聚焦超声换能器焦距与直径比值对高强度聚焦超声透过条状障碍物的生物学焦域的影响

目的探讨聚焦超声换能器的物理参数换能器焦距与直径的比值（f-number）对高强度聚焦超声（HIFU）透过条状障碍物的生物学焦域的影响。方法分别选用f-number为0．65（1．0—200—130）和f-number为0．85（1．0—200—170）型换能器在离体牛肝中进行HIFU辐照。将肋骨置于换能器与焦平面之间,HIFU声束轴线在B超的引导下,分别沿肋间隙正中聚焦、肋骨边缘聚焦和正对肋骨聚焦。在每种聚焦方式下,肋骨置于距焦平面3、6、9cm处。HIFU声束透过肋骨聚焦,在牛肝中的辐照深度为20mm,辐照功率250W,辐照时间10S;辐照方式采用定点辐照。辐照结束后切开牛肝,观察和记录生物学焦域的形成率与体积。结果在其他辐照参数相同的情况下,f-number为0．65透过肋骨后生物学焦域的形成率和体积均较f-number为0．85时大（除f-number为0．85正对肋骨聚焦,肋骨距焦平面3cm外）。结论聚焦超声换能器f-number不同,HIFU透过肋骨所形成的生物学焦域形成率与体积不同。     

声通道上的条状障碍物对高强度聚焦超声声场的影响

目的 研究高强度聚焦超声(HIFU)透过用条状障碍物模拟的肋骨后的声场分布.方法 引导HIFU声束透过肋间隙、肋缘及正对肋骨,在每种情况下将肋骨分别置于距焦平面3、6、9 cm处,采用水听器描绘出了每种情况下声场的分布.结果 轴向声压分布:在3种障碍物分布情况下,声通道上由于肋骨的存在,声压幅值较自由场下降了60%～80%,相对于自由场,-6 dB焦域的尺寸增大0.5～1.5 mm.焦点的位置相对于自由场,也发生了前移,焦点向换能器方向靠近0.1～2.3 mm.径向声压分布:在3种障碍物分布情况下,当肋骨距焦平面3、6 cm时,声压的分布出现多峰的现象,相对于自由场,声压幅值降低.当肋骨距焦平面9 cm时,在经过了肋骨之后,波束基本上还是保持了原来的形状,声压分布与自由场接近.结论 声通道上存在肋骨时HIFU焦域的声压幅值明显降低,声压幅值的降低与声束轴线与肋骨的相对位置以及肋骨距焦平面的距离有关.声通道上存在肋骨时对HIFU声焦域有影响,-6 dB焦域尺寸增加.     

声通道上的肋骨对高强度聚焦超声在羊肝内形成凝固性坏死的影响

目的从有效性、安全性和剂量学的角度探讨声通道上的肋骨对高强度聚焦超声（HIFU）损伤山羊肝的影响。方法HIFU分别辐照声通道上有肋骨（对照组）和声通道上肋骨被手术切除（实验组）的羊肝。辐照结束后2d处死动物，观察靶区凝固性坏死形成情况，测量凝固性坏死的体积并计算能效因子（energy efficiency factor，EEF）。结果实验组的凝固性坏死形成率明显高于对照组，EEF远远小于对照组。结论声通道上的肋骨明显影响凝固性坏死的形成率和EEF，提高HIFU治疗受肋骨阻挡的肝癌的治疗效率非常重要。     

高强度聚焦超声联合微泡损伤山羊肝的增效性研究

目的 探讨超声造影剂SonoVue用于增强高强度聚焦超声(HIFU)损伤山羊肝组织的可行性.方法 南江黄羊15只,采用自身对照,分为HIFU治疗组(对照组)和HIFU联合造影剂治疗组(实验组).治疗深度30 mm,分别在声功率为150 W、250 W、350 W条件下对肝定点辐照15 S.辐照后24 h处死动物,解剖观察凝固性坏死情况,并作病理切片分析.结果 在相同声辐照参数下,实验组凝固性坏死发生率及凝固性坏死区域长、宽、厚、体积均明显大于对照组(P＜0.05),随功率增加实验组凝固性坏死体积增加幅度较对照组更明显,实验组能效因子(EEF)明显小于对照组.凝固性坏死区与正常肝组织分界清楚,且病理切片显示损伤为不可逆性,分界处可见大量空泡.结论 HIFU联合微泡造影剂能在山羊肝中形成完全的凝固性坏死,同时提高凝固性坏死的损伤率,增大凝固性坏死体积,提高HIFU治疗效率.     

