Exploring the Acceptable Delay for Elective Treatment of Patients With an Abdominal Aortic Aneurysm: A Reflection During a Pandemic and an Exploratory Analysis.

INTRODUCTION: This study sought to determine the rupture risk of asymptomatic abdominal aortic aneurysms (AAAs) undergoing interventions as a function of time to establish a maximal acceptable surgical delay. METHODS: A literature review was performed from inception to August 30, 2021, to assess the risk of rupture of aneurysms over time. The analysis was limited to men with asymptomatic AAAs. The data on AAA rupture risk according to diameter and follow-up time were extracted. The acceptable mortality risk for AAA patients as a function of surgical delay was further evaluated. This acceptable mortality risk was based on the acceptable risk of cardiovascular death associated with the accepted delays of coronary revascularization in coronary artery disease populations. Data on estimated surgical delays and risks were extracted using a free web-based software (WebPlotDigitizer) and plotted using Microsoft Excel. RESULTS: Our study identified minimal evidence as it pertains to AAA rupture risk as a function of surgical delay. The data on rupture risk of AAAs according to diameter and time were extracted from a single review and a single meta-analysis (Figure 1). The acceptable delays of semiurgent and nonurgent invasive treatment for coronary artery disease found in literature are 6 and 12 wks respectively. These acceptable delays are associated with an estimated acceptable cardiovascular mortality risk threshold of 0.47% at 6 and 12 wks. Using this threshold of estimated maximum acceptable risk and the data on the natural history of AAAs found in our review, we found that the acceptable surgical delays for AAAs would be estimated at 13-27 ds for AAAs ≥ 7 cm, 20-42 ds for 6-6.9 cm, and 32-49 ds for 5.5-5.9 cm (Figure 1). CONCLUSIONS: This study identified estimated surgical delays for patients with AAAs based on the acceptable maximum risk. These estimations may be used cautiously to triage patients with asymptomatic AAAs, particularly in the setting of triaging patients during local and global crises.

Ruptured AAA: bridging the gap between international guidelines and local clinical realities.

BACKGROUND: Treatment of asymptomatic Abdominal Aortic Aneurysms (AAA) presents a clinical challenge, requiring a delicate balance between rupture risk, patient comorbidities, and intervention-related complications. International guidelines recommend intervention for specific AAA size thresholds, but these are based on historical trials with limited female representation. We aimed to analyse disease characteristics, AAA size at rupture, and intervention outcomes in patients with ruptured AAA from 2009 to 2023 to investigate the gap between guidelines and local realities. METHODS: This single-centre retrospective cohort study analysed electronic health records of patients treated for a ruptured AAA, excluding those who were managed palliatively. The study assessed patients' demographics, risk factors, comorbidities, clinical presentation, radiological characteristics, and outcomes. RESULTS: Of 164 patients (41 females, 123 males, median age 73.5), 93.3% presented with abdominal or back pain. The median AAA size at rupture was 8.0 cm in males and 7.6 cm in females. No significant correlations were found between demographic characteristics, risk factors, AAA size, repair modality, and outcomes. Trends show a decline in AAA prevalence and rupture rates, aligning with global health initiatives. Post-intervention survival rates at 30 days were 70.7% (67.5% in males and 80.0% in females), and at 2 years were 65.85% (61.7% in males and 70.0% in females). CONCLUSION: Evolving AAA trends and improved post-intervention survival rates warrant a critical reassessment of existing intervention recommendations. Adjusting intervention thresholds to larger sizes may be justified to optimise the risk-benefit ratio.

Unveiling rupture risk and clinical outcomes in midline aneurysms: A matched cohort analysis investigating the impact of localization within the anterior or posterior circulation.

