Ferumoxytol-enhanced magnetic resonance angiography is a feasible method for the clinical evaluation of lower extremity arterial disease.

BACKGROUND: Renal toxicity from conventional, iodinated, intravenous contrast agents is a common complication in patients with peripheral artery disease (PAD). Similarly, the potential for serious side effects prevents the use of gadolinium-based agents in many patients with depressed renal function. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a novel technique that uses an intravenous, ultrasmall, superparamagnetic, iron oxide preparation, currently approved by the Food and Drug Administration for the treatment of iron deficiency anemia in adults with chronic kidney disease. Our objective was to determine the feasibility of Fe-MRA for clinical decision making in PAD patients. METHODS: This was a prospective pilot study assessing 10 patients with suspected arterial occlusive disease with contrast-enhanced MRA of the aorta and lower extremities. Of those, 5 had renal insufficiency and were imaged with Fe-MRA, whereas the remainder underwent gadolinium-enhanced MRA. Qualitative and quantitative evaluations of deidentified images at each arterial station were independently performed by 4 blinded vascular surgeons. RESULTS: All patients were men, with an average age of 68 ± 4 years. The 2 groups had similar incidences of diabetes, hypertension, hyperlipidemia, and coronary artery disease. Patients undergoing Fe-MRA had significantly decreased renal function (estimated glomerular filtration rate, 35.4 vs. 77.6; P = 0.02). There were no adverse events during contrast administration in either group. No difference was found in the overall quality of the ferumoxytol versus the gadolinium studies (7.1 ± 2.0 vs. 7.4 ± 2.4, P = 0.67). Similarly, reviewers felt comfortable basing clinical decisions on the images 89% of the time with both the ferumoxytol and gadolinium groups (P = 1.00). CONCLUSIONS: This is the first report of an important alternative to conventional computed tomography angiography and MRA in PAD patients, particularly in the setting of renal insufficiency. Fe-MRA provides a useful tool in patients with suspected lower extremity PAD without the potential risks of gadolinium.

Height and body surface area versus wall stress for stratification of mid-term outcomes in ascending aortic aneurysm.

Objectives: Current diameter-based guidelines for ascending thoracic aortic aneurysms (aTAA) do not consistently predict risk of dissection/rupture. ATAA wall stresses may enhance risk stratification independent of diameter. The relation of wall stresses and diameter indexed to height and body surface area (BSA) is unknown. Our objective was to compare aTAA wall stresses with indexed diameters in relation to all-cause mortality at 3.75 years follow-up. Methods: Finite element analyses were performed in a veteran population with aortas ≥ 4.0 cm. Three-dimensional geometries were reconstructed from computed tomography with models accounting for pre-stress geometries. A fiber-embedded hyperelastic material model was applied to obtain wall stress distributions under systolic pressure. Peak wall stresses were compared across guideline thresholds for diameter/BSA and diameter/height. Hazard ratios for all-cause mortality and surgical aneurysm repair were estimated using cause-specific Cox proportional hazards models. Results: Of 253 veterans, 54 (21 %) had aneurysm repair at 3.75 years. Indexed diameter alone would have prompted repair at baseline in 17/253 (6.7 %) patients, including only 4/230 (1.7 %) with diameter < 5.5 cm. Peak wall stresses did not significantly differ across guideline thresholds for diameter/BSA (circumferential: p = 0.15; longitudinal: p = 0.18), but did differ for diameter/height (circumferential: p = 0.003; longitudinal: p = 0.048). All-cause mortality was independently associated with peak longitudinal stresses (p = 0.04). Peak longitudinal stresses were best predicted by diameter (c-statistic = 0.66), followed by diameter/height (c-statistic = 0.59), and diameter/BSA (c-statistic = 0.55). Conclusions: Diameter/height improved stratification of peak wall stresses compared to diameter/BSA. Peak longitudinal stresses predicted all-cause mortality independent of age and indexed diameter and may aid risk stratification for aTAA adverse events.

Temporal Evolution of Ascending Aortic Aneurysm Wall Stress Predicts All-Cause Mortality.

