Comparative Study of Conventional MR Images With Synthetically Reconstructed MR Images of the Brain

Validation of 3D Synthetic MRI for Neuroimaging - Prospective, Multicenter, Multireader Investigation

This study is being conducted for evaluation of 3D Synthetic MRI (SyMRI 15, 3D) for neuroimaging,

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Clinical Indication for Brain MRI
• Intervention / Treatment: Device: SyMRI 15 (3D)

Detailed Description

This study is a prospective, blinded, multi-center, multi-reader clinical study that is statistically powered for demonstrating non-inferiority of synthetic 3D MR images compared to conventional MR images with respect to sensitivity and specificity of pathological findings.

The study consists of three parts:

• Clinical MR acquisition,
• Synthetic MR post-processing
• Blinded image evaluation of conventional and synthetic images for each subject.

The study will enroll eligible subjects with an already scheduled brain MRI and also healthy volunteers, that meet applicable site MR safety criteria. The routine MRI scan will include approximately 5-20 minutes extra time for the additional images to be taken. This time will be added to the length of the scheduled scan. It is only the time in the MRI scanner that will differ from standard procedures, no other examinations will be performed.

The study consists of one visit, without additional follow-up.

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Florida
    • Naples, Florida, United States, 34110
      • ProScan Imaging
    • Orlando, Florida, United States, 32827
      • Nemours Children's Health, Nemours Children's Hospital, Florida
  • Illinois
    • Chicago, Illinois, United States, 606117110
      • SimonMed imaging Streeterville
  • New York
    • New York, New York, United States, 14226
      • Dent Neurosciences Research Center
  • Washington
    • Seattle, Washington, United States, 98195
      • Diagnostic Imaging Sciences Center (DISC) University of Washington Medical Center (UWMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Any gender, aged 0-99 years
• Subject scheduled for MRI of the brain OR Healthy control with passed screening form
• Subject suitable for MRI as judged by investigator
• Subject agrees to 5-20 min extra MRI scan time
• Subject able to understand written and verbal information in English or Spanish
• Provision of informed consent (and assent if applicable)

Exclusion Criteria:

