氩氦刀冷冻手术中冻结与复温问题的数值模拟

目的 通过对Endocare型氩氦冷刀的工作性能进行数值模拟,考察其优缺点,为肿瘤冷冻治疗提供参考。方法 针对组织的冷冻及复温,用等效比热法及等热流边界条件预测刀头外周组织的温度变化及组织内冰球的生长演化过程,并分析活体组织内的传热行为。结果 氩氦刀冷冻时,刀头附近组织能在短时间内下降到很低的温度;冰球在冷冻初期增长很快,此后增长速率明显下降,当工质由氩切换为氦后,冰球很快熔化;相同冷冻条件下,氩氦刀在不同组织中产生的冰球的增长速度差别较大。结论 氩氦刀具有较好的快速冷冻和复温性能,但其有效杀灭范围十分有限,对大块肿瘤,需采用多刀联用。     

氩氦刀冷冻消融时间与冰球大小关系的实验研究

目的研究氩氦刀冷冻时间与冰球大小的关系,为临床确定最佳冷冻时间及冷冻靶区设计提供理论依据.方法离体猪肝在37℃恒温液中接受氩氦刀冷冻,分别即时测量2、3 mm氩氦刀冷冻以及两把3 mm氩氦刀间距30 mm冷冻不同时间点时形成冰球长径与横径,进行统计分析.结果直径2 mm刀最大冰球体积分别可达(71×50×50)mm3,直径3 mm刀最大冰球体积(75×56×56)mm3;2把直径3 mm以及3把直径3 mm的氩氦刀组合冷冻时,最大冰球范围分别可达(90×80×56)mm3和(105×100×80)mm3大小.无论哪种方式冷冻,在30 min以内冰球纵径和横径增加明显(P＜0.05),30 min以后冰球体积无明显增长(P＞0.05).结论 氩氦冷冻肿瘤时,靶区消融疗效确切,一般冷冻时间选择在25～30 min较为适宜.     

氩氦靶向治疗对肺癌细胞的灭活作用

目的 研究体内、外氩氦靶向治疗对肺癌细胞的灭活作用。方法 观察氩氦刀对体外培养的肺癌细胞、实验动物及肺癌患者，治疗前后温度响应曲线、病理等方面的变化。结果 体外实验发现氩氦刀在空气及水中均有快速降温及升温作用，在水中能快速形成冰球及融化冰球。氩氦刀对体外培养的肺癌细胞有明显的破坏作用，在人体中也证实能灭活肺癌细胞，在1个月内，肿瘤细胞呈凝固性坏死，在3个月后则被纤维组织代替。动物实验可见，氩氦刀在肌肉组织中快速形成冰球。结论 氩氦刀有快速升、降温作用，体内、外均能灭活肺癌细胞。     

氩氦刀冷冻消融序贯重组人血管内皮抑制素治疗晚期复治非小细胞肺癌的临床研究

目的 探讨氩氦刀冷冻消融序贯重组人血管内皮抑制素注射液(商品名为恩度,以下简称恩度)治疗复治的晚期非小细胞肺癌的临床疗效.方法 30例化、放疗无效的Ⅲ和Ⅳ期非小细胞肺癌患者分为两组:一组18例接受经皮穿刺氩氦刀冷冻消融联合恩度治疗;另一组12例单纯行氩氦刀冷冻消融治疗.以胸部CT动态观察治疗前后的变化,随访患者生存时间.结果 治疗结束后1个月CT复查:两组患者的临床受益率基本一致.而术后3个月及6个月CT复查后进行疗效评价则显示:氩氦刀联合恩度治疗组临床受益率明显优于单纯氩氦刀治疗组.远期生存分析:氩氦刀联合恩度治疗组中位生存时间为279 d,单纯氩氦刀治疗组的中位生存时间为258 d,前者中位生存期明显延长(P<0.01).结论 氩氦刀联合恩度治疗晚期复治非小细胞肺癌有较好的临床疗效.     

CT引导配合氩氦刀治疗肺癌的应用

目的 探讨CT引导在氩氦刀治疗肺癌中的正确应用.方法 对无手术适应证的晚期肺癌患者,在CT引导下准确定位,经皮穿刺行氩氦刀冷冻治疗.结果 本组22例肺癌患者均在CT引导下完成氩氦刀冷冻治疗,共26处病灶;其中17处完全被冰球覆盖,9处病灶冰球覆盖80%以上.近期总有效率达100%.术后测量冷冻区的CT值较术前平均下降35～55 Hu.结论 应用CT影像引导氩氦刀治疗可准确确定肿瘤部位及与周围组织的关系,方便选定进针角度和深度,使手术过程简化、安全.术后可实时观察冰球的大小,判断治疗效果.     

