Marc Sirol

Neovascularization in Human Atherosclerosis

In the absence of disease, the vasa vasorum nurture the outer component of the vessel wall, and the intima is fed by oxygen diffusion from the lumen. As disease progresses, the intima thickens, and oxygen diffusion is impaired. As a result, vasa become the major source for nutrients to the vessel wall.1 The vasa vasorum structure consists of a network of small arteries and veins, as shown in Figure 1. In the coronary arteries, vasa originate from bifurcation segments of epicardial vessels; in the ascending aorta, vasa originate from coronary and brachiocephalic arteries; and in the descending thoracic aorta, vasa originate from intercostal, lumbar, and mesenteric arteries.1 Figure 1. A, Volume-rendered high-resolution, 3-dimensional micro-CT image of the descending aorta vasa vasorum. B and C, Corresponding histological cross sections demonstrate atherosclerotic lesions in the inferior vena cava (black arrow). D, Highlighted differentiated arterial (red) and venous (blue) vasa vasorum. Masson trichrome stain; bar=500 μm. Reproduced with permission from Langheinrich AC, Michniewicz A, Sedding DG, Walker G, Beighley PE, Rau WS, Bohle RM, Ritman EL. Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(−/−)/low-density lipoprotein(−/−) double knockout mice. Arterioscler Thromb Vasc Biol . 2006;26:347–352. Copyright 2006, American Heart Association. Sympathetic fibers help vasa to regulate blood flow, as shown in Figure 2. Vasa react to adenosine and endothelin-1.2,3 However, vasa appear to be relatively insensitive to thromboxane A2, norepinephrine, and angiotensin II, providing neuronal protection against ischemia during sustained sympathetic activity.3 The vasa vasorum are also sensitive to acetylcholine, histamine, isoprenaline, adenosine triphosphate, adenosine diphosphate, adenosine, and sodium nitroprusside.4 Additionally, precontracted vasa exhibit endothelium-dependent vasodilatation to bradykinin and substance P, which are mediated by endothelium-dependent hyperpolarization and nitric oxide, respectively.4 As a result, vasa response to some agonists …

Lipid-Rich Atherosclerotic Plaques Detected by Gadofluorine-Enhanced In Vivo Magnetic Resonance Imaging

Background—MRI of specific components in atherosclerotic plaque may provide information on plaque stability and its potential to rupture. We evaluated gadofluorine in atherosclerotic rabbits using a new MR sequence that allows plaque detection within 1 hour after injection and assessed enhancement in lipid-rich and non–lipid-rich plaques. Methods and Results—Twelve rabbits with aortic plaque and 6 controls underwent MRI before and up to 24 hours after gadofluorine injection (50 μmol/kg). Two T1-weighted, segmented gradient-echo sequences (TFL) were compared to enhance vessel wall delineation after injection: (1) an inversion-recovery prepulse (IR-TFL) or (2) a combination of inversion-recovery and diffusion-based flow suppression prepulses (IR-DIFF-TFL). With the use of IR-TFL at 1 hour after injection, the vessel wall was not delineated because of poor flow suppression; at 24 hours after injection, the enhancement was 37% (P<0.01). IR-DIFF-TFL showed significant enhancement after versus before contrast (1 hour: 164% [P<0.005]; 24 hours: 207% [P<0.001]). At 1 hour and 24 hours after injection, the contrast-to-noise ratio was higher with the use of IR-DIFF-TFL than with IR-TFL (1 hour: 13.0±7.7 versus −19.8±10.3 [P<0.001]; 24 hours: 15.2±5.9 versus 11.4±8.9, respectively [P=0.052]). There was no enhancement in the vessel wall after gadofluorine injection in the control group. A strong correlation was found (r2=0.87; P<0.001) between the lipid-rich areas in histological sections and signal intensity in corresponding MR images. This suggests a high affinity of gadofluorine for lipid-rich plaques. Conclusions—Gadofluorine-enhanced MRI improves atherosclerotic plaque detection. The IR-DIFF-TFL method allows early detection of atherosclerotic plaque within 1 hour after gadofluorine injection.

