Histologic Validation of Quantitative Magnetic Resonance Relaxation Time Biomarkers for Thrombus Chronicity: A...

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 relaxation times correlate with histologic thrombus composition and remodeling in freshly retrieved ex vivo human venous thrombi.

Fourteen fresh human venous thrombi retrieved during clinical intervention were imaged ex vivo at 9.4T before formalin fixation. T1 relaxation times were measured using rapid acquisition with relaxation enhancement, T2 using multi-slice multi-echo imaging, and T2* using multi-gradient echo imaging. Digitized histology slides were analyzed with pixel-thresholding to quantify red blood cell, fibrin/platelet, and collagen/extracellular matrix 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.

Of 14 patients, 11 thrombi were retrieved within 14 days of symptom onset or presentation, while 3 had longer intervals of 36, 73, and 104 days. Mean patient age was 58.9 ± 13.6 years, and mean BMI 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 = 0.00792) and T2* (r = -0.676, p = 0.0194), but not with T1 (r = +0.330, p = 0.249). T1 showed a strong inverse correlation with red blood cell content (r = -0.765, p = 0.00143). Histologic composition was heterogeneous, with red blood cell content ranging from 1% to 89%, fibrin/platelet content from 10% to 65%, and collagen/extracellular matrix content from 0% to 89%. Thrombi ≥14 days had lower T2 values than thrombi <14 days (58.5 ms vs 83.4 ms, p = 0.0360). Fibrotic thrombi had higher collagen/extracellular matrix content (39.0% vs 0.0%, p = 0.00078), were older (25 vs 4 days, p = 0.0111), had lower red blood cell content (17.3% vs 64.0%, p = 0.0166), and showed higher organization scores (3.0 vs 0.5, p = 0.00453).

Quantitative MRI relaxation times reflect distinct thrombus phenotypes. T1 primarily captures red blood cell-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.