Role of lung lobar sliding on parenchymal distortion during breathing.

Sliding between lung lobes along lobar fissures is a poorly understood aspect of lung mechanics. The objective of this study was to test the hypothesis that lobar sliding helps reduce distortion in the lung parenchyma during breathing. Finite element models of left lungs with geometries and boundary conditions derived from medical images of human subjects were developed. Effect of lobar sliding was studied by comparing nonlinear finite elastic contact mechanics simulations that allowed and disallowed lobar sliding. Lung parenchymal distortion during simulated breath-holds and tidal breathing was quantified with the model's spatial mean anisotropic deformation index (ADI), a measure of directional preference in volume change that varies spatially in the lung. Models that allowed lobar sliding had significantly lower mean ADI (i.e., lesser parenchymal distortion) than models that disallowed lobar sliding under simulations of both tidal breathing (5.3% median difference, P = 0.008, n = 8) and lung deformation between breath-holds at total lung capacity and functional residual capacity (3.2% median difference, P = 0.03, n = 6). This effect was most pronounced in the lower lobe where lobar sliding reduced parenchymal distortion with statistical significance, but not in the upper lobe. In addition, more lobar sliding was correlated with greater reduction in distortion between sliding and nonsliding models in our study cohorts (Pearson's correlation coefficient of 0.95 for tidal breathing, 0.87 for breath-holds, and 0.91 for the combined dataset). These findings are consistent with the hypothesis that lung lobar sliding reduces parenchymal distortion during breathing.NEW & NOTEWORTHY The role of lobar sliding in lung mechanics is poorly understood. Delineating this role could help explain how breathing is affected by anatomical differences between subjects such as incomplete and missing lobar fissures. We used computational contact mechanics models of lungs from human subjects to delineate the effect of lobar sliding by comparing simulations that allowed and disallowed sliding. We found evidence consistent with the hypothesis that lung lobar sliding reduces parenchymal distortion during breathing.

Parallel neurodegenerative phenotypes in sporadic Parkinson's disease fibroblasts and midbrain dopamine neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they differed in their nature and scale. Furthermore, statistical analysis revealed potential novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments.

Parallel Neurodegenerative Phenotypes in Sporadic Parkinson's Disease Fibroblasts and Midbrain Dopamine Neurons.

Understanding the mechanisms causing Parkinson's disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they also differed in their nature and scale. Furthermore, statistical analysis revealed novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments.

Risk factors for hemolysis with centrifugal pumps in pediatric extracorporeal membrane oxygenation: Is pump replacement an answer?

INTRODUCTION: Hemolysis during pediatric extracorporeal membrane oxygenation (ECMO) is associated with increased risk for renal failure and mortality. OBJECTIVES: We aim to describe risk factors for hemolysis in pediatric ECMO supported by centrifugal pumps. METHODS: We conducted an analysis of retrospective data collected at an academic children's hospital from January 2017 to December 2019. MEASUREMENTS AND RESULTS: Plasma-free hemoglobin (PFH) levels were measured daily, and hemolysis was defined as PFH>50 mg/dL. Of 46 ECMO runs over 528 ECMO days, hemolysis occurred in 23 (58%) patients over a total of 40 (8%) ECMO days. In multivariable logistic regression models, VA-ECMO (aOR=4.69, 95% CI: 1.01-21.83) and higher hemoglobin (aOR = 1.38, 95% CI: 1.06-1.81) were independently associated with hemolysis. There were also non-significant trends toward increased risk for hemolysis with higher rotational pump speed (aOR=2.39, 95% CI: 0.75-7.65), higher packed red blood cell transfusions (aOR=1.15, 95% CI: 0.99-1.34), and higher cryoprecipitate transfusions (aOR=2.01, 95% CI: 0.83-4.86). Isolated pump exchanges that were performed in 12 patients with hemolysis led to significant decreases in PFH levels within 24 h (89 vs 11 mg/dL, p<0.01). CONCLUSIONS: Hemolysis is common in pediatric ECMO using centrifugal pumps. Avoidance of high pump speeds and conservative administration of blood products may help to mitigate the risk for hemolysis. Furthermore, pump exchange may be an effective first-line treatment for hemolysis.

Semiautomated 3D mapping of aneurysmal wall enhancement with 7T-MRI.