Intracranial aneurysms (IAs) located in the anterior and posterior circulations of the Circle of Willis present differential rupture risks. This study aimed to compare the rupture risk and clinical outcomes of anterior communicating artery aneurysms (AcomA) and basilar tip aneurysms (BAs); two IA types located along the midline within the Circle of Willis. We retrospectively collected data from 1026 patients presenting with saccular IAs. Only AcomA and BAs with a 3D angiography were included. Out of 186 included IAs, a cohort of 32 BAs was matched with AcomA based on the patients' pre-existing conditions and morphological parameters of IAs. Clinical outcomes, including rupture risk, hydrocephalus development, vasospasm incidence, and patients' outcome, were compared. The analysis revealed no significant difference in rupture risk, development of hydrocephalus, need for ventricular drainage, or vasospasm incidence between the matched AcomA and BA cohorts. Furthermore, the clinical outcomes post-rupture did not significantly differ between the two groups, except for a higher Fisher Grade associated with BAs. Once accounting for morphological and patient factors, the rupture risk between AcomA and BAs is comparable. These findings underscore the importance of tailored management strategies for specific IA types and suggest that further investigations should focus on the role of individual patient and aneurysm characteristics in IA rupture risk and clinical outcomes.

Small intracranial aneurysms of the anterior circulation: A negligible risk?

BACKGROUND AND PURPOSE: According to the International Study of Unruptured Intracranial Aneurysms, small (<7 mm) unruptured intracranial aneurysms (IAs) of the anterior circulation (aC) carry a neglectable 5-year rupture risk. In contrast, some studies report frequencies of >20% of all ruptured IAs being small IAs of the aC. This contradiction was addressed in this study by analyzing the rates and risk factors for rupture of small IAs within the aC. METHODS: Of the institutional observational cohort, 1676 small IAs of the aC were included. Different demographic, clinical, laboratory, and radiographic characteristics were collected. A rupture risk score was established using all independent prognostic factors. The score performance was checked using receiver operating characteristic curve analysis. RESULTS: Of all registered small IAs of the aC, 20.1% were ruptured. The developed small IAs of the aC (SIAAC) score (range = -4 to +13 points) contained five major risk factors: IA location and size, arterial hypertension, alcohol abuse, and chronic renal failure. In addition, three putative protective factors were also included in the score: hypothyroidism, dyslipidemia, and peripheral arterial disease. Increasing rates of ruptured IA with increasing SIAAC scores were observed, from 0% (≤-1 points) through >50% (≥8 points) and up to 100% in patients scoring ≥12 points. The SIAAC score achieved excellent discrimination (area under the curveSIAAC  = 0.803) and performed better than the PHASES (Population,Hypertension, Age, Size of the aneurysm, Earlier SAH from another aneurysm, Site of aneurysm) score. CONCLUSIONS: Small IAs of the aC carry a considerable rupture risk. After external validation, the proposed rupture risk score might provide a basis for better decision-making regarding the treatment of small unruptured IAs of the aC.

Prediction of abdominal aortic aneurysm growth by artificial intelligence taking into account clinical, biologic, morphologic, and biomechanical variables.

OBJECTIVES: To develop a prediction model that could risk stratify abdominal aortic aneurysms (AAAs) into high and low growth rate groups, using machine learning algorithms based on variables from different pathophysiological fields. METHODS: A cohort of 40 patients with small AAAs (maximum diameter 32-53 mm) who had at least an initial and a follow-up CT scan (median follow-up 12 months, range 3-36 months) were included. 29 input variables from clinical, biological, morphometric, and biomechanical pathophysiological aspects extracted for predictive modeling. Collected data were used to build two supervised machine learning models. A gradient boosting (XGboost) and a support vector machines (SVM) algorithm were trained with 60% and tested with 40% of the data to predict which AAA would achieve a growth rate higher than the median of our study cohort. Receiver operating characteristics (ROC) curves and areas under the curve (AUC) were used for the evaluation of the developed algorithms. RESULTS: XGboost achieved the highest AUC in predicting high compared to low AAA growth rate with an AUC of 81.2% (95% CI from 61.1 to 100%). SVM achieved the second highest performance with an AUC of 68.8% (95% CI from 46.5 to 91%). Based on the best performing algorithm, variable importance was estimated. Diameter-diameter ratio (maximum diameter/neck diameter), Tortuosity from Renal arteries to aortic bifurcation, and maximum thickness of the intraluminal thrombus were found to be the most important factors for model predictions. Other factors were also found to play a significant but less important role. CONCLUSIONS: A prediction model that can risk stratify AAAs into high and low growth rate groups could be developed by analyzing several factors implicated in the multifactorial pathophysiology of this disease, with the use of machine learning algorithms. Future studies including larger patient cohorts and implementing additional risk markers may aid in the establishment of such methodology during AAA rupture risk estimation.

