Contrast-Enhanced Magnetic Resonance Imaging Based T1 Mapping and Extracellular Volume Fractions Are Associated with Peripheral Artery Disease.

BACKGROUND: Extracellular volume fraction (ECV), measured with contrast-enhanced magnetic resonance imaging (CE-MRI), has been utilized to study myocardial fibrosis, but its role in peripheral artery disease (PAD) remains unknown. We hypothesized that T1 mapping and ECV differ between PAD patients and matched controls. METHODS AND RESULTS: A total of 37 individuals (18 PAD patients and 19 matched controls) underwent 3.0T CE-MRI. Skeletal calf muscle T1 mapping was performed before and after gadolinium contrast with a motion-corrected modified look-locker inversion recovery (MOLLI) pulse sequence. T1 values were calculated with a three-parameter Levenberg-Marquardt curve fitting algorithm. ECV and T1 maps were quantified in five calf muscle compartments (anterior [AM], lateral [LM], and deep posterior [DM] muscle groups; soleus [SM] and gastrocnemius [GM] muscles). Averaged peak blood pool T1 values were obtained from the posterior and anterior tibialis and peroneal arteries. T1 values and ECV are heterogeneous across calf muscle compartments. Native peak T1 values of the AM, LM, and DM were significantly higher in PAD patients compared to controls (all p < 0.028). ECVs of the AM and SM were significantly higher in PAD patients compared to controls (AM: 26.4% (21.2, 31.6) vs. 17.3% (10.2, 25.1), p = 0.046; SM: 22.7% (19.5, 27.8) vs. 13.8% (10.2, 19.1), p = 0.020). CONCLUSIONS: Native peak T1 values across all five calf muscle compartments, and ECV fractions of the anterior muscle group and the soleus muscle were significantly elevated in PAD patients compared with matched controls. Non-invasive T1 mapping and ECV quantification may be of interest for the study of PAD.

Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling to Assess Peripheral Artery Disease.

Background Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). Methods and Results The computational microvascular model was used to study skeletal calf muscle perfusion in 56 individuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer rate constant, a measure of vascular leakiness; the interstitial permeability to fluid flow which reflects the permeability of the microvasculature; porosity, a measure of the fraction of the extracellular space; the outflow filtration coefficient; and the microvascular pressure with known markers of patients with PAD. Transfer rate constant, interstitial permeability to fluid flow, and microvascular pressure were higher, whereas porosity and outflow filtration coefficient were lower in patients with PAD than those in matched controls (all P values ≤0.014). In pooled analyses of all participants, the model parameters (transfer rate constant, interstitial permeability to fluid flow, porosity, outflow filtration coefficient, microvascular pressure) were significantly associated with the resting and exercise ankle-brachial indexes, claudication onset time, and peak walking time (all P values ≤0.013). Among patients with PAD, interstitial permeability to fluid flow, and microvascular pressure were higher, while porosity and outflow filtration coefficient were lower in treadmill noncompleters compared with treadmill completers (all P values ≤0.001). Conclusions Computational microvascular model parameters differed significantly between patients with PAD and matched controls. Thus, computational microvascular modeling could be of interest in studying lower extremity ischemia.

Comparison of Longitudinal Skeletal Thigh Muscle Findings With Magnetic Resonance Imaging in Patients With Peripheral Artery Disease With-Versus-Without Diabetes Mellitus.

The aim of this secondary analysis of ELIMIT (The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial) was to determine longitudinal changes over 24 months in skeletal thigh muscle volumes and individual muscle compartments in patients with peripheral artery disease (PAD) with and without diabetes. A total of 48 patients with available magnetic resonance imaging of the distal superficial femoral artery at baseline and 2 years were included in this analysis. Muscle volumes and superficial femoral artery wall, lumen, and total vessel volumes were quantified. Intrareader reproducibility of muscle tracings was assessed with the intraclass correlation coefficient using a 2-way model. Baseline characteristics were similar between patients with PAD with and without diabetes, except for smoking history (p = 0.049), cholesterol levels (p <0.050), and calf walking pain (p = 0.049). Interobserver reproducibility of the muscle volume tracings was excellent for all muscle groups (all intraclass correlation coefficients >0.86, confidence interval 0.69 to 0.94). Total muscle and total leg volumes increased significantly between baseline and 24 months among patients with PAD without diabetes (31 ± 6.4 cm3 vs 32 ± 7.0 cm3, p <0.001; 18 ± 4.4 cm3 vs 19 ± 4.8 cm3, p = 0.045), whereas there was no change in patients with PAD and diabetes. Total muscle volume was inversely associated with age and body mass index in patients with PAD both with and without diabetes (p <0.05). In conclusion, magnetic resonance imaging-quantified thigh muscle volumes are highly reproducible and may be of interest in assessing PAD patients with and without diabetes.

