Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research.

Quantifying injury expansion in the cervical spinal cord with intravital ultrafast contrast-enhanced ultrasound imaging.

Spinal cord injury is characterized by hemodynamic disruption at the injury epicenter and hypoperfusion in the penumbra, resulting in progressive ischemia and cell death. This degenerative secondary injury process has been well-described, though mostly using ex vivo or depth-limited optical imaging techniques. Intravital contrast-enhanced ultrasound enables longitudinal, quantitative evaluation of anatomical and hemodynamic changes in vivo through the entire spinal parenchyma.

The Brain and Spinal Microvasculature in Normal Aging.

Changes in the brain and spinal cord microvasculature during normal aging contribute to the "sensitive" nature of aged central nervous system tissue to ischemic insults. In this review, we will examine alterations in the central nervous system microvasculature during normal aging, which we define as aging without a dominant pathology such as neurodegenerative processes, vascular injury or disease, or trauma. We will also discuss newer technologies to improve the study of central nervous system microvascular structure and function.

Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction in quality of life for patients. Currently, no therapies are available that can repair spinal cord tissue. After the primary SCI, an acute inflammatory response induces further tissue damage in a process known as secondary injury.

A decrease in the neuroprotective effects of acute spinal cord decompression according to injury severity: introducing the concept of a ceiling effect.

Objective: Acute traumatic spinal cord injury (tSCI) is followed by a prolonged period of secondary neuroglial cell death. Neuroprotective interventions, such as surgical spinal cord decompression, aim to mitigate secondary injury. In this study, the authors explore whether the effect size of posttraumatic neuroprotective spinal cord decompression varies with injury severity.

Blood Flow Changes Associated with Spinal Cord Injury Assessed by Non-linear Doppler Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is clinically used to image the microcirculation at lower imaging frequencies (<2 MHz). Recently, plane-wave acquisitions and Doppler processing have revealed improved microbubble sensitivity, enabling CEUS use at higher frequencies (15 MHz) and the ability to image simultaneously blood flow in the micro- and macrocirculations. We used this approach to assess acute and chronic blood flow changes within contused spinal cord in a rodent spinal cord injury model.

Viable human brain microvessels for the study of aging and neurodegenerative diseases.

The brain microvasculature is altered in normal aging and in the presence of disease processes, such as neurodegeneration or ischemia, but there are few methods for studying living tissues. We now report that viable microvessels (MV) are readily isolated from brain tissue of subjects enrolled in studies of neurodegenerative diseases who undergo rapid autopsy (performed with <12 h postmortem interval - PMI). We find that these MV retain their morphology and cellular components and are fairly uniform in size.

Super-Resolution Ultrasound Localization Microscopy Through Deep Learning.

Ultrasound localization microscopy has enabled super-resolution vascular imaging through precise localization of individual ultrasound contrast agents (microbubbles) across numerous imaging frames. However, analysis of high-density regions with significant overlaps among the microbubble point spread responses yields high localization errors, constraining the technique to low-concentration conditions. As such, long acquisition times are required to sufficiently cover the vascular bed.

High-Frequency Nonlinear Doppler Contrast-Enhanced Ultrasound Imaging of Blood Flow.

Current methods for in vivo microvascular imaging (<1 mm) are limited by the tradeoffs between the depth of penetration, resolution, and acquisition time. Ultrasound Doppler approaches combined at elevated frequencies (<7.5 MHz) are able to visualize smaller vasculature and, however, are still limited in the segmentation of lower velocity blood flow from moving tissue.

Contrast-Enhanced Ultrasound for Assessment of Local Hemodynamic Changes Following a Rodent Contusion Spinal Cord Injury.

Introduction: Severe trauma to the spinal cord leads to a near complete loss of blood flow at the injury site along with significant hypoperfusion of adjacent tissues. Characterization and monitoring of local tissue hypoperfusion is currently not possible in clinical practice because available imaging techniques do not allow for assessment of blood flow with sufficient spatial and temporal resolutions. The objective of the current study was to determine whether ultrafast contrast-enhanced ultrasound (CEUS) imaging could be used to visualize and quantify acute hemodynamic changes in a rat traumatic spinal cord injury (SCI) model.

