Magnetic Resonance Plaque Imaging Research Articles

Diagnostic accuracy of carotid plaque magnetic resonance imaging compared to histopathology in symptomatic carotid artery stenosis

IntroductionVulnerable plaques have been shown to predict ipsilateral cerebral ischemic events and identifying them leads to appropriate secondary stroke prevention strategies. We evaluated the diagnostic accuracy of MR carotid plaque imaging in identifying plaque vulnerability when compared with histopathological findings in patients with symptomatic carotid stenosis who underwent carotid endarterectomy (CEA). MethodsA prospective cohort of forty-five consecutive patients with moderate to severe symptomatic carotid stenosis who underwent CEA at a tertiary Indian hospital had 3 T MRI plaque imaging with multi-parametric protocol between November 2021 and December 2022. Images were analyzed by a vascular radiologist blinded to histopathological data. High-risk plaque characteristics such as lipid rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous cap and ulceration were assessed and correlated with histopathological findings as per American Heart Association (AHA) classification using Cohen’s kappa statistics to obtain diagnostic accuracies. ResultsOf the 45 patients, 38(84 %) were males. The mean age was 65 ± 7.7 years and mean duration to CEA from the most recent event was 57 days (57 ± 46 days). A significant correlation between MR plaque imaging and histopathology was noted for IPH (sensitivity-91 %, specificity-86 %, κ = 0.774, p < 0.001), LRNC (sensitivity-92.1 %, specificity-85.7 %, κ = 0.697, p < 0.001), and plaque ulceration (sensitivity-84.6 %, specificity-78.1 %, κ = 0.563, p < 0.001). MRI had an overall sensitivity and specificity of 92.3 % and 84.2 % respectively (κ = 0.77, p < 0.001) in discriminating high risk plaques. ConclusionMR plaque imaging shows a very good correlation with histopathology and can identify unstable high-risk plaques with high accuracy. This may have implication in selection of patients for carotid revascularization in symptomatic carotid stenosis.

Arterial transit artifacts and carotid Plaque-RADS may predict symptoms in patients with carotid stenosis

AimTo analyze the correlation of carotid stenosis severity, the Plaque Reporting and Data System (RADS) score, arterial transit artifacts (ATAs), and cerebral blood flow (CBF) with clinical cerebral ischemic symptoms in patients with carotid artery stenosis (CAS). Materials and methodsSixty-one patients with unilateral internal carotid artery stenosis or occlusion (≥50% stenosis) diagnosed by ultrasound, Computed Tomography(CT) angiography, or Magnetic Resonance(MR) angiography in Yichang City Central People's Hospital from January 2022 to February 2024 were retrospectively enrolled and divided into two groups according to the presence or absence of symptoms. Both groups underwent MR plaque imaging and arterial spin labeling (ASL)-based 3.0 T MRI to compare the differences in stenosis degree, Plaque-RADS score, ATA grade, and CBF between the two groups. Binary regression analysis was used to identify the parameters with statistically significant differences between the two groups and to evaluate their diagnostic efficacy using the area under the workup curve of the subjects. ResultsThe Plaque-RADS score, ATA grade, and CBF differences in the anterior cerebral artery(ACA)blood supply region were correlated with symptoms, and the areas under the ROC curves for the CBF differences in the ACA blood supply region, Plaque-RADS score, ATA grade and a joint model that combines all three to predict symptoms in CAS patients were 0.672, 0.796, 0.788 and 0.919, respectively. ConclusionsCBF, Plaque-RADS and ATAs were identified as independent risk factors for symptoms in patients with CAS and have a certain predictive value for symptoms, and the combined predictive value is greater, potentially providing a more effective imaging modality for clinical treatment and evaluation.

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophage-affinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn0.4Fe2.6O4) as T1 contrast agents were synthesized and modified with dopamine, 3,4-dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T1 relaxivity for different surface charged Zn0.4Fe2.6O4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn0.4Fe2.6O4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.

