vascuCAP is a medical image analysis system that allows the processing, review, analysis, communication and media interchange of multi-dimensional digital images acquired with contrast from CT imaging devices.

vascuCAP is intended to assist trained physicians in the stratification of patients identified to have atherosclerosis. The software post processes images obtained using a multidetector CT. The package provides tools for the measurement and visualization (color coded maps) of arterial vessels.

Clinicians can select any artery to view the following anatomical references: the highlighted vessel in 3D, two rotatable curved MPR vessel views displayed at angles orthogonal to each other, and cross sections of the vessel. Cross-sectional measurements can be obtained using standard vascuCAP software measuring tools. Clinicians can semi-automatically determine contrasted lumen boundaries, stenosis measurements, and maximum lumen diameters. In addition, clinicians can edit lumen boundaries and examine Hounsfield unit or signal intensity statistics. Clinicians can also manually measure vessel length along the centerline in standard curved MPR views.

The measurements provided by vascuCAP are not intended to provide a diagnosis or clinical recommendations. vascuCAP is intended as a tool to complement standard of care.

Device Description

vascuCAP is an image analysis software package for evaluating CT images of arterial vessels. It allows the processing, review, analysis, communication, and media interchange of multidimensional digital images acquired from CT scanners. vascuCAP provides multi-dimensional visualization of digital images to aid clinicians in their analysis of anatomy and tissue characteristics. The vascuCAP software application user interface follows typical clinical workflow patterns to process, review, and analyze digital images.

AI/ML Overview

The provided text describes the performance data for the vascuCAP A.1.2 device, comparing it to a predicate device. Here's a breakdown of the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as pass/fail thresholds against which the device was evaluated. Instead, it presents "analytic performance metrics" as established results from the testing. For each metric, the reported performance includes bias, intercept, slope, quadratic term, and R^2, along with 95% confidence intervals. The "tested range" indicates the range of true values for the measurand.

Table: Reported Device Performance Metrics (Implicit Acceptance Criteria)

Structure/Composition	Measurand (Tested Range)	Reported Performance (Point Estimate [95% Confidence Interval])
Structure	Lumen Area (0.3 - 290.1mm²)	Bias: 0.81mm² [0.3, 1.9], Intercept: 0.65mm² [-0.6, 0.9], Slope: 1.01 [0.9, 1.0], Quadratic term: 0.0 [0.0, 0.0], R²: 0.9987
	Wall Area (9.4 - 448.6mm²)	Bias: 0.50mm² [-1.08, 1.29], Intercept: -0.59mm² [-4.1, 2. 8.0], Slope: 1.0 [0.99, 1.04], Quadratic term: 0.0 [0.0, 0.0], R²: 0.9974
	Stenosis** (33-69%)	Vessels ≥5.9mm: Bias: 3.7% [1.29, 4.47], Intercept: 5.99% [-0.81, 9.93], Slope: 0.96 [0.84, 1.1], Quadratic term: -0.01 [-0.02, 0.01], R²: 0.8034 Vessels <5.9mm: Bias: 9.3% [2.14, 12.72], Intercept: 34.0% [-2.3, 38.9], Slope: 0.55 [0.42, 1.21], Quadratic term: 0.001 [-0.02, 0.06], R²: 0.9549
	Wall Thickness (1.0 - 9.0mm)	Bias: 0.5mm [0.3, 0.6], Intercept: 0.27mm [-0.1, 0.5], Slope: 1.05 [1.01, 1.1], Quadratic term: -0.008 [-0.02, 0.01], R²: 0.9855
	Plaque Burden (0.4 -1.0 ratio)	Bias: -0.01 [-0.01, .004], Intercept: 0.01 [-0.1, 0.04], Slope: 0.99 [0.9, 1.1], Quadratic term: 0.03 [-0.1, 0.3], R²: 0.9794
Composition	Calcified Area (0.0 - 51.2mm²)	Difference: 0.15mm² [-0.5, 0.97], Intercept: 0.4mm² [-0.02, 1.6], Slope: 0.9 [0.6, 1.1], Quadratic term: -0.01 [-0.1, 0.04], R²: 0.875
	LRNC Area (0.0 - 26.8mm²)	Difference: 0.8mm² [-0.7, 2.6], Intercept: 1.44mm² [0.2, 3.4], Slope: 0.8 [0.2, 1.1], Quadratic term: 0.004 [-0.1, 0.3], R²: 0.5222
	Matrix Area (2.6 - 57.1mm²)	Difference: -1.6mm² [-3.6, 0.32], Intercept: 2mm² [-3, 5], Slope: 0.83 [0.7, 1.0], Quadratic term: -0.01 [-0.04, 0.01], R²: 0.7469