Imaging Approaches to the Diagnosis of Vascular Diseases.

PURPOSE OF REVIEW: Vascular imaging is a complex field including numerous modalities and imaging markers. This review is focused on important and recent findings in atherosclerotic carotid artery plaque imaging with an emphasis on developments in magnetic resonance imaging (MRI) and computed tomography (CT). RECENT FINDINGS: Recent evidence shows that carotid plaque characteristics and not only established measures of carotid plaque burden and stenosis are associated independently with cardiovascular outcomes. On carotid MRI, the presence of a lipid-rich necrotic core (LRNC) has been associated with incident cardiovascular disease (CVD) events independent of wall thickness, a traditional measure of plaque burden. On carotid MRI, intraplaque hemorrhage (IPH) presence has been identified as an independent predictor of stroke. The presence of a fissured carotid fibrous cap has been associated with contrast enhancement on CT angiography imaging. Carotid artery plaque characteristics have been associated with incident CVD events, and advanced plaque imaging techniques may gain additional prominence in the clinical treatment decision process.

Relation of Magnetic Resonance Imaging Based Arterial Signal Enhancement to Markers of Peripheral Artery Disease.

Peripheral artery disease (PAD) is associated with impaired lower extremity function. We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) based arterial signal enhancement (SE) measures are associated with markers of PAD. A total of 66 participants were enrolled, 10 were excluded due to incomplete data, resulting in 56 participants for the final analyses (36 PAD, 20 matched controls). MR imaging was performed postreactive hyperemia using bilateral thigh blood-pressure cuffs. First pass-perfusion images were acquired at the mid-calf region with a high-resolution saturation recovery gradient echo pulse sequence, and arterial SE was measured for the lower extremity arteries. As expected, peak walking time (PWT) was reduced in PAD patients compared with controls (282 [248 to 317] sec, vs 353 [346 to 360] sec; p = 0.002), and postexercise ankle brachial index (ABI) decreased in PAD patients but not in controls (PAD: 0.75 ± 0.2, 0.60 [0.5 to 0.7]; p <0.001; vs Controls: 1.17 ± 0.1, 1.19 [1.1 to 1.2]; p = 0.50). Intraclass correlation coefficients were excellent for inter- and intraobserver variability of arterial tracings (n = 10: 0.95 (95%-confidence interval [CI]: 0.94 to 0.96), n = 9: 1.0 (CI: 1.0 to 1.0). Minimum arterial SE was reduced in PAD patients compared with matched controls (128 [110 to 147] A.U. vs 192 [149 to 234] A.U., p = 0.003). Among PAD patients but not in controls the maximum arterial SE was associated with the estimated glomerular filtration rate (eGFR), a marker of renal function (n = 36, ß = 1.37, R2 = 0.12, p = 0.025). In conclusion, CE-MRI first-pass arterial perfusion is impaired in PAD patients compared with matched controls and associated with markers of lower extremity ischemia.

Magnetic resonance imaging based modeling of microvascular perfusion in patients with peripheral artery disease.

Peripheral artery disease (PAD) is associated with an increased risk of adverse cardiovascular events, impaired lower extremity blood flow and microvascular perfusion abnormalities in the calf muscles which can be determined with contrast-enhanced magnetic resonance imaging (CE-MRI). We developed a computational model of the microvascular perfusion in the calf muscles. We included 20 patients (10 PAD, 10 controls) and utilized the geometry, mean signal intensity and arterial input functions from CE-MRI calf muscle perfusion scans. The model included the microvascular pressure (pv), outflow filtration coefficient (OFC), transfer rate constant (kt), porosity (φ), and the interstitial permeability (Ktissue). Parameters were fitted and the simulations were compared across PAD patients and controls. Intra-observer reproducibility of the simulated mean signal intensities was excellent (intraclass correlation coefficients >0.995). kt and Ktissue were higher in PAD patients compared with controls (4.72 interquartile range (IQR) 3.33, 5.56 vs. 2.47 IQR 2.10, 2.85; p = 0.003; and 3.68 IQR 3.18, 4.41 vs. 1.81 IQR 1.81, 1.81; p < 0.001). Conversely, porosity (φ) was lower in PAD patients compared with controls (0.52 IQR 0.49, 0.54 vs. 0.61 IQR 0.58, 0.64; p = 0.016). Porosity (φ) was correlated with the ankle brachial index (r = 0.64, p = 0.011). The proposed computational microvascular model is robust and reproducible, and essential model parameters differ significantly between PAD patients and controls.