David Saloner

Aneurysm Growth Occurs at Region of Low Wall Shear Stress Patient-Specific Correlation of Hemodynamics and Growth in a Longitudinal Study

Background and Purpose— Evolution of intracranial aneurysmal disease is known to be related to hemodynamic forces acting on the vessel wall. Low wall shear stress (WSS) has been reported to have a negative effect on endothelial cells normal physiology and may be an important contributor to local remodeling of the arterial wall and to aneurysm growth and rupture. Methods— Seven patient-specific models of intracranial aneurysms were constructed using MR angiography data acquired at two different time points (mean 16.4±7.4 months between the two time points). Numeric simulations of the flow in the baseline geometries were performed to compute WSS distributions. The lumenal geometries constructed from the two time points were manually coregistered, and the radial displacement of the wall was calculated on a pixel-by-pixel basis. This displacement, corresponding to the local growth of the aneurysm, was compared to the time-averaged wall shear stress (WSSTA) through the cardiac cycle at that location. For statistical analysis, radial displacement was considered to be significant if it was larger than half of the MR pixel resolution (0.3 mm). Results— Mean WSSTA values obtained for the areas with a displacement smaller and greater than 0.3 mm were 2.55±3.6 and 0.76±1.5 Pa, respectively (P<0.001). A linear correlation analysis demonstrated a significant relationship between WSSTA and surface displacement (P<0.001). Conclusions— These results indicate that aneurysm growth is likely to occur in regions where the endothelial layer lining the vessel wall is exposed to abnormally low wall shear stress.

High-Resolution CT Imaging of Carotid Artery Atherosclerotic Plaques

BACKGROUND AND PURPOSE: Plaque morphologic features have been suggested as a complement to luminal narrowing measurements for assessing the risk of stroke associated with carotid atherosclerotic disease, giving rise to the concept of “vulnerable plaque.” The purpose of this study was to evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard. MATERIALS AND METHODS: Eight patients with transient ischemic attacks who underwent carotid CTA and “en bloc” endarterectomy were enrolled in a prospective study. An ex vivo micro-CT study of each endarterectomy specimen was obtained, followed by histologic examination. A systematic comparison of CTA images with histologic sections and micro-CT images was performed to determine the CT attenuation associated with each component of the atherosclerotic plaques. A computer algorithm was subsequently developed that automatically identifies the components of the carotid atherosclerotic plaques, based on the density of each pixel. A neuroradiologists reading of this computer analysis was compared with the interpretation of the histologic slides by a pathologist with respect to the types and characteristics of the carotid plaques. RESULTS: There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (κ = 0.796; P < .001) and large hemorrhages (κ = 0.712; P = .102). CTA performed well in detecting ulcerations (κ = 0.855) and in measuring the fibrous cap thickness (R2 = 0.77; P < .001). CONCLUSION: The composition of carotid atherosclerotic plaques determined by CTA reflects plaque composition defined by histologic examination.

Numerical Analysis of Flow Through a Severely Stenotic Carotid Artery Bifurcation

The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits. In this study, a model based on an endarterectomy specimen of the plaque in a carotid bifurcation was examined. The flow conditions include steady flow at Reynolds numbers of 300, 600, and 900 as well as unsteady pulsatile flow. Both dynamic pressure and wall shear stress are very high, with shear values up to 70 N/m2, proximal to the stenosis throat in the internal carotid artery, and both vary significantly through the flow cycle. The wall shear stress gradient is also strong along the throat. Vortex shedding is observed downstream of the most severe occlusion. Two turbulence models, the Chien and Goldberg varieties of k-epsilon, are tested and evaluated for their relevance in this geometry. The Chien model better captures phenomena such as vortex shedding. The flow distal to stenosis is likely transitional, so a model that captures both laminar and turbulent behavior is needed.

Assessment of carotid artery stenosis by ultrasonography, conventional angiography, and magnetic resonance angiography: Correlation with ex vivo measurement of plaque stenosis

PURPOSE Several studies have investigated the correlation between Doppler ultrasonography (DUS), angiography (CA), and magnetic resonance angiography (MRA) in the evaluation of stenosis of the carotid bifurcation. However, these studies suffer from the lack of a true control-the lesion itself-and therefore conclusions about the diagnostic accuracy of each method remain relative. To determine the absolute accuracy of these modalities, we have prospectively studied lesion size with DUS, MRA, and CA in 28 patients undergoing 31 elective carotid endarterectomies and compared the percent of carotid stenosis determined by each technique to the carotid atheroma resected en bloc. METHODS All patients were evaluated by each modality within 1 month before the thromboendarterectomy. With DUS, stenosis size was determined by standard flow criteria. For angiography and MRA, stenosis was defined as residual lumenal diameter/estimated normal arterial diameter (European Carotid Surgery Trial criteria). At surgery the carotid atheroma was removed en bloc in all patients. Patients in whom the lesion could not be removed successfully without damage were excluded from the study. Stenosis of the atheroma was determined ex vivo with high-resolution (0.03 mm3) magnetic resonance and confirmed by acrylic injection of the specimen under pressure and measurement of the atheroma wall and lumen. RESULTS The measurements of the ex vivo stenosis by high-resolution magnetic resonance imaging correlated closely with the size of stenosis determined by the acrylic specimen casts (r = 0.92). By ex vivo measurement, the lesions were placed in the following size categories: 40% to 59% stenosis (n = 2), 60% to 79% stenosis (n = 6), 80% to 89% stenosis (n = 7), and 90% to 99% stenosis (n = 16). CONCLUSIONS In general, the correlation of measurements of ex vivo stenosis with all modalities was good in these severely diseased arteries, although it was better for DUS (r = 0.80; p < 0.001) and MRA (r = 0.76; p < 0.001) than for CA (r = 0.56; p < 0.05).

