Self-Scanned HIFU Ablation of Moving Tissue Using Real-Time Hybrid US-MR Imaging.

OBJECTIVE: High intensity focused ultrasound (HIFU) treatment in the abdominal cavity is challenging due to the respiratory motion. In the self-scanning HIFU ablation method, the focal spot is kept static and the heating pattern is obtained through natural tissue motion. This paper describes a novel approach for modulating the HIFU power during self-scanning in order to compensate for the effect of tissue motion on thermal buildup. METHODS: The therapy, using hybrid ultrasound (US)/magnetic resonance (MR) imaging, consists of detecting and tracking speckle on US images in order to predict the next tissue position, and modulating the HIFU power according to the tissue speed in order to obtain a rectilinear pattern of uniform temperature elevation. Experiments were conducted on ex vivo tissue subjected to a breathing-like motion generated by an MR-compatible robot and sonicated by a phased array HIFU transducer. RESULTS: US and MR data were free from interferences. For both periodic and non-periodic motion, MR temperature maps showed a substantial improvement in the uniformity of the temperature elevation by using acoustic power modulation. CONCLUSION: The presented method does not require a learning stage and enables a duty cycle close to 100%, higher average acoustic intensity and avoidance of side lobe effects versus performing HIFU beam steering to compensate tissue motion. SIGNIFICANCE: To our knowledge, the proposed method provides the first experimental validation of the self-scanning HIFU ablation paradigm via a real-time hybrid MRI/US imaging, opening the path toward self-scanning in vivo therapies.

Leveraging respiratory organ motion for non-invasive tumor treatment devices: a feasibility study.

In noninvasive abdominal tumor treatment, research has focused on minimizing organ motion either by gating, breath holding or tracking of the target. The paradigm shift proposed in this study takes advantage of the respiratory organ motion to passively scan the tumor. In the proposed self-scanning method, the focal point of the HIFU device is held fixed for a given time, while it passively scans the tumor due to breathing motion. The aim of this paper is to present a treatment planning method for such a system and show by simulation its feasibility. The presented planning method minimizes treatment time and ensures complete tumor ablation under free-breathing. We simulated our method on realistic motion patterns from a patient specific statistical respiratory model. With our method, we achieved a shorter treatment time than with the gold-standard motion-compensation approach. The main advantage of the proposed method is that electrically steering of the focal spot is no longer needed. As a consequence, it is much easier to find an optimal solution for both avoiding near field heating and covering the whole tumor. However, the reduced complexity on the beam forming comes at the price of an increased complexity on the planning side as well as a reduced efficiency in the energy distribution. Although we simulate the approach on HIFU, the idea of self-scanning passes over to other tumor treatment modalities such as proton therapy or classical radiation therapy.

Kidney injury molecule-1 expression in rat proximal tubule after treatment with segment-specific nephrotoxicants: a tool for early screening of potential kidney toxicity.

Dose-response expression of kidney injury molecule-1 (KIM-1) gene in kidney cortex and its correlation with morphology and traditional biomarkers of nephrotoxicity (plasma creatinine and blood urea nitrogen, BUN) or segment-specific marker of proximal tubule injury (kidney glutamine synthetase, GSK) were studied in male rats treated with proximal tubule segment-specific nephrotoxicants. These included hexachloro-1:3-butadiene (HCBD, S(3) segment-specific), potassium dichromate (chromate, S(1)-S(2) segment-specific), and cephaloridine (Cph, S(2) segment-specific). Rats were treated with a single intraperitoneal (ip) injection of HCBD 25, 50, and 100 mg/kg, subcutaneous (sc) injection of chromate 8, 12.5, and 25 mg/kg; or ip injection of Cph 250, 500, and 1,000 mg/kg. KIM-1 gene showed a dose-dependent up-regulation induced by all segment-specific nephrotoxicants. Interestingly, magnitude of the up-regulation reflected the severity of microscopic tubular changes (degeneration, necrosis, and regeneration). Even low-severity microscopic observations were evidenced by significant gene expression changes. Furthermore, KIM-1 showed significant up-regulation even in the absence of morphological changes. In contrast, traditional and specific markers demonstrated low sensitivity or specificity. In conclusion, this study suggested KIM-1 as a sensitive molecular marker of different levels of tubular injury, and it is likely to represent a potential tool for early screening of nephrotoxicants.