OBJECTIVES: Diameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over three to five years and subsequent all-cause mortality. METHODS: Male veterans with <5.5-cm ascending aortic aneurysms and computed tomography at baseline and 3 to 5-years follow-up underwent three-dimensional aneurysm model construction. Peak circumferential and longitudinal wall stresses at systole were calculated using finite element analysis. Temporal trends were assessed by mixed-effects modelling. Changes in aortic wall stresses, diameter, and length over time were evaluated as predictors of subsequent 3-year all-cause mortality by Cox proportional hazards modelling. RESULTS: Sixty-two male veterans were included in the study. Yearly changes in geometric and biomechanical measures were 0.12 mm/yr (95% CI, 0.04-0.20) for aortic diameter, 0.41 mm/yr (0.12-0.71) for aortic length, 1.19 kPa/yr (-5.94-8.33) for peak circumferential stress, and 0.48 kPa/yr (-3.89-4.84) for peak longitudinal stress. Yearly change in peak circumferential stress was significantly associated with hazard of death-hazard ratio for peak circumferential stress growth per 10 kPa/yr, 1.27 (95% CI, 1.02-1.60; p = 0.037); hazard ratio for peak circumferential stress growth ≥ 32 kPa/yr, 8.47 (95% CI, 2.42-30; p < 0.001). CONCLUSIONS: In this population of nonsurgical aneurysm patients, large temporal changes in peak circumferential stress, but not aortic diameter or length, was associated with all-cause mortality. Biomechanical stress and stress changes over time may be beneficial as additional risk factors for elective surgery in small aneurysms.

Diagnosis of intracranial aneurysms by computed tomography angiography using deep learning-based detection and segmentation.

BACKGROUND: Detecting and segmenting intracranial aneurysms (IAs) from angiographic images is a laborious task. OBJECTIVE: To evaluates a novel deep-learning algorithm, named vessel attention (VA)-Unet, for the efficient detection and segmentation of IAs. METHODS: This retrospective study was conducted using head CT angiography (CTA) examinations depicting IAs from two hospitals in China between 2010 and 2021. Training included cases with subarachnoid hemorrhage (SAH) and arterial stenosis, common accompanying vascular abnormalities. Testing was performed in cohorts with reference-standard digital subtraction angiography (cohort 1), with SAH (cohort 2), acquired outside the time interval of training data (cohort 3), and an external dataset (cohort 4). The algorithm's performance was evaluated using sensitivity, recall, false positives per case (FPs/case), and Dice coefficient, with manual segmentation as the reference standard. RESULTS: The study included 3190 CTA scans with 4124 IAs. Sensitivity, recall, and FPs/case for detection of IAs were, respectively, 98.58%, 96.17%, and 2.08 in cohort 1; 95.00%, 88.8%, and 3.62 in cohort 2; 96.00%, 93.77%, and 2.60 in cohort 3; and, 96.17%, 94.05%, and 3.60 in external cohort 4. The segmentation accuracy, as measured by the Dice coefficient, was 0.78, 0.71, 0.71, and 0.66 for cohorts 1-4, respectively. VA-Unet detection recall and FPs/case and segmentation accuracy were affected by several clinical factors, including aneurysm size, bifurcation aneurysms, and the presence of arterial stenosis and SAH. CONCLUSIONS: VA-Unet accurately detected and segmented IAs in head CTA comparably to expert interpretation. The proposed algorithm has significant potential to assist radiologists in efficiently detecting and segmenting IAs from CTA images.

Left ventricular pressure gating in ovine cardiac studies: a software-based method.

Cardiac imaging using magnetic resonance requires a gating signal in order to compensate for motion. Human patients are routinely scanned using an electrocardiogram (ECG) as a gating signal during imaging. However, we found that in sheep the ECG is not a reliable method for gating. We developed a software based method that allowed us to use the left ventricular pressure (LVP) as a reliable gating signal. By taking the time derivative of the LVP (dP/dt), we were able to start imaging at both end-diastole for systolic phase images, and end-systole for diastolic phase images. We also used MR tissue tagging to calculate 3D strain information during diastole. Using the LVP in combination with our digital circuit provided a reliable and time efficient method for ovine cardiac imaging. Unlike the ECG signal the left ventricular pressure was a clean signal and allowed for accurate, nondelay based triggering during systole and diastole.