Aneurysm wall enhancement (AWE) after the administration of contrast gadolinium is a potential biomarker of unstable intracranial aneurysms. While most studies determine AWE subjectively, this study comprehensively quantified AWE in 3D imaging using a semi-automated method. Thirty patients with 33 unruptured intracranial aneurysms prospectively underwent high-resolution imaging with 7T-MRI. The signal intensity (SI) of the aneurysm wall was mapped and normalized to the pituitary stalk (PS) and corpus callosum (CC). The CC proved to be a more reliable normalizing structure in detecting contrast enhancement (p < 0.0001). 3D-heatmaps and histogram analysis of AWE were used to generate the following metrics: specific aneurysm wall enhancement (SAWE), general aneurysm wall enhancement (GAWE) and focal aneurysm wall enhancement (FAWE). GAWE was more accurate in detecting known morphological determinants of aneurysm instability such as size ≥ 7 mm (p = 0.049), size ratio (p = 0.01) and aspect ratio (p = 0.002). SAWE and FAWE were aneurysm specific metrics used to characterize enhancement patterns within the aneurysm wall and the distribution of enhancement along the aneurysm. Blebs were easily identified on 3D-heatmaps and were more enhancing than aneurysm sacs (p = 0.0017). 3D-AWE mapping may be a powerful objective tool in characterizing different biological processes of the aneurysm wall.

Insights into the pathogenesis of cerebral fusiform aneurysms: high-resolution MRI and computational analysis.

BACKGROUND: Intracranial fusiform aneurysms are complex and poorly characterized vascular lesions. High-resolution magnetic resonance imaging (HR-MRI) and computational morphological analysis may be used to characterize cerebral fusiform aneurysms. OBJECTIVE: To use advanced imaging and computational analysis to understand the unique pathophysiology, and determine possible underlying mechanisms of instability of cerebral fusiform aneurysms. METHODS: Patients with unruptured intracranial aneurysms prospectively underwent imaging with 3T HR-MRI at diagnosis. Aneurysmal wall enhancement was objectively quantified using signal intensity after normalization of the contrast ratio (CR) with the pituitary stalk. Enhancement between saccular and fusiform aneurysms was compared, as well as enhancement characteristics of fusiform aneurysms. The presence of microhemorrhages in fusiform aneurysms was determined with quantitative susceptibility mapping (QSM). Three distinct types of fusiform aneurysms were analyzed with computational fluid dynamics (CFD) and finite element analysis (FEA). RESULTS: A total of 130 patients with 160 aneurysms underwent HR-MRI. 136 aneurysms were saccular and 24 were fusiform. Fusiform aneurysms had a significantly higher CR and diameter than saccular aneurysms. Enhancing fusiform aneurysms exhibited more enhancement of reference vessels than non-enhancing fusiform aneurysms. Ten fusiform aneurysms underwent QSM analysis, and five aneurysms showed microhemorrhages. Microhemorrhage-positive aneurysms had a larger volume, diameter, and greater enhancement than aneurysms without microhemorrhage. Three types of fusiform aneurysms exhibited different CFD and FEA patterns. CONCLUSION: Fusiform aneurysms exhibited more contrast enhancement than saccular aneurysms. Enhancing fusiform aneurysms had larger volume and diameter, more enhancement of reference vessels, and more often exhibited microhemorrhage than non-enhancing aneurysms. CFD and FEA suggest that various pathophysiological processes determine the formation and growth of fusiform aneurysms.

Methodology for Estimation of Annual Risk of Rupture for Abdominal Aortic Aneurysm.

