3%, Positive Read: 98.3%
- Specific Accuracy for Vizamyl (Overall, Kappa, Neg, Pos)	Overall: 98.7%, Kappa: 0.97, Negative Read: 97.2%, Positive Read: 100.0%

2. Sample Sizes Used for the Test Set and Data Provenance

The testing involved several datasets:

SUVr Calculation & Centiloid Conversion Equation Validation:
- Test set: "Tracer-specific patient cohorts available from the GAAIN database." No specific number of subjects is provided in this section, but it is implied to be diverse enough to establish robust linear regressions.
- Data Provenance: GAAIN (Global Alzheimer's Association Interactive Network) database. This is a multi-national effort, so the data would likely originate from various countries. The nature (retrospective/prospective) is not explicitly stated but often large databases like GAAIN contain retrospective patient data.
Centiloid Calculation Accuracy (against GAAIN-published Centiloid values):
- Test set: "Tracer data cohorts from the GAAIN database." Again, specific numbers are not given but are implied to be from the same cohorts used in the validation above.
- Data Provenance: GAAIN database. Multi-national, likely retrospective.
Accuracy against Consensus Expert Visual Reads:
- Test Set:
  - Amyvid: 100 scans from the ADNI2 study.
  - Neuraceq: 109 scans from a multi-center Phase II clinical trial.
  - Vizamyl: 79 scans from a multi-center Phase II clinical trial.
- Data Provenance:
  - ADNI2: Alzheimer's Disease Neuroimaging Initiative, primarily US-based, prospective and longitudinal study.
  - Multi-center Phase II clinical trials: These are typically prospective studies conducted in multiple sites, often internationally, but specific countries are not mentioned for Neuraceq and Vizamyl beyond being "multi-center."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document mentions "consensus expert visual reads as the standard of truth" for the accuracy assessment of Centiloid quantification. However, it does not explicitly state:

The number of experts who performed these visual reads.
The qualifications of these experts (e.g., "radiologist with 10 years of experience").

It refers to various clinical trials and studies (ADNI2, Phase II clinical trials for Neuraceq and Vizamyl) which typically involve trained medical professionals for such assessments, but precise details about the adjudicating experts for the visual reads are missing from this summary.

4. Adjudication Method for the Test Set

The document uses the term "consensus expert visual reads." This implies that multiple experts reviewed the scans and reached an agreement on the amyloid status. However, the specific adjudication method (e.g., 2-out-of-3 majority vote, discussion to consensus, initial independent reads followed by consensus panel) is not explicitly stated.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and 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 explicitly described in this document. The study described focuses on the standalone performance of the algorithm in calculating Centiloid values and comparing these to established quantitative methods (GAAIN-published values) and clinical expert visual reads. There is no mention of human readers using or not using the AI (MIM - Centiloid Scaling) and measuring their performance improvement.

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

Yes, a standalone study was done. The entire "Testing and Performance Data" section describes the performance of the MIM - Centiloid Scaling algorithm by itself:

It calculates SUVr values and compares them to published GAAIN values.
It generates Centiloid conversion equations using linear regression.
It calculates Centiloid values and compares them to GAAIN-published Centiloid values.
It compares its Centiloid quantification results to "consensus expert visual reads."

In all these cases, the MIM - Centiloid Scaling algorithm is operating independently to produce results that are then compared against established standards or expert interpretations.

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

The study uses a combination of ground truth types:

Quantitative Reference Standard: For SUVr calculation and the initial Centiloid calculation accuracy, the "GAAIN-published SUVr values" and "GAAIN-published Centiloid values" are used as the reference standard. These are highly standardized and accepted quantitative metrics in the field.
Expert Consensus (Binary Classification): For the assessment of accuracy against visual interpretations, "consensus expert visual reads" are used. This typically involves human experts making a qualitative judgment (e.g., amyloid positive/negative) which serves as the ground truth for that part of the evaluation.

8. The Sample Size for the Training Set

The document does not explicitly mention the sample size for the training set. The described testing focuses on validation using external datasets (GAAIN, ADNI2, clinical trials). It states that the device "extends the features of MIM - Additional Tracers" but does not detail how the Centiloid scaling functionality itself was developed or trained if it involved machine learning models requiring a specific training dataset. The methodology references "The Centiloid Project," which defines a standardized method, implying the device is implementing this method rather than purely learning from data in a traditional machine learning sense.