碳酸氢铵溶液增效HIFU消融新鲜离体牛肝的研究

目的 研究碳酸氢铵溶液增效HIFU消融离体牛肝的作用。方法 用HIFU以不同功率消融离体牛肝,比较不同浓度的碳酸氢铵溶液的实验组与注射PBS的对照组在灰度差值、灰度区域面积及凝固性坏死体积的差别并进行统计学分析。结果 当HIFU消融功率为150w时,各浓度碳酸氢铵溶液组在灰度差值、灰度面积及凝固性坏死体积方面均显著高于PBS对照组（P＜0.05）;而以其他功率进行HIFU消融时,情况并不完全一致。结论 在功率合适时,碳酸氢铵溶液具备增效HIFU消融离体牛肝的作用。     

不同剂量微泡造影剂在高强度聚焦超声消融活体羊肝组织中的增效效应

目的 探讨不同剂量超声造影剂对高强度聚焦超声(HIFU)消融活体羊肝组织的增效效应.方法 南疆黄羊20只,随机分为4组.第1组为HIFU联合0.01 ml/kg SonoVue.第2组为HIFU联合0.03 ml/kg SonoVue,第3组为HIFU联合0.05 ml/kg SonoVue,第4组为单纯HIFU组.麻醉状态下,微泡造影剂于HIFU辐照前静脉团注,20 s后开始HIFU辐照.每组采用定点辐照,所用辐照参数为频率0.8 MHz、声强19 100 W/cm2、辐照深度30 mm、辐照时间15 s.HIFU辐照结束后1周处死动物.观察并测量凝同性坏死大小,对凝固性坏死作组织病理分析.结果 在相同声辐照参数下,1、2、3组凝同性坏死区域均大于第4组,差异有统计学意义(P<0.05),且凝固性坏死体积随SonoVue剂量的增加而逐渐增大,差异有统计学意义(P<0.05).组织病理学检查发现凝同性坏死区内无正常组织残留.除实验3组出现消融灶邻近组织和皮肤损伤外,其余各组均未出现明显并发症.结论 微泡造影剂在HIFU消融过程中的增效效应与微泡造影剂的剂量有关,微泡造影剂的剂量越大,所形成的凝固性坏死的体积越大,增效越明显.     

多功能超声造影剂体外超声-磁共振双模态显像及增效高强度聚焦超声的实验研究

目的 制备一种新型的多功能超声造影剂,体外观察其超声、磁共振(MR)成像效果及增强高强度聚焦超声(high-intensity focused ultrasound,HIFU)消融效果.方法 采用双乳化法合成载超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)纳米颗粒的高分子微球(s-PLGA),检测其一般性质.制备体外成像模型,应用超声诊断仪及磁共振扫描仪对不同浓度s-PLGA分别行超声及MR成像.另取新鲜离体牛肝,局部注射s-PLGA后,给予不同HIFU辐照参数,通过计算辐照区凝固性坏死体积评价s-PLGA增强HIFU消融效果.结果 制备的s-PLGA呈球形,平均直径为(885.6±133.2)nm.体外超声显像,sPLGA呈高回声,回声强度随浓度及机械指数减小而降低;磁共振T2WI呈负增强显像.注射s-PLGA后行HIFU辐照,辐照区凝固性坏死体积明显增大(P＜0.05).结论 自制的多功能超声造影剂-载超顺磁性氧化铁高分子微球具备超声、MR双模态复合成像与增效HIFU的功能.     

碳酸氢铵溶液增效高强度聚焦超声消融新鲜离体牛肝的实验研究

目的研究碳酸氢铵溶液增效高强度聚焦超声(HIFU)消融离体牛肝的作用。方法以不同功率(120 W、150 W、180 W、210 W)HIFU消融离体牛肝,比较注射碳酸氢铵溶液的实验组与注射PBS溶液的对照组的凝固性坏死体积、灰度差及灰度区域面积。结果 HIFU消融功率为120 W时,实验组出现凝固性坏死,体积约(11.53±4.93)mm~3,而对照组无明显凝固性坏死;功率为150 W时,实验组凝固性坏死体积为(50.41±33.7)mm~3,显著大于对照组[(8.60±4.14)mm~3],差异有统计学意义(P0.05);消融功率为180 W时,实验组凝固性坏死体积与对照组比较差异无统计学意义;消融功率为210 W时,实验组凝固性坏死体积为(39.84±13.62)mm~3,显著小于对照组[(62.79±11.32)mm~3],差异有统计学意义(P0.05)。当HIFU消融功率为120 W、150 W时,实验组灰度差和灰度区域面积均显著高于对照组,差异均有统计学意义(均P0.05)。结论在功率120 W、150 W时,碳酸氢铵溶液具备增效HIFU消融离体牛肝的作用。     