氩氦刀冷冻治疗颅内肿瘤12例

目的 探讨氩氦刀在颅内肿瘤治疗中的应用效果。方法 在12例较大的颅内肿瘤(胶质母细胞瘤7例,脑膜瘤3例,星形细胞瘤2例,最大径为5.5～12cm。)的治疗中,依肿瘤大小选择合适的冷冻刀进行冷冻,在20s内达到-140℃左右,维持5min后快速复温达37℃。如此冷冻-复温重复进行2～3次。然后按冷冻范围切除肿瘤。术后常规放、化疗,并予跟踪随访。结果 肿瘤全切11例,大部切除1例,术中出血极少。3例胶质母细胞瘤和1例垦形细胞瘤分别于术后第7个月(2例)、9个月、12个月复发,其中2例已死亡。其余8例已随访11～13个月,尚无复发迹象。结论 在颅内肿瘤切除术中应用氩氦刀进行冷冻处置,可以极大减少术中出血,降低手术风险,延缓恶性肿瘤的复发。但其远期疗效尚有待观察。     

氩氦刀冷冻治疗肺癌的CT影像学分析

目的:分析氩氦刀靶向治疗肺癌的CT影像学征象及临床意义。方法:选择16例肺部肿瘤患者,在CT引导下,应用氩氦刀微创、靶向冷冻治疗,并分析其影像学表现特点。结果:氩氦刀冷冻形成的冰球能达到覆盖病灶体积的90%~100%,术前、术中和术后有不同的CT影像学表现。治疗后1~3月复查CT,肿块均有较大程度的缩小或消失。结论:CT影像学表现能够直接客观地评价氩氦刀治疗肺部肿瘤的临床意义及预后。     

氩氦刀冷冻消融治疗联合肝动脉化疗栓塞术对原发性肝癌生存的影响

目的：观察氩氦刀冷冻消融联合肝动脉化疗栓塞术对原发性肝癌生存的影响。方法：103例中晚期原发性肝癌患者入组;随机分入分入肝动脉化疗栓塞（TACE）组（31例）、氲氦刀冷冻消融组（32例）、TACE联合氩氦刀冷冻消融组（40例）。术后每月复查AFP、T细胞亚群、上腹部CT观察肿瘤坏死情况;随访26个月,观察患者6个月及1年生存率情况。结果：肝动脉化疗栓塞组、氩氦刀冷冻消融组、氩氦刀冷冻消融联合肝动脉化疗栓塞组完全坏死率分别为32．2％、50．0％、50．0％;经统计学检验,P〈0．05,各组之间差异具有统计学意义。1年生存率分别为54．8％、56．2％、75．0％,联合治疗组较单纯TACE组和氩氦刀冷冻消融组明显提高,差异具有统计学意义。结论：TACE联合氩氦刀冷冻消融更有利于改善患者长期生存,不良反应可耐受。     

CT引导下经皮穿刺氩氦刀靶向冷冻治疗肾癌

目的初步建立氩氦超导手术系统(简称氩氦刀)靶向冷冻治疗肾癌的技术和探讨其原理、安全性及近期疗效。方法7例肾癌患者采用氩氦刀,在CT引导下经皮穿刺对肿瘤病灶行冷冻治疗。结果7例患者冷冻治疗后未出现出血、皮肤冻伤、感染或穿刺道种植转移等严重并发症。7例在冷冻治疗后1个月,CT显示病灶区内出现低密度坏死区,5例肿瘤大小无改变,2例瘤体有不同程度缩小。结论CT引导经皮穿刺氩氦刀冷冻治疗肾癌是一种安全、有效、微创治疗,特别是对于不能行手术切除的肾癌病例。     

氩氦靶向冷冻和联合化疗治疗晚期非小细胞肺癌219例临床研究

目的 探讨经皮穿刺氩氦靶向冷冻治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效,分析氩氦靶向冷冻联合化疗对肺癌局部控制及生存曲线的影响。方法 219例ⅢB和Ⅳ期NSCLC患者根据治疗情况分为单纯接受氩氦靶向冷冻治疗组（118例）和氩氦靶向冷冻联合化疗组（101例）,评估治疗后近期局部控制情况及生存时间,并采用Cox回归模型对联合化疗组进行多因素生存分析。结果 单纯氩氦靶向冷冻治疗组与联合化疗组患者氩氦靶向冷冻冰球覆盖率差异比较无统计学意义（P>0.05）;瘤体直径<4 cm患者较直径≥4 cm冷冻冰球覆盖率高,差异比较有统计学意义（P<0.05);氩氦靶向冷冻联合化疗组术后3个月局部有效控制情况较单纯氩氦靶向冷冻组高,差异比较有统计学意义（P<0.05）;单纯氩氦靶向冷冻与联合化疗组中位生存时间分别为（15.00±1.48）个月和（20.00±2.21）个月,差异比较有统计学意义（P<0.05）;对联合化疗组行多因素分析显示肿瘤大小、诊断分期及术后局部控制情况是影响远期生存率的独立危险因素（P<0.05）。结论 经皮穿刺氩氦靶向冷冻联合化疗治疗晚期NSCLC的近期局部控制情况及生存时间均优于单纯氩氦冷冻治疗;肺癌分期较早、瘤体较小及近期局部控制较好者相对预后较好。     

