The association of wall mechanics and morphology: a case study of abdominal aortic aneurysm growth.

The purpose of this study is to evaluate the potential correlation between peak wall stress (PWS) and abdominal aortic aneurysm (AAA) morphology and how it relates to aneurysm rupture potential. Using in-house segmentation and meshing software, six 3-dimensional (3D) AAA models from a single patient followed for 28 months were generated for finite element analysis. For the AAA wall, both isotropic and anisotropic materials were used, while an isotropic material was used for the intraluminal thrombus (ILT). These models were also used to calculate 36 geometric indices characteristic of the aneurysm morphology. Using least squares regression, seven significant geometric features (p < 0.05) were found to characterize the AAA morphology during the surveillance period. By means of nonlinear regression, PWS estimated with the anisotropic material was found to be highly correlated with three of these features: maximum diameter (r = 0.992, p = 0.002), sac volume (r = 0.989, p = 0.003) and diameter to diameter ratio (r = 0.947, p = 0.033). The correlation of wall mechanics with geometry is nonlinear and reveals that PWS does not increase concomitantly with aneurysm diameter. This suggests that a quantitative characterization of AAA morphology may be advantageous in assessing rupture risk.

Quantitative assessment of abdominal aortic aneurysm geometry.

Recent studies have shown that the maximum transverse diameter of an abdominal aortic aneurysm (AAA) and expansion rate are not entirely reliable indicators of rupture potential. We hypothesize that aneurysm morphology and wall thickness are more predictive of rupture risk and can be the deciding factors in the clinical management of the disease. A non-invasive, image-based evaluation of AAA shape was implemented on a retrospective study of 10 ruptured and 66 unruptured aneurysms. Three-dimensional models were generated from segmented, contrast-enhanced computed tomography images. Geometric indices and regional variations in wall thickness were estimated based on novel segmentation algorithms. A model was created using a J48 decision tree algorithm and its performance was assessed using ten-fold cross validation. Feature selection was performed using the χ2-test. The model correctly classified 65 datasets and had an average prediction accuracy of 86.6% (κ=0.37). The highest ranked features were sac length, sac height, volume, surface area, maximum diameter, bulge height, and intra-luminal thrombus volume. Given that individual AAAs have complex shapes with local changes in surface curvature and wall thickness, the assessment of AAA rupture risk should be based on the accurate quantification of aneurysmal sac shape and size.

Adenosine A1 receptor knockout mice develop lethal status epilepticus after experimental traumatic brain injury.

Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy--and inhibits progression to status epilepticus (SE). Seizures after traumatic brain injury (TBI) may contribute to pathophysiology. Thus, we hypothesized that endogenous adenosine, acting via A1 receptors, mediates antiepileptic benefit after experimental TBI. We subjected A1-receptor knockout (ko) mice, heterozygotes, and wild-type (wt) littermates (n=115) to controlled cortical impact (CCI). We used four outcome protocols in male mice: (1) observation for seizures, SE, and mortality in the initial 2 h, (2) assessment of seizure score (electroencephalogram (EEG)) in the initial 2 h, (3) assessment of mortality at 24 h across injury levels, and (4) serial assessment of arterial blood pressure, heart rate, blood gases, and hematocrit. Lastly, to assess the influence of gender on this observation, we observed female mice for seizures, SE, and mortality in the initial 2 h. Seizure activity was noted in 83% of male ko mice in the initial 2 h, but was seen in no heterozygotes and only 33% of wt (P<0.05). Seizures in wt were brief (1 to 2 secs). In contrast, SE involving lethal sustained (>1 h) tonic clonic activity was uniquely seen in ko mice after CCI (50% incidence in males), (P<0.05). Seizure score was twofold higher in ko mice after CCI versus either heterozygote or wt (P<0.05). An injury-intensity dose-response for 24 h mortality was seen in ko mice (P<0.05). Physiologic parameters were similar between genotypes. Seizures were seen in 100% of female ko mice after CCI versus 14% of heterozygotes and 25% wt (P<0.05) and SE was restricted to the ko mice (83% incidence). Our data suggest a critical endogenous anticonvulsant action of adenosine at A1 receptors early after experimental TBI.