Optimization of ex vivo CT- and MR- Imaging of Atherosclerotic Vessel Wall Changes

OBJECTIVE: To optimize a methodology for ex vivo imaging of atherosclerotic vessel wall changes using multidetector-row computed tomography (MDCT) and multi-contrast magnetic resonance imaging (MRI). METHODS: In phantom studies and studies on intact ex vivo porcine and human hearts, various filling mixtures of MDCT and MRI contrast agents have been evaluated, to enable filling and distension of the coronary arteries for optimal visualization of atherosclerotic vessel wall changes with both techniques. Various proportions of methyl cellulose, iodine-containing CT contrast agent and paramagnetic MR contrast agent containing iron-oxide particles have been tested. Imaging parameters have been optimized for high resolution plaque imaging using a four detector-row CT scanner and a 1.5 T MR system. RESULTS: Phantom studies and studies on ex vivo porcine and human hearts demonstrated optimal proportion of methyl cellulose and CT contrast agent to be 98% vs. 2%, and 75% vs. 25% of methyl cellulose vs. MR contrast agent, respectively. These proportions provided optimal opacification of the vessel lumen in the MDCT images with 250 Hounsfield Units, and good signal suppression within the vessel lumen in the MR images, resembling in vivo imaging techniques. After retrospective matching with histopathology, atherosclerotic lesions of the human ex vivo specimens could be identified on MRI and MDCT images. CONCLUSION: Using an optimized mixture of methyl cellulose, MDCT and MRI contrast agents, visualization of atherosclerotic vessel wall changes is feasible, and applicable to various ex vivo models.     

颈动脉粥样硬化斑块MR成像的研究

目的 探讨多对比加权的MRI序列对颈动脉粥样硬化斑块检出并定性分析的价值。方法 采用采用1．5T磁共振仪、多对比加权序列3D—TOF、FSEPDWI、FSE—DIRT．WI、FSE—DIRPDWI、FSE—DIRT2WI对24例动脉粥样硬化的患者的35个颈动脉斑块进行MRI成像．分析斑块信号特征。结果 35个粥粥样斑块中18个斑块在所有序列上信号单一均匀；17个斑块在一个或多个序列上信号混杂，其中9个斑块含有脂质核心信号；9个斑块含钙化信号；1个表现为血管腔内血栓形成管腔闭塞。10个斑块可见厚纤维帽信号；23个表现为薄纤维帽信号特征；2个斑块表面不光滑。结论 采用多对比加权的MRI序列可以检出颈动脉粥样硬化斑块．并在一定程度上可对其进行成分分析。     

Contrast enhancement by lipid‐based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

The use of contrast‐enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium‐based contrast agents to enhance atherosclerotic plaques in ApoE^?/? mice was evaluated with MRI. We obtained a kinetic profile for contrast enhancement, as the literature data on optimal imaging time points is scarce, and assessed the longer‐term kinetics. Signal enhancement in the wall of the aortic arch, following intravenous injection of paramagnetic micelles and liposomes, was followed for 1 week. In vivo T₁‐weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy of NIR₆₆₄ incorporated in the contrast agents and quantification of tissue and blood Gd–DTPA. Both micelles and liposomes enhanced contrast in T₁‐weighted MR images of plaques in the aortic arch. The average contrast‐to‐noise ratio increased after liposome or micelle injection to 260 or 280% respectively, at 24 h after injection, compared with a pre‐scan. A second wave of maximum contrast enhancement was observed around 60–72 h after injection, which only slowly decreased towards the 1 week end‐point. Confocal fluorescence microscopy and whole body fluorescence imaging confirmed MRI‐findings of accumulation of micelles and liposomes. Plaque permeation of contrast agents was not strongly dependent on the contrast agent size in this mouse model. Our results show that intraplaque accumulation over time of both contrast agents leads to good plaque visualization for a long period. This inherent intraplaque accumulation might make it difficult to discriminate passive from targeted accumulation. This implies that, in the development of targeted contrast agents on a lipid‐based backbone, extensive timing studies are required. Copyright © 2012 John Wiley & Sons, Ltd.     

