Intravoxel incoherent motion (IVIM) diffusion-weighted MRI can simultaneously measure diffusion and perfusion characteristics in a non-invasive way. This study aimed to determine the potential utility of IVIM in characterizing brain diffusion and perfusion properties for clinical stroke. The multi-b-value diffusion-weighted images of 101 patients diagnosed with acute/subacute ischemic stroke were retrospectively evaluated. The diffusion coefficient D, representing the water apparent diffusivity, was obtained by fitting the diffusion data with increasing high b-values to a simple mono-exponential model. The IVIM-derived perfusion parameters, pseudodiffusion coefficient D*, vascular volume fraction f and blood flow-related parameter fD*, were calculated with the bi-exponential model. Additionally, the apparent diffusion coefficient (ADC) was fitted according to the mono-exponential model using all b-values. The diffusion parameters for the ischemic lesion and normal contralateral region were measured in each patient. Statistical analysis was performed using the paired Student t-test and Pearson correlation test. Diffusion data in both the ischemic lesion and normal contralateral region followed the IVIM bi-exponential behavior, and the IVIM model showed better goodness of fit than the mono-exponential model with lower Akaike information criterion values. The paired Student t-test revealed significant differences for all diffusion parameters (all P < 0.001) except D* (P = 0.218) between ischemic and normal areas. For all patients in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001) and f (r = 0.541, P < 0.001; r = 0.262, P = 0.008); significant correlation was also found between ADC and fD* in the ischemic region (r = 0.254, P = 0.010). For all pixels within the region of interest from a representative subject in both ischemic and normal regions, ADC was significantly positively correlated with D (both r = 1, both P < 0.001), f (r = 0.823, P < 0.001; r = 0.652, P < 0.001) and fD* (r = 0.294, P < 0.001; r = 0.340, P < 0.001). These findings may have clinical implications for the use of IVIM imaging in the assessment and management of acute/subacute stroke patients. Copyright © 2016 John Wiley & Sons, Ltd.

3 J. Magn. Reson. Imaging 2017;45:722-730.

Progressive neurological deterioration poses enormous burden on the aging population with ischemic stroke and neurodegenerative disease patients, such as Alzheimers' disease and Parkinson's disease. The past two decades have witnessed remarkable advances in the research of neurovascular unit dysfunction, which is emerging as an important pathological feature that underlies these neurological disorders. Dysfunction of the unit allows penetration of blood-derived toxic proteins or leukocytes into the brain and contributes to white matter injury, disturbed neurovascular coupling and neuroinflammation, which all eventually lead to cognitive dysfunction. Recent evidences suggest that aging-related oxidative stress, accumulated DNA damage and impaired DNA repair capacities compromises the genome integrity not only in neurons, but also in other cell types of the neurovascular unit, such as endothelial cells, astrocytes and pericytes. Combating DNA damage or enhancing DNA repair capacities in the neurovascular unit represents a promising therapeutic strategy for vascular and neurodegenerative disorders. In this review, we focus on aging related mechanisms that underlie DNA damage and repair in the neurovascular unit and introduce several novel strategies that target the genome integrity in the neurovascular unit to combat the vascular and neurodegenerative disorders in the aging brain.

Stroke is followed by an intricate immune interaction involving the engagement of multiple immune cells, including neutrophils. As one of the first responders recruited to the brain, the crucial roles of neutrophils in the ischemic brain damage are receiving increasing attention in recent years. Notably, neutrophils are not homogenous, and yet there is still a lack of full knowledge about the extent and impact of neutrophil heterogeneity. The biological understanding of the neutrophil response to both innate and pathological conditions is rapidly evolving as single-cell-RNA sequencing uncovers overall neutrophil profiling across maturation and differentiation contexts. In this review, we scrutinize the latest research that points to the multifaceted role of neutrophils in different conditions and summarize the regulatory signals that may determine neutrophil diversity. In addition, we list several potential targets or therapeutic strategies targeting neutrophils to limit brain damage following ischemic stroke.