The slow life of clinical spectroscopy
agnetic resonance imaging has taken off like a rocket and become the diagnostic runner of the last twenty years, but MR spectroscopy has stayed in the back rooms of the researchers. There are two main reasons for this development: there are not many clinical applications for MR spectroscopy, and there is no reimbursement for such examinations in most countries. This makes the method unattractive for physicians, hospitals, and in particular for private practices.
One of the first papers on medical MR spectroscopy applications was published in the New England Journal of Medicine in 1981 by Ross and his collaborators. They described spectroscopic changes of phosphorus in McArdle's syndrome .
McArdle's syndrome is not a major global disease, nor are other muscular diseases in which MR spectroscopy has shown changes of phosphorus or proton spectra.
Thus, it is understandable that both the clinical users and the manufacturers of MR machines have reduced or even ceased to use whole-body MR spectroscopy machines. In 1990, a spokesman for one of the major manufacturers of whole-body MRI/MRS equipment stated that there are no clinically efficient applications for MR spectroscopy. Therefore, his company and other producers of high-field equipment have limited their investments in whole-body MR machines below 2 Tesla although in recent years some higher field machines have reached the market.
However, this trend is not reflected by the research output – MR spectroscopy research is thriving. In 1982, at the first meeting of the Society of Magnetic Resonance in Medicine in Boston only two papers dealt with MRS. In 1983 less than 100 papers were published about MRS, in 1991 MedLine counted 500, and in 1999 700 publications. As well as there being more papers, there was also an increase in complexity.
The following statement is typical of many articles dealing with MR spectroscopy and its applications:
“It is hoped that the new information provided by (in this case) multidimensional spectroscopic imaging of metabolites in vivo will further enhance the clinical and scientific value of this technology .”
The overwhelming majority of publications about MRS either focus on anecdotal clinical cases, in which some changes in spectra were (or were not) seen, or they discuss improvements of MRS technology. It is always 'hoped' that one day MRS will enhance the horizons of medicine.
MR spectroscopists sometimes claim that whole-body MRS is not accepted by clinicians because the latter cannot read and interpret the spectra. They postulate that:
“The arrogance of the ignorants hinders the development of spectroscopy.”
This might be partly true because radiologists are not trained in biochemistry or in reading and recalculating spectra.
However, the ball is played back into the spectroscopists' court by the physicians. The latter underline that spectroscopists, with a background in chemistry or physics, have no idea of the possible medical relevance of spectra and are, by and large, only interested in playing scientific games. They also claim that spectroscopists create a sea of irrelevant data in which potentially useful information is drowned.
Another important argument is that spectroscopy is insensitive. Phosphorus spectroscopy is sometimes dubbed 'the Twin Peaks of MR', although in reality there are three main peaks in in vivo phosphorus spectra.
The technique of phosphorus spectroscopy suffers because of the large volumes (50-100 ccm) that are necessary to acquire decent spectra within the time period a patient can remain motionless in the magnet. However, tissue volumes of 50-100 ccm are of no relevance to clinical diagnosis. When examining brain tumors, an MRS examination volume usually includes vital tumor tissue, the necrotic tumor center, edema, perhaps hemorrhage, and also normal non-involved tissue. This type of volume is too inhomogeneous to clarify or even grade such a tumor. Follow-up examinations may reveal whether a tumor responds to therapy, but even this is doubtful.
However, proton spectroscopy has a greater sensitivity and possesses a wider range of metabolic information than phosphorus MRS. It saves between a half and two-thirds of the time necessary to acquire a similar phosphorus spectrum at 1.5 T.
Spectroscopic data usually require spectral analysis to indicate the metabolite concentration, ratios, and tissue pH. These data give a momentary picture of macroscopic local metabolism and the distribution of metabolites. To date, both time and space resolution are restricting factors of MRS, and therefore MRS examinations cannot compete directly with single photon emission computed tomography (SPECT) or positron emission tomography (PET). However, MRI can now begin to compete with these radioisotope technologies.
It is also possible to convert the spectroscopic result into metabolic maps. Thus, images can be created that reflect the concentrations of certain metabolites on an anatomical background.
Maps of phosphates or other metabolites can deliver spectroscopic information as pictures that can be more easily understood by radiologists. Proton spectra might become the solution for creating such maps because numerous metabolites such as creatine, choline, and lactate can be depicted.
The interpretation of such maps still requires considerable knowledge of diagnostic biochemistry. Because today's radiologists are not trained in this field, this is a job for skilled spectroscopists. Worldwide, there are few scientists with such knowledge, and training is limited because of financial restrictions.
The question remains as to how MRS can be accepted by clinicians using whole-body MR machines.
First, relevant clinical and diagnostic applications have to be found. These applications must be better than competing techniques, and if possible, the MRS examinations must become faster and cheaper than comparable diagnostic methods. In addition, for its implementation in clinical routine, there should be a therapy for the patient's disease. MRS must be able to exclude certain differential diagnoses better than other diagnostic techniques, and/or MRS must be superior to other diagnostic methods in the follow-up period.
Second, MR spectroscopy must be easy-to-use and accepted by radiologists, otherwise it will stay a research tool.
On the other hand, there is no doubt that MRS has already contributed greatly to the furtherance of medical knowledge and the understanding of certain aspects of human physiology and pathophysiology. MRS examinations of muscle metabolism, tumors, tissue damage caused by ischemia and infarction, and transplant rejection have added to the understanding of these diseases.
Still, to date, most examinations have not proved useful for daily medical routine. And, what makes it even more difficult for medical spectroscopy, functional and dynamic magnetic resonance imaging have become possible during the last few years. Functional imaging allows users to depict some of the working mechanisms in the body such as the response of the visual cortex of the brain upon light, enabling almost direct assessment of neuronal function.
However, unrelated events can influence and boost medical techniques – such as diseases of presidents or monarchs or wars. MR spectroscopy of the brain, for instance, hit the frontpages of newspapers when a research group was able to show brain abnormalities in veteran military personnel after the Gulf War .
1. Bottomley PA, Charles HC, Roemer PB, Flamig D, Engeseth H, Edelstein WA, Mueller OM. Human in vivo phosphate metabolite imaging with 31P NMR. Magn Reson Med 1988; 7: 319-336.
2. Haley RW, Marshall WW, McDonald GG, Daugherty MA, Petty F, Fleckenstein JL. Brain abnormalities in Gulf War syndrome: evaluation with MR spectroscopy. Radiology 2000; 215: 807-817.
3. Ross BD, Radda GK, Gadian DG, Rocker G, Esiri M, Falconer-Smith J. Examination of a case of suspected McArdle’s syndrome by 31-P nuclear magnetic resonance. N Engl J Med 1981; 304: 1338-1342.