Differences of signal evolution of intraplaque hemorrhage and associated stenosis between symptomatic and asymptomatic atherosclerotic carotid arteries: an in vivo high-resolution magnetic resonance imaging follow-up study

To evaluate the differences of signal evolution of intraplaque hemorrhage (IPH) and associated stenosis between symptomatic and asymptomatic atherosclerotic carotid arteries. Thirty-three carotid arteries (15 symptomatic and 18 asymptomatic plaques) with recent carotid IPH underwent serial high-resolution MRI examinations on a 3.0-Tesla (3.0T) MRI scanner over a period of 18 months. MR sequences included three-dimensional time-of-flight (3D-TOF), quadruple-inversion-recovery T1-weighted imaging (QIR T1 WI), proton density-weighted imaging (PDWI), and T2-weighted imaging (T2WI). The contrast-to-noise ratios (CNRs) of subsequent IPH during the follow-up period between symptomatic and asymptomatic carotid IPH showed a significant difference on 3D-TOF (P = 0.029), T1 WI (P = 0.005), and PDWI (P = 0.028), except for that on T2WI (P = 0.362). Compared with no significant signal intensity change of symptomatic IPH, CNRs of asymptomatic IPH exhibited a gradually descending trend on all contrast weighted images (P < 0.05). Compared with asymptomatic arteries, the degree of diameter stenosis associated with IPH increased significantly in the symptomatic atherosclerotic carotid arteries between baseline and the 18th month (10.53 ± 12.29% vs. 1.65 ± 7.74%, P = 0.017). Symptomatic and asymptomatic carotid IPH demonstrated different MRI signal evolution and associated carotid stenosis. Repeated carotid IPH may be more common in symptomatic plaques than in asymptomatic plaques and might produce a stronger stimulus for progression of atherosclerosis than one-time carotid IPH.     

Magnetic resonance imaging of the kidney.

High tissue contrast, multiplanar image capabilities, and tissue characterization render MR into an ideal imaging modality for effective evaluation of a wide range of renal disorders. It provides high details of anatomy and can suggest the composition of lesions. Improvements of MRI technology during the last years have made MRI increasingly attractive for body imaging. Fast imaging sequences and parallel imaging techniques have proved to be useful in minimizing artifacts from respiratory motion and magnetic susceptibility differences providing superior imaging quality. Additionally, the use of renally eliminated paramagnetic contrast agents permits assessment of parenchymal perfusion and visualization of the excretion of the contrast medium providing information on renal function.     

Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque

Interest in the use of contrast‐enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium‐based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A tapered cast was implanted around the right carotid artery of apoE^?/? mice to induce two different plaque phenotypes: a thin cap fibroatheroma (TCFA) and a non‐TCFA lesion. Both plaques were allowed to develop over 6 and 9 weeks, leading to an intermediate and advanced lesion, respectively. Signal enhancement in the carotid artery wall, following intravenous injection of Gd‐HP‐DO3A as well as paramagnetic micelles and liposomes was evaluated. In vivo T₁‐weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy and correlated to lesion phenotype. The two smallest contrast agents, i.e. Gd‐HP‐DO3A and micelles, were found to enhance contrast in T₁‐weighted MR images of all investigated plaque phenotypes. Maximum contrast enhancement ranged between 53 and 70% at 6 min after injection of Gd‐HP‐DO3A with highest enhancement and longest retention in the non‐TCFA lesion. Twenty‐four hours after injection of micelles maximum contrast enhancement ranged between 24 and 35% in all plaque phenotypes. Administration of the larger liposomes did not cause significant contrast enhancement in the atherosclerotic plaques. Confocal fluorescence microscopy confirmed the MRI‐based differences in plaque permeation between micelles and liposomes. Plaque permeation of contrast agents was strongly dependent on size. Our results implicate that, when equipped with targeting ligands, liposomes are most suitable for the imaging of plaque‐associated endothelial markers due to low background enhancement, whereas micelles, which accumulate extravascularly on a long timescale, are suited for imaging of less abundant markers inside plaques. Low molecular weight compounds may be employed for target‐specific imaging of highly abundant extravascular plaque‐associated targets. Copyright © 2010 John Wiley & Sons, Ltd.     

Molecular MRI of Inflammation in Atherosclerosis

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents.     

冠状动脉粥样硬化斑块磁共振成像研究进展

当前直接显示冠状动脉管壁和粥样斑块为磁共振成像(MRI)研究的热点之一,这是因为不引起冠状动脉管腔50%以上狭窄程度的粥样硬化斑块常为具有破裂倾向的易损斑块,斑块破裂随后血栓形成是导致心肌梗死的主要原因。无创性、高分辨率MRI具有显示冠状动脉粥样硬化斑块、判定斑块成分的潜力。本综述总结冠脉斑块MR成像原理,描述现有MRI技术下斑块的信号特点,并讨论MR在斑块成像的新对比剂、靶向分子成像等方面的研究进展。     

Molecular MRI of Atherosclerosis with USPIO

Inflammation in atherosclerosis is a risk factor for plaque rupture and atherothrombosis. USPIO-enhanced MRI is capable of evaluating the inflammatory activity in vivo on a cellular as well as a sub-cellular level. This paper reviews the recent advances in USPIO-enhanced MRI of atherosclerotic plaque inflammation. Imaging strategies for evidentiating the presence of the USPIO label in plaques take advantage of the susceptibility effect induced by the nanoparticles in their surroundings to obtain a negative contrast (T2* weighted imaging) or a positive contrast (the White Maker and Susceptibility Gradient Mapping). Quantitative methods have more recently been adapted to in vivo imaging of USPIO in atherosclerotic plaques, and showed great promise in detecting treatment responses. When they are not taken up rapidly from blood by the reticulo-endothelial system (RES), USPIOs nanoparticles passively target inflammation in atherosclerosis by engulfment in intra-plaque phagocytic cells. This has been demonstrated in both animal models and human patients. However, by modifying the surface of coating materials, nanoparticles can actively target atherosclerosis molecular and cellular actors in animal models. The goal of molecular imaging of atherosclerotic plaques is to identify events in the early onset of the disease, as well as critical evolution to vulnerable plaques. USPIO agents are preferred as basis to develop targeted agents because of the ability to overcome the toxicity issue of long-term body residence of Gd-based agents, and their lower sensitivity based on their relaxivity properties. MRI agents capable of efficiently targeting oxidized LDL, cell adhesion molecules (VCAM-1, P-selectin, E-selection), apoptosis and activated platelets have been demonstrated in animal models. The use of these methodologies at the clinical level will depend on the availability and toxicity profiles of the agents, and will require standardized state of the art imaging techniques.     

磁共振动态增强扫描(DCE-MRI)检测易损性动脉粥样硬化斑块应用价值实验研究

目的通过动物实验探讨磁共振动态增强扫描成像(Dynamic Contrast Enhanced MRI DCE-MRI)检测易损性动脉粥样硬化斑块临床应用价值。方法测定磁共振动态增强扫描动脉粥样硬化斑块首过时相斜率S及斑块峰值信号强度强化后120s信号强度下降率Soutflow,使用免疫组化方法标记动脉粥样硬化斑块内新生微血管内皮细胞与巨噬细胞。分析磁共振动态增强扫描参数与新生微血管内皮细胞计数(CD31免疫组化表达)和巨噬细胞计数(CD68免疫组化表达)相关性。结果磁共振动态增强扫描参数S和Soutflow与动脉粥样硬化斑块内新生微血管和巨噬细胞呈正相关(R=0.479,P0.01、R=0.452,P0.05R=0.415,P0.05、R=0.469,P0.01)。结论通过测定MR动态增强扫描参数评价动脉粥样硬化斑块内新生微血管量和炎症反应水平,MR动态增强扫描可以作为一项检测动脉粥样硬化斑块易损性影像学检查方法。     

Modified lipoproteins as contrast agents for imaging of atherosclerosis

The ability to detect and characterize atherosclerosis with targeted contrast agents may enable initiation of therapy for atherosclerotic lesions prior to becoming symptomatic. Since lipoproteins such as high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) play a critical role in the regulation of plaque biology through the transport of lipids into and out of atherosclerotic lesions, modifying HDL and LDL with radioisotopes for nuclear imaging, chelates for magnetic resonance imaging (MRI) or other possible contrast agents for computed tomography imaging techniques may aid in the detection and characterization of atherosclerosis. This review focuses on the literature employing lipoproteins as contrast agents for imaging atherosclerosis and the feasibility of this approach. Copyright © 2007 John Wiley & Sons, Ltd.     

重视MRI对易损斑块的研究

研究已表明,易损斑块是导致急性冠脉综合征（ACS）和脑卒中的主要原因。利用简便、准确、无创的诊断技术对易损斑块进行早期检测以及对其致病机制进行研究,是当前心脑血管疾病研究的热点和难点。近年来,随着磁共振软、硬件技术的发展,MRI可以直接观察血管管壁情况,对斑块的大小、体积及斑块成分提供较为准确的信息,广泛应用于动脉粥样硬化斑块的检测和预后评估。本组专题围绕易损斑块的定义和诊断标准、影像学检查方法、MRI检测易损斑块的优势与不足、以及MRI评价易损斑块的临床新进展等内容进行全面系统地阐述,同时,并对MRI检测易损斑块的发展方向及其面临的挑战进行展望。     

Current Development of Molecular Coronary Plaque Imaging using Magnetic Resonance Imaging towards Clinical Application

Cardiovascular disease (CVD) remains the leading cause of death in Western countries despite improvements in prevention, diagnosis and treatment. Atherosclerosis is a chronic inflammatory disease that remains clinically silent for many decades. Sudden rupture of “high-risk/vulnerable” plaques has been shown to be responsible for the majority of acute cardiovascular events, including myocardial infarction and stroke. Therefore, early detection of biological processes associated with atherosclerosis progression and plaque instability may improve diagnosis and treatment and help to better monitor the effectiveness of therapeutic interventions. Molecular magnetic resonance imaging (MRI) is a promising tool to detect molecular and cellular changes in the carotid, aortic and coronary vessel wall including endothelial dysfunction, inflammation, vascular remodelling, enzymatic activity, intraplaque haemorrhage and fibrin deposition and thus may allow early detection of unstable lesions and improve the prediction of future coronary events. Evaluation of atherosclerosis at both, the preclinical and clinical level includes non-contrast-enhanced (NCE) and contrast-enhanced (CE) MRI with and without the use of MR contrast agents. To increase the biological information obtained by MRI a variety of targeted-specific molecular probes have been developed for the non-invasive visualization of particular biological processes at the molecular and cellular level. This review will discuss the recent advances in molecular MRI of atherosclerosis, covering both pulse sequence development and also the design of novel contrast agents, for imaging atherosclerotic disease in vivo.     

Comparison of high-resolution MRI with CT angiography and digital subtraction angiography for the evaluation of middle cerebral artery atherosclerotic steno-occlusive disease

Intracranial atherosclerotic disease is increasingly recognized as a major stroke subtype worldwide. Current diagnostic evaluation of atherosclerotic disease of the middle cerebral artery (MCA) relies on detection of stenoses with luminographic imaging studies that do not directly visualize plaque unlike high-resolution MRI. This retrospective study seeks to evaluate the accuracy of high-resolution MRI vessel wall imaging, computed tomographic angiography (CTA) and digital subtraction angiography (DSA) in measuring the degree of stenosis within the MCA. 28 recently symptomatic patients with MCA territory symptoms underwent preliminary imaging with CTA followed by high-resolution MRI at 3-Tesla and definitive imaging with DSA for detection of M1 territory steno-occlusive lesions. Measurements of MCA segments on MRI and CTA were compared with reference to DSA values. Sensitivity and specificity of high-resolution MRI vessel wall imaging, CTA using maximum intensity projection (MIP) and CTA using volume rendering (VR) for the detection of stenosis > 50 % and occlusion were 80.0 and 53.6 %, 72.2 and 72.7 %, and 77.8 and 18.2 %, respectively. MRI-derived values correlated better with DSA (Spearman R = 0.68, p < 0.01) than CTA MIP and VR (Spearman R = 0.45, 0.22; p = 0.02, 0.24, respectively). High-resolution MRI of the MCA is capable of accurately measuring the degree of stenosis and is more sensitive than CTA in a sample of high-risk, symptomatic patients. This study, combined with previous reports, supports the potential of morphological MRI to measure intracranial atherosclerotic plaque non-invasively.     

易损斑块的影像学检查方法

目前动脉粥样硬化斑块的影像学检查方法主要包括无创性（如多普勒超声、CT和MRI）和有创性（如DSA、血管内超声、血管内MRI）检查,每种检查方法各有优缺点,无创影像学评估易损斑块的比较研究有利于优化影像学检查技术。多种方法的联合应用,可以大大提高诊断准确率。     

Experimental evaluation of the detectability of submillimeter atherosclerotic lesions in ex vivo human iliac arteries with ultrahigh-field (7.0 T) magnetic resonance imaging

Background To evaluate the ability of ultrahigh-field magnetic resonance imaging (MRI) to accurately depict the composition of the human arterial vessel wall ex vivo and to detect early atherosclerotic lesion formation in comparison to histology. Methods Eight iliac artery specimens with low-grade atherosclerotic lesions obtained from human organ donors were studied. Three-dimensional, high-resolution MRI (spatial resolution: 79 × 79 × 109 μm) was performed using T1-, T2- and proton density (PD)-weightings (7.0 Tesla MR system, Bruker Pharmascan). A total of 36 MR slices and corresponding histological sections were matched for comparative evaluation of area measurements of lumen, media and adventitia and—if present—plaque size. Statistical correlation between histology and MR measurements was tested and a ROC-analysis was performed to determine the plaque size being predictive of correctly identifying atherosclerotic lesions with MRI. Results The areas of vessel lumen and media as measured on T1-, T2- and PD-weighted MR images showed a strong correlation with the corresponding histological measurements (r = 0.84 to r = 0.89; P < 0.01), however, a systematic overestimation of 34–41% was found. For the area of adventitia, only a moderate, though significant, correlation (r = 0.55 to r = 0.62; P < 0.01) could be demonstrated with a similar overestimation by MRI (38–43%). With T1-weighted MRI, sensitivity and specificity for the detection of plaques > 4.0 mm² were 79% and 91%, respectively. With T2- and PD-weighted MRI, however, sensitivity and specificity for the detection of plaques > 0.4 mm² were 93% and 89%. Conclusions In an experimental ex vivo setting, ultrahigh-field MRI of the human arterial vessel wall resulted in an accurate visualization of vessel wall composition when compared to histology and, thus, allowed for a quantitative assessment. T2- and PD-weighted MRI proved capable of reliably detecting submillimeter atherosclerotic lesions. Cosima Jahnke and Thore Dietrich contributed equally to the work.     

Molecular imaging: challenges of bringing imaging of intracellular targets into common clinical use

Molecular imaging (MI) takes advantage of several new techniques to detect biomarkers or biochemical and cellular processes, with the goal of obtaining high sensitivity, specificity and signal‐to‐noise ratio imaging of disease. The imaging modalities bearing the most promise for MI are positron emission tomography (PET), single photon emission computer tomography (SPECT) and different optical imaging techniques with high sensitivity. Also magnetic resonance imaging (MRI) with contrast agents like ultra‐small superparamagnetic iron oxide particles (USPIO), magnetic resonance spectroscopy and ultrasound imaging with contrast agents may be useful approaches. MI techniques have been used in the clinic for many years, i.e. PET imaging using ¹⁸ F‐labeled fluorodeoxyglucose. Animal studies have during the last years revealed great potential for MI also with several other agents. The focus of the present article is the challenges of clinical imaging of intracellular targets following intravenous injection of the agents. Thus, the great challenge of getting enough contrast agent into the cytosol and at the same time obtaining a low signal from tissue just outside the diseased area is discussed. Copyright © 2012 John Wiley & Sons, Ltd.     

Detection of colo-rectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 Tesla MR with extracellular and reticulo-endothelial cell specific contrast agents

Background

To compare contrast-enhanced US (CE-US), multidetector-CT (MDCT), 1.5 Tesla MR with extra-cellular (Gd-enhanced) and intracellular (SPIO-enhanced) contrast agents and PET/CT, in the detection of hepatic metastases from colorectal cancer.

Materials and methods

A total of 34 patients with colo-rectal adenocarcinoma underwent preoperatively CE-US, MDCT, Gd- and SPIO-enhanced MR imaging (MRI), and PET/CT. Each set of images was reviewed independently by two blinded observers. The ROC method was used to analyze the results, which were correlated with surgical findings, intraoperative US, histopathology, and MDCT follow-up.

Results

A total of 57 hepatic lesions were identified: 11 hemangiomas, 29 cysts, 1 focal fatty liver, 16 metastases (dimensional distribution: 5/16 < 5 mm; 3/16 between 5 mm and <10 mm; 8/16 ≥ 10 mm). Six of 34 patients were classified as positive for the presence of at least one metastasis. Considering all the metastases and those ≥10 mm, ROC areas showed no significant differences between Gd- and SPIO-enhanced MRI, which performed significantly better than the other modalities (P < 0.05). Considering the lesions <10 mm, ROC areas showed no significant differences between all modalities; however MRI presented a trend to perform better than the other techniques. Considering the patients, ROC areas showed no significant differences between all the modalities; however PET/CT seemed to perform better than the others.

Conclusions

Gd- and SPIO-enhanced MRI seem to be the most accurate modality in the identification of liver metastases from colo-rectal carcinoma. PET/CT shows a trend to perform better than the other modalities in the identification of patients with liver metastases.     

磁共振成像技术在肝细胞癌中的应用进展

目的探讨磁共振成像在肝细胞癌诊断、预后评价、治疗方案选择、疗效评估中的应用进展。材料与方法收集并分析国内外最新相关文献。结果功能磁共振成像及肝脏特异性对比剂等磁共振新技术的发展与应用使磁共振成像不仅有助于早期诊断肝细胞癌,还可以反映肿瘤的发病机制、生物学行为特点和细胞水平的基因表达异常,为肝细胞癌的预后评价、治疗方案的选择及疗效评估提供了重要信息。结论磁共振成像是诊断、评估、监测、随访肝细胞癌重要的有效手段。