9. How the Ground Truth for the Training Set Was Established

Since the document does not explicitly describe a "training set" for the Centiloid Scaling feature (but rather implementation and validation of a standardized project), this information is not provided. The ground truth for the validation process is, as described above, GAAIN-published values and expert consensus visual reads.

Summary

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May 20, 2024

MIM Software Inc. Sydney Lindner Senior Clinical Engineer 25800 Science Park Drive Suite 180 Cleveland, Ohio 44122

Re: K233620

Trade/Device Name: MIM - Centiloid Scaling Regulation Number: 21 CFR 892.2050 Regulation Name: Medical Image Management And Processing System Regulatory Class: Class II Product Code: LLZ Dated: April 19, 2024 Received: April 19, 2024

Dear Sydney Lindner:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,

Daniel M. Krainak, Ph.D. Assistant Director DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

Submission Number (if known)

K233620

Device Name

MIM - Centiloid Scaling

Indications for Use (Describe)

· Receive, transmit, store, retrieve, display, print, and process medical images and DICOM objects.

· Create, display, and print reports from medical images.

· Registration, fusion display, and review of medical images for diagnosis, treatment evaluation, and treatment planning.

· Evaluation of cardiac left ventricular function and perfusion, including left ventricular end-diastolic volume, end-systolic volume, and ejection fraction.

· Localization and definition of objects such as tumors and normal tissues in medical images.

· Quantitative and statistical analysis of PET/SPECT brain scans by comparing to other registered PET/SPECT brain scans.

· Planning and evaluation of permanent implant brachytherapy procedures (not including radioactive microspheres).

· Calculating absorbed radiation dose as a result of administering a radionuclide.

Lossy compressed mammoaraphic images and digitized film screen images must not be reviewed for primary image interpretations. Images that are printed to film must be printed using an FDAapproved printer for the diagnosis of digital mammography images. Mammographic images must be viewed on a display system that has been cleared by the FDA for the diagnosis of digital mammography images. The software is not to be used for mammography CAD.

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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25800 Science Park Drive - Suite 180 Cleveland, OH 44122 866-421-2536 www.mimsoftware.com

K233620

510(k) Summary (The following information is in conformance with 21 CFR 807.92)

Submitter

MIM Software Inc. 25800 Science Park Drive - Suite 180 Cleveland, OH 44122

Phone:	216-455-0600
Fax:	216-455-0601
Contact Person:	Sydney Lindner
Date Summary Prepared:	April 19, 2024

Device Name

Trade Name:

Common Name:

Requlation Number / Product Code:

Classification Name:

MIM - Centiloid Scaling

Medical Imaging Software

21 CFR 892.2050 Product Code LLZ

System, Imaging Processing, Radiological

Predicate Devices

K223800 MIM - Additional Tracers Primary: Secondary: K060816 MIM 4.0 (NEURO)

MIM Software Inc. MIM Software Inc.

Intended Use

MIM software is intended for trained medical professionals including, but not limited to, radiologists, oncologists, physicians, medical technologists, dosimetrists and physicists.

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MIM is a medical image and information management system that is intended to receive, transmit, store, retrieve, display, print, and process digital medical images, as well as create, display, and print reports from those images. The medical modalities of these medical imaging systems include, but are not limited to, CT, MR, CR, DX, MG, US, SPECT, PET and XA as supported by ACR/NEMA DICOM 3.0.

MIM provides the user with the means to display, register, and fuse medical images from multiple modalities. Additionally, it evaluates cardiac left ventricular function and perfusion, including left ventricular end-diastolic volume, end-systolic volume, and ejection fraction.

The Region of Interest (ROI) feature reduces the time necessary for the user to define objects in medical image volumes by providing an initial definition of object contours. The objects include, but are not limited to, tumors and normal tissues.

MIM provides tools to quickly create, transform, and modify contours for applications including, but not limited to, quantitative analysis, aiding adaptive therapy, transferring contours to radiation therapy treatment planning systems and archiving contours for patient follow-up and management.

