Acquisition and Analysis of Excised Neocortex from Pediatric Patients with Focal Cortical Dysplasia Using Mesoscale Diffusion MRI.

Non-invasive classification of focal cortical dysplasia (FCD) subtypes remains challenging from a radiology perspective. Quantitative imaging biomarkers (QIBs) have the potential to distinguish subtypes that lack pathognomonic features and might help in defining the extent of abnormal connectivity associated with each FCD subtype. A key motivation of diagnostic imaging is to improve the localization of a "lesion" that can guide the surgical resection of affected tissue, which is thought to cause seizures.

Mapping the acute time course of immune cell infiltration into an ECM hydrogel in a rat model of stroke using F MRI.

Extracellular matrix (ECM) hydrogel implantation into a stroke-induced tissue cavity invokes a robust cellular immune response. However, the spatio-temporal dynamics of immune cell infiltration into peri-infarct brain tissues versus the ECM-bioscaffold remain poorly understood. We here tagged peripheral immune cells using perfluorocarbon (PFC) nanoemulsions that afford their visualization by F magnetic resonance imaging (MRI).

Physical therapy exerts sub-additive and suppressive effects on intracerebral neural stem cell implantation in a rat model of stroke.

Intracerebral cell therapy (CT) is emerging as a new therapeutic paradigm for stroke. However, the impact of physical therapy (PT) on implanted cells and their ability to promote recovery remains poorly understood. To address this translational issue, a clinical-grade neural stem cell (NSC) line was implanted into peri-infarct tissue using MRI-defined injection sites, two weeks after stroke.

Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration.

Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold's regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke.

ECM hydrogel improves the delivery of PEG microsphere-encapsulated neural stem cells and endothelial cells into tissue cavities caused by stroke.

Intracerebral implantation of neural stem cells (NSCs) to treat stroke remains an inefficient process with <5% of injected cells being retained. To improve the retention and distribution of NSCs after a stroke, we investigated the utility of NSCs' encapsulation in polyethylene glycol (PEG) microspheres. We first characterized the impact of the physical properties of different syringes and needles, as well as ejection speed, upon delivery of microspheres to the stroke injured rat brain.

A systematic optimization of F MR image acquisition to detect macrophage invasion into an ECM hydrogel implanted in the stroke-damaged brain.

F-MR imaging of perfluorocarbon (PFC)-labeled macrophages can provide a unique insight into their participation and spatio-temporal dynamics of inflammatory events, such as the biodegradation of an extracellular matrix (ECM) hydrogel implanted into a stroke cavity. To determine the most efficient acquisition strategy for F-MR imaging, five commonly used sequences were optimized using a design of experiment (DoE) approach and compared based on their signal-to-noise ratio (SNR). The fast imaging with steady-state precession (FISP) sequence produced the most efficient detection of a F signal followed by the rapid acquisition with relaxation enhancement (RARE) sequence.

Biodegradation of ECM hydrogel promotes endogenous brain tissue restoration in a rat model of stroke.

The brain is considered to have a limited capacity to repair damaged tissue and no regenerative capacity following injury. Tissue lost after a stroke is therefore not spontaneously replaced. Extracellular matrix (ECM)-based hydrogels implanted into the stroke cavity can attract endogenous cells.

Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery.

Intracerebral implantation of cell suspensions is finding its clinical translation with encouraging results in patients with stroke. However, the survival of cells in the brain remains poor. Although the biological potential of neural stem cells (NSCs) is widely documented, the biomechanical effects of delivering cells through a syringe-needle remain poorly understood.

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume.

Unlabelled: Salvaging or functional replacement of damaged tissue caused by stroke in the brain remains a major therapeutic challenge. In situ gelation and retention of a hydrogel bioscaffold composed of 8mg/mL extracellular matrix (ECM) can induce a robust invasion of cells within 24h and potentially promote a structural remodeling to replace lost tissue. Herein, we demonstrate a long-term retention of ECM hydrogel within the lesion cavity.

Biological effects of dosing aerobic exercise and neuromuscular electrical stimulation in rats.

Aerobic exercise (AE) and non-aerobic neuromuscular electric stimulation (NMES) are common interventions used in physical therapy. We explored the dose-dependency (low, medium, high) of these interventions on biochemical factors, such as brain derived neurotrophic growth factor (BDNF), vascular endothelial growth factor-A (VEGF-A), insulin-like growth factor-1 (IGF-1) and Klotho, in the blood and brain of normal rats, as well as a treadmill-based maximum capacity test (MCT). A medium dose of AE produced the most improvement in MCT with dose-dependent changes in Klotho in the blood.

Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke.

Extracellular matrix (ECM) is widely used as an inductive biological scaffold to repair soft tissue after injury by promoting functional site-appropriate remodeling of the implanted material. However, there is a lack of non-invasive analysis methods to monitor the remodeling characteristics of the ECM material after implantation and its biodegradation over time. We describe the use of diamagnetic chemical exchange saturation transfer (CEST) magnetic resonance imaging to monitor the distribution of an ECM hydrogel after intracerebral implantation into a stroke cavity.

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate.

Brain tissue loss following stroke is irreversible with current treatment modalities. The use of an acellular extracellular matrix (ECM), formulated to produce a hydrogel in situ within the cavity formed by a stroke, was investigated as a method to replace necrotic debris and promote the infiltration of host brain cells. Based on magnetic resonance imaging measurements of lesion location and volume, different concentrations of ECM (0, 1, 2, 3, 4, 8 mg/mL) were injected at a volume equal to that of the cavity (14 days post-stroke).

DNA-gadolinium-gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells.

The unambiguous imaging of transplanted cells remains a major challenge to understand their biological function and therapeutic efficacy. In vivo imaging of implanted cells is reliant on tagging these to differentiate them from host tissue, such as the brain. We here characterize a gold nanoparticle conjugate that is functionalized with modified deoxythymidine oligonucleotides bearing Gd(III) chelates and a red fluorescent Cy3 moiety to visualize in vivo transplanted human neural stem cells.

Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity.

Unlabelled: Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form.