In vivo assessment of endothelial permeability of coronary lesions with variable degree of stenosis using an albumin-binding MR probe.

MR imaging with an albumin-binding probe enables the visualization of endothelial permeability and damage in the arterial system. The goal of this study was to compare signal enhancement of lesions with different grades of stenosis segments on molecular CMR in combination with the albumin-binding probe gadofosveset. This prospective clinical study included patients with symptoms suggestive of coronary artery disease (CAD). Patients underwent gadofosveset-enhanced cardiovascular magnetic resonance (CMR) imaging and x-ray angiography (QCA) within 24 h. CMR imaging was performed prior to and 24 h following the administration of gadofosveset. Contrast-to-noise ratios (CNRs) between segments with different grades of stenosis were compared. Overall, n = 203 segments of 26 patients were included. Lesions with more than > 70% stenosis demonstrated significantly higher CNRs compared to lesions < 70% (7.6 ± 8.3 vs. 2.5 ± 4.9; p < 0.001). Post-stenotic segments of lesions > 70% stenosis showed significant higher signal enhancement compared to segments located upstream of these lesions (7.3 ± 8.8 vs. 2.8 ± 2.2; p = 0.02). No difference in signal enhancement between segments proximal and distal of lesions with stenosis greater than 50% was measured (3.3 ± 2.8 vs. 2.4 ± 2.7; p = 0.18). ROC analysis for the detection of lesions ≥ 70% revealed an area under the curve of 0.774 (95% CI 0.681-0.866). This study suggests that relevant coronary stenosis and their down-stream segments are associated with increased signal enhancement on Gadofosveset-enhanced CMR, suggesting a higher endothelial permeability in these lesions. An albumin-binding MR probe could represent a novel in vivo biomarker for the identification and characterization of these vulnerable coronary segments.

Comprehensive multimodality characterization of hemodynamically significant and non-significant coronary lesions using invasive and noninvasive measures.

BACKGROUND: There is limited knowledge about morphological molecular-imaging-derived parameters to further characterize hemodynamically relevant coronary lesions. OBJECTIVE: The aim of this study was to describe and differentiate specific parameters between hemodynamically significant and non-significant coronary lesions using various invasive and non-invasive measures. METHODS: This clinical study analyzed patients with symptoms suggestive of coronary artery disease (CAD) who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-angiography). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability, respectively. RESULTS: Overall 29 coronary segments from 14 patients were examined. Segments containing lesions with a QFR <0.8 (n = 9) were associated with significantly higher signal enhancement on Gadofosveset-enhanced CMR as compared to segments containing a lesions without significant stenosis (lesion-QFR>0.8; n = 19) (5.32 (4.47-7.02) vs. 2.42 (1.04-5.11); p = 0.042). No differences in signal enhancement were seen on native T1-weighted CMR (2.2 (0.68-6.75) vs. 2.09 (0.91-6.57), p = 0.412). 66.7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions. CONCLUSION: The findings of this pilot study suggest that signal enhancement on albumin-binding probe-enhanced CMR but not on T1-weighted CMR is associated with hemodynamically relevant coronary lesions.

Noninvasive Imaging of Endothelial Damage in Patients With Different HbA1c Levels: A Proof-of-Concept Study.

The aim of this study was to compare endothelial permeability, which is considered a hallmark of coronary artery disease, between patients with different HbA1c levels using an albumin-binding magnetic resonance (MR) probe. This cross-sectional study included 26 patients with clinical indication for X-ray angiography who were classified into three groups according to HbA1c level (<5.7% [<39 mmol/mol], 5.7-6.4% [39-47 mmol/mol], and ≥6.5% [48 mmol/mol]). Subjects underwent gadofosveset-enhanced coronary magnetic resonance and X-ray angiography including optical coherence within 24 h. Contrast-to-noise ratios (CNRs) were assessed to measure the probe uptake in the coronary wall by coronary segment, excluding those with culprit lesions in X-ray angiography. In the group of patients with HbA1c levels between 5.7 and 6.4%, 0.30 increased normalized CNR values were measured, compared with patients with HbA1c levels <5.7% (0.30 [95% CI 0.04, 0.57]). In patients with HbA1c levels ≥6.5%, we found 0.57 higher normalized CNR values compared with patients with normal HbA1c levels (0.57 [95% CI 0.28, 0.85]) and 0.26 higher CNR values for patients with HbA1c level ≥6.5% compared with patients with HbA1c levels between 5.7 and 6.4% (0.26 [95% CI -0.04, 0.57]). Additionally, late atherosclerotic lesions were more common in patients with high HbA1c levels (HbA1c ≥6.5%, n = 14 [74%]; HbA1c 5.7-6.4%, n = 6 [60%]; and HbA1c <5.7%, n = 10 [53%]). In conclusion, coronary MRI in combination with an albumin-binding MR probe suggests that both patients with intermediate and patients with high HbA1c levels are associated with a higher extent of endothelial damage of the coronary arteries compared with patients with HbA1c levels <5.7%.

Novel Approach for In Vivo Detection of Vulnerable Coronary Plaques Using Molecular 3-T CMR Imaging With an Albumin-Binding Probe.

OBJECTIVES: This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS). BACKGROUND: ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA). METHODS: A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was quantified within coronary segments in comparison with blood signal. RESULTS: A total of 207 coronary segments were analyzed on GE-CMR. Segments containing a culprit lesion in ACS patients (n = 11) showed significant higher signal enhancement (CNR) following gadofosveset-trisodium application than segments without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p < 0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11 segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162 of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than segments without coronary plaque or segments containing early atherosclerotic lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001). CONCLUSIONS: In this study, we demonstrated for the first time the noninvasive detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary arteries in vivo by using GE-CMR. This method may represent a novel approach for noninvasive cardiovascular risk prediction.