Intimal predominant calcification is associated with plaque instability in the vertebrobasilar artery by vessel wall magnetic resonance imaging and computed tomography

Background and aimsIt remains unknown about the relationship between vertebrobasilar artery (VBA) calcification and plaque instability. We aimed to investigate the characteristics of VBA calcification using vessel wall magnetic resonance imaging (MRI) and computed tomography (CT) and its association with acute cerebral infarction (ACI). MethodsNine hundred and thirty patients with VBA stenosis who underwent vessel wall MRI and CT examinations were evaluated retrospectively. Calcification morphology was classified as either intimal or non-intimal predominant using a CT-pathology-validated grading method. Qualitative and quantitative plaque MRI variables and calcification characteristics were compared between culprit and non-culprit lesions. The association between VBA calcification and the occurrence of culprit lesions was investigated using multivariate logistic regression. ResultsA total of 150 patients with ACI and 142 patients without ACI were eligible for subsequent analyses, respectively. In the qualitative analysis, T1 hyperintensity (p < 0.001) and intimal predominant calcification (p = 0.021) were more frequently observed in the culprit than non-culprit lesions. In the quantitative analyses, culprit lesions had a larger stenosis degree, plaque length, normal wall index, contrast enhancement ratio, lower calcification density and smaller calcification volume than non-culprit lesions (p all < 0.05). Intimal predominant calcification (odds ratio [OR], 2.51; 95 % confident interval [CI], 1.31–4.82, p = 0.006) and calcification density (OR, 0.53; 95 % CI, 0.35–0.78, p = 0.001) were independently associated with the presence of ACI after adjusting for clinical risk factors and plaque variables. ConclusionsIntimal predominant calcification in vertebrobasilar atherosclerosis is associated with the likelihood of having caused acute cerebral infarction. The morphology and density of VBA calcification may provide insight into stroke risk stratification in the posterior circulation.

T1-T2 Mismatch Sign as a Predictor of Ipsilateral Ischemic Change After Carotid Artery Stenting

Magnetic resonance (MR)-plaque imaging reflects the characteristics of carotid plaque. We evaluated the relationship between MR-plaque images and ischemic change after carotid artery stenting (CAS). MR-plaque images were acquired from patients with carotid artery stenosis before CAS treatment. We calculated the relative signal intensity of plaque components compared with that of the sternocleidomastoid muscle and evaluated the presence/absence of T1-T2 mismatch and match sign. We then assessed the appearance of new ischemic lesions after CAS on diffusion-weighted imaging (DWI). Factors associated with the appearance of a high-intensity lesion on DWI were retrospectively analyzed. A total of 64 patients with carotid artery stenoses treated with CAS were included in this study. In univariate analysis, T1-T2 mismatch sign was associated with the appearance of high-intensity lesions on DWI after CAS (odds ratio [OR], 12.00; 95% confidence interval [CI], 3.593-40.072; P < 0.0001), whereas T1-T2 match sign and high intensity on T2-weighted imaging were negatively associated (OR, 0.061, 95% CI, 0.007-0.502, P= 0.009 and OR, 0.085; 95% CI, 0.022-0.334, P= 0.0004, respectively). In multivariate logistic regression analysis, T1-T2 mismatch sign was independently associated with the appearance of a high-intensity lesion on DWI after CAS (OR, 16.695; 95% CI, 1.324-210.52; P= 0.0295). T1-T2 mismatch sign on MR-plaque imaging is significantly associated with the appearance of new ischemic lesions after CAS. T1-T2 mismatch sign may be useful in considering treatment strategies for carotid artery stenosis.

MR Imaging of Carotid Artery Atherosclerosis: Updated Evidence on High-Risk Plaque Features and Emerging Trends.

MR imaging is well-established as the criterion standard for carotid artery atherosclerosis imaging. The capability of MR imaging to differentiate numerous plaque components has been demonstrated, including those features that are associated with a high risk of sudden changes, thrombosis, or embolization. The field of carotid plaque MR imaging is constantly evolving, with continued insight into the imaging appearance and implications of various vulnerable plaque characteristics. This article will review the most up-to-date knowledge of these high-risk plaque features on MR imaging and will delve into 2 major emerging topics: the role of vulnerable plaques in cryptogenic strokes and the potential use of MR imaging to modify carotid endarterectomy treatment guidelines.

