Histologic validation of quantitative magnetic resonance relaxation time biomarkers for thrombus chronicity: A feasibility study
6 affiliations
- 1DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX
- 2Heart and Vascular Center, Semmelweis University, Budapest, Hungary
- 3School of Engineering Medicine, Texas A&M School of Engineering Medicine, Houston, TX
- 4University of Birmingham, Birmingham, UK
- 5Department of Cardiovascular Pathology Research, Texas Heart Institute/Baylor College of Medicine, Houston, TX
- 6Translational Imaging Center, Houston Methodist Research Institute, Houston, TX
Abstract
Background: Medical anticoagulation remains the standard treatment for venous thromboembolism, but mechanical thrombectomy is increasingly used in selected patients. Patient selection remains limited because thrombus age, composition, organization, and fibrosis are difficult to determine before intervention. To evaluate whether quantitative magnetic resonance imaging (MRI) relaxation times correlate with histologic thrombus composition and remodeling in freshly retrieved ex vivo human venous thrombi.
Methods: Fourteen fresh human venous thrombi retrieved during clinical intervention were imaged ex vivo at 9.4 T before formalin fixation. T1 relaxation times were measured using rapid acquisition with relaxation enhancement, T2 using multislice multiecho imaging, and T2∗ using multigradient echo imaging. Digitized histology slides were analyzed with pixel-thresholding to quantify red blood cell (RBC), fibrin/platelet, and collagen/extracellular matrix (ECM) content. Fibrosis and organization were scored semiquantitatively. Associations between clinical thrombus age, MRI relaxation times, and histologic parameters were assessed using Spearman correlations and Mann-Whitney U tests.
Results: Of 14 patients, 11 thrombi were retrieved within 14 days of symptom onset or presentation, whereas three had longer intervals of 36, 73, and 104 days. Mean patient age was 58.9 ± 13.6 years, and mean body mass index was 31.0 ± 5.3 kg/m2. Median relaxation times were 1719.2 ms for T1, 81.1 ms for T2, and 9.48 ms for T2∗. Increasing thrombus age correlated with shorter T2 (r = −0.676; P = .00792) and T2∗ (r = −0.676; P = .0194), but not with T1 (r = +0.330; P = .249). T1 showed a strong inverse correlation with RBC content (r = −0.765; P = .00143). Histologic composition was heterogeneous, with RBC content ranging from 1% to 89%, fibrin/platelet content from 10% to 65%, and collagen/ECM content from 0% to 89%. Thrombi ≥14 days had lower T2 values than thrombi <14 days (58.5 vs 83.4 ms; P = .0360). Fibrotic thrombi had higher collagen/ECM content (39.0% vs 0.0%; P = .00078), were older (25 vs 4 days; P = .0111), had lower RBC content (17.3% vs 64.0%; P = .0166), and showed higher organization scores (3.0 vs 0.5; P = .00453).
Conclusions: Quantitative MRI relaxation times reflect distinct thrombus phenotypes. T1 primarily captures RBC-rich composition, whereas T2 and T2∗ reflect thrombus age, organization, and fibrotic remodeling. This histology-validated ex vivo high-field-strength framework may provide a basis for prospective validation at clinically available lower field strengths, with the ultimate goal of evaluating MRI-based patient selection for venous thrombectomy.
Clinical relevance: Patient selection for venous intervention remains challenging because symptom duration is an imprecise surrogate for thrombus biology. In clinical practice, thrombi with similar reported age may differ substantially in red blood cell content, collagen deposition, fibrosis, and organization, factors that are likely relevant to mechanical behavior and treatment response. In this feasibility study, quantitative magnetic resonance relaxation times measured in freshly retrieved human venous thrombi were histologically validated against thrombus composition and remodeling. T1 was most strongly associated with red blood cell-rich thrombus composition, whereas T2 and T2∗ were more closely associated with thrombus age, collagen/extracellular matrix deposition, fibrosis, and organization. These findings support quantitative magnetic resonance relaxometry as a candidate biomarker-based approach to thrombus chronicity and phenotype, with potential future value for improving preprocedural characterization of thrombi before thrombectomy or thrombolysis. Although this work was performed ex vivo at 9.4 T, it establishes biologic feasibility and a translational framework for subsequent validation at lower clinical field strengths, with the long-term goal of bringing thrombus phenotyping closer to a more precise clinical decision-making.