Phase-contrast magnetic resonance imaging measurements in intracranial aneurysms in vivo of flow patterns, velocity fields, and wall shear stress: comparison with computational fluid dynamics.

Evolution of intracranial aneurysms is known to be related to hemodynamic forces such as wall shear stress (WSS) and maximum shear stress (MSS). Estimation of these parameters can be performed using numerical simulations with computational fluid dynamics (CFD), but can also be directly measured with magnetic resonance imaging (MRI) using a time‐dependent 3D phase‐contrast sequence with encoding of each of the three components of the velocity vectors (7D‐MRV). To study the accuracy of 7D‐MRV in estimating these parameters in vivo, in comparison with CFD, 7D‐MRV and patient‐specific CFD modeling was performed for 3 patients who had intracranial aneurysms. Visual and quantitative analyses of the flow pattern and distribution of velocities, MSS, and WSS were performed using the two techniques. Spearmans coefficients of correlation between the two techniques were 0.56 for the velocity field, 0.48 for MSS, and 0.59 for WSS. Visual analysis and Bland–Altman plots showed good agreement for flow pattern and velocities but large discrepancies for MSS and WSS. These results indicate that 7D‐MRV can be used in vivo to measure velocity flow fields and for estimating MSS and WSS. Currently, however, this method cannot accurately quantify the latter two parameters. Magn Reson Med 61:409–417, 2009.

Clinical evaluation of aortic coarctation with 4D flow MR imaging

To show that 4D Flow is a clinically viable tool for evaluation of collateral blood flow and demonstration of distorted blood flow patterns in patients with treated and untreated aortic coarctation.

Giant Intracranial Aneurysms: Evolution of Management in a Contemporary Surgical Series

BACKGROUND Many significant microsurgical series of patients with giant aneurysms predate changes in practice during the endovascular era. OBJECTIVE A contemporary surgical experience is presented to examine changes in management relative to earlier reports, to establish the role of open microsurgery in the management strategy, and to quantify results for comparison with evolving endovascular therapies. METHODS During a 13-year period, 140 patients with 141 giant aneurysms were treated surgically. One hundred aneurysms (71%) were located in the anterior circulation, and 41 aneurysms were located in the posterior circulation. RESULTS One hundred eight aneurysms (77%) were completely occluded, 14 aneurysms (10%) had minimal residual aneurysm, and 16 aneurysms (11%) were incompletely occluded with reversed or diminished flow. Three patients with calcified aneurysms were coiled after unsuccessful clipping attempts. Eighteen patients died in the perioperative period (surgical mortality, 13%). Bypass-related complications resulted from bypass occlusion (7 patients), aneurysm hemorrhage due to incomplete aneurysm occlusion (4 patients), or aneurysm thrombosis with perforator or branch artery occlusion (4 patients). Thirteen patients were worse at late follow-up (permanent neurological morbidity, 9%; mean length of follow-up, 23 ± 1.9 months). Overall, good outcomes (Glasgow Outcome Score 5 or 4) were observed in 114 patients (81%), and 109 patients (78%) were improved or unchanged after therapy. CONCLUSION A heavy reliance on bypass techniques plus indirect giant aneurysm occlusion distinguishes this contemporary surgical experience from earlier ones, and obviates the need for hypothermic circulatory arrest. Experienced neurosurgeons can achieve excellent results with surgery as the “first-line” management approach and endovascular techniques as adjuncts to surgery.

Shape Memory Polymer Stent With Expandable Foam: A New Concept for Endovascular Embolization of Fusiform Aneurysms

We demonstrate a new concept for endovascular embolization of nonnecked fusiform aneurysms. A device prototype consisting of a stent augmented with expandable foam, both made from shape memory polymer, was fabricated and deployed in an in vitro model. Visual observation indicated that the foam achieved embolization of the aneurysm while the stent maintained an open lumen in the parent artery. The shape memory polymer stent-foam device is a potential tool for treatment of nonnecked fusiform aneurysms, as well as an alternative to stent- and balloon-assisted coil embolization of wide-necked aneurysms

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone.

Cerebral Ischemia and Infarction From Atheroemboli <100 μm in Size

Background and Purpose— To determine the importance of emboli not trapped by carotid angioplasty filtration devices, we examined fragments <100 &mgr;m released with ex vivo angioplasty and asked if fragment composition and size correlated with brain injury. Methods— Human carotid plaques (21) were excised en bloc, and ex vivo carotid angioplasty was performed. Eight plaques were selected as either highly calcified (4) or highly fibrotic (4) by high-resolution MRI (200 &mgr;m3). Fragments were counted by a Coulter counter. Before injection into male Sprague-Dawley rats, fragments from calcified and fibrotic plaques were sized with 60-, 100-, and 200-&mgr;m filters. Brain ischemia and infarction were assessed by MRI scans (7-T small-bore magnet) and by immunohistologic staining for HSP70 and NueN. Results— All 5 animals injected with 100- to 200-&mgr;m calcified fragments had infarctions. One was lethal. After injection of 60- to 100-&mgr;m calcified fragments, 7 of 12 animals had cerebral infarctions, whereas only 1 of 11 had infarctions with fibrous fragments (P <0.02). HSP70 staining showed that ischemia was more common and more extensive than infarction. Ischemia was found in 10 of 12 animals after injection of calcified fragments and in 9 of 11 after injection of fibrous fragments. The mean number of 60- to 100-&mgr;m fragments released was 375±510; the mean number of 20- to 60-&mgr;m fragments was 34 196 (range, 2230 to 186 927). Conclusions— Hundreds of thousands of microemboli can be shed during carotid angioplasty. Fragments from calcified plaques cause greater levels of infarction than fragments from fibrous plaques, although ischemia is common with both fragment types.