Picture it: why researchers need better imaging techniques.
magnetic resonance imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures. (MRI 1. (application) MRI - Magnetic Resonance Imaging.
2. MRI - Measurement Requirements and Interface. ) has made it possible to visualize and understand much about the underlying pathology of the disease.
But lesions (areas of tissue damage) seen using conventional MRI techniques do not necessarily correlate with clinical relapses or disease progression. Advanced technologies now exist that may eventually help to pinpoint early disease markers, clarify areas of damage, or predict disease course. If we are to truly demystify de·mys·ti·fy
tr.v. de·mys·ti·fied, de·mys·ti·fy·ing, de·mys·ti·fies
To make less mysterious; clarify: an autobiography that demystified the career of an eminent physician. the unpredictable nature of MS, we need to capture a much clearer picture of this disease.
This need is a particularly crucial issue in MS research today. It's an exciting time, in which we are finding new therapeutic targets by the dozen. Innovative strategies such as transplanting myelin-making cells are within our reach in terms of animal models and early clinical trials. But all this means nothing if we cannot picture whether these strategies are working or not. We need to develop noninvasive imaging methods, for example, that can track cells to sites of damage, watch if repair occurs, and determine if repair is occurring for myelin myelin /my·elin/ (mi´e-lin) the lipid-rich substance of the cell membrane of Schwann cells that coils to form the myelin sheath surrounding the axon of myelinated nerve fibers. , for axons, or for both.
What's in the imaging pipeline?
Here's a brief roundup of technologies under study for their usefulness in measuring MS-related damage and therapeutic success:
* OCT OCT ornithine carbamoyltransferase; oxytocin challenge test.
ornithine carbamoyl transferase, a liver specific enzyme.
OCT Oxytocin stress test, see there (optical coherence tomography Optical coherence tomography (OCT) is an interferometric, non-invasive optical tomographic imaging technique offering millimeter penetration (approximately 2-3 mm in tissue) with micrometer-scale axial and lateral resolution. ): a tool that is relatively easy to use and that utilizes infrared light to measure the thickness of the nerve fiber layer The nerve fiber layer (or layer of nerve fibers or stratum opticum) is formed by the expansion of the fibers of the optic nerve; it is thickest near the porus opticus, gradually diminishing toward the ora serrata. of the retina in the back of the eye, and its connection to the optic nerve. Studies are beginning to suggest a role for OCT in assessing nerve fiber damage and in evaluating the success of neuroprotective therapies.
* DTI Diffusion tensor imaging (DTI)
A refinement of magnetic resonance imaging that allows the doctor to measure the flow of water and track the pathways of white matter in the brain. (diffusion transfer imaging): this method measures the random flow of water in tissues. In the brain, the normal direction of flow tends to be parallel to the nerve fiber tracts. The rate of diffusion and direction of flow are altered by destruction of myelin and axons.
* MRS MRS - Modifiable Representation System.
An integration of logic programming into Lisp.
["A Modifiable Representation System", M. Genesereth et al, HPP 80-22, CS Dept Stanford U 1980]. (magnetic resonance spectroscopy): this technique uses MRI to analyze the chemical components of brain tissue and creates a graphic display showing the amount of each molecule detected. One molecule of interest is NAA NAA
Nomina Anatomica Avium. (N-acetyl-aspartate), which is found largely in nerve fibers. Low levels of NAA reflect axonal axonal
pertaining to or arising from an axon.
an axon dies and cannot be replaced if its cell body is destroyed. damage in the brain.
* fMRI (functional MRI): This technique measures small metabolic changes in the brain related to the flow of blood and oxygen to specific parts of the brain. Whereas the methods discussed above evaluate various aspects of the structure of the nervous system, fMRI evaluates functional activity of various parts of the nervous system.
* PET (positron emission tomography positron emission tomography: see PET scan.
positron emission tomography (PET)
Imaging technique used in diagnosis and biomedical research. ): PET utilizes small amounts of radioactive tracers to evaluate the functional activity and structural aspects of various parts of the nervous system. It may ultimately be useful for visualizing myelin and cells within the nervous system. There are still a few hurdles to overcome, such as finding the best tracer molecules for identifying specific cells within the brain.
How the Society is moving imaging along
The National MS Society is funding 34 grants that are investigating how to measure MS disease activity, for a multiyear total of nearly $10 million. These grants include research that spans many imaging technologies, patient populations, and symptoms. Here are just two examples:
* Advanced imaging techniques are crucial to tracking MS in children, especially during the course of clinical trials of medications to help this population. Amy T. Waldman, MD (Hospital of the University of Pennsylvania (body, education) University of Pennsylvania - The home of ENIAC and Machiavelli.
Address: Philadelphia, PA, USA. , Philadelphia) reported at last year's World Congress of MS Research that OCT is feasible in children with MS aged 5 years and older, and that retinal nerve fiber thickness differs between children with and without MS. (Her work was funded by the Society's Greater Delaware Valley Chapter.)
* Providing clinicians with an accurate assessment tool for cognitive dysfunction in MS may lead to earlier diagnosis and more focused therapies that treat underlying cognitive problems. In a project supported by the Brodsky Family Foundation, Susan M. Courtney, PhD (Johns Hopkins University Johns Hopkins University, mainly at Baltimore, Md. Johns Hopkins in 1867 had a group of his associates incorporated as the trustees of a university and a hospital, endowing each with $3.5 million. Daniel C. , Baltimore) used fMRI scans to measure tissue injury in the pathways that allow brain regions involved in cognitive function to communicate with each other. Her results, reported at an imaging meeting in 2008, indicate that different aspects of cognitive performance correlated with MS-related damage in different brain areas.
As a driving force of MS research, we do not just fund investigations, but we help guide the field. With this in mind, the Society convened a workshop in August 2008 to discuss noninvasive methods for detecting and measuring nervous system protection and repair in people with MS, under the auspices of our International Advisory Committee on Clinical Trials. Co-chaired by Frederik Barkhof, MD, PhD (VU Medical Centre, Amsterdam) and Peter Calabresi, MD (Johns Hopkins University, Baltimore), 50 participants from North America and Europe met for three days to grapple with to enter into contest with, resolutely and courageously.
See also: Grapple key questions about where we are now and where we need to go in terms of applying emerging technologies to clinical trials of repair and protection therapies.
The group is publishing a paper based on this meeting, which will include recommendations on the imaging outcomes that should be used in studies of neuroprotective or nerve repair strategies, and on studies that need to be done to validate these imaging outcomes.
Imaging technology is truly a cutting edge of MS research, and we must bring these techniques to bear in our efforts to erase MS.
by John R. Richert, MD
Dr. John Richert is executive vice president for the Society's Research & Clinical Programs.