Intelligent Medical Imaging, Inc.'s MICRO21™ with Cerebrospinal Fluid (CSF) is a laboratory instrument used to perform cytological analysis by locating, digitally storing and displaying nucleated cells in human cerebrospinal fluid preparations. Examination of cellular morphology and classification must be performed by qualified individuals.

Device Description

The MICRO21™ with Cerebrospinal Fluid is a new procedure for the MICRUZ/ with the tollowing in vitro diagnostic intended use: Intelligent Medical Imaging, Inc.'s MICRO21™ with Cerebrospinal Fluid (CSF) is a laboratory instrument used to perform cytological analysis by locating, digitally storing and displaying nucleated cells in human cerebrospinal fluid preparations. Examination of cellular morphology and classification must be performed by qualified individuals.

A summary of the MICRO21 with Cerebrospinal Fluid process is as follows:

Patient CSF samples are prepared using the cytocentrifugation method for specimen concentration 1. using the Cytospin® centrifuge. . .
Each slide has a black mask over the non-frosted portion with a hole in the mask for specimen 2. placement.
1. The slide is stained using Wright's stain.
The slides are barcoded and placed into a frame holder, and the frame is placed on the MICRO21 for 4. processing.
ડ. The MICRO21 locates nucleated cells.
The nucleated cell images are stored by the instrument and displayed on a color monitor for review by 6. a technologist.
The technologist reviews the images and confirms each cell type. 7.
1. A report of the CSF result for each patient is printed.

AI/ML Overview

The provided text describes information relevant to the regulatory submission for the MICRO21™ with Cerebrospinal Fluid, an automated cell locating device. Based on the document, here's a structured breakdown of the acceptance criteria and the study conducted:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of quantitative acceptance criteria with corresponding performance metrics. Instead, it describes various test methods and concludes that these tests "confirm the safety and effectiveness" for the intended use. Therefore, the "acceptance criteria" are implied by the successful completion and correlation reported in the "Conclusion" section for the specified tests.

Test Method	Implied Acceptance Criteria (Qualitative)	Reported Device Performance
Method Verification and Sensitivity	Ability to locate cells at low and high power, distinguishing real cells from non-cells (e.g., stain precipitate).	"The ability of the instrument to locate cells at low and high power was determined by manually confirming the location of real cells or the location of non-cells such as stain precipitate." (Implies successful confirmation of ability to locate and differentiate).
Precision	Consistent and reproducible results (intra-instrument within slide precision) on repeated analyses of the same specimens by the device.	"The results were correlated to provide intra-instrument within slide precision." (Implies satisfactory precision, as it supports the overall conclusion of safety and effectiveness).
Correlation Study Performance	Satisfactory correlation between Cerebrospinal Cell Differentials (CCDs) obtained from MICRO21 images and those performed manually by qualified technologists.	"CCDs obtained from images located and displayed by the MICRO21 were correlated with CCDs performed manually by qualified technologists." (Implies successful correlation, as it supports the overall conclusion of safety and effectiveness. No specific correlation coefficient is given).

2. Sample Size and Data Provenance for the Test Set

Test Method 1 (Method Verification and Sensitivity):
- Sample Size: "Ten slides" were processed.
- Data Provenance: Not explicitly stated, but implied to be human CSF preparations for testing the device's main function. Retrospective or prospective is not specified.
Test Method 2 (Precision):
- Sample Size: "Three CSF specimen slides" were processed.
- Data Provenance: Not explicitly stated. Retrospective or prospective is not specified.
Test Method 3 (Correlation Study Performance):
- Sample Size: "Fifty CSF specimens" were used.
- Data Provenance: "obtained from various geographic sites." This suggests a multi-site data collection, which could be a mix of retrospective or prospective data. The document does not specify.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

Test Method 1 (Method Verification and Sensitivity): The manual confirmation was done by an unspecified number of individuals, but implies medical professionals capable of identifying cells and precipitates. No specific qualifications are given.
Test Method 2 (Precision): "The resulting images were presented to a technologist for review." Implies one technologist. Qualifications are "technologist," with no further detail.
Test Method 3 (Correlation Study Performance):
- Manual Method Ground Truth: "two technologists processed and examined each slide by bright-field microscopy." Qualifications: "qualified technologists." (No specific experience level or certifications provided beyond "qualified").
- MICRO21 Image Review: "two technologists independently reviewed the stored images for each specimen and classified all nucleated cells accordingly." Qualifications: "technologists."

