National Physical Laboratory

Development of Magnetic Resonance Spectroscopy thermometry standards

Magnetic Resonance Spectroscopy (MRS) is a specialist, non-invasive technique in medicine for observing and characterising body tissue. There is a variety of ways that MRI spectroscopy can be used, for example in determining the internal temperature of parts of the body.

Figure 1: MRS thermometry temperature standard
Figure 1: MRS thermometry temperature
standard

Proton resonance frequency in water molecules shifts with the temperature and this has been recently investigated with reference to a particular metabolite in the body (n-acetyl aspartate, in the brain). Currently, the method of MRS thermometry is in the research phase and the results are promising. However, given that clinical decisions in the future may be made on these measurements, it is very important to relate the measured frequency shift with a reliable (i.e. traceable) temperature.

Temperature reference phantoms

NPL conceived the idea of designing an artefact to provide a reliable reference, against which MRS thermometry measurements could be validated, and has now been working for a number of years to develop temperature reference phantoms (artefacts that imitate fixed, and known, conditions) suitable for use in high magnetic fields. A typical artefact, to NPL's design, is shown in Figure 1. There are two types: those with a fixed reference temperature (based on organic reference materials such as di-phenol ether (26.3 °C) or ethylene carbonate (36.3 °C)) and those with a variable temperature (which operate from about 20 °C to 50 °C).

Method

Figure 2: MRS fixed point phantom in frozen state
Figure 2: MRS fixed point phantom in
frozen state

The artefacts are used as follows to introduce temperature traceability into MRS thermometry. Figure 1 shows an artefact which is used as a fixed-temperature phantom:

  • Into the inner vessel, a solution of the metabolite is introduced. The concentration can be varied to span the natural variation of the metabolite in the body.
  • Into the outer vessel, the reference material is introduced.
  • To begin, the artefact is heated; upon complete melting of both the reference material and metabolite solution, then cooling is used to initiate the freezing transition in the reference material (the frozen state is shown in Figure 2).

As the metabolite solution is almost completely surrounded by the reference material - which is passing through its freezing transition, and therefore is at the fixed, and known, freezing temperature - the metabolite solution rapidly reaches the freezing temperature of the reference material. The artefact is then introduced into the MRI scanner (whilst the reference material is still in the freezing transition), and a scan taken through the artefact. The central region, where the metabolite solution is located, is still at the temperature of the fixed reference point allowing precise calibration of the differential frequency between water and the metabolite.

In the case of the variable-temperature phantom, the temperature of the metabolite is measured with a calibrated fibre-optic thermometer which is compatible with MRI scanners and allows simultaneous measurement of the temperature with each scan taken. Several temperature points over a range may be attained in sequence, but with a somewhat higher uncertainty than with the fixed-point phantom. This variable-temperature artefact allows a complete calibration curve of frequency shift with temperature, for a particular metabolite concentration, to be determined.

Current and future activity

NPL provided artefacts, and training, such that proof-of-concept studies could be performed in the 1.5 T MRI scanner at the University of Manchester (Imaging Science and Brain Injury Research Group). Typical results of this work are shown in Figures 3 and 4:

Figure 3: Preliminary ITS -90 traceable calibration curve for MRS thermometry (x -axis temperature in °C; y -axis resonance frequency shift in Hz [ppm]) with n -acetyl aspartate of differing concentrations
Figure 3: Preliminary ITS -90 traceable calibration curve for MRS thermometry (x -axis temperature in °C; y -axis resonance frequency shift in Hz [ppm]) with n -acetyl aspartate of differing concentrations

 

Figure 4: A fixed-point phantom freezing plateau, measured with a contact sensor
Figure 4: A fixed-point phantom freezing plateau, measured with a contact sensor. As soon as the freeze process has begun, the phantom is ready to be placed into the MRI scanner, and ensures that the metabolite solution is kept at the known known temperature for more than four hours.


This work is being followed by more extensive studies (currently under way), with a different metabolite, in a 3 T MRI scanner at the School of Cancer Sciences, University of Birmingham.

More details on the work can be found in these publications:

  • Babourina-Brooks, B., Simpson, R., Arvanitis, T.N., Machin, G., Peet, A.C. and Davies, N.P., 'MRS thermometry calibration: Effects of protein, Ionic concentration and magnetic field strength', DOI:10.1002/nbm.3303 (2015)
  • Vescovo, E., Levick, A.P., Childs, C., Machin, G., Zhao, S., and Williams, S.R., 'High Precision Calibration of MRS Thermometry using Validated Temperature Standards: Effects of Ionic Strength and Protein Content on the Calibration', NMR in Biomedicine. DOI:10.1002/nbm.2840, Wiley Online Library (2012)
  • Vescovo, E., Levick, A.P., Zhao, S., Machin, G., Childs, C., Rainey, T., and Williams, S.R., 'High Precision Calibration of MRS Thermometry using Validated Temperature Standards', Proceedings of the International Society of Magnetic Resonance in Medicine, 18, p 50 (2010)

The concept has been proven, and these artefacts now provide temperature traceability (to ITS-90). They are world-first and have the power to make diagnostic conclusions from this technique a reliable and repeatable process.

Considerable work still remains to be done in refining the performance of the fixed-point artefacts and variable-temperature reference standards and also in establishing ITS-90 traceability for MRS thermometry for a variety of important metabolites in the body. In addition, studies into the reliability of the fibre-optic thermometer used for assigning the ITS-90 temperature in the variable temperature phantom need to be made.

Contact

For further information, please contact Graham Machin or Rob Simpson

Last Updated: 12 Aug 2015
Created: 12 Aug 2015

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