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Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Pharmacokinetic Modeling: Initial Experience in Patients
Karen I Maijer1, Christiaan van der Leij1, Maria J H de Hair1
1Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Objective:
Analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using pharmacokinetic modeling (PKM) provides quantitative measures that mirror microvessel integrity and can be used as an objective marker of the level of synovial inflammation. The aim of this study was to investigate the PKM parameters K(trans) , kep , and ve in a prospective cohort of disease-modifying antirheumatic drug (DMARD)-naive patients with early arthritis, and to validate the results by assessing their correlation with the number of synovial endothelial cells (ECs).
Methods:
Forty-seven patients with early arthritis (arthritis duration <1 year, DMARD naive; comprising 14 patients with rheumatoid arthritis, 22 with unclassified arthritis, 6 with spondyloarthritis [SpA], and 5 with other arthritides) were included. At baseline, DCE-MRI was performed on an inflamed knee joint of each patient. These images were used to calculate the K(trans) (volume transfer constant between the plasma and extracellular extravascular space [EES]), the kep (transfer constant between the EES and plasma), and the ve (fractional volume of the EES). Second, markers of disease activity were collected. Finally, vascularity was evaluated by immunohistochemical analysis of synovial tissue samples obtained from the inflamed knee joints, using antibodies to detect von Willebrand factor (vWF), a marker of ECs.
Results:
The 3 PKM parameters differed significantly between diagnostic groups at baseline, with the highest K(trans) value being observed in patients with SpA (median 0.050/minute, interquartile range [IQR] 0.041- 0.069). Furthermore, the K(trans) , kep , and ve values correlated significantly with markers of disease activity. Finally, the PKM parameters K(trans) and kep , but not ve , correlated significantly with synovial expression of vWF (r = 0.647, P = 0.004 for K(trans) ; r = 0.614, P = 0.007 for kep ; r = 0.398, P = 0.102 for ve ).
Conclusion:
These results suggest that the K(trans) , kep , and ve can be used to detect synovial inflammation in patients with early arthritis, and these PKM parameters may be helpful in differential diagnosis. This approach may also be useful in translational research analyzing tissue microcirculation and angiogenesis.
Insights
Dynamic contrast-enhanced MRI (DCE-MRI) pharmacokinetic modeling (PKM) parameters accurately detect synovial inflammation in early arthritis. These measures correlate with disease activity and endothelial cell markers, aiding differential diagnosis.
Area of Science:
- Rheumatology and Medical Imaging
- Quantitative analysis of joint inflammation
Background:
- Synovial inflammation is a key feature of early arthritis.
- Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with pharmacokinetic modeling (PKM) offers quantitative insights into microvessel integrity.
- PKM parameters can serve as objective markers for assessing synovial inflammation levels.
Purpose of the Study:
- To investigate PKM parameters Ktrans, kep, and ve in DMARD-naive early arthritis patients.
- To validate PKM findings by correlating them with synovial endothelial cell counts.
- To explore the utility of PKM in differential diagnosis of early arthritis.
Main Methods:
- Prospective cohort study of 47 DMARD-naive early arthritis patients (arthritis duration <1 year).
- DCE-MRI performed on inflamed knee joints to calculate Ktrans, kep, and ve.
- Immunohistochemical analysis of synovial tissue for von Willebrand factor (vWF) as an endothelial cell marker.
Main Results:
- Significant differences in PKM parameters (Ktrans, kep, ve) were observed across diagnostic groups.
- Ktrans, kep, and ve values showed significant correlations with disease activity markers.
- Ktrans and kep correlated significantly with synovial vWF expression, indicating microvascular changes.
Conclusions:
- PKM parameters (Ktrans, kep, ve) effectively detect synovial inflammation in early arthritis.
- These PKM parameters show potential for differential diagnosis in early arthritis.
- The DCE-MRI PKM approach is valuable for translational research on tissue microcirculation and angiogenesis.
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