In Vivo Magnetic Resonance Imaging Of Atherosclerotic Plaque And Biomechanical Analysis Of Middle Cerebral Artery

Intracranial atherosclerosis is a major subcategory of ischemic stroke,accounting for up to 10% of strokes in western societies, and 55% of strokes in Asian populations. Overall, about 40% of intracranial atherosclerotic diseaseis located in the MCA. Significant data exists linking specific carotid plaque features to ischemic cerebrovascular events, and the high risk features including plaque haemorrhage (PH), a large lipid-rich necrotic core and thin fibrous cap (FC). However, there is little data on whether plaque features in intracranial MCA atherosclerosis can help assess disease severity and distinguish clinical presentation.Although conventional angiographic methods, including magnetic resonance angiography (MRA) and computed tomography angiography (CTA), provide detailed information about intracranial arterial luminal dimension, large plaques may not exhibit luminal encroachment due to arterial wall remodeling and expansion and thus those traditional techniques would fall short in fully characterizing atherosclerotic disease. The importance of defining plaque compositional features has been advocated in carotid atherosclerosis. With the fast developing of plaque MR imaging during last decade, especially the high field in vivo high-resolution, multi-contrast magnetic resonance imaging (hrMRI), the morphological structure and components of carotid plaque can been reveal reliably. In recent years, hrMRI have been gradually used for the researches of intracranial atherosclerotic disease as the improvement of MR hardware and software.On the other hand, when coronary or carotid plaque with such so called high-risk morphological features, these plaques do not always cause acute ischemic symptoms after long-term follow up. Therefore, besides morphological factors, there may be other mechanisms to induce plaque unstability.From a material viewpoint, rupture could possibly occur when the external loading exceeds the plaques material strength. Atherosclerotic plaques continually undergo large deformations due to blood pressure and flow. Moreover, the geometrical morphology and components of plaque can also affect the stress/strain burden, as well as local blood pressure. Therefore, biomechanical analysis may provide complementary information to plaque structure and luminal stenosis in determining vulnerability, and even provide valuable information for guiding treatment. Consequently, this thesis was focus on patients with symptomatic stenotic MCA of atherosclerotic disease. By the use of hrMRI and biomechanical analysis to detect the morphological features of MCA plaques, quantify the morphological indexes of culprit plaque, clarity the correlations between stenosis and local blood flow and pressure, and finally explore the biomechanical characters of symptomatic MCA plaque. And each part of this thesis was briefly introduced as follows:In Part I, the hrMRI was used to evaluate the morphological characteristics of symptomatic plaque of atherosclerotic MCA, and explore the high risk features of acute stroke related MCA plaque. The results showed that among the 141 enrolled patients,86 (60.99%) patients belong to TIA group,15 (10.64%) in chronic infarction group and 40 (28.37%) in acute infarction group. Significantly, more heterogeneous plaques were found in acute infarction group in each sequence than those in TIA group or chronic infarction group (P<0.0001; P<0.0001; P=0.0006). Moreover, the plaque enhancement ratios were highest (0.77±0.605) in acute infarction group (P=0.0413).. So it can be concluded that acute stroke related high-risk MCA plaques have heterogeneous signal intensity and relatively obvious contrast enhancement.In Part II of this thesis, our aim was to quantify the incremental value of hrMRI to define culprit atherosclerotic lesions in the MCA over luminal stenosis, suggesting an optimal combination of anatomic parameters to identify lesions responsible for clinical symptoms. MR data from 165 lesions (112 culprit and 53 non-culprit) in 139 individuals were included. Culprit lesions were larger and longer with a narrower lumen and increased PB compared with non-culprit lesions. More culprit lesions showed contrast enhancement. Further analysis demonstrated that combinations of PB, MLA and stenosis could improve positive predictive value and specificity significantly. For evaluating culprit plaque of MCA, the optimal combination of morphological characters were stenosis≥50%, PB≥77% and MLA≤2.0mm2. In conclusion, hrMRI plaque imaging provides incremental information to luminal stenosis in differentiating patient clinical presentations. Both luminal and plaque-based measures should be considered in an integrative way for the accurate identification of MCA culprit plaques.In Part III, arterial flow rate and pressure measurements proximal to stenotic MCA had been measured by PC-MRI and invasive microcatheter probe respectively. The purpose was for further biomechanical analysis. Forty patients with symptomatic unilateral MCA atherosclerotic diseases who were scheduled for cerebral vascular intervention were recruited.Of all the 40 patients, the average value of Vaverage was 58.47±12.81 cm/s, and the average value of Qaverage were 2.71±1.00 ml/s. There was a weak positive correlation between stenosis and Vaverage, and there was a weak negative correlation between stenosis and Qaverage.The systolic pressure and dynamic pressure in patients with mild/moderate stenosis (<70%) was significantly higher than the values in patients with severe stenosis (≥70%), and the relationship between stenosis and systolic/dynamic pressure was negative correlation. It can be assumed that the clinical symptoms in patients with different degrees of stenosis may be due to different mechanisms, so more factors other than stenosis alone should be considered to guide the intervention therapy for stratified MCA atherosclerosis.In Part IV of this thesis, based on the in vivo hrMRI of 12 symptomatic atherosclerotic MCA,3D fully coupled fluid-structure interaction (FSI) models were constructed to assess biomechanical behaviors of the vulnerability of MCA plaque. Twelve symptomatic patients with unilateral atherosclerotic stenosis of MCA who were prepared to be treated by interventional therapy (stent angioplasty and/or balloon dilatation) were enrolled in our study. For the correlation analysis between mechanical and morphological data of MCA plaques, there were positive correlations between MPSMax/MPSMin/MPSD and lumen area (Alumen), and the STRETCH-P1 and plaque burden (PB) was negative correlation. The FMSS and PB was positive correlation, but FMSS and Alumen was negative correlation. For different plaque component analyzing, both MPS-related values and STRETCH-P1 were higher in plaque slices with ’lipid core’ than those in ’fibrosis’ ones, but FMSS in ’lipid’ plaque was significant lower. This study indicated that relatively big plaque suffered lower stress/strain burden and lipid-rich plaque has relatively higher risk of rupture.Part IMorphological Characteristics of Symptomatic Plaque of Atherosclerotic Middle Cerebral Artery by High-resolution Magnetic Resonance ImagingObjectives:By high-resolution magnetic resonance imaging (hrMRI), the aim of this study was to evaluate the morphological characteristics of symptomatic plaque of atherosclerotic middle cerebral artery (MCA), and explore the high risk features of acute stroke related MCA plaque.Materials and Methods:Patients from April 2013 to May 2014 with symptomatic atherosclerosis of MCA were enrolled in this study (Clinical research registration number: ChiCTR-DDT-14004284). The MRI program included cranial 3D TOF-MRA, hrMRI of bilateral MCA and whole brain diffusion weighted imaging (DWI) by 3.0T MR imaging system. According to the clinical symptom and DWI, the patients were divided into the following three groups:TIA group, chronic infarction group and acute infarction group. As the reference of the signal intensity of extraocular muscle, the plaque were describes as isointense, hyperintense, hypointense or heterogeneous. For quantitative analysis, the minimal diameter of stenotic lumen and thickness of plaque were measured; the remodeling ratio and contrast enhancement ratio were calculated as well.Results:Finally,141 patients were enrolled for analysis, among them 96 (68.09%) patients were male and the mean age was 53.6±10.05 years. Among them,86(60.99%) patients belong to TIA group,15 (10.64%) in chronic infarction group and 40 (28.37%) in acute infarction group. Significantly, more heterogeneous plaques were found in acute infarction group in each sequence (T1WI, T2WI or STIR) than those in TIA groupor chronic infarction group (P<0.0001; P<0.0001; P=0.0006). For quantitative analysis, the minimal diameters of stenotic lumen in acute infarction group (0.97±0.738) were significantly less than those in TIA (1.56±0.670) group and chronic infarction group (1.23±0.778) (P<0.0001). The plaque thicknesses in chronic and acute infarction groups (2.01±1.004; 1.99±0.746) were significantly greater than those in TIA group (1.44±0.4878) (P=0.0003). The average remodeling ratio in acute group (1.12±0.186) was the largest (P=0.0846), and the average contrast enhancement ratio in acute group (0.77±0.605) was also the greatest (P=0.0413).Conclusions:Taking advantage of hrMRI, it is feasible to evaluate morphological and signal characteristics of the symptomatic MCA plaque noninvasively. Acute stroke related high-risk MCA plaques have heterogeneous intensity on multi sequences of hrMRI and show relatively obvious contrast enhancement.Part Ⅱ An Assessment on the Incremental Value of High-resolution Magnetic Resonance Imaging to Identify Culprit Plaques in Atherosclerotic Disease of the Middle Cerebral ArteryObjectives:This study was designed to quantify the incremental value of high-resolution, multi-contrast magnetic resonance imaging (hrMRI) to define culprit atherosclerotic lesions in the middle cerebral artery (MCA) over luminal stenosis, suggesting an optimal combination of anatomic parameters to identify lesions responsible for clinical symptoms.Materials and Methods:Patients suspected with atherosclerotic stenosis of MCA underwent hrMRI. Luminal stenosis was measured from TOF images. Lumen and outer wall boundary were manually segmented, allowing calculation of plaque burden (PB), volume (PV), length (PL) and minimum luminal area (MLA).A culprit plaque was defined as a lesion arising on the ipsilateral side to an ischemic stroke on neuro-imaging with accompanying clinical symptoms, whilst a non-culprit plaque was defined as either a plaque occurring in a contralateral artery of a symptomatic patient or one in asymptomatic controls.Results:MR data from 165 lesions (112 culprit and 53 non-culprit) in 139 individuals were included. Culprit lesions were larger and longer with a narrower lumen and increased PB compared with non-culprit lesions. More culprit lesions showed contrast enhancement. Both PB and MLA were better indicators than stenosis in differentiating lesion types with AUC being 0.649,0.732 and 0.737 for stenosis, PB and MLA, respectively. Further analysis demonstrated that combinations of PB, MLA and stenosis could improve positive predictive value (PPV) and specificity significantly. An optimal combination of stenosis≥50%, PB≥77% and MLA<2.0mm2 produced a PPV=85.7%, negative predictive value=54.1%, sensitivity=69.6%, specificity=75.5%, and accuracy=71.5%.Conclusions:hrMRI plaque imaging provides incremental information to luminal stenosis in differentiating patient clinical presentations. Both luminal and plaque-based measures should be considered in an integrative way for the accurate identification of MCA culprit plaques.PartⅢThe Correlations between Luminal Stenosis and Local Blood Flow or Pressure in Patients with Atherosclerotic Middle Cerebral Artery DiseaseObjectives:Mechanical analysis has been shown to be complementary to atheroslcerotic plaque structure in determining clinical presentation and subsequent ischemic events, in both the coronary and carotid circulation. Mechanical analysis may also be beneficial for patients with middle cerebral artery (MCA) atheroslcerotic disease, however there is currently little data on arterial flow rate and pressure measurements in patients who have an MCA stenosis. This information is necessary if accurate and reproducible analyses are to be performed.Materials and Methods:Forty patients with symptomatic unilateral MCA atherosclerotic diseases who were scheduled for cerebral vascular intervention were recruited. Firstly, intracranial MRI program was performed, including 1) TOF-MRA for locating the stenotic MCA; 2) phase contrast (PC) for detecting flow velocity and volume flow rate at the proximal site of the stenotic lumen, and the specific parameters during one cardiac cycle were as follows:average flow velocity (Vaverage) and average flow rate (Qaverage); 3) DWI for examining related cerebral ischemic lesions. Secondly, there were 18 patients among the all 40 patients agreed to undergo traumatic measurement of MCA pressure during