Table 1.

Pros and cons of each MPUS method and molecular test.

	PROS	CONS
Qualitative USE	Non-invasive No contrast medium Safe Same probe and US machine of B-mode evaluation Defined in some guidelines Not overly time-consuming Good intra-observed agreement	Subjective evaluation (low inter-observed agreement) Non-univocal classification (4- or 5-point scale scoring systems) Soft carcinoma evaluation (thyroid follicular carcinoma) Undefined thyroiditis influence Calcific nodule may be wrongly assessed Cystic nodule may be wrongly assessed
Semi-Quantitative USE	Non-invasive No contrast medium Safe Same probe and US machine of B-mode evaluation Defined in some guidelines Not overly time-consuming Good intra-observed agreement Good inter-observed agreement	Univocal cut-off missing Soft carcinoma evaluation (thyroid follicular carcinoma) Undefined thyroiditis influence Calcific nodule may be wrongly assessed Cystic nodule may be wrongly assessed
Quantitative USE	Non-invasive No contrast medium Safe Same probe and US machine of B-mode evaluation Defined in some guidelines Not overly time-consuming Good intra-observed agreement Good inter-observed agreement	Univocal cut-off missing Two different measurement units (m/s and kPa) Soft carcinoma evaluation (thyroid follicular carcinoma) Undefined thyroiditis influence Calcific nodule may be wrongly assessed Cystic nodule may be wrongly assessed
CEUS qualitative	Minimally invasive Safe (anaphylactic reactions very rare) Same probe and US machine of B-mode evaluation	Sulfur-based contrast medium use Not approved in clinical practice by the guidelines (only approved for research) Undefined intra-observed agreement Undefined inter-observed agreement More time-consuming than USE
CEUS quantitative (T/I curve)	Minimally invasive Safe (anaphylactic reactions very rare) Same probe and US machine of B-mode evaluation	Sulfur-based contrast medium use Not approved in clinical practice by the guidelines (only approved for research) Undefined intra-observed agreement Undefined inter-observed agreement More time-consuming than USE
US CAD System	Non-invasive No contrast medium Safe Same probe and US machine of B-mode evaluation Not overly time-consuming Good intraobserved agreement Good interobserved agreement Improves the accuracy of inexperienced or non-specialist radiologists	Not approved in clinical practice by the guidelines (only approved for research) Accuracy not superior to experienced radiologists
Molecular test	May be performed on cytological specimens	Cost-effective only in carefully selected nodules Variable performance according to the pre-test probability of malignancy High costs (still unavailable/unaffordable in many countries)