Small Business Grants

Magnetic Resonance Imaging (MRI) is the gold-standard method for the detection and diagnosis of brain disease and surgical planning. Neurosurgery is closely guided by preoperative neuroimaging with MRI which can accurately localize and delineate lesions, map functionally critical brain regions, or probe tissue metabolism to guide clinical management. While the preoperative images are regularly consulted in the OR, the surgeon’s ability to navigate with these maps is degraded by tissue deformation and brain shifts that occur during surgery.

The goal of this project is to create two prototypes of a novel live spike sorting system which can be used by investigators to spike sort streams of neural data recorded by multi-channel, high channel and ultra-high channel probes. In most in-vivo extracellular recording conditions, an electrode can pick up neural spikes from several nearby neurons resulting in so-called “multi-unit” activity in the recording trace.

The ability to measure and manipulate local brain circuit activity in living, behaving animals is essential to understanding the complexities of brain function and dysfunction.

Electroencephalography (EEG) measures the brain’s local field potential from the surface of the scalp. This method is useful for studying cognitive processes, neurological states, and medical conditions. Its relative low- cost, ease-of use, and non-invasiveness increase its utility in brain monitoring for both research and medical applications. Unfortunately, the process of acquiring EEG is often not inclusive of all research subjects. EEG typically requires scalp abrasion and application of conductive gels to create a low impedance contact between exposed skin and the electrode tips.

In this SBIR grant proposal, “Ultra-low distortion and noise electronics to enable a clinical MPI imaging platform,” we will develop the RF subsystem for a clinical magnetic particle imaging (MPI) platform to enable three classes of MPI applications: cell tracking, functional imaging, and endogenous contrast imaging.

Whole-brain mapping at the cellular and subcellular levels is crucial to systematically understand brain functions and disorders. Recent developments in tissue transformation techniques, such as CLARITY, SHIELD, MAP, ExM, CUBIC, and DISCO-based methods, have made significant progress towards whole-organ molecular labeling and microscopic imaging by rendering intact tissue chemically permeable and optically transparent.

This Phase II project describes the commercial development of HyperAxon™, highly innovative software for performing automated segmentation, tracing, reconstruction and quantitative analysis of all axonal fibers (with and without signs of acute axonal injury) visible in two- and three-dimensional (2D and 3D) microscopy images of central nervous system (CNS) areas, even those with extremely high axonal fiber density.

Non-invasive brain stimulation (NIBS) has attracted considerable interest in the cognitive neuroscience community, providing an important basic research tool to study brain function, with emerging clinical applications to enhance function in individuals with neurological disorders. Despite this potential, an emerging literature has highlighted concerns regarding the reliability and robustness of transcranial electric stimulation (tES), the primary NIBS method used to induce changes in brain plasticity through the application of subthreshold stimulation.

Cardiac arrest in infants is a medical emergency requiring rapid resuscitation to restore circulation. However, resuscitation often results in significant brain injury, caused by ischemia/reperfusion injury. Only 36% of infants (<1yr old) treated for out-of-hospital cardiac arrest and 69% of infants that suffer in-hospital cardiac arrest are successfully resuscitated. These infants currently have no therapeutic options to limit brain injury. The current standard treatment for post-cardiac arrest brain injury is therapeutic hypothermia.

Histone modifications carry rich information of cellular memory and gene regulatory mechanisms. Single cell analysis of histone modification in conjunction with transcriptome could recover this critical layer of cell identity and help to dissect the cellular and molecular composition of complex tissues such as the brain. We recently developed an ultra-high throughput single cell multi-omics assay, Paired-Tag, that can jointly map transcriptome and histone modifications from up to a million single cells in parallel.