The Experts below are selected from a list of 6255 Experts worldwide ranked by ideXlab platform
Shengkwei Song - One of the best experts on this subject based on the ideXlab platform.
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histopathological correlation of diffusion basis spectrum imaging metrics of a biopsy proven inflammatory demyelinating brain lesion a brief report
Multiple Sclerosis Journal, 2019Co-Authors: Afsaneh Shirani, Robert T Naismith, Kathryn Trinkaus, Shengkwei Song, Peng Sun, Robert E Schmidt, Anne H CrossAbstract:Diffusion basis spectrum imaging (DBSI) models diffusion-weighted magnetic resonance imaging (MRI) signals as a combination of discrete anisotropic diffusion tensors and a spectrum of isotropic diffusion tensors. Here, we report the histopathological correlates of DBSI in the biopsied brain tissue of a patient with an inflammatory demyelinating lesion typical of multiple sclerosis (MS). Increased radial Diffusivity (marker of demyelination), decreased fiber fraction (apparent axonal density), elevated nonrestricted isotropic fraction (marker of vasogenic edema), but unchanged Axial Diffusivity (marker of integrity of residual axons) seen in the lesion appeared consistent with histopathological findings of inflammatory demyelination with relative axonal sparing. Our report supports the application of DBSI as a biomarker in human studies of MS.
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quantifying white matter tract diffusion parameters in the presence of increased extra fiber cellularity and vasogenic edema
NeuroImage, 2014Co-Authors: Chiawen Chiang, Kathryn Trinkaus, Anne H Cross, Yong Wang, Peng Sun, Tsenhsuan Lin, Shengkwei SongAbstract:The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA) and increased radial Diffusivity, while less significantly increased Axial Diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and Axial Diffusivity with limited impact on radial Diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, Axial or radial Diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice.
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optic nerve diffusion tensor imaging parameters and their correlation with optic disc topography and disease severity in adult glaucoma patients and controls
Journal of Glaucoma, 2014Co-Authors: Sidney T Chang, Kathryn Trinkaus, Shengkwei Song, Melike Pekmezci, Stella N Arthur, Edward M BarnettAbstract:Purpose: To evaluate optic nerve diffusion tensor imaging (DTI) parameters in glaucoma patients and controls, and to correlate DTI parameters with the rim area obtained with Heidelberg retina tomography (HRT) and with the severity of glaucomatous damage using the Glaucoma Staging System. Design: Pilot study. Methods: Twenty-seven patients with glaucoma and 12 control subjects underwent DTI and HRT imaging. Main outcome measures included: fractional anisotropy, mean Diffusivity, Axial Diffusivity, radial Diffusivity, HRT rim area, and Glaucoma Staging System stage. Results: In group comparison, mean Diffusivity (1.33 vs. 0.91 mu m(2)/ms, P = 0.0002), Axial Diffusivity (1.70 vs. 1.43 mu m(2)/ms, P = 0.036), and radial Diffusivity (1.24 vs. 0.71 mu m(2)/ms, P 0.05). Conclusions: DTI may be a useful technique for detection and evaluation of glaucomatous damage in the optic nerve, particularly for patients in whom conventional imaging and perimetry are not possible. Future studies are needed to evaluate how DTI parameters change longitudinally with glaucomatous damage within the visual pathways and address cerebrospinal fluid partial volume effects in diffusion tensor quantification, especially for patients with advanced glaucoma stage.
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increased radial Diffusivity in spinal cord lesions in neuromyelitis optica compared with multiple sclerosis
Multiple Sclerosis Journal, 2012Co-Authors: Eric C Klawiter, Robert T Naismith, Tammie L S Benzinger, Joshua S Shimony, Kathryn Trinkaus, Shengkwei Song, Samantha Lancia, Abraham Z Snyder, Anne H CrossAbstract:Background:Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology.Objective:Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions.Methods:Subjects greater than or equal to 12 months from a clinical episode of transverse myelitis underwent a novel transAxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS and 10 healthy controls were included.Results:Within T2 affected white matter regions, radial Diffusivity was increased in both NMO and MS compared with healthy controls (p<0.001, respectively), and to a greater extent in NMO than MS (p<0.001). Axial Diffusivity was decreased in T2 lesions in both NMO and MS compared with controls (p<0.001, p=0.001), but did not differ between the two diseases. Radial Diffusivity and fractional anisotropy within white matter regions upstream and downstream of T2 lesions were different from controls in ea...
