Copyright
©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Reproducibility of thrombus volume quantification in multicenter computed tomography pulmonary angiography studies
Audrey E Kaufman, Alison N Pruzan, Ching Hsu, Sarayu Ramachandran, Adam Jacobi, Indravadan Patel, Lee Schwocho, Michele F Mercuri, Zahi A Fayad, Venkatesh Mani
Audrey E Kaufman, Alison N Pruzan, Sarayu Ramachandran, Adam Jacobi, Indravadan Patel, Lee Schwocho, Michele F Mercuri, Zahi A Fayad, Venkatesh Mani, Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Audrey E Kaufman, Alison N Pruzan, Sarayu Ramachandran, Zahi A Fayad, Venkatesh Mani, Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York, NY 10029, United States
Ching Hsu, Indravadan Patel, Lee Schwocho, Michele F Mercuri, Daiichi Sankyo Inc., Basking Ridge, NJ 07920, United States
Author contributions: All authors designed the experiment; Kaufman AE, Pruzan AN, Ramachandran S, Mani V performed the experiment; Kaufman AE and Pruzan AN performed the image analysis; Hsu C, Pruzan AN and Mani V performed statistical analysis; Kaufman AE and Mani V wrote the draft of the manuscript; all authors critically reviewed the manuscript.
Institutional review board statement: This study was submitted to the Institutional Review Board (IRB) of the Icahn School of Medicine at Mount Sinai but was deemed that no IRB approval was necessary for conduct of this study [See Determination regarding engagement in human research letter from the program for protection of research subjects (PPHS) office IRB].
Informed consent statement: Waiver of informed consent was obtained from the Institutional Review Board as only deidentified data was used in this study. The images analyzed for this study were anonymized and devoid of any Protected Health Information.
Conflict-of-interest statement: Ching Hsu, Indravadan Patel, Lee Schwocho, Michele F Mercuri are employees of Daiichi Sankyo Inc. All other authors have no conflicts to disclose.
Data sharing statement: Once published and after appropriate safeguard to ensure that the data is devoid of any identifiers, the data used for the analysis for this study will be shared on the Mount Sinai data sharing portal according to Institutional guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Venkatesh Mani, PhD, Associate Professor, Department of Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, United States.
venkatesh.mani@mountsinai.org
Telephone: +1-212-8248454 Fax: +1-646-5379589
Received: June 1, 2018
Peer-review started: June 1, 2018
First decision: July 23, 2018
Revised: July 27, 2018
Accepted: August 4, 2018
Article in press: August 4, 2018
Published online: October 28, 2018
Processing time: 148 Days and 8.4 Hours
ARTICLE HIGHLIGHTS
Research background
In regard to clinical evaluation of pulmonary embolism (PE), clot burden is not a principal marker for clinical risk stratification, however clot burden is being used to assess for pharmaceutical characteristics in clinical drug trials in multicenter settings. To this point the technique has been studied with data obtained from a single imaging center using one fixed computed tomography pulmonary angiogram (CTPA) imaging protocol.
Research motivation
Data obtained from multicenter sites has not previously been studied. Thus, in order to validate the methods employed in multicenter clinical pharmaceutical trials of drugs such as thrombolytics, this study was commenced to assess for repeatability and consistency of clot volume measurements being obtained using semi-automated region growing techniques. Confirming the reliability of these measures has value in furthering the assessment of drug effectiveness, drug potency and in determination of optimal duration of therapy.
Research objectives
The key objective is to evaluate reproducibility of PE clot volume quantification using a semi-automated region growing algorithm on CTPA data in a multicenter setting.
Research methods
Anonymized CTPA data was acquired from 23 scanners from 18 imaging centers using each site’s standard PE protocol. Two independent analysts measured PE volumes using a semi-automated region-growing algorithm on an FDA-approved image analysis platform. Total thrombus volume was calculated per patient as the primary endpoint. Secondary endpoints were individual thrombus volume, Qanadli score and modified Qanadli score per patient. Inter- and intra-observer reproducibility were assessed using intra-class correlation coefficient (ICC) and Bland-Altman analysis. The methods employed in this study were novel in that they previously have not been used in a multicenter setting.
Research results
The results showed excellent reproducibility of inter- and intra-observer variability measurements using the semi-automated region-growing method for quantifying PE volume burden. ICC for all endpoints was greater than 0.95 for inter- and intra-observer analysis. Bland-Altman analysis indicated no significant biases. The results confirm the validity of the methods used in multicenter pharmaceutical trials thereby allowing for advancement in this field.
Research conclusions
Semi-automated region growing algorithm for quantifying PE is reproducible using data from multiple scanners and is a suitable method for image analysis in multicenter clinical trials. The utility of validating this method could affect the advancement of thrombolytic therapy and other interventions that may be used to treat PE.
Research perspectives
Computer-assisted image analysis has a growing role in both diagnostic and investigative imaging. This study solidifies the foundation of semi-automated region growing for volume quantification by proving the repeatability of the technique when used in a multicenter setting.
