磁共振功能成像在高级别胶质瘤疗效监测的研究进展

高级别胶质瘤的治疗是复杂多变的。目前高级别胶质瘤的标准治疗方案是手术+放疗+口服化疗。持续的后期脑磁共振成像(magnetic resonance imaging,MRI)检查区分治疗反应与治疗效果可能具有困难,影响临床决策。各种先进的MRI技术(例如扩散加权成像、灌注加权成像、波谱分析、多参数成像)现在可以结合新的生理和生化参数,提供新的方法来帮助区分肿瘤进展,即假性进展和假性反应。本文总结了MR功能成像在监测高级别胶质瘤疗效方面的最新进展和挑战。     

Multiparametric Magnetic Resonance Imaging in Pulmonary Hypertension

Quantitative magnetic resonance imaging provides a comprehensive and non-invasive assessment of the heart and lungs in patients with suspected pulmonary hypertension with the potential for accurate assessment of disease severity and response to treatment. Magnetic resonance imaging (MRI) can provide detailed reliable information of heart structure and function as the heart responds to elevated right ventricle afterload in patients with progressive pulmonary vascular disease; notably, progressive changes in right ventricle volume and function are of prognostic value independent of established biomarkers. This article reviews the current literature on MRI in pulmonary hypertension and also describes new and exciting developments in imaging of the heart, pulmonary vasculature and lungs, including assessment of myocardial changes with late gadolinium-enhanced imaging and T1 mapping, evaluating changes in the proximal pulmonary vasculature using image-based computational modelling and quantitative assessment of the capillary bed using MRI perfusion analysis.     

Perfusion MR imaging of brain tumors

Brain tumors rank second as the cause of cancer-related deaths in children and adults younger than 34 years old, and they are seen in adults of all ages. Primary malignant brain tumors are associated with the third highest cancer-related mortality rate and a disproportionate level of disability and morbidity. Considering this, accurate diagnosis and grading of brain tumors are critical to determining prognosis and therapy. Equally important is to evaluate for tumor status during therapy to assess for therapeutic response and treatment-related complications. Brain tumors can be characterized as a heterogeneous group of neoplasm with a correspondingly wide variation in malignant phenotype and a diverse array of imaging features. Magnetic resonance (MR) imaging with intravenous contrast agent is the test of choice to diagnose and monitor brain tumors before, during, and after therapy. Recent advances in imaging methods such as diffusion-weighted imaging, perfusion imaging, and spectroscopic imaging all have in common the ability to provide quantitative cellular, hemodynamic, and metabolic information that may enhance our understanding of brain tumor biology, help us to better assess treatment response, more accurately determine tumor activity during therapy, and differentiate recurrent tumor and treatment related complications. In this article, we will review the basics of brain tumor imaging and focus on the role of perfusion MR imaging in improving accurate diagnosis and monitoring brain tumors during therapy. Both strengths and shortcomings of perfusion MR imaging over standard anatomic MR imaging will be discussed as will important pitfalls of the technique.     

MR imaging evaluation of the hepatic vasculature

Assessment of the hepatic vasculature is essential for tumor staging, surgical planning, and understanding of liver disease. Technological advances have made contrast-enhanced magnetic resonance (MR) imaging comparable to multidetector-row computed tomography for diagnostic vascular imaging with respect to spatial resolution. Unenhanced MR angiographic sequences enable reasonable clinical assessment of vessels without contrast agents in patients with contraindications or renal insufficiency. Furthermore, MR angiography may be used to provide directional information through manipulation of the signal intensity of flowing blood. A major limitation to consistent contrast-enhanced MR angiography is the timing of MR image acquisition with arrival of the contrast bolus in the structures of interest. In this article, the authors discuss currently available techniques for imaging of the hepatic vasculature.     

Preclinical evaluation of tumor microvascular response to a novel antiangiogenic/antitumor agent RO0281501 by dynamic contrast-enhanced MRI at 1.5 T

Inhibition of tumor angiogenesis is a promising approach in cancer treatment. The purpose of this study was to evaluate the vascular response of human lung tumor xenografts in vivo to RO0281501, an inhibitor of tyrosine kinase receptors, including vascular endothelial growth factor receptor 2, fibroblast growth factor receptor, and platelet-derived growth factor receptor, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Human non-small cell lung carcinoma (H460a) xenografts grown s.c. in athymic nu/nu mice were treated p.o. with the antiangiogenic agent RO0281501. Treatment-induced changes in tumor volume, epiphyseal growth plate thickness, and microvessel density assessed by CD31 immunohistochemistry were analyzed. Tumor vascular permeability and perfusion were measured in tumors using DCE-MRI with gadopentetate dimeglumine on a 1.5 T clinical scanner to assess vascular function. Treatment with RO0281501 resulted in significant growth retardation of H460a tumors. RO0281501-treated tumors showed histologic evidence of growth plate thickening and relatively lower microvessel density compared with the controls. Regarding DCE-MRI variables, the initial slope of contrast uptake and Ak(ep) were significantly decreased on day 7 of treatment. RO0281501 is a novel antiangiogenic/antitumor agent, which is active in the H460a xenograft model. Its effects on tumor vasculature can be monitored and assessed by DCE-MRI on a 1.5 T human MR scanner with clinically available gadopentetate dimeglumine contrast, which will facilitate clinical trials with this or similar agents.     

Evaluation of cancer therapy using diffusion magnetic resonance imaging

Assessment of the effectiveness of cancer therapy traditionally relies on comparison of tumor images acquired before and after therapeutic intervention by inspection of gross anatomical images to evaluate changes in tumor size. The potential for imaging to provide additional insights related to the therapeutic impact would be enhanced if a specific parameter or combination of parameters could be identified that reflect tissue changes at the cellular or physiological level. This information could also provide a more sensitive and earlier indicator of treatment response in an individual animal or patient. Diffusion magnetic resonance imaging can detect relatively small changes in tissue structure at the cellular level and thus provides an opportunity to quantitatively and serially follow therapeutic-induced changes in solid tumors. This article provides an overview of the use of diffusion magnetic resonance imaging as a surrogate marker for quantitating treatment responsiveness in both preclinical and clinical studies.     

Hepatic perfusion imaging: concepts and application

Hepatic perfusion imaging with magnetic resonance (MR) imaging is an emerging technique for quantitative assessment of diffuse hepatic disease and hepatic lesion blood flow. The principal method that has been used is based on T1 dynamic contrast-enhanced MR imaging. Perfusion imaging shows promise in the assessment of tumor therapy response, staging of liver fibrosis, and evaluation of hepatocellular carcinoma. The future standardization of imaging protocols and MR imaging pulse sequences will allow for broader clinical applications.     

Dynamic contrast-enhanced brain perfusion imaging: Technique and clinical applications

Magnetic resonance (MR) and computed tomographic (CT) perfusion imaging are evolving noninvasive imaging techniques that, unlike conventional MR and CT angiographic methods, can be used to evaluate capillary level tissue perfusion. These techniques can provide early, highly accurate delineation of ischemic tissue, allowing the underlying hemodynamic disturbances of disorders such as stroke and vasospasm to be further analyzed, as well as defining abnormal regions of blood pool in brain tumors. Because MR perfusion (MRP) and CT perfusion (CTP) imaging can assess physiologic parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), they offer additional data that can be useful in the detection and characterization of entities such as tumor, infection, inflammation, and infarction, which all can have similar appearances on both contrast and noncontrast enhanced conventional CT and MR images. They can also facilitate the further evaluation of processes such as early dementia, psychiatric illnesses, and migraine headaches, which may appear normal on routine CT and MR imaging. MRP and CTP might also be of value in distinguishing residual or recurrent tumor from treatment effects such as radiation-induced necrosis. This article reviews the background principles, scanning techniques, and clinical applications of noninvasive cerebral perfusion imaging.     