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CXCR7 antagonism prevents axonal injury during experimental autoimmune encephalomyelitis as revealed by in vivo Axial Diffusivity
Journal of neuroinflammation, 2011Co-Authors: Lillian Cruz-orengo, Shengkwei Song, Ying-jr Chen, Joong Hee Kim, Denise A. Dorsey, Robert S. KleinAbstract:Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestration of CXCL12, thereby enhancing the abluminal localization of CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry of leukocytes and amelioration of ongoing disease during EAE. Of note, animals that received high doses of CXCR7 antagonist recovered to baseline function, as assessed by standard clinical scoring. Because functional recovery reflects axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE. C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then evaluated by DTI to assess for axonal injury. After imaging, spinal cords underwent histological analysis of myelin and oligodendrocytes via staining with luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and glutathione S-transferase-π (GST-π). Detection of non-phosphorylated neurofilament H (NH-F) was also performed to detect injured axons. Statistical analysis for EAE scores, DTI parameters and non-phosphorylated NH-F immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For all statistical analysis a p < 0.05 was considered significant. In vivo DTI maps of spinal cord ventrolateral white matter (VLWM) Axial diffusivities of naive and CXCR7 antagonist-treated mice were indistinguishable, while vehicle-treated animals exhibited decreased Axial diffusivities. Quantitative differences in injured axons, as assessed via detection of non-phosphorylated NH-F, were consistent with Axial Diffusivity measurements. Overall, qualitative myelin content and presence of oligodendrocytes were similar in all treatment groups, as expected by their radial Diffusivity values. Quantitative assessment of persistent inflammatory infiltrates revealed significant decreases within the parenchyma of CXCR7 antagonist-treated mice versus controls. These data suggest that CXCR7 antagonism not only prevents persistent inflammation but also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease severity and recovery during EAE, suggesting a role for this molecule in both phases of disease.
Ronald M Harper - One of the best experts on this subject based on the ideXlab platform.
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rostral brain axonal injury in congenital central hypoventilation syndrome
Journal of Neuroscience Research, 2010Co-Authors: Rajneesh Kumar, Paul M Macey, Mary A Woo, Ronald M HarperAbstract:Brain injury underlying the state-related loss of ventilatory drive, autonomic, cognitive, and affective deficits in congenital central hypoventilation syndrome (CCHS) patients appears throughout the brain, as demonstrated by magnetic resonance (MR) T2 relaxometry and mean Diffusivity studies. However, neither MR measure is optimal to describe types of axonal injury essential for assessing neural interactions responsible for CCHS characteristics. To evaluate axonal integrity and partition the nature of tissue damage (axonal vs. myelin injury) in CCHS, we measured water diffusion parallel (Axial Diffusivity) and perpendicular (radial Diffusivity) to rostral brain fibers, indicative of axonal and myelin changes, respectively, with diffusion tensor imaging (DTI). We performed DTI in 12 CCHS (age 18.5 ± 4.9 years, 7 male) and 30 control (17.7 ± 4.6 years, 18 male) subjects, using a 3.0-Tesla MR imaging scanner. Axial and radial Diffusivity maps were calculated, spatially normalized, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). Significantly increased radial Diffusivity, primarily indicative of myelin injury, emerged in fibers of the corona radiata, internal capsule, corpus callosum, hippocampus through the fornix, cingulum bundle, and temporal and parietal lobes. Increased Axial Diffusivity, suggestive of axonal injury, appeared in fibers of the internal capsule, thalamus, corona radiata, and occipital and temporal lobes. Multiple brain regions showed both higher Axial and radial Diffusivity, indicative of loss of tissue integrity with a combination of myelin and axonal injury, including basal ganglia, bed nucleus, and limbic, occipital, and temporal areas. The processes underlying injury are unclear, but likely stem from both hypoxic and developmental processes. © 2010 Wiley-Liss, Inc.