• Have contraindication(s) to MRI scanning per the routine MR Safety Screening policy of the investigational site
• Have severe trauma, disability or pre-existing pathology that is expected to interfere with normal conduct of MRI scanning or complete scanning of the brain
• Have medical condition(s) such as those requiring urgent medical care that, in the opinion of a physician investigator, would prevent safe participation in the study
• Adult subjects (aged 18-99 years) in need of anesthesia during MRI scanning
• Pregnancy at time of enrollment determined according to the clinic's MR Safety Screening policy
• Previous enrollment in this investigation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neurologic Synthetic and Conventional MRI; MR images of the brain acquired for post-processing with software (SyMRI 15, 3D). Comparison is done between the conventional MR images and the post-processed synthetic MR images	Device: SyMRI 15 (3D); Neurological MRI image collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of Pathological Findings (Full Analysis Set)	Sensitivity of pathological findings (true number of participants with pathological findings over assessed number of participants with pathological findings by reader) for synthetic and conventional MR images on the full analysis set. Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Specificity of Pathological Findings (Full Analysis Set)	Specificity of pathological findings (true number of participants with normal/no finding over assessed number of participants with normal/no finding by reader) for synthetic and conventional MR images on the full analysis set. Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Classification of Pathological Findings	Diagnostic accuracy of radiological findings (radiological finding class) for synthetic and conventional MR images on the full analysis set. Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Sensitivity (Adult Population)	Sensitivity of pathological findings (true number of participants with pathological findings over assessed number of participants with pathological findings) for synthetic and conventional MR images in adult population (18-99 years). Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Selectivity (Adult Population)	Specificity of pathological findings (true number of participants with normal/no finding over assessed number of participants with normal/no finding) for synthetic and conventional MR images on the in adult population (18-99 years). Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Classification of Pathological Findings (Adult Population)	Diagnostic accuracy of radiological findings (radiological finding class) for synthetic and conventional MR images in adult population (18-99 years). Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Sensitivity (Pediatric Population)	Sensitivity of pathological findings (true number of participants with pathological findings over assessed number of participants with pathological findings) for synthetic and conventional MR images in pediatric population (0-17 years). Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Selectivity (Pediatric Population)	Specificity of pathological findings (true number of participants with normal/no finding over assessed number of participants with normal/no finding) for synthetic and conventional MR images on the in pediatric population (0-17 years). Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Classification of Pathological Findings (Pediatric Population)	Diagnostic accuracy of radiological findings (radiological finding class) for synthetic and conventional MR images in pediatric population (0-17 years). Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The ground truth is the site-determined diagnosis.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Legibility T1w (Full Analysis Set)	Legibility of anatomical structures, per structure, on the full analysis set for T1w images. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The result for each anatomical structure per image type, independent of reading period, is summarized in corresponding row below.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Legibility T2w (Full Analysis Set)	Legibility of anatomical structures, per structure, on the full analysis set for T2w images. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The result for each anatomical structure per image type, independent of reading period, is summarized in corresponding row below.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Artifacts T1w(Full Analysis Set)	Presence and type of artifacts determined for synthetic T1w images, on the full analysis set determined by all readers. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The result for each artifact per image type, independent of reading period, is summarized in corresponding row below.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Artifacts T2w(Full Analysis Set)	Presence and type of artifacts determined for synthetic T2w images, on the full analysis set determined by all readers. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The result for each artifact per image type, independent of reading period, is summarized in corresponding row below.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Inter-rater Agreement (Full Analysis Set)	Inter-rater agreement between all reader's assessment of pathological finding, as well as radiological finding classes, on the full analysis set. Each image was evaluated only once per reader and the agreement is independent of reading session. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The agreement was assessed separately per image type over both reading periods using overall agreement, Fleiss' kappa coefficient, and Gwet's AC1 coefficient. The first reading begun after all image processing was complete.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Inter-method Agreement (Full Analysis Set)	Inter-method agreement between the different reader's assessment of pathological finding, as well as radiological finding classes, on the full analysis set. Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The agreement was evaluated for all images, independent of reading period and image type, using overall agreement, Fleiss' kappa coefficient, and Gwet's AC1 coefficient. The first reading begun after all image processing was complete.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Image Quality Score (Full Analysis Set)	Image quality score (1 (Unacceptable) - 5 (Excellent)) per contrast weighting (T1w, T2w) per both image types (conventional and synthetic) where 3,4,5 are deemed acceptable for diagnostic use and 1,2 unacceptable for diagnostic use. Each image was evaluated only once per reader. The images were split between two readings, with a wash-out period of 4 weeks in between. Both readings contained both types of images, synthetic and conventional. The first reading begun after all image processing was complete. The result presented, independent of reading period, is the averaged score per contrast weight and image type with the standard deviation.	Conventional images and necessary MRI information acquired from participant on exam day (1 day). Synthetic images generated before first reading. Analysis by readers in two readings, first reading: week 0-2, second reading: week 7-8
Safety (Full Analysis Set)	Incidence of Adverse Events (AE), Adverse Device Effects (ADE), Serious Adverse Events (SAE), Serious Adverse Device Effects (SADE), Unanticipated Adverse Device Effect (UADE), Unanticipated Serious Adverse Device Effect (USADE) and Device Deficiencies (DD). The measurement was assessed in two periods: during exam day after signing consent form (all incidents applicable) and when generating the synthetic images (only device deficiencies) after all exams were performed.	Exam day (1 day), Generation of Synthetic Images (up to 7 weeks)

Collaborators and Investigators

• Sponsor: SyntheticMR
• Investigators: Principal Investigator: Jeffrey H Miller, MD, Phoenix Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Actual): February 10, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: June 15, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: neuroimaging
• Other Study ID Numbers: CIP-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes