281 Non-invasive imaging biomarkers 3 substances containing gadolinium, enhance relaxation of the excited nuclear spins and thus add information about tissue perfusion. MRI-imaging is less widely available, more complex, lengthy and costly than US and CT, but provides unsurpassable soft-tissue contrast without the use of ionizing radiation. The classic spin and gradient echo sequences resulting in T1-, T2-, proton density- and susceptibilityweighted sequences seem to have limited classification value in indeterminate thyroid nodules. Effective T2-mapping (T2*-mapping) was explored by Shi et al. in 28 patients with thyroid nodules of different cytological subclasses, subjected to (therapeutic and diagnostic) surgery, describing 100% specificity and 84-90% sensitivity to distinguish malignant and benign thyroid nodules [419]. The used of dynamic gadolinium contrast-enhanced MRI has found conflicting results [420, 421]. A much larger body of evidence has been found for diffusion-weighted MRI (DWI) and proton-magnetic resonance spectroscopy (MRS). Diffusion weighted magnetic resonance imaging DWI is a specific form of MR imaging that is sensitive to the random Brownian motion of water molecules within a voxel of tissue. The easier water molecules diffuse and move around in a region, the higher the isotropic signal will be at higher degrees of diffusion weighting (b-value). Apparent Diffusion Constant (ADC [mm2/s]) imaging results from a series of conventional DWI-sequences with different b-values. The change in signal is proportional to the rate of diffusion. An ADC-image thus is an MRI-image that more specifically shows diffusion than conventional DWI, by eliminating the T2weighting that is otherwise inherent to conventional DWI. Contrary to DWI, the standard greyscale of ADC-images is to represent a smaller magnitude of diffusion as darker. Generally, highly cellular tissues or those with cellular swelling exhibit lower ADC-values. The use of DWI in cytologically indeterminate thyroid nodules is limited and methodology varies largely. Nakahira et al. evaluated the role of the ADC in 42 nodules, including 15 (36%) with indeterminate cytology (Bethesda System was not taken into account) [319]. The final diagnosis was confirmed by surgery and mean ADCs (acquired with b-values of 0 and 1,000 s/mm²) were compared between benign and malignant nodules (all with indeterminate cytology). Malignant nodules showed significantly lower ADCs than benign nodules. For all nodules, a cut-off value for malignant nodules of 1.60 × 10-3 mm²/s yielded a sensitivity, specificity, and accuracy of 95%, 83%, and 88%, respectively. It was concluded that ADC measurements could potentially quantitatively differentiate between benign and malignant thyroid nodules, even those of indeterminate cytology [319]. Chung et al. investigated the value of histogram analysis of ADC maps in the differentiation of follicular thyroid carcinoma from follicular adenoma in 17 Bethesda III and IV indeterminate nodules on USguided core needle biopsy [422]. Histogram parameters were derived from ADC values (acquired with b-values of 0 and 800 s/mm²) obtained from the entire tumour volume and compared with the histopathological diagnosis. It was found that 10th, 25th, and 50th percentiles of the ADC values
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