Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting dist...Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.展开更多
Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input...Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life(Kupers and Ptito,2014).More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of展开更多
Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructu...Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructural changes within brain tissue are expected to precede this volumetric decline.The tissue microstructure can be assayed non-invasively using diffusion MRI,which also allows a tractographic analysis of brain connectivity.Methods:We here used ex vivo diffusion MRI(11.7 T)to measure microstructural changes in different brain regions of end-stage(14 weeks of age)wild type and R6/2 mice(male and female)modeling Huntington's disease.To probe the microstructure of different brain regions,reduce partial volume effects and measure connectivity between different regions,a 100μm isotropic voxel resolution was acquired.Results:Although fractional anisotropy did not reveal any difference between wild-type controls and R6/2 mice,mean,axial,and radial diffusivity were increased in female R6/2 mice and decreased in male R6/2 mice.Whole brain streamlines were only reduced in male R6/2 mice,but streamline density was increased.Region-to-region tractography indicated reductions in connectivity between the cortex,hippocampus,and thalamus with the striatum,as well as within the basal ganglia(striatum—globus pallidus—subthalamic nucleus—substantia nigra—thalamus).Conclusions:Biological sex and left/right hemisphere affected tractographic results,potentially reflecting different stages of disease progression.This proof-of-principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions.In a translation setting,these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models,as well as patients with Huntington's disease.展开更多
Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerat...Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.展开更多
We demonstrate in situ non-invasive relay imaging through a medium without inserting physical optical components.We show that a virtual optical graded-index(GRIN)lens can be sculpted in the medium using in situ reconf...We demonstrate in situ non-invasive relay imaging through a medium without inserting physical optical components.We show that a virtual optical graded-index(GRIN)lens can be sculpted in the medium using in situ reconfigurable ultrasonic interference patterns to relay images through the medium.Ultrasonic wave patterns change the local density of the medium to sculpt a graded refractive index pattern normal to the direction of light propagation,which modulates the phase front of light,causing it to focus within the medium and effectively creating a virtual relay lens.We demonstrate the in situ relay imaging and resolving of small features(22μm)through a turbid medium(optical thickness=5.7 times the scattering mean free path),which is normally opaque.The focal distance and the numerical aperture of the sculpted optical GRIN lens can be tuned by changing the ultrasonic wave parameters.As an example,we experimentally demonstrate that the axial focal distance can be continuously scanned over a depth of 5.4mm in the modulated medium and that the numerical aperture can be tuned up to 21.5%.The interaction of ultrasonic waves and light can be mediated through different physical media,including turbid media,such as biological tissue,in which the ultrasonically sculpted GRIN lens can be used for relaying images of the underlying structures through the turbid medium,thus providing a potential alternative to implanting invasive endoscopes.展开更多
基金supported by NIH grants NS084967,NS121037 (to AEK) and NS110609 (to COB)。
文摘Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their life.Although a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.
基金supported by National Institutes of Health Contracts P30-EY008098 and T32-EY017271-06(BethesdaMD)+14 种基金United States Department of Defense DM090217(ArlingtonVA)Alcon Research Institute Young Investigator Grant(Fort WorthTX)Eye and Ear Foundation(PittsburghPA)Research to Prevent Blindness(New YorkNY)Aging Institute Pilot Seed GrantUniversity of Pittsburgh(PittsburghPA)Postdoctoral Fellowship Program in Ocular Tissue Engineering and Regenerative OphthalmologyLouis J.Fox Center for Vision RestorationUniversity of Pittsburgh and UPMC(PittsburghPA)
文摘Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life(Kupers and Ptito,2014).More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of
文摘Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructural changes within brain tissue are expected to precede this volumetric decline.The tissue microstructure can be assayed non-invasively using diffusion MRI,which also allows a tractographic analysis of brain connectivity.Methods:We here used ex vivo diffusion MRI(11.7 T)to measure microstructural changes in different brain regions of end-stage(14 weeks of age)wild type and R6/2 mice(male and female)modeling Huntington's disease.To probe the microstructure of different brain regions,reduce partial volume effects and measure connectivity between different regions,a 100μm isotropic voxel resolution was acquired.Results:Although fractional anisotropy did not reveal any difference between wild-type controls and R6/2 mice,mean,axial,and radial diffusivity were increased in female R6/2 mice and decreased in male R6/2 mice.Whole brain streamlines were only reduced in male R6/2 mice,but streamline density was increased.Region-to-region tractography indicated reductions in connectivity between the cortex,hippocampus,and thalamus with the striatum,as well as within the basal ganglia(striatum—globus pallidus—subthalamic nucleus—substantia nigra—thalamus).Conclusions:Biological sex and left/right hemisphere affected tractographic results,potentially reflecting different stages of disease progression.This proof-of-principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions.In a translation setting,these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models,as well as patients with Huntington's disease.
基金supported by the Wings for Life Foundation, Contract #: WFL-US-004/12
文摘Spinal cord injury (SCi) results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCi is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCi. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCi. A plethora of biomaterials is available and has been tested in various models of SCi. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCi.
基金supported,in part,by the NSF Expeditions grant#1730147.
文摘We demonstrate in situ non-invasive relay imaging through a medium without inserting physical optical components.We show that a virtual optical graded-index(GRIN)lens can be sculpted in the medium using in situ reconfigurable ultrasonic interference patterns to relay images through the medium.Ultrasonic wave patterns change the local density of the medium to sculpt a graded refractive index pattern normal to the direction of light propagation,which modulates the phase front of light,causing it to focus within the medium and effectively creating a virtual relay lens.We demonstrate the in situ relay imaging and resolving of small features(22μm)through a turbid medium(optical thickness=5.7 times the scattering mean free path),which is normally opaque.The focal distance and the numerical aperture of the sculpted optical GRIN lens can be tuned by changing the ultrasonic wave parameters.As an example,we experimentally demonstrate that the axial focal distance can be continuously scanned over a depth of 5.4mm in the modulated medium and that the numerical aperture can be tuned up to 21.5%.The interaction of ultrasonic waves and light can be mediated through different physical media,including turbid media,such as biological tissue,in which the ultrasonically sculpted GRIN lens can be used for relaying images of the underlying structures through the turbid medium,thus providing a potential alternative to implanting invasive endoscopes.
