Supply Chain Vulnerability: Considerations for the Case
C. El contexto de la logística en América Latina
In its current form, the MRT method described in this thesis is not yet ready for clinical implementation. A number of problems described in Chapters 3 and 4 would affect the confidence with which this MRT technique could be applied. The absolute accuracy of temperature estimations (determined to be ±1.3°C in healthy tissue) is one such problem, as most of the temperature variation observed within both healthy volunteers and stroke patients was less than 2.5°C, and therefore the possibility that the temperature variation was zero cannot be ruled out in most cases. However, the estimations should be accurate enough to allow researchers to detect the 3-4°C temperature decrease targeted in clinical trials such as CHIL. The greater concern is the variation demonstrated in the apparent accuracy of temperature estimations between different data subsets (see Table 3.2.3). This raises the possibility that if another series of spectra was acquired and analysed the
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apparent accuracy of the temperature estimations would be even poorer. The confidence that can be placed in any particular temperature estimation is therefore quite limited. Furthermore it is expected that in ischaemic tissue, particularly tissue that has already infarcted, the accuracy of temperature estimations based on MR spectroscopy will be poorer regardless of the individual method used to acquire and process the spectra, but the magnitude of this effect cannot be quantified with any confidence, particularly since it is likely to vary from patient to patient. The experiments in this thesis indicate that it is possible to conduct temperature estimations in infarcted tissue, but did not indicate what level of confidence should be attached to these temperature estimations. On a more promising note, the temperature of the infarct is not typically as important to clinicians as the temperature of the penumbra, and the spectra from the penumbra did tend to be of similar quality to those from healthy tissue in the small cohort of patients examined in this thesis, suggesting that the accuracy of temperature estimations should also be similar. It is possible that using line-fitting algorithms to determine the proton resonance frequency of the water and reference metabolites would improve the accuracy of temperature estimations based on these resonance frequencies. Indeed, line-fitting is considered mandatory by many authors with regards to MR thermography [105, 110, 115, 217]. The standard Siemens Syngo line-fitting algorithm was found to be insufficient for the purposes of MR thermography during the course of the early phantom experiments described in Chapter 3.1. One of the goals of this thesis was to test a method of MR thermography that would be widely and easily accessible to clinicians conducting trials of therapeutic
hypothermia. The need to export data to a separate work-station before processing, not to mention the expense of purchasing specialised software may act as a barrier to the
widespread utilisation of any thermography technique dependent on software packages such as LCModel. Therefore the decision was made to avoid using specialised MR spectroscopy software that could have allowed automated interpretation of the spectra. The resulting temperature estimations were not found to be adequate for their intended use, and other methods of processing spectra for MR thermography, that have only recently become available, may provide a better alternative. For example, the latest version of jMRUI [187] is available with a ‘thermography plug-in’ [218]. This is promising as jMRUI is available free to academic users. This temperature plug-in requires further validation but is worth investigating as a possible alternative to the MRT method described
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in this thesis.
Improvements could also be made to the process of acquiring the spectra. The lack of an unsuppressed water reference has already been described as a major weakness of this study. This flaw has already been corrected as far as future acquisitions go by the updates to the Siemens Syngo software, which now collect a separate (unsuppressed) water
reference by default. Careful manual shimming may also improve the quality of the spectra acquired in vivo, and allow greater consistency in the spectral quality across different regions of the brain. Improved methods of automatic shimming have also become more widely available since these experiments were conducted. Techniques such as “FASTMAP” and “PACMAP” [219] allow highly accurate shimming while preserving the generalisability of the protocol that was one of the intended features of the MRT paradigm tested in this thesis.
The possibility cannot be ruled out that MR thermography will never be accurate enough to provide worthwhile clinical data on individual patients. Many of the problems encountered with MR thermography in this thesis are not unique to the processing method described here. For example the accuracy of the temperature estimations, both in vitro and in vivo, was comparable to those found in previous studies (as mentioned in Chapters 3.1 and 3.2). The variation in the apparent accuracy of the temperature estimations between different data subsets in Chapter 3.2 is still a concern, but no other MR thermography technique has been subjected to this form of cross-data-set analysis (or at least, the results of such analysis have not been published). It may therefore be the case that other methods of MR thermography would display similarly problematic results were they subjected to such an analysis. The inability to quantify the effects of tissue injury on the accuracy of
temperature estimations from ischaemic tissue is a factor regardless of the method of MR thermography processing used.
It is possible that simple measures such as increasing the field strength of the MRI scanner, or using a different spectral processing method such as the jMRUI plug-in or other
specialised MR spectroscopy software will allow accurate and reliable temperature estimations in stroke patients. In order to have full confidence in these temperature estimations validation experiments in animals would arguably be required. The possible structure of these experiments will be discussed below. It is also worth noting that, since
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Siemens have changed the way the water signal is acquired for MRS scans in their latest version of the Syngo scanner software, the processing method described in this thesis is no longer readily applicable. Even old Siemens scanners will typically have received a software upgrade and now collect a separate, unsuppressed water signal against which other
metabolite PRFs could be compared. This, combined with the problems outlined above, means that the MR thermography method described will probably never be widely used, but does not detract from the validity of the experiments described in this thesis. As mentioned above, there are many difficulties and uncertainties involved in MR
thermography and these may never be overcome. Nevertheless this remains an important avenue of research as there are still very little data available regarding temperature changes in the brain after a stroke. Furthermore, the other avenue of investigating these changes discussed in this thesis, computer modelling of heat exchange, also requires more in vivo data before it can be developed further, and some of this data will probably have to come from MR thermography or much more invasive neurosurgical techniques.