Magnetic resonance is an exceptionally powerful and versatile measurement technique. The basic structure of a magnetic resonance experiment has remained largely unchanged for almost 50 years, being mainly restricted to the qualitative probing of only a limited set of the properties that can in principle be accessed by this technique. Here we introduce an approach to data acquisition, post-processing and visualization—which we term ‘magnetic resonance fingerprinting’ (MRF)—that permits the simultaneous non-invasive quantification of multiple important properties of a material or tissue. MRF thus provides an alternative way to quantitatively detect and analyse complex changes that can represent physical alterations of a substance or early indicators of disease. MRF can also be used to identify the presence of a specific target material or tissue, which will increase the sensitivity, specificity and speed of a magnetic resonance study, and potentially lead to new diagnostic testing methodologies. When paired with an appropriate pattern-recognition algorithm, MRF inherently suppresses measurement errors and can thus improve measurement accuracy. A new approach to magnetic resonance, ‘magnetic resonance fingerprinting', is reported, which combines a data acquisition scheme with a pattern-recognition algorithm that looks for the ‘fingerprints’ of interest within the data. Although nuclear magnetic resonance is a powerful analytical tool for many scientific and medical disciplines, usually only a fraction of its potential power is harnessed. Most implementations are qualitative, and restricted in the range of properties that are probed. Dan Ma and colleagues introduce a new approach — termed magnetic resonance fingerprinting — aimed at greatly enhancing the amount of quantitative information that can be obtained in one measurement. Their approach combines a data-acquisition scheme that is indiscriminate in the material properties that it probes with pattern-recognition algorithms that look for the 'fingerprints' of interest within the data. Magnetic resonance fingerprinting has the potential to detect and analyse early indicators of disease or complex changes in materials, as well as increasing the sensitivity, specificity and speed of magnetic resonance studies.

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Magnetic resonance fingerprinting

We exploit the intrinsic difference in magnetic resonance spin-spin relaxation time, T2, between water associated with myelin sheaths and water in other central nervous system tissue in order to measure myelin water content within any region of an image or to generate indirectly a myelin map of the brain. In normal volunteers, myelin water maps give the expected myelin distribution. In multiple sclerosis patients, lesions exhibit different myelin water contents providing insight into the demyelination process unavailable from conventional magnetic resonance images. In vivo myelin measurement has important applications in the clinical management of multiple sclerosis and other white matter diseases.

In vivo visualization of myelin water in brain by magnetic resonance

Relaxation time measurements at 3.0 T are reported for both gray and white matter in normal human brain. Measurements were made using a 3.0 T Bruker Biospec magnetic resonance imaging (MRI) scanner in normal adults with no clinical evidence of neurological disease. Nineteen subjects, 8 female and 11 male, were studied for T1 and T2 measurements, and 7 males were studied for T2. Measurements were made using a saturation recovery method for T1, a multiple spin-echo experiment for T2, and a fast low-angle shot (FLASH) sequence with 14 different echo times for T2. Results of the measurements are summarized as follows. Average T1 values measured for gray matter and white matter were 1331 and 832 msec, respectively. Average T2 values measured for gray matter and white matter were 80 and 110 msec, respectively. The average T2 values for occipital and frontal gray matter were 41.6 and 51.8 msec, respectively. Average T2 values for occipital and frontal white matter were 48.4 and 44.7 msec, respectively. ANOVA tests of the measurements revealed that for both gray and white matter there were no significant differences in T1 from one location in the brain to another. T2 in occipital gray matter was significantly higher (0.0001 < P < .0375) than the rest of the gray matter, while T2 in frontal white matter was significantly lower (P < 0.0001). Statistical analysis of cerebral hemispheric differences in relaxation time measurements showed no significant differences in T1 values from the left hemisphere compared with the right, except in insular gray matter, where this difference was significant at P = 0.0320. No significant difference in T2 values existed between the left and right cerebral hemispheres. Significant differences were apparent between male and female relaxation time measurements in brain.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291522-2586%28199904%299%3A4%3C531%3A%3AAID-JMRI4%3E3.0.CO%3B2-L

NMR relaxation times in the human brain at 3.0 tesla.

Using a 32-echo imaging pulse sequence, T2 relaxation decay curves were acquired from five white- and six gray-matter brain structures outlined in 12 normal volunteers. The water contents of white and gray matter were 0.71 (0.01) and 0.83 (0.03) g/ml, respectively. All white-matter structures had significantly higher myelin water percentages (signal percentage with T2 between 10 and 50 ms) than all gray-matter structures. The range in geometric mean T2 of the main peak for both white and gray matter was from 70 to 86 ms. T2 distributions from the posterior internal capsules and splenium of the corpus callosum were significantly wider (width is related to water environment inhomogeneity) than those from any other white- or gray-matter structures. Thus, quantitative measurement and analysis of T2 relaxation reveals differences in brain tissue water environments not discernible on conventional MR images. These differences may make short T2 components reliable markers for normal myelin.

