Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly used to assess white matter pr... more Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly used to assess white matter properties after stroke. Novel work is utilizing constrained spherical deconvolution (CSD) to estimate complex intra-voxel fiber architecture unaccounted for with tensor-based fiber tractography. However, the reliability of CSD-based tractography has not been established in people with chronic stroke. Establishing the reliability of CSD-based DW-MRI in chronic stroke. High-resolution DW-MRI was performed in ten adults with chronic stroke during two separate sessions. Deterministic region of interest-based fiber tractography using CSD was performed by two raters. Mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), tract number, and tract volume were extracted from reconstructed fiber pathways in the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). Callosal fiber pathways connecting the primary motor cortices were also evaluated. Inter-rater and test-retest reliability were determined by intra-class correlation coefficients (ICCs). ICCs revealed excellent reliability for FA and ADC in ipsilesional (0.86-1.00; p<0.05) and contralesional hemispheres (0.94-1.00; p<0.0001), for CST and SLF fibers; and excellent reliability for all metrics in callosal fibers (0.85-1.00; p<0.05). ICC ranged from poor to excellent for tract number and tract volume in ipsilesional (-0.11 to 0.92; p≤0.57) and contralesional hemispheres (-0.27 to 0.93; p≤0.64), for CST and SLF fibers. Like other select DW-MRI approaches, CSD-based tractography is a reliable approach to evaluate FA and ADC in major white matter pathways, in chronic stroke. Future work should address the reproducibility and utility of CSD-based metrics of tract number and tract volume.
Nano-engineering materials-based diagnosis and treatment of central nervous systems (CNS) ailment... more Nano-engineering materials-based diagnosis and treatment of central nervous systems (CNS) ailments has significantly advanced with our deepened knowledge of the pathophysiology of the blood–brain barrier. Unlike other nanoparticle-based tissue engineering strategies, the use of nanoparticles in the CNS must be specifically engineered to circumvent or penetrate the blood–brain barrier, which selectively inhibits drugs and nanoparticles from infiltrating. Current research in the field of CNS nanoparticles has future applications in the fields of diagnostic imaging, drug delivery, specific drug targeting, and tissue regeneration. This chapter highlights some of the nano-engineering of these promising nanoparticle-based biomaterials and their applications in the diagnosis and treatment of brain and spinal cord disease.
Canadian Association of Radiologists journal, Apr 18, 2023
Purpose Rapid identification of hematoma expansion (HE) risk at baseline is a priority in intrace... more Purpose Rapid identification of hematoma expansion (HE) risk at baseline is a priority in intracerebral hemorrhage (ICH) patients and may impact clinical decision making. Predictive scores using clinical features and Non-Contract Computed Tomography (NCCT)-based features exist, however, the extent to which each feature set contributes to identification is limited. This paper aims to investigate the relative value of clinical, radiological, and radiomics features in HE prediction. Methods Original data was retrospectively obtained from three major prospective clinical trials [“Spot Sign” Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy (SPOTLIGHT)NCT01359202; The Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT)NCT00810888] Patients baseline and follow-up scans following ICH were included. Clinical, NCCT radiological, and radiomics features were extracted, and multivariate modeling was conducted on each feature set. Results 317 patients from 38 sites met inclusion criteria. Warfarin use (p=0.001) and GCS score (p=0.046) were significant clinical predictors of HE. The best performing model for HE prediction included clinical, radiological, and radiomic features with an area under the curve (AUC) of 87.7%. NCCT radiological features improved upon clinical benchmark model AUC by 6.5% and a clinical & radiomic combination model by 6.4%. Addition of radiomics features improved goodness of fit of both clinical (p=0.012) and clinical & NCCT radiological (p=0.007) models, with marginal improvements on AUC. Inclusion of NCCT radiological signs was best for ruling out HE whereas the radiomic features were best for ruling in HE. Conclusion NCCT-based radiological and radiomics features can improve HE prediction when added to clinical features.
