This study tests the suitability of a tumour-mimic for targeting magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU). An agarose-based tumour-mimic was injected as a warm solution that polymerized in tissue. Thermal characteristics and acoustic absorption of the mimic were observed within the values reported for tissues. The relaxation times at 3T were 1679 ± 15 ms for T1 and 41 ± 1 ms for T2. The mimic was clearly visible on in vivo images. With lower contrast the tumour-mimic was visible on T2-weighted images, where it was possible to detect the ablated tissue surrounding the mimic after sonications. HIFU sonications were performed to induce thermal ablation on and around the mimic using a Sonalleve system (Philips). MR thermometry maps were performed during HIFU. The average temperature when the sonication was done at the tumour-mimic was 67.6 ± 8.0 °C in vitro and 67.6 ± 5.0 °C in vivo. The average temperature for sonications at tissues was 68.4 ± 8.7 °C in vitro (liver) and 66.0 ± 2.6 °C in vivo (muscle), with no significant difference between tissue and tumour-mimic (p > 0.05). The tumour-mimic behaviour when using MR-guided HIFU was similar to tissues, showing that this mimic can be used as an alternative to tumour models for validating MR-guided HIFU devices targeting.
BackgroundA device was devised which aimed to reduce the time and expertise required to perform sonoporation on adherent cell cultures. This prototype device was used to examine the superficial effect of bath temperature on sonoporation efficacy.MethodsThe prototype device consisted of six ultrasound transducers affixed beneath an Opticell stage. Six transducers with nominal diameters of 20 mm were constructed and the acoustic field of each was characterized using hydrophone scanning. A near field treatment plane was chosen for each transducer to minimize field heterogeneity in the near field.Cervical cancer-derived SiHa cells were exposed to nine different treatments in the presence of plasmid DNA-expressing green fluorescent protein (GFP). Ultrasound treatment with Definity ultrasound contrast agent (US+UCA) present, ultrasound treatment without contrast agent present (US), and a sham ultrasound treatment in the presence of ultrasound contrast agent (CA) were each performed at bath temperatures of 37, 39.5, and 42 °C. Each treatment was performed in biological triplicate. GFP expression and PARP expression following treatment were measured using fluorescent microscopy and digital image processing. Cell detachment was measured using phase contrast microscopy before and after treatment.ResultsMean (± s.d.) transfection rates for the US+UCA treatment were 5.4(±0.92), 5.8(±1.3), and 5.3(±1.1) % at 37, 39.5, and 42 °C, respectively. GFP expression and cell detachment were both significantly affected by the presence of ultrasound contrast agent (p < 0.001, p < 0.001). Neither GFP expression, PARP expression, or detachment differed significantly between bath temperatures.ConclusionsBath temperature did not impact the efficacy of sonoporation treatment on SiHa cells in vitro. The prototype device was found to be suitable for performing sonoporation on adherent cell cultures and will reduce the time and expertise required for conducting sonoporation experiments on adherent cell cultures in the future.
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