Baseline vessel wall magnetic resonance imaging characteristics associated with in-stent restenosis for intracranial atherosclerotic stenosis.

BACKGROUND: Imaging factors, specifically baseline plaque features on high-resolution magnetic resonance vessel wall imaging (HR-VWI) that could be associated with in-stent restenosis (ISR), are still unknown. We aimed to investigate the presenting clinical and plaque features on HR-VWI associated with ISR. METHODS: Sixty-four patients with intracranial stent placement for intracranial atherosclerotic stenosis who had pre- and post-contrast T1-weighted HR-VWI on 3.0T prior to stenting were included in this analysis. Student's t-test, Mann-Whitney U test, χ2 test, or the Cochran-Mantel-Haenszel (CMH) test were used to compare clinical and baseline HR-VWI characteristics of the patients between the ISR and non-ISR groups. Univariable and multivariable logistic analysis were used to test the clinical and imaging factors associated with ISR. RESULTS: Among the 64 patients, 9 patients (14.06%) developed ISR during the 2-year follow-up period. Plaque burden (median 0.89 vs 0.92, P=0.04), minimum lumen area (0.009 cm2 vs 0.006 cm2, P=0.04), plaque eccentricity (55.6% vs 89.1%, P＜0.01), enhancement ratio (1.36 vs 0.84, P＜0.01), and enhancement involvement (type 2 represents ≥50% cross-sectional wall involvement; 100% vs 63.6%, P=0.03) all significantly differed between patients with and without ISR. Multivariable analysis revealed that lower frequency of plaque eccentricity (OR 0.18, 95% CI 0.04 to 0.96, P=0.04) and higher enhancement ratio (OR 3.57, 95% CI 1.02 to 12.48, P=0.04) were independently associated with ISR. CONCLUSIONS: Preliminary findings showed that ISR was independently associated with plaque concentricity and higher enhancement ratios on pre-stenting HR-VWI for patients with symptomatic intracranial atherosclerotic stenosis.

Aortic area/height ratio, peak wall stresses, and outcomes in veterans with tricuspid versus bicuspid aortic valve-associated ascending thoracic aortic aneurysms.

BACKGROUND: In ascending thoracic aortic aneurysm risk stratification, aortic area/height ratio is a reasonable alternative to maximum diameter. Biomechanically, aortic dissection may be initiated by wall stress exceeding wall strength. Our objective was to evaluate the association between aortic area/height and peak aneurysm wall stresses in relation to valve morphology and 3-year all-cause mortality. METHODS: Finite element analysis was performed on 270 ascending thoracic aortic aneurysms (46 associated with bicuspid and 224 with tricuspid aortic valves) in veterans. Three-dimensional aneurysm geometries were reconstructed from computed tomography and models developed accounting for prestress geometries. Fiber-embedded hyperelastic material model was applied to obtain aneurysm wall stresses during systole. Correlations of aortic area/height ratio and peak wall stresses were compared across valve types. Area/height ratio was evaluated across peak wall stress thresholds obtained from proportional hazards models of 3-year all-cause mortality, with aortic repair treated as a competing risk. RESULTS: Aortic area/height 10 cm2/m or greater coincided with 23/34 (68%) 5.0 to 5.4 cm and 20/24 (83%) 5.5 cm or greater aneurysms. Area/height correlated weakly with peak aneurysm stresses: for tricuspid valves, r = 0.22 circumferentially and r = 0.24 longitudinally; and for bicuspid valves, r = 0.42 circumferentially and r = 0.14 longitudinally. Age and peak longitudinal stress, but not area/height, were independent predictors of all-cause mortality (age: hazard ratio, 2.20 per 9-year increase, P = .013; peak longitudinal stress: hazard ratio, 1.78 per 73-kPa increase, P = .035). CONCLUSIONS: Area/height was more predictive of high circumferential stresses in bicuspid than tricuspid valve aneurysms, but similarly less predictive of high longitudinal stresses in both valve types. Peak longitudinal stress, not area/height, independently predicted all-cause mortality. VIDEO ABSTRACT.