Introduction: Cell based therapies have shown a considerable ability to improve functional outcom... more Introduction: Cell based therapies have shown a considerable ability to improve functional outcome when administered after experimental stroke. Intra-arterial (IA) cell transplantation has been shown to be a valuable alternative transplantation method for cell treatment. The success of IA therapy depends on the targeted homing and subsequent migration of cells to the injured brain area. This process is reliant on neural stem cell (NSC) expression of chemokines and their receptors. Understanding the differences in cell expression of these molecules and the resulting differences in chemotaxis will help identify ideal cell types for transplantation. Previously, we compared mRNA from human and mouse NSCs and found that only a 10% overlap in chemokine expression. We wanted to determine if there are also variations between different cell types from the same species. We compared NSCs obtained from induced pluripotent stem cells (iPS NSCs), to fetal NSCs (F NSC). We used RT-qPCR, in vitro cell migration, and quantification of cell secretion to compare chemokine and ligand expression in F NSCs and iPS NSCs. Methods: Secondary neurospheres originating from FVB mice were generated from either fetal primary NSCs from E17.5 mice (F NSC), or derived by transducing neurospheres originating from E3 mice with Oct4 (iPS NSC). Cells were grown as neurospheres in growth media treated with EGF and FGF. RT-qPCR was performed on extracted RNA using microarray technology for chemokine receptors and ligands. Luminex immunological assay was completed to assess secreted cytokines and inflammatory proteins. The Boyden chamber migration assay was used to determine migration to SDF-1 or MCP-1 at varying concentrations. Results: RNA expression was detected for 58% of the factors assessed. F NSCs alone expressed 6% (e.g. mmp2, Cxcl10), iPS NSCs alone expressed 16% (e.g. CCL2, CCL7, LIF), and both iPS NSCs and F NSCs expressed 20% (e.g. BDNF, HIF1a, CXCR4) of the detected factors. We assessed 26 secreted proteins, 73% occurred at detectable levels, of these 74% were expressed more highly in F NSCs than in iPS NSCs, including, il-1α, CCL3, CCL5, TNF-α, and VEGF; iPS NSCs secreted higher levels of MCP3, Il-3, and substantially more MCP-1 (113.7 ± 1.44 vs 52.78 ±4.221 pg/ml). iPS NSCs also had a higher migratory response to MCP-1 than F NSCs did (p < 0.001). Cell migration to SDF-1 did not differ between cell types (p = 0.905). Conclusions: Several chemokines and their receptors were differentially expressed in mouse iPS and F NSCs. These differences may result in variations in the NSC response to the ischemic brain. The profile of chemokine and chemokine receptor expression on NSCs should be strongly considered when selecting cell types for post stroke treatment.
Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly used to assess white matter pr... more Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly used to assess white matter properties after stroke. Novel work is utilizing constrained spherical deconvolution (CSD) to estimate complex intra-voxel fiber architecture unaccounted for with tensor-based fiber tractography. However, the reliability of CSD-based tractography has not been established in people with chronic stroke. Establishing the reliability of CSD-based DW-MRI in chronic stroke. High-resolution DW-MRI was performed in ten adults with chronic stroke during two separate sessions. Deterministic region of interest-based fiber tractography using CSD was performed by two raters. Mean fractional anisotropy (FA), apparent diffusion coefficient (ADC), tract number, and tract volume were extracted from reconstructed fiber pathways in the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). Callosal fiber pathways connecting the primary motor cortices were also evaluated. Inter-rater and test-retest reliability were determined by intra-class correlation coefficients (ICCs). ICCs revealed excellent reliability for FA and ADC in ipsilesional (0.86-1.00; p<0.05) and contralesional hemispheres (0.94-1.00; p<0.0001), for CST and SLF fibers; and excellent reliability for all metrics in callosal fibers (0.85-1.00; p<0.05). ICC ranged from poor to excellent for tract number and tract volume in ipsilesional (-0.11 to 0.92; p≤0.57) and contralesional hemispheres (-0.27 to 0.93; p≤0.64), for CST and SLF fibers. Like other select DW-MRI approaches, CSD-based tractography is a reliable approach to evaluate FA and ADC in major white matter pathways, in chronic stroke. Future work should address the reproducibility and utility of CSD-based metrics of tract number and tract volume.
Nano-engineering materials-based diagnosis and treatment of central nervous systems (CNS) ailment... more Nano-engineering materials-based diagnosis and treatment of central nervous systems (CNS) ailments has significantly advanced with our deepened knowledge of the pathophysiology of the blood–brain barrier. Unlike other nanoparticle-based tissue engineering strategies, the use of nanoparticles in the CNS must be specifically engineered to circumvent or penetrate the blood–brain barrier, which selectively inhibits drugs and nanoparticles from infiltrating. Current research in the field of CNS nanoparticles has future applications in the fields of diagnostic imaging, drug delivery, specific drug targeting, and tissue regeneration. This chapter highlights some of the nano-engineering of these promising nanoparticle-based biomaterials and their applications in the diagnosis and treatment of brain and spinal cord disease.