Noninvasive, In-pen Approach Test for Laboratory-housed Pigs.

Traumatic brain injury (TBI) incidences have increased in both civilian and military populations, and many researchers are adopting a porcine model for TBI. Unlike rodent models for TBI, there are few behavioral tests that have been standardized. A larger animal requires more invasive handling in test areas than rodents, which potentially adds stress and variation to the animals' responses.

Spontaneous Nucleation of Stable Perfluorocarbon Emulsions for Ultrasound Contrast Agents.

Phase-change contrast agents are rapidly developing as an alternative to microbubbles for ultrasound imaging and therapy. These agents are synthesized and delivered as liquid droplets and vaporized locally to produce image contrast. They can be used like conventional microbubbles but with the added benefit of reduced size and improved stability.

Contrast-enhanced ultrasound to visualize hemodynamic changes after rodent spinal cord injury.

OBJECTIVE Traumatic spinal cord injury (tSCI) causes an almost complete loss of blood flow at the site of injury (primary injury) as well as significant hypoperfusion in the penumbra of the injury. Hypoperfusion in the penumbra progresses after injury to the spinal cord and is likely to be a major contributor to progressive cell death of spinal cord tissue that was initially viable (secondary injury). Neuroprotective treatment strategies seek to limit secondary injury.

Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury.

Objective: Demyelination that results from disease or traumatic injury, such as spinal cord injury (SCI), can have a devastating effect on neural function and recovery. Many researchers are examining treatments to minimize demyelination by improving oligodendrocyte availability in vivo. Transplantation of stem and oligodendrocyte progenitor cells is a promising option, however, trials are plagued by undirected differentiation.

Sacrificial Crystal Templated Hyaluronic Acid Hydrogels As Biomimetic 3D Tissue Scaffolds for Nerve Tissue Regeneration.

Pores are key features of natural tissues and the development of tissues scaffolds with biomimetic properties (pore structures and chemical/mechanical properties) offers a route to engineer implantable biomaterials for specific niches in the body. Here we report the use of sacrificial crystals (potassium dihydrogen phosphate or urea) that act as templates to impart pores to hyaluronic acid-based hydrogels. The mechanical properties of the hydrogels were analogous to the nervous system (in the Pascal regime), and we investigated the use of the potassium dihydrogen phosphate crystal-templated hydrogels as scaffolds for neural progenitor cells (NPCs), and the use of urea crystal-templated hydrogels as scaffolds for Schwann cells.

Localized and sustained release of brain-derived neurotrophic factor from injectable hydrogel/microparticle composites fosters spinal learning after spinal cord injury.

Damaged axons in the adult mammalian central nervous system (CNS), including those of the spinal cord, have extremely limited endogenous capacity to regenerate. This is the result of both the intrinsic and extrinsic inhibitory factors that limit the regeneration of adult neurons. Despite attempts to limit or eliminate the extrinsic inhibitory components, regeneration of adult neurons in the CNS is still limited.

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure.

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology.

Temporal and Spatial Evolution of Raised Intraspinal Pressure after Traumatic Spinal Cord Injury.

Traumatic spinal cord injury (SCI) often leads to permanent neurological impairment. Currently, the only clinically effective intervention for patients with acute SCI is surgical decompression by removal of impinging bone fragments within 24 h after injury. Recent clinical studies suggest that elevated intraparenchymal spinal pressure (ISP) limits functional recovery following SCI.

Hyaluronic acid and neural stem cells: implications for biomaterial design.

While in the past hyaluronic acid (HA) was considered a passive component with a primarily structural role in tissues, research over the past few decades has revealed its diverse and complex biological functions, resulting in a major ideological shift. HA is abundant during normal central nervous system (CNS) development and, although down-regulated, remains ubiquitous in adult extracellular matrix (ECM). Significant changes in HA content are associated with pathological conditions, including stroke, traumatic injury and multiple sclerosis, and these changes likely disrupt repair by endogenous neural stem cells (NSCs).