Changes in Distance Between the Flexor Pollicis Longus Tendon and Volar Locking Plate: An Ultrasonographic Study.

PURPOSE: Flexor pollicis longus rupture is a major complication after volar locking plate fixation of distal radius fractures. Although the distance between the flexor pollicis longus tendon and the plate (plate-tendon distance) measured by ultrasonography is used to predict tendon rupture risk, the timing of the ultrasonography can affect the measurements. Therefore, this study aimed to analyze the chronological change of the plate-tendon distance between the tendon and plate. METHODS: A total of 166 wrists underwent the plate-tendon distance measurement twice or more times within 15 months after surgery. Longitudinal ultrasonography scans with the wrist in a neutral position and the thumb flexed were used to measure the plate-tendon distance. The plate-tendon distances at 0-5 months, 5-10 months, and 10-15 months after surgery were compared. A multiple linear regression analysis was performed to evaluate the influence of the interval between surgery and examination, Soong grade, and plate type on the plate-tendon distance. RESULTS: The plate-tendon distance decreased as the interval between surgery and examination increased. The plate-tendon distance was an average of 2.0 ± 1.1 mm, 1.4 ± 0.9 mm, and 1.2 ± 0.9 mm at 0-5 months, 5-10 months, and 10-15 months after surgery, respectively. Significant differences were observed between 0-5 months and 5-10 months and between 5-10 months and 10-15 months after surgery. A multiple linear regression showed that significant predictors of the plate-tendon distance were the intervals between surgery and examination and Soong grade. CONCLUSIONS: The plate-tendon distance decreased as the time since surgery increased. When ultrasonography is used for the assessment of tendon rupture risk, it should be considered that the plate-tendon distance decreases as the interval between the surgery and examination increases. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Comment on the Invited Discussion on "Assessment of Risk Factors for Rupture in Breast Reconstruction Patients with Macrotextured Breast Implants".

We here present a few comments on the invited discussion of Dr. van Heijningen on the paper "Assessment of Risk Factors for Rupture in Breast Reconstruction Patients with Macrotextured Breast Implants". Dr. van Heijningen made some reservations regarding paper conclusions due to the high dropout rate, the adopted exclusion criteria and the location and mechanism of implant rupture. First of all, a high dropout rate is not unbeknown to researchers in surveys-based studies and may be expected when recalling in 6 months a population observed during last 20 years. In our study data are missing at random not affecting the risk of bias, while the population accurately depicts the people we care, mainly but not only reconstructive. Patients who did not respond to the questionnaire could not participate to the survey, while those who did not hold recent imaging were excluded because of the risk of false negative due to possible silent rupture, accounting to 10% in some reports. MRI imaging often shows that implants fold back on their selves when capsular contracture reduces implant pocket. As the use of the underwire bra prevents implant inferior displacement, repeated muscular contraction may worsen implant folds and the chronic wear-and-tear mechanism may be responsible for the rupture. Finally, folding is presumably easier to occur at the upper quadrants where anatomical implant shell is thinnest and gel concentration reduced than the opposite, therefore is not surprising that the higher percentage of ruptures is located in the upper implant quadrants.Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Assessment of Risk Factors for Rupture in Breast Reconstruction Patients with Macrotextured Breast Implants.