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diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome
Pediatric Research, 2008Co-Authors: Rajneesh Kumar, Paul M Macey, Mary A Woo, Jeffry R Alger, Ronald M HarperAbstract:Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely Axial Diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial Diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and Axial and radial Diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased Axial Diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphe, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial Diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.
Rajneesh Kumar - One of the best experts on this subject based on the ideXlab platform.
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rostral brain axonal injury in congenital central hypoventilation syndrome
Journal of Neuroscience Research, 2010Co-Authors: Rajneesh Kumar, Paul M Macey, Mary A Woo, Ronald M HarperAbstract:Brain injury underlying the state-related loss of ventilatory drive, autonomic, cognitive, and affective deficits in congenital central hypoventilation syndrome (CCHS) patients appears throughout the brain, as demonstrated by magnetic resonance (MR) T2 relaxometry and mean Diffusivity studies. However, neither MR measure is optimal to describe types of axonal injury essential for assessing neural interactions responsible for CCHS characteristics. To evaluate axonal integrity and partition the nature of tissue damage (axonal vs. myelin injury) in CCHS, we measured water diffusion parallel (Axial Diffusivity) and perpendicular (radial Diffusivity) to rostral brain fibers, indicative of axonal and myelin changes, respectively, with diffusion tensor imaging (DTI). We performed DTI in 12 CCHS (age 18.5 ± 4.9 years, 7 male) and 30 control (17.7 ± 4.6 years, 18 male) subjects, using a 3.0-Tesla MR imaging scanner. Axial and radial Diffusivity maps were calculated, spatially normalized, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). Significantly increased radial Diffusivity, primarily indicative of myelin injury, emerged in fibers of the corona radiata, internal capsule, corpus callosum, hippocampus through the fornix, cingulum bundle, and temporal and parietal lobes. Increased Axial Diffusivity, suggestive of axonal injury, appeared in fibers of the internal capsule, thalamus, corona radiata, and occipital and temporal lobes. Multiple brain regions showed both higher Axial and radial Diffusivity, indicative of loss of tissue integrity with a combination of myelin and axonal injury, including basal ganglia, bed nucleus, and limbic, occipital, and temporal areas. The processes underlying injury are unclear, but likely stem from both hypoxic and developmental processes. © 2010 Wiley-Liss, Inc.
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diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome
Pediatric Research, 2008Co-Authors: Rajneesh Kumar, Paul M Macey, Mary A Woo, Jeffry R Alger, Ronald M HarperAbstract:Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely Axial Diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial Diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and Axial and radial Diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased Axial Diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphe, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial Diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.
Matthew D Budde - One of the best experts on this subject based on the ideXlab platform.
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noninvasive detection of brainstem and spinal cord axonal degeneration in an amyotrophic lateral sclerosis mouse model
NMR in Biomedicine, 2011Co-Authors: Joong Hee Kim, Matthew D Budde, Jinmoo Lee, Shengkwei SongAbstract:Degeneration of motor neurons and their associated axons is a hallmark of amyotrophic lateral sclerosis, but reliable noninvasive lesion detection is lacking. In vivo diffusion tensor imaging was performed to evaluate neurodegeneration in the brainstem and cervical spinal cord of wild-type and G93A-SOD1 transgenic mice, an animal model of amyotrophic lateral sclerosis. A statistically significant reduction in the apparent diffusion coefficient was observed in the motor nuclei VII and XII of G93A-SOD1 transgenic mice relative to wild-type mice. No significant difference in diffusion anisotropy was observed in dorsal white or gray matter in cervical and lumbar segments of the spinal cord. In contrast, statistically significant decreases in Axial Diffusivity (Diffusivity parallel to the axis of the spinal cord) and apparent diffusion coefficient were found in the ventrolateral white matter of G93A-SOD1 mice in both the cervical and lumbar spinal cord. The reduction in Axial Diffusivity, suggestive of axonal injury, in the white matter of the spinal cord of G93A-SOD1 mice was verified by immunostaining with nonphosphorylated neurofilament. The present study demonstrates that in vivo diffusion tensor imaging-derived Axial Diffusivity may be used to accurately evaluate axonal degeneration in an animal model of amyotrophic lateral sclerosis.
