MR-guided focused ultrasound (MRgFUS) is a noninvasive technique for the treatment of painful bone metastases. Proton resonant frequency shift (PRF) thermometry is the standard for monitoring temperature during MRgFUS interventions. It can precisely measure the changes in temperature in water-based tissues, but fails to detect temperature changes in bone and in tissues with high lipid content, such as bone marrow.

Current clinical protocols for bone treatments rely on measurement of the temperature change of adjacent muscle to estimate the temperature of the bone. This approach carries a significant risk of overtreatment in that more energy might be used than is needed to ablate the target. In fact, we observe in HIFU treatments of bone metastases that the highest temperature in soft tissue is only reached 10-15 seconds after the end of the sonication. Collateral treatment of the near-field soft tissues during MRgFUS increases the risk for muscle and vascular injury, which can result in significant perioperative or chronic pain.

Deeper penetration of the ablation through the cortical bone into the bone marrow or tumor is often desired for local control of osseous lesions. In the treatment of osteoid osteomas, complete ablation of the nidus is required for pain relief and to avoid recurrence, but the thickened cortical bone makes ultrasound penetration difficult. Therefore, temperature measurement within the bone is needed.

Previous studies have shown a change in T2 of subcutaneous fat, red and yellow bone marrow in controlled calibration experiments and during treatments with focused ultrasound (1-4). The goal of this study was to determine if T2 based thermometry could be used to monitor the temperature change in ex-vivo and in-vivo bone marrow during focused ultrasound ablation of intact bone.

All experiments were performed using an ExAblate 2100 system (InSightec, Haifa, Israel) integrated with a 3.0 Tesla MR scanner (GE Healthcare, Waukesha, WI, USA). Bone marrow T2 was quantified with a double-echo fast spin-echo sequence with water suppression (TE = 35/186 ms, TR = 1500 ms, echo train length = 40, FOV = 32 cm, 128 x 128 matrix size, 10mm slice thickness, 15 sec/slice).

For ex-vivo validation, we performed MRgFUS ablation in an ex-vivo porcine femur (sonication: 20 sec, acoustic power: 30W). The focus of the sonication was placed in the middle of the marrow, but due to the high ultrasound absorption of cortical bone most of the energy is absorbed in the cortical bone.

Focused ultrasound ablation was also performed in a swine model. All experimental procedures were done in accordance with NIH guidelines for humane handling of animals and received prior approval from the local Institutional Animal Care and Use Committee. A total of 12 sonications were performed on the distal diaphysis (6 sonications, 35 W, 20 sec) and proximal diaphysis (6 sonications, 17 W, 40 sec) of the femur. As in the ex vivo validation, the focus was placed in the middle of the marrow. At the end of the focused ultrasound, pre- and post-contrast 3D Fast SPGR images were acquired.

Figure 1 shows the results of the ex-vivo experiment, where we measured a T2 elevation of 269 ms. Assuming the T2/temp coefficient of 7 ms/°C (1), this corresponds to a temperature rise of 38°. The ex-vivo experiment shows that it takes on the order of 15 minutes for the marrow to return to the baseline temperature.

Figure 2 shows the results of the in vivo experiment in a swine model. We measured a T2 rise of 231 ms within the bone marrow, which corresponds to temperature change of 33°C from baseline. The in-vivo experiment showed excellent correspondence between the area of T2 elevation in marrow during the ablation and the resulting non-enhancing area in the post-contrast images.

In this study we have demonstrated for the first time that T2-based thermometry can be used in vivo to measure the heating in the marrow during bone ablation. The ability to monitor the temperature within the bone marrow allowed visualization of the heat penetration into the bone, which is important for local lesion control and treatment of osteoid osteomas. Therefore, T2 based temperature mapping, in addition to PRF-based thermometry could be used to monitor heating during the bone focused ultrasound treatments and improve safety and efficacy of MRgFUS bone applications.