Deep Learning-based Post Hoc CT Denoising for the Coronary Perivascular Fat Attenuation Index

Coronary inflammation related to high-risk hemorrhagic plaques can be captured by the perivascular fat attenuation index (FAI) using coronary computed tomography angiography (CCTA). Since the FAI is susceptible to image noise, we believe deep learning (DL)-based post hoc noise reduction can improve diagnostic capability. We aimed to assess the diagnostic performance of the FAI in DL-based denoised high-fidelity CCTA images compared with coronary plaque magnetic resonance imaging (MRI) delivered high-intensity hemorrhagic plaques (HIPs). We retrospectively reviewed 43 patients who underwent CCTA and coronary plaque MRI. We generated high-fidelity CCTA images by denoising the standard CCTA images using a residual dense network that supervised the denoising task by averaging three cardiac phases with nonrigid registration. We measured the FAIs as the mean CT value of all voxels (range of -190 to -30 HU) located within a radial distance from the outer proximal right coronary artery wall. The diagnostic reference standard was defined as HIPs (high-risk hemorrhagic plaques) using MRI. The diagnostic performance of the FAI in the original and denoised images was assessed using receiver operating characteristic curves. Of 43 patients, 13 had HIPs. The denoised CCTA improved the area under the curve (0.89 [95% confidence interval (CI) 0.78-0.99]) of the FAI compared with that in the original image (0.77 [95% CI, 0.62-0.91], p=0.008). The optimal cutoff value for predicting HIPs in denoised CCTA was -69 HU with 0.85 (11/13) sensitivity, 0.79 (25/30) specificity, and 0.80 (36/43) accuracy. DL-based denoised high-fidelity CCTA improved the AUC and specificity of the FAI for predicting HIPs.

The 2nd European Carotid Surgery Trial (ECST-2): rationale and protocol for a randomised clinical trial comparing immediate revascularisation versus optimised medical therapy alone in patients with symptomatic and asymptomatic carotid stenosis at low to intermediate risk of stroke

BackgroundCarotid endarterectomy is currently recommended for patients with recently symptomatic carotid stenosis ≥50%, based on randomised trials conducted 30 years ago. Several factors such as carotid plaque ulceration, age and associated comorbidities might influence the risk-benefit ratio of carotid revascularisation. A model developed in previous trials that calculates the future risk of stroke based on these features can be used to stratify patients into low, intermediate or high risk. Since the original trials, medical treatment has improved significantly. Our hypothesis is that patients with carotid stenosis ≥50% associated with a low to intermediate risk of stroke will not benefit from additional carotid revascularisation when treated with optimised medical therapy. We also hypothesise that prediction of future risk of stroke in individual patients with carotid stenosis can be improved using the results of magnetic resonance imaging (MRI) of the carotid plaque.MethodsPatients are randomised between immediate revascularisation plus OMT versus OMT alone. Suitable patients are those with asymptomatic or symptomatic carotid stenosis ≥50% with an estimated 5-year risk of stroke of <20%, as calculated using the Carotid Artery Risk score. MRI of the brain at baseline and during follow-up will be used as a blinded measure to assess the incidence of silent infarction and haemorrhage, while carotid plaque MRI at baseline will be used to investigate the hypotheses that plaque characteristics determine future stroke risk and help identify a subgroup of patients that will benefit from revascularisation. An initial analysis will be conducted after recruitment of 320 patients with baseline MRI and a minimum of 2 years of follow-up, to provide data to inform the design and sample size for a continuation or re-launch of the study. The primary outcome measure of this initial analysis is the combined 2-year rate of any clinically manifest stroke, new cerebral infarct on MRI, myocardial infarction or periprocedural death.DiscussionECST-2 will provide new data on the efficacy of modern optimal medical therapy alone versus added carotid revascularisation in patients with carotid stenosis at low to intermediate risk of future stroke selected by individualised risk assessment. We anticipate that the results of baseline brain and carotid plaque MRI will provide data to improve the prediction of the risk of stroke and the effect of treatment in patients with carotid stenosis.Trial registrationISRCTN registry ISRCTN97744893. Registered on 05 July 2012