BACKGROUND: Breast implants (BI) are widely used in plastic surgery, though they are not lifetime devices. Average life before rupture is reported to be around 10-15 years. No consensus exists regarding which factors are involved. OBJECTIVES: Following FDA recommendations, this study aims at identifying potential risk factors by evaluating their effect on BI rupture cases. METHODS: In this observational study, 763 BI patients were operated between 2003 and 2019, with a mean implant indwelling of 12.2 years. Patients that returned for follow-up were administered a questionnaire regarding postoperative lifestyle and habits. Implant rupture rate was 15.1%, while BI lifespan was 10.1 years. We obtained complete data from 191 breast implant patients (288 implants). Twenty-three potential risk factors were evaluated and divided in four categories: patient-related, surgery-related, postoperative complications/symptoms, and postoperative care/lifestyle habits. Odds Ratio (OR) for each factor was calculated. Linear regression analysis was calculated for those with a significant OR. RESULTS: We report 120 patients (195 implants) with intact and 71 (93 implants) with ruptured devices. BIs were macrotextured in 95.1% of cases (86.8% Allergan BIOCELL). OR was significant for underwire bra use (OR: 2.708), car seat belts (OR: 3.066), mammographic imaging (OR: 2.196), weightlifting (OR: 0.407) and carry-on heavy purses and backpacks (OR: 0.347). CONCLUSION: Wearing underwire bras, seat belts and undergoing mammography increases the risk of rupture. Weightlifting and carry heavy bags do not increase that risk. Implant rupture is directly linked with time of indwelling. Postoperative recommendations in BI patients should consider findings from our study, though larger multicenter studies should be encouraged. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Narrative Review of Risk Assessment of Abdominal Aortic Aneurysm Rupture Based on Biomechanics-Related Morphology.

CLINICAL IMPACT: Studies have shown that the biomechanical indicators based on multi-scale models are more effective in accurately assessing the rupture risk of AAA. To meet the need for clinical monitoring and rapid decision making, the typical morphological parameters associated with AAA rupture and their relationships with the mechanical environment have been summarized, which provide a reference for clinical preoperative risk assessment of AAA.

Unruptured intracranial aneurysms: relation between morphology and wall strength.

AIM OF THE STUDY: To determine the morphological features distinguishing small unruptured saccular intracranial aneurysms (sIAs) with high and low wall strength (WS) in post mortem subjects. CLINICAL RATIONALE FOR THE STUDY: Subarachnoid haemorrhage caused by sIA rupture is associated with increased mortality and morbidity. Analysis of the morphology and biomechanical properties of sIAs might facilitate the identification of clinically relevant risk factors for sIA rupture. MATERIAL AND METHODS: Eight single unruptured sIAs were found among eight subjects during 184 post mortem examinations. After assessment of the dimensions, aspect ratio (AR), size ratio (SR), height/width ratio (HW), bottleneck factor (BNF), and shape, sIAs with adjacent cerebral arteries were subjected to quasi-static increasing pressure until the wall of the cerebral artery or sIA ruptured. RESULTS: In three specimens, the sIA ruptured at a significantly lower average pressure than the other cases, in which the rupture occurred within the wall of the adjacent cerebral artery (769 vs. 1,259 mmHg; p = 0.035). The sIAs with low WS, i.e. sIAs that ruptured during experiments, were characterised by significantly increased dome dimensions compared to sIAs with high WS (p < 0.05). At the same time, no significant differences were observed between high and low WS categories regarding AR, SR, HW, and BNF, or the presence of an irregular dome shape. CONCLUSIONS AND CLINICAL IMPLICATIONS: Dome dimension was the only feature that distinguished unruptured sIAs as having low or high WS, and this supports observations that sIAs with increased dome dimensions are characterised by an increased risk of rupture. Thus, dome dimension may be more useful than other morphometric parameters, such as AR, SR, HW and BNF, in assessing the rupture risk assessment of small unruptured sIAs.

Biomechanical indices are more sensitive than diameter in predicting rupture of asymptomatic abdominal aortic aneurysms.