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diffusion tensor imaging at 3 hours after traumatic spinal cord injury predicts long term locomotor recovery
Journal of Neurotrauma, 2010Co-Authors: Joong H Kim, Kathryn Trinkaus, Matthew D Budde, Robert E Schmidt, David Loy, Qing Wang, Shengkwei SongAbstract:Abstract Accurate diagnosis of spinal cord injury (SCI) severity must be achieved before highly aggressive experimental therapies can be tested responsibly in the early phases after trauma. These studies demonstrate for the first time that Axial Diffusivity (λ||), derived from diffusion tensor imaging (DTI) within 3 h after SCI, accurately predicts long-term locomotor behavioral recovery in mice. Female C57BL/6 mice underwent sham laminectomy or graded contusive spinal cord injuries at the T9 vertebral level (5 groups, n = 8 for each group). In-vivo DTI examinations were performed immediately after SCI. Longitudinal measurements of hindlimb locomotor recovery were obtained using the Basso mouse scale (BMS). Injured and spared regions of ventrolateral white matter (VLWM) were reliably separated in the hyperacute phase by threshold segmentation. Measurements of λ|| were compared with histology in the hyperacute phase and 14 days after injury. The spared normal VLWM determined by hyperacute λ|| and 14-day hi...
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Axial Diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord a quantitative pixelwise analysis
The Journal of Neuroscience, 2009Co-Authors: Matthew D Budde, Anne H Cross, Shengkwei SongAbstract:The dissociation between magnetic resonance imaging (MRI) and permanent disability in multiple sclerosis (MS), termed the clinicoradiological paradox, can primarily be attributed to the lack of specificity of conventional, relaxivity-based MRI measurements in detecting axonal damage, the primary pathological correlate of long-term impairment in MS. Diffusion tensor imaging (DTI) has shown promise in specifically detecting axonal damage and demyelination in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). To quantify the specificity of DTI in detecting axonal injury, in vivo DTI maps from the spinal cords of mice with EAE and quantitative histological maps were both registered to a common space. A pixelwise correlation analysis between DTI parameters, histological metrics, and EAE scores revealed a significant correlation between the water diffusion parallel to the white matter fibers, or Axial Diffusivity, and EAE score. Furthermore, Axial Diffusivity was the primary correlate of quantitative staining for neurofilaments (SMI31), markers of axonal integrity. Both Axial Diffusivity and neurofilament staining were decreased throughout the entire white matter, not solely within the demyelinated lesions seen in EAE. In contrast, although anisotropy was significantly correlated with EAE score, it was not correlated with axonal damage. The results demonstrate a strong, quantitative relationship between Axial Diffusivity and axonal damage and show that anisotropy is not specific for axonal damage after inflammatory demyelination.
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axonal injury detected by in vivo diffusion tensor imaging correlates with neurological disability in a mouse model of multiple sclerosis
NMR in Biomedicine, 2008Co-Authors: Matthew D Budde, Anne H Cross, Hsiaofang Liang, John H Russell, Shengkwei SongAbstract:Recent studies have suggested that axonal damage, and not demyelination, is the primary cause of long-term neurological impairment in Multiple Sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The Axial and radial diffusivities derived from diffusion tensor imaging (DTI) have shown promise as noninvasive surrogate markers of axonal damage, and demyelination, respectively. In the current study, in vivo DTI of the spinal cords from mice with chronic EAE was performed to determine if Axial Diffusivity correlated with neurological disability in EAE assessed by the commonly used clinical scoring system. Axial Diffusivity in the ventrolateral white matter had a significant negative correlation with EAE clinical score and was significantly lower in mice with severe EAE than mice with moderate EAE. Furthermore, the greater decreases in Axial Diffusivity were associated with greater amounts of axonal damage as confirmed by quantitative staining for non-phosphorylated neurofilaments (SMI-32). Radial Diffusivity and relative anisotropy could not distinguish between the groups of mice with moderate EAE and those with severe EAE. The results further the notion that Axial Diffusivity is a noninvasive marker of axonal damage in white matter and could provide the necessary link between pathology and neurological disability.
