Luca Biasiolli

Aortic Dilation in Bicuspid Aortic Valve Disease Flow Pattern Is a Major Contributor and Differs With Valve Fusion Type

Background— Ascending aortic dilation is important in bicuspid aortic valve (BAV) disease, with increased risk of aortic dissection. We used cardiovascular MR to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function, and aortic dilation. Methods and Results— A total of 142 subjects underwent cardiovascular MR (mean age, 40 years; 95 with BAV, 47 healthy volunteers). Patients with BAV had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3±3.3 versus 15.2±2.2 mm/m2; P <0.001), and higher rotational (helical) flow (31.7±15.8 versus 2.9±3.9 mm2/s; P <0.001), systolic flow angle (23.1°±12.5° versus 7.0°±4.6°; P <0.001), and systolic wall shear stress (0.85±0.28 versus 0.59±0.17 N/m2; P <0.001) compared with healthy volunteers. BAV with right-handed flow and right-non coronary cusp fusion (n=31) showed more severe flow abnormalities (rotational flow, 38.5±16.5 versus 27.8±12.4 mm2/s; P <0.001; systolic flow angle, 29.4°±10.9° versus 19.4°±11.4°; P <0.001; in-plane wall shear stress, 0.64±0.23 versus 0.47±0.22 N/m2; P <0.001) and larger aortas (19.5±3.4 versus 17.5±3.1 mm/m2; P <0.05) than right–left cusp fusion (n=55). Patients with BAV with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger patients with BAV showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the pathogenesis of aortic dilation. Aortic function measures (distensibility, aortic strain, and pulse wave velocity) were similar across all groups. Conclusions— Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities and may allow better risk prediction and selection of patients for earlier surgical intervention.Background—Ascending aortic dilation is important in bicuspid aortic valve (BAV) disease, with increased risk of aortic dissection. We used cardiovascular MR to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function, and aortic dilation. Methods and Results—A total of 142 subjects underwent cardiovascular MR (mean age, 40 years; 95 with BAV, 47 healthy volunteers). Patients with BAV had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3±3.3 versus 15.2±2.2 mm/m2; P<0.001), and higher rotational (helical) flow (31.7±15.8 versus 2.9±3.9 mm2/s; P<0.001), systolic flow angle (23.1°±12.5° versus 7.0°±4.6°; P<0.001), and systolic wall shear stress (0.85±0.28 versus 0.59±0.17 N/m2; P<0.001) compared with healthy volunteers. BAV with right-handed flow and right-non coronary cusp fusion (n=31) showed more severe flow abnormalities (rotational flow, 38.5±16.5 versus 27.8±12.4 mm2/s; P<0.001; systolic flow angle, 29.4°±10.9° versus 19.4°±11.4°; P<0.001; in-plane wall shear stress, 0.64±0.23 versus 0.47±0.22 N/m2; P<0.001) and larger aortas (19.5±3.4 versus 17.5±3.1 mm/m2; P<0.05) than right–left cusp fusion (n=55). Patients with BAV with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger patients with BAV showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the pathogenesis of aortic dilation. Aortic function measures (distensibility, aortic strain, and pulse wave velocity) were similar across all groups. Conclusions—Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities and may allow better risk prediction and selection of patients for earlier surgical intervention.

Black-Blood Multicontrast Imaging of Carotid Arteries with DANTE-prepared 2D and 3D MR Imaging

