Abstract
Under magnetic resonance (MR) guidance, high intensity focused ultrasound (HIFU) is capable of precise and accurate delivery of thermal dose to tissues. Given the excellent soft tissue imaging capabilities of MRI, but the lack of data on the correlation of MRI findings to histology following HIFU, we sought to examine tumor response to HIFU ablation to determine whether there was a correlation between histological findings and common MR imaging protocols in the assessment of the extent of thermal damage. Female FVB mice (n = 34), bearing bilateral neu deletion tumors, were unilaterally insonated under MR guidance, with the contralateral tumor as a control. Between one and five spots (focal size 0.5 × 0.5 × 2.5 mm3) were insonated per tumor with each spot receiving approximately 74.2 J of acoustic energy over a period of 7 seconds. Animals were then imaged on a 7T MR scanner with several protocols. T1 weighted images (with and without gadolinium contrast) were collected in addition to a series of T2 weighted and diffusion weighted images (for later reconstruction into T2 and apparent diffusion coefficient maps), immediately following ablation and at 6, 24, and 48 hours post treatment. Animals were sacrificed at each time point and both insonated/treated and contralateral tumors removed and stained for NADH-diaphorase, caspase 3, or with hematoxylin and eosin (H&E). We found the area of non-enhancement on contrast enhanced T1 weighted imaging immediately post ablation correlated with the region of tissue receiving a thermal dose CEM43 ≥ 240 min. Moreover, while both tumor T2 and apparent diffusion coefficient values changed from pre-ablation values, contrast enhanced T1 weighted images appeared to be more senstive to changes in tissue viability following HIFU ablation.
Highlights
Magnetic resonance guided focused ultrasound (MRgFUS) is a noninvasive method for the application of thermal and mechanical therapies
The non-perfused volume (NPV) could not be compared to the thermal dose since real time temperature monitoring (performed with magnetic resonance thermometry (MRT), via the proton resonance frequency shift method), was only performed on a single slice at the focus of the ultrasound during the ablation to increase temporal resolution
We found agreement between the non-perfused area (NPA) and the area of tissue receiving a thermal dose of at least cumulative equivalent minutes at 43°C (CEM43) = 240 min, which suggests that the thermal dose maps generated during an ablation procedure are of great utility in predicting final tissue death
Summary
Magnetic resonance guided focused ultrasound (MRgFUS) is a noninvasive method for the application of thermal and mechanical therapies. MRI guidance provides a high degree of precision in localizing the focal point of the ultrasound beam in addition to providing 2D or 3D temperature maps in real time for monitoring energy deposition in tissue and calculating thermal dose maps peri- and post treatment [1,2,3,4,5]. In addition to MRI guidance, thermal therapies can be guided by ultrasound [7], x-ray computed tomography (CT) [8], or via the use of an interstitial temperature probe. The latter, while easy to use and accurate, provides only a single spatial measurement point leaving thermal dose away from the probe uncertain, which can be especially problematic in larger tumors. X-ray CT offers high temporal and spatial resolution, but entails ionizing radiation exposure and exogenous contrast agents are typically required
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