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detecting axon damage in spinal cord from a mouse model of multiple sclerosis
Neurobiology of Disease, 2006Co-Authors: Joong Hee Kim, Anne H Cross, Robert S. Klein, Hsiaofang Liang, Matthew D Budde, John H Russell, Shengkwei SongAbstract:In the current study, the feasibility and reproducibility of in vivo diffusion tensor imaging (DTI) of the spinal cord in normal mice are illustrated followed by its application to mice with experimental allergic encephalomyelitis (EAE) to detect and differentiate axon and myelin damage. Axial Diffusivity, describing water movement along the axonal fiber tract, in all regions of spinal cord white matter from EAE-affected C57BL/6 mice was significantly decreased compared to normal mice, whereas there was no statistically significant change in radial Diffusivity, describing water movement across the fiber tract. Furthermore, a direct comparison between DTI and histology from a single mouse demonstrated a decrease in Axial Diffusivity that was supported by widespread staining of antibody against beta-amyloid precursor protein. Regionally elevated radial Diffusivity corresponded with locally diminished Luxol fast blue staining in the same tissue from the EAE mouse cord. Our findings suggest that axonal damage is more widespread than myelin damage in the spinal cord white matter of mice with EAE and that in vivo DTI may provide a sensitive and specific measure of white matter injury.
Anne H Cross - One of the best experts on this subject based on the ideXlab platform.
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histopathological correlation of diffusion basis spectrum imaging metrics of a biopsy proven inflammatory demyelinating brain lesion a brief report
Multiple Sclerosis Journal, 2019Co-Authors: Afsaneh Shirani, Robert T Naismith, Kathryn Trinkaus, Shengkwei Song, Peng Sun, Robert E Schmidt, Anne H CrossAbstract:Diffusion basis spectrum imaging (DBSI) models diffusion-weighted magnetic resonance imaging (MRI) signals as a combination of discrete anisotropic diffusion tensors and a spectrum of isotropic diffusion tensors. Here, we report the histopathological correlates of DBSI in the biopsied brain tissue of a patient with an inflammatory demyelinating lesion typical of multiple sclerosis (MS). Increased radial Diffusivity (marker of demyelination), decreased fiber fraction (apparent axonal density), elevated nonrestricted isotropic fraction (marker of vasogenic edema), but unchanged Axial Diffusivity (marker of integrity of residual axons) seen in the lesion appeared consistent with histopathological findings of inflammatory demyelination with relative axonal sparing. Our report supports the application of DBSI as a biomarker in human studies of MS.
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quantifying white matter tract diffusion parameters in the presence of increased extra fiber cellularity and vasogenic edema
NeuroImage, 2014Co-Authors: Chiawen Chiang, Kathryn Trinkaus, Anne H Cross, Yong Wang, Peng Sun, Tsenhsuan Lin, Shengkwei SongAbstract:The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA) and increased radial Diffusivity, while less significantly increased Axial Diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and Axial Diffusivity with limited impact on radial Diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, Axial or radial Diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice.
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increased radial Diffusivity in spinal cord lesions in neuromyelitis optica compared with multiple sclerosis
Multiple Sclerosis Journal, 2012Co-Authors: Eric C Klawiter, Robert T Naismith, Tammie L S Benzinger, Joshua S Shimony, Kathryn Trinkaus, Shengkwei Song, Samantha Lancia, Abraham Z Snyder, Anne H CrossAbstract:Background:Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology.Objective:Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions.Methods:Subjects greater than or equal to 12 months from a clinical episode of transverse myelitis underwent a novel transAxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS and 10 healthy controls were included.Results:Within T2 affected white matter regions, radial Diffusivity was increased in both NMO and MS compared with healthy controls (p<0.001, respectively), and to a greater extent in NMO than MS (p<0.001). Axial Diffusivity was decreased in T2 lesions in both NMO and MS compared with controls (p<0.001, p=0.001), but did not differ between the two diseases. Radial Diffusivity and fractional anisotropy within white matter regions upstream and downstream of T2 lesions were different from controls in ea...