Association of 3-Year All-Cause Mortality and Peak Wall Stresses of Ascending Thoracic Aortic Aneurysms in Veterans.

Risk of aortic dissection in ascending thoracic aortic aneurysms is not sufficiently captured by size-based metrics. From a biomechanical perspective, dissection may be initiated when wall stress exceeds wall strength. Our objective was to assess the association between aneurysm peak wall stresses and 3-year all-cause mortality. Finite element analysis was performed in 273 veterans with chest computed tomography for surveillance of ascending thoracic aortic aneurysms. Three-dimensional geometries were reconstructed and models developed accounting for prestress geometries. A fiber-embedded hyperelastic material model was applied to obtain circumferential and longitudinal wall stresses under systolic pressure. Patients were followed up to 3 years following the scan to assess aneurysm repair and all-cause mortality. Fine-Gray subdistribution hazards were estimated for all-cause mortality based on age, aortic diameter, and peak wall stresses, treating aneurysm repair as a competing risk. When accounting for age, subdistribution hazard of mortality was not significantly increased by peak circumferential stresses (p = 0.30) but was significantly increased by peak longitudinal stresses (p = 0.008). Aortic diameter did not significantly increase subdistribution hazard of mortality in either model (circumferential model: p = 0.38; longitudinal model: p = 0.30). The effect of peak longitudinal stresses on subdistribution hazard of mortality was maximized at a binary threshold of 355kPa, which captured 34 of 212(16%) patients with diameter <5 cm, 11 of 36(31%) at 5.0-5.4 cm, and 11 of 25(44%) at ≥5.5 cm. Aneurysm peak longitudinal stresses stratified by age and diameter were associated with increased hazard of 3-year all-cause mortality in a veteran cohort. Risk prediction may be enhanced by considering peak longitudinal stresses.

Ascending thoracic aortic aneurysm elongation occurs in parallel with dilatation in a nonsurgical population.

OBJECTIVES: Rapid diameter growth is a criterion for ascending thoracic aortic aneurysm repair; however, there are sparse data on aneurysm elongation rate. The purpose of this study was to assess aortic elongation rates in nonsyndromic, nonsurgical aneurysms to understand length dynamics and correlate with aortic diameter over time. METHODS: Patients with <5.5-cm aneurysms and computed tomography angiography imaging at baseline and 3-5 years follow-up underwent patient-specific three-dimensional aneurysm reconstruction using MeVisLab. Aortic length was measured along the vessel centreline between the annulus and aortic arch. Maximum aneurysm diameter was determined from imaging in a plane normal to the vessel centreline. Average rates of aneurysm growth were evaluated using the longest available follow-up. RESULTS: Over the follow-up period, the mean aortic length for 67 identified patients increased from 118.2 (95% confidence interval: 115.4-121.1) mm to 120.2 (117.3-123.0) mm (P = 0.02) and 15 patients (22%) experienced a change in length of ≥5% from baseline. The mean annual growth rate for length [0.38 (95% confidence interval: 0.11-0.65) mm/year] was correlated with annual growth rate for diameter [0.1 (0.03-0.2) mm/year] (rho = 0.30, P = 0.01). Additionally, annual percentage change in length [0.3 (0.1-0.5)%/year] was similar to percentage change in diameter [0.2 (0.007-0.4)%/year, P = 0.95]. CONCLUSIONS: Aortic length increases in parallel with aortic diameter at a similar percentage rate. Further work is needed to identify whether elongation rate is associated with dissection risk. Such studies may provide insight into why patients with aortic diameters smaller than surgical guidelines continue to experience dissection events.

Silent intralesional microhemorrhage as a risk factor for brain arteriovenous malformation rupture.