智能响应性磁共振纳米分子成像探针研究进展

智能响应性纳米分子探针可以实现肿瘤靶向定位、快速响应、灵敏诊断、精确治疗疾病,这需要精确的成像来监测探针的分布和肿瘤的位置。近年来,磁共振成像(MRI)由于其具有高灵敏度,低背景噪声等特点受到了广泛的关注。磁共振成像作为临床上最为广泛和安全诊断方法之一,为疾病诊断和肿瘤靶向治疗提供影像学指导。研究者对智能响应性MR纳米分子成像探针检测如pH变化、酶活性、还原环境和乏氧等方面进行了深入的研究。这篇文章将对智能响应性磁共振纳米分子成像探针的成像最新研究进展进行综述。     

Optimized time‐resolved imaging of contrast kinetics (TRICKS) in dynamic contrast‐enhanced MRI after peptide receptor radionuclide therapy in small animal tumor models

Anti‐tumor efficacy of targeted peptide‐receptor radionuclide therapy (PRRT) relies on several factors, including functional tumor vasculature. Little is known about the effect of PRRT on tumor vasculature. With dynamic contrast‐enhanced (DCE‐) MRI, functional vasculature is imaged and quantified using contrast agents. In small animals DCE‐MRI is a challenging application. We optimized a clinical sequence for fast hemodynamic acquisitions, time‐resolved imaging of contrast kinetics (TRICKS), to obtain DCE‐MRI images at both high spatial and high temporal resolution in mice and rats. Using TRICKS, functional vasculature was measured prior to PRRT and longitudinally to investigate the effect of treatment on tumor vascular characteristics. Nude mice bearing H69 tumor xenografts and rats bearing syngeneic CA20948 tumors were used to study perfusion following PRRT administration with ¹⁷⁷lutetium octreotate. Both semi‐quantitative and quantitative parameters were calculated. Treatment efficacy was measured by tumor‐size reduction. Optimized TRICKS enabled MRI at 0.032 mm³ voxel size with a temporal resolution of less than 5 s and large volume coverage, a substantial improvement over routine pre‐clinical DCE‐MRI studies. Tumor response to therapy was reflected in changes in tumor perfusion/permeability parameters. The H69 tumor model showed pronounced changes in DCE‐derived parameters following PRRT. The rat CA20948 tumor model showed more heterogeneity in both treatment outcome and perfusion parameters. TRICKS enabled the acquisition of DCE‐MRI at both high temporal resolution (T_res) and spatial resolutions relevant for small animal tumor models. With the high T_res enabled by TRICKS, accurate pharmacokinetic data modeling was feasible. DCE‐MRI parameters revealed changes over time and showed a clear relationship between tumor size and K_trans. Copyright © 2015 John Wiley & Sons, Ltd.     

DWI与1H MRS基本原理及其在脑肿瘤中的应用

磁共振扩散加权成像（DWI）及磁共振波谱（MRS）是目前较先进的磁共振成像技术,二者能提供常规MRI所不能获得的信息。DWI及MRS在脑肿瘤的鉴别诊断、分级、肿瘤边界的界定、疗效及预后评估等方面的研究发展很快,本文就DWI及1HMRS的基本原理及其在脑肿瘤中的临床应用作一综述。     

Differential diagnostic approach to MR imaging of white matter diseases

OBJECTIVES: The purpose of this article is to explore the magnetic resonance (MR) imaging features and the advanced MR techniques for differential diagnosis of white matter diseases of the brain. RESULTS: Magnetic resonance imaging is exquisitely sensitive for detecting brain abnormalities. Particularly in the evaluation of white matter diseases, MR far outperforms any other imaging technique. Lesions that may be quite subtle or even invisible on computed tomography are often clearly seen on the MR scan. The MR signal characteristics of white matter lesions are similar and relatively nonspecific, but other distinguishing features are often present to assist in diagnosis, such as the pattern of the abnormality, location, signal intensities, and enhancement features. Advanced MR techniques, such as diffusion-weighted imaging, MR spectroscopy, and perfusion imaging, provide additional specificity to the diagnosis of demyelinating diseases. CONCLUSIONS: Conventional MR images and advanced MR techniques are very helpful in distinguishing various types of white matter disease, for assessing disease burden, and for separating acute and chronic lesions.     

