The 35 year evolution of in vivo magnetic resonance and spectroscopy

In the last 35 years, nuclear magnetic resonance has developed from a one dimensional chemical analytical method of spectroscopy to a four dimensional method for studying in vivo human physiology and diseases. These advances have evolved from the first carbon-13 spectroscopic studies in test tubes with electromagnets and in vivo proton imaging of biological objects to new methods of imaging in vivo metabolism of carbon compounds with field strengths 20 times those in the beginning. The modern techniques have been enabled by high magnetic field technologies, gradient and RF coil designs in combinations with pulse sequence strategies, and hyperpolarization methods to overcome the inherent low sensitivity of magnetic resonance for low abundance nuclei. The barriers to overcoming low sensitivity (e.g., only 0.0006 % at 2 Tesla) are the limitations of current density for conventional superconducting conductors and concerns regarding physiological effects from high magnetic fields. The conductor problem that limits whole body systems to 8 Tesla can be overcome by use of different conductor material (e.g. niobium tin vs. niobium titanium). Health effects up to 12 T are not expected but there is reason for caution as we approach 20 T (e.g. nerve conduction velocity decreases). Magnetic resonance instruments at 7 T open entirely new biological and medical science horizons mainly due to the relationships between the signal-to-noise, the magnetic field strength and the square root of time. For example, a previously intractable goal of multiple quantum imaging of potassium and sodium in the brain and heart could be achieved with 10 mm resolution in less than 15 minutes at 7 T, but the same study would require 5 hours at 1.5 T. The potential applications are to understanding membrane physiology in mental disorders such as manic-depressive and obsessive-compulsive disorders. In addition the high field provides the spectral resolution that together with hyperpolarized substrate in- - jections allow one to study metabolic pathways not obtainable in living subjects by any other methods. These metabolic pathways are of essential importance to understanding diabetes, obesity and heart failure.