J Cachexia Sarcopenia Muscle (2012) 3:181–190 [36]. Nevertheless, it cannot be ignored that the first operative definition is dated more than 10 years, and during this time, several steps forward have been made in refining imaging techniques as well as understanding the sarcopenia phenomenon. The identification of the “gold standard” for the quanti- tative evaluation of muscle mass in clinical trials (which is currently lacking) should be based on criteria of accuracy (i.e., the degree of conformity of a measure to a standard or a true value), precision (i.e., the degree of refinement with which an operation is performed or a measurement stated), reproducibility (i.e., the quality of being reproducible under the same operating conditions over a period of time or by different operators), sensitivity to change (i.e., the degree of being modified by interventions), and accessibility (i.e., its usual availability in research and clinical centers). DXA currently represents the more accessible technique for body composition assessment. It may accurately provide esti- mates of lean, fat, and bone tissues in the entire body or in specific regions. Moreover, it is inexpensive and quick to be performed. The radiation exposure associated with DXA is low and highly acceptable (about 1 mrem, a quantity similar to that of a 3-day background). The main limitations of this imaging approach reside in some analytical differences across manufac- turers and models, and the risk of biased results due to the low differentiation between water and bone-free lean tissue. CT accurately measures a direct physical property of the muscle (e.g., cross-sectional area and volume). It also allows the evaluation of muscle density (a parameter related to intramyocellular lipid deposits) as well as subcutaneous and intramuscular adipose tissue deposition. The radiation exposure associated with this technique is higher (i.e., about 15 mrem) than with DXA. Magnetic resonance imaging (MRI) presents a high agree- ment with CT and provides similar measures. It does not involve radiation exposure and also has the additional capac- ity of multiple slice acquisition, thus rendering 3D volumetric estimates. The lack of radiation exposure makes MRI the method of choice for many studies where ethics committee or national authority approval is more difficult to obtain for CT. The major limitations of this methodology reside in the higher technical complexity and costs, and in the inapplica- bility to subjects with older models of implanted metal devices (e.g., joint prostheses, pace-makers, etc.). Both CT and MRI may be limited in the ability to accommodate very obese individuals. Finally, it needs to be emphasized that imaging provides information only about one of the two sarcopenia dimensions. As discussed earlier, changes in muscle function and quantity do not necessarily follow similar trajectories with aging [37]. Therefore, interventions able to increase lean mass may not necessarily produce parallel gains in strength and vice versa [38]. To overcome this issue and include the two components 185 of sarcopenia in the same variable, it has been proposed to compute an index of skeletal muscle quality derived from the ratio between strength and mass [15, 39, 40]. One of the most recently developed techniques which might find larger application in the near future for the evaluation of sarcopenia is the electrical impedance myography (EIM) [41]. This is a noninvasive, painless approach based on the surface application and measurement of a high-frequency, low- intensity electrical current applied to specific muscles. EIM detects changes in the conductivity and permittivity of skeletal muscle caused by alterations in muscle composition and struc- ture. EIM is repeatable and sensitive to skeletal muscle changes in patients with amyotrophic lateral sclerosis [42]. Moreover, its changes over time may also have clinical relevance as they are predictive of survival in animal models of amyotrophic lateral sclerosis [43]. Finally, it is also noteworthy that the EIM phase shows a consistent inverse relationship with age [44]. An alternative method to measure skeletal muscle size is by ultrasonography. This technique has shown to be a valid (versus MRI-based measurements) and highly reliable way for assessing cross-sectional areas of large individual human muscles [45]. It is particularly useful in mobility-impaired subjects who cannot easily be transported to scanners such as CT or MRI machines. Also remarkable is the development of mass isotopomer distribution analysis based on the evaluation of protein and proteome synthesis rate obtained by heavy water labeling [46, 47]. Although this technique can still be considered suitable mainly for research settings, its flexibility and the large amount of information it provides about a wide spec- trum of proteins make it extremely promising. Other techniques are also available to detect sarcopenia, but their limited validation, low accuracy, and difficult large- scale implementation discourage their use. For example, bio- electrical impedance analysis (BIA) is a popular, very simple, and low-cost technique, but its results are far from being accurate. The BIA technique is based on the notion that tissues rich in water and electrolytes are less resistant to the electrical passage than adipose tissue. The BIA is therefore based on a single body resistance parameter (not a direct measure of skeletal muscle), and its results can be easily altered by fluid retention and health status in general. For these reasons, a recent consensus paper by the Society of Sarcopenia, Cachex- ia and Wasting Disorders has discouraged the use of BIA for the assessment of sarcopenia [9]. 6 Definition of critical thresholds There is still resistance to accept sarcopenia as a clinical condition despite its well-established relationship with major health-related negative events (in particular, mobility and physical disability) [8]. This issue might (at least partly) be