The recent emergence at the clinical level of minimally-invasive focal therapy such as laser-induced thermal therapy (LITT) has demonstrated promise in the management of brain metastasis , although control over the spatial pattern of heating is limited. Delivery of HIFU from minimally-invasive applicators enables high spatial control of the heat deposition in biological tissues, large treatment volumes and high treatment rate in well chosen conditions [2,3]. In this study, the feasibility of MRI-guided interstitial ultrasound therapy in brain was studies in-vivo in a porcine model. A prototype system originally developed for transurethral ultrasound therapy [4,5,6] was used in this study. Two burr holes of 12 mm in diameter were created in the animal's skull to allow the insertion of the therapeutic ultrasound applicator (probe) into the brain at two locations (right and left frontal lobe). A 4-element linear ultrasound transducer (f = 8 MHz) was mounted at the tip of a 25-cm linear probe (6 mm in diameter). The target boundary was traced to cover in 2D a surface compatible with the treatment of a 2 cm brain tumor. Acoustic power of each element and rotation rate of the device were adjusted in real-time based on MR-thermometry feedback control to optimize heat deposition at the target boundary [2,4,5]. Two MRT-controlled ultrasound brain treatments per animal have been performed using a maximal surface acoustic power of 10W.cm-2. In all cases, it was possible to increase accurately the temperature of the brain tissues in the targeted region over the 55°C threshold necessary for the creation of irreversible thermal lesion. Tissue changes were visible on T1w contrast-enhanced images immediately after treatment. These changes were also evident on T2w FSE images taken 2 hours after the 1st treatment and correlated well with the temperature image. On average, the targeted volume was 4.7 ± 2.3 cm3 and the 55°C treated volume was 6.7 ± 4.4 cm3. The volumetric undertreatment and overtreatment were respectively 0.1 ± 0.1 cm3 and 0.7 ± 0.6 cm3. The radial targeting accuracy was on average 1 ± 3 mm. Treatments were completed within 7 ± 3 min, that is an treatment rate of 0.9 ± 0.7 cm3/min. MRI-controlled interstitial ultrasound therapy of brain tissue is feasible. This minimally-invasive approach avoids the need to propagate ultrasound through the skull and allows spatially controlled heating which could be used for tissue ablation or drug delivery.