Magnetic resonance approaches to brain aging and Alzheimer disease-associated neuropathology

The noninvasive, nonradioactive, quantitative nature of magnetic resonance techniques has propelled them to the forefront of neuroscience and neuropsychiatric research. In particular, recent advances have confirmed their enormous potential in patients with Alzheimer disease (AD). Structural and functional magnetic resonance (MR) imaging have demonstrated significant correlation with clinical outcomes and underlying pathology and are used increasingly in the AD clinic. This review will highlight the role of high-resolution structural MR imaging and functional magnetic resonance imaging in the identification of atrophic and hemodynamic changes in AD and their potential as diagnostic biomarkers and surrogates of therapeutic response. Advanced MR techniques based on diffusion, perfusion, and neurochemical abnormalities in the aging brain will be presented briefly. These newer techniques continue to expand our understanding of neuropathology in the aging brain and are likely to play an important clinical role in the future.     

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。     

多模态磁共振成像在脑胶质瘤分级诊断及预后评估中的研究进展

脑胶质瘤是中枢神经系统中常见的恶性肿瘤,其具有弥漫性浸润生长的特点,在治疗的过程中具有较大的难度,肿瘤恶性程度高,容易复发、预后较差。多模态磁共振成像技术多用于肿瘤术前的初步诊断,在胶质瘤分级判断以及预测预后方面具有重要的价值。本文就扩散加权磁共振成像、弥散张量磁共振成像、动态磁敏感对比灌注加权成像、动态对比增强磁共振成像、动脉自旋标记成像和磁共振波谱成像等几种多模态磁共振成像技术在脑胶质瘤术前分级诊断及预后评估方面的研究进展进行综述。      

Detection of tumor response to a vascular disrupting agent by hyperpolarized 13C magnetic resonance spectroscopy

Nuclear spin hyperpolarization can dramatically increase the sensitivity of the (13)C magnetic resonance experiment, allowing dynamic measurements of the metabolism of hyperpolarized (13)C-labeled substrates in vivo. Here, we report a preclinical study of the response of lymphoma tumors to the vascular disrupting agent (VDA), combretastatin-A4-phosphate (CA4P), as detected by measuring changes in tumor metabolism of hyperpolarized [1-(13)C]pyruvate and [1,4-(13)C(2)]fumarate. These measurements were compared with dynamic contrast agent-enhanced magnetic resonance imaging (DCE-MRI) measurements of tumor vascular function and diffusion-weighted MRI (DW-MRI) measurements of the tumor cell necrosis that resulted from subsequent loss of tumor perfusion. The rate constant describing flux of hyperpolarized (13)C label between [1-(13)C]pyruvate and lactate was decreased by 34% within 6 hours of CA4P treatment and remained at this lower level at 24 hours. The rate constant describing production of labeled malate from hyperpolarized [1,4-(13)C(2)]fumarate increased 1.6-fold and 2.5-fold at 6 and 24 hours after treatment, respectively, and correlated with the degree of necrosis detected in histologic sections. Although DCE-MRI measurements showed a substantial reduction in perfusion at 6 hours after treatment, which had recovered by 24 hours, DW-MRI showed no change in the apparent diffusion coefficient of tumor water at 6 hours after treatment, although there was a 32% increase at 24 hours (P < 0.02) when regions of extensive necrosis were observed by histology. Measurements of hyperpolarized [1-(13)C]pyruvate and [1,4-(13)C(2)]fumarate metabolism may provide, therefore, a more sustained and sensitive indicator of response to a VDA than DCE-MRI or DW-MRI, respectively.     

Pharmacokinetics of Gd(DO3A‐Lys) and MR imaging studies in an orthotopic U87MG glioma tumor model

Pharmacokinetics of Gd(DO3A‐Lys), a macrocyclic gadolinium‐based magnetic resonance imaging (MRI) contrast agent functionalized with a lysine derivative, was studied in Wistar rats. Kinetic data were fitted using a two‐compartment model and revealed Gd(DO3A‐Lys) to have a distribution half‐life, t_1/2(α), of 1.3 min, an elimination half‐life, t_1/2(β), of 24.9 min and a large volume of distribution, V_D, of 0.49 L/kg indicative of the agent being able to rapidly distribute into tissues and organs. Contrast‐enhanced magnetic resonance angiography (CE‐MRA) in an orthotopic U87MG glioma mouse model demonstrated considerable enhancement of both the tumor and surrounding vasculature after intravenous administration of Gd(DO3A‐Lys). Applying dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) in the glioma of different sizes further showed distinct uptake characteristics and patterns of enhancement, which suggests the potential for differentiating changes at different stages of tumor growth. Our results indicate that Gd(DO3A‐Lys) could be a promising candidate for glioma MR imaging. Copyright © 2015 John Wiley & Sons, Ltd.     