BACKGROUND AND PURPOSE: We investigated whether brain arteriovenous malformation silent intralesional microhemorrhage, that is, asymptomatic bleeding in the nidal compartment, might serve as a marker for increased risk of symptomatic intracranial hemorrhage (ICH). We evaluated 2 markers to assess the occurrence of silent intralesional microhemorrhage: neuroradiological assessment of evidence of old hemorrhage-imaging evidence of bleeding before the outcome events-and hemosiderin positivity in hematoxylin and eosin-stained paraffin block sections. METHODS: We identified cases from our brain arteriovenous malformation database with recorded neuroradiological data or available surgical paraffin blocks. Using 2 end points, index ICH or new ICH after diagnosis (censored at treatment, loss to follow-up, or death), we performed logistic or Cox regression to assess evidence of old hemorrhage and hemosiderin positivity adjusting for age, sex, deep-only venous drainage, maximal brain arteriovenous malformation size, deep location, and associated arterial aneurysms. RESULTS: Evidence of old hemorrhage was present in 6.5% (n=975) of patients and highly predictive of index ICH (P<0.001; OR, 3.97; 95% CI, 2.1-7.5) adjusting for other risk factors. In a multivariable model (n=643), evidence of old hemorrhage was an independent predictor of new ICH (hazard ratio, 3.53; 95% CI, 1.35-9.23; P=0.010). Hemosiderin positivity was found in 36.2% (29.6% in unruptured; 47.8% in ruptured; P=0.04) and associated with index ICH in univariate (OR, 2.18; 95% CI, 1.03-4.61; P=0.042; n=127) and multivariable models (OR, 3.64; 95% CI, 1.11-12.00; P=0.034; n=79). CONCLUSIONS: The prevalence of silent intralesional microhemorrhage is high and there is evidence for an association with both index and subsequent ICH. Further development of means to detect silent intralesional microhemorrhage during brain arteriovenous malformation evaluation may present an opportunity to improve risk stratification, especially for unruptured brain arteriovenous malformations.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics.

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

Ascending thoracic aortic aneurysm growth is minimal at sizes that do not meet criteria for surgical repair.

BACKGROUND: Historic studies of nonsyndromic ascending thoracic aortic aneurysms (aTAAs) reported that the typical aTAA growth rate was approximately 0.6 mm/year, but data were limited due to relatively few studies using computed tomography (CT) imaging. Our purpose was to reevaluate the annual growth rate of nonsyndromic aTAAs that do not meet criteria for surgical repair in veterans in the contemporary era, using modern CT imaging suitable for highly accurate and reproducible aneurysm measurement. METHODS: Nonsurgical patients (diameter <5.5 cm) undergoing aneurysm surveillance at a Veterans Affairs Medical Center with repeat CT imaging performed 3 to 5 years apart were identified. Maximum diameter was determined by a single radiologist using multiplanar reformat-based measurements. Average rate of aneurysm growth was evaluated based on longest available follow-up. RESULTS: Sixty-seven patients were included. Average follow-up time was 4.06±0.83 years. Patients were exclusively male, with average age of 68.1±6.0 years, and the majority had a history of smoking (n=52, 78%), hypertension (n=52, 78%), and dyslipidemia (n=48, 72%). Average baseline aneurysm diameter was 44.0±3.2 mm and average growth rate was 0.11±0.31 mm/year, with no difference in growth rate between patients with initial diameter ≤45 vs. >45 mm. Only 3 patients experienced clinically significant changes in diameter with magnitude greater than 5% of baseline. CONCLUSIONS: In this veteran population, most patients did not experience significant annual aneurysm growth over up to 5 years of follow-up, regardless of initial diameter. Thus, in the modern era, aTAAs may not grow as quickly as previously described, which will be important in determining appropriate intervals for aneurysm surveillance based upon risk-benefit ratio.

Association of diameter and wall stresses of tricuspid aortic valve ascending thoracic aortic aneurysms.

