Quantitative assessment of device-clot interaction for stent retriever thrombectomy

PURPOSE: Rapid revascularization in emergent large vessel occlusion with endovascular embolectomy has proven clinical benefit. We sought to measure device-clot interaction as a potential mechanism for efficient embolectomy. METHODS: Two different radiopaque clot models were injected to create a middle cerebral artery occlusion in a patient-specific vascular phantom. A radiopaque stent retriever was deployed within the clot by unsheathing the device or a combination of unsheathing followed by pushing the device (n=8/group). High-resolution cone beam CT was performed immediately after device deployment and repeated after 5 min. An image processing pipeline was created to quantitatively evaluate the volume of clot that integrates with the stent, termed the clot integration factor (CIF). RESULTS: The CIF was significantly different for the two deployment variations when the device engaged the hard clot (p=0.041), but not the soft clot (p=0.764). In the hard clot, CIF increased significantly between post-deployment and final imaging datasets when using the pushing technique (p=0.019), but not when using the unsheathing technique (p=0.067). When we investigated the effect of time on CIF in the different clot models disregarding the technique, the CIF was significantly increased in the final dataset relative to the post-deployment dataset in both clot models (p=0.004-0.007). CONCLUSIONS: This study demonstrates in an in vitro system the benefit of pushing the Trevo stent during device delivery in hard clot to enhance integration. Regardless of delivery technique, clot-device integration increased in both clot models by waiting 5 min

Functional MRI and Diffusion Tensor Imaging of Brain Reorganization After Experimental Stroke

The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models

MRI of bilateral sensorimotor network activation in response to direct intracortical stimulation in rats after unilateral stroke

Reinstatement of perilesional activation and connectivity may underlie functional recovery after stroke. To measure activation responsiveness in perilesional cortex in relation to white matter integrity, we performed functional functional magnetic resonance imaging during stimulation of the contralesional cortex, together with diffusion tensor imaging, 3 and 28 days after stroke in rats. Despite disturbed sensorimotor function and abnormal callosal appearance at day 3, activation amplitudes were preserved in the perilesional sensorimotor cortex, although time-to-peak was significantly delayed. This indicates that in spite of dysfunction, perilesional cortical tissue can be activated subacutely after stroke, while delay of the hemodynamic activation response suggests impaired neurovascular coupling

Correspondence between altered functional and structural connectivity in the contralesional sensorimotor cortex after unilateral stroke in rats: a combined resting-state functional MRI and manganese-enhanced MRI study

This study shows a significant correlation between functional connectivity, as measured with resting-state functional magnetic resonance imaging (MRI), and neuroanatomical connectivity, as measured with manganese-enhanced MRI, in rats at 10 weeks after unilateral stroke and in age-matched controls. Reduced interhemispheric functional connectivity between the contralesional primary motor cortex (M1) and ipsilesional sensorimotor cortical regions was accompanied by a decrease in transcallosal manganese transfer from contralesional M1 to the ipsilesional sensorimotor cortex after a large unilateral stroke. Increased intrahemispheric functional connectivity in the contralesional sensorimotor cortex was associated with locally enhanced neuroanatomical tracer uptake, which underlines the strong link between functional and structural reorganization of neuronal networks after stroke

Stress-induced alterations in large-scale functional networks of the rodent brain

Stress-related psychopathology is associated with altered functioning of large-scale brain networks. Animal research into chronic stress, one of the most prominent environmental risk factors for development of psychopathology, has revealed molecular and cellular mechanisms potentially contributing to human mental disease. However, so far, these studies have not addressed the system-level changes in extended brain networks, thought to critically contribute to mental disorders. We here tested the effects of chronic stress exposure (10. days immobilization) on the structural integrity and functional connectivity patterns in the brain, using high-resolution structural MRI, diffusion kurtosis imaging, and resting-state functional MRI, while confirming the expected changes in neuronal dendritic morphology using Golgi-staining. Stress effectiveness was confirmed by a significantly lower body weight and increased adrenal weight. In line with previous research, stressed animals displayed neuronal dendritic hypertrophy in the amygdala and hypotrophy in the hippocampal and medial prefrontal cortex. Using independent component analysis of resting-state fMRI data, we identified ten functional connectivity networks in the rodent brain. Chronic stress appeared to increase connectivity within the somatosensory, visual, and default mode networks. Moreover, chronic stress exposure was associated with an increased volume and diffusivity of the lateral ventricles, whereas no other volumetric changes were observed. This study shows that chronic stress exposure in rodents induces alterations in functional network connectivity strength which partly resemble those observed in stress-related psychopathology. Moreover, these functional consequences of stress seem to be more prominent than the effects on gross volumetric change, indicating their significance for future research

White matter fractional anisotropy values from seed-based analysis of fractional anisotropy maps.

<p>DTI fractional anisotropy was measured in four different white matter seed regions. Boxplots display for 5-HTT^-/- and 5-HTT^+/+ animals the average value in each of the regions. Fractional anisotropy was significantly lower in the genu of the corpus callosum of 5-HTT^-/- animals (two-sample <i>t</i>-test, <i>t</i>  =  -3.33, false discovery rate (FDR)-adjusted <i>p</i> < 0.05).</p

Maps of seed-based resting-state fMRI functional connectivities.

<p>The resting-state fMRI signal of a seed region was correlated with all voxels in the brain. For each voxel, a one-sample <i>t</i>-test was performed to determine whether the signal at that location correlated significantly with the seed-region. Group-level resting-state fMRI-based functional connectivity maps are displayed for three different seed regions. Voxels that exhibit significant (<i>p</i> < 0.01, cluster-corrected) functional connectivity with a seed region in (A) ventromedial prefrontal cortex, (B) thalamic nuclei, and (C) caudate-putamen, are color-coded according to <i>Z</i>-value thresholded at 2.3 (<i>p</i> < 0.01) for both positive (red to yellow) and negative (blue to light blue) correlations between the filtered time-varying signals, and overlaid on a multi-slice anatomical rat brain template.</p

Network parameters from seed-based graph analysis of resting-state fMRI functional connectivity.

<p>Functional brain networks were constructed from seed-based resting-state fMRI functional connectivity values. The boxplots display three global network parameters that capture key properties of the functional brain networks, and were calculated on weighted graphs: the clustering coefficient (i.e., average of local clustering coefficients), the characteristic path length (i.e., average of shortest path lengths), and the small-worldness (i.e., ratio of normalized clustering coefficient and normalized characteristic path length).</p

Network parameters from seed-based graph analysis of DTI tractography data.

<p>Structural brain networks were constructed from DTI-based fiber tracts among 23 bilaterally positioned cortical and subcortical gray matter ROIs. The edges between the regions were weighted by the mean fractional anisotropy along the tracts. The boxplots display three global network parameters that capture key properties of the networks: the clustering coefficient (i.e., average of local clustering coefficients), the characteristic path length (i.e., average of shortest path lengths), and the small-worldness (i.e., ratio of normalized clustering coefficient and normalized characteristic path length).</p