BACKGROUND AND OBJECTIVE: Estimating patient specific annual risk of rupture of abdominal aortic aneurysm (AAA) is currently based only on population. More accurate knowledge based on patient specific data would allow surgical treatment of only those AAAs with significant risk of rupture. This would be beneficial for both patients and health care system. METHODS: A methodology for estimating annual risk of rupture (EARR) of abdominal aortic aneurysms (AAA) that utilizes Bayesian statistics, mechanics and patient-specific blood pressure monitoring data is proposed. EARR estimation takes into consideration, peak wall stress in AAA computed by patient-specific finite element modeling, the probability distributions of wall thickness, wall strength, systolic blood pressure and the period of time that the patient is known to have already survived with the intact AAA. Initial testing of proposed approach was performed on fifteen patients with intact AAA (mean maximal diameter 51mm±8mm). They were equipped with a pressure holter and their blood pressure was recorded over 24 hours. Then, we calculated EARR values for four possible scenarios - without considering any days of survival prior identification of AAA at computed tomography scans (EARR_0), considering past survival of 30 (EARR_30), 90 (EARR_90) and 180 days (EARR_180). Finally, effect of patient-specific blood pressure variability was analyzed. RESULTS: Consideration of past survival does indeed significantly improve predictions of future risk: EARR_30 (1.04%± 0.87%), EARR_90 (0.67%± 0.56%) and EARR_180 (0.47%± 0.39%) which are unrealistically high otherwise (EARR_0 5.02%± 5.24%). Finally, EARR values were observed to vary by an order as a consequence of blood pressure variability and by factor of two as a consequence of neglected growth. CONCLUSIONS: Methodology for computing annual risk of rupture of AAA was developed for the first time. Sensitivity analyses showed respecting patient specific blood pressure is important factor and should be included in the AAA rupture risk assessment. Obtained EARR values were generally low and in good agreement with confirmed survival time of investigated patients so proposed method should be further clinically validated.

Investigation of the observed rupture lines in abdominal aortic aneurysms using crack propagation simulations.

OBJECTIVE: To use crack propagation simulation to study the rupture site characteristics in ruptured abdominal aortic aneurysms (AAA). METHODS: Rupture lines were precisely documented in four ruptured AAA harvested whole from cadavers. Wall thickness and material parameters were experimentally determined. Using subject-specific 3D geometry and subject-specific finite elastic model parameters, crack propagation simulations were conducted based on basic fracture mechanics principles to investigate if and how localized weak spots may have led to the observed rupture lines. RESULTS AND CONCLUSION: When an initial crack was imposed at the site of peak wall stress, the propagated path did not match the observed rupture line. This indicates that in this study population, the peak wall stress was unlikely to have caused the observed rupture. When cracks were initiated at random locations in the AAA along random orientations for random initial lengths, the orientation of the resulting propagated rupture line was consistently longitudinal. This suggests that the AAA morphology predisposes the AAA to rupture longitudinally, which is consistent with observations. It was found that, in this study population, rupture may have initiated at short segments of less than about 1 cm that then propagated to form the observed rupture lines. This suggests that ex vivo experimental and in vivo elastography studies should seek a spatial resolution (approx. 1 cm) to reliably identify weak spots in AAA. The small study population and lack of a reliable failure model for AAA tissue make these findings preliminary.

Iron nanoparticle contrast enhanced microwave imaging for emergent stroke: A pilot study.

Emergent stroke is mostly evaluated using hospital based imaging. Quick imaging allows for rapid administration of IV thrombolysis and outcome improvement. Microwave imaging (MI) is an emerging portable imaging modality. Iron oxide nanoparticles are known to interact with microwave frequency electromagnetic radiation. In this manuscript, we provide proof of concept for a novel iron oxide nanoparticle enhanced microwave imaging device for differentiating emergent ischemic stroke from hemorrhagic stroke. A MI device was constructed. Attenuation of the microwave signal transmitted with or without iron oxide nanoparticles was measured over a 1-2 GHz frequency range in a silicone brain phantom, in New Zealand white rabbits, and in a human. Observed differences in signal attenuation were used to reconstruct an image following induction of a left sided anterior circulation stroke in a New Zealand white rabbit. An increase in microwave signal attenuation exists across a frequency range of 1.3-2 GHz when iron oxide nanoparticles are introduced into a silicone phantom model, in New Zealand white rabbits, and in a human volunteer. Using this increase in signal attenuation following nanoparticle administration, we localize induced ischemia in a New Zealand white rabbit. To the best of out knowledge, we provide the first evidence that superparamagnetic Iron oxide nanoparticles may be used as contrast in the setting of MI. Our data suggest infusion of intravenous iron oxide nanoparticles with follow on microwave imaging may ultimately allow for more timely administration of thrombolytic mediation in the setting of acute ischemic stroke.

A Role for Nrf2 Expression in Defining the Aging of Hippocampal Neural Stem Cells.