MIM aids in the assessment of PET/SPECT brain scans. It provides automated quantitative and statistical analysis by automatically registering PET/SPECT brain scans to a standard template and comparing intensity values to a reference database or to other PET/SPECT scans on a voxel-by-voxel basis, within stereotactic surface projections or standardized regions of interest.

MIM allows the dose distribution of an implant to be individually shaped for each patient and is a general-purpose brachytherapy planning system used for prospective and confirmation dose calculations for patients undergoing a course of brachytherapy using permanent implants of various radioisotopes (not including radioactive microspheres).

MIM allows voxel-based dose calculations for patients who have been administered radioisotopes or radioactive microspheres.

Indications for Use

MIM software is used by trained medical professionals as a tool to aid in the evaluation and information management of digital medical images. The medical image modalities include, but are not limited to, CT, MR, CR, DX, MG, US, SPECT, PET and XA as supported by ACR/NEMA DICOM 3.0. MIM assists in the following indications:

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Receive, transmit, store, retrieve, display, print, and process medical images and ● DICOM objects.
Create, display, and print reports from medical images.
Registration, fusion display, and review of medical images for diagnosis, treatment evaluation, and treatment planning.
Evaluation of cardiac left ventricular function and perfusion, including left . ventricular end-diastolic volume, end-systolic volume, and ejection fraction.
. Localization and definition of objects such as tumors and normal tissues in medical imaqes.
· Creation, transformation, and modification of contours for applications including, but not limited to, quantitative analysis, aiding adaptive therapy, transferring contours to radiation therapy treatment planning systems, and archiving contours for patient follow-up and management.
Quantitative and statistical analysis of PET/SPECT brain scans by comparing to . other registered PET/SPECT brain scans.
Planning and evaluation of permanent implant brachytherapy procedures (not including radioactive microspheres).
. Calculating absorbed radiation dose as a result of administering a radionuclide.

When using the device clinically, within the United States, the user should only use FDA-approved radiopharmaceuticals. If used with unapproved ones, this device should only be used for research purposes.

Lossy compressed mammographic images and digitized film screen images must not be reviewed for primary image interpretations. Images that are printed to film must be printed using an FDA-approved printer for the diagnosis of digital mammography images. Mammographic images must be viewed on a display system that has been cleared by the FDA for the diagnosis of digital mammography images. The software is not to be used for mammography CAD.

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Image /page/6/Picture/0 description: The image is a logo for MIM Software. The logo consists of two overlapping rounded squares, one gray and one red, with a white circle where they overlap. To the right of the squares is the text "mim" in a sans-serif font, with the word "SOFTWARE" below it in a smaller font.

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Image /page/9/Picture/0 description: The image shows the logo for MIM Software. The logo consists of two overlapping rounded squares, one gray and one red, with a white circle where they overlap. To the right of the squares is the text "mim" in a bold, sans-serif font, with the word "SOFTWARE" in a smaller font below it. The logo is simple and modern, with a focus on the company's name.

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Device Description

MIM - Centiloid Scaling is a standalone software application that extends the functionality of the predicate device by providing:

· Conversion of SUVr calculations to a standardized Centiloid scale for PET-based amyloid burden measurement with Florbetapir (Amvvid®), Florbetaben (Neuraceq®), and Flutemetamol (Vizamyl™)

Substantial Equivalence

MIM - Centiloid Scaling is substantially equivalent to the predicate devices, MIM -Additional Tracers (K223800) and MIM 4.0 (NEURO) (K060816).

Testing and Performance Data

Software verification and validation testing was performed for the three FDA-cleared amyloid tracers: Florbetapir (Amyvid®), Florbetaben (Neuraceg®), and Flutemetamol (Vizamyl™); Testing was performed for the qualification of the MIM pipeline to the Centiloid scale and to evaluate the accuracy of Centiloid quantification using consensus expert visual reads as the standard of truth.

