Treatment time reduction for large thermal lesions by using a multiple 1D ultrasound phased array system

To generate large thermal lesions in ultrasound thermal therapy, cooling intermissions are usually introduced during the treatment to prevent near-field heating, which leads to a long treatment time. A possible strategy to shorten the total treatment time is to eliminate the cooling intermissions. In this study, the two methods, power optimization and acoustic window enlargement, for reducing power accumulation in the near field are combined to investigate the feasibility of continuously heating a large target region (maximally 3.2 x 3.2 x 3.2 cm3). A multiple 1D ultrasound phased array system generates the foci to scan the target region. Simulations show that the target region can be successfully heated without cooling and no near-field heating occurs. Moreover, due to the fact that there is no cooling time during the heating sessions, the total treatment time is significantly reduced to only several minutes, compared to the existing several hours.     

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.     

Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood–brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood–brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.     

Opening of the Blood-Brain Barrier by Low-Frequency (28-kHz) Ultrasound: A Novel Pinhole-Assisted Mechanical Scanning Device

Disruption of the blood-brain barrier (BBB) may be transiently achieved via high-frequency focused spherical ultrasound in the presence of microbubbles. In this experimental animal study, we sought to determine whether focal reversible opening of the BBB may be achieved using low-frequency (i.e., 20–30 kHz) planar ultrasonic waves. In the presence of microbubbles, we were able to obtain BBB opening using non-focused ultrasound irradiation with a frequency as low as 28 kHz. We also achieved a tight regulation of the ultrasound patterns by using a mechanical scanning device equipped with a pinhole. Histologic examination of the brains supported the feasibility of our system. The areas of BBB disruption obtained with this method were large enough to cover a typical circumscribed cerebral tumor mass. The inherent advantages of our BBB opening method include an improved portability, the possibility to obtain fairly wide areas of BBB opening and a low incidence of hemorrhagic complications. In addition, our system has the potential to reduce the need for image guidance for treating superficial brain lesions. (E-mail: haoliliu@mail.cgu.edu.tw).     

河南新乡2008年手足口病病原分离鉴定及病毒基因组特征

目的:对2008年分离自河南新乡手足口病患者粪便标本的病原进行分离鉴定及全基因组序列测定,并同相关毒株序列进行同源性比对和进化分析,以了解新分离病毒基因组序列特征及可能的传播来源.方法:将手足口病患者粪便标本接种敏感细胞进行分离传代培养,制备抗原片进行间接免疫荧光检测,采用特异性引物进行PCR鉴定,将病毒基因组分为8个片段进行RT-PCR扩增,扩增产物纯化后进行PCR测序.通过末端重叠序列拼接成全长病毒基因组序列,利用生物信息学软件对序列进行比对分析,绘制进化树.结果:测序获得的3株EV71病毒基因组全长均为7 405 nt,VPI氨基酸序列同源性达100%.Blast分析表明F3(F8)-Henan-08毒株均与安徽阜阳2008年分离的EV71毒株同源性最高,而F4-Henan-08毒株与我国台湾省2004年分离的EV71毒株同源性最高.序列进化分析表明,新分离毒株属于C4基因亚型.结论:新分离的河南EV71毒株与安徽阜阳分离的毒株可能具有相同来源.     

