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Morphological evolution of symptomatic intracranial atherosclerotic plaques: a 10-year longitudinal study by 3-dimensional rotational angiography
Introduction: Patients with symptomatic high-grade intracranial atherosclerotic disease (ICAD) are at risk of stroke recurrence even under stringent medical therapy. Understanding how the plaque evolves in these patients may help prevent recurrent stroke.Methods: In a prospective, multicenter referral, longitudinal study, we recruited 40 patients (mean age = 61.1 years) with symptomatic high-grade ICAD (70-99% stenosis) confirmed by 3-dimensional rotational angiography (3DRA) from July 2007 to Feb 2016. All patients had 3DRA at baseline and 1 year. All patients received contemporary optimal medical treatment. We assessed the morphological features of qualifying ICAD lesions in the paired 3DRA images. A plaque was considered progressive if the plaque surface evolved from being smooth to irregular/ulcerated or from irregular to ulcerated, or the affected artery occluded at 1 year. We explored factors associated with plaque progression.Results: The qualifying ICAD lesions were in average 77.7% stenosis at baseline. The point of maximum stenosis was located at the distal end of the plaques in 21 (52.5%) cases, and 38 (95.0%) patients had eccentric plaques at baseline. The mean upstream plaque shoulder angulation was 46.4° at baseline. Eleven (27.5%) ICAD lesions progressed from baseline to 1 year. Longer lesions (p=0.038) with a smaller upstream plaque shoulder angulation (p=0.038) and the maximum stenosis locating at the distal end of the lesion (p=0.056) at baseline were more likely to progress in the plaque morphology over 1 year.Conclusions: Under modern medical treatment, although the majority of symptomatic ICAD lesions might regress over 1 year after an index stroke, lesions of a longer length, a smaller upstream angulation, or with the maximum stenosis located at the distal end were more likely to progress in terms of the plaque morphology.Author Disclosures: X. Leng: None. L. Wang: None. X. Zou: None. Y.O. Soo: None. A.Y. Chan: None. V.H. Ip: None. F.S. Fan: None. V.C. Mok: None. L.K. Wong: None. S.C. Yu: None. T.W. Leung: None.
Morphology of acute symptomatic intracranial atherosclerotic plaques
Introduction: Intracranial atherosclerotic disease (ICAD) is an important subtype of ischemic stroke worldwide. Understanding the morphologic features of acutely symptomatic plaques may help identify vulnerable lesions and guide treatment.Methods: We prospectively recruited 170 patients (median age = 60.5 years) with acute ischemic stroke attributed to ICAD (≥60% stenosis) confirmed by 3-dimensional rotational angiography (3DRA) from May 2007 to Feb 2017. We evaluated the morphology of the index atherosclerotic plaques in 3DRA. We categorized plaques with irregular or ulcerated surface as complicated plaques. We compared the morphological features of smooth and complicated plaques.Results: The median interval between symptom onset and 3DRA exam was 22 days. The median severity of luminal stenosis was 75%. The median maximum plaque thickness was 1.3mm and lesion length was 8.8mm. The plaque surface was smooth, irregular, or ulcerated in 50 (29.4%), 90 (52.9%), and 27 (15.9%) cases, respectively. The point of maximum stenosis was located in the distal end of the lesions in 88 (51.8%) cases. A majority (85.3%) of the plaques were eccentric. The median angulation between the upstream plaque shoulder and an imagined “normal” vessel wall (assuming there were no plaque) was 33.4°. Overall, complicated plaques led to more severe luminal stenosis (medians 77.0 vs 73.0%; p=0.032); the lesions were longer (medians 10.0 vs 6.9 mm; p<0.001), and the upstream shoulders were steeper (median angles 34.3 vs 28.0°; p=0.048) than smooth plaques.Conclusions: We identified the morphologic pattern of symptomatic high-grade intracranial atherosclerotic plaques during the acute phase that are significantly different between smooth and complicated plaques. The current findings warrant a comparison with silent ICAD lesions for validation.Author Disclosures: X. Leng: None. L. Wang: None. X. Zou: None. Y.O. Soo: None. A.Y. Chan: None. V.H. Ip: None. F. Fan: None. V.C. Mok: None. L.K. Wong: None. S.C. Yu: None. T.W. Leung: None.
