284 chapter 3 Multiparametric MRI Both DWI and 1H-MRS seem promising in the evaluation of indeterminate thyroid nodules, but a multiparametric approach has not been extensively studied. Aydin et al. were the first to describe multiparametric MRI, being DW-MRI and 1H-MRS, in unselected thyroid nodules [435]. Other approaches combined ADC values and descriptions of the time-signal intensity curves of dynamic contrast enhanced MRI, finding an accuracy of 91% [436], used ADC values and T1-weighted and T2weighted tumour-to-non tumour ratios with accuracies over 90% [437] or compared DWI with proton transfer imaging and found DWI to be superior [438]. Wang et al. investigated conventional MRI, DWI, and DCE in a retrospective cohort of 181 consecutive subjects (148 benign and 111 unstratified malignant nodules, confirmed by pathological results) [439]. The multivariable analysis revealed that ADC value, irregular shape, ring sign in the delayed phase, and cystic degeneration were independent predictors of malignancy, with an AUC, sensitivity, and specificity of these variables combined of 99%, 97%, and 95%, respectively. Song et al. investigated intravoxel incoherent motion MRI and DCE in 38 unstratified nodules and found that parameters were significantly different between benign and malignant nodules [440]. Multiparametric radiomics has also been investigated in a dataset of 120 PTC patients to predict aggressiveness based on 1393 radiomic features extracted from T1-weighted, T2-weighted, and ADC-images. The dataset was split into a training (N=96) and test set (N=24) and machine learning was performed for feature selection and classification, resulting in an AUC in the test set of 92% (compared to 56% for clinical characteristics alone) [441]. Another T1, T2, and ADC radiomics approach in 132 PTC (92 training, 40 test) used a machine learning algorithm to detect extrathyroidal extension, resulting in an AUC in the test set of 87% [442]. [99mTc]Tc-MIBI scintigraphy Scintigraphy is a 2D functional imaging technique that in vivo localises gamma-emitting isotopes such as technetium-99m using a gamma camera. Scintigraphy with the radiopharmaceutical [99mTc] Tc-MIBI reflects perfusion and the number of active mitochondria in cells [293]. It is primarily known for its use in myocardial perfusion imaging, the evaluation of hyperparathyroidism, and molecular breast imaging. [99mTc]Tc-MIBI scintigraphy has been investigated for the differentiation between benign and malignant nodules based on the uptake and by assessing an eventual increase in uptake within the nodule over time. [99mTc]Tc-MIBI is more suitable than [99mTc]pertechnetate or radioisotopes of iodine (123I, 124I (PET), 131I). Iodine radioisotopes are often used to assess thyroid nodule functioning (“hot” or “cold”), which are unspecific and ineffective for the further stratification of cytologically indeterminate thyroid nodules. Whereas malignant nodules are almost solely cold, as cell dedifferentiation results in a decrease of the sodium-iodide symporter and thereby
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