Histotripsy is the controlled use of ultrasound cavitation to mechanically fractionate tissue volumes noninvasively under image guidance. With an appropriate understanding of the dynamics of bubble cloud initiation and extinction, a precise volume of tissue can be fractionated with very narrow boundaries between normal and affected tissue. Since the fractionation occurs at the tissue, cellular, and molecular levels, the results are easily seen by both ultrasound and MR imaging. Moreover, the degree of fractionation is correlated with survival of cells in the treated volume. As fractionation (or liquefaction) progresses, the amount of backscattered sound decreases as well a cell survival. Eventually, when the tissue is highly fractionated, no recognizable cellular organelles can be observed, even with electron microscopy, and the homogenized tissue looks like a fluid with few remaining ultrasound scattering particles. Since the effects of histotripsy are apparent in standard images both during and after treatment, the opportunity to develop image based feedback schemes correlating image parameters with eventual clinical outcomes is obvious. Unlike many other ablation techniques, the imaging based feedback approaches proposed herein can now be developed on a rational basis since the tissue effects can be easily seen and characterized by histological analysis and chronic animal studies where some clinical outcome can be determined. Thus, we will develop methods to predict clinical outcome from image parameters available both during and after treatment. This will provide an answer to the critical question for most noninvasive ablative technologies, i.e., when should the treatment be stopped and what will be the spatial extent of the desired treatment? Development of these image guidance techniques could result in a significant transformation in the effectiveness of ablative therapies in a wide range of clinical applications, e.g., prostate cancer, benign prostatic hyperplasia (BPH), breast cancer, fibroadenomas of the breast, liver cancer and metastases, kidney cancer, uterine fibroids, thrombolysis, cardiac ablations for arrhythmia control, lung and brain cancer (under certain conditions), treatment of infected wounds and abscesses, etc.