SUVr calculation within MIM - Centiloid Scaling was validated by following the processes described in The Centiloid Project' for calibrating a non-PiB tracer to the Centiloid scale. This process involves computing and comparing MIM SUVr values to the GAAIN-published SUVr values for each subject with tracer-specific patient cohorts

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Image /page/11/Picture/0 description: The image shows the logo for MIM Software. The logo consists of two overlapping squares, one gray and one red, with a white circle where they overlap. To the right of the squares is the text "mim" in a bold, sans-serif font, with the word "SOFTWARE" in a smaller font below it. The logo is clean and modern, with a simple color scheme.

available from the GAAIN database. SUVr values were first computed using the published GAAIN Regions in MIM's PET registration pipeline and then recomputed using the Florbetapir Clark Regions. To assess the accuracy of SUVr calculation in MIM - Centiloid Scaling in comparison to the GAAIN-published values, these results were compared to a previously published study using Clark Regions for Centiloid calculation. SUVr calculation in MIM - Centiloid Scaling yielded linear regressions with R2 values greater than 0.97 for GAAIN Regions and greater than 0.96 for Clark regions across all three tracers. These results are comparable to those in Navitsky et al.2, where SUVr results with GAAIN regions yielded an R² of 0.89 and an R² of 0.90 using Clark Regions.

To create Centiloid conversion equations for each tracer, the next test described in The Centiloid Project' was to see if a linear regression of MIM-calculated SUVr with Clark regions for each tracer and GAAIN-published SUVr for PiB scans for the same subjects yielded an R2 > 0.70. Regression plots for each tracer yielded R2 > 0.91, therefore the regression equations (Tracer SUVr = PiB SUVr *slope - intercept) were validated for use in the Centiloid conversion equation.

The Centiloid equation for a non-PiB tracer is defined as,

$$^{\text{Tracer}}\text{Centiloid} = \frac{^{pIB-Calc}{SUbr}{\text{Tracer}} - ^{\text{PIB}}\text{SUbr}{\text{Yc}-0}}{^{pIB}{SUbr} - ^{\text{PIB}}\text{SUbr}{\text{Yc}-0}} ^{\ast}\mathbf{100}$$

where $SUVr_{Tracer}^{PIB-Calc}$ is computed using the previously validated regression equations from tracer SUVr to PiB SUVr. The healthy control cohort (YC-0) and AD patient cohort (AD-100) values are the Centiloid scale anchor points, defined as the mean PiB SUVr values for a standard cohort of young (<45 years) healthy controls and AD patients, respectively. Because MIM - Centiloid Scaling does not support PiB quantification, the anchor points used were not computed using MIM amyloid processing and instead were sourced from Navitsky et al.2 and Klunk et al.1 Using the tracer data cohorts from the GAAIN database and the GAAIN-published Centiloid values for each scan, the accuracy of Centillod calculation in MIM - Centiloid Scaling was evaluated. Linear regression yielded R2 values of 0.97, 0.98, and 0.96 for Amyvid, Neuraceg, and Vizamyl, respectively. Bland-Altman plots showed minimal bias (all <1.51 Centiloids) and no trending differences.

To further assess the accuracy of Centiloid quantification in MIM - Centiloid Scaling, comparison was made to consensus expert visual reads for 100 Amyvid scans from the ADNI2 study. 109 Neuraceg scans from a multi-center Phase II clinical trial®, and 79

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Vizamyl scans from a multi-center Phase II clinical trial'. The Centiloid quantification across all three tracers had a combined accuracy of 95.1% (range 92.0-98.7%) with a Kappa of 0.90 (range 0.84-0.97).

Tracer	OverallAccuracy	ClassificationAccuracy(Kappa)	#Correct/Total	NegativeReadAccuracy	PositiveReadAccuracy
Amyvid	92.0%	0.84	92/100	90.7%	93.5%
Neuraceq	95.4%	0.90	104/109	92.3%	98.3%
Vizamyl	98.7%	0.97	78/79	97.2%	100.0%

