The thermal dose by high intensity focused ultrasound (HIFU) compared with histology is important for optimal treatment and safety issue, especially for brain therapy. The aim of the thermal dose experiment is to compare the accurately-controlled thermal dose with histology in the pig brain with human calvarium. Another aim is to investigate the possibility of apoptosis initiation with long sonication at a certain lower temperature. The 3rd aim is to explore the different responses of white and gray matters in the brain to the same thermal dose. A closed loop system will be developed to give feedback to control the duty cycle or/and power of the Insightec ExAblate 650 kHz system based on MR thermometry in real time, and to keep a certain temperature for elongated time at the focal area of the brain tissue. The developed system would be tested in a phantom to sonicate longer time in the order of few tens of minutes at a relatively low temperature measured in MRI images. Then a trial pig experiment will be performed with two pigs to test the pig experimental protocol with longer sonication time at a target temperature. The pilot experimental study with 8 pigs will be followed to investigate the three aims.