OBJECTIVE: Several studies of biomechanical rupture risk assessment (BRRA) showed its advantage over the diameter criterion in rupture risk assessment of abdominal aortic aneurysm (AAA). However, BRRA studies have not investigated the predictability of biomechanical risk indices at different time points ahead of rupture, nor have they been performed blinded for biomechanical analysts. The objective of this study was to test the predictability of the BRRA method against diameter-based risk indices in a quasi-prospective patient cohort study. METHODS: In total, 12 women and 31 men with intact AAAs at baseline have been selected retrospectively at two medical centers. Within 56 months, 19 cases ruptured, whereas 24 cases remained intact within 2 to 56 months. This outcome was kept confidential until all biomechanical activities in this study were finished. The biomechanical AAA rupture risk was calculated at baseline using high-fidelity and low-fidelity finite element method models. The capability of biomechanics-based and diameter-based risk indices to predict the known outcomes at 1 month, 3 months, 6 months, 9 months, and 12 months after baseline was validated. Besides common cohort statistics, the area under the curve (AUC) of receiver operating characteristic curves has been used to grade the different rupture risk indices. RESULTS: Up to 9 months ahead of rupture, the receiver operating characteristic analysis of biomechanics-based risk indices showed a higher AUC than diameter-based indices. Six months ahead of rupture, the largest difference was observed with an AUC of 0.878 for the high-fidelity biomechanical risk index, 0.859 for the low-fidelity biomechanical risk index, 0.789 for the diameter, and 0.821 for the sex-adjusted diameter. In predictions beyond 9 months, none of the risk indices proved to be superior. CONCLUSIONS: High-fidelity biomechanical modeling improves the predictability of AAA rupture. Asymptomatic AAA patients with high biomechanical AAA rupture risk indices have an increased risk of rupture. Integrating biomechanics-based diagnostic indices may significantly decrease the false-positive rate in AAA treatment. CLINICAL RELEVANCE: Rupture of abdominal aortic aneurysm (AAA) is the tenth leading cause of death in men older than 60 years; however, the currently used maximal diameter criterion has a high false-positive rate. In this study, we have compared this criterion with biomechanical rupture risk assessment on the unique data set of 43 asymptomatic AAAs, of which 19 ruptured later. Moreover, the AAA outcome was blinded to the operator for the first time. Our data demonstrated that the biomechanical rupture risk assessment is superior to maximal diameter in predicting AAA rupture up to 9 months ahead and significantly decreases the false-positive rate.

Anatomical Differences Between Intact and Ruptured Large Abdominal Aortic Aneurysms.

Purpose: To compare different anatomical characteristics between intact and ruptured large abdominal aortic aneurysms (rAAA >80 mm) with the goal of refining the process of estimating rupture risk. Materials and Methods: A retrospective study involving 62 male patients with large (>80 mm) aneurysms matched for age and smoking produced a 31-patient elective group with a mean maximum aneurysm diameter of 92±9.7 mm and a 31-patient rAAA group (mean maximum aneurysm diameter 95.7±12 mm). Preoperative computed tomography angiography scans were analyzed with a dedicated workstation, and anatomical characteristics of the aortic neck, iliac arteries, and aneurysm were compared in multivariable regression analyses; the outcomes are given as the odds ratio (OR) with 95% confidence interval (CI). The prognostic utility of several characteristics as predictors of rupture occurrence was examined with receiver operating characteristic (ROC) curves. Results: Anatomical characteristics differing significantly between elective and ruptured aneurysms were the infrarenal aortic neck diameters at 5 mm, 10 mm and 15 mm; the neck length and calcification; the common iliac artery (CIA) lengths; the iliac artery indexes; the left CIA and external iliac artery diameters; and the total and true lumen aneurysm volumes. Intraluminal thrombus (ILT) volume did not differ (p=0.76), although its distribution in elective vs ruptured cases did [absent: 0% vs 19%, respectively (p=0.025); circumferential: 61% vs 35%, respectively (p=0.04)]. Total aneurysm volume was higher in rAAA (442±140 mL) vs intact AAA (331±143 mL, p=0.014), while the ILT/total aneurysm volume rate was lower in rAAA (55%) vs intact AAA (70%, p=0.02). Multivariate analysis determined that a shorter left CIA (OR 1.07, 95% CI 1.01 to 1.1, p=0.016) and a smaller total aneurysm volume (OR 1.007, CI. 1.001 to 1.014, p=0.016) were associated with intact AAA. After a ROC curve analysis, left CIA length <50 mm demonstrated a lower incidence of rupture (sensitivity 60% and specificity 78%), while total aneurysm volume <380 mL had 60% sensitivity and specificity. Conclusion: Large rAAAs seem to have different anatomical characteristics than similarly sized intact AAAs. Large intact AAAs have lower total aneurysm volumes and shorter left CIAs, with higher ILT/aneurysm volume rates.