intervention, and the arterial pressure proximal to the stenotic site was measured successfully in 15 patients. Luminal stenosis was quantified according to WASID method.Results:Of all the 40 patients, the average values of Vaverage was 58.47±12.81 cm/s; the average values of Qaverage was 2.71±1.00 ml/s. There was a weak positive correlation between stenosis and Vaverage, and there was a weak negative correlation between stenosis and Qaverage. For the DWI, severe stenosis had more ipsilateral cerebral infarctions than those of mild/moderate stenosis (12 vs.7, P=0.0045), especially acute infarctions (8 vs.4, P=0.0094). The systolic pressure in patients with mild/moderate stenosis (<70%) was significantly higher than the value in patients with severe stenosis (≥70%) (92.0±7.3 vs. 73.9±16.1 mmHg; P=0.02), as was the dynamic pressure (22.8±6.4 vs.11.1±8.3 mmHg; P=0.01), and the relationship between stenosis and systolic/dynamic pressure was negative correlation. However, the diastolic pressure remained unaffected (69.2±9.3 vs. 62.8±19.0 mmHg; P=0.60).Conclusions:As luminal stenosis increased, the local flow velocity may slightly increased and flow rate may slightly decreased, and the local arterial pressure proximal to the stenosis may significantly decreased. Clinical symptoms in patients with different degrees of stenosis may be due to different mechanisms, so more factors other than stenosis alone should be considered to guide the intervention therapy for stratified MCA atherosclerosis.Part IVThe Study of Symptomatic Atherosclerotic Plaque of Middle Cerebral Artery by in vivo MRI-Based 3D Fluid-Structure InteractionObjectives:based on the in vivo high-resolution magnetic resonance imaging (hrMRI) of 12 symptomatic atherosclerotic middle cerebral artery (MCA),3D fully coupled fluid-structure interaction (FSI) models were constructed to assess biomechanical behaviors of the vulnerability of MCA plaque.Materials and Methods:Twelve symptomatic patients with unilateral atherosclerotic stenosis of MCA who were prepared to be treated by interventional therapy (stent angioplasty and/or balloon dilatation) were enrolled in our study. Firstly, affected MCA was examined by hrMRI, and the geometric data were extracted from the wall images of hrMRI for constructing FSI models. Secondly, the flow rate and regional blood pressure proximal to the stenotic MCA were measured by phase-contrast MRI and invasive pressure probe of microcatheter. After a series of pre-processing steps of 3D reconstruction, shrink-stretch process and mesh generation process, the coupled FSI models were solved by a finite-element package ADINA. Finally, the plaque stress/strain (MPSMax, MPSMin, MPSD, STRETCH-P1) and flow shear stress (FMSS) related data were extracted from 3D FSI solutions.Results:The average age of all patients was 60.8±9.60 years, and 5 (41.67%) were male. For the correlation analysis between mechanical and morphological data of MCA plaques, there were positive correlations between MPSMax/MPSMin/MPSD and lumen area (Alumen) (the correlation coefficients and P values were as follows:0.3570,0.0278; 0.3804, 0.0185; 0.1656,0.3205), and there were negative correlations between MPSMax/MPSMin/MPSD and plaque burden (PB) (the correlation coefficients and P values were as follows:-0.4622,0.0035;-0.4666,0.0032;-0.3025,0.0649). The STRETCH-P1 and plaque burden (PB) was negative correlation (-0.3596,0.0266). The FMSS and PB was positive correlation (0.6877,<0.0001), but FMSS and Alumen was negative correlation (-0.5872,0.0001). For different plaque component analyzing, MPSMax/MPSMin/MPSD values were higher in plaque slices with ’lipid core’ than those in plaque slices with ’fibrosis’ components, despite the differences were no significant. Plaque slices with ’lipid core’ suffered significant higher STRETCH-P1 than ’fibrosis’ plaque slices (P=0.0169), and significant lower FMSS (P=0.0021).Conclusions:There were negative correlations between MPS/STRETCH-P1 and PB in symptomatic plaques of atherosclerotic middle cerebral artery, which indicate relatively big plaque suffered lower stress/strain burden. Moreover, plaque with ’lipid core’ possessed higher MPS/STRETCH-PI than ’fibrosis’ plaque, which means lipid-rich plaque has relatively higher risk of rupture. However, larger sample size studies and pathological control studies are required to further validate the results of this study.