Chapter 1. 3: Non-invasive Thermography
1.3.8 Previous validation studies
Cady et al [115] tested MRS thermography in a phantom, and in a piglet using a 7T research scanner. They found that reducing the pH in the phantom to 2.8 did not alter the slope of the PRF/temperature model, but did shift the intercept by the equivalent of approximately 3°C. This would obviously affect the accuracy of any absolute temperature estimations that did not account for changes of this magnitude in the pH of the sample. However, the pH changes in the piglet resulting from induced cerebral ischaemia did not affect temperature measurements. Overall, MRS-based thermography was found to be accurate to within ±0.75°C in vivo using this technique. It should be noted that clinical (non-research) scanners are currently limited to 3T, which reduces the level of accuracy that can be achieved in the clinic. Cady et al also found in a subsequent study that the accuracy and reproducibility of temperature estimations could be improved by calculating an amplitude- weighted average of the temperatures from each reference metabolite (i.e. Choline, Creatine and NAA) [116].
Corbett et al tested a single-voxel technique in healthy pigs [105] and then in stroke- affected dogs [118] using a 1.5T clinical MRI scanner. They found that their MR thermography measurements were accurate to within approximately ±1.0°C in vivo. Importantly, they found the relationship between PRF and temperature was independent of tissue injury (24 hours after stroke onset) or scanner parameters such as echo time (TE). However, they did report a significant difference in the temperature measured using choline as a reference compared to NAA in the stroke-affected animals (whereas in the non stroke-affected pigs the measurements were similar enough that they could be averaged). The reasons for this are unknown, but should be considered before the practice of
averaging the temperatures from different metabolites is globally applied to improve the accuracy of MR thermography.
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Marshall et al [110] tested an MRSI sequence in a homogenous phantom, and in healthy volunteers using a 1.5T clinical scanner. The calibration of this technique relied on using the figure 0.01ppm/°C from the literature as the slope of the PRF/temperature graph. They derived the intercept of the graph by scanning 20 healthy volunteers, and assumed that their average brain temperature was 37°C. This is not ideal as a method of calibration, but did allow the authors to compare differences in average temperature across different tissue-types when they applied the technique to stroke patients [121, 122]. The authors also found that the quality and reliability of the MRS spectra collected in vivo were significantly degraded compared to in vitro measurements, and many voxels had to be discarded as being too poor to process. The authors were therefore restricted to making group comparisons, rather than deriving data that might influence treatment in individual patients. These group comparisons were put to good use in a number of subsequent studies [123-125].
Weis et al tested another MRSI technique which provided much better spatial resolution (using voxel sizes of less than 7 cubic mm) at the expense of spectral information. This study was conducted in pigs with brain temperature being monitored by MR-compatible fibre-optic probes which provided a reference temperature that the authors could be quite confident in, but produced spectra that did not allow the analysis of refence metabolites such as NAA (only the water PRF could be determined). Thus, the technique tested would only be useful for monitoring relative changes in temperature. The authors found similar problems to Marshall et al in terms of failed voxels [126], with fifty percent of all spectra collected in vivo being rejected by the authors for poor quality or unrealistic temperatures. Thrippleton et al compared the reproducibility of MRSI-derived temperature maps at 1.5T and 3T [127]. This study found that the biggest source of variation was between voxels within the same examination, rather than between patients or between days.
Reproducibility was found to be better at 3T than at 1.5T, with residual variation at 3T approximately half that at 1.5T (0.14°C vs 0.36°C).
Childs et al [111] tested both an SVS and an MRSI technique in a phantom and in healthy volunteers. They found spectra collected by SVS to be significantly more reliable than those collected by MRSI. They went on to perform temperature measurements in healthy volunteers, but used the PRF/temperature equation published by Corbett et al, rather than
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calibrating their own technique, which may impede the accuracy of their absolute temperature measurements.
Other authors [109, 128] have published improved sequences for MRSI, which may make this technique more useful in the near future. For the moment, however, the data available on the reliability or accuracy of temperature measurements made using these sequences are very limited, and the sequences themselves are not widely available for further experimentation.
Zhu et al [119] tested a single voxel technique in an 11.74T, small-bore research scanner. This technique demonstrated an accuracy of ±0.5°C in a mouse, using NAA as the single reference. This result is extremely encouraging although clinical scanners which use much lower field strengths are unlikely to replicate this level of accuracy.
Covaciu et al [117] validated temperature measurements from MRS in a phantom using NAA, choline and creatine. Their results were similar to those of previous studies. However they were the first to demonstrate that that accuracy could be improved by taking the average of these 3 temperatures for any given scan.