灰度相关函数应用于HIFU监控的离体研究

目的探讨在高强度聚焦超声(HIFU)辐照过程中,超声图像与HIFU辐照产生凝固性坏死的关系,以提高监控超声对HIFU凝固性坏死的判断灵敏度。方法在相同声强、辐照时间、辐照深度情况下,HIFU定点辐照离体牛肝,观测靶区辐照前及辐照结束后即刻、1、2、3、4、5 min的声像图变化和灰度值变化,并进行靶区声像图相关函数运算,用支撑矢量机(support vector machine,SVM)筛选参数并得到决策超平面。结果超声图像相关系数可以评价HIFU凝固性坏死情况,其灵敏度高于用灰度评价(χ~2=18.716,P0.05)。结论声像图相关系数判断HIFU辐照的靶组织有无凝固性坏死优于灰度评价。     

HIFU体外块"切除"动物肝脏、肾脏和肌肉的剂量研究

目的　用能效因子( energy- efficiency factor,EEF)作为高强度聚焦超声( high intensity focused ultrasound,HIFU)治疗剂量学评价指标来研究HIFU切除组织块的治疗剂量。方法　按照由束损伤→片损伤→块损伤的治疗原则,使用声强为70 0 0～2 770 0 W/ cm2 ,扫描线长3 0 mm,扫描速度3 mm/ s,束损伤的空间间距5～1 0 mm,片损伤的空间间距5 mm,在山羊肝脏、肾脏和肌肉中形成一个凝固性坏死块。并把形成单位体积凝固性坏死所需的超声能量叫做HIFU治疗的EEF,用EEF作为HIFU治疗剂量学评价指标。结果　按照束损伤→片损伤→块损伤的组合方式能在山羊肝脏、肾脏、肌肉中形成一个完整的凝固性坏死块,且中间没有正常组织残留。在山羊肾脏中形成一个凝固性坏死块的EEF明显大于在山羊肝脏中形成一个凝固性坏死块的EEF,而相比于肾脏和肝脏,在山羊肌肉中形成一个凝固性坏死块的EEF最小。结论　本研究表明同一超声能量在不同的靶组织中所产生的凝固性坏死体积不同,组织的结构、功能状态对HIFU治疗肿瘤的效果具有较大的影响,HIFU治疗剂量学的研究有望为临床治疗肿瘤提供剂量学指导     

Focusing of High-Intensity Ultrasound Through the Rib Cage Using a Therapeutic Random Phased Array

A method for focusing high-intensity ultrasound (HIFU) through a rib cage that aims to minimize heating of the ribs while maintaining high intensities at the focus (or foci) was proposed and tested theoretically and experimentally. Two approaches, one based on geometric acoustics and the other accounting for diffraction effects associated with propagation through the rib cage, were investigated theoretically for idealized source conditions. It is shown that for an idealized radiator, the diffraction approach provides a 23% gain in peak intensity and results in significantly less power losses on the ribs (1% vs. 7.5% of the irradiated power) compared with the geometric one. A 2-D 1-MHz phased array with 254 randomly distributed elements, tissue-mimicking phantoms and samples of porcine rib cages are used in experiments; the geometric approach is used to configure how the array is driven. Intensity distributions are measured in the plane of the ribs and in the focal plane using an infrared camera. Theoretical and experimental results show that it is possible to provide adequate focusing through the ribs without overheating them for a single focus and several foci, including steering at ± 10–15 mm off and ± 20 mm along the array axis. Focus splitting caused by the periodic spatial structure of ribs is demonstrated both in simulations and experiments; the parameters of splitting are quantified. The ability to produce thermal lesions with a split focal pattern in ex vivo porcine tissue placed beyond the rib phantom is also demonstrated. The results suggest that the method is potentially useful for clinical applications of HIFU, for which the rib cage lies between the transducer(s) and the targeted tissue. (E-mail: vera@apl.washington.edu)     

Mechanics of intercostal space and actions of external and internal intercostal muscles.

It is conventionally considered that because of their fiber orientations, the external intercostal muscles elevate the ribs, whereas the internal interosseous intercostals lower the ribs. The mechanical action of the intercostal muscles, however, has never been studied directly, and the electromyographic observations supporting this conventional thinking must be interpreted with caution. In the present studies, the external and internal interosseous intercostal muscles have been separately stimulated in different interspaces at, above, and below end-expiratory rib cage volume in anesthetized dogs. The axial (cephalo-caudal) displacements of the ribs were measured using linear displacement transducers. The results indicate that when contracting in a single interspace and other muscles are relaxed, both the external and internal intercostals have a net rib elevating action at end-expiratory rib cage volume. This action increases as rib cage volume decreases, but it progressively decreases as rib cage volume increases such that at high rib cage volumes, both the external and internal intercostals lower the ribs. Stimulating the intercostal muscles in three adjacent intercostal spaces simultaneously produced similar directional rib motion results. We conclude that (a) in contrast with the conventional thinking, the external and internal interosseous intercostals acting alone have by and large a similar effect on the ribs into which they insert; (b) this effect is very much dependent on rib cage (lung) volume; and (c) intercostal muscle action is primarily determined by the resistance of the upper ribs to caudad displacement relative to the resistance of the lower ribs to cephalad displacement. The lateral intercostals, however, might be more involved in postural movements than in respiration. Their primary involvement in rotations of the trunk might account for the presence of two differently oriented muscle layers between the ribs.     

