Abstract
ObjectivesThe aim of the current study was to describe a method that assesses the hyperemic microvascular blood plasma volume of the calf musculature. The reversibly albumin binding contrast agent gadofosveset was used in dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) to assess the microvascular status in patients with peripheral arterial disease (PAD) and healthy controls. In addition, the reproducibility of this method in healthy controls was determined.Materials and MethodsTen PAD patients with intermittent claudication and 10 healthy control subjects were included. Patients underwent contrast-enhanced MR angiography of the peripheral arteries, followed by one DCE MRI examination of the musculature of the calf. Healthy control subjects were examined twice on different days to determine normative values and the interreader and interscan reproducibility of the technique. The MRI protocol comprised dynamic imaging of contrast agent wash-in under reactive hyperemia conditions of the calf musculature. Using pharmacokinetic modeling the hyperemic fractional microvascular blood plasma volume (Vp, unit: %) of the anterior tibial, gastrocnemius and soleus muscles was calculated.Results Vp was significantly lower for all muscle groups in PAD patients (4.3±1.6%, 5.0±3.3% and 6.1±3.6% for anterior tibial, gastrocnemius and soleus muscles, respectively) compared to healthy control subjects (9.1±2.0%, 8.9±1.9% and 9.3±2.1%). Differences in Vp between muscle groups were not significant. The coefficient of variation of Vp varied from 10–14% and 11–16% at interscan and interreader level, respectively.ConclusionsUsing DCE MRI after contrast-enhanced MR angiography with gadofosveset enables reproducible assessment of hyperemic fractional microvascular blood plasma volume of the calf musculature. Vp was lower in PAD patients than in healthy controls, which reflects a promising functional (hemodynamic) biomarker for the microvascular impairment of macrovascular lesions.
Highlights
Functional measurements in peripheral arterial disease (PAD) are used for diagnostic purposes and for quantifying the hemodynamic consequences of obstructive arterial lesions [1,2,3,4]
Vp was significantly lower for all muscle groups in PAD patients (4.361.6%, 5.063.3% and 6.163.6% for anterior tibial, gastrocnemius and soleus muscles, respectively) compared to healthy control subjects (9.162.0%, 8.961.9% and 9.362.1%)
Vp was lower in PAD patients than in healthy controls, which reflects a promising functional biomarker for the microvascular impairment of macrovascular lesions
Summary
Functional measurements in peripheral arterial disease (PAD) are used for diagnostic purposes and for quantifying the hemodynamic consequences of obstructive arterial lesions [1,2,3,4]. Used functional measures in DCE MRI are the rate constant (k) and the transfer constant (Ktrans), which both describe the wash-in of a contrast agent. These measures reflect a combination of the rate of microvascular reactivity and permeability, both of which may be significantly impaired in patients with PAD [14,19,22,23]. Introduced blood pool agents are largely prevented from leaking into the interstitial space by a strong, reversible albumin binding and theoretically allow a more reliable assessment of microvascular blood plasma volume with DCE MRI [27,28]
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