Chronic Thrombus Detection With In Vivo Magnetic Resonance Imaging and a Fibrin-Targeted Contrast Agent

Background—Arterial thrombosis plays a critical role in acute coronary syndromes and stroke. Therefore, the ability to detect thrombus in vivo has a significant clinical implication. Magnetic resonance imaging (MRI) has shown promise in noninvasive thrombus detection. However, thrombus characterization and age definition remain difficult. We sought to evaluate the use of a fibrin-targeted peptide (EP-2104R) for MR thrombus detection and to compare this modality with non–contrast-enhanced (NCE) MRI and with Gd-DTPA injection at various ages and time points after thrombus generation. Methods and Results—Carotid artery thrombosis was induced by external injury and stasis in 18 rabbits. T1-weighted MRI was performed before and after contrast agent injection, within 6 hours of thrombus induction, at 48 hours, at 1 week, and every week up to 8 weeks after injury. Correlation with histopathology was performed. The fibrin-targeted contrast agent accurately detected all thrombi, regardless of their size, location, and age. Although thrombus signal intensity after injection decreased with thrombus age (P<0.001), enhancement at 8 weeks was still present. Gd-DTPA injection was not associated with an improvement of thrombus detection. EP-2104R was superior to both NCE and Gd-DTPA injection (P<0.001). Histopathologic examination showed thrombus organization over time. Fibrin was gradually replaced by fibrous tissue. A strong correlation was found between thrombus enhancement and collagen content of the organizing thrombus with time (R=−0.89; P<0.001). Conclusions—In an experimental animal model of carotid thrombosis, we have demonstrated the superiority of a fibrin-targeted MR contrast agent for in vivo detection of chronic or organized thrombus, compared with NCE MRI and Gd-DTPA injection.

Preoperative detection of hepatic metastases: Comparison of diffusion-weighted, T2-weighted fast spin echo and gadolinium-enhanced MR imaging using surgical and histopathologic findings as standard of reference

PURPOSE The purpose of this study was to retrospectively compare the respective sensitivities of diffusion-weighted (DW), T2-weighted fast spin-echo (T2WFSE) and gadolinium chelate-enhanced MR imaging in the preoperative detection of hepatic metastases using intraoperative ultrasonographic and histopathologic findings as the standard of reference. MATERIALS AND METHODS Twenty-seven patients with 64 surgically and histopathologically proven hepatic metastases had MR imaging of the liver, including DW, T2WFSE and dynamic gadolinium chelate-enhanced MR imaging. Images from each MR sequence were separately analyzed by two readers with disagreements resolved by consensus readings. The findings on MR images were compared with intraoperative ultrasonographic and histopathologic findings on a lesion-by-lesion basis to determine the sensitivity of each MR sequence. Statistical review of the lesion-by-lesion analysis was performed with the McNemar test. RESULTS DW, T2WFSE and gadolinium chelate-enhanced MR imaging allowed the depiction of 54/64 (84.4%; 95% CI: 73.1-92.2%), 44/64 (68.8%; 95% CI: 55.9-79.8%), and 51/64 (79.7%; 95% CI: 67.8-88.7%) hepatic metastases respectively. DW MR images allowed depiction of significantly more hepatic metastases than did T2WFSE and was equivalent to gadolinium chelate-enhanced MR imaging (P=.002 and P=.375, respectively). CONCLUSION DW MR imaging is superior to T2WFSE imaging and equivalent to gadolinium chelate-enhanced MR imaging for the preoperative detection of hepatic metastases. Further studies however are needed to determine at what extent DW MR imaging can be used as an alternative to gadolinium chelate-enhanced MR imaging for the preoperative depiction of hepatic metastases.

Increased neovascularization in advanced lipid-rich atherosclerotic lesions detected by gadofluorine-M-enhanced MRI: implications for plaque vulnerability.

Background—Inflammation and neovascularization may play a significant role in atherosclerotic plaque progression and rupture. We evaluated gadofluorine-M–enhanced MRI for detection of plaque inflammation and neovascularization in an animal model of atherosclerosis. Methods and Results—Sixteen rabbits with aortic plaque and 6 normal control rabbits underwent gadofluorine-M–enhanced MRI. Eight rabbits had advanced atherosclerotic lesions, whereas the remaining 8 had early lesions. Magnetic resonance atherosclerotic plaque enhancement was meticulously compared with plaque inflammation and neovessel density as assessed by histopathology. Advanced plaques and early atheroma were enhanced after gadofluorine-M injection. Control animals displayed no enhancement. After accounting for the within-animal correlation of observations, mean contrast-to-noise ratio was significantly higher in advanced plaques than compared with early atheroma (4.29±0.21 versus 3.00±0.32; P=0.004). Macrophage density was higher in advanced plaques in comparison to early atheroma (geometric mean=0.50 [95% CI, 0.19 to 1.03] versus 0.25 [0.07 to 0.42]; P=0.05). Furthermore, higher neovessel density was observed in advanced plaques (1.83 [95% CI, 1.51 to 2.21] versus 1.29 [0.99 to 1.69]; P=0.05). The plaque accumulation of gadofluorine-M correlated with increased neovessel density as shown by linear regression analysis (r=0.67; P<0.001). Confocal and fluorescence microscopy revealed colocalization of gadofluorine-M with plaque areas containing a high density of neovessels. Conclusion—Gadofluorine-M–enhanced MRI is effective for in vivo detection of atherosclerotic plaque inflammation and neovascularization in an animal model of atherosclerosis. These findings suggest that gadofluorine-M enhancement reflects the presence of high-risk plaque features believed to be associated with plaque rupture. Gadofluorine-M plaque enhancement may therefore provide functional assessment of atherosclerotic plaque in vivo.

