The use of focused ultrasound thermal ablation to treat hepatocarcinoma and other liver tumors produces promising clinical results. However, one of the major drawbacks is the high absorption of ultrasonic energy by the rib, making partial rib removal necessary in many cases. This study numerically investigated the feasibility of using a spherical ultrasound phased array for transrib liver-tumor thermal ablation. An independently array-element activitation scheme, which switches off the transducer elements obstructed by the ribs based on feedback anatomical medical imaging, was proposed to reduce the rib-overheating problem. The numerical results showed that the proposed treatment planning strategy can effectively reduce the specific energy absorbed by the rib while maintaining the energy at the target position, which both reduces the rib-overheating problem and increases the possibility of treating a target lesion under an intact rib. The analysis also demonstrated that the target position and the ultrasound frequency play key roles in the treatment. Patients with diverse characteristics were also tested to show the generality of the proposed strategy. The proposed treatment planning strategy also provides useful information for evaluating the treatment effectiveness prior to clinically performing transrib ultrasound liver-tumor thermal ablation.
BackgroundTuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of multiple hamartomas in many internal organs. Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the development of TSC. More than two-thirds of TSC patients are sporadic cases, and a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have been reported.MethodsMutational analysis of TSC1 and TSC2 genes was performed in 84 Taiwanese TSC families using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing.ResultsMutations were identified in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2 familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty-one of the 64 mutations found have not been described previously. The phenotype association is consistent with findings from other large studies, showing that disease resulting from mutations to TSC1 is less severe than disease due to TSC2 mutation.ConclusionThis study provides a representative picture of the distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained TSC cases in the Taiwanese population. Although nearly half of the mutations identified were novel, the kinds and distribution of mutation were not different in this population compared to that seen in larger European and American studies.
In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe 3 O 4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity ( r 2 ) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity ( r 1 ) ( r 2 / r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T 2 -weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.
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