重症监护病房搬进层流病区前后的目标性监测及病原菌构成比变化

目的了解ICU导管相关性感染的现状、分析发展趋势,为干预措施的制定提供参考,同时观察ICU从一般病区搬至层流病区前后病原菌构成的变化,为控制医院感染提供依据。方法 2010年开展多重耐药菌前瞻性病例调查,同时开展重症监护病区的目标性监测,根据卫生部ICU目标性监测要求对于每例研究期间人住ICU>48h及出ICU<48h患者进行监测,计算导管使用率及各类导管相关性感染发病率。结果 2010年4～9月ICU共收住患者76人次,发生院内感染22人42人次,感染历次率为55.26%,感染率为28.96%,患者日感染率59.57‰;ICU总住院天数为705d,呼吸机的平均使用率为51.49%,呼吸机相关性肺炎(VAP)的发病率为49.59‰;中心静脉导管的平均使用率为51.21%、中心静脉导管相关性血流感染(CRBSI)的发病率为8.31‰;导尿管的平均使用率为98.01%、导尿管相关性尿路感染(CAUTI)的发病率为8.68‰。病原菌检出观察设ICU.老病区为对照组,ICU新病区为干预组。阴性杆菌占的比例对照组是74.42%,干预组为67.5%,搬后第二季度为47.62%;阳性球菌对照组占16.28%,干预组15.0%,第二季度28.57%;真菌对照组占23.26%,干预组17.5%,搬后第二季度22.22%。结论 ICU易发生以下呼吸道为主的条件致病菌感染,搬进层流病区后阴性杆菌检出比例减少,3个季度降低近27个点;ICU的院内感染以下呼吸道感染为主,搬迁后由78.95%,降到64.29%,搬后第二季度降至48.57%,三个季度比例降了30个点,说明干预措施有效。     

Effects of NT-4 gene modified fibroblasts transplanted into AD rats

It is well known that fibroblasts can act as a cell vector to express functional protein, like neurotrophin-4 (NT-4). The present study evaluated the effect of NT-4 gene modified fibroblasts grafted into the hippocampus of AD rat model. AD rats were reproduced by bilateral transection of the hippocampal fimbria-fornix. The transplanted fibroblasts steadily expressed NT-4 proteins at least 2 months after transplantation. This correlated with a significant rescue in the number of cholinergic neurons in the host hippocampus. Morris water maze tests demonstrated significant improvements in learning and memory, especially in rats receiving NT-4-modified fibroblasts. The present results showed that NT-4 gene modified fibroblasts could provide a long-term and steady expression of NT-4, and it significantly improved the behavior of AD rats. These findings should have important clinical applications in providing a long-term NT-4 Secretion for the treatment of AD.     

In vivo assessment of macrophage CNS infiltration during disruption of the blood�Cbrain barrier with focused ultrasound: a magnetic resonance imaging study

Focused ultrasound has been discovered to locally and reversibly increase permeability of the blood–brain barrier (BBB). However, inappropriate sonication of the BBB may cause complications, such as hemorrhage and brain tissue damage. Tissue damage may be controlled by selecting optimal sonication parameters. In this study, we sought to investigate the feasibility of labeling cells with superparamagnetic iron oxide particles to assess the inflammatory response during focused-ultrasound-induced BBB opening. We show that infiltration of phagocytes does not occur using optimal parameters of sonication. Taken together, the results of our study support the usefulness and safety of focused-ultrasound-induced BBB opening for enhancing drug delivery to the brain. These findings may have implications for the optimization of sonication parameters.     

Kinetics of a Criegee intermediate that would survive high humidity and may oxidize atmospheric SO2

Criegee intermediates are thought to play a role in atmospheric chemistry, in particular, the oxidation of SO₂, which produces SO₃ and subsequently H₂SO₄, an important constituent of aerosols and acid rain. However, the impact of such oxidation reactions is affected by the reactions of Criegee intermediates with water vapor, because of high water concentrations in the troposphere. In this work, the kinetics of the reactions of dimethyl substituted Criegee intermediate (CH₃)₂COO with water vapor and with SO₂ were directly measured via UV absorption of (CH₃)₂COO under near-atmospheric conditions. The results indicate that (i) the water reaction with (CH₃)₂COO is not fast enough (k_H2O < 1.5 × 10⁻¹⁶ cm³s⁻¹) to consume atmospheric (CH₃)₂COO significantly and (ii) (CH₃)₂COO reacts with SO₂ at a near–gas-kinetic-limit rate (k_SO2 = 1.3 × 10⁻¹⁰ cm³s⁻¹). These observations imply a significant fraction of atmospheric (CH₃)₂COO may survive under humid conditions and react with SO₂, very different from the case of the simplest Criegee intermediate CH₂OO, in which the reaction with water dimer predominates in the CH₂OO decay under typical tropospheric conditions. In addition, a significant pressure dependence was observed for the reaction of (CH₃)₂COO with SO₂, suggesting the use of low pressure rate may underestimate the impact of this reaction. This work demonstrates that the reactivity of a Criegee intermediate toward water vapor strongly depends on its structure, which will influence the main decay pathways and steady-state concentrations for various Criegee intermediates in the atmosphere.Unsaturated hydrocarbons are emitted into the atmosphere in large quantities from either human or natural sources. Ozonolysis of unsaturated hydrocarbons produces highly reactive Criegee intermediates (CIs) (1), which may (i) decompose to radical species like OH radicals or (ii) react with a number of atmospheric species, for example, with SO₂ to form SO₃ and with NO₂ to form NO₃ (2, 3). The SO₂ oxidation by CIs has gained special attentions because the SO₃ product would be converted into H₂SO₄, an important constituent of aerosols and acid rain (4–8). For example, Mauldin et al. (4) have speculated that Criegee intermediate reactions with SO₂ may account for the discrepancy between the observed and modeled concentrations of H₂SO₄ in a boreal forest region, where various alkenes are emitted by trees.Recently, Welz et al. (2) demonstrated an efficient method to prepare a CI in a laboratory by the reaction of iodoalkyl radical with O₂ (for example, CH₂I + O₂ → CH₂OO + I). This method can produce a CI of high enough concentration that allows direct detection. With photoionization mass spectrometry (PIMS) detection, Welz et al. (2) measured the rate coefficients of the simplest CI (CH₂OO) reactions with SO₂ and NO₂. Notably, these new rate coefficients, confirmed by a few later investigations (9–11), are orders of magnitude larger than those previously used (12, 13) in atmospheric models (e.g., MCM v3.3, available at mcm.leeds.ac.uk/MCM/browse.htt?species=CH2OO), suggesting a greater role of CIs in atmospheric chemistry. This result also indicates previous ozonolysis analyses may be affected by complicated and partly unknown side reactions and may contain errors in some of the reported rate coefficients.Typical water concentration in the troposphere (1.3 × 10¹⁷ to 8.3 × 10¹⁷ cm⁻³ at the dew point of 0–27 °C) is orders of magnitude higher than those of atmospheric trace gases like SO₂, NO₂, and volatile organic compounds (VOC) (on the order of 10¹² cm⁻³ or less). Although it has been shown that CIs may react very fast with SO₂, NO₂, and organic acids (2, 3, 14), the reactions of CIs with atmospheric water vapor would still strongly influence the fates and concentrations of atmospheric CIs (see Fig. 1 for a simplified schematic). As expected, the reactivity of CIs toward water vapor would govern the modeling results of atmospheric H₂SO₄ formation from CIs (8, 15, 16).Open in a separate windowFig. 1.Reaction scheme showing competitions for CIs between reactions with water (monomer and dimer) and with SO₂.However, there had been discrepancies about the reactivity of CIs toward water. Whereas studies (17–20) using C₂H₄ ozonolysis as a CH₂OO source show substantial reactivity of CH₂OO toward water vapor, despite a large scatter (10⁻¹⁷ to 10⁻¹² cm³s⁻¹) in the reported rate coefficient, other studies (2, 10, 21) using the CH₂I+O₂ reaction as a CH₂OO source reported negative observation for the CH₂OO reaction with water vapor.More recently, Chao et al. (22) and Berndt et al. (23) investigated the reaction of CH₂OO with water vapor using the CH₂I+O₂ reaction and the C₂H₄ ozonolysis as their CH₂OO sources, respectively. Both groups observed clear second-order kinetics with respect to the concentration of water and concluded that reaction with water dimer predominates in the decay of CH₂OO under atmospheric conditions and that previous studies may require some reinterpretations. The reported rate coefficient of the CH₂OO reaction with water dimer is large, about 7 × 10⁻¹² cm³s⁻¹ (22), leading to extremely fast decay rate of CH₂OO under typical tropospheric conditions (