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MicroCT and Histological Analysis of Clot Composition in Acute Ischemic Stroke

A Comparative Study of MT-Retrieved Clots and Clot Analogs

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Abstract

Purpose

Assessing clot composition on prethrombectomy computed tomography (CT) imaging may help in stroke treatment planning. In this study we seek to use microCT imaging of fabricated blood clots to understand the relationship between CT radiographic signals and the biological makeup.

Methods

Clots (n = 10) retrieved by mechanical thrombectomy (MT) were collected, and 6 clot analogs of varying RBC composition were made. We performed paired microCT and histological image analysis of all 16 clots using a ScanCo microCT 100 (4.9 µm resolution) and standard H&E staining (imaged at 40×). From these data types, first order statistic (FOS) radiomics were computed from microCT, and percent composition of RBCs (%RBC) was computed from histology. Polynomial and linear regression (LR) were used to build statistical models based on retrieved thrombus microCT and %RBC that were evaluated for their ability to predict the %RBC of clot analogs from mean HU. Correlation analyses of microCT FOS with composition were completed for both retrieved clots and analogs.

Results

The LR model fits relating MT-retrieved clot %RBC with mean (R2 = 0.625, p = 0.006) and standard deviation (R2 = 0.564, p < 0.05) in HUs on microCT were significant. Similarly, LR models relating analog histological %RBC to analog protocol %RBC (R2 = 0.915, p = 0.003) and mean HUs on microCT (R2 = 0.872, p = 0.007) were also significant. When the LR model built using MT-retrieved clots was used to predict analog %RBC from mean HUs, significant correlation was observed between predictions and actual histological %RBC (R2 = 0.852, p = 0.009). For retrieved clots, significant correlations were observed for energy and total energy with %RBC and %FP (|R| > 0.7, q < 0.01). Analogs further demonstrated significant correlation between FOS energy, total energy, variance and %WBC (|R| > 0.9, q < 0.01).

Conclusion

MicroCT can be used to build models that predict AIS clot composition from routine CT parameters and help us to better understand radiomic signatures associated with clot composition and first pass outcomes. In future work, such observations can be used to better infer clot composition and inform thrombectomy prognostics from pretreatment CTs.

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Acknowledgements

The authors would like to acknowledge Jay Shah for assistance in clot fabrication. Histology data in this study was generated with the assistance of the Histology Core Laboratory at the University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences. MicroCT data were acquired at the University of Buffalo’s Optical Imaging and Analysis Facility.

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Authors and Affiliations

  1. Canon Stroke and Vascular Research Center, University at Buffalo, 875 Ellicott Street, 14203, Buffalo, NY, USA

    Briana A. Santo, TaJania D. Jenkins, Shiau-Sing K. Ciecierska, Ammad A. Baig, Elad I. Levy, Adnan H. Siddiqui & Vincent M. Tutino

  2. Department of Pathology and Anatomical Sciences, University at Buffalo, Buffalo, NY, USA

    Briana A. Santo, TaJania D. Jenkins & Vincent M. Tutino

  3. Department of Neurosurgery, University at Buffalo, Buffalo, NY, USA

    Ammad A. Baig, Elad I. Levy, Adnan H. Siddiqui & Vincent M. Tutino

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  1. Briana A. Santo
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Correspondence to Vincent M. Tutino.

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Conflict of interest

B.A. Santo, T.D. Jenkins, S.-S.K. Ciecierska and A.A. Baig declare that they have no competing interests. E.I. Levy—Board Membership: Stryker, NeXtGen Biologics, MedX Health, Cognition Medical, EndoStream; Consultancy: Claret Medical, GLG Consulting, Guidepoint, Imperative Care, Medtronic, Rebound Therapeutics, StimMed; Employment: University at Buffalo Neurosurgery Inc; Expert Testimony: renders medical/legal opinions as an expert witness; Stock/Stock Options: NeXtGen Biologics, Cognition Medical, Rapid Medical, Claret Medical, Imperative Care, Rebound Therapeutics, StimMed. A.H. Siddiqui—Financial interest/investor/stock options/ownership: Adona Medical, Inc., Amnis Therapeutics, BlinkTBI, Inc., Boston Scientific Corp. (for purchase of Claret Medical), Buffalo Technology Partners, Inc., Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc., Cognition Medical, Endostream Medical, Ltd, Imperative Care, Inc., International Medical Distribution Partners, Neurovascular Diagnostics, Inc., Q’Apel Medical, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (purchased 2019 by Integra Lifesciences, Corp.), Rist Neurovascular, Inc., Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, Spinnaker Medical, Inc., StimMed, Synchron, Three Rivers Medical, Inc., Vastrax, LLC, VICIS, Inc., Viseon, Inc.; consultant/advisory board: Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Inc., Cerebrotech Medical Systems, Inc., Cerenovus, Corindus, Inc., Endostream Medical, Ltd, Imperative Care, Inc., Integra LifeSciences Corp., Medtronic, MicroVention, Minnetronix Neuro, Inc., Northwest University—DSMB Chair for HEAT Trial, Penumbra, Q’Apel Medical, Inc., Rapid Medical, Rebound Therapeutics Corp., Serenity Medical, Inc., Silk Road Medical, StimMed, Stryker, Three Rivers Medical, Inc., VasSol, W.L. Gore & Associates; national PI/steering committees: Cerenovus LARGE trial and ARISE II trial, Medtronic SWIFT PRIME and SWIFT DIRECT trials, MicroVention FRED Trial and CONFIDENCE study, MUSC POSITIVE trial, Penumbra 3D Separator trial, COMPASS trial, INVEST trial; research grants: co-investigator, NIH/NINDS 1R01NS091075 Virtual Intervention of Intracranial Aneurysms; role: co-principal investigator, NIH-NINDS R21 NS109575-01 Optimizing Approaches to Endovascular Therapy of Acute Ischemic Stroke. V.M. Tutino—Financial interest/investor/stock options/ownership: Neurovascular Diagnostics, Inc., QAS.AI, Inc.; Consultant/advisory board: Canon Medical Systems USA; Research grants: Principal investigator, National Science Foundation Award No. 1746694 and NIH NINDS award R43 NS115314‑0; awardee of a Brain Aneurysm Foundation grant, a Center for Advanced Technology grant, and a Cummings Foundation grant.

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The authors Briana A. Santo and TaJania D. Jenkins contributed equally to the manuscript.

Supplementary Information

62_2023_1380_MOESM1_ESM.pdf

Supplemental Table 1: Percent Compositions of All Retrieved Clots. Supplemental Table 2: Summary of radiomic feature and histological composition correlations for retrieved clots and synthetic clot analogs.  Supplemental Figure 1: Iodine-stained and unstained thrombi were qualitatively and quantitatively comparable by histology. Supplemental Figure 2: Summary of thrombectomy outcome and clot image data for the patient cohort. Supplemental Figure 3: Clot analog histological compositions reflected RBC proportions used in the experimental protocol

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Santo, B.A., Jenkins, T.D., Ciecierska, SS.K. et al. MicroCT and Histological Analysis of Clot Composition in Acute Ischemic Stroke. Clin Neuroradiol (2024). https://doi.org/10.1007/s00062-023-01380-1

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