Advanced non-invasive MRI of neuroplasticity in ischemic stroke: Techniques and applications

Abstract

Ischemic stroke represents a serious medical condition which could cause survivors suffer from long-term and even lifetime disabilities. After a stroke attack, the brain would undergo varying degrees of recovery, in which the central nervous system could be reorganized spontaneously or with the help of appropriate rehabilitation. Magnetic resonance imaging (MRI) is a non-invasive technique which can provide comprehensive information on structural, functional and metabolic features of brain tissue. In the last decade, there has been an increased technical advancement in MR techniques such as voxel-based morphological analysis (VBM), diffusion magnetic resonance imaging (dMRI), functional magnetic resonance imaging (fMRI), arterial spin-labeled perfusion imaging (ASL), magnetic sensitivity weighted imaging (SWI), quantitative sensitivity magnetization (QSM) and magnetic resonance spectroscopy (MRS) which have been proven to be a valuable tool to study the brain tissue reorganization. Due to MRI indices of neuroplasticity related to neurological outcome could be translated to the clinic. The ultimate goal of this review is to equip readers with a fundamental understanding of advanced MR techniques and their corresponding clinical application for improving the ability to predict neuroplasticity that are most suitable for stroke management.

Introduction

Stroke is among the principal causes of death worldwide and the leading cause of permanent acquired disability [1]. Most of the strokes are ischemic, resulted from blockage of the cerebral vessels, leading to functional impairment. The resulting neurological deficits have an enormous impact on daily life activities, quality of life, and health costs [2]. Recombinant tissue plasminogen activator (rtPA) is currently turned out to be the only effective drug in the treatment of ischemic stroke. Unfortunately, the “time window” of rtPA therapy and risk of hemorrhage conversion limit its clinical application. Only a small percentage of patients could be accessed and treated within effective treatment [3]. A series of complex molecular cascade reactions, including dysfunctional cellular energy metabolism, cell membrane depolarization, excitotoxicity, production of reactive oxygen species, complex inflammatory reaction of activated microglia and destruction of the blood-brain barrier, could be caused by ischemia and hypoxia eventually leading to the death of nerve cells. However, most of the mature nerve cells cannot regenerate after death, which has a significant impact on the functional recovery of the central nervous system [4].

In general, patients with ischemic stroke demonstrate a degree of spontaneous improvement in the sub-acute phase through neuroplasticity, which can be further enhanced with appropriate prolonged rehabilitation [[5], [6], [7], [8]]. Animal models indicate that stroke lesions are accompanied by a strong trend to establish new structural and functional connection between specific areas [9]. Early intervention may be particularly important for experimental techniques designed to enhance neural plasticity in perilesional tissue, which could accelerate plastic reorganization. Cell-based and pharmacology-based neural repair therapies enhance the endogenous repair mechanism of damaged pathways and axon remodeling. Thereby improving the functional recovery within a few weeks after a stroke attack [10]. Neuroplasticity is closely related to the mechanism of regeneration, including neurogenesis, gliogenesis, angiogenesis and neuronal remodeling [11]. Neurogenesis, gliogenesis, angiogenesis refer to development and formation of new neurons and blood vessels in the brain, which plays an important role in restoring blood supply in the ischemic area, protecting ischemic neurons, and guiding axon regeneration [[12], [13], [14]]. Neuronal remodeling includes synaptic remodeling and axon sprouting, which promote the reconstruction of neural circuits and compensates for the innervation of damaged areas [15]. However, there is no commonly accepted therapy targeted on neuroplasticity [12,16], therefore, in-depth study of neuroplasticity are closely related to neurological outcome.

Current understanding of neuroplasticity after stroke, however, derives mainly from invasive methods such as histology, immunohistochemistry, electron and multi-photon microscopy, which do not allow dynamic assessment of functional recovery and tissue remodeling [17,18]. In contrast, MRI can noninvasively monitor the temporal profiles after stroke and in vivo. Since the difference in relaxation rates produces sufficient signal contrast, an excellent morphological description can be obtained and they enable investigators to evaluate the entire brain in an objective and automatic manner. In the last decade, there has been an increased technical advancement in MR sequences, such as VBM, diffusion tensor imaging (DTI), diffusion tensor tractography (DTT), diffusion spectrum imaging (DSI), neurite orientation dispersion and density imaging (NODDI), fMRI, ASL, SWI,QSM and MRS which have been proven to be a valuable tool to study the brain tissue reorganization (Fig. 1). Due to MRI indices of neuroplasticity related to neurological outcome in preclinical stroke study could be translated to the clinic. Therefore, the purpose of this article is to review technical aspects of each of these advanced MR imaging techniques, with a particular focus on their clinical application in neuroplasticity after stroke.