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Axial Diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord a quantitative pixelwise analysis
The Journal of Neuroscience, 2009Co-Authors: Matthew D Budde, Anne H Cross, Shengkwei SongAbstract:The dissociation between magnetic resonance imaging (MRI) and permanent disability in multiple sclerosis (MS), termed the clinicoradiological paradox, can primarily be attributed to the lack of specificity of conventional, relaxivity-based MRI measurements in detecting axonal damage, the primary pathological correlate of long-term impairment in MS. Diffusion tensor imaging (DTI) has shown promise in specifically detecting axonal damage and demyelination in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). To quantify the specificity of DTI in detecting axonal injury, in vivo DTI maps from the spinal cords of mice with EAE and quantitative histological maps were both registered to a common space. A pixelwise correlation analysis between DTI parameters, histological metrics, and EAE scores revealed a significant correlation between the water diffusion parallel to the white matter fibers, or Axial Diffusivity, and EAE score. Furthermore, Axial Diffusivity was the primary correlate of quantitative staining for neurofilaments (SMI31), markers of axonal integrity. Both Axial Diffusivity and neurofilament staining were decreased throughout the entire white matter, not solely within the demyelinated lesions seen in EAE. In contrast, although anisotropy was significantly correlated with EAE score, it was not correlated with axonal damage. The results demonstrate a strong, quantitative relationship between Axial Diffusivity and axonal damage and show that anisotropy is not specific for axonal damage after inflammatory demyelination.
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disability in optic neuritis correlates with diffusion tensor derived directional diffusivities
Neurology, 2009Co-Authors: Robert T Naismith, Junqian Xu, Nhial T Tutlam, A Z Snyder, Tammie L S Benzinger, Joshua S Shimony, J Shepherd, Kathryn Trinkaus, Anne H Cross, Shengkwei SongAbstract:Objective: To determine the potential of directional diffusivities from diffusion tensor imaging (DTI) to predict clinical outcome of optic neuritis (ON), and correlate with vision, optical coherence tomography (OCT), and visual evoked potentials (VEP). Methods: Twelve cases of acute and isolated ON were imaged within 30 days of onset and followed prospectively. Twenty-eight subjects with a remote clinical history of ON were studied cross-sectionally. Twelve healthy controls were imaged for comparison. DTI data were acquired at 3T with a surface coil and 1.3 × 1.3 × 1.3 mm 3 isotropic voxels. Results: Normal DTI parameters (mean ± SD, μm 2 /ms) were Axial Diffusivity = 1.66 ± 0.18, radial Diffusivity = 0.81 ± 0.26, apparent diffusion coefficient (ADC) = 1.09 ± 0.21, and fractional anisotropy (FA) = 0.43 ± 0.15. Axial Diffusivity decreased up to 2.5 SD in acute ON. The decrease in Axial Diffusivity at onset correlated with visual contrast sensitivity 1 month ( r = 0.59) and 3 months later ( r = 0.65). In three subjects followed from the acute through the remote stage, radial Diffusivity subsequently increased to >2.5 SD above normal, as did Axial Diffusivity and ADC. In remote ON, radial Diffusivity correlated with OCT ( r = 0.81), contrast sensitivity ( r = 0.68), visual acuity ( r = 0.56), and VEP ( r = 0.54). Conclusion: In acute and isolated demyelination, Axial Diffusivity merits further investigation as a predictor of future clinical outcome. Diffusion parameters are dynamic in acute and isolated optic neuritis, with an initial acute decrease in Axial Diffusivity. In remote disease, radial Diffusivity correlates with functional, structural, and physiologic tests of vision.