Redox mechanisms are emerging as essential to stem cell function given their capacity to influence a number of important signaling pathways governing stem cell survival and regenerative activity. In this context, our recent work identified the reduced expression of nuclear factor (erythroid-derived 2)-like 2, or Nrf2, in mediating the decline in subventricular zone neural stem progenitor cell (NSPC) regeneration during aging. Since Nrf2 is a major transcription factor at the heart of cellular redox regulation and homeostasis, the current study investigates the role that it may play in the aging of NSPCs that reside within the other major mammalian germinal niche located in the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Using rats from multiple aging stages ranging from newborn to old age, and aging Nrf2 knockout mice, we first determined that, in contrast with subventricular zone (SVZ) NSPCs, Nrf2 expression does not significantly affect overall DG NSPC viability with age. However, DG NSPCs resembled SVZ stem cells, in that Nrf2 expression controlled their proliferation and the balance of neuronal versus glial differentiation particularly in relation to a specific critical period during middle age. Also, importantly, this Nrf2-based control of NSPC regeneration was found to impact functional neurogenesis-related hippocampal behaviors, particularly in the Morris water maze and in pattern separation tasks. Furthermore, the enrichment of the hippocampal environment via the transplantation of Nrf2-overexpressing NSPCs was able to mitigate the age-related decline in DG stem cell regeneration during the critical middle-age period, and significantly improved pattern separation abilities. In summary, these results emphasize the importance of Nrf2 in DG NSPC regeneration, and support Nrf2 upregulation as a potential approach to advantageously modulate DG NSPC activity with age.

Detection of microbleeds associated with sentinel headache using MRI quantitative susceptibility mapping: pilot study.

OBJECT: Sentinel headaches (SHs) associated with cerebral aneurysms (CAs) could be due to microbleeds, which are considered a sign that an aneurysm is unstable. Despite the prognostic importance of these microbleeds, they remain difficult to detect using routine imaging studies. The objective of this pilot study is to detect microbleeds associated with SH using a magnetic resonance imaging (MRI) quantitative susceptibility mapping (QSM) sequence and then evaluate the morphological characteristics of unstable aneurysms with microbleeds. METHODS: Twenty CAs in 16 consecutive patients with an initial presentation of headache (HA) leading to a diagnosis of CA were analyzed. Headaches in 4 of the patients (two of whom had 2 aneurysms each) met the typical definition of SH, and the other 12 patients (two of whom also had 2 aneurysms each) all had migraine HA. All patients underwent imaging with the MRI-QSM sequence. Two independent MRI experts who were blinded to the patients' clinical history performed 3D graphical analysis to evaluate for potential microbleeds associated with these CAs. Computational flow and morphometric analyses were also performed to estimate wall shear and morphological variables. RESULTS: In the 4 patients with SH, MRI-QSM results were positive for 4 aneurysms, and hence these aneurysms were considered positive for non-heme ferric iron (microbleeds). The other 16 aneurysms were negative. Among aneurysm shape indices, the undulation index was significantly higher in the QSM-positive group than in the QSM-negative group. In addition, the spatial averaged wall shear magnitude was lower in the aneurysm wall in direct contact with microbleeds. CONCLUSIONS: MRI-QSM allows for objective detection of microbleeds associated with SH and therefore identification of unstable CAs. CAs with slightly greater undulation indices are associated with positive MRI-QSM results and hence with microbleeds. Studies with larger populations are needed to confirm these preliminary findings.

Accuracy of detecting enlargement of aneurysms using different MRI modalities and measurement protocols.