References for Testing and Performance Data

1. Klunk WE, Koeppe RA, Price JC, et al. The Centiloid Project: Standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015:11(1):1. doi:10.1016/j.jalz.2014.07.003https://aibl.csiro.au/adni/imaging.htm
1. Navitsky M. Joshi AD. Kennedy I. et al. Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale. Alzheimers Dement. 2018;14(12):1565-1571. doi:10.1016/j.jalz.2018.06.1353
1. Joshi AD, Pontecorvo MJ, Clark CM, et al. Performance Characteristics of Amyloid PET with Florbetapir F 18 in Patients with Alzheimer's Disease and Cognitively Normal Subjects. J Nucl Med. 2012;53(3):378-384. doi:10.2967/jnumed.111.090340
1. Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-ß plaques: a prospective cohort study. Lancet Neurol. 2012;11(8):669-678. doi:10.1016/S1474-4422(12)70142-4
1. - Laboratory of Neuro Imaging. ADNI | Study Design. Alzheimer's Disease Neuroimaging Initiative. Accessed September 27, 2023. https://adni.loni.usc.edu/study-design/
1. Barthel H, Gertz HJ, Dresel S, et al. Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011:10(5):424-435. doi:10.1016/S1474-4422(11)70077-1
1. Pemberton HG, Buckley C, Battle M, et al. Software compatibility analysis for quantitative measures of [18F]flutemetamol amyloid PET burden in mild cognitive impairment. EJNMMI Res. 2023;13(1):48. doi:10.1186/s13550-023-00994-3

*Data used in preparation of this article were obtained from the Alzheimaging Initiative (ADN) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADN and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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Image /page/13/Picture/0 description: The image is a logo for MIM Software. The logo consists of two overlapping rounded squares, one gray and one red, with a white circle where they overlap. To the right of the squares is the text "mim" in a bold, sans-serif font, with the word "SOFTWARE" underneath in a smaller font. The logo is simple and modern, with a focus on the company's name.

Conclusion

Based on the Device Description and Testing and Performance Data above, the proposed device demonstrates substantial equivalence as the predicate devices, MIM – Additional Tracers (K223800) and MIM 4.0 (NEURO) (K060816).

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).