Implementation of an International Vessel Wall MR Plaque Imaging Research Network: Experience with the ChAMPION Study

Background and Objective: Intracranial atherosclerosis (ICAS) is one of the most common causes of stroke worldwide. High-resolution Vessel Wall MR imaging (VW-MR) is commonly used to study ICAS, but in order to accelerate advances in the field of VW-MR ICAS research, the establishment of a multicenter research network is needed. We introduce our experience in establishing a collaborative international VW-MR ICAS research network in China and North America using an innovative, disease-specific ICAS imaging phantom for standardization of VW-MR sequences at the sites. Methods: Both the Medical University of South Carolina and Peking Union Medical College functioned as Central Coordinating Centers in the network. PUMC identified research centers within China that had the potential for collaboration on VW-MR ICAS research based on networking and prior experience. All selected centers refined MRI sequences using an ICAS phantom with study principal investigators virtually present in real-time during scanning. MRI sequences were efficiently calibrated utilizing the broad expertise of all members of the research team. All centers further validated MRI sequences with human subjects. Results: We identified 11 Chinese hospitals as the potential collaborating sites for the network. Of the 11 selected sites, six sites were able to complete the required VW-MR scanning and sequence refinement using the ICAS phantom and subsequent human subjects. Conclusion: The study demonstrated the feasibility of establishing a cross-continent collaborative VW-MR research network and the use of a disease-specific phantom to facilitate convenient and efficient sequence modification for image quality standardization, which is needed for future multicenter VW-MR studies.

Factors contributing to restenosis after carotid artery stenting and the usefulness of magnetic resonance plaque imaging: A study of 308 consecutive patients

PurposeCarotid artery stenting (CAS) is an alternative treatment strategy to carotid endarterectomy. However, post-intervention in-stent restenosis (ISR) remains a complication. The timing, frequency, and prognostic factors of ISR are unclear. The incidence and timing of post-CAS ISR were investigated, including plaque imaging to investigate the prognostic factors. MethodsWe retrospectively investigated 308 patients diagnosed with carotid stenosis who underwent CAS between April 2008 and April 2020. The patients also underwent carotid ultrasonography (US) at 1, 3, 6, and 12 months postinterventionally and every 6 months thereafter. Contributory factors in patients with ISR were also investigated. ResultsThe percentage value of ISR was 4.9% (15/308). The median time from the procedure to ISR was 7 months. The ISR rate was higher for patients with a plaque/muscle ratio of ≤ 2.30 on T2-weighted imaging (T2WI) on black-blood magnetic resonance imaging (BB MRI) (p = 0.022). A plaque/muscle ratio of ≤ 2.30 on BB MRI T2WI was identified as an independent risk factor for ISR. A comparison of the incidence of ISR and the plaque/muscle ratio level on MRI T2WI was also significant (p < 0.001). In T2WI imaging of BB MRI, the cutoff value for detecting ISR from the Plaque/Muscle ratio was 1.310 [area under the curve (AUC) = 0.935, Sensitivity = 100%, specificity = 85.2%]. ConclusionsThe incidence of post-CAS ISR was 4.9%, at a median time of 7 months after stenting. Plaque/muscle ratio on T2WI in pre-intervention MRI plaque imaging may be a useful predictor of post-intervention ISR.