OBJECTIVE: Aneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical MRI is still unknown. The purpose of this study was to assess the agreement rate of detecting aneurysm enlargement employing generally used MRI modalities. METHODS: Three silicone flow phantom models, each with 8 aneurysms of various sizes at different sites, were used in this study. The aneurysm models were identical except for an incremental increase in the sizes of the 8 aneurysms, which ranged from 0.4 mm to 2 mm. The phantoms were imaged on 1.5-T and 3-T MRI units with both time-of-flight (TOF) and contrast-enhanced MR angiography. Three independent expert neuroradiologists measured the aneurysms in a blinded manner using different measurement approaches. The individual and agreement detection rates of aneurysm enlargement among the 3 experts were calculated. RESULTS: The mean detection rate of any increase in any aneurysmal dimension was 95.7%. The detection rates of the 3 observers (observers A, B, and C) were 98.0%, 96.6%, and 92.7%, respectively (p = 0.22). The detection rates of each MRI modality were 91.3% using 1.5-T TOF, 97.2% using 1.5-T with Gd, 95.8% using 3.0-T TOF, and 97.2% using 3.0-T with Gd (p = 0.31). On the other hand, the mean detection rate for aneurysm enlargement was 54.8%. Specifically, the detection rates of observers A, B, and C were 49.0%, 46.1%, and 66.7%, respectively (p = 0.009). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. The use of 1.5-T Gd improved the detection rate for small incremental enlargement (e.g., 0.4­1 mm) of the aneurysm (p = 0.04). The location of the aneurysm also affected the detection rate for aneurysm enlargement (p < 0.0001). CONCLUSIONS: The detection rate and interobserver agreement were very high for aneurysm enlargement of 0.4­2 mm. The detection rate for at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or measurement protocol. Use of Gd improved the accuracy of measurement. Aneurysm location may influence the accuracy of detecting enlargement.

Aneurysm Morphology and Prediction of Rupture: An International Study of Unruptured Intracranial Aneurysms Analysis.

BACKGROUND: There are conflicting data between natural history studies suggesting a very low risk of rupture for small, unruptured intracranial aneurysms and retrospective studies that have identified a much higher frequency of small, ruptured aneurysms than expected. OBJECTIVE: To use the prospective International Study of Unruptured Intracranial Aneurysms cohort to identify morphological characteristics predictive of unruptured intracranial aneurysm rupture. METHODS: A case-control design was used to analyze morphological characteristics associated with aneurysm rupture in the International Study of Unruptured Intracranial Aneurysms database. Fifty-seven patients with ruptured aneurysms during follow-up were matched (by size and location) with 198 patients with unruptured intracranial aneurysms without rupture during follow-up. Twelve morphological metrics were measured from cerebral angiograms in a blinded fashion. RESULTS: Perpendicular height (P = .008) and size ratio (ratio of maximum diameter to the parent vessel diameter; P = .01) were predictors of aneurysm rupture on univariate analysis. Aspect ratio, daughter sacs, multiple lobes, aneurysm angle, neck diameter, parent vessel diameter, and calculated aneurysm volume were not statistically significant predictors of rupture. On multivariate analysis, perpendicular height was the only significant predictor of rupture (Chi-square 7.1, P-value .008). CONCLUSION: This study underscores the importance of other morphological factors, such as perpendicular height and size ratio, that may influence unruptured intracranial aneurysm rupture risk in addition to greatest diameter and anterior vs posterior location.

Modeling Outcomes: Modified Aortic Arch Advancement for Neonatal Hypoplastic Arch.

OBJECTIVE: Numerous surgical approaches regarding aortic arch advancement for neonatal arch hypoplasia have been described. These repairs can be classified into two categories: those that incorporate a patch and those that do not. The decision between repairs remains largely experiential, rather than empirical, because of the limited number of reported outcomes. We report early outcomes from neonates undergoing modified aortic arch advancement with an anterior patch and our experience using computational fluid dynamic modeling to better understand the hemodynamic consequences associated with this repair. METHODS: A retrospective review of neonates undergoing aortic arch advancement with anterior patch in 2014 at a single institution was performed. Anatomical, perioperative, and follow-up data were collected. Three-dimensional cardiac magnetic resonance images were used to generate computational fluid dynamic models of the modified anterior patch and direct end-to-side repairs. Cardiac waveform inputs were simulated and hemodynamic analyzed. RESULTS: Ten neonates underwent modified aortic arch advancement. No hemodynamically significant gradients were observed at a median follow-up of 0.77 (0.30-1.2) years. Asymmetrical flow was observed in the end-to-side repair, whereas more concentric laminar flow was observed throughout the modified model. Spatial variations in velocities immediately distal to the anastomosis were greater in the end-to-side model (0.35 vs 0.17 m/s, P < 0.001). Time-averaged variations in wall shear stress during systole were greater in the end-to-side model at the same location (3.44 vs 1.98 dynes/cm, P < 0.001). CONCLUSIONS: Early outcomes after the use of an anterior patch for neonatal hypoplastic aortic arch repair show favorable hemodynamic outcomes.

Efficacy of Flow Monitoring During ECMO.