PURPOSE To prospectively compare the black-blood ( BB black blood ) imaging efficiency of a delay alternating with nutation for tailored excitation ( DANTE delay alternating with nutation for tailored excitation ) preparation module with conventional double inversion-recovery ( DIR double inversion recovery ) and motion-sensitive driven equilibrium ( MSDE motion-sensitive driven equilibrium ) preparation modules and to introduce a new three-dimensional ( 3D three-dimensional ) T1-weighted magnetic resonance (MR) imaging sequence. MATERIALS AND METHODS Carotid artery wall imaging was performed in 10 healthy volunteers and 15 patients in accordance with an institutional review board-approved protocol. Two-dimensional ( 2D two-dimensional ) turbo spin-echo ( TSE turbo spin echo ) and 3D three-dimensional fast low-angle shot ( FLASH fast low-angle shot ) sequences served as readout modules. DANTE delay alternating with nutation for tailored excitation -prepared T1-, T2-, and proton density-weighted 2D two-dimensional TSE turbo spin echo images, as well as T1-weighted 3D three-dimensional DANTE delay alternating with nutation for tailored excitation -prepared FLASH fast low-angle shot (hereafter, 3D three-dimensional DASH DANTE-prepared FLASH ) images, were acquired in the region of the carotid artery bifurcation. For comparison, 2D two-dimensional DIR double inversion recovery -prepared, 2D two-dimensional MSDE motion-sensitive driven equilibrium -prepared multicontrast TSE turbo spin echo , and 3D three-dimensional MSDE motion-sensitive driven equilibrium -prepared FLASH fast low-angle shot (hereafter, 3D three-dimensional MERGE MSDE-prepared FLASH ) MR images were also acquired. The effective contrast-to-noise ratio ( CNReff effective contrast-to-noise ratio ) per unit time was calculated for all sequences. Paired t tests were performed to test within-group differences in vessel wall CNReff effective contrast-to-noise ratio . RESULTS The CNReff effective contrast-to-noise ratio of DANTE delay alternating with nutation for tailored excitation -prepared T1-, T2-, and proton density-weighted sequences was 27.3, 14.7, and 25.7 mm(-1)min(-1/2), respectively; this represented an improvement of approximately 25%-100% (P < .05) when compared with the CNReff effective contrast-to-noise ratio attained with existing methods. The 3D three-dimensional DASH DANTE-prepared FLASH technique proved to be a fast (<2 seconds per section) and high-spatial-resolution (0.6 mm isotropic) BB black blood technique with higher (75%-100% improvement, P < .001) signal-to-noise ratio efficiency than the 3D three-dimensional MERGE MSDE-prepared FLASH technique. CONCLUSION The DANTE delay alternating with nutation for tailored excitation -prepared multicontrast 2D two-dimensional BB black blood technique is a promising new tool for MR imaging of carotid artery walls. Additionally, the 3D three-dimensional DASH DANTE-prepared FLASH sequence enables 3D three-dimensional high-spatial-resolution fast T1-weighted imaging of carotid artery walls. ©RSNA, 2014 Online supplemental material is available for this article .

In-vivo quantitative T2 mapping of carotid arteries in atherosclerotic patients: segmentation and T2 measurement of plaque components

BackgroundAtherosclerotic plaques in carotid arteries can be characterized in-vivo by multicontrast cardiovascular magnetic resonance (CMR), which has been thoroughly validated with histology. However, the non-quantitative nature of multicontrast CMR and the need for extensive post-acquisition interpretation limit the widespread clinical application of in-vivo CMR plaque characterization. Quantitative T2 mapping is a promising alternative since it can provide absolute physical measurements of plaque components that can be standardized among different CMR systems and widely adopted in multi-centre studies. The purpose of this study was to investigate the use of in-vivo T2 mapping for atherosclerotic plaque characterization by performing American Heart Association (AHA) plaque type classification, segmenting carotid T2 maps and measuring in-vivo T2 values of plaque components.MethodsThe carotid arteries of 15 atherosclerotic patients (11 males, 71 ± 10 years) were imaged at 3 T using the conventional multicontrast protocol and Multiple-Spin-Echo (Multi-SE). T2 maps of carotid arteries were generated by mono-exponential fitting to the series of images acquired by Multi-SE using nonlinear least-squares regression. Two reviewers independently classified carotid plaque types following the CMR-modified AHA scheme, one using multicontrast CMR and the other using T2 maps and time-of-flight (TOF) angiography. A semi-automated method based on Bayes classifiers segmented the T2 maps of carotid arteries into 4 classes: calcification, lipid-rich necrotic core (LRNC), fibrous tissue and recent IPH. Mean ± SD of the T2 values of voxels classified as LRNC, fibrous tissue and recent IPH were calculated.ResultsIn 37 images of carotid arteries from 15 patients, AHA plaque type classified by multicontrast CMR and by T2 maps (+ TOF) showed good agreement (76% of matching classifications and Cohen’s κ = 0.68). The T2 maps of 14 normal arteries were used to measure T2 of tunica intima and media (T2 = 54 ± 13 ms). From 11865 voxels in the T2 maps of 15 arteries with advanced atherosclerosis, 2394 voxels were classified by the segmentation algorithm as LRNC (T2 = 37 ± 5 ms) and 7511 voxels as fibrous tissue (T2 = 56 ± 9 ms); 192 voxels were identified as calcification and one recent IPH (236 voxels, T2 = 107 ± 25 ms) was detected on T2 maps and confirmed by multicontrast CMR.ConclusionsThis carotid CMR study shows the potential of in-vivo T2 mapping for atherosclerotic plaque characterization. Agreement between AHA plaque types classified by T2 maps (+TOF) and by conventional multicontrast CMR was good, and T2 measured in-vivo in LRNC, fibrous tissue and recent IPH demonstrated the ability to discriminate plaque components on T2 maps.

Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.

Background Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. Objectives The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. Methods Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta. Results There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was –3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (–4.30 mg/dl [range: –8.5 to –0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test. Conclusions There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930)

Quantification of Lipid-Rich Core in Carotid Atherosclerosis Using Magnetic Resonance T2 Mapping: Relation to Clinical Presentation.

Objectives The aim of this study was to: 1) provide tissue validation of quantitative T2 mapping to measure plaque lipid content; and 2) investigate whether this technique could discern differences in plaque characteristics between symptom-related and non–symptom-related carotid plaques. Background Noninvasive plaque lipid quantification is appealing both for stratification in treatment selection and as a possible predictor of future plaque rupture. However, current cardiovascular magnetic resonance (CMR) methods are insensitive, require a coalesced mass of lipid core, and rely on multicontrast acquisition with contrast media and extensive post-processing. Methods Patients scheduled for carotid endarterectomy were recruited for 3-T carotid CMR before surgery. Lipid area was derived from segmented T2 maps and compared directly to plaque lipid defined by histology. Results Lipid area (%) on T2 mapping and histology showed excellent correlation, both by individual slices (R = 0.85, p < 0.001) and plaque average (R = 0.83, p < 0.001). Lipid area (%) on T2 maps was significantly higher in symptomatic compared with asymptomatic plaques (31.5 ± 3.7% vs. 15.8 ± 3.1%; p = 0.005) despite similar degrees of carotid stenosis and only modest difference in plaque volume (128.0 ± 6.0 mm3 symptomatic vs. 105.6 ± 9.4 mm3 asymptomatic; p = 0.04). Receiver-operating characteristic analysis showed that T2 mapping has a good ability to discriminate between symptomatic and asymptomatic plaques with 67% sensitivity and 91% specificity (area under the curve: 0.79; p = 0.012). Conclusions CMR T2 mapping distinguishes different plaque components and accurately quantifies plaque lipid content noninvasively. Compared with asymptomatic plaques, greater lipid content was found in symptomatic plaques despite similar degree of luminal stenosis and only modest difference in plaque volumes. This new technique may find a role in determining optimum treatment (e.g., providing an indication for intensive lipid lowering or by informing decisions of stents vs. surgery).

Loss of fine structure and edge sharpness in fast‐spin‐echo carotid wall imaging: Measurements and comparison with multiple‐spin‐echo in normal and atherosclerotic subjects

To test whether the k‐space acquisition strategy used by fast‐spin‐echo (FSE) is a major source of blurring in carotid wall and plaque imaging, and investigate an alternative acquisition approach.

