Imaging Biological Pathways in Abdominal Aortic Aneurysms Using Positron Emission Tomography.
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ABSTRACT:
SUBMITTER: Bell M
PROVIDER: S-EPMC7610660 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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Imaging Biological Pathways in Abdominal Aortic Aneurysms Using Positron Emission Tomography.
Bell Michael M Gandhi Richa R Shawer Heba H Tsoumpas Charalampos C Bailey Marc A MA
Arteriosclerosis, thrombosis, and vascular biology 20210325 5
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Project description:This study aims at identifying genes involved in this metabolic activation potentially related to rupture. A genome-wide transcriptomic analysis was performed on biopsies collected from patients with a Fluorodeoxyglucose (FDG) uptake both in the positive spot (A+Pos) and in a distant negative site of the same aneurysm (A+Neg). These paired biopsies were further compared to samples collected from (abdominal aortic aneurysms) AAA patients with no FDG uptake (A0) in order to discriminate biological alterations associated with FDG uptake, to detect new systemic biomarkers correlated with a higher risk of rupture and to identify new pathways involved in the progression and rupture of AAA).
2015-02-09 | E-MTAB-3175 | biostudies-arrayexpress
Project description:ObjectivesInflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA.Materials and methodsFifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation.ResultsWhen all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake.ConclusionsBoth (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.
| S-EPMC4829709 | biostudies-literature
Project description:Both inflammation and neoangiogenesis contribute to abdominal aortic aneurysm (AAA) disease. Arg-Gly-Asp-based molecular imaging has been shown to detect the integrin ?v?3. We studied a clinical dimeric (18)F-labeled Arg-Gly-Asp positron-emission tomography (PET) agent ((18)F-FPPRGD2) for molecular imaging of experimental AAAs.Murine AAAs were induced in Apo-E-deficient mice by angiotensin II infusion, with monitoring of aortic diameter on ultrasound. AAA (n=10) and saline-infused control mice (n=7) were injected intravenously with (18)F-FPPRGD2, as well as an intravascular computed tomography contrast agent, then scanned using a small-animal PET/computed tomography scanner. Aortic uptake of (18)F-FPPRGD2 was quantified by percentage-injected dose per gram and target-to-=0.003; median target-to-=0.0008). Ex vivo autoradiography demonstrated high uptake of (18)F-FPPRGD2 into the AAA wall, with immunohistochemistry showing substantial cluster of differentiation (CD)-11b(+) macrophages and CD-31(+) neovessels. Target-to-=-0.29, P=0.41) but did strongly correlate with both mural macrophage density (r=0.79, P=0.007) and neovessel counts (r=0.87, P=0.001) on immunohistochemistry.PET imaging of experimental AAAs using (18)F-FPPRGD2 detects biologically active disease, correlating to the degree of vascular inflammation and neoangiogenesis. This may provide a clinically translatable molecular imaging approach to characterize AAA biology to predict risk beyond size alone.
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Project description:ObjectiveCurrent management of aortic aneurysms (AAs) relies primarily on size criteria to determine whether invasive repair is indicated to preempt rupture. We hypothesized that emerging molecular imaging tools could be used to more sensitively gauge local inflammation. Because macrophages are key effector cells that destabilize the extracellular matrix in the arterial wall, it seemed likely that they would represent suitable imaging targets. We here aimed to develop and validate macrophage-targeted nanoparticles labeled with fluorine-18 ((18)F) for positron emission tomography-computed tomography (PET-CT) detection of inflammation in AAs.Methods and resultsAneurysms were induced in apolipoprotein E-/- mice via systemic administration of angiotensin II. Mice were imaged using PET-CT and a monocyte/macrophage-targeted nanoparticle. AAs were detected by contrast-enhanced micro-CT and had a mean diameter of 1.85 ± 0.08 mm, whereas normal aortas measured 1.07 ± 0.03 (P < 0.05). The in vivo PET signal was significantly higher in aneurysms (standard uptake value, 2.46 ± 0.48) compared with wild-type aorta (0.82 ± 0.05, P < 0.05). Validation with scintillation counting, autoradiography, fluorescence, and immunoreactive histology and flow cytometry demonstrated that nanoparticles localized predominantly to monocytes and macrophages within the aneurysmatic wall.ConclusionsPET-CT imaging with (18)F-labeled nanoparticles allows quantitation of macrophage content in a mouse model of AA.
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Project description:Abdominal aortic aneurysm (AAA) disease is characterized by an asymptomatic, permanent, focal dilatation of the abdominal aorta progressing towards rupture, which confers significant mortality. Patient management and surgical decisions rely on aortic diameter measurements via abdominal ultrasound surveillance. However, AAA rupture can occur at small diameters or may never occur at large diameters, implying that anatomical size is not necessarily a sufficient indicator. Molecular imaging may help identify high-risk patients through AAA evaluation independent of aneurysm size, and there is the question of the potential role of positron emission tomography (PET) and emerging role of novel radiotracers for AAA. Therefore, this review summarizes PET studies conducted in the last 10 years and discusses the usefulness of PET radiotracers for AAA risk stratification. The most frequently reported radiotracer was [18F]fluorodeoxyglucose, indicating inflammatory activity and reflecting the biomechanical properties of AAA. Emerging radiotracers include [18F]-labeled sodium fluoride, a calcification marker, [64Cu]DOTA-ECL1i, an indicator of chemokine receptor type 2 expression, and [18F]fluorothymidine, a marker of cell proliferation. For novel radiotracers, preliminary trials in patients are warranted before their widespread clinical implementation. AAA rupture risk is challenging to evaluate; therefore, clinicians may benefit from PET-based risk assessment to guide patient management and surgical decisions.
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Project description:Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA with-out FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+(Pos)) and at a paired distant negative site (A+(Neg)) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+(Pos) compared with A+(Neg). Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+(Neg) and A+(Pos) compared with the A0. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.
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Project description:Aortic valve stenosis (AVS) is an increasingly prevalent disease in our aging population. Although multiple risk factors for AVS have been elucidated, medical therapies capable of slowing down disease progression remain unavailable. Molecular imaging technologies are opening up avenues for the non-invasive assessment of disease progression, allowing the assessment of (early) medical interventions. This review will focus on the role of positron emission tomography of the aortic valve with 18F-fluorodeoxyglucose and 18F-sodium fluoride but will also shed light on novel tracers which have potential in AVS, ranging from the healthy aortic valve to end-stage valvular disease.
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Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia among the elderly population. The good correlation between the density and neocortical spread of neurofibrillary tangles (NFTs) and the severity of cognitive impairment offers an opportunity to use a noninvasive imaging technique such as positron emission tomography (PET) for early diagnosis and staging of the disease. PET imaging of NFTs holds promise not only as a diagnostic tool but also because it may enable the development of disease-modifying therapeutics for AD. In this review, we focus on the structural diversity of tau PET tracers, the challenges related to identifying high-affinity and highly selective NFT ligands, and recent progress in the clinical development of tau PET radioligands.
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Project description:A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers).
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Project description:BackgroundThe monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (64Cu-DOTA-ECL1i).MethodsAAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of β-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer.ResultsBiodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; P<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; P<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues.ConclusionsCCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.
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