Suspected Anastomotic Recurrence of Crohn Disease after Ileocolic Resection: Evaluation with CT Enteroclysis

PURPOSE To determine the utility of computed tomographic (CT) enteroclysis for characterization of the status of the anastomotic site in patients with Crohn disease who had previously undergone ileocolic resection. MATERIALS AND METHODS Written informed consent was prospectively obtained from all patients, and the institutional review board approved the study protocol. CT enteroclysis findings in 40 patients with Crohn disease who had previously undergone ileocolic resection were evaluated independently by two readers. Endoscopic findings, histopathologic findings, and/or the Crohn disease activity index was the reference standard. Interobserver agreement between the two readers was calculated with kappa statistics. Associations between CT enteroclysis findings and anastomotic site status were assessed at univariate analysis. The sensitivity, specificity, and accuracy of CT enteroclysis, with corresponding 95% confidence intervals (CIs), for the diagnosis of normal versus abnormal anastomosis and the diagnosis of anastomotic recurrence versus fibrostenosis were estimated. RESULTS Interobserver agreement regarding CT enteroclysis criteria was good to perfect (kappa = 0.72-1.00). At univariate analysis, stratification and anastomotic wall thickening were the two most discriminating variables in the differentiation between normal and abnormal anastomoses (P < .001). Stratification (P < .001) and the comb sign (P = .026) were the two most discriminating variables in the differentiation between anastomotic recurrence and fibrostenosis. In the diagnosis of anastomotic recurrence, severe anastomotic stenosis was the most sensitive finding (95% [20 of 21 patients]; 95% CI: 76.18%, 99.88%), both comb sign and stratification had 95% specificity (18 of 19 patients; 95% CI: 73.97%, 99.87%), and stratification was the most accurate finding (92% [37 of 40 patients]; 95% CI: 79.61%, 98.43%). In the diagnosis of fibrostenosis, both severe anastomotic stenosis and anastomotic wall thickening were 100% sensitive (eight of eight patients; 95% CI: 63.06%, 100.00%), and using an association among five categorical variables, including severe anastomotic stenosis, anastomotic wall thickening with normal or mild mucosal enhancement, absence of comb sign, and absence of fistula, yielded 88% sensitivity (seven of eight patients; 95% CI: 47.35%, 99.68%), 97% specificity (31 of 32 patients; 95% CI: 83.78%, 99.92%), and 95% accuracy (38 of 40 patients; 95% CI: 83.08%, 99.39%). CONCLUSION CT enteroclysis yields objective and relatively specific morphologic criteria that help differentiate between recurrent disease and fibrostenosis at the anastomotic site after ileocolic resection for Crohn disease. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09091165/-/DC1.

High-Resolution MR Imaging of the Cervical Arterial Wall: What the Radiologist Needs to Know

The emergence of high-resolution rapid imaging methods has enabled magnetic resonance (MR) imagers to noninvasively image the fine internal structure of cervical arterial walls. In this article, a comprehensive guide to performing high-resolution MR imaging of cervical arteries is provided, including the choice of coils, sequences, and imaging parameters, as well as tips for optimal image quality. Explanations and illustrations are given of using high-resolution MR imaging to quantify plaque volume, determine atherosclerotic plaque burden, depict plaque composition, and ultimately identify unstable plaque before it leads to a clinical event. Finally, the role of high-resolution MR imaging in the diagnosis of cervical dissection and inflammatory disease of the arterial wall is emphasized.

Increased Neovascularization in Advanced Lipid-Rich Atherosclerotic Lesions Detected by Gadofluorine-M Enhanced Magnetic Resonance Imaging (MRI): Implications for Plaque Vulnerability

