Vascular Calcification in ex Vivo Carotid Specimens: Precision and Accuracy of Measurements with Multi–Detector Row CT

Hoffmann, Udo; Kwait, Dylan C.; Handwerker, Jason; Chan, Raymond C. K.; LaMuraglia, Glenn M.; Brady, Thomas J.

doi:10.1148/radiol.2292021016

Cited by 47 publications

(32 citation statements)

References 29 publications

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“…In the slightly larger study mentioned, this method was capable of establishing inverse relationships between osteoblast-dependent bone formation and arterial calcification (9). However, other specialized methods-such as phantom-calibrated arterial mineral mass measurements using summed computed tomography (CT) numbers from thresholded multidetector CT scans-can be used to robustly quantify calcium content in any arterial segment (29,30). Mineral mass measurement has advantages in that it is less biased (29,30) and is a continuous variable (29), like measures of vascular compliance.…”

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confidence: 99%

“…However, other specialized methods-such as phantom-calibrated arterial mineral mass measurements using summed computed tomography (CT) numbers from thresholded multidetector CT scans-can be used to robustly quantify calcium content in any arterial segment (29,30). Mineral mass measurement has advantages in that it is less biased (29,30) and is a continuous variable (29), like measures of vascular compliance. Demer unambiguously demonstrated that arterial calcification does contribute to vessel wall stiffness on direct assessment of balloon catheter pressure-volume relationships (31).…”

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confidence: 99%

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Calciotropic Hormones and Arterial Physiology

Towler¹

2007

Journal of the American Society of Nephrology

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V ascular calcification increasingly afflicts our aging and dysmetabolic population (1). In the past decade, vascular calcification has emerged as an actively regulated form of calcified tissue metabolism, resembling mineralization of endochondral and membranous bone (1). Demer and colleagues (2) were the first to provide molecular insights into disease pathobiology. In 1993, they identified expression of the powerful bone morphogen, BMP2, in calcium-laden type Vb atherosclerotic plaques. Detailed studies have confirmed contributions of osteogenic BMP2 and Wnt signaling cascades not only in atherosclerotic disease (2) but also during medial artery calcification of diabetes (3) and calcific aortic stenosis (4). Executive cell types that are familiar to bone biologists are seen in calcifying macrovascular specimens, controlling calcified matrix remodeling via paracrine signals that include osteopontin, matrix Gla protein, and inorganic pyrophosphate (1,3,5). Ectopic skeletal morphogens divert aortic mesoangioblasts, mural pericytes, and valve myofibroblasts to osteogenic fates (1,3,6). Ectopic vascular expression of pro-osteogenic morphogens is entrained to physiologic stimuli that promote calcification (1,3). Inflammation, mechanical shear, oxidative stress, hyperphosphatemia, and elastinolysis provide stimuli that promote osteogenic matrix remodeling and compromise vascular defenses that limit calcium deposition (1,3).In ESRD, a "perfect storm" of metabolic, mechanical, and inflammatory insults challenges vascular health, leading to cardiovascular mortality rates that approach 20% per annum (7). Perturbations in parathyroid hormone (PTH) production that compromise normal bone formation increase the risk for vascular calcium load (8,9). Indeed, in patients stage 5 chronic kidney disease, low-turnover osteoporosis with inappropriately normal PTH levels is a strong risk factor for vascular calcium accumulation (9). Vascular calcification contributes to vascular stiffening-abnormal aortofemoral Windkessel physiology that generates systolic hypertension, increases myocardial workload, and compromises distal tissue perfusion (10).In this issue of JASN, London et al. (11) again advance our understanding of human arterial physiology and calciotropic hormones, highlighting the importance of adequate vitamin D nutrition to maintenance of vascular structure and function in ESRD (8). As expected (10), age and hypertension strongly contribute to risk for reduced arterial compliance, evidenced by reduced brachial artery (BA) distensibility, increased aortic pulse wave velocity (PWV), and diminished flow-mediated dilation (FMD). As a sensitive index of perturbed intimal-medial signaling, reduced FMD identifies and confirms dysfunction in arterial physiology (10). The BA distensibility relationship also is important; this assessment of arterial compliance is not altered significantly by blood's rheologic properties and, like PWV, quantifies how vascular material and geometric properties integrate to determine arterial stiffnes...

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Calciotropic Hormones and Arterial Physiology

Towler¹

2007

Journal of the American Society of Nephrology

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“…Despite there being promising studies initially that involved the use of EBCT and MDCT for carotid calcium measurement, there is an ongoing debate as to whether calcium scoring is a reliable indicator of cerebrovascular risk detection and in determining the course of management [3,7,36]. One controversy arises from the substantial measurement variability (up to 30%) of the conventional Agatson score if applied to the carotid bifurcation [37]. Another potential limitation is that helical CT is well known to be sensitive (88%) but not very specific (52%) in detecting a .50% coronary stenosis [38].…”

Section: Discussionmentioning

confidence: 99%

Correlation between carotid bifurcation calcium burden on non-enhanced CT and percentage stenosis, as confirmed by digital subtraction angiography

