Relaxation times blues

Rinckside 1991; 2,1: 5-7.

utstanding soft-tissue contrast is among the main characteristics of MR imaging that have enabled the technology to be developed so rapidly. This contrast is basically the result of the relaxation phenomena, T1 and T2.

Following the impulse a proton is given by a radiofrequency burst, the process of returning to a state of equilibrium from an excited state is called the longitudinal or spin-lattice relaxation process. It is characterized by the T1 relaxation time, which commonly lies in the range of several hundred milliseconds. The T2 relaxation time characterizes the dephasing of the spins (i.e., the separation of neighboring spins from each other), and therefore it is called the spin-spin or the transverse relaxation process. T2 times of tissues are much shorter than T1 times.

For example, at a magnetic-field strength of 0.5 T, human kidney tissue has a T1 relaxation time of approximately 500 ms and a T2 relaxation time of approximately 80 ms. Although other factors contribute to contrast on an MR image, the three dominant factors are T1 and T2 times and proton density, the latter reflecting the water content.

   Peter Mansfield of the University of Nottingham stated in 1980 [5] that

“NMR imaging of anatomical detail is feasible based purely on the measurement of water content.”

He was wrong; however, he also pointed out that images could reflect a combination of water content and relaxation times.

Proton density does not change much between different tissues. For instance, its difference between gray and white brain matter in an adult is approximately 10%, and the difference between brain pathologies and surrounding uninvolved brain tissue may be even less. Thus, proton density or water-content imaging of the human body is not particularly useful.

Today, magnetic resonance pictures dubbed as proton density-weighted images always depict a combination of water content and the two relaxation times; nobody uses pure water-content pictures for medical diagnostics. Usually, T1- or T2-weighted images are acquired in MR imaging because the two main relaxation processes govern the contrast in medical MR imaging.

   Tumors, as well as other brain pathologies such as multiple sclerosis (MS) or brain infarctions, are barely visible on water-content images. This was demonstrated in the early days of MR imaging when, in a number of cases, already known brain lesions could not be discovered.

The introduction of T2-weighted spin-echo pulse sequences changed this. On these images, many pathologies are seen easily. The importance of T2- influenced pictures was demonstrated at a magnetic resonance conference in San Francisco in 1983 [9]. Soon afterwards, all manufacturers started offering this feature with their machines, and now it is part of any MR examination.

   The use of relaxation times for medical applications was introduced in 1955/1956 by Erik Odeblad and Gunnar Lindström [7,8]. Since then, this idea has occupied the minds of many researchers because the ultimate goals of diagnostic medicine are noninvasive tissue characterization and the external identification of cell structures within the human body, without even touching the body.

In 1974 Raymond Damadian and his collaborators attempted and patented a method for relaxation time measurements in malignant diseases [1]. At that time, Damadian was a medical doctor at the State University of New York at Brooklyn.

Originally, he did not intend to use the relaxation times for imaging but for malignant tissue characterization. The method, for which he gained a U.S. patent, was aimed at screening humans for cancer cells. He had to retract his assertion that he could non-invasively diagnose cancer tissue during a press conference in 1977. It didn't work — and was not an imaging method as he claimed later.

Damadian's claim that relaxation-time changes highlight cancer cells seemed to be the pivotal step in medical progress. Thus, it is understandable that relaxation has been described as the Holy Grail of magnetic resonance — one of the many Holy Grails.

Damadian was a colorful and controversial figure in magnetic resonance circles. He had antagonistic and cynical articles written about him in all major US newspapers, mostly because he was more of his time businessman than medical doctor. However, he didn't bother because — as the Wall Street Journal finally pointed out — "Raymond Damadian is, according to an old friend, 'the most egotistical person I've ever met [4]." His friend and other people who know him certainly agree — egotism is a severely unpleasant and injurious personal trait.

Damadian invested massively in public relations and sponsored several books written about him [3,6] — even, as painful as it sounds, a children's book [2]. He had many opponents, not only because of his exuberant character and unrestrained behavior at conferences but also because of his (un-) scientific publications. Immediately after his first publication, his opponents showed that his claims were only founded on particular cases and not on any specific disease; his claim was a fallacy — further details about relaxation times can be found here. However, this did not stop him continuing to propose his hypotheses.

In spite of Damadian's critics and his deceit, nobody can deny that his description of relaxation-time changes in cancer tissue was one of the main motivations for the introduction of magnetic resonance into medicine. His assertion that this method can detect cancer has proved to be partly true, but in a completely different way: MR imaging with pictures influenced by relaxation times has become one of the main medical technologies applied in cancer diagnosis and follow-up.

   However, the basic idea of obviating the need for hospital pathology departments and replacing them with MR imaging did not materialize.

In vivo relaxation time measurements based on MR imaging have been tried out over the years by a large number of people, who have used relaxation-time values for tissue characterization in the brain, body, muscles, and bones. The task proved to be in vain because all efforts to characterize or even type tissue largely failed.

The reasons are manifold and include systematic measurement errors, inaccuracy of two-point plotting methods of relaxation curves, inherent variability of tissue composition, partial volume effects, and interobserver variability. Researchers realized that it is futile to measure a point or a region of interest within a tumor because too many different components such as tumor and necrotic cells, small vessels, calcifications, and other structures can be found within a volume of interest. In addition, T1 and T2 values overlap with those of other pathologies and sometimes normal tissue: T1 and T2 of normal tissue change with age and hormonal cycles, breast tissue being a good example.

Already several months after Damadian's publication, Donald P. Hollis and his collaborators showed that the T1 relaxation times of tumors are not necessarily longer than those of other diseased or normal tissues [10, 11]. In 1985, it was realized that even very carefully performed in vivo T2 measurements cannot be used as a diagnostic method in cancer detection, characterization, or typing [12].

After absolute T1 or T2 values had been used unsuccessfully by researchers, combinations of T1 and T2, histogram techniques, and more sophisticated 3-D display techniques of factor representations were applied. However, the heterogeneity of normal tissues as well as of pathological benign and malignant tissues did not allow the pathologist's view through the microscope to be replaced with MR techniques.

Damadian also claimed that T1 values of tumorous tissue are always higher than those of normal tissue. His dream of MR being the perfect screening method for cancer tissue in the human body was finally shattered when this claim was refuted. T1 values depend on the magnetic field strength (i.e., they increase with the magnetic field). Some tumor values can be lower than the values of normal tissue in certain fields while others are the same in certain fields, and therefore they cannot be distinguished.

Every year, the literature reports new attempts to change the relaxation-times blues into something more swinging. There are some positive stories about the successful use of relaxation-time measurements in vivo.

Among the many studies is the measurement of apparently uninvolved white brain matter in MS patients. MS plaques in the brain have longer T2 relaxation times than surrounding tissue, which enables them to be visualized on T2-weighted spin-echo images. However, the inconspicuous-looking white matter in the rest of the brain is also changed by the disease. Relaxation-time measurements revealed longer T2 values than in normal subjects. This is not enough to diagnose MS, but it might be of use in follow-up therapy or in helping with the differential diagnosis [13].

Since I am the first author of the latter paper I am allowed to say: I wouldn't rely on such measurements if I were the patient.

References

1. Damadian R. Tumor detection by nuclear magnetic resonance. Science 1971; 171: 1151-1153; and Damadian R, Zaner K, Hor D, Dimaio T. Human tumors by NMR. Physiol Chem and Physics 1973; 5: 381-402.
2. Kjelle, Marylou M. Raymond Damadian and the Development of MRI. Hockessin, Delaware, U.S.A.: Mitchell Lane Publishers. 2004.
3. Kleinfield S. A machine called Indomitable. New York: Times Books. 1985.
4. Landers P. Nobel award now a prize fight. The Wall Street Journal. 13 October 2003.
5. Mansfield P, Morris PG, Ordidge RJ, Pykett IL, Bangert V, Coupland RE. Human whole body imaging and detection of breast tumours by NMR. Phil Trans R Soc Lond 1980; B289: 503-510.
6. Mattson J, Simon M. The pioneers of NMR and magnetic resonance in medicine. The story of MRI. Ramat Gan: Bar-Ilan University Press. 1997.
7. Odeblad E, Bhar BN, Lindström G. Proton magnetic resonance of human red blood cells in heavy water exchange experiments. Arch Biochem Biophys 1956; 63: 221-225.
8. Rinck PA. Europe celebrates the forgotten pioneer of MRI — Dr. Erik Odeblad. Rinckside 2012; 23,6: 11-12.
9. Rinck PA, Bielke G, Meves M. Modified spin-echo sequence in tumor diagnosis. Magn Reson Med 1984; 1: 237.
10. Hollis DP, Saryan LA, Morris HP. A nuclear magnetic resonance study of water in two Morris hepatomas. Johns Hopkins Med J. 1972; 131(6): 441-444.
11. Hollis DP, Economou JS, Parks LC, Eggleston JC, Saryan LA, Czeisler JL. Nuclear magnetic resonance studies of several experimental and human malignant tumors. Cancer Research 1973; 33: 2156-2160.
12. Rinck PA, Meindl S, Higer HP, Bieler EU, Pfannenstiel P. MR imaging of brain tumors: discrimination and attempt of typing by CPMG sequences and in vivo T2 measurements. Radiology 1985; 157: 103-106.
13. Rinck PA, Appel B, Moens E. Relaxationszeitmessungen der weissen und grauen Substanz bei Patienten mit multipler Sklerose. Fortschr Röntgenstr 1987; 147: 661-663.

A short history of MRI can be downloaded free of charge from here.

Citation: Rinck PA. Relaxation times blues. Rinckside 1991; 2,1: 5-7.

A digest version of this column was published as:
Relaxation times blues.
Hospimedica. 1991; 9,3: 16-20.

Reprinted and updated several times.
Latest updated print version: Rinck PA. Relaxation times blues. in: Rinck PA. Magnetic Resonance in Medicine. A Critical Introduction. 12th ed. BoD, Norderstedt, Germany. 2018|2020. ISBN 978-3-7460-9518-9. pp. 97-101.

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