Risk Factors and Mouse Models of Abdominal Aortic Aneurysm Rupture.

Abdominal aortic aneurysm (AAA) rupture is an important cause of death in older adults. In clinical practice, the most established predictor of AAA rupture is maximum AAA diameter. Aortic diameter is commonly used to assess AAA severity in mouse models studies. AAA rupture occurs when the stress (force per unit area) on the aneurysm wall exceeds wall strength. Previous research suggests that aortic wall structure and strength, biomechanical forces on the aorta and cellular and proteolytic composition of the AAA wall influence the risk of AAA rupture. Mouse models offer an opportunity to study the association of these factors with AAA rupture in a way not currently possible in patients. Such studies could provide data to support the use of novel surrogate markers of AAA rupture in patients. In this review, the currently available mouse models of AAA and their relevance to the study of AAA rupture are discussed. The review highlights the limitations of mouse models and suggests novel approaches that could be incorporated in future experimental AAA studies to generate clinically relevant results.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): uncertainty quantification of geometric rupture risk parameters.

BACKGROUND: Geometric parameters have been proposed for prediction of cerebral aneurysm rupture risk. Predicting the rupture risk for incidentally detected unruptured aneurysms could help clinicians in their treatment decision. However, assessment of geometric parameters depends on several factors, including the spatial resolution of the imaging modality used and the chosen reconstruction procedure. The aim of this study was to investigate the uncertainty of a variety of previously proposed geometric parameters for rupture risk assessment, caused by variability of reconstruction procedures. MATERIALS: 26 research groups provided segmentations and surface reconstructions of five cerebral aneurysms as part of the Multiple Aneurysms AnaTomy CHallenge (MATCH) 2018. 40 dimensional and non-dimensional geometric parameters, describing aneurysm size, neck size, and irregularity of aneurysm shape, were computed. The medians as well as the absolute and relative uncertainties of the parameters were calculated. Additionally, linear regression analysis was performed on the absolute uncertainties and the median parameter values. RESULTS: A large variability of relative uncertainties in the range between 3.9 and 179.8% was found. Linear regression analysis indicates that some parameters capture similar geometric aspects. The lowest uncertainties < 6% were found for the non-dimensional parameters isoperimetric ratio, convexity ratio, and ellipticity index. Uncertainty of 2D and 3D size parameters was significantly higher than uncertainty of 1D parameters. The most extreme uncertainties > 80% were found for some curvature parameters. CONCLUSIONS: Uncertainty analysis is essential on the road to clinical translation and use of rupture risk prediction models. Uncertainty quantification of geometric rupture risk parameters provided by this study may help support development of future rupture risk prediction models.

China Intracranial Aneurysm Project (CIAP): protocol for a registry study on a multidimensional prediction model for rupture risk of unruptured intracranial aneurysms.

BACKGROUND: Ruptured aneurysms, the commonest cause of nontraumatic subarachnoid hemorrhage, can be catastrophic; the mortality and morbidity of affected patients being very high. Some risk factors, such as smoking, hypertension and female sex have been identified, whereas others, such as hemodynamics, imaging, and genomics, remain unclear. Currently, no accurate model that includes all factors for predicting such rupture is available. We plan to use data from a large cohort of Chinese individuals to set up a multidimensional model for predicting risk of rupture of unruptured intracranial aneurysms (UIAs). METHODS: The China Intracranial Aneurysm Project-2 (CIAP-2) will comprise screening of a cohort of 500 patients with UIA (From CIAP-1) and focus on hemodynamic factors, high resolution magnetic resonance imaging (HRMRI) findings, genetic factors, and biomarkers. Possible risk factors for rupture of UIA, including genetic factors, biomarkers, HRMRI, and hemodynamic factors, will be analyzed. The first project of the China Intracranial Aneurysm Project (CIAP-1; chaired by the Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China) will prospectively collect a cohort of 5000 patients with UIA from 20 centers in China, and collect baseline information for each patient. Multidimensional data will be acquired in follow-up assessments. Statistically significant clinical features in the UIA cohort will also be analyzed and integrated into the model for predicting risk of UIA rupture. After the model has been set up, the resultant evidence-based prediction will provide a preliminary theoretical basis for treating aneurysms at high risk of rupture. DISCUSSION: This study will explore the risk of rupture of aneurysms and develop a scientific multidimensional model for predicting rupture of unruptured intracranial aneurysms. Clinical Trials registration A Study on a Multidimensional Prediction Model for Rupture Risk of Unruptured Intracranial Aneurysms (CIAP-2), NCT03133624. Registered: 16 April 2017. https://clinicaltrials.gov/ct2/show/NCT03133624.

