Win-Li Lin

Second-law analysis on a pin-fin array under crossflow

Abstract Second-law analysis on a pin-fin array under crossflow was conducted, from which the entropy generation rate was evaluated. Increase in the crossflow fluid velocity would enhance the heat transfer rate and hence, reduce the heat transfer irreversibility. Nevertheless, owing to the simultaneous increase in drag force exerting on the fin bodies, the hydrodynamic irreversibility increases as well. An optimal Reynolds number thereby exists over wide operating conditions. Optimal design/operational conditions were searched for on the basis of entropy generation minimized. Comparisons between the staggered and the in-line pinfin alignments were made in this report.

Feasibility of transrib focused ultrasound thermal ablation for liver tumors using a spherically curved 2D array: a numerical study.

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.

Quantitative and qualitative investigation into the impact of focused ultrasound with microbubbles on the triggered release of nanoparticles from vasculature in mouse tumors.

Ultrasound-mediated microbubble destruction may enhance the release of nanoparticles from vasculature to tumor tissues. In this study, we used four different sizes of lipid-coated CdSe quantum dot (LQD) nanoparticles ranging from 30 to 180 nm, 1.0-MHz pulsed focused ultrasound (FUS) with a peak acoustic pressure of 1.2-MPa, and an ultrasound contrast agent (UCA; SonoVue) at a dose of 30 microL/kg to investigate any enhancement of targeted delivery. Tumor-bearing male Balb/c mice were first injected with UCA intravenously, were then sonicated at the tumors with FUS, and were finally injected with 50 microL of the LQD solution after the sonication. The mice were sacrificed about 24h after the sonication, and then we quantitatively and qualitatively evaluated the deposition of LQDs in the tumors by using graphite furnace atomic absorption spectrometry (GF-AAS), photoluminescence spectrometry (PL), and harmonic generation microscopy (HGM). Further, immunoblotting analysis served to identify the biochemical markers reflecting the vascular rupture. The experimental results show that the amount of LQDs deposited in tumor tissues was greater in cases of FUS/UCA application, especially for smaller LQDs, being 4.47, 2.27, 0.99, and 0.82 (microg Cd)/(g tumor) for 30, 80, 130, and 180 nm of LQDs, respectively; compared to 1.12, 0.75, 0.26, and 0.34 (microg Cd)/(g tumor) in absence of FUS/UCA. The immunoblotting analysis further indicates that FUS-induced UCA oscillation/destruction results in rupture areas in blood vessels increasing the vascular permeability and thus justifying for the higher quantity of nanoparticles deposited in tumors.

Molecular and clinical analyses of 84 patients with tuberous sclerosis complex

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.

Optimization of temperature distributions in scanned, focused ultrasound hyperthermia

Scanned, focused ultrasound systems (SFUS) have considerable flexibility in shaping the power deposition field during hyperthermia treatments. When utilizing this adaptability many complicated, interacting decisions must be made to obtain an optimal steady-state temperature distribution. This optimization problem is studied using a 3-D, radially symmetric simulation program which searches for a set of optimal scan parameters. The conjugate-gradient optimization technique with a golden section search was used to obtain the optimal temperature distributions attainable with a single circular scan of a tumour. The variable scan parameters of the single transducer heating system optimized (and under the control of the therapist) are: transducer tilt and rotation angles, focal depth, output acoustical power, and scan radius. This single scan study includes the effects of tumour and normal tissue blood perfusions, tumour depth, skin temperature boundary condition, as well as tumour size and shape. A similar, but less comprehensive, study was done for larger tumours using two concentric circular scans. The results show that (1) the optimization process can produce a set of scan parameters that give a considerably better temperature distribution than could be obtained ad hoc, and (2) the optimal scan parameter configuration obtained produces a close-to-ideal tumour temperature distribution for a wide variety of clinically relevant conditions. Thus, when extended to include data from individual patients such optimization should be a very useful tool in patient treatment planning, and should enhance the present capabilities of clinical scanned, focused ultrasound systems.

Effect of the directional blood flow on thermal dose distribution during thermal therapy: an application of a Green's function based on the porous model.

This study presents the effects of directional blood flow and heating schemes on the distributions of temperature and thermal dose during thermal therapy. In this study, a transient bioheat transfer equation based on the porous medium property is proposed to encompass the directional effect of blood flow. A Greens function is used to obtain the temperature distribution for this modified bioheat transfer equation, and the thermal dose equivalence is used to evaluate the heating results for a set of given parameters. A 10 x 10 x 10 mm3 tumour tissue is heated by different heating schemes to investigate the thermal dose variation with the clinical therapeutic arrangement. For a rapid heating scheme, the domain of thermal lesion can effectively cover the desired therapeutic region. However, this domain of thermal lesion may extend to the downstream normal tissue if the porosity is high and the averaged blood velocity has a larger value.

Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system

Chemotherapy for brain cancer tumors remains a big challenge for clinical medicine due to the inability to transport sufficient drug across the blood-brain barrier (BBB) and the poor penetration of drug into the tumors. To effectively treat brain tumors and reduce side effects on normal tissues, both des-octanoyl ghrelin and folate conjugated with polymersomal doxorubicin (GFP-D) was developed in this study to help transport across the BBB and target the tumor as well. The size measurements revealed that this BBB-penetrating cancer cell-targeting GFP-D was about 85 nm. In-vitro experiments with a BBB model and C6 glioma cells demonstrated that GFP-D owned a robust penetrating-targeting function for drug delivery. In C6 cell viability tests, GFP-D exhibited an inhibitory effect significantly different from the unmodified polymersomal doxorubicin (P-D). In-vivo antitumor experiments showed that GFP-D performed a much better anti-glioma effect and presented a significant improvement in the overall survival of the tumor-bearing mice as compared to the treatments with free doxorubicin (Dox), liposomal doxorubicin (L-D), P-D, or single ligand conjugated P-D. In addition, Cy 5.5 was used as a probe to investigate the delivery property of this penetrating-targeting delivery system. The overall experimental results indicate that this BBB-penetrating cancer cell-targeting GFP is a highly potential nanocarrier for the treatment of brain tumors.

EFFECTS OF FOCUSED ULTRASOUND AND MICROBUBBLES ON THE VASCULAR PERMEABILITY OF NANOPARTICLES DELIVERED INTO MOUSE TUMORS

Ultrasound sonication with microbubbles (MBs) was evaluated for enhancement of the release of nanoparticles from vasculature to tumor tissues. In this study, tumor-bearing Balb/c mice were insonicated with focused ultrasound (FUS) in the tumors after the injection of MBs (SonoVue) and then lipid-coated quantum dot (LQD) nanoparticles (130 +/- 25 nm) were injected through the tail vein. We studied the effects of the injected MB dose (0-300 microL/kg), sonication duration (0-300 s) and treatment-procedure sequence on the accumulation of nanoparticles in the tumors 24 h after the treatment and the time response of the accumulation (0.5-24 h). After the treatment, the mice were sacrificed and perfused and then the tumor tissues were harvested for quantifying the amount of nanoparticles using graphite furnace atomic absorption spectrometry (GF-AAS). The results showed that pulsed-FUS sonication with MBs can effectively enhance the vascular permeability for LQD nanoparticle delivery into the sonicated tumors. It indicates that this technique is promising for a better nanodrug delivery for tumor chemotherapy.

Effect of effective tissue conductivity on thermal dose distributions of living tissue with directional blood flow during thermal therapy

Abstract This study proposes a modified transient bioheat transfer equation based on combing the porous medium property and the scalar effective thermal conductivity equation in order to include the directional effect of blood flow. By applying the porous medium model to describe the collective behavior of the heat transfer in living tissue with many small blood vessels, an analytical solution can be obtained by Greens function. Simulation results quantitatively show that the blood perfusion rate, the averaged blood velocity, the porosity and the heating period are the crucial factors determining the distribution of thermal dose for thermal therapies. In addition, longer heating schemes induce dependencies of both the blood perfusion and the enhanced thermal conductivity on increased temperature.

Enhancement of focused ultrasound with microbubbles on the treatments of anticancer nanodrug in mouse tumors

Ultrasound sonication with microbubbles (MBs) has the potential to enhance the delivery of nanoparticles into the sonicated tumors. In this study, we investigated the feasibility of focused ultrasound (FUS) sonication with MBs to improve nanodrug delivery and tumor treatment. Tumor-bearing mice were first injected with MBs (SonoVue) intravenously, were then sonicated at the tumors with FUS sonication, and were finally injected with the PEGylated liposomal doxorubicin (DOX). The accumulation of DOX in tumors with time, the tumor growth responses for initial treated tumor size and DOX dosage, and the response for an additional sonication after DOX injection were studied. The results demonstrate that FUS sonication with MBs can significantly enhance DOX accumulation in the sonicated tumor at 24 hours after treatment. A significant hindrance to tumor growth is achieved for a small tumor with a low dose, whereas large tumors require a higher dose.