OBJECTIVE: Ascending thoracic aortic aneurysms carry a risk of acute type A dissection. Elective repair guidelines are designed around size thresholds, but the 1-dimensional parameter of maximum diameter cannot predict acute events in small aneurysms. Biomechanically, dissection can occur when wall stress exceeds strength. Patient-specific ascending thoracic aortic aneurysm wall stresses may be a better predictor of dissection. Our aim was to compare wall stresses in tricuspid aortic valve-associated ascending thoracic aortic aneurysms based on diameter. METHODS: Patients with tricuspid aortic valve-associated ascending thoracic aortic aneurysm and diameter 4.0 cm or greater (n = 221) were divided into groups by 0.5-cm diameter increments. Three-dimensional geometries were reconstructed from computed tomography images, and finite element models were developed taking into account prestress geometries. A fiber-embedded hyperelastic material model was applied to obtain longitudinal and circumferential wall stress distributions under systolic pressure. Median stresses with interquartile ranges were determined. The Kruskal-Wallis test was used for comparisons between size groups. RESULTS: Peak longitudinal wall stresses for tricuspid aortic valve-associated ascending thoracic aortic aneurysm were 290 (265-323) kPa for size 4.0 to 4.4 cm versus 330 (296-359) kPa for 4.5 to 4.9 cm versus 339 (320-373) kPa for 5.0 to 5.4 cm versus 318 (293-351) kPa for 5.5 to 5.9 cm versus 373 (363-449) kPa for 6.0 cm or greater (P = 8.7e-8). Peak circumferential wall stresses were 460 (421-543) kPa for size 4.0 to 4.4 cm versus 503 (453-569) kPa for 4.5 to 4.9 cm versus 549 (430-588) kPa for 5.0 to 5.4 cm versus 540 (471-608) kPa for 5.5 to 5.9 cm versus 596 (506-649) kPa for 6.0 cm or greater (P = .0007). CONCLUSIONS: Circumferential and longitudinal wall stresses are higher as diameter increases, but size groups had large overlap of stress ranges. Wall stress thresholds based on aneurysm wall strength may be a better predictor of patient-specific risk of dissection than diameter in small ascending thoracic aortic aneurysms.

Regional wall stress differences on tricuspid aortic valve-associated ascending aortic aneurysms.

OBJECTIVES: Ascending thoracic aortic aneurysms (aTAAs) carry a risk of acute type A dissection. Elective repair guidelines are based on diameter, but complications often occur below diameter threshold. Biomechanically, dissection can occur when wall stress exceeds wall strength. Aneurysm wall stresses may better capture dissection risk. Our aim was to investigate patient-specific aTAA wall stresses associated with a tricuspid aortic valve (TAV) by anatomic region. METHODS: Patients with aneurysm diameter ≥4.0 cm underwent computed tomography angiography. Aneurysm geometries were reconstructed and loaded to systemic pressure while taking prestress into account. Finite element analyses were conducted to obtain wall stress distributions. The 99th percentile longitudinal and circumferential stresses were determined at systole. Wall stresses between regions were compared using one-way analysis of variance with post hoc Tukey HSD for pairwise comparisons. RESULTS: Peak longitudinal wall stresses on aneurysms (n = 204) were 326 [standard deviation (SD): 61.7], 246 (SD: 63.4) and 195 (SD: 38.7) kPa in sinuses of Valsalva, sinotubular junction (STJ) and ascending aorta (AscAo), respectively, with significant differences between AscAo and both sinuses (P < 0.001) and STJ (P < 0.001). Peak circumferential wall stresses were 416 (SD: 85.1), 501 (SD: 119) and 340 (SD: 57.6) kPa for sinuses, STJ and AscAo, respectively, with significant differences between AscAo and both sinuses (P < 0.001) and STJ (P < 0.001). CONCLUSIONS: Circumferential and longitudinal wall stresses were greater in the aortic root than AscAo on aneurysm patients with a TAV. Aneurysm wall stress magnitudes and distribution relative to respective regional wall strength could improve understanding of aortic regions at greater risk of dissection in a particular patient.

Quantitative analysis of unruptured intracranial aneurysm wall thickness and enhancement using 7T high resolution, black blood magnetic resonance imaging.