The hypothesis that blood flow monitoring could serve as an effective early indicator of distal obstruction during extracorporeal membrane oxygenation (ECMO) was tested under controlled experimental conditions. The ECMO circuit typically includes (or could be easily modified to include) a shunt that bifurcates from the main line returning a small amount of blood to the pump with access points for drug infusions. Distal circuit obstructions in the oxygenator and beyond will result in an increased diversion of flow from the distal line to the shunt. Thus, elevations in flow through the shunt can serve as a marker for distal circuit obstruction. An ECMO training circuit was adapted with a resistance chamber that simulates controlled and varying levels of distal obstructions. Experiments were conducted under pediatric and adult pump target flow rates simulating different levels of distal obstructions while documenting the shunt flow and pressure drop across the obstruction. There was measurable and statistically significant elevation in the shunt flow at all flow rates because of different levels of obstruction from baseline values and hence consistent with the hypothesis that shunt flow can serve as an indicator of distal obstruction in the ECMO circuit. Flow monitoring is over the tube, hands free, continuous, and easy to implement. Therefore, it has the potential to serve as an early nonspecific indicator of elevated distal resistance in the ECMO circuit, which can then trigger other measurements (such as pressure drop across the oxygenator) for a more specific assessment of the source for distal resistance.

Volumetry and biomechanical parameters detected by 3D and 2D ultrasound in patients with and without an abdominal aortic aneurysm.

The objective was to demonstrate the ability of ultrasound (US) with 3D properties to evaluate volumetry and biomechanical parameters of the aorta in patients with and without abdominal aortic aneurysm (AAA). Thirty-one patients with normal aortas (group 1), 46 patients with AAA measuring 3.0-5.5 cm (group 2) and 31 patients with AAA ⩾ 5.5 cm (group 3) underwent a 2D/3D-US examination of the infra-renal aorta, and the images were post-processed prior to being analyzed. In the maximum diameter, the global circumferential strain and the global maximum rotation assessed by 2D speckle-tracking algorithms were compared among the three groups. The volumetry data obtained using 3D-US from 40 AAA patients were compared with the volumetry data obtained by a contemporary computed tomography (CT) scan. The median global circumferential strain was 2.0% (interquartile range (IR): 1.0-3.0), 1.0% (IR: 1.0-2.0) and 1.0% (IR: 1.0-1.75) in groups 1, 2 and 3, respectively (p < 0.001). The median global maximum rotation decreased progressively from group 1 to group 3 (1.38º (IR: 0.77-2.13), 0.80º (IR: 0.57-1.0) and 0.50º (IR: 0.31-0.75), p < 0.001). AAA volume estimations by 3D-US correlated well with CT (R(2) = 0.76). In conclusion, US with 3D properties is non-invasive and has the potential to evaluate volumetry and biomechanical characteristics of AAA.

Assessment of image-derived risk factors for natural course of unruptured cerebral aneurysms.

OBJECTIVE: The goal of this prospective longitudinal study was to test whether image-derived metrics can differentiate unruptured aneurysms that will become unstable (grow and/or rupture) from those that will remain stable. METHODS: One hundred seventy-eight patients harboring 198 unruptured cerebral aneurysms for whom clinical observation and follow-up with imaging surveillance was recommended at 4 clinical centers were prospectively recruited into this study. Imaging data (predominantly CT angiography) at initial presentation was recorded. Computational geometry was used to estimate numerous metrics of aneurysm morphology that described the size and shape of the aneurysm. The nonlinear, finite element method was used to estimate uniform pressure-induced peak wall tension. Computational fluid dynamics was used to estimate blood flow metrics. The median follow-up period was 645 days. Longitudinal outcome data on these aneurysm patients-whether their aneurysms grew or ruptured (the unstable group) or remained unchanged (the stable group)-was documented based on follow-up at 4 years after the beginning of recruitment. RESULTS: Twenty aneurysms (10.1%) grew, but none ruptured. One hundred forty-nine aneurysms (75.3%) remained stable and 29 (14.6%) were lost to follow-up. None of the metrics-including aneurysm size, nonsphericity index, peak wall tension, and low shear stress area-differentiated the stable from unstable groups with statistical significance. CONCLUSIONS: The findings in this highly selected group do not support the hypothesis that image-derived metrics can predict aneurysm growth in patients who have been selected for observation and imaging surveillance. If aneurysm shape is a significant determinant of invasive versus expectant management, selection bias is a key limitation of this study.

