Reference: Rinck PA: Relaxation times blues. Hospimedica.
1991; 9,3: 16-20.
Reprinted
and updated several times, last printed version 2003. Translated into Italian,
Portuguese, Russian, German, and Chinese.
Key Words: Magnetic resonance; relaxation
times; tissue typing; normalcy; Raymond Damadian, fallacy.
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|  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 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 [3] 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 [6].
Later,
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 [5]. 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 tissue characterization.
The method, for which he gained a U.S. patent, was aimed at screening humans for
cancer cells. It was not an imaging method. 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 malignant cells within the human body, without even touching
the body. 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 invested
massively in public relations and even sponsored several books written about him
[2,4]. He had many opponents, not only because of his exuberant character and
unrestrained behavior at conferences but also because of his 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. However, this did not stop him continuing to propose his hypotheses. In
spite of Damadian's critics, 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 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. In
1985, it was realized that even carefully performed in vivo T2 measurements
cannot be used as a diagnostic method in cancer detection, characterization, or
typing [7]. 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 [8]. |
| |
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. Kleinfield S. A machine called indomitable.
New York: Times Books. 1985.
3. 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.
4. Mattson J, Simon M. The
pioneers of NMR and magnetic resonance in medicine. The story of MRI. Ramat Gan:
Bar-Ilan University Press. 1997.
5. 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.
6. Rinck PA, Bielke G, Meves M. Modified
spin-echo sequence in tumor diagnosis. Magn Reson Med 1984; 1: 237.
7. 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.
8.
Rinck PA, Appel B, Moens E. Relaxationszeitmessungender weissen und grauen Substanz
bei Patienten mit multipler Sklerose. Fortschr Röntgenstr 1987; 147: 661-663.
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March 1991
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