	Subject Device:	Primary Predicate Device:	Secondary Predicate Device:
ITEM	MIM - Centiloid Scaling(K233620)	MIM - Additional Tracers(K223800)	MIM 4.0 (NEURO)(K060816)
Clearance Date	TBD	January 17, 2023	May 16, 2006
Intended Use	MIM software is intended fortrained medical professionalsincluding, but not limited to,radiologists, oncologists,physicians, medicaltechnologists, dosimetrists,and physicists.MIM is a medical image andinformation managementsystem that is intended toreceive, transmit, store,retrieve, display, print andprocess digital medicalimages, as well as create,display, and print reports fromthose images. The medicalmodalities of these medicalimaging systems include, butare not limited to, CT, MR,CR, DX, MG, US, SPECT,PET and XA as supported byACR/NEMA DICOM 3.0.	MIM software is intended fortrained medical professionalsincluding, but not limited to,radiologists, oncologists,physicians, medicaltechnologists, dosimetrists,and physicists.MIM is a medical image andinformation managementsystem that is intended toreceive, transmit, store,retrieve, display, print andprocess digital medicalimages, as well as create,display, and print reports fromthose images. The medicalmodalities of these medicalimaging systems include, butare not limited to, CT, MRI,CR, DX, MG, US, SPECT,PET and XA as supported byACR/NEMA DICOM 3.0.	MIM 4.0 (NEURO) is asoftware package thatprovides the physician with themeans to display, register andfuse medical images frommultiple modalities.
	MIM provides the user withthe means to display, registerand fuse medical images frommultiple modalities.Additionally, it evaluatescardiac left ventricularfunction and perfusion,including left ventricularend-diastolic volume,end-systolic volume, andejection fraction.	MIM provides the user withthe means to display, registerand fuse medical images frommultiple modalities.Additionally, it evaluatescardiac left ventricularfunction and perfusion,including left ventricularend-diastolic volume,end-systolic volume, andejection fraction.	Additionally, it evaluatescardiac left ventricular functionand perfusion including leftventricular end-diastolicvolume, end-systolic volume,and ejection fraction.
	The Region of Interest (ROI)feature reduces the timenecessary for the user todefine objects in medicalimage volumes by providingan initial definition of objectcontours. The objects include,but are not limited to, tumorsand normal tissues.MIM provides tools to quicklycreate, transform, and modify	The Region of Interest (ROI)feature reduces the timenecessary for the user todefine objects in medicalimage volumes by providingan initial definition of objectcontours. The objects include,but are not limited to, tumorsand normal tissues.MIM provides tools to quicklycreate, transform, and modify	The Region of Interest (ROI)feature reduces the timenecessary for the physician todefine objects in medicalimage volumes by providingan initial definition of objectcontours. The objects includebut are not limited to tumorsand organs.
	contours for applicationsincluding, but not limited to,quantitative analysis, aidingadaptive therapy, transferringcontours to radiation therapytreatment planning systemsand archiving contours forpatient follow-up andmanagement.	contours for applicationsincluding, but not limited to,quantitative analysis, aidingadaptive therapy, transferringcontours to radiation therapytreatment planning systemsand archiving contours forpatient follow-up andmanagement.	MIM 4.0 (NEURO) also aidsthe physician in theassessment of PET/SPECTbrain scans. It providesautomated quantitative andstatistical analysis byautomatically registeringPET/SPECT brain scans to astandard template andcomparing intensity values to areference database or to otherPET/SPECT scans on a voxelby voxel basis, withinstereotactic surfaceprojections, or withinstandardizedregions of interest.
	MIM aids in the assessmentof PET/SPECT brain scans. Itprovides automatedquantitative and statisticalanalysis by automaticallyregistering PET/SPECT brainscans to a standard templateand comparing intensityvalues to a referencedatabase or to otherPET/SPECT scans on avoxel-by-voxel basis, withinstereotactic surfaceprojections or standardizedregions of interest.	MIM aids in the assessmentof PET/SPECT brain scans. Itprovides automatedquantitative and statisticalanalysis by automaticallyregistering PET/SPECT brainscans to a standard templateand comparing intensityvalues to a referencedatabase or to otherPET/SPECT scans on avoxel-by- voxel basis, withinstereotactic surfaceprojections or standardizedregions of interest.
	MIM allows the dosedistribution of an implant to beindividually shaped for eachpatient and is ageneral-purposebrachytherapy planningsystem used for prospectiveand confirmation dosecalculations for patientsundergoing a course ofbrachytherapy usingpermanent implants of variousradioisotopes (not includingradioactive microspheres).	MIM allows the dosedistribution of an implant to beindividually shaped for eachpatient and is ageneral-purposebrachytherapy planningsystem used for prospectiveand confirmation dosecalculations for patientsundergoing a course ofbrachytherapy usingpermanent implants of variousradioisotopes (not includingradioactive microspheres).
	MIM allows voxel-based dosecalculations for patients whohave been administeredradioisotopes or radioactivemicrospheres.	MIM allows voxel-based dosecalculations for patients whohave been administeredradioisotopes or radioactivemicrospheres.