BACKGROUND: This study was performed to quantify intracranial aneurysm wall thickness (AWT) and enhancement using 7T MRI, and their relationship with aneurysm size and type. METHODS: 27 patients with 29 intracranial aneurysms were included. Three-dimensional T1 weighted pre- and post-contrast fast spin echo with 0.4 mm isotropic resolution was used. AWT was defined as the full width at half maximum on profiles of signal intensity across the aneurysm wall on pre-contrast images. Enhancement ratio (ER) was defined as the signal intensity of the aneurysm wall over that of the brain parenchyma. The relationships between AWT, ER, and aneurysm size and type were investigated. RESULTS: 7T MRI revealed large variations in AWT (range 0.11-1.24 mm). Large aneurysms (>7 mm) had thicker walls than small aneurysms (≤7 mm) (0.49±0.05 vs 0.41±0.05 mm, p<0.001). AWT was similar between saccular and fusiform aneurysms (p=0.546). Within each aneurysm, a thicker aneurysm wall was associated with increased enhancement in 28 of 29 aneurysms (average r=0.65, p<0.05). Thicker walls were observed in enhanced segments (ER >1) than in non-enhanced segments (0.53±0.09 vs 0.38±0.07 mm, p<0.001). CONCLUSION: Improved image quality at 7T allowed quantification of intracranial AWT and enhancement. A thicker aneurysm wall was observed in larger aneurysms and was associated with stronger enhancement.

Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.

Brain arteriovenous malformations (bAVMs) are relatively rare, although their potential for secondary intracranial haemorrhage (ICH) makes their diagnosis and management essential to the community. Currently, invasive therapies (surgical resection, stereotactic radiosurgery and endovascular embolisation) are the only interventions that offer a reduction in ICH risk. There is no designated medical therapy for bAVM, although there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs. In this single-arm pilot study, two patients with large bAVMs (deemed unresectable by an interdisciplinary team) received bevacizumab 5 mg/kg every 2 weeks for 12 weeks. Due to limitations of external funding, the intended sample size of 10 participants was not reached. Primary outcome measure was change in bAVM volume from baseline at 26 and 52 weeks. No change in bAVM volume was observed 26 or 52 weeks after bevacizumab treatment. No clinically important adverse events were observed during the 52-week study period. There were no observed instances of ICH. Sera vascular endothelial growth factor levels were reduced at 26 weeks and returned to baseline at 52 weeks. This pilot study is the first to test bevacizumab for patients with bAVMs. Bevacizumab therapy was well tolerated in both subjects. No radiographic changes were observed over the 52-week study period. Subsequent larger clinical trials are in order to assess for dose-dependent efficacy and rarer adverse drug effects. Trial registration number: NCT02314377.

Wall stress analyses in patients with ≥5 cm versus <5 cm ascending thoracic aortic aneurysm.

OBJECTIVE: Current guidelines for elective surgery of ascending thoracic aortic aneurysms (aTAAs) use aneurysm size as primary determinant for risk stratification of adverse events. Biomechanically, dissection may occur when wall stress exceeds wall strength. Determining patient-specific aTAA wall stresses by finite element analysis can potentially predict patient-specific risk of dissection. This study compared peak wall stresses in patients with ≥5.0 cm versus <5.0 cm aTAAs to determine correlation between diameter and wall stress. METHODS: Patients with aTAA ≥5.0 cm (n = 47) and <5.0 cm (n = 53) were studied. Patient-specific aneurysm geometries obtained from echocardiogram-gated computed tomography were meshed and prestress geometries determined. Peak wall stresses and stress distributions were determined using LS-DYNA finite element analysis software (LSTC Inc, Livermore, Calif), with user-defined fiber-embedded material models under systolic pressure. RESULTS: Peak circumferential stresses at systolic pressure were 530 ± 83 kPa for aTAA ≥5.0 cm versus 486 ± 87 kPa for aTAA <5.0 cm (P = .07), whereas peak longitudinal stresses were 331 ± 57 kPa versus 310 ± 54 kPa (P = .08), respectively. For aTAA ≥5.0 cm, correlation between peak circumferential stresses and size was 0.41, whereas correlation between peak longitudinal wall stresses and size was 0.33. However, for aTAA <5.0 cm, correlation between peak circumferential stresses and size was 0.23, whereas correlation between peak longitudinal stresses and size was 0.14. CONCLUSIONS: Peak patient-specific aTAA wall stresses overall were larger for ≥5.0 cm than aTAA <5.0 cm. Although some correlation between size and peak wall stresses was found in aTAA ≥5.0 cm, poor correlation existed between size and peak wall stresses in aTAA <5.0 cm. Patient-specific wall stresses are particularly important in determining patient-specific risk of dissection for aTAA <5.0 cm.

