Sodium MRI shows arthritis long before onset of physical symptoms
9 February 2009
Dr Garry Gold, an associate professor of radiology at the Stanford
University School of Medicine has improved an old imaging technology
called sodium MRI to diagnose osteoarthritis as long as decades before
the onset of physical symptoms.
Gold is collecting young athletes who’ve suffered damage to the
anterior cruciate ligament, or ACL, in their knee — an injury afflicting
several hundred thousand people annually in the United States alone.
This knee insult is especially common among female athletes. “A good
fraction of the Stanford women’s basketball and soccer teams either have
torn their ACL sometime in the past or will tear it while they’re still
at Stanford,” Gold said.
Even when the initial ligament lesion is repaired surgically, victims
remain at almost doubled risk for symptomatic osteoarthritis in the
injured knee a decade or two down the road, compared with uninjured
Using the new imaging technology, Gold and colleagues have been able
to spot, soon after such an injury, telltale signs of cartilage
deterioration consistent with the development of osteoarthritis.
MRI now in routine use works by pulsing the area to be observed with
electromagnetic energy, at a frequency that preferentially excites the
protons in water molecules. As the protons settle back to a relaxed
state, they send out an electromagnetic burst of their own, which can be
picked up by sensors in the apparatus. Because cartilage has lots of
water compared with nearby bone, it shows up on a computer-generated
image of the region.
While standard MRI gives a reasonable display of overall cartilage
structure, it doesn’t tell a diagnostician much about the quality of
“If you look into a big house and you see that it’s standing up,”
Gold said, “you may assume it’s going to be safe in the event of an
earthquake. But without closer inspection, you don’t know much about the
integrity of the structure.”
If standard MRI is akin to a view of standing timber in the house,
the version Gold is using, called sodium MRI, enables the visualization
of dry rot infecting and weakening the wood.
A key structural material in cartilage, called glycosaminoglycan,
occurs in a complex with sodium, an elemental metal that has its own set
of excitation and relaxation frequencies and is more restricted to
cartilage than water is.
Sodium MRI has been around for years, but until recently it couldn’t
be used in clinical settings. For one thing, the magnets employed to
excite sodium atoms were too puny, making crisp resolution possible only
with tiny creatures such as mice. Gold and his colleague Brian
Hargreaves, PhD, assistant professor of radiology at Stanford, have
designed improved magnets and software to scale up the technology for
"They’re on the right track," said Ari Borthakur, a University of
Pennsylvania scientist who is not involved in Gold’s research but has
done pioneering work with sodium MRI since writing his PhD thesis on it
some years ago. “Everything his lab has developed is going to be
applicable in the clinics,” said Borthakur. “As America ages, we’re
expecting to see a huge increase in osteoarthritis, and any technique
that could be used for its early diagnosis, or that could help
developing therapies for curing it, or even slowing the progression of
cartilage loss, would be tremendous.”
Gold and Hargreaves’ project is being conducted with funding from the
National Institutes of Health and GlaxoSmithKline, an international
pharmaceutical company. Neither researcher owns stock in, or receives
consulting fees from, the company.
Working with Hargreaves, Gold has imaged the knees of about a dozen
volunteers who have suffered a recent ACL injury. In every case so far,
significant losses of glycosaminoglycan can be glimpsed under sodium MRI
scanning, despite the absence of any sign of damage to cartilage
observed with standard MRI.
Almost invariably, sodium MRI scans of the injured knee — but not of
the other, uninjured one — reveal glycosaminoglycan deficits within
three years of the injury, potentially enabling a vastly accelerated
This ought to speed the development of new therapies, and radically
lower the cost of doing so, Gold said. The idea is to be able to use
glycosaminoglycan loss as a “surrogate marker” of impending
osteoarthritis, much as high LDL levels are used to flag people at risk
of heart disease — perhaps years before actual symptoms of heart disease
While not everybody with elevated LDL develops cardiovascular
disease, this marker has been sufficiently predictive of that condition
that regulatory authorities routinely approve drugs based on their
ability to lower LDL.
Catching osteoarthritis during its stealth phase may spur clinical
trials that would be prohibitively time-consuming and costly if standard
MRI were employed, because of the huge lag from the time of an ACL
injury until the time cartilage deterioration can be detected by that
With sodium MRI, cohorts of treated vs. untreated at-risk patients
could be imaged over time to see if, within a few years of the injury, a
drug or a lifestyle change is reducing or arresting the loss of
glycosaminoglycan from the ligament. Once promising drugs or lifestyle
changes are identified, they could then be administered to at-risk
patients long before symptoms surface, Gold said.
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