Multicontrast MRI registration of carotid arteries in atherosclerotic and normal subjects

Clinical studies on atherosclerosis agree that multi-contrast MRI is the most promising technique for in-vivo characterization of carotid plaques. Multi-contrast image registration is essential for this application, because it corrects misalignments caused by patient motion during MRI acquisition. To date, it has not been determined which automatic method provides the best registration accuracy in carotid MRI. This study tries to answer this question by presenting an iterative coarse-to-fine algorithm that co-registers multi-contrast images of carotid arteries using three similarity metrics: Correlation Ratio (CR), Mutual Information (MI) and Gradient MI (GMI). The registration algorithm is first applied on the entire images and then only on the Region of Interest (ROI) of the carotid arteries using sub-pixel accuracy. The ROI is defined by an automatic carotid detection algorithm, which was tested on a group of 20 patients with different types of atherosclerotic plaques (sensitivity 91% and specificity 88%). Automatic registration was compared with image alignment obtained by manual operators (clinically qualified vascular specialists). Registration accuracies were measured using a novel MRI validation procedure, in which the gold standard is represented by in-plane rigid transformations applied by the MRI system to mimic neck movements. Overall, automatic methods (GMI = 181 ± 104 μm) produced lower registration errors than manual operators (365 ± 102 μm). GMI performed slightly better than CR and MI, suggesting that anatomical information improves registration accuracy in the carotid ROI.

Quantification of carotid plaque lipid content with magnetic resonance T2 mapping in patients undergoing carotid endarterectomy

Background and purpose Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the wall of the artery. Methods Since plaque lipid is a key determinant of plaque behaviour we used a newly validated, high-sensitivity T2-mapping MR technique for a systematic survey of the quantity and distribution of plaque lipid in patients undergoing endarterectomy. Lipid percentage was quantified in 50 carotid endarterectomy patients. Lipid distribution was tested, using two imaging indices (contribution of the largest lipid deposit towards total lipid (LLD %) and a newly-developed LAI ‘lipid aggregation index’). Results The bifurcation contained maximal lipid volume. Lipid percentage was higher in symptomatic vs. asymptomatic patients with degree of stenosis (DS ≥ 50%) and in the total cohort (P = 0.013 and P = 0.005, respectively). Both LLD % and LAI was higher in symptomatic patients (P = 0.028 and P = 0.018, respectively), suggesting that for a given plaque lipid volume, coalesced deposits were more likely to be associated with symptomatic events. There was no correlation between plaque volume or lipid content and degree of luminal stenosis measured on ultrasound duplex (r = -0.09, P = 0.53 and r = -0.05, P = 0.75), respectively. However, there was a strong correlation in lipid between left and right carotid arteries (r = 0.5, P <0.0001, respectively). Conclusions Plaque lipid content and distribution is associated with symptomatic status of the carotid plaque. Importantly, plaque lipid content was not related to the degree of luminal stenosis assessed by ultrasound. Determination of plaque lipid content may prove useful for stratification of asymptomatic patients, including selection of optimal invasive treatments.

Inherited Aortopathy Assessment in Relatives of Patients With a Bicuspid Aortic Valve

Bicuspid aortic valve disease (BAV) is commonly associated with aortopathy, which may be in part hemodynamically mediated [(1)][1]. BAV is known to cluster in families (≤25% family members affected) [(2)][2]. Due to this increased incidence in first-degree relatives (FDR), many clinicians will

OXSA: An open-source magnetic resonance spectroscopy analysis toolbox in MATLAB

In vivo magnetic resonance spectroscopy provides insight into metabolism in the human body. New acquisition protocols are often proposed to improve the quality or efficiency of data collection. Processing pipelines must also be developed to use these data optimally. Current fitting software is either targeted at general spectroscopy fitting, or for specific protocols. We therefore introduce the MATLAB-based OXford Spectroscopy Analysis (OXSA) toolbox to allow researchers to rapidly develop their own customised processing pipelines. The toolbox aims to simplify development by: being easy to install and use; seamlessly importing Siemens Digital Imaging and Communications in Medicine (DICOM) standard data; allowing visualisation of spectroscopy data; offering a robust fitting routine; flexibly specifying prior knowledge when fitting; and allowing batch processing of spectra. This article demonstrates how each of these criteria have been fulfilled, and gives technical details about the implementation in MATLAB. The code is freely available to download from https://github.com/oxsatoolbox/oxsa.