Imaging of abdominal aortic aneurysm disease activity and implications for endovascular aneurysm repair

BACKGROUND: Abdominal aortic aneurysm treatment pathways are initiated when an aortic size threshold of 55 mm is reached as this signifies a high annual risk of rupture due to presumed active aneurysm disease. Endovascular aneurysm repair (EVAR) is one treatment modality which reduces the procedural morbidity and mortality associated with open surgical repair. However, EVAR patients can develop complications such as leaks behind their stent graft (endoleak) which reduces the long-term benefit of EVAR. Here, we explore the use of two potential imaging biomarkers, periaortic adipose tissue (on computed tomography) and sodium [18F]fluoride positron emission tomography, in different abdominal aortic aneurysm disease states to better understand the disease process and to assess its implications in EVAR. METHODS: First, we assessed periaortic adipose tissue attenuation in 70 patients with untreated abdominal aortic aneurysm disease (asymptomatic, symptomatic and rupture patients) and 18 control subjects (Chapter 3). Then, in 25 patients with an abdominal aortic aneurysm, we developed a method of quantifying sodium [18F]fluoride uptake on positron emission tomography, which we termed aortic microcalcification activity (AMA) (Chapter 4). We then considered sodium [18F]fluoride uptake in 10 patients before and after their aneurysm was treated with EVAR (Chapter 5). Following this, we assessed sodium [18F]fluoride uptake in 37 patients whose aneurysm had been treated with EVAR, in 15 of whom this had been complicated by endoleak formation (Chapter 6). RESULTS: There were no differences in the periaortic adipose tissue attenuation in aneurysmal and non-aneurysmal segments of the aorta in asymptomatic patients (-81.4±7 versus -75.4±8 Hounsfield units, HU) and comparable segments in control subjects (-83.3±9 versus -78.8±6 HU, p>0.05 for all comparisons). However, symptomatic patients demonstrated higher periaortic adipose tissue attenuation in both aneurysmal (-57.9±7 HU, p<0.0001) and non-aneurysmal segments (-58.2±8 HU, p<0.0001). There was moderate-to-good agreement between mean tissue-to-background ratio and aortic microcalcification activity (AMA) measurements (intraclass correlation co-efficient, 0.88). These, sequentially improved with the application of thresholding (intraclass correlation coefficient 0.93, 95% confidence interval 0.89–0.95) and variable diameter (intraclass correlation coefficient 0.97, 95% confidence interval 0.94–0.99) techniques. The optimised method had good intra-observer (mean 1.57 ± 0.42, bias 0.08, coefficient of repeatability 0.36 and limits of agreement -0.43 to 0.43) and inter-observer (mean 1.57 ± 0.42, bias 0.08, co-efficient of repeatability 0.47 and limits of agreement -0.53 to 0.53) repeatability. We found that following EVAR, sodium [18F]fluoride uptake was markedly reduced in the suprarenal (0.62 reduction, p=0.03), neck (0.72 reduction, p=0.02) and body of the aneurysm (0.69 reduction, p=0.02) while it remained unchanged in the thoracic aorta (0.11 reduction, p=0.41). When compared to those without an endoleak, patients with an endoleak had higher AMA in the thoracic (1.22±0.2 versus 1.07±0.2, p0.05). CONCLUSION: Periaortic adipose tissue attenuation is not increased in stable abdominal aortic aneurysm disease. The generalised increase in patients with symptomatic disease likely reflects the systemic consequences of acute rupture. Aortic microcalcification activity (AMA) provides repeatable measures of sodium [18F]fluoride uptake that are comparable to established methods. EVAR is associated with a reduction in AMA within the stented aortic segment, whilst endoleaks after EVAR are associated with higher AMA in aortic regions outside the aneurysm. These findings suggest that whilst EVAR can modify aortic disease activity within the treated aneurysm, aortic degeneration appears to continue beyond the aneurysm. Aortic sodium [18F]fluoride uptake is a promising non-invasive measure of aneurysm disease activity that may inform treatment strategies and provide additional prognostic information

MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies

BACKGROUND: High throughput gene expression profiling (GEP) is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option. GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported. RESULTS: MAF (MicroArray Facility) is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking), data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF. CONCLUSION: MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for shared facilities and industry service providers alike

Computed tomography attenuation of periaortic adipose tissue in abdominal aortic aneurysms

Purpose: To assess periaortic adipose tissue attenuation on CT angiography indifferent abdominal aortic aneurysm disease states.Materials and Methods: In a retrospective observational study from January 2018 to December 2022, periaortic adipose tissue attenuation was assessed on CT angiography in patients with asymptomatic or symptomatic (including rupture) abdominal aortic aneurysms, and control individuals without aneurysms. Adipose tissue attenuation was measured using semi-automated software in periaortic aneurysmal and non-aneurysmal segments of the abdominal aorta, and in subcutaneous and visceral adipose tissue. Periaortic adipose tissue attenuation values between the three groups was assessed using Students t-test and Wilcoxon rank sum test followed by a multi-regression model.Results: Eighty-eight individuals (median age, 70 [IQR, 65-78] years; 78 male and 10 female) were included: 70 patients with abdominal aortic aneurysms (40 asymptomatic and 30 symptomatic including 24 with rupture), and 18 controls. There was no evidence of differences in the periaortic adipose tissue attenuation in the aneurysmal segment in asymptomatic patients versus controls ((-81.44±7 versus -83.27±9 HU, Hounsfield units, P=0.43) and attenuation in non-aneurysmal segments between asymptomatic patients versus controls (-75.43±8 versus -78.81±6 HU, P=0.08). However, symptomatic patients demonstrated higher periaortic adipose tissue attenuation in both aneurysmal (-57.85±7 HU, P&lt;0.0001) and non-aneurysmal segments (-58.16±8 HU, P&lt;0.0001) when compared with the other two groups.Conclusions: Periaortic adipose tissue CT attenuation was not increased in stableabdominal aortic aneurysm disease. There was a generalised increase in attenuation in patients with symptomatic disease, likely reflecting the systemic consequences of acute rupture

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions

MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies

Abstract Background High throughput gene expression profiling (GEP) is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option. GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported. Results MAF (MicroArray Facility) is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking), data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF. Conclusion MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for shared facilities and industry service providers alike.</p

Aortic sodium [18 F]fluoride uptake following endovascular aneurysm repair

Objective: In patients with abdominal aortic aneurysms, sodium [18F]fluoride positron emission tomography identifies aortic microcalcification and disease activity. Increased uptake is associated with aneurysm expansion and adverse clinical events. The effect of endovascular aneurysm repair (EVAR) on aortic disease activity and sodium [18F]fluoride uptake is unknown. This study aimed to compare aortic sodium [18F]fluoride uptake before and after treatment with EVAR. Methods: In a preliminary proof-of-concept cohort study, preoperative and post-operative sodium [18F]fluoride positron emission tomography-computed tomography angiography was performed in patients with an infrarenal abdominal aortic aneurysm undergoing EVAR according to current guideline-directed size treatment thresholds. Regional aortic sodium [18F]fluoride uptake was assessed using aortic microcalcification activity (AMA): a summary measure of mean aortic sodium [18F]fluoride uptake. Results: Ten participants were recruited (76±6 years) with a mean aortic diameter of 57±2 mm at time of EVAR. Mean time from EVAR to repeat scan was 62±21 months. Prior to EVAR, there was higher abdominal aortic AMA when compared with the thoracic aorta (AMA 1.88 vs 1.2; p&lt;0.001). Following EVAR, sodium [18F]fluoride uptake was markedly reduced in the suprarenal (ΔAMA 0.62, p=0.03), neck (ΔAMA 0.72, p=0.02) and body of the aneurysm (ΔAMA 0.69, p=0.02) while it remained unchanged in the thoracic aorta (ΔAMA 0.11, p=0.41). Conclusions: EVAR is associated with a reduction in AMA within the stented aortic segment. This suggests that EVAR can modify aortic disease activity and aortic sodium [18F]fluoride uptake is a promising non-invasive surrogate measure of aneurysm disease activity