Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies
Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies
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DOI：
10.1159/000336116
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发表时间：
2012-01-01
影响因子：
2.9
通讯作者：
Dijkhuizen, Rick M.
中科院分区：
文献类型：
--
作者：
Deddens, Lisette H.;Van Tilborg, Geralda A. F.;Dijkhuizen, Rick M.
自从大约十年前出现第一份报告以来，越来越多地探索用于研究中风后神经炎症过程时空概况的细胞和分子磁共振成像（MRI）策略。这些策略最常采用（超）顺磁性造影剂，例如氧化铁和钆螯合物的（超）小颗粒，用于基于MRI的特定白细胞群体或参与中风或可塑性病理生理学的分子炎症标记物的检测。本文就临床前和临床脑卒中神经炎症的细胞和分子MRI研究进展、局限性和展望作一综述。在啮齿动物中风模型中的几项研究已经证明了MRI造影剂在单核细胞浸润成像中的应用，这为中风患者中的试点（小规模概念验证）细胞MRI研究奠定了基础。这可以通过在全身给药之前通过体外孵育负载造影剂的分离细胞来实现。或者，可以将超顺磁性氧化铁颗粒直接注射到循环中以允许吞噬细胞的体内摄取。这两种策略已成功地用于测量单核细胞在实验性中风模型中脑缺血性病变中及其周围的侵袭的时空分布。使用靶向特异性造影剂的分子MRI研究已经显示了在实验性卒中后体内检测分子标记物的能力。例如，用特异性细胞粘附分子（例如E-选择素和血管细胞粘附分子1（VCAM-1））的配体（例如抗体）功能化的（超）顺磁性微米或纳米颗粒可以靶向发炎的活化内皮，其存在随后可以用MRI检测。目前的应用仍然有限，因为大多数目前可用的造影剂提供相对较差的对比度增强，其不容易与组织对比度的内源性来源区分开。然而，目前开发的更有效的颗粒，如生物相容性脂质体，胶束和纳米乳液，可以包含高有效载荷的（超）顺磁性材料以及其他物质，如染料和药物，可能会打开一个窗口的机会，有前途的翻译多模态成像策略，使体内评估（神经炎症）疾病标志物，治疗目标以及药物输送后中风。版权所有（C）2012 S. Karger AG，巴塞尔
Cellular and molecular magnetic resonance imaging (MRI) strategies for studying the spatiotemporal profile of neuro-inflammatory processes after stroke are increasingly being explored since the first reports appeared about a decade ago. These strategies most often employ (super) paramagnetic contrast agents, such as (ultra) small particles of iron oxide and gadolinium chelates, for MRI-based detection of specific leukocyte populations or molecular inflammatory markers that are involved in the pathophysiology of stroke or plasticity. In this review we describe achievements, limitations and prospects in the field of cellular and molecular MRI of neuroinflammation in preclinical and clinical stroke. Several studies in rodent stroke models have demonstrated the application of MRI contrast agents for imaging of monocyte infiltration, which served as the foundation for pilot (small-scale proof-of-concept) cellular MRI studies in stroke patients. This may be achieved with isolated cells that are loaded with contrast agent through in vitro incubation prior to systemic administration. Alternatively, superparamagnetic iron oxide particles may be directly injected into the circulation to allow in vivo uptake by phagocytic cells. Both strategies have been successfully employed to measure the spatiotemporal profile of invasion of monocytes in and around cerebral ischemic lesions in experimental stroke models. Molecular MRI studies with target-specific contrast agents have shown the capability for in vivo detection of molecular markers after experimental stroke. For example, (super) paramagnetic micro-or nanoparticles that are functionalized with a ligand (e.g. an antibody) for specific cell adhesion molecules, such as E-selectin and vascular cell adhesion molecule 1 (VCAM-1), can target inflamed, activated endothelium, whose presence can subsequently be detected with MRI. Present applications remain limited as most of the currently available contrast agents provide relatively poor contrast enhancement, which is not easily discriminated from endogenous sources of tissue contrast. Nevertheless, current developments of more efficient particles, such as biocompatible liposomes, micelles and nanoemulsions that can contain high payloads of (super) paramagnetic material as well as other substances, such as dyes and drugs, may open a window of opportunities for promising translational multimodal imaging strategies that enable in vivo assessment of (neuroinflammatory) disease markers, therapeutic targets as well as drug delivery after stroke. Copyright (C) 2012 S. Karger AG, Basel