Nonfasting Triglyceride as an Independent Predictor of Carotid Restenosis After Carotid Endarterectomy or Carotid Artery Stenting

Nonfasting serum triglyceride (TG) level is attracting more and more attention as an atherosclerosis-promoting factor. However, no study has investigated the relationships between nonfasting TG levels and carotid restenosis after carotid endarterectomy (CEA) or carotid artery stenting (CAS). This study was conducted to investigate if nonfasting TG levels can be used to assess a risk for carotid restenosis after CEA or CAS. This was a single-center retrospective study. We reviewed 201 consecutive primary carotid artery revascularization procedures (39 CEAs and 162 CASs), which were performed from 2008 to 2018 for 179 patients (163 men and 16 women) with atherosclerotic carotid stenosis, and were followed up for at least 1 year. Clinical variables including nonfasting lipid profiles and findings of magnetic resonance plaque imaging were compared between groups with and without postprocedural carotid restenosis (≥50% stenosis on ultrasonography). During a mean follow-up period of 1413 days, 24 of 201 carotid stenosis procedures (11.9%) suffered restenosis after successful revascularization procedures. Multivariate analyses demonstrated that nonfasting TG level was the only independent risk factor of postprocedural restenosis. The receiver operating characteristic curve analyses revealed that a cutoff value of nonfasting TG to discriminate postprocedural carotid restenosis was 127.5 mg/dL, which was much lower than the upper limit of normal. This study showed that nonfasting TG level may be a useful marker to predict carotid restenosis after CEA or CAS, and could be a new therapeutic target to prevent carotid restenosis after revascularization procedures.

A literature review of MRI techniques used to detect amyloid-beta plaques in Alzheimer’s disease patients

In this review, we aim to provide an overview of the imaging techniques most commonly used to study Alzheimer's disease (AD). Neuroimaging biomarkers can be used to evaluate these abnormalities, improve the ability of early diagnosis and help predict disease progression. These signs mainly include local brain atrophy on structural MRI, hypometabolic foci, and amyloid plaque deposition in the brain detected by specific imaging. These techniques not only have their unique advantages, but can complement each other in multimodal imaging evaluation of patients with cognitive impairment and dementia. A literature search was performed on PubMed using the search term combinations "Alzheimer's disease", "Amyloid-beta plaques", and "MRI". We discuss various magnetic resonance imaging (MRI) based techniques, including direct imaging, indirect imaging, amyloid-beta (Aβ) plaque and radiomics, Hybrid PET/MRI and MRI imaging technology in the future, placing a special emphasis on multimodal imaging, and focus our review on the MRI features of Aβ plaques (AD biomarkers). After a lot of research and reasonable selection, multimodal imaging composed of MRI and PET can significantly improve the diagnosis and treatment of AD patients, and the complementary information can be obtained by the new PET/MR instrument at the same time. The findings of this review emphasize that multimodal imaging is likely to be the preferred method for future AD research and clinical practice.

Lipid Core Burden Index Assessed by Near-Infrared Spectroscopy of Symptomatic Carotid Plaques: Association with Magnetic Resonance T1-Weighted Imaging

Introduction: Vulnerable plaques are a strong predictor of cerebrovascular ischemic events, and high lipid core plaques (LCPs) are associated with an increased risk of embolic infarcts during carotid artery stenting (CAS). Recent developments in magnetic resonance (MR) plaque imaging have enabled noninvasive assessment of carotid plaque vulnerability, and the lipid component and intraplaque hemorrhage (IPH) are visible as high signal intensity areas on T1-weighted MR images. Recently, catheter-based near-infrared spectroscopy (NIRS) has been shown to accurately distinguish LCPs without IPH. This study aimed to determine whether the results of assessment of high LCPs by catheter-based NIRS correlate with the results of MR plaque imaging. Methods: We recruited 82 consecutive symptomatic carotid artery stenosis patients who were treated with CAS under NIRS and MR plaque assessment. Maximum lipid core burden index (max-LCBI) at minimal luminal areas (MLA), defined as max-LCBI_MLA, and max-LCBI for any 4-mm segment in a target lesion, defined as max-LCBI_AREA, were assessed by NIRS. Correlations were investigated between max-LCBI and MR T1-weighted plaque signal intensity ratio (T1W-SIR) and MR time-of-flight signal intensity ratio (TOF-SIR) in the same regions as assessed by NIRS. Results: Both T1W-SIR_MLA and T1W-SIR_AREA were significantly lower in the high LCP group (max-LCBI >504, p < 0.001 for both), while TOF-SIR_MLA and TOF-SIR_AREA were significantly higher in the high LCP group (p < 0.001 and p = 0.004, respectively). A significant linear correlation was present between max-LCBI_MLA and both TIW-SIR_MLA and TOF-SIR_MLA (r = −0.610 and 0.452, respectively, p < 0.0001 for both). Furthermore, logistic regression analysis revealed that T1W-SIR_MLA and TOF-SIR_MLA were significantly associated with a high LCP assessed by NIRS (OR, 44.19 and 0.43; 95% CI: 6.55–298.19 and 0.19–0.96; p < 0.001 and = 0.039, respectively). Conclusions: A high LCP assessed by NIRS correlates with the signal intensity ratio of MR imaging in symptomatic patients with unstable carotid plaques.