Aortic Lumen Area Is Increased in Ruptured Abdominal Aortic Aneurysms and Correlates to Biomechanical Rupture Risk.

PURPOSE: To investigate how 2-dimensional geometric parameters differ between ruptured and asymptomatic abdominal aortic aneurysms (AAAs) and provide a biomechanical explanation for the findings. METHODS: The computed tomography angiography (CTA) scans of 30 patients (mean age 77±10 years; 23 men) with ruptured AAAs and 60 patients (mean age 76±8 years; 46 men) with asymptomatic AAAs were used to measure maximum sac diameter along the center lumen line, the cross-sectional lumen area, the total vessel area, the intraluminal thrombus (ILT) area, and corresponding volumes. The CTA data were segmented to create 3-dimensional patient-specific models for finite element analysis to compute peak wall stress (PWS) and the peak wall rupture index (PWRI). To reduce confounding from the maximum diameter, 2 diameter-matched groups were selected from the initial patient cohorts: 28 ruptured AAAs and another with 15 intact AAAs (diameters 74±12 vs 73±11, p=0.67). A multivariate model including the maximum diameter, the lumen area, and the ILT area of the 60 intact aneurysms was employed to predict biomechanical rupture risk parameters. RESULTS: In the diameter-matched subgroup comparison, ruptured AAAs had a significantly larger cross-sectional lumen area (1954±1254 vs 1120±623 mm2, p=0.023) and lower ILT area ratio (55±24 vs 68±24, p=0.037). The ILT area (2836±1462 vs 2385±1364 mm2, p=0.282) and the total vessel area (3956±1170 vs 4338±1388 mm2, p=0.384) did not differ statistically between ruptured and intact aneurysms. The PWRI was increased in ruptured AAAs (0.80 vs 0.48, p<0.001), but the PWS was similar (249 vs 284 kPa, p=0.194). In multivariate regression analysis, lumen area was significantly positively associated with both PWS (p<0.001) and PWRI (p<0.01). The ILT area was also significantly positively associated with PWS (p<0.001) but only weakly with PWRI (p<0.01). The lumen area conferred a higher risk increase in both PWS and PWRI when compared with the ILT area. CONCLUSION: The lumen area is increased in ruptured AAAs compared to diameter-matched asymptomatic AAAs. Furthermore, this finding may in part be explained by a relationship with biomechanical rupture risk parameters, in which lumen area, irrespective of maximum diameter, increases PWS and PWRI. These observations thus suggest a possible method to improve prediction of rupture risk in AAAs by measuring the lumen area without the use of computational modeling.

Diffusion-compensated tofts model suggests contrast leakage through aneurysm wall.