Magnetic resonance imaging of the liver: assessing response to treatment

Imaging plays a critical role in evaluating tumor response to treatment. Change in tumor size on cross-sectional imaging has been widely accepted and used to guide clinical decision making. Until recently, researchers used the World Health Organization (WHO) criteria to determine tumor response. A new set of criteria recently has been adopted by the WHO, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer. These criteria, called the Response Evaluation Criteria in Solid Tumors (RECIST), attempt to unify response assessment of treated lesions. Magnetic resonance imaging plays an important role in evaluating treatment response to new therapies directed toward hepatic lesion treatment. In this article, we describe the new RECIST criteria and the role of magnetic resonance imaging in assessing tumor response. We also discuss the magnetic resonance imaging findings after surgical resection, liver transplantation, and tissue ablation techniques currently available for the management of patients with liver tumors.     

Imaging Tumor Growth Non-invasively Using Expression of MagA or Modified Ferritin Subunits to Augment Intracellular Contrast for Repetitive MRI

Purpose

The bacterial gene MagA imparts magnetic properties to mammalian cells and provides a basis for cell tracking by magnetic resonance imaging (MRI). In a mouse model of tumor growth from transplanted cells, we used repetitive MRI to demonstrate the in vivo imaging potential of MagA expression relative to a modified ferritin overexpression system, lacking regulation through iron response elements (HF?+?LF).

Procedures

Subcutaneous tumor xenografts were monitored weekly from days 2 to 34 post-injection. Small animal MRI employed balanced steady-state free precession. Imaging was correlated with tumor histology using hematoxylin, Prussian Blue, Ki-67, and BS-1 lectin.

Results

Tumor heterogeneity with respect to tissue morphology and magnetic resonance (MR) contrast was apparent within a week of cell transplantation. In MagA- and HF?+?LF-expressing tumors, MR contrast enhancement was recorded up to day 20 post-injection and 0.073-cm³ tumor volumes. MagA-expressing tumors showed increases in both quantity and quality of MR contrast as measured by fractional void volume and contrast-to-noise ratio, respectively. MR contrast in both MagA- and HF?+?LF-expressing tumors was maximal by day 13, doubling fractional void volume 1 week ahead of controls.

Conclusions

MagA- and HF?+?LF-expressing tumor xenografts augment MR contrast after 1 week of growth. MagA expression increases MR contrast within days of cell transplantation and provides MR contrast comparable to HF?+?LF. MagA has utility for monitoring cell growth and differentiation, with potential for in vivo detection of reporter gene expression using MRI.     

多模态磁共振技术预测脑胶质瘤MGMT启动子甲基化状态的研究进展

胶质瘤是最常见的原发性中枢神经系统恶性肿瘤。O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化是胶质瘤一个重要的分子特征,与烷化剂化疗敏感性、预后、风险分层、肿瘤复发等密切相关。当前仅使用手术标本通过基因检测分析来确定MGMT启动子甲基化状态,这一过程有局限性。MRI是目前应用最广泛的脑肿瘤非侵入性检查方法,近年来已有多种先进磁共振成像技术被用于术前无创性评估MGMT甲基化状态,这将有助于预测治疗反应和预后。本文就近几年化学交换饱和转移成像和酰胺质子转移成像、灌注加权成像（动态磁敏感对比增强成像、动态对比增强灌注成像、动脉自旋标记、基于流入的血管空间占位）、扩散成像（扩散张量成像、扩散峰度成像、体素内不相干运动、限制光谱成像）、磁敏感加权成像、波谱成像等磁共振成像技术预测MGMT甲基化状态的研究进展及MGMT甲基化临床意义进行综述,以期为患者个体化治疗方案的制定提供术前依据。