Fifteen years of use of functional imaging in multiple myeloma: where we started and where we are going.

Bone disease represents a hallmark feature of multiple myeloma (MM), affecting nearly all patients during the disease course. Morphological imaging techniques play a crucial role in detecting bone disease, whereas functional ones are also fundamental for the differentiation of active from inactive disease and prognostic stratification. The International Myeloma Working Group (IMWG) currently recommends whole-body low-dose computed tomography (WBLDCT) as the first-choice imaging technique for the diagnosis of bone disease, whereas magnetic resonance imaging (MRI) is recommended in cases without further myeloma-defining events. However, 18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG-PET/CT) currently represents the standard imaging technique, because it combines both morphological and functional data. Indeed, it allows detection of bone lesions (alternatively to WBLDCT), prognostic stratification, and monitoring of treatment response, being recommended by the IMWG for the assessment of imaging minimal residual disease. The IMPeTUs (Italian Myeloma criteria for PET Use) have proposed a visual descriptive assessment of 18F-FDG-PET/CT, with standardized definitions of metabolic responses. However, the use of further functional imaging techniques is being investigated, with diffusion-weighted (DW)-MRI being related to very promising results regarding both staging and response assessment, to the extent that myeloma response assessment and diagnosis system guidelines have recently proposed a standardization of acquisition, interpretation and reporting of this technique in MM, and the British guidelines consider DW-MRI an alternative to 18F-FDG-PET/CT. This review summarizes current knowledge on the use of functional imaging techniques in MM and their incorporation in recommendations/guidelines, and discusses potential future developments in this setting.