Survey of brain imaging techniques with implications for nanomedicine
Stephen S. Flitman*
Cognitive Neurology Section,
Barrow Neurological Institute,
Phoenix, Arizona 85013 USA
This is an abstract
for a presentation given at the
Foresight Conference on Molecular Nanotechnology.
The full article is available at http://www.foresight.org/Conferences/MNT8/Papers/Flitman/index.html.
Nanotechnology has tremendous potential for advancing medicine. As a neurologist, I see incurable brain diseases daily: e.g., Alzheimer's and related disorders. However, diagnosis has improved greatly, driving progress as clinical trials of new treatments need cohorts of well-characterized patients. Non-invasive imaging of the patient's brain has proven invaluable in this context, evolving dramatically since the 1970s when it was realized that computer processing of X-ray densitometry could create tomograms (slices) of any X-ray permeable object such as the human skull. This led to now-ubiquitous CT (computed tomography) scans; prior to their advent, the only way to image the brain was via pneumoencephalography, which required introducing air into the ventricles of the brain for an air-contrasted skull X-ray, and early nuclear brain scans.
The 1980s brought the next level of achievement in the form of magnetic resonance imaging (MRI), which offers better resolution and discrimination than CT, which often fails to distinguish grey and white matter regions. MRI has excellent discrimination since instead of densitometry it relies on recording RF emissions stimulated from protons resonating in a high magnetic field by carefully timed pulse sequences. The theoretical maximum resolution of MRI is 100 microns, sufficient to see individual neurons in some parts of the brain, and the technique has been optimized in modern machines to the point where a whole brain volume can be acquired in under 3 seconds.
However, CT and MR show only static images of the brain's structure. SPECT and PET scans map brain function using a radioisotope adaptation of the CT principle; PET has superior resolution than single-photon SPECT because it uses positron-emitting isotopes and looks for the dual photons emitted by positron-electron annihilations. These scans detect regional blood flow rates which correlate to activity of large neuron populations in the cerebral cortex. Recently, a rapid MRI technique termed functional MRI has demonstrated better spatial and temporal resolution by imaging blood flow patterns at 200 ms per slice, opening the door to direct observation of cognitive activities such as willed movements, reading, hearing, or speaking.
A mature medical nanotechnology can be envisioned which grows out of data provided by these techniques. Already there are CT- and MR-based systems which guide surgeons' instruments and help place neurostimulators to control Parkinson's disease and tremor. Non-invasive ablation of tumors by focused gamma rays is in use at a handful of centers, guided by MRI images. Given the existing ability to transform a composite structural-functional image to a standard coordinate system, it may be possible to devise motile nanodevices which take up addressable positions within the brain. Such devices could become visible on MRI by desequestration of paramagnetic gadolinium, communicating by varying their effective brightness on MRI, and respond like resonant protons to coded RF pulses. Critical applications of this technology would include delivering drugs and growth factors to specific locations, control of epileptic discharges, impression of sensory information directly into relevant cortex, which could open the way to a deeper understanding of how the brain functions in health and disease.
Stephen S. Flitman, MD
Director, Cognitive Neurology Section
Barrow Neurological Institute
350 West Thomas
Phoenix, Arizona 85013 USA