A Comparative Study of Carotid Magnetic Resonance Plaque Imaging in Predicting the Early Progression of Acute Anterior Circulation Mild Stroke

To analyze the biological properties of carotid lumen stenosis and plaque before and after bifurcation of the bilateral carotid arteries in patients with acute anterior circulation mild stroke (AACMS) by 3.0 T high-resolution magnetic resonance imaging (HR-MRI) with the aim to clarify the predictive effect of 3.0 T HR-MRI on early progression and poor prognosis in patients with AACMS. Random division of 96 patients with AACMS into a stroke progression group and a non-progression group. The bilateral cervical vessels of the patients were detected by HR-MRI. The degree of carotid artery stenosis before and after bilateral carotid bifurcation was evaluated using a vascular plaque imaging diagnostic system. There were significant differences in the maximum and average wall standardization index, maximum wall thickness, maximum wall area, plaque composition, proportion of plaque fibrous cap rupture, and proportion of VI complex plaques in the progressive group. There was no significant difference in the related indexes of bilateral vessels in the non-progressive group (P &gt;0.05). There are significant differences in MRI morphological characteristics of bilateral carotid plaques in patients with AACMS progression. Through a comparative analysis of the plaque load and plaque composition of bilateral carotid arteries using 3.0 T HR-MRI in patients with early-stage AACMS, the type and stability of complex plaques can be identified, which serve as prognostic factors in predicting the early progression of stroke and guiding clinical treatment.

Cervical Carotid Plaque MRI : Review of Atherosclerosis Imaging Features and their Histologic Underpinnings.

Magnetic resonance (MR) imaging is considered the gold standard for non-invasive evaluation of carotid artery plaque morphology and composition. Anumber of studies have demonstrated the clinical utility of MR plaque imaging in the risk stratification of carotid atherosclerotic disease, determination of stroke etiology, and identification of surgical and endovascular candidates for carotid revascularization procedures. The MR plaque imaging also provides researchers and clinicians with valuable insights into the pathogenesis, natural history and composition of carotid atherosclerotic disease. Nevertheless, the field of MR plaque imaging is complex, and requires athorough knowledge of the histologic basis for how various plaque features appear on imaging. This article details the pathogenesis and histology of atherosclerosis, reviews the expected appearance of different plaque components, and describes how MR imaging features may be related to symptomatology or predict future ischemic events.

Pre‐clinical dose ranging efficacy testing of ADx: A contrast agent for magnetic resonance imaging of amyloid burden in Alzheimer’s disease

