This application describes an apparatus and method of convection-enhanced delivery of drugs into the brain and other solid tissue structures. The method involves positioning the tip of an infusion catheter within a tissue structure and supplying an agent through the catheter while maintaining a pressure gradient from the tip of the catheter during infusion. The catheter is connected to a pump which delivers the desired drug and maintains a desired pressure gradient throughout delivery of the agent.

Subarachnoid hemorrhage (SAH) occurs in 28,000 people per year in North America. Symptomatic vasospasm occurs in the majority of individuals suffering SAH and is the most common cause of morbidity and mortality in patients reaching neurological care. Specifically, vasospasm causes cerebral ischemia or stroke, and the prevention of vasospasm could prevent stroke and death as well as allow physicians more freedom in scheduling surgery when the operative risks are lower.

This invention describes several novel MRI "stains" to measure and display water diffusion anisotropy data obtained by diffusion tensor MRI (DT-MRI). One problem that this invention overcomes is that it significantly reduces the statistical bias in the mean and variance of the measured anisotropy of water diffusion caused by background noise in the MR images. These benefits are achieved by exploiting the idea that fiber tracts exhibiting diffusion anisotropy vary continuously in most regions.

A microtome device is used in a variety of microcopy techniques to remove very thin (e.g., in the tens of nanometers range) portions from the top of a sample between successive images. This technology discloses a design for a microtome device that offers several unique features and advantages over commercially available microtomes. A prototype of the microtome has been built and demonstrated to work with a serial block-face scanning electron microscopy in order to serially collect ultrathin sections from plastic embedded biological tissues, specifically from brain tissues.

The magnetic resonance imaging (MRI) systems are used for a variety of imaging application. The present invention discloses an improving MRI device and method by amplifying signals received by resonant NMR coils of MRI systems. It utilizes positive feedback from low-noise Field-Effect Transistor to amplify the signal current that can be coupled out to receiving loops positioned externally without loss in sensitivity. Therefore, the NMR coil can be flexibly positioned near internal tissues and used to develop high-resolution images in highly invasive situations.

This invention includes human induced pluripotent stem cell (iPSC) lines that harbor a single copy dCas9-BFP-KRAB at the CLYBL safe harbor locus (mediating CRISPR inhibition of human gene expression) and/or a single copy of dox-inducible NGN2 at the AAVS1 locus (enabling the differentiation of the iPSCs into neurons). The CRISPR-mediated inhibition of human gene expression is maintained into the differentiated neurons, permitting functional studies of targeted genes in neurons.

Investigators at the NIH have identified a series of novel, small molecule antagonists of the dopamine D2 receptor. Among the dopamine receptor (DAR) subtypes, D2 DAR is arguably one of the most validated drug targets in neurology and psychiatry. For instance, all receptor-based anti-Parkinsonian drugs work via stimulating the D2 DAR, whereas all FDA approved antipsychotic agents are antagonists of this receptor. Unfortunately, most agents that act as antagonists of D2 DAR are problematic, either they are less efficacious than desired or cause multiple adverse effects.

Nestin is an intermediate filament protein first described in early embryonic neuroepithelial stem cells. Although not found in most cells of the mature CNS, nestin is the predominant marker used to detect the small population of undifferentiated cells. The presence of nestin identifies stem, progenitor and some tumor cells in the CNS, and also labels areas of reactive gliosis in the CNS. Available methods to detect nestin use antibodies generated against rat nestin protein.

Cell transplantation therapy typically involves transplanting primary cells or immortalized cells into patients. The promising but still inconsistent data stemming from those clinical trials using primary cells in Parkinson's disease are believed to be due to an insufficient number, function and uniformity of the transplanted cells. In an effort to overcome these problems an improved method for isolating, growing and differentiating precursor cells into dopaminergic neurons has been developed.

Many experimental therapies will rely on the local parenchymal delivery of macromolecules or nucleic acids for their success. However, the volume of distribution of many of these potential therapeutic agents is restricted by their interactions with the extracellular matrix and cellular receptors.