Monitoring the biological activity of abdominal aortic aneurysms<i>Beyond Ultrasound</i>

Forsythe, Rachael; Newby, David E.; Robson, J. M.

doi:10.1136/heartjnl-2015-308779

Cited by 39 publications

(47 citation statements)

References 50 publications

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“…6,7 Newer molecular imaging techniques also show uptake of 18 F-fludeoxyglucose and ultrasmall superparamagnetic particles of iron oxide into the ILT 8,9 as a marker of cellular deposition, migration, and decomposition. 10 In finite elements simulations using computed tomography angiography scans from AAA patients, cracks and fissures in the ILT increase wall stress on the underlying AAA wall. 11 Differences in ILT composition may result in different quantities and compositions of biologically active proteins accumulating near and in the AAA wall.…”

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confidence: 99%

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Andersen

Lindholt

Urbonavičius

et al. 2018

ATVB

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Objective-Porosity of the intraluminal thrombus (ILT) is believed to convey biologically active components from the bloodstream toward the aneurismal wall. Accumulation of molecules in the abdominal aortic aneurysmatic tissue may influence vascular protein turnover and regulate abdominal aortic aneurysm growth. We sought to identify proteins with concentrations in the ILT and the abdominal aortic aneurysm wall which associate with aneurysmal expansion rate. Approach and Results-Proteomic analysis by liquid chromatography tandem-mass spectrometry of separated wall and ILT samples was correlated with preoperative aneurysmal growth rate in 24 individuals operated electively for infrarenal abdominal aortic aneurysm. The median preoperative growth rate was 3.8 mm/y (interquartile range, 3) and the mean observational time was 3.3±1.7 years. Plasma components dominated the group of proteins with tissue concentrations, which correlate positively with growth rates (P<0.001, Fisher exact test, both in the ILT and the wall). In contrast, in the wall and thrombus samples, ECM (extracellular matrix) proteins were significantly more prevalent in the group of proteins with negative correlations to growth rates (P<0.05, Fisher exact test). Similarly, a long series of proteins, related to cellular functions correlated negatively to growth rates. Conclusions-When the preoperative aneurysmatic growth rate has been high, the concentration of many plasma proteins residing in the ILT and the aneurysmatic tissue is also high, compatible with the hypothesis of increased tissue porosity and accumulation of plasma components as a driver of aneurysm expansion. Moreover, many matrix and cellular proteins which are found in high concentrations in slower-growing aneurysms provides new knowledge about potential treatment targets. Visual Overview-An online visual overview is available for this article.

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confidence: 99%

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Andersen

Lindholt

Urbonavičius

et al. 2018

ATVB

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“…Each of these imaging modalities was shown to have a high diagnostic sensitivity for the detection 291 of aortic aneurysms in vivo (Thompson, et al 2002) as well as a high spatial resolution and soft 292 tissue contrast (Buijs, et al 2013, Forsythe, et al 2016, Hong, et al 2010, Sakalihasan, et al 2005. regions, which shows a close agreement.…”

Section: Interreader Agreement For the Assessment Of Thrombus Size Usmentioning

confidence: 86%

In Vivo High-Frequency Ultrasound for the Characterization of Thrombi Associated with Aortic Aneurysms in an Experimental Mouse Model

Jansen

Brangsch

Reimann

et al. 2017

Ultrasound in Medicine & Biology

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The development of abdominal aortic aneurysm (AAA) associated thrombi plays an important role during the onset and progression of AAAs. The aim of this study was to evaluate the potential of high-frequency ultrasound for characterization of AAA associated thrombi in an apolipoprotein-E-deficient mouse-model. Ultrasound measurements were performed using a high-resolution ultrasound system (Vevo770, FUJIFILM VisualSonics, Inc., Toronto, ON, Canada) with a 30 MHz linear-array transducer (RMV707 B). Magnetic resonance imaging with a 3 Tesla scanner (Achieva MR system, Philips Healthcare, Best, The Netherlands) and a single-loop microscopy coil was performed as a reference standard. All stages of aneurysm development were evaluated by histologic analyses. The "signal-thrombus-matrix" to "signal-blood" ratio on high-frequency ultrasound measurements showed a strong correlation (R = 0.81, p <0.05) with the state of extracellular matrix remodeling. Furthermore, size measurements derived from the high-frequency ultrasound correlated well with magnetic resonance imaging and histology. This study demonstrated that high-frequency ultrasound enables the reliable in vivo quantification of extracellular matrix remodeling at various stages of thrombus development, based on the thrombus echogenicity.

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“…This finding provides strong support for the concept that imaging the biology of abdominal aortic aneurysm may be a promising new approach to risk stratify and manage patients with this disease. 11 The rate of abdominal aortic aneurysm growth has previously been shown to be predicted by smoking status, aneurysm size, and the presence of common iliac aneurysms. 9,28 Indeed, a smoking habit is the principal modifiable risk factor for abdominal aortic aneurysm progression and rupture and is the main focus of lifestyle modification in these patients.…”

Section: Discussionmentioning

confidence: 99%

“…Last, ≤20% of ruptured abdominal aortic aneurysms are <55 mm in diameter, and 40% of patients with aneurysm diameters between 70 and 100 mm do not experience aneurysm rupture. 10 Therefore, an unmet clinical need exists to identify more reliable methods of identifying those patients at risk of abdominal aortic aneurysm expansion and rupture, 11,12 and techniques that assess both the structure and biology of aneurysms hold considerable promise.Ultrasmall superparamagnetic particles of iron oxide (USPIO) constitute a class of magnetic resonance imaging (MRI) contrast agent taken up by tissue-resident macrophages and can be used to identify cellular inflammation within tissues, 13,14 including abdominal aortic aneurysms. 15,16 In a small pilot study of 29 patients with abdominal aortic aneurysm, 15 we have previously demonstrated that USPIO enhancement on MRI is associated with macrophage infiltration of the abdominal aortic aneurysm wall and more rapid rates of abdominal aortic aneurysm expansion.…”

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confidence: 99%

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture and Need for Surgical Repair

2017

Journal of Vascular Surgery

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BACKGROUND:Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIOenhanced MRI can predict aneurysm growth rates and clinical outcomes. METHODS:In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. RESULTS:Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1. 1-22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P<0.0001) and current smoking habit (P=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935-0.7936).CONCLUSIONS: USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. CLINICAL TRIAL REGISTRATION: Abdominal aortic aneurysms have a prevalence of 5% in 65-to 74-year-old men and, when ruptured, are associated with a mortality of ≤90%. 1At a population level, ruptured aortic aneurysms are a major cause of death, being the 13th most common cause of death and accounting for >150 000 deaths in 2013.2 Preemptive elective open surgical or endovascular repair can be life-saving and is considered when the abdominal aortic aneurysm diameter is >55 mm, is rapidly expanding (≥10 mm/year), or causes symptoms. [3][4][5] Abdominal aortic aneurysms are usually associated with no symptoms and are often identified incidentally or as part of an ultrasound-based screening program. Population screening has been established in some countries and is associated...

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Monitoring the biological activity of abdominal aortic aneurysmsBeyond Ultrasound

Cited by 39 publications

References 50 publications

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

Abdominal Aortic Aneurysms Growth Is Associated With High Concentrations of Plasma Proteins in the Intraluminal Thrombus and Diseased Arterial Tissue

In Vivo High-Frequency Ultrasound for the Characterization of Thrombi Associated with Aortic Aneurysms in an Experimental Mouse Model

Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture and Need for Surgical Repair

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