Canadian Association of Radiologists journal, Apr 18, 2023
Purpose Rapid identification of hematoma expansion (HE) risk at baseline is a priority in intrace... more Purpose Rapid identification of hematoma expansion (HE) risk at baseline is a priority in intracerebral hemorrhage (ICH) patients and may impact clinical decision making. Predictive scores using clinical features and Non-Contract Computed Tomography (NCCT)-based features exist, however, the extent to which each feature set contributes to identification is limited. This paper aims to investigate the relative value of clinical, radiological, and radiomics features in HE prediction. Methods Original data was retrospectively obtained from three major prospective clinical trials [“Spot Sign” Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy (SPOTLIGHT)NCT01359202; The Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT)NCT00810888] Patients baseline and follow-up scans following ICH were included. Clinical, NCCT radiological, and radiomics features were extracted, and multivariate modeling was conducted on each feature set. Results 317 patients from 38 sites met inclusion criteria. Warfarin use (p=0.001) and GCS score (p=0.046) were significant clinical predictors of HE. The best performing model for HE prediction included clinical, radiological, and radiomic features with an area under the curve (AUC) of 87.7%. NCCT radiological features improved upon clinical benchmark model AUC by 6.5% and a clinical & radiomic combination model by 6.4%. Addition of radiomics features improved goodness of fit of both clinical (p=0.012) and clinical & NCCT radiological (p=0.007) models, with marginal improvements on AUC. Inclusion of NCCT radiological signs was best for ruling out HE whereas the radiomic features were best for ruling in HE. Conclusion NCCT-based radiological and radiomics features can improve HE prediction when added to clinical features.
Introduction: Cell based therapies have shown a considerable ability to improve functional outcom... more Introduction: Cell based therapies have shown a considerable ability to improve functional outcome when administered after experimental stroke. Intra-arterial (IA) cell transplantation has been shown to be a valuable alternative transplantation method for cell treatment. The success of IA therapy depends on the targeted homing and subsequent migration of cells to the injured brain area. This process is reliant on neural stem cell (NSC) expression of chemokines and their receptors. Understanding the differences in cell expression of these molecules and the resulting differences in chemotaxis will help identify ideal cell types for transplantation. Previously, we compared mRNA from human and mouse NSCs and found that only a 10% overlap in chemokine expression. We wanted to determine if there are also variations between different cell types from the same species. We compared NSCs obtained from induced pluripotent stem cells (iPS NSCs), to fetal NSCs (F NSC). We used RT-qPCR, in vitro cell migration, and quantification of cell secretion to compare chemokine and ligand expression in F NSCs and iPS NSCs. Methods: Secondary neurospheres originating from FVB mice were generated from either fetal primary NSCs from E17.5 mice (F NSC), or derived by transducing neurospheres originating from E3 mice with Oct4 (iPS NSC). Cells were grown as neurospheres in growth media treated with EGF and FGF. RT-qPCR was performed on extracted RNA using microarray technology for chemokine receptors and ligands. Luminex immunological assay was completed to assess secreted cytokines and inflammatory proteins. The Boyden chamber migration assay was used to determine migration to SDF-1 or MCP-1 at varying concentrations. Results: RNA expression was detected for 58% of the factors assessed. F NSCs alone expressed 6% (e.g. mmp2, Cxcl10), iPS NSCs alone expressed 16% (e.g. CCL2, CCL7, LIF), and both iPS NSCs and F NSCs expressed 20% (e.g. BDNF, HIF1a, CXCR4) of the detected factors. We assessed 26 secreted proteins, 73% occurred at detectable levels, of these 74% were expressed more highly in F NSCs than in iPS NSCs, including, il-1α, CCL3, CCL5, TNF-α, and VEGF; iPS NSCs secreted higher levels of MCP3, Il-3, and substantially more MCP-1 (113.7 ± 1.44 vs 52.78 ±4.221 pg/ml). iPS NSCs also had a higher migratory response to MCP-1 than F NSCs did (p < 0.001). Cell migration to SDF-1 did not differ between cell types (p = 0.905). Conclusions: Several chemokines and their receptors were differentially expressed in mouse iPS and F NSCs. These differences may result in variations in the NSC response to the ischemic brain. The profile of chemokine and chemokine receptor expression on NSCs should be strongly considered when selecting cell types for post stroke treatment.
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Papers by Angela Auriat