Sarıkaya

Lohman

McKinney³

et al. 2012

BJR

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Objectives: Previous evidence supports a direct relationship between the calcium burden (volume) on post-contrast CT with the percent internal carotid artery (ICA) stenosis at the carotid bifurcation. We sought to further investigate this relationship by comparing non-enhanced CT (NECT) and digital subtraction angiography (DSA). Methods: 50 patients (aged 41-82 years) were retrospectively identified who had undergone cervical NECT and DSA. A 64-multidetector array CT (MDCT) scanner was utilised and the images reviewed using preset window widths/levels (30/300) optimised to calcium, with the volumes measured via three-dimensional reconstructive software. Stenosis measurements were performed on DSA and luminal diameter stenoses .40% were considered ''significant''. Volume thresholds of 0.01, 0.03, 0.06, 0.09 and 0.12 cm 3 were utilised and Pearson's correlation coefficient (r) was calculated to correlate the calcium volume with percent stenosis. Results: Of 100 carotid bifurcations, 88 were available and of these 7 were significantly stenotic. The NECT calcium volume moderately correlated with percent stenosis on DSA r50.53 (p,0.01). A moderate-strong correlation was found between the square root of calcium volume on NECT with percent stenosis on DSA (r50.60, p,0.01). Via a receiver operating characteristic curve, 0.06 cm 3 was determined to be the best threshold (sensitivity 100%, specificity 90.1%, negative predictive value 100% and positive predictive value 46.7%) for detecting significant stenoses. Conclusion: This preliminary investigation confirms a correlation between carotid bifurcation calcium volume and percent ICA stenosis and is promising for the optimal threshold for stenosis detection. Future studies could utilise calcium volumes to create a ''score'' that could predict high grade stenosis.

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“…43 Multidetector CT was used recently to calculate calcium content in CEA specimens. 44 They found that volume scores were not as reliable as mineral mass. Mineral mass can be calculated from our CT data, but volume quantitation seemed to be the best way to initially compare MR and CT.…”

Section: Discussionmentioning

confidence: 99%

“…For ICP-MS measurements, digestion of ashed specimens was first performed in a closed vessel nitric acid procedure. Dectection and quantitation of calcium and total phosphorus were based on the 44 Ca and 31 P ions using scandium as the internal standard. Results were generated in parts per million and the mass of each element then calculated based on the mass of the ashed specimen.…”

Section: Ash Weights and Chemical Analysismentioning

confidence: 99%

Mineral Volume and Morphology in Carotid Plaque Specimens Using High-Resolution MRI and CT

Wolf

Wehrli

Popescu

et al. 2005

ATVB

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Objective-High-resolution MRI methods have been used to evaluate carotid artery atherosclerotic plaque content. The purpose of this study was to assess the performance of high-resolution MRI in evaluation of the quantity and pattern of mineral deposition in carotid endarterectomy (CEA) specimens, with quantitative micro-CT as the gold standard. Methods and Results-High-resolution MRI and CT were compared in 20 CEA specimens. Linear regression comparing mineral volumes generated from CT (V CT ) and MRI (V MRI ) data demonstrated good correlation using simple thresholding (V MRI ϭϪ0.01ϩ0.98V CT ; R 2 ϭ0.90; thresholdϭ4ϫnoise) and k-means clustering methods (V MRI ϭϪ0.005ϩ1.38V CT ; R 2 ϭ0.93). Bone mineral density (BMD) and bone mineral content (BMC [mineral mass]) were calculated for CT data and BMC verified with ash weight. Patterns of mineralization like particles, granules, and sheets were more clearly depicted on CT. Conclusions-Mineral volumes generated from MRI or CT data were highly correlated. CT provided a more detailed depiction of mineralization patterns and provided BMD and BMC in addition to mineral volume. Key Words: magnetic resonance imaging Ⅲ computed tomography Ⅲ carotid arteries Ⅲ calcium A significant fraction of all ischemic strokes is caused by carotid atherosclerosis. Degree of stenosis is a major risk factor, but factors unrelated to the extent of vascular constriction play a role in causing neurological symptoms, including the morphology and composition of the atherosclerotic plaque. 1,2 Components of plaque associated with symptoms ("vulnerable plaque") include surface ulceration, thinning of fibrous cap, presence of hemorrhage, lipid core, and inflammation and neovascularity. [3][4][5][6] Dystrophic calcification (mineralization) and even lamellar bone have been described in carotid plaques. 7,8 There is evidence for an association between plaque lipid and dystrophic mineralization. 9 Using confocal microscopy, Sarig et al 10 found that cholesterol or associated lipids may act as a nucleus for hydroxyapatite crystal formation. It is unclear to what extent carotid plaque calcification affects the risk of embolic stroke. Certain patterns of calcification may help grade lesions and provide an indicator of stability. 11 The potential role of MRI for noninvasive assessment of plaque morphology and lesion burden quantification has been addressed in several investigations ex vivo and in vivo. [12][13][14][15][16][17][18][19][20][21][22][23][24] The appearance of plaque calcification has been described as uniformly dark in signal intensity on all MRI sequences. 18,25,26 However, there are other components of atherosclerotic plaque that may show decreased signal intensity on some or all pulse sequences; for example, solid cholesterol hydrate may be present and plaque lipids may exhibit T2 shortening secondary to liquid crystal behavior, depending on the lipid composition and cholesterol content. 20,27 Induced magnetic field inhomogeneities caused by differences in diamagnetic susceptibility betw...

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Vascular Calcification in ex Vivo Carotid Specimens: Precision and Accuracy of Measurements with Multi–Detector Row CT

Cited by 47 publications

References 29 publications

Calciotropic Hormones and Arterial Physiology

Calciotropic Hormones and Arterial Physiology

Correlation between carotid bifurcation calcium burden on non-enhanced CT and percentage stenosis, as confirmed by digital subtraction angiography

Mineral Volume and Morphology in Carotid Plaque Specimens Using High-Resolution MRI and CT

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