283 Non-invasive imaging biomarkers 3 shift of a nucleus to observe, identify and quantify biologically important compounds in tissue. An anatomical MR image is acquired, on which a volume of interest is selected, and the MR spectrum is acquired. As protons in water are far more abundant than the metabolites of interest (104:1), the water signal should be suppressed during MRS-pulse sequences. The use of MRS specifically in indeterminate thyroid nodules was rather limited. Therefore, we focused on MRS in the differentiation of thyroid carcinoma in general. The use of magnetic resonance principles in thyroid cancer is in fact not new, but originates from ex vivo proteomic and metabolomic research [425]. MRS of cytology and biopsy specimens was attempted to overcome the limitations of FNAC [426, 427]. Also, ex vivo operative specimens have been analysed, for the identification of the morphologic features of malignancies in the first place; with the advancement of the technology followed by the differentiation between benign and malignant neoplasms [428]. Ex vivo spectra showed lower content of lipids and higher concentrations of amino acids in malignant compared to benign nodules [429]. The first in vivo study by King et al. succeeded in discriminating thyroid carcinomas from normal thyroid tissue based on the 1.5 Tesla 1H-MRS spectra [430]. In their cohort of eight patients (three anaplastic carcinomas, two papillary carcinomas, one follicular carcinoma) and five healthy controls, they found that choline-to-creatine ratio seemed a useful marker for the pre-operative differentiation. This was confirmed by other studies, showing that a choline-peak was rather specific for malignancies [431, 432]. It should be noted that these studies considered the absolute choline peak, without the creatine reference. Creatine is considered a convenient internal standard, for its relatively constant level in metabolically active tissues. More recently, the choline-to-creatine ratio was further evaluated by Aghaghazvini et al. in a cohort of 9 malignant (7 papillary, 2 follicular) and 23 benign nodules using 3 Tesla 1H-MRS [433]. At an echo time of 136 ms, a choline-to-creatine ratio of 2.5 corresponded best with histopathology with a sensitivity, specificity, PPV and NPV of 75%, 100%, 100%, and 92%, respectively. Whereas the MRS choline-to-creatine ratio seems a promising biomarker for the differentiation of thyroid nodules, all presented studies were performed in small cohorts and with varying methodology. To the best of our knowledge, only four papers on in vivo MRS in thyroid nodules were published in almost two decades, which might indicate limited clinical interest or limited feasibility. In contrast, the field of MRS is emerging and in recent years, the use of MRS in clinical practice has increased, because of the installation of human MRI systems with high field strengths (≥7 Tesla). Higher field strengths result in spectral dispersion, i.e., a larger frequency between peaks, improving the resolution, which allows more accurate quantification of tissue compounds in smaller lesions [434]. Future studies should validate these preliminary findings and also cast light on costeffectiveness.
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