4. Adjudication Method (Test Set)

Test Method 1 (Method Verification and Sensitivity): "manually confirming the location of real cells or the location of non-cells". The adjudication method is not specified (e.g., if there were disagreements, how they were resolved).
Test Method 2 (Precision): Not applicable for explicit adjudication as it focuses on instrument reproducibility, with a single technologist reviewing results.
Test Method 3 (Correlation Study Performance):
- Manual Method: "two technologists processed and examined each slide". It's not explicitly stated if there was an adjudication process if their classifications differed. It is possible they performed their counts and classifications independently, and the aggregated results were used for correlation.
- MICRO21 Image Review: "two technologists independently reviewed the stored images... and classified all nucleated cells accordingly." Similar to the manual method, it's not specified if there was an adjudication process for discrepancies between the two technologists' independent reviews.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study as typically understood (comparing human readers with AI assistance vs. without AI assistance to measure an effect size) was not explicitly described.

The "Correlation Study Performance" compared the device's output (images reviewed by technologists) with the manual method performed by technologists. While it involves multiple readers (technologists) and multiple cases (50 CSF specimens), it's more of a standalone performance evaluation of the device in a clinical workflow context, aiming to show agreement with current standard practice, rather than an MRMC study designed to quantify the improvement of human readers through AI assistance. The device's role is to locate, store, and display cells, with technologists performing the final classification.

6. Standalone Performance Study

Yes, a standalone (algorithm only without human-in-the-loop performance) study was performed for the locating component of the device.

Test Method 1 (Method Verification and Sensitivity): This test determined "the ability of the instrument to locate cells at low and high power." While manual confirmation was used to verify the accuracy of the locations, the initial "locating" was an algorithm-only step.
Test Method 2 (Precision): This test assessed the instrument's intra-instrument precision, focusing on the reproducibility of the locating and imaging process, which is largely an algorithmic function.

Even for the "Correlation Study Performance," the MICRO21 "located" and "captured" the images. The subsequent human technologists reviewed these captured images. Thus, the locating capability itself is a standalone function of the algorithm, which was then presented to human readers for final classification.

7. Type of Ground Truth Used

The ground truth for the test set was:

Expert Consensus/Expert Review: For all test methods, the ultimate "ground truth" or reference standard involved human experts (technologists) making classifications or confirming locations.
- For Test Method 1 and 2, it involved technologists manually confirming cell locations or reviewing images.
- For Test Method 3 (Correlation Study), the "manual method" performed by two qualified technologists served as the reference standard against which the device's performance (images reviewed by other technologists) was compared. While "consensus" isn't explicitly stated for the manual method, it's implied that their independent processing and examination established the manual CCDs.

8. Sample Size for the Training Set

The document does not provide information about the sample size used for the training set of the MICRO21™ device. This information is typically found in development documentation and is often distinct from the regulatory submission's test set.

9. How Ground Truth for the Training Set Was Established

The document does not provide information on how the ground truth for the training set was established. Given the device's function (locating cells and displaying images for human review), it's highly probable that the training data would have involved slides prepared with known cellular content, manually annotated or classified by expert cytotechnologists or pathologists to teach the system to identify and locate target cells. However, this is an inference and not explicitly stated in the provided text.

Summary

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SEP 1 6 1997

510(k) Summary

Prepared by:	Ronald Lee Bartley, B.S., MT, NCA (CLS/C
Title:	Sr. Product Development Manager
Date:	April 18, 1997
Trade Name:
Classification Name:	Automated Cell Locating Device
Classification Number:	81JOY
Class:	II
Regulation Number:	864.5260

Description:

A summary of the MICRO21 with Cerebrospinal Fluid process is as follows:

Patient CSF samples are prepared using the cytocentrifugation method for specimen concentration 1. using the Cytospin® centrifuge. . .
Each slide has a black mask over the non-frosted portion with a hole in the mask for specimen 2. placement.
1. The slide is stained using Wright's stain.
The slides are barcoded and placed into a frame holder, and the frame is placed on the MICRO21 for 4. processing.
ડ. The MICRO21 locates nucleated cells.
The nucleated cell images are stored by the instrument and displayed on a color monitor for review by 6. a technologist.
The technologist reviews the images and confirms each cell type. 7.
1. A report of the CSF result for each patient is printed.