Wall Stress Distribution in Bicuspid Aortic Valve-Associated Ascending Thoracic Aortic Aneurysms.

BACKGROUND: Bicuspid aortic valve-associated ascending thoracic aortic aneurysms (BAV-aTAAs) carry a risk of acute type A dissection. Biomechanically, dissection may occur when wall stress exceeds wall strength. Our aim was to develop patient-specific computational models of BAV-aTAAs to determine magnitudes of wall stress by anatomic regions. METHODS: Patients with BAV-aTAA diameter greater than 4.5 cm (n = 41) underwent electrocardiogram-gated computed tomography angiography. Three-dimensional aneurysm geometries were reconstructed after accounting for prestress and loaded to systemic pressure. Finite element analyses were performed with fiber-embedded hyperelastic material model using LS-DYNA software (LSTC Inc, Livermore, CA) to obtain wall stress distributions. The 99th percentile longitudinal and circumferential stresses were determined at systole. RESULTS: The 99th percentile longitudinal wall stresses for BAV-aTAAs at sinuses of Valsalva, sinotubular junction (STJ), and ascending aorta were 361 ± 59.8 kPa, 295 ± 67.2 kPa, and 224 ± 37.6 kPa, respectively, with significant differences in ascending aorta vs sinuses (P< 1 × 10-13) and STJ (P < 1 × 10-6). The 99th percentile circumferential wall stresses were 474 ± 88.2 kPa, 634 ± 181.9 kPa, and 381 ± 54.0 kPa for sinuses, the STJ, and the ascending aorta, respectively, with significant differences in the ascending aorta vs sinuses (P = .002) and STJ (P < 1 × 10-13). CONCLUSIONS: Wall stresses, both circumferential and longitudinal, were greater in the aortic root, sinuses, and STJ than in the ascending aorta on BAV-aTAAs. These results fill a fundamental knowledge gap regarding biomechanical stress distribution in BAV-aTAA patients, which when related to wall strength may provide prognostication of aTAA dissection risk by patient-specific modeling.

MR imaging during endovascular procedures: an evaluation of the potential for catheter heating.

MRI in catheterized patients is considered unsafe due to the potential for focal heating. This concern arises from the continuous metallic braid that is incorporated into catheters to provide their desired physical properties. The potential for catheter heating during MR scanning was assessed in an in vitro model simulating a patient undergoing a neurovascular procedure in which MR scans of the brain will be performed. Heating adjacent to endovascular devices was assessed with fluoroptic temperature probes in a polyacrylamide gel. The effect of variable immersion lengths, lateral and longitudinal offsets, position along the endovascular device, physical MR system, and specific absorption rate (SAR) level were studied to determine their effect on catheter heating. A rapid temperature rise was evident next to endovascular devices during MR scanning and varied moderately with immersed length, position within the bore, measurement point on the device, and MR system used. Peak heating rates were less than 1 degree C/min with maximal SAR exposure and anatomically realistic geometries. Heating scaled linearly with SAR and SAR values below 0.2 W/kg produced negligible heating near catheters. For the evaluated application, substantial SAR restrictions, coupled with limited imaging durations, are proposed as sufficient to permit MRI without concern for thermal injury.

Wall stress on ascending thoracic aortic aneurysms with bicuspid compared with tricuspid aortic valve.

OBJECTIVE: Guidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts. METHODS: Patients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress. RESULTS: Bicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007). CONCLUSIONS: Circumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction.