Opportunities from modulating ultrasound, from tissue ablation to tissue regeneration

The potential use of ultrasound for therapeutic purposes is known since the early decades of the last century. To date, only a few applications for clinical use are already a therapeutic reality, such as the ablative treatment of uterine fibroids, prostate cancer and palliative treatment for pain of bone metastases. Much more disparate are the ongoing biological research and clinical trial on the use of low and high intensity ultrasound predominantly, but not exclusively, in the oncology and neurologic fields. This review explores, in a systematic mode, the biological effects produced by modulating ultrasound beams from low to ablative intensities, revealing their enormous potential therapeutic implications. However, many efforts are still needed to translate these opportunities into clinical practices. Indeed, while ablation techniques need to be improved in sensibility and specificity of tumour and neurologic targets ablation, drug delivery and the other more fine cell killing methods need to be better studied through in vitro and preclinical researches, as a great variability of results are reported among similar type of experiments. Particularly, still there is the lack of the "acoustic dose" concept, adapted to each kind of biologic system, as the same ultrasound parameters can results in completely different responses, both for the lack of technical reproducibility in acoustic irradiation, both because the biologic response is tightly cell and tissue-type dependent. In this regard, the support of deep proteo-genomic analysis could help in the understanding of molecular signalling induced by ultrasound on specific biological models.