Contrast-Enhanced MR Fingerprinting With Delta-Relaxometry: Investigating a New Avenue for Tumor Characterization

MRI contrast agents enhance lesion characterization by altering tissue relaxation properties. However, quantitative assessment of contrast enhancement is limited by variability in contrast administration parameters, and lack of efficient and precise contrast concentration independent relaxivity (r ₁, r ₂) measurement techniques. MR Fingerprinting (MRF) rapidly, simultaneously and accurately measures T ₁ and T ₂, enabling for the first time efficient clinical estimation of relaxivity ratios (r ₁/r ₂).

To introduce an MRF-derived delta-relaxometry method for mapping contrast-specific relaxivity ratios (r ₁/r ₂) by accurately measuring ΔR ₁/ΔR ₂. We hypothesize that delta-relaxometry ratios offer dose-independent, reproducible measures of tissue enhancement, with potential advantages over conventional contrast-enhanced MRI.

Prospective, observational.

Phantom studies and 29 patients (15 glioblastoma, 14 brain metastases).

3 T; pre- and post-contrast 3D whole-brain MR Fingerprinting.

Mathematical derivations established a relationship between ΔR ₁/ΔR ₂ and r ₁/r ₂. Phantom studies assessed the concentration-dependency of ΔR ₁/ΔR ₂ compared to ΔT ₁ and ΔT ₂. Reproducibility was assessed by the inter-subject coefficient of variation (CoV). In vivo tumor type differentiation was assessed with whole-lesion histograms.

Coefficient of variation; coefficient of determination; Mann-Whitney U tests with Benjamini-Hochberg correction.

ΔR ₁/ΔR ₂ is theoretically equivalent to r ₁/r ₂, showing contrast-dose independence in phantom studies. ΔR ₁/ΔR ₂ showed no dependence on injected dose or timing (p > 0.05), unlike ΔT ₁ and ΔT ₂. Delta-relaxometry ratios were highly reproducible, selectively elevated in tumors versus normal tissue, and showed a difference between tumor core and edema (p < 0.05). ΔR ₁/ΔR ₂ showed higher intra-subject reproducibility (median CoV: GBM = 27.3%, MET = 22.0%) as compared to ΔT ₁ (GBM = 57.1%, MET = 106.2%; p < 0.001). Whole-lesion histogram analysis of delta-relaxometry ratios demonstrated GBM versus metastasis differentiation (p < 0.05). "DATA" CONCLUSIONS: In this proof-of-concept study, MRF-derived ΔR ₁/ΔR ₂ ratios show potential for reproducible, clinically feasible, dose-independent relaxivity quantification. Delta-relaxometry ratios may offer a novel approach to tissue characterization with minimal background enhancement, distinct from perfusion imaging. Our results suggest delta-relaxometry as a tumor imaging marker worthy of further investigation.

3 (retrospective cohort study with imperfectly applied reference standard).

1 (feasibility study with quantitative assessment, requires a comparison with standard of care).