AbstractBackgroundEarly detection of amyloid plaque deposits is crucial for identifying pre‐symptomatic Alzheimer’s disease (AD) patients. An amyloid imaging magnetic resonance imaging (MRI) contrast agent would have substantial utility in the clinic due to its ease of distribution and the standard use of MRI in AD patient workup. In this work, we describe dose‐ranging efficacy study of an amyloid‐targeted liposomal macrocyclic gadolinium (Gd) contrast agent, ADx‐001, for in vivo MRI of amyloid plaques.Method In vivo studies were performed in an APPswe/PSEN1dE9 double transgenic mouse model of early‐onset Alzheimer’s disease that develop amyloid plaques starting at 6‐7 months of age. ADx‐001 was tested at three dose levels: 0.10, 0.15 and 0.20 (mmol Gd/kg). At each dose level, ADx‐001 was tested in transgenic (n=6) and age‐matched wild‐type (mice that lacked both mutations) mice (n=6). MRI was performed on a 1 Tesla permanent magnet MR scanner using a T1‐weighted spin‐echo (T1w‐SE) sequence and a fast‐spin echo inversion recovery (FSE‐IR) sequence that approximates a fluid‐attenuated inversion recovery (FLAIR) sequence. Images were acquired pre‐contrast and at 4 days after intravenous administration of ADx‐001. Animals were euthanized after post‐contrast imaging for post‐mortem histological evaluation of amyloid plaques. Pre‐contrast and delayed post‐contrast MR images were qualitatively and quantitatively analyzed to determine sensitivity, specificity and accuracy against post‐mortem histological identification of Aβ plaque.ResultADx‐001‐enhanced MRI showed significant brain signal enhancement (p &lt; 0.05) in transgenic mice (amyloid‐positive) relative to wild‐type (amyloid‐negative) mice in T1w‐SE (Figure 1) and FSE‐IR (Figure 2) images at all dose levels (Figure 3). ADx‐001‐enhanced T1w‐SE imaging showed high sensitivity (&gt;80%) at 0.2 and 0.1 mmol Gd/kg dose levels while FSE‐IR showed high sensitivity (&gt;80%) at 0.2 and 0.15 mmol Gd/kg doses (Table 1). ADx‐001‐enhanced MRI showed excellent specificity (100%) at all dose levels. Microscopy confirmed co‐localization of ADx‐001 with amyloid plaque deposits in cortex and hippocampus regions of the brain in transgenic mice (Figure 4).ConclusionADx‐001 demonstrated high sensitivity and excellent specificity for in vivo MRI of amyloid plaques in transgenic mice even at moderate and low concentrations. An MRI‐based amyloid imaging agent holds great promise for early detection of AD and potential therapeutic studies.

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events

It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. To assess associations of CA MRI plaque characteristics with incident CVD events. The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated. The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Magnetic resonance imaging of carotid plaques: current status and clinical perspectives.

Rupture of a vulnerable carotid plaque is one of the leading causes of stroke. Carotid magnetic resonance imaging (MRI) is able to visualize all the main hallmarks of plaque vulnerability. Various MRI sequences have been developed in the last two decades to quantify carotid plaque burden and composition. Often, a combination of multiple sequences is used. These MRI techniques have been extensively validated with histological analysis of carotid endarterectomy specimens. High agreement between the MRI and histological measures of plaque burden, intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), fibrous cap (FC) status, inflammation and neovascularization has been demonstrated. Novel MRI sequences allow to generate three-dimensional isotropic images with a large longitudinal coverage. Other new sequences can acquire multiple contrasts using a single sequence leading to a tremendous reduction in scan time. IPH can be easily identified as a hyperintense signal in the bulk of the plaque on strongly T1-weighted images, such as magnetization-prepared rapid acquisition gradient echo images, acquired within a few minutes with a standard neurovascular coil. Carotid MRI can also be used to evaluate treatment effects. Several meta-analyses have demonstrated a strong predictive value of IPH, LRNC, thinning or rupture of the FC for ischemic cerebrovascular events. Recently, in a large meta-analysis based on individual patient data of asymptomatic and symptomatic individuals with carotid artery stenosis, it was shown that IPH on MRI is an independent risk predictor for stroke, stronger than any known clinical risk parameter. Expert recommendations on carotid plaque MRI protocols have recently been described in a white paper. The present review provides an overview of the current status and applications of carotid plaque MR imaging and its future potential in daily clinical practice.

Dilated microvessel with endothelial cell proliferation involves intraplaque hemorrhage in unstable carotid plaque.

