Methods of Determining Homeostatic Perturbations

Biological homeostasis is a state of steady internal, physical, and chemical conditions maintained by a living organism observed at the cellular level.  Biological homeostasis can vary in order to alter the cellular physical and chemical conditions. Thus, it acts as a mechanism to define the physiological state of cellular activity; for instance resting states or active states (e.g., intensive physical or mental activity or intensive physical or mental stimulation).  Deviations or perturbations from biological homeostasis, even at the cellular level, can be caused by pathological conditions such as diseases within the organism.  Such deviations result in physical and chemical conditions that feedback to prolong pathological states as part of an injury or disease.  In the extreme case, cell death can be characterized by a complete loss of homeostasis.  In these ways, states of biological homeostasis are linked to physiological and pathological activities occurring at various levels of the organism (e.g., organelle, cell, tissue, organ).  States of biological homeostasis can be difficult to detect using conventional analytical techniques.

The disclosed technology consists of methods to determine a homeostatic steady-state of a biological entity.  Also disclosed are methods to use Nuclear Magnetic Resonance (NMR) or Magnetic Resonance Imaging (MRI) to quantify a water exchange rate between at least two compartments in a biological system, to characterize physiological water transport, and methods for non-invasively measuring transmembrane exchange rates of endogenous water in a biological system under steady-state or non-steady-state conditions in near-real time.

Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development are highly motivated in seeking licensing and/or collaboration partners further to develop methods and/or assays arising out of these technologies. An ideal partner would enter into both a Cooperative Research and Development Agreement (CRADA) and an exclusive license agreement towards commercialization of this diagnostic in the area of neurology or another suitable field.

Competitive Advantages:

• Absolute measurement—can directly detect the homeostatic state—does not require a relative reading. 
• Uses endogenous water—does not require a tracer or contrast agent
• Less invasive than the current state of the art methods to measure spreading depolarization

Commercial Applications:

• Diagnosis of benign tumors capable of immune stimulation (“hot”)
• Diagnosis of abnormal central nervous system (CNS) states (ex: those caused by stroke, brain aneurysm, traumatic brain injury, migraine aura, and seizure)
• Determining the physiological or functional activity state of the central nervous system (CNS) (e.g. sleep, wake, intense stimulation)
• Evaluating CNS therapeutics and their mechanism of action