Note on "Acceptance Criteria": The document doesn't define explicit numerical acceptance criteria (e.g., "Bias must be less than X"). Instead, the presentation of these metrics with their 95% confidence intervals implies that the demonstrated performance as reported is considered acceptable for substantial equivalence to the predicate device. The narrative emphasizes "demonstrating that the product meets defined system requirements and features" and "established analytic performance metrics," without listing specific pre-defined thresholds.

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

The document indicates that "Validation testing using phantom and clinical images was conducted."

Phantom Data:
- Sample size: Not explicitly stated as a number of phantom images or measurements, but it mentions, "The mean tested phantom vessel size is 8.7mm [3.9mm]."
- Provenance: This is lab-generated data from anthropomorphic phantoms. No country of origin is specified, but it's typically an in-house or contracted lab study.
- Retrospective/Prospective: Phantom studies are inherently prospective, as they are designed experiments.
Clinical Image Data:
- Sample size: Not explicitly stated as a number of clinical images/patients.
- Provenance: The document refers to "histopathologic specimens" which were "ex vivo tissue specimens with paired CTA." "The tissue specimens are from the carotid artery." No country of origin is specified.
- Retrospective/Prospective: The use of "ex vivo tissue specimens with paired CTA" and "clinically-accepted scanning protocols" suggests these were likely retrospective collections of clinical images and corresponding tissue samples.

3. Number of Experts and Qualifications for Ground Truth

Structural measurements (from phantoms):
- Number of Experts: Not applicable, as ground truth for anthropomorphic phantoms is established using "micrometer measurements."
- Qualifications: "Micrometer measurements on anthropomorphic objects."
Composition (tissue types from clinical images):
- Number of Experts:
  - Pathologists: Three (3) independent pathologists for histopathology interpretation.
  - Radiologists: Two (2) independent radiologist users for aligning annotated sections with 3D radiology volume.
- Qualifications:
  - Pathologists: "Board certified pathologists."
  - Radiologists: Not explicitly stated, but inferred to be qualified radiologists ("independent radiologist users").

4. Adjudication Method for the Test Set

Composition (tissue types):
- Pathologist Agreement: "Three independent annotations were used for these results to account for acknowledged discordance in histopathology interpretation." This implies that the ground truth for pathology was derived from the consensus or agreement among these three pathologists, though the specific adjudication rule (e.g., majority vote, specific expert's decision) is not detailed.
- Radiologist Agreement: "four combinations resulting from two unique positioners crossed with two independent radiologist users were used for these results to account for differences in judgment on where the annotated section data applies within the in vivo volume, blinded to vascuCAP results." Similar to pathologists, this suggests a method to account for variability in radiologist interpretation for ground truthing, though the specific adjudication rule is not provided.
Structural measurements (phantom data): Adjudication is not applicable as the ground truth is micrometric measurements.

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

There is no indication of an MRMC comparative effectiveness study that assesses how much human readers improve with AI vs. without AI assistance. The study focuses on the analytical performance of the device's measurements compared to ground truth, not on human reader performance.

6. Standalone Performance

The study primarily describes the standalone (algorithm only without human-in-the-loop performance) of the vascuCAP device. The performance metrics presented (bias, slope, R^2) are direct measures of the algorithm's accuracy against established ground truth for various vascular measurements and compositions.

7. Type of Ground Truth Used

Structural Measurements (Lumen Area, Wall Area, Wall Thickness, Plaque Burden):
- Phantom Data: Micrometer measurements on anthropomorphic objects.
Stenosis: Derived from the lumen diameters, with ground truth for lumen diameters from micrometer measurements on phantoms.
Composition (Calcified Area, LRNC Area, Matrix Area):
- Clinical Data: Expert consensus/interpretation by "board certified pathologists of histopathologic specimens" with paired CT angiogram (CTA) data. This is further refined by "three independent annotations" from pathologists and "four combinations" from two radiologists for positioning. This suggests a multi-expert consensus ground truth for tissue characterization.