Sustaining cerebral perfusion in intracranial atherosclerotic stenosis: The roles of antegrade residual flow and leptomeningeal collateral flow
<jats:p> We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR ( p < 0.001) rather than LMC scale in those with a moderate (50–69%) MCA stenosis, which, however, was only significantly associated with LMC scale ( p = 0.051) in those with a severe (70–99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis. </jats:p>
Collateral circulation alters downstream hemodynamic stress caused by intracranial atherosclerotic stenosis
OBJECTIVES: Fractional flow reserve (FFR) accurately predicts the degree of stenosis and is now widely used to identify clinically significant severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to determine the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF with the severity of stenosis and collateral circulation. METHODS: Patients with symptomatic ICAS (70-99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination with the use of pressure sensors and was measured as a ratio, comparing measurements distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of leptomeningeal collateralization was graded from zero (absent) to four (complete compensatory). The correlation between FF, anatomical stenosis, and collateral status was then analyzed. RESULTS: Twenty-five patients with a mean age of 55.6 years were analyzed. The median percentage of stenosis and median FF were 82.3 and 0.68%, respectively. Eleven patients were found to have poor collateralization (grade 0-2), and fourteen patients were identified with good collateral circulation (grade 3-4). Overall, the hemodynamic impact of an atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis increased, although this did not reach statistical significance (r = -0.398, p = 0.06). However, the status of collateralization significantly altered this correlation, worsening the hemodynamic impact in patients with poor collateral circulation (r = -0.677, p = 0.032). There was no difference in patients with good collateral circulation (r = -0.279, p = 0.356). CONCLUSION: An anatomically severe (70-99%) symptomatic ICAS lesion may generate significant hemodynamic stress downstream as assessed by the indicator FF, particularly in patients with poor collateral circulation. Further, good collateralization may mitigate this hemodynamic impact, partially explaining the protective effect of collateral circulation against recurrent stroke in such patients.
Functional assessment of cerebral artery stenosis: A pilot study based on computational fluid dynamics
The fractional pressure ratio is introduced to quantitatively assess the hemodynamic significance of severe intracranial stenosis. A computational fluid dynamics-based method is proposed to non-invasively compute the FPRCFD and compared against fractional pressure ratio measured by an invasive technique. Eleven patients with severe intracranial stenosis considered for endovascular intervention were recruited and an invasive procedure was performed to measure the distal and the aortic pressure ( Pd and Pa). The fractional pressure ratio was calculated as [Formula: see text]. The computed tomography angiography was used to reconstruct three-dimensional (3D) arteries for each patient. Cerebral hemodynamics was then computed for the arteries using a mathematical model governed by Navier-Stokes equations and with the outflow conditions imposed by a model of distal resistance and compliance. The non-invasive [Formula: see text], [Formula: see text], and FPRCFD were then obtained from the computational fluid dynamics calculation using a 16-core parallel computer. The invasive and non-invasive parameters were tested by statistical analysis. For this group of patients, the computational fluid dynamics method achieved comparable results with the invasive measurements. The fractional pressure ratio and FPRCFD are very close and highly correlated, but not linearly proportional, with the percentage of stenosis. The proposed computational fluid dynamics method can potentially be useful in assessing the functional alteration of cerebral stenosis.
Cortical microinfarcts in patients with middle cerebral artery stenosis
BACKGROUND: Cortical microinfarcts (CMIs) have been correlated to cognitive decline and dementia. It was previously considered only visible on microscope, but was recently reported to be visible on 3.0 Tesla magnetic resonance imaging (MRI) and linked to presence of intracranial stenosis. We aimed to investigate CMIs on 3.0 Tesla MRI in patients with M1 middle cerebral artery (MCA-M1) stenosis. METHODS: Patients with a recent non-cardioembolic ischemic stroke or transient ischemic attack and an atherosclerotic MCA-M1 stenosis were recruited. The severity of MCA stenosis was defined as moderate (50%-69%) or severe (70%-99% or focal flow void) on time-of-flight MR angiography (MRA). The distal to proximal signal intensity ratio (SIR) of MCA stenosis was measured on time-of-flight MRA to represent its hemodynamic significance. The presence of CMI(s) in the ipsilateral hemisphere was assessed on axial T1- or T2-weighted images and T2-weighted fluid-attenuated inversion-recovery images. RESULTS: Overall, 86 patients (mean age: 62.8 years; 77.9% males) were analyzed, 66 (76.7%) and 20 (23.3%), respectively, having moderate and severe MCA-M1 stenoses. The median SIR was .91. Forty-five (52.3%) patients had ipsilateral CMI(s). Multivariate logistic regression showed a history of dyslipidemia (odds ratio [OR] = 6.83, P = .008), and an SIR lower than the median (OR = 4.73, P = .014) were independently associated with presence of CMI(s) in ipsilateral hemisphere to an MCA-M1 stenosis. CONCLUSIONS: Patients with stroke and intracranial stenosis had a high burden of CMI. Except for a history of dyslipidemia, the hemodynamic significance of the arterial stenosis may contribute to the presence of ipsilateral CMI(s) in these patients, which warrants further investigation in prospective, longitudinal studies.