Deploying Novel Imaging Modalities Towards a Three-dimensional (3D) CARDIOvascular PATHology

Coronary Artery Disease Clinical Trial

— 3D-CARDIOPATH  

Official title:

Deploying Novel Imaging Modalities Towards a Three-dimensional (3D) CARDIOvascular PATHology: the 3D-CARDIOPATH Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05975567
• Other study ID #: 5039/69589
• Status: Not yet recruiting
• Start date: September 1, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: August 2023
• Source: Aristotle University Of Thessaloniki
• Contact: Andreas S Papazoglou, MD, MSc
• Phone: +306945317584
• Email: anpapazoglou[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of the 3D-CARDIOPATH study is to investigate the potential added value of emerging 3D imaging modalities by imaging ex vivo cardiac specimens (diseased coronary arteries, calcific aortic valves, and thrombotic materials) in 3D. Specifically, 20 cadaveric coronary artery segments with advanced atherosclerosis will be received from 10 patients with SCD. These segments will first be scanned with intravascular imaging modalities, namely optical coherence tomography (OCT) and intravascular ultrasound (IVUS), and then with micro-computed tomography (micro-CT) and light sheet fluorescence microscopy (LSFM). Additionally, 30 thrombotic specimens aspirated from patients with ST-elevated myocardial infarction, will also be scanned using micro-CT. Finally, 30 surgically removed aortic valves will undergo scanning with micro-CT and LSFM. Traditional histopathological assessment will also be performed on the scanned specimens. Patient laboratory profiles, past medical histories, demographic characteristics, and therapeutic management will be recorded, where applicable.

Description:

The 3D-CARDIOPATH study aims to provide 3D volumetric insights into well-characterized disease entities such as Coronary artery disease (CAD) and calcific aortic valvular disease (CAVD). Therefore, this study aims to visualize in 3D: 1. cadaveric coronary artery samples collected from adults with sudden cardiac death (SCD); 2. thrombotic specimens aspirated during percutaneous coronary intervention (PCI) procedures in patients with ST-elevated myocardial infarction (STEMI); and 3. calcific aortic valves surgically removed from patients with CAVD undergoing cardiac surgery for valve replacement. The utilized 3D imaging means will be: 1. optical coherence tomography (OCT), intravascular ultrasound (IVUS), micro-computed tomography (micro-CT) and light sheet fluorescence microscopy (LSFM) for the assessment of the collected cadaveric coronary arteries; 2. micro-CT for the assessment of the aspirated thrombotic material 3. LSFM and micro-CT for the assessment of the resected aortic valves. Finally, the scanned specimens will be histopathologically assessed at the First Department of Pathology in Athens, Greece by experienced pathologist.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: June 1, 2025
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >18 years.
• Patients with sudden cardiac death for coronary artery imaging.
• Patients with STEMI undergoing PCI and thrombus aspiration for thrombus imaging.
• Patients with CAVD undergoing cardiac replacement of calcific aortic valve for valve imaging.

Exclusion Criteria:

• Patients dying after the execution of their cardiac surgery.
• Patients with altered mental status; unable or unwilling to provide informed consent for specimen imaging and clinical follow-up.

Related Conditions & MeSH terms

• Aortic Valve Calcification
• Aortic Valve Disease
• Cardiovascular Pathology
• Coronary Artery Disease
• STEMI

Intervention

Other:
• Three-dimensional imaging of the collected cardiac specimens
The cadaveric coronary artery segments will first be scanned with intravascular imaging modalities, namely optical coherence tomography (OCT) and intravascular ultrasound (IVUS), and then with micro-computed tomography (micro-CT) and light sheet fluorescence microscopy (LSFM). The thrombotic specimens aspirated from patients with ST-elevated myocardial infarction, will also be scanned using micro-CT. The surgically removed aortic valves will undergo scanning with micro-CT and LSFM. Traditional histopathological assessment will also be performed on the scanned specimens.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	National and Kapodistrian University of Athens, University of Southampton

References & Publications (4)

Karagiannidis E, Papazoglou AS, Sofidis G, Chatzinikolaou E, Keklikoglou K, Panteris E, Kartas A, Stalikas N, Zegkos T, Girtovitis F, Moysidis DV, Stefanopoulos L, Koupidis K, Hadjimiltiades S, Giannakoulas G, Arvanitidis C, Michaelson JS, Karvounis H, Sianos G. Micro-CT-Based Quantification of Extracted Thrombus Burden Characteristics and Association With Angiographic Outcomes in Patients With ST-Elevation Myocardial Infarction: The QUEST-STEMI Study. Front Cardiovasc Med. 2021 Apr 21;8:646064. doi: 10.3389/fcvm.2021.646064. eCollection 2021. — View Citation

Karagiannidis E, Papazoglou AS, Stalikas N, Deda O, Panteris E, Begou O, Sofidis G, Moysidis DV, Kartas A, Chatzinikolaou E, Keklikoglou K, Bompoti A, Gika H, Theodoridis G, Sianos G. Serum Ceramides as Prognostic Biomarkers of Large Thrombus Burden in Patients with STEMI: A Micro-Computed Tomography Study. J Pers Med. 2021 Jan 31;11(2):89. doi: 10.3390/jpm11020089. — View Citation

Papazoglou AS, Karagiannidis E, Liatsos A, Bompoti A, Moysidis DV, Arvanitidis C, Tsolaki F, Tsagkaropoulos S, Theocharis S, Tagarakis G, Michaelson JS, Herrmann MD. Volumetric Tissue Imaging of Surgical Tissue Specimens Using Micro-Computed Tomography: An Emerging Digital Pathology Modality for Nondestructive, Slide-Free Microscopy-Clinical Applications of Digital Pathology in 3 Dimensions. Am J Clin Pathol. 2023 Mar 13;159(3):242-254. doi: 10.1093/ajcp/aqac143. Erratum In: Am J Clin Pathol. 2023 Jan 28;: — View Citation