8. Sample Size for the Training Set

The document does not specify the sample size used for the training set. It focuses on the validation testing performance.

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

Since the training set size is not provided, the method for establishing its ground truth is also not described in this document. The description of ground truth establishment is specifically for the test set used in performance validation.

Summary

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December 21, 2018

Elucid Bioimaging, Inc. Andrew Buckler President 225 Main Street, Suite 15 WENHAM, MA 01984

Re: K183012

Trade/Device Name: vascuCAP Regulation Number: 21 CFR 892.2050 Regulation Name: Picture Archiving And Communications System Regulatory Class: Class II Product Code: LLZ Dated: December 17, 2018 Received: December 17, 2018

Dear Andrew Buckler:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's

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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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Hse 2. Nils

for Robert A. Ochs, Ph.D. Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K183012

Device Name vascuCAP

Indications for Use (Describe)

The measurements provided by vascuCAP are not intended to provide a diagnosis or clinical recommendations. vascuCAP is intended as a tool to complement standard of care.

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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K183012

510(K) SUMMARY

510(k) SUMMARY
510(k) submitter:	Elucid Bioimaging, Inc.225 Main Street, Suite 15Wenham, MA 01984
	Ph. 978-468-0508Fax: 978-468-0527
Contact person:	Andrew J. Buckler, President and CTO, Elucid Bioimaging Inc.
Date prepared:
Device:
Name of device:	vascuCAP™
Common or usual name:	Image processing system
Classification name:	Picture archiving and communications system
Regulatory class:	II
Product code:	LLZ

Predicate device:

Elucid Bioimaging Inc. vascuCAP A.1.1 (K163071)

Device Description:

Intended Use:

Clinicians can select any artery to view the following anatomical references: the highlighted vessel in 3D. two rotatable curved MPR vessel views displayed at angles orthogonal to each other, and cross sections of the vessel. Cross-sectional measurements can be obtained using standard vascuCAP software measuring tools. Clinicians can semi-automatically determine contrasted lumen boundaries, stenosis measurements, and maximum and minimum lumen

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diameters. In addition, clinicians can edit lumen boundaries and examine Hounsfield unit or signal intensity statistics. Clinicians can also manually measure vessel length along the centerline in standard curved MPR views.

The measurements provided by vascuCAP are not intended to provide a diagnosis or clinical recommendations. vascuCAP is intended as a tool to complement standard of care.

Technological Characteristics Comparing to the Predicate:

vascuCAP A.1.2 has all the same technological characteristics and features as vascuCAP A.1, but refines processing algorithms to improve measurement performance.

Performance Data:

Software verification and validation: Software verification consistent with FDA quidance on "General Principles of Software Validation" was conducted, comprising quality planning, requirements analysis, design reviews, software construction, and testing. Verification testing addressed installation and operation qualification, demonstrating that the product meets defined system requirements and features.

Performance testing: Validation testing using phantom and clinical images was conducted to address performance qualification of the subject device under typical operating conditions. Clinical images were evaluated using vascuCAP. Objectives evaluated included calculations of anatomic structure (compared to anthropomorphic phantoms) and calculations of tissue characteristics (compared to expert annotation by board certified pathologists of histopathologic specimens). As a result of this testing, the following analytic performance metrics have been established*:

Structure	Lumen Area,tested range 0.3 - 290.1mm²	Bias: 0.81mm² [0.3, 1.9], Intercept: 0.65mm² [-0.6, 0.9],Slope: 1.01 [0.9, 1.0], Quadratic term: 0.0 [0.0, 0.0], R²: 0.9987
	Wall Area,tested range 9.4 - 448.6mm²	Bias: 0.50mm² [-1.08, 1.29], Intercept: -0.59mm² [-4.1, 2. 8.0],Slope: 1.0 [0.99, 1.04], Quadratic term: 0.0 [0.0, 0.0], R²: 0.9974
	Stenosis**,tested range 33-69%	Vessels ≥5.9mm: Bias: 3.7% [1.29, 4.47], Intercept: 5.99% [-0.81, 9.93],Slope: 0.96 [0.84, 1.1], Quadratic term: -0.01 [-0.02, 0.01], R²: 0.8034Vessels <5.9mm: Bias: 9.3% [2.14, 12.72], Intercept: 34.0% [-2.3, 38.9],Slope: 0.55 [0.42, 1.21], Quadratic term: 0.001 [-0.02, 0.06], R²: 0.9549
	Wall Thickness,tested range 1.0 - 9.0mm	Bias: 0.5mm [0.3, 0.6], Intercept: 0.27mm [-0.1, 0.5],Slope: 1.05 [1.01, 1.1], Quadratic term: -0.008 [-0.02, 0.01], R²: 0.9855
	Plaque Burden,tested range 0.4 -1.0 (ratio)	Bias: -0.01 [-0.01, .004], Intercept: 0.01 [-0.1, 0.04],Slope: 0.99 [0.9, 1.1], Quadratic term: 0.03 [-0.1, 0.3], R²: 0.9794
Composition	Calcified Area,tested range 0.0 - 51.2mm²	Difference: 0.15mm² [-0.5, 0.97], Intercept: 0.4mm² [-0.02, 1.6],Slope: 0.9 [0.6, 1.1], Quadratic term: -0.01 [-0.1, 0.04], R²: 0.875
	LRNC Area,tested range 0.0 - 26.8mm²	Difference: 0.8mm² [-0.7, 2.6], Intercept: 1.44mm² [0.2, 3.4],Slope: 0.8 [0.2, 1.1], Quadratic term: 0.004 [-0.1, 0.3], R²: 0.5222
	Matrix Area,tested range 2.6 - 57.1mm²	Difference: -1.6mm² [-3.6, 0.32], Intercept: 2mm² [-3, 5],Slope: 0.83 [0.7, 1.0], Quadratic term: -0.01 [-0.04, 0.01], R²: 0.7469

*brief explanatory notes to help interpret the table:

Range indicates the smallest and largest true value for the measurand tested. .

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. Each metric is presented as a point estimate followed by a 95% confidence interval (CI). The CI is computed from the statistics of the observed data. It is acknowledged that wide confidence intervals make the established metric quite uncertain, and in general stem from the number of tested data points and metric specific factors.
Bias for structural measurands and plaque burden are derived from phantom experiments such that ground truth is assessed using micrometer measurements on anthropomorphic objects. Width of confidence intervals follow from the relative difficulty of each phantom geometry and typical variation experienced across clinically-accepted scanning protocols. The mean tested phantom vessel size is 8.7mm [3.9mm]. For stenosis, the mean tested vessel size of the vessels ≥5.9mm bin was 5.2mm [3.9mm], and for the vessels <5.9mm bin was 11.9mm [7.9mm, 23.9mm].
. Systematic difference from histopathology for tissue types is estimated relative to pathologist annotation of ex vivo tissue specimens with paired CTA such that ground truth is assessed based on expert interpretation that the relevant scientific and clinical community relies upon for diagnosis or other specific categorization of the studied tissue. The mean tested specimen vessel size is 7.9mm [3.6mm, 12.9mm]. The tissue specimens are from the carotid artery, and that as a result, may not account for errors due to motion that may be present in imaging of small vessels depending on the use of ECG gating. Width of confidence interval follows from:
- agreement of pathologists (three independent annotations were used for these results to O account for acknowledged discordance in histopathology interpretation),
- certainty of positioning of annotated sections into 3D radiology volume (four combinations o resulting from two unique positioners crossed with two independent radiologist users were used for these results to account for differences in judgment on where the annotated section data applies within the in vivo volume, blinded to vascuCAP results),
- relative difficulty of physiologic presentation, and O
- o typical variation experienced across clinically-accepted scanning protocols.

**important note regarding stenosis by diameter: given the reliance of stenosis by diameter as being computed from lumen diameters, and the relative difficulty of accurately estimating lumen diameter as the lumens become appreciably smaller than the finite voxel size, the stenosis may be overestimated. This issue is not unique to vascuCAP but rather a known issue for any interpretation of CTA as lumen size decreases. It is important to follow current clinical training to disregard quantitative calculations of stenosis by diameter from CTA when the lumen is not readily visualized and instead for it to be judged qualitatively. Use of such calculations as %stenosis by area, also available from vascuCAP, mitigates but does not completely avoid this issue.

See User Guide for tables of scanner makes, models, and settings used in the testing as well as patient characteristics of the tested population.

Conclusions:

Based on software verification and validation comprising bench and clinical testing under typical operating conditions, Elucid Bioimaging concludes that vascuCAP A.1.2 is as safe and effective as the predicate device for the intended use.

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).