The purpose of the present study was to clarify the characteristics of endothelial cell (EC) proliferation in intraplaque microvessels in vulnerable plaques and impact on clinical results. The present study included 76 patients who underwent carotid endarterectomy. Patients were classified into three groups based on their symptoms: asymptomatic, symptomatic without recurrent ischemic event, and symptomatic with recurrent ischemic event. MR plaque imaging was performed and surgical specimens underwent immunohistochemical analysis. The number of CD31+ microvessels, and Ki67+ and CD105+ ECs in the carotid plaques was quantified, as measurements of maximum CD31+ microvessel diameter. MR plaque imaging yielded 41 subjects (54.0%) diagnosed with plaque with intraplaque hemorrhage (IPH), 14 subjects (18.4%) diagnosed with fibrous plaques, and 21 (27.6%) subjects diagnosed with lipid-rich plaques. The average largest diameter of microvessel in fibrous plaques, lipid-rich plaques, and plaque with IPH was 12.7 ± 4.1 μm, 31.3 ± 9.3 μm, and 56.4 ± 10.0 μm, respectively (p < 0.01). Dilated microvessels (>40 μm) were observed in 9.6% of plaques with IPH but only in 2.8% of lipid-rich plaques and 0% of fibrous plaques (p < 0.01). Ki67+/CD31+ ECs were identified in 2.8 ± 1.2% of fibrous plaques, 9.6 ± 6.9% of lipid-rich plaques, and in 19.5 ± 5.9% of plaques with IPH (p < 0.01). The average largest diameter of microvessels in the asymptomatic group was 17.1 ± 8.7 μm, 32.3 ± 10.8 μm in the symptomatic without recurrence group, and 55.2 ± 13.2 μm in the symptomatic with recurrence group (p < 0.01). Dilated microvessels with proliferative ECs may play a key role in IPH pathogenesis. Furthermore, dilated microvessels are likely related to clinical onset and the recurrence of ischemic events. The purpose of the present study was to clarify the characteristics of EC proliferation in intraplaque microvessels in vulnerable plaques and their impact on clinical results, focusing on dilated intraplaque microvessels.

High-intensity vessel sign on fluid-attenuated inversion recovery imaging: a novel imaging marker of high-risk carotid stenosis-a MRI and SPECT study.

Measurement of luminal stenosis and determination of plaque instability using MR plaque imaging are effective strategies for evaluating high-risk carotid stenosis. Nevertheless, new methods are required to identify patients with carotid stenosis at risk of future stroke. We aimed to clarify the mechanisms and clinical implications of the hyperintense vessel sign (HVS) as a marker of high-risk carotid stenosis. We included 148 patients who underwent carotid stent (CAS) or carotid endarterectomy (CEA). MRI FLAIR was performed to detect HVS prior to and within 7 days after CAS/CEA. MR plaque imaging and 123I-iodoamphetamine SPECT was performed prior to CEA/CAS. Detailed characteristics of HVS were categorized in terms of symptomatic status, hemodynamic state, plaque composition, and HVS on time series. Forty-six of 80 symptomatic hemispheres (57.5%) and 5 of 68 asymptomatic hemispheres (7.4%) presented HVS (P < 0.01). Of the 46 symptomatic hemispheres with HVS, 19 (41.3%) presented with hemodynamic impairment and 27 (58.7%) presented without hemodynamic impairment. Of 19 hemispheres with hemodynamic impairment, 12 subjects (63.2%) showed high intensity and 7 (36.8%) showed iso-intensity plaques on T1WI. All 27 hemispheres without hemodynamic impairment showed high-intensity plaques. Of the five asymptomatic and HVS-positive hemispheres, one showed hemodynamic impairment; MR plaque imaging revealed T1 iso-intensity. The other four hemispheres that did not show hemodynamic impairment showed T1WI high-intensity plaques. There are two possible mechanisms of HVS, hemodynamic impairment due to severe carotid stenosis and micro-embolism from unstable plaques. HVS could be a radiological marker for high-risk carotid stenosis.