Papazoglou AS, Karagiannidis E, Moysidis DV, Sofidis G, Bompoti A, Stalikas N, Panteris E, Arvanitidis C, Herrmann MD, Michaelson JS, Sianos G. Current clinical applications and potential perspective of micro-computed tomography in cardiovascular imaging: A systematic scoping review. Hellenic J Cardiol. 2021 Nov-Dec;62(6):399-407. doi: 10.1016/j.hjc.2021.04.006. Epub 2021 May 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-destructive nature of the deployed imaging modalities (Number of specimens with scanning-induced alterations)	The primary study outcome is to demonstrate the feasibility of ex vivo imaging of the collected cardiac specimens. Specifically, OCT, IVUS, LSFM and micro-CT will be used to scan cadaveric coronary arteries and the researchers will investigate that they can non-destructively image those specimens. Micro-CT will also be used for thrombotic material assessment and aortic valve imaging. Post-scanning histopathological assessment will be performed to confirm the non-destructiveness of the deployed imaging modalities and identify any radiation-induced or ischemic alterations within the scanned specimens.	2 years
Primary	Successful 3D visualization of the scanned specimens (generation of 3D datasets)	Co-primary study aim is to successfully scan all the collected specimens and produce 3D projections of the scanned specimens (i.e., 3D datasets).	2 years
Secondary	Micro-CT based quantification of the density (IU) within the scanned specimens	Quantitative density-related information will be received from micro-CT scanning of the 1) atherosclerotic plaques within the cadaveric coronary artery segments; 2) aspirated thrombotic samples; and 3) resected aortic valves (the measured density will represent the calcification).	2 years
Secondary	Micro-CT based volumetric quantification (mm3) of the scanned specimens	Quantitative volumetric information can be received from micro-CT scanning of the 1) atherosclerotic plaque volume within the cadaveric coronary artery segments; 2) aspirated thrombotic volume; and 3) resected aortic valve volume.	2 years
Secondary	Correlation of the derived images with histopathological data and visualization of regions of interest	The derived scans will be co-registered with the digital images (sections) generated by the histopathological assessment. IVUS, OCT, micro-CT and LSFM images will be matched to histopathological images (with immunohistochemistry and immunofluorescence analyses also performed). This might enable the identification of regions of interest (ROI) within the artery segments (intima, lipid-rich plaques and thrombi), the thrombotic specimens (red/white thrombus, WBC, platelets, hemosiderin) and the aortic valves (valvular cusps, amyloid, collagen and elastic fibers, valve annulus, leaflet and rest anatomic components).	2 years
Secondary	Between-modality comparison of the image resolution achieved	Minimum voxel size and maximum resolution will be recorded and compared among the different imaging modalities, where applicable.	2 years
Secondary	Between-modality comparison of the time required for image acquisition	Scanning and post-scanning reconstruction time will be recorded and compared among the different imaging modalities, where applicable.	2 years
Secondary	IVUS-based quantification of areas of interest (mm2) within the scanned cadaveric arteries	Specific measurements of coronary areas of interest (Minimum lumen area, Lumen area stenosis, and Plaque area) will be derived from IVUS scanning of the cadaveric coronary artery segments.	2 years
Secondary	IVUS-based quantification of diameters of interest (mm) within the scanned cadaveric arteries	Specific measurements of diameters of interest (Minimum lumen diameter, largest reference lumen diameter and distance from the distal to proximal reference site) will be derived from IVUS scanning of the cadaveric coronary artery segments.	2 years
Secondary	IVUS-based determination of plaque characteristics within the scanned cadaveric arteries	Specific plaque characteristics will be determined (Plaque burden and Plaque type: Thick-cap fibroatheroma, Fibrotic plaque or Fibrocalcific plaque) through IVUS scanning of the cadaveric coronary artery segments.	2 years
Secondary	IVUS-based determination of thrombotic characteristics within the scanned cadaveric arteries	If any thrombi are identified within the cadaveric coronary artery segments through IVUS scanning, thrombus characteristics will be determined according to the existing classification: 1) Acute thrombus (having an acoustic in-homogenous bright 'spontaneous contrast' appearance with sharp delineation and no clear signal attenuation), 2) Subacute thrombus (having a more homogeneous acoustic appearance and thus appearing darker), and 3) Organized thrombus (being the most acoustic homogeneous type of thrombus).	2 years
Secondary	IVUS-based quantification of the thrombus score within the scanned cadaveric arteries	The thrombus score (derived from the SPECTRUM trial) will be calculated with IVUS scanning of the cadaveric coronary artery segments: 1-point adjudication for a total thrombus length >14.5 mm, 1-point for occlusive thrombus length >1.5 mm and 1-point for maximum thrombus angle 260°; this will be summarized as low (0-1 points) and high (2-3 points) thrombus burden.	2 years
Secondary	OCT-based quantification of the assessed pathologies within the scanned cadaveric arteries	Specific measurements will be derived from OCT (attenuation coefficients for intimal tissue, lipid-rich tissue and thrombus) after scanning the cadaveric coronary artery segments.	2 years
Secondary	LSFM-based quantification of the full-width half-maximum (FWHM) within the scanned cadaveric arteries	The FWHM of the light-sheet thickness will be calculated in the Z- and -Y directions, after scanning the cadaveric coronary artery segments.	2 years
Secondary	LSFM-based quantification of the confocal parameter within the scanned cadaveric arteries	The confocal parameter will be calculated from LSFM scanning of the cadaveric coronary artery segments.	2 years