In vivo measurement of T2 distributions and water contents in normal human brain

Magnetic resonance (MR) techniques have had a major impact in the last 10-15 years in understanding and managing multiple sclerosis. This review summarizes the current uses of MR in multiple sclerosis, based on the proceedings of a recent international workshop, under four headings: (i) technical issues; (ii) role in diagnosis; (iii) natural history studies in understanding the disease; (iv) application in clinical trials. The theory and methodology of relevant technical issues is outlined, in order to provide a framework with which to understand the potential and limitations of MR in addressing biological and clinical questions in multiple sclerosis. The principles underlying signal-to-noise and contrast-to-noise ratio are discussed, along with the techniques and clinical results for conventional and fast spin echo T2-weighted imaging, fluid-attenuated inversion recovery, detection of blood-brain barrier break down and hypointense lesions on T1-weighted images, magnetization transfer, T2 decay-curve analysis, MR spectroscopy, spinal cord imaging, diffusion imaging, and quantification of lesion load and atrophy. MRI has an extremely valuable role in confirming the clinical diagnosis of multiple sclerosis. T2-weighted brain imaging remains the standard diagnostic tool, but in some instances it is usefully complemented with gadolinium enhancement and spinal imaging. The caveat that the diagnosis of multiple sclerosis remains primarily a clinical one cannot be over-emphasized. Serial MRI studies have added much to our understanding of the natural history and pathophysiology of the disease. Blood-brain barrier breakdown is a consistent early feature of new lesion development in relapsing-remitting and secondary progressive multiple, sclerosis, and this usually correlates with active inflammation and myelin breakdown. A number of the acute MR changes are reversible, but chronic persistent abnormalities in a number of MR parameters, such as reduced N-acetyl aspartate, low magnetization transfer ratios, atrophy and T1-hypointensity, suggest the presence of demyelination and/or axonal degeneration in many chronic lesions. The presence and extent of T2-weighted MRI abnormalities at first presentation with a clinically isolated syndrome suggestive of demyelination strongly predicts the risk of developing clinically definite multiple sclerosis in the next few years. In established multiple sclerosis, however, the correlations between T2 abnormalities and disability are modest. This poor relationship partly relates to the discrepancy between lesion site and function in attempting to correlate locomotor disability with brain MRI findings. However, the correlations between brain lesion load and cognitive dysfunction in multiple sclerosis, whilst more evident, are still modest. A more important limitation is the low pathological specificity of abnormalities seen on T2-weighted images. Stronger correlations have been found between disability and new putative MR markers for demyelination and/or axonal degeneration. Serial studies using multiple MR techniques are now needed to further clarify pathophysiological mechanisms in multiple sclerosis. Serial MR has become an important tool in monitoring treatment efficacy. It provides data which can be readily analysed in a blinded fashion and which directly inspects the pathological evolution; it also enables a rapid and sensitive measure of treatment outcome in early relapsing-remitting and secondary progressive disease. Because of the modest clinical correlations it is, however, still appropriate that the definitive determinant of treatment efficacy remains a clinical one. Further work is needed to address issues of quality control in serial studies, statistical calculation of appropriate sample sizes, and optimization of the nature and frequency of MR outcomes measured.

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The role of magnetic resonance techniques in understanding and managing multiple sclerosis

Many studies have investigated the use of magnetic resonance relaxation times for tissue characterization. A number have been performed in vivo with clinical whole-body imagers. Unfortunately, the results have yet to establish the role of quantitative tissue relaxation time measurements in clinical diagnosis. One of the major problems is that the techniques used in many of these studies are error prone, making the results inconclusive. In the present study, the problems associated with clinical T2 measurements were systematically evaluated in an attempt to obtain reliable in vivo quantitation. The authors demonstrate that spoiler gradients are the most effective technique for artifact suppression but that they render ineffective radio-frequency phase schemes such as the Meiboom-Gill modification to the Carr-Purcell sequence to compensate experimental imperfections. The present study results in a more reliable multi-echo sequence for T2 measurement. Preliminary clinical results in brain and cervix demonstrate the performance of the new technique.

Colin S. Poon

Papers

Practical T2 quantitation for clinical applications

Fat/water quantitation and differential relaxation time measurement using chemical shift imaging technique.