Diffusion Tensor Imaging Biomarkers to Predict Motor Outcomes in Stroke: A Narrative Review

Will you quit with this recovery prediction crapola. There is not a survivor in the world that cares about that. They want 100% recovery. WHAT THE HELL ARE YOU DOING TO GET THERE?  ANYTHING AT ALL?

Diffusion Tensor Imaging Biomarkers to Predict Motor Outcomes in Stroke: A Narrative Review

Luciana M. Moura^1*, Rafael Luccas¹, Joselisa P. Q. de Paiva², Edson Amaro Jr.^2,3, Alexander Leemans⁴, Claudia da C. Leite³, Maria C. G. Otaduy³ and Adriana B. Conforto^1,2*

• ¹Neurostimulation Laboratory, Neurology Department, Hospital das Clínicas/São Paulo University, São Paulo, Brazil
• ²Hospital Israelita Albert Einstein, São Paulo, Brazil
• ³Lim 44, Department of Radiology and Oncology, Faculdade de Medicina, Hospital das Clínicas/São Paulo University, São Paulo, Brazil
• ⁴PROVIDI Lab, Image Sciences Institute, UMC Utrecht, Utrecht, Netherlands

Stroke is a leading cause of disability worldwide. Motor impairments occur in most of the patients with stroke in the acute phase and contribute substantially to disability. Diffusion tensor imaging (DTI) biomarkers such as fractional anisotropy (FA) measured at an early phase after stroke have emerged as potential predictors of motor recovery. In this narrative review, we: (1) review key concepts of diffusion MRI (dMRI); (2) present an overview of state-of-art methodological aspects of data collection, analysis and reporting; and (3) critically review challenges of DTI in stroke as well as results of studies that investigated the correlation between DTI metrics within the corticospinal tract and motor outcomes at different stages after stroke. We reviewed studies published between January, 2008 and December, 2018, that reported correlations between DTI metrics collected within the first 24 h (hyperacute), 2–7 days (acute), and >7–90 days (early subacute) after stroke. Nineteen studies were included. Our review shows that there is no consensus about gold standards for DTI data collection or processing. We found great methodological differences across studies that evaluated DTI metrics within the corticospinal tract. Despite heterogeneity in stroke lesions and analysis approaches, the majority of studies reported significant correlations between DTI biomarkers and motor impairments. It remains to be determined whether DTI results could enhance the predictive value(Why do you want to predict this? It doesn't get any survivor better recovery.) of motor disability models based on clinical and neurophysiological variables.

Introduction

Stroke is the second cause of death and the third leading cause of loss of DALYs (Disability-Adjusted Life Years) worldwide. Despite substantial advances in prevention and treatment, the global burden of this condition remains massive (1). In ischemic stroke (IS; 80–85% of the cases), hypoperfusion leads to cell death and tissue loss while in hemorrhagic stroke (HS), primary injury derives from hematoma formation and secondary injury, from a cascade of events resulting in edema and cellular death (2). In IS, cytotoxic edema is a result of glucose and oxygen deprivation, leading to a failure of ion pumps in the cell membranes and consequently to collapse of osmotic regulation, when water shifts from the extracellular to the intracellular compartment (3). In HS, heme degradation products are the primary cytotoxic event and secondarily, an inflammatory process based on degradation of the hematoma takes place (4).

Diffusion MRI (dMRI) is a powerful diagnostic tool in acute IS (5) and is widely used in clinical practice (6). dMRI sequences are sensitive to water displacement. Acute infarcts appear hyperintense on diffusion-weighted imaging (DWI) reflecting the decrease in the apparent diffusion coefficient of water molecules. DWI can be acquired and interpreted over a few minutes. It provides key information for eligibility to reperfusion therapies from 6 to 24 h after onset of symptoms (DAWN study) (7) and in wake-up strokes (8). A search on MEDLINE using the terms “stroke” and “diffusion MRI” yielded 1 article in 1991 and 279, in 2018. Diffusion tensor imaging (DTI) involves more complex post-processing, mathematical modeling of the DW signal (9) and provides measures associated with white matter (WM) microstructural properties (10).

Stroke can directly injure WM tracts and also lead to Wallerian degeneration, the anterograde distal degeneration of injured axons accompanied by demyelination (11). DTI metrics have been studied as biomarkers of recovery or responsiveness to rehabilitation interventions (12–14). The bulk of DTI studies addressed specifically the corticospinal tract (CST), crucial for motor performance or recovery (12, 15), and frequently affected by stroke lesions. Paresis occurs in the majority of the subjects in the acute phase and contributes substantially to disability (16). It is thus understandable that the CST is in the spotlight of research in the field.

Two meta-analyses included from six to eight studies and reported strong correlations between DTI metrics and upper-limb motor recovery in IS and HS (17, 18). In both meta-analyses, heterogeneity between the studies was moderate. In addition, the quality of the evidence of DTI as a predictor of motor recovery was considered only moderate by a systematic review of potential biomarkers (19). The main limitations of the reviewed studies were the lack of cross-validation and evaluation of minimal clinically important differences for motor outcomes as well as the small sample sizes. Heterogeneity in DTI data collection and analysis strategies may also contribute to inconsistencies and hinder comparisons between studies.

In this narrative review, first we review the key concepts of dMRI. Second, we present an overview of state-of-art methodological practices in DTI processing. Third, we critically review challenges of DTI in stroke and results of studies that investigated the correlation between DTI metrics in the CST and motor outcomes at different stages after stroke, according to recommendations of the Stroke Recovery and Rehabilitation Roundtable taskforce (20).

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