PURPOSE: The purpose of this study was to investigate the diffusional transport of contrast agent and its effects on kinetic modeling of dynamic contrast enhanced (DCE) images. METHODS: We performed simulations of our diffusion-compensated model and compared these results to human intracranial aneurysms (IAs). We derive an easy-to-use parameterization of diffusional effects that can provide an accurate estimate of diffusion corrected contrast agent leakage rates (ktrans ). Finally, we performed re-ansalysis of an existing data set to determine whether diffusion-corrected kinetic parameters improve the identification of high-risk IAs, thereby providing a new MRI-based imaging metric of IA stability based on wall integrity. RESULTS: Probability distributions of simulated versus measured data show contrast leakage away from the aneurysm wall. Parameterization of diffusional effects on ktrans showed high correlation with long-chain methods in both surrounding tissue and near the aneurysm wall (r2 = 0.91 and r2 = 0.90, respectively). Finally, size, ktrans , and ( ktrans-kDCtrans) showed significant univariate relationships with rupture risk (P < 0.05). CONCLUSIONS: We report the first evidence of diffusion-compensated permeability modeling in intracranial aneurysms and propose a parameterization of diffusional effects on ktrans . Furthermore, a comparison of measured versus simulated data suggests that contrast leakage occurs across the aneurysm wall. Magn Reson Med 78:2388-2398, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Gene Expression Profiling in Abdominal Aortic Aneurysms After Finite Element Rupture Risk Assessment.

PURPOSE: To investigate the association between local biomechanical rupture risk calculations from finite element analysis (FEA) and whole-genome profiling of the abdominal aortic aneurysm (AAA) wall to determine if AAA wall regions with highest and lowest estimated rupture risk show different gene expression patterns. METHODS: Six patients (mean age 74 years; all men) scheduled for open surgery to treat asymptomatic AAAs (mean diameter 55.2±3.5 mm) were recruited for the study. Rupture risk profiles were estimated by FEA from preoperative computed tomography angiography data. During surgery, AAA wall samples of ~10 mm2 were extracted from the lowest and highest rupture risk locations identified by the FEA. Twelve samples were processed for RNA extraction and subsequent whole genome expression profiling. Expression of single genes and of predefined gene groups were compared between vessel wall areas with highest and lowest predicted rupture risk. RESULTS: Normalized datasets comprised 15,079 gene transcripts with expression above background. In biopsies with high rupture risk, upregulation of 18 and downregulation of 18 genes was detected when compared to the low-risk counterpart. Global analysis of predefined gene groups revealed expression differences in genes associated with extracellular matrix (ECM) degradation (p<0.001), matrix metalloproteinase activity (p<0.001), and chemokine signaling (p<0.001). CONCLUSION: Increased expression of genes involved in degrading ECM components was present in AAA wall regions with highest biomechanical stress, supporting the thesis of mechanotransduction. More experimental studies with cooperation of multicenter vascular biobanks are necessary to understand AAA etiologies and identify further parameters of FEA model complementation.

Biomechanical Indices for Rupture Risk Estimation in Abdominal Aortic Aneurysms.

PURPOSE: To review the use of biomechanical indices for the estimation of abdominal aortic aneurysm (AAA) rupture risk, emphasizing their potential use in a clinical setting. METHODS: A search of the PubMed, Embase, Scopus, and Compendex databases was made up to June 2015 to identify articles involving biomechanical analysis of AAA rupture risk. Outcome variables [aneurysm diameter, peak wall stress (PWS), peak wall shear stress (PWSS), wall strain, peak wall rupture index (PWRI), and wall stiffness] were compared for asymptomatic intact AAAs vs symptomatic or ruptured AAAs. For quantitative analysis of the pooled data, a random effects model was used to calculate the standard mean differences (SMDs) with the 95% confidence interval (CI) for the biomechanical indices. RESULTS: The initial database searches yielded 1894 independent articles of which 19 were included in the analysis. The PWS was significantly higher in the symptomatic/ruptured group, with a SMD of 1.11 (95% CI 0.93 to 1.26, p<0.001). Likewise, the PWRI was significantly higher in the ruptured or symptomatic group, with a SMD of 1.15 (95% CI 0.30 to 2.01, p=0.008). After adjustment for the aneurysm diameter, the PWS remained higher in the ruptured or symptomatic group, with a SMD of 0.85 (95% CI 0.46 to 1.23, p<0.001). Less is known of the wall shear stress and wall strain indices, as too few studies were available for analysis. CONCLUSION: Biomechanical indices are a promising tool in the assessment of AAA rupture risk as they incorporate several factors, including geometry, tissue properties, and patient-specific risk factors. However, clinical implementation of biomechanical AAA assessment remains a challenge owing to a lack of standardization.