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Image /page/1/Picture/0 description: The image shows the logo for Intelligent Medical Imaging, Inc. The logo features the letters "IMI" in a bold, sans-serif font. Above and to the left of the letters is a graphic of interconnected dots and lines. Below the letters is the full name of the company, "Intelligent Medical Imaging, Inc."

Test Method 1: Method Verification and Sensitivity

Ten slides were processed using a quality control protocol to determine the detection sensitivity of the instrument. The ability of the instrument to locate cells at low and high power was determined by manually confirming the location of real cells or the location of non-cells such as stain precipitate.

Test Method 2: Precision

To confirm the MICRO21 intra-instrument precision, three CSF specimen slides were processed eight times, each in random order. Using blinded experimental methods, the resulting images were presented to a technologist for review. The results were correlated to provide intra-instrument within slide precision.

Test Method 3: Correlation Study Performance

Cerebrospinal Cell Differentials (CCDs) obtained from images located and displayed by the MICRO21 were correlated with CCDs performed manually by qualified technologists. Fifty CSF specimens obtained from various geographic sites were used for the study.

For the manual method, two technologists processed and examined each slide by bright-field microscopy. Depending on the cellularity of the specimen, a cumulative differential of up to 250 nucleated cells were counted and classified. Any non-nucleated cells or micro-organisms were recorded if present. In addition, any cell clustering or cell packing (confluent layer of cells) was noted.

The same slides were then loaded onto the MICRO21 and processed using the routine procedure as outlined in the Product Description. For each slide, up to 250 images were captured. The number of images captured varied depending on the cellularity of the specimen and preparation quality. Non-cellular images typically included stain precipitate, smudge cells and stained protein clumps which were recognized and discarded. The number of non-cells found was directly dependent upon the quality of the slide preparation and the nature of the specimen.

For differential analysis, two technologists independently reviewed the stored images for each specimen and classified all nucleated cells accordingly. In addition, any non-nucleated cells, micro-organisms, cell clustering or cell packing was also recorded if present.

In order to provide an accurate correlation measurement between the MICRO2/ and the Manual Methods, an equivalent number of cells was used for comparison analysis. The number of cells used for the comparative analysis was determined by cells counted by the MICRO21.

Conclusion

The method verification and sensitivity, precision and correlation testing performed in the Test Methods confirm the safety and effectiveness of the MICRO21 with CSF for the intended use of performing cytological analysis by locating, digitally storing and displaying nucleated cells in human Cerebrospinal Fluid preparations.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. R. Otto Stellner Vice President, Requlatory Compliance Intelligent Medical Imaging, Inc. 4360 Northlake Boulevard SEP 1 6 1997 Suite 214 Palm Beach Gardens, Florida 33410 Re: K971470/S1 Trade Name: MICRO 21™ with Cerebrospinal Fluid

Regulatory Class: II Product Code: JOY Dated: July 21, 1997 Received: July 22, 1997

Dear Mr. Stellner:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, qood manufacturing practice, labeling, and prohibitions aqainst misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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K971470 510(k) Number (if known):

Device Name: MICRO21™ with Cerebrospinal Fluid

Indications for Use:

For In Vitro Diagnostic Use

Intelligent Modical Imaging, Inc.'s MICRO21 ™ with Cerebrospinal Fluid (CSP) is a laboratory instrument used to perform cytological analysis by locating, digitally storing and displaying nucleated colls in a reform used to perform cytological analyals of coulding elganisy morphology and classification must be performed by qualified individuals.

(PLEASE: DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number

Regulation Number and Section

§ 864.5260 Automated cell-locating device.

(a)
Identification. An automated cell-locating device is a device used to locate blood cells on a peripheral blood smear, allowing the operator to identify and classify each cell according to type. (Peripheral blood is blood circulating in one of the body's extremities, such as the arm.)(b)
Classification. Class II (performance standards).