Indications forUse	MIM software is used bytrained medical professionalsas a tool to aid in evaluationand information managementof digital medical images. Themedical image modalitiesinclude, but are not limited to,	MIM software is used bytrained medical professionalsas a tool to aid in evaluationand information managementof digital medical images. Themedical image modalitiesinclude, but are not limited to,	The MIM software programshould be used for theregistration, fusion and displayof medical images frommulti-modalities, such asSPECT, PET, CT, and MRI.
CT, MR, CR, DX, MG, US,SPECT, PET and XA assupported by ACR/NEMADICOM 3.0. MIM assists inthe following indications:	CT, MRI, CR, DX, MG, US,SPECT, PET and XA assupported by ACR/NEMADICOM 3.0. MIM assists inthe following indications:
• Receive, transmit, store,retrieve, display, print, andprocess medical images andDICOM objects.	• Receive, transmit, store,retrieve, display, print, andprocess medical images andDICOM objects.
• Create, display, and printreports from medical images.	• Create, display and printreports from medical images.
• Registration, fusion display,and review of medical imagesfor diagnosis, treatmentevaluation, and treatmentplanning.	• Registration, fusion display,and review of medical imagesfor diagnosis, treatmentevaluation, and treatmentplanning.
• Evaluation of cardiac leftventricular function andperfusion, including leftventricular end-diastolicvolume, end-systolic volume,and ejection fraction.	• Evaluation of cardiac leftventricular function andperfusion, including leftventricular end-diastolicvolume, end-systolic volume,and ejection fraction.
• Localization and definition ofobjects such as tumors andnormal tissues in medicalimages.	• Localization and definition ofobjects such as tumors andnormal tissues in medicalimages.	MIM assists in definition ofstructures in medical imagesincluding tumors, organs, andcardiac left ventricular cavity.
• Creation, transformation,and modification of contoursfor applications including, butnot limited to, quantitativeanalysis, aiding adaptivetherapy, transferring contoursto radiation therapy treatmentplanning systems, andarchiving contours for patientfollow-up and management.	• Creation, transformation,and modification of contoursfor applications including, butnot limited to, quantitativeanalysis, aiding adaptivetherapy, transferring contoursto radiation therapy treatmentplanning systems, andarchiving contours for patientfollow-up and management.
• Quantitative and statisticalanalysis of PET/SPECT brainscans by comparing to otherregistered PET/SPECT brainscans.	• Quantitative and statisticalanalysis of PET/SPECT brainscans by comparing to otherregistered PET/SPECT brainscans.	MIM aids in the assessment ofPET/SPECT brain scans byproviding quantitative andstatistical comparisons to otherregistered PET/SPECT brainscans.
• Planning and evaluation ofpermanent implantbrachytherapy procedures(not including radioactivemicrospheres).	• Planning and evaluation ofpermanent implantbrachytherapy procedures(not including radioactivemicrospheres).
	• Calculating absorbedradiation dose as a result ofadministering a radionuclide.	• Calculating absorbedradiation dose as a result ofadministering a radionuclide.	• Calculating absorbedradiation dose as a result ofadministering a radionuclide.
	When using the deviceclinically, within the UnitedStates, the user should onlyuse FDA approvedradiopharmaceuticals. If usedwith unapproved ones, thisdevice should only be usedfor research purposes.	When using this deviceclinically within the UnitedStates, the user should onlyuse FDA-approvedradiopharmaceuticals. If usedwith unapproved ones, thisdevice should only be usedfor research purposes.	When using this deviceclinically within the UnitedStates, the user should onlyuse FDA-approvedradiopharmaceuticals. If usedwith unapproved ones, thisdevice should only be usedfor research purposes.
	Lossy compressedmammographic images anddigitized film screen imagesmust not be reviewed forprimary image interpretations.Images that are printed to filmmust be printed using aFDA-approved printer for thediagnosis of digitalmammography images.Mammographic images mustbe viewed on a displaysystem that has been clearedby the FDA for the diagnosisof digital mammographyimages. The software is not tobe used for mammographyCAD.	Lossy compressedmammographic images anddigitized film screen imagesmust not be reviewed forprimary image interpretations.Images that are printed to filmmust be printed using aFDA-approved printer for thediagnosis of digitalmammography images.Mammographic images mustbe viewed on a displaysystem that has been clearedby the FDA for the diagnosisof digital mammographyimages. The software is not tobe used for mammographyCAD.	Lossy compressedmammographic images anddigitized film screen imagesmust not be reviewed forprimary image interpretations.Images that are printed to filmmust be printed using aFDA-approved printer for thediagnosis of digitalmammography images.Mammographic images mustbe viewed on a displaysystem that has been clearedby the FDA for the diagnosisof digital mammographyimages. The software is not tobe used for mammographyCAD.
OperatingPlatform	Microsoft Windows, Apple®OS X, Linux-based OS	Microsoft Windows, Apple®OS X, Linux-based OS	Microsoft Windows
SupportedImagingModalities	CT, MR, CR, DX, MG, US,NM, PET, XA, and otherDICOM modalities	CT, MR, CR, DX, MG, US,NM, PET, XA, and otherDICOM modalities	CT, MR, NM, PET, OT, andother DICOM modalities
Receive,transmit,display, generalmanipulation(window/level,pan, zoom,cross-hairs,slicenavigation),andco-registrationof medicalimages	Yes	Yes	Yes
Radiopharmaceutical-specifictemplate	Yes, unchanged from MIM –Additional Tracers (K223800)	Yes	Yes
registration
Amyloid PETQuantification	Voxel-based z-scores,regional z-scores, regionalSUVr, global SUVr,Centiloid scaling	Voxel-based z-scores,regional z-scores, regionalSUVr, global SUVr	Voxel-based z-scores, regionalz-scores, regional SUVr, globalSUVr