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BibTeX
@article{pomozi2026histologic,
title = {{Histologic validation of quantitative magnetic resonance relaxation time biomarkers for thrombus chronicity: A feasibility study}},
author = {Eniko Pomozi and Caroline Jordan and Alexander Crichton and Judit Csore and Deborah Vela and Christof Karmonik and Trisha Roy},
journal = {Journal of Vascular Surgery: Venous and Lymphatic Disorders},
year = {2026},
month = sep,
doi = {10.1016/j.jvsv.2026.102620},
url = {https://doi.org/10.1016/j.jvsv.2026.102620},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Histologic validation of quantitative magnetic resonance relaxation time biomarkers for thrombus chronicity: A feasibility study
AU - Eniko Pomozi
AU - Caroline Jordan
AU - Alexander Crichton
AU - Judit Csore
AU - Deborah Vela
AU - Christof Karmonik
AU - Trisha Roy
PY - 2026
DA - 2026/09/16
JO - Journal of Vascular Surgery: Venous and Lymphatic Disorders
DO - 10.1016/j.jvsv.2026.102620
UR - https://doi.org/10.1016/j.jvsv.2026.102620
AB - Background: Medical anticoagulation remains the standard treatment for venous thromboembolism, but mechanical thrombectomy is increasingly used in selected patients. Patient selection remains limited because thrombus age, composition, organization, and fibrosis are difficult to determine before intervention. To evaluate whether quantitative magnetic resonance imaging (MRI) relaxation times correlate with histologic thrombus composition and remodeling in freshly retrieved ex vivo human venous thrombi. Methods: Fourteen fresh human venous thrombi retrieved during clinical intervention were imaged ex vivo at 9.4 T before formalin fixation. T1 relaxation times were measured using rapid acquisition with relaxation enhancement, T2 using multislice multiecho imaging, and T2∗ using multigradient echo imaging. Digitized histology slides were analyzed with pixel-thresholding to quantify red blood cell (RBC), fibrin/platelet, and collagen/extracellular matrix (ECM) content. Fibrosis and organization were scored semiquantitatively. Associations between clinical thrombus age, MRI relaxation times, and histologic parameters were assessed using Spearman correlations and Mann-Whitney U tests. Results: Of 14 patients, 11 thrombi were retrieved within 14 days of symptom onset or presentation, whereas three had longer intervals of 36, 73, and 104 days. Mean patient age was 58.9 ± 13.6 years, and mean body mass index was 31.0 ± 5.3 kg/m2. Median relaxation times were 1719.2 ms for T1, 81.1 ms for T2, and 9.48 ms for T2∗. Increasing thrombus age correlated with shorter T2 (r = −0.676; P = .00792) and T2∗ (r = −0.676; P = .0194), but not with T1 (r = +0.330; P = .249). T1 showed a strong inverse correlation with RBC content (r = −0.765; P = .00143). Histologic composition was heterogeneous, with RBC content ranging from 1% to 89%, fibrin/platelet content from 10% to 65%, and collagen/ECM content from 0% to 89%. Thrombi ≥14 days had lower T2 values than thrombi <14 days (58.5 vs 83.4 ms; P = .0360). Fibrotic thrombi had higher collagen/ECM content (39.0% vs 0.0%; P = .00078), were older (25 vs 4 days; P = .0111), had lower RBC content (17.3% vs 64.0%; P = .0166), and showed higher organization scores (3.0 vs 0.5; P = .00453). Conclusions: Quantitative MRI relaxation times reflect distinct thrombus phenotypes. T1 primarily captures RBC-rich composition, whereas T2 and T2∗ reflect thrombus age, organization, and fibrotic remodeling. This histology-validated ex vivo high-field-strength framework may provide a basis for prospective validation at clinically available lower field strengths, with the ultimate goal of evaluating MRI-based patient selection for venous thrombectomy. Clinical relevance: Patient selection for venous intervention remains challenging because symptom duration is an imprecise surrogate for thrombus biology. In clinical practice, thrombi with similar reported age may differ substantially in red blood cell content, collagen deposition, fibrosis, and organization, factors that are likely relevant to mechanical behavior and treatment response. In this feasibility study, quantitative magnetic resonance relaxation times measured in freshly retrieved human venous thrombi were histologically validated against thrombus composition and remodeling. T1 was most strongly associated with red blood cell-rich thrombus composition, whereas T2 and T2∗ were more closely associated with thrombus age, collagen/extracellular matrix deposition, fibrosis, and organization. These findings support quantitative magnetic resonance relaxometry as a candidate biomarker-based approach to thrombus chronicity and phenotype, with potential future value for improving preprocedural characterization of thrombi before thrombectomy or thrombolysis. Although this work was performed ex vivo at 9.4 T, it establishes biologic feasibility and a translational framework for subsequent validation at lower clinical field strengths, with the long-term goal of bringing thrombus phenotyping closer to a more precise clinical decision-making.
SN - 2213-333X
SN - 2213-3348
ER -