Beside the well-known safety and the economic issues related to the different types of imaging modalities, there are some important feasibility issues that should guide the use of one modality over the other. Patients with MPS are considered the most difficult category to study for several reasons. One of these is the fact that many of these patients are paediatric subjects who are intellectually impaired and cannot cooperate. In addition, most of these patients have walking problems and several contractures, thus making execution of the different examinations difficult both for postural reasons and for the patients inability to maintain the same position for a long time. The study of spinal stenosis requiring sagittal images might be difficult to realise because of the presence of scoliosis or kyphosis. While radiography is instrumental for a baseline assessment of dysostosis [5], no internationally recognized criteria for the evaluation of therapeutic radiological/imaging findings in MPS exist. Quantification of minor skeletal changes in dysostosis multiplex is a major challenge if we consider the great variety in bone alterations among individuals with MPS. The availability of a reproducible scoring system for an objective assessment would be very useful for the basal evaluation, during the follow-up, and for the appraisal of the response to therapy. Standardized assessment of radiological findings could provide insight into the natural course of bone disease in the different types of MPS. On the other hand, the regular use of radiography to monitor the progression of the disease and the impact of the therapy has to be balanced against the side effect of x-rays, considering that most patients, when first diagnosed, are just a few years old [4]. In our experience, considering the series of radiographs to be performed at the initial evaluation (as suggested by Muenzer et al. [29]) and the average relative effective dose (mSv) of a single examination, the overall effective dose for a 2-year-old child (height 80 cm, weight 11 kg) corresponds to 0.28 mSv and it increases to 0.60 mSv for a 10-year-old boy (height 140 cm, weight 32 kg). These values, compared with natural radiation exposure (2.4 mSv), are approximately equivalent to 1 and 3 months of exposure to background radiation, respectively, increasing the stochastic radio-induced risk. If we refer to the effective dose of posteroanterior chest x-ray (0.01 mSv in both ages), the effective dose for a plain film of the full column (0.14 mSv for a 2-year-old child and 0.43 mSv for a 10-year-old boy) basically corresponds to the effective dose for 14 and 43 chest x-ray examinations, respectively (Table 3).
New strategies have also been developed, such as luminescence, radiometric, and magnetic/electron resonance-based probes. These tools allow the generation of oxygenation maps in humans at the micro and macro levels and provide detailed insight into disease mechanisms and treatment responses. However, they are still subjected to problems that differentiates from class to class, such as the low spatial resolution of the images, the exposure to radiation, the requirement of expensive instrumentation, and low sensibility in detecting areas away from the skin surface. Another relevant challenge is their efficient and targeted delivery, which is particularly difficult for ischemic and cancer regions, which can lie many cell layers away from the blood supply. Although many promising studies have been reported using these probes, their use on human beings is still far from being fully explored due to regulatory hurdles.
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