脂肪及肌肉组织对高强度聚焦超声消融能量沉积及焦域形态的影响

目的比较高强度聚焦超声(HIFU)通过不同厚度脂肪及肌肉组织消融猪肉靶点时的能量衰减情况。方法在MRI监控下分别选择脂肪厚度为0 mm、20 mm、28 mm的猪肉靶点,以输出功率200 W、辐照时间10 s进行单点消融,比较相同辐照条件下所产生的凝固性坏死体积。进一步选择脂肪厚度25 mm带皮猪肉及无皮和脂肪猪肉,分别将焦点置于距肌肉表面深度20 mm、30 mm的靶点进行单点辐照。结果随着脂肪厚度的增加,相同辐照条件下产生凝固性坏死区体积逐渐缩小,长轴逐渐增加,短轴逐渐缩小。当辐照无脂肪的猪肉组织时,随肌肉厚度的增加,损伤体积缩小;但相同厚度的脂肪组织对超声能量的衰减大于肌肉组织。结论 HIFU通过离体脂肪组织、肌肉组织时均有能量衰减;脂肪组织对超声能量的衰减程度高于肌肉组织。     

The use of a segmented transducer for rib sparing in HIFU treatments

The use of focused ultrasound as a minimally invasive treatment for tumours is rapidly expanding. Target organs include the liver and kidneys. Both single element and phased array transducers may be used in the clinic. The presence of the rib cage presents a problem in high intensity focused ultrasound (HIFU) treatment planning, due to its high attenuation of the HIFU beam resulting in a loss of power at the focus as well as an increase in the risk of damage at the rib and to overlying tissues, including the skin. In this paper, a linearly segmented transducer, in which all active elements are driven in phase, has been investigated. The aim of the study was to investigate how a beam with a clinically useful profile could be achieved by removing the contribution of edge segments from one side of the transducer to the field. We have considered the case in which the HIFU beam approaches the rib cage during a treatment and investigated configurations of the transducer for which up to three segments on the edge are switched off. This problem has been studied initially using a linear acoustic field program to model the segmented transducer's acoustic beam profile. Experimental measurements of the transducer's acoustic field were performed using an automated beam plotting system. Temperature measurements were made on a rib surface for two transducer configurations using a fine wire thermocouple. A thermochromic liquid crystal material was used to assess qualitatively the heating pattern generated by the ultrasound beam. We show the rib sparing potential of the segmented transducer during HIFU treatment by demonstrating a reduction in the prefocal width of the ultrasound beam when edge segments are switched off. This has been predicted with the acoustic field model and demonstrated experimentally by acoustic field measurements and observations of the heating pattern generated by the ultrasound beam. A significant decrease in the temperature rise on a rib was observed in the case for which three edge segments were switched off compared with when all segments were active. We conclude that a segmented transducer extends the potential for treating liver tumours. In the case where the tumour lies behind, but close to the edge of, the ribs, energy loss at the focus and excessive heating in the rib and overlying tissue can be avoided by switching off edge segments.     

Study of a "biological focal region" of high-intensity focused ultrasound

The aim of this study was to explore a law of energy deposition of high-intensity focused ultrasound (HIFU) in various tissues and the expression of such a law. A focused ultrasound (US) tumor therapeutic system was used to apply a focused US beam to tissues both in vivo and in vitro. The formation of individual ellipsoid-shaped regions of coagulative necrosis has been observed. Results showed that the volume of the ellipsoid-shaped coagulative necrosis region was different from that of the acoustic focal region (AFR), both in vitro and in vivo. Acoustic intensities ranging from 7 x 10(3) W/cm(2) to 27.7 x 10(3) W/cm(2) and exposure times from 1 to 20 s gave volumes of ellipsoid-shaped coagulative necrosis of 0.2 to 2000 mm(3). Although the HIFU doses applied were identical, the volumes of individual ellipsoid-shaped coagulative necrotic regions varied with the structures of tissues, their functional status and the irradiation depths. Individual ellipsoid-shaped regions of coagulative necrosis induced by HIFU can be added to produce coagulative necrosis of an entire tumor. We define the individual ellipsoid-shaped coagulative necrosis produced by the US energy deposition of a single exposure as the "biological focal region" (BFR) of HIFU. This serves as the basic unit for HIFU ablation of tumors, and is plotted as a function of AFR, acoustic intensity, exposure time, irradiation depth, the tissue structure and its functional status.