Background—Inflammation and neovascularization may play a significant role in atherosclerotic plaque progression and rupture. We evaluated gadofluorine-M–enhanced MRI for detection of plaque inflammation and neovascularization in an animal model of atherosclerosis. Methods and Results—Sixteen rabbits with aortic plaque and 6 normal control rabbits underwent gadofluorine-M–enhanced MRI. Eight rabbits had advanced atherosclerotic lesions, whereas the remaining 8 had early lesions. Magnetic resonance atherosclerotic plaque enhancement was meticulously compared with plaque inflammation and neovessel density as assessed by histopathology. Advanced plaques and early atheroma were enhanced after gadofluorine-M injection. Control animals displayed no enhancement. After accounting for the within-animal correlation of observations, mean contrast-to-noise ratio was significantly higher in advanced plaques than compared with early atheroma (4.29±0.21 versus 3.00±0.32; P=0.004). Macrophage density was higher in advanced plaques in comparison to early atheroma (geometric mean=0.50 [95% CI, 0.19 to 1.03] versus 0.25 [0.07 to 0.42]; P=0.05). Furthermore, higher neovessel density was observed in advanced plaques (1.83 [95% CI, 1.51 to 2.21] versus 1.29 [0.99 to 1.69]; P=0.05). The plaque accumulation of gadofluorine-M correlated with increased neovessel density as shown by linear regression analysis (r=0.67; P<0.001). Confocal and fluorescence microscopy revealed colocalization of gadofluorine-M with plaque areas containing a high density of neovessels. Conclusion—Gadofluorine-M–enhanced MRI is effective for in vivo detection of atherosclerotic plaque inflammation and neovascularization in an animal model of atherosclerosis. These findings suggest that gadofluorine-M enhancement reflects the presence of high-risk plaque features believed to be associated with plaque rupture. Gadofluorine-M plaque enhancement may therefore provide functional assessment of atherosclerotic plaque in vivo.

Differentiation between cavernous hemangiomas and untreated malignant neoplasms of the liver with free-breathing diffusion-weighted MR imaging: Comparison with T2-weighted fast spin-echo MR imaging

OBJECTIVE To test interobserver variability of ADC measurements and compare the diagnostic performances of free-breathing diffusion-weighted (FBDW) with that of T2-weighted FSE (T2WFSE) MR imaging for differentiating between cavernous hemangiomas and untreated malignant hepatic neoplasms. MATERIALS AND METHODS Thirty-five patients with cavernous hemangiomas and 35 with untreated hepatic malignant neoplasms had FBDW and T2WFSE MR imaging. Hepatic lesions were characterized with ADC measurement and visual evaluation. Interobserver agreement for ADC measurement was calculated. Association between ADC value and lesion type was assessed using univariate analysis. Sensitivity, specificity and accuracy of ADC values and visual evaluation of MR images for the diagnosis of untreated malignant hepatic neoplasm were compared. RESULTS ADC measurements showed excellent interobserver correlation (intraclass correlation coefficient=0.980). Malignant neoplasms had lower ADC values than hemangiomas for the two observers (1.11×10(-3) mm2/s±.21×10(-3) vs. 1.77×10(-3) mm2/s±.29×10(-3) for observer 1 and 1.11×10(-3) mm2/s±.19×10(-3) vs. 1.79×10(-3) mm2/s±.32×10(-3) for observer 2) and univariate analysis found significant correlations between lesion type and ADC values. Depending on ADC threshold value, accuracy for the diagnosis of malignant neoplasm varied from 82.9% to 94.3%. Using visual evaluation, FBDW showed better specificity and accuracy than T2WFSE MR images for the diagnosis of malignant neoplasm (97.1% vs. 77.1% and 94.3% vs. 62.9%, respectively). CONCLUSION FBDW imaging provides reproducible quantitative information and surpasses the value of T2WFSE MR imaging for differentiating between cavernous hemangiomas and untreated malignant hepatic neoplasms.

Complementary results of computed tomography and magnetic resonance imaging of the heart and coronary arteries: a review and future outlook☆

MR and CT imaging are emerging as promising complementary imaging modalities in the primary diagnosis of CAD and for the detection of subclinical atherosclerotic disease. For the detection or exclusion of significant CAD, both cardiac CT (including coronary calcium screening and non-invasive coronary angiography), and cardiac MRI (using stress function and stress perfusion imaging) are becoming widely available for routine clinical evaluation. Their high negative predictive value, especially when combining two or more of these modalities, allows the exclusion of significant CAD with high certainty, provided that patients are selected appropriately. The primary goal of current investigations using this combined imaging approach is to reduce the number of unnecessary diagnostic coronary catheterizations, and not to replace cardiac catheterization altogether. For the diagnosis of obstructive coronary atherosclerosis and for screening for subclinical disease, CT and MRI have shown potential to directly image the atherosclerotic lesion, measure atherosclerotic burden, and characterize the plaque components. The information obtained may be used to assess progression and regression of atherosclerosis and may open new areas for diagnosis, prevention, and treatment of coronary atherosclerosis. Further clinical investigation is needed to define the technical requirements for optimal imaging, develop accurate quantitative image analysis techniques, outline criteria for image interpretation, and define the clinical indications for both MR or CT imaging. Additional studies are also needed to address the cost effectiveness of such a combined approach versus other currently available imaging modalities.