Comparison of the association of sac growth and coil compaction with recurrence in coil embolized cerebral aneurysms.

BACKGROUND AND PURPOSE: In recurrent cerebral aneurysms treated by coil embolization, coil compaction is regarded as the presumptive mechanism. We test the hypothesis that aneurysm growth is the primary recurrence mechanism. We also test the hypothesis that the coil mass will translate a measurable extent when recurrence occurs. METHODS: An objective, quantitative image analysis protocol was developed to determine the volumes of aneurysms and coil masses during initial and follow-up visits from 3D rotational angiograms. The population consisted of 15 recurrence and 12 non-recurrence control aneurysms initially completely coiled at a single center. An investigator sensitivity study was performed to assess the objectivity of the methods. Paired Wilcoxon tests (p<0.05, one-tailed) were performed to assess for aneurysm and coil growth. The translation of the coil mass center at follow-up was computed. A Mann Whitney U-Test (p<0.05, one-tailed) was used to compare translation of coil mass centers between recurrence and control subjects. RESULTS: Image analysis protocol was found to be insensitive to the investigator. Aneurysm growth was evident in the recurrence cohort (p=0.003) but not the control (p=0.136). There was no evidence of coil compaction in either the recurrence or control cohorts (recurrence: p=0.339; control: p=0.429). The translation of the coil mass centers was found to be significantly larger in the recurrence cohort than the control cohort (p=0.047). CONCLUSION: Aneurysm sac growth, not coil compaction, was the primary mechanism of recurrence following successful coil embolization. The coil mass likely translates to a measurable extent when recurrence occurs and has the potential to serve as a non-angiographic recurrence marker.

Stratification of a population of intracranial aneurysms using blood flow metrics.

Indices of the intra-aneurysm hemodynamic environment have been proposed as potentially indicative of their longitudinal outcome. To be useful, the indices need to be used to stratify large study populations and tested against known outcomes. The first objective was to compile the diverse hemodynamic indices reported in the literature. Furthermore, as morphology is often the only patient-specific information available in large population studies, the second objective was to assess how the ranking of aneurysms in a population is affected by the use of steady flow simulation as an approximation to pulsatile flow simulation, even though the former is clearly non-physiological. Sixteen indices of aneurysmal hemodynamics reported in the literature were compiled and refined where needed. It was noted that, in the literature, these global indices of flow were always time-averaged over the cardiac cycle. Steady and pulsatile flow simulations were performed on a population of 198 patient-specific and 30 idealised aneurysm models. All proposed hemodynamic indices were estimated and compared between the two simulations. It was found that steady and pulsatile flow simulations had a strong linear dependence (r ≥ 0.99 for 14 indices; r ≥ 0.97 for 2 others) and rank the aneurysms in an almost identical fashion (ρ ≥ 0.99 for 14 indices; ρ ≥ 0.96 for other 2). When geometry is the only measured piece of information available, stratification of aneurysms based on hemodynamic indices reduces to being a physically grounded substitute for stratification of aneurysms based on morphology. Under such circumstances, steady flow simulations may be just as effective as pulsatile flow simulation for estimating most key indices currently reported in the literature.

From medical images to flow computations without user-generated meshes.

Biomedical flow computations in patient-specific geometries require integrating image acquisition and processing with fluid flow solvers. Typically, image-based modeling processes involve several steps, such as image segmentation, surface mesh generation, volumetric flow mesh generation, and finally, computational simulation. These steps are performed separately, often using separate pieces of software, and each step requires considerable expertise and investment of time on the part of the user. In this paper, an alternative framework is presented in which the entire image-based modeling process is performed on a Cartesian domain where the image is embedded within the domain as an implicit surface. Thus, the framework circumvents the need for generating surface meshes to fit complex geometries and subsequent creation of body-fitted flow meshes. Cartesian mesh pruning, local mesh refinement, and massive parallelization provide computational efficiency; the image-to-computation techniques adopted are chosen to be suitable for distributed memory architectures. The complete framework is demonstrated with flow calculations computed in two 3D image reconstructions of geometrically dissimilar intracranial aneurysms. The flow calculations are performed on multiprocessor computer architectures and are compared against calculations performed with a standard multistep route.