MR-guided interstitial cryotherapy of the liver with a novel,nitrogen-cooled cryoprobe

The purpose of the study was to test a newly developed, MR-compatible, liquid nitrogen-cooled cryoprobe. The probe has an outer diameter of 3.5 mm and was specifically developed for percutaneous, MR-guided, interstitial cryotherapy. The probe was inserted percutaneously into the livers of 10 rabbits. The cryotherapy procedure was monitored with a surface coil in a 1.5 Tesla magnet using a gradient echo sequence. Follow-up examinations were performed 3 and 7 days after the freezing procedure using T₁- and T₂-weighted spin echo sequences. At 7 days the animals were sacrificed and the cryolesions were examined histologically. The cryoprobe enabled artifact-free MR imaging of the “ice-ball” formation during freezing of the rabbit liver. After 1 min of freezing, the iceball at the tip of the probe showed an average maximum diameter of 10.8 mm. No bleeding complications were observed during or after the freezing procedure. Histologic examination 7 days after cryotherapy confirmed that the liver lesions were the same size as had been predicted by the images of the acute iceball. This new, percutaneously inserted, MR-compatible, liquid-nitrogen cooled cryoprobe allows accurate, artifact-free MR imaging of interstitial cryotherapy.     

MR导向冷冻消融猪肾脏的动态影像学研究

目的:评价冷冻消融对猪肾实质、肾脏微循环、集合系统的影响,为临床冷冻消融肾脏肿瘤的可行性及安全性提供实验理论依据。方法:五指山小型实验猪实验组6头,ipath200光学系统导引下1.47mm氩氦冷冻探针植入集合系统周围,冻融两个循环;对照组2头,仅行穿刺。术中动态监测冰球形成情况。术后1天、14天、30天分别行1.5T高场磁共振检查。结果:实验猪均穿刺并冷冻消融成功。冷冻10min,冰球最大并大部分位于靶组织内,显示为椭圆形极低信号影。术后1.5TMR显示靶区组织T1WI、T2WI均呈低信号伴周围不连续的斑片状高信号出血带。周围可见水肿信号。注入GD-DTPA后,冷冻中心无明显强化,周边见均匀强化环。结论:MR导向穿刺准确率高,未发现继发于冷冻的集合系统损伤,对于小肾癌、局限性的累及集合系统的肾肿瘤安全可行。     

低温手术过程多维传热有限元分析

目的 通过有限元分析,给出低温手术过程组织三维瞬态温度场;考察人体血液灌注和代谢产热对其影响,为优化设计冷刀提供参考。方法 充分考虑组织物性和内热源的非线性,使用基于有限容积法的大型商业有限元软件Ansys求解描述低温手术过程组织传热问题的经典生物传热方程。结果 考虑血液灌注和代谢产热后,组织局部降／复温速率降低、所经历的最低温度绝对数值减少;对应时刻,组织内局部温度梯度增加;相同手术方案下,组织内冻结区域减小,且冰球生长过程减慢。结论 人体血液灌注和代谢产热对低温手术过程影响显著,体外实验由于无法模拟血液灌注和代谢产热效果而对冷刀的优化设计作用有限,必须进行在体实验以优化冷刀及其相应的低温手术方案。     

Treatment of frostbite with i.v. streptokinase: an experimental study in rabbits

Experiments were conducted in 32 rabbits to determine whether treatment with IV streptokinase can effectively limit the extent of tissue damage associated with frostbite injury of the hind limbs. Other variables studied were the temperature of the tissue during freezing, the time taken to rewarm the exposed limbs, and the delay between the initiation of treatment with streptokinase and cessation of freezing. A control group of 16 rabbits was not given streptokinase. The extent of tissue damage was estimated by sequential radionuclide perfusion scans of the exposed limbs. This estimate was based on the proportional loss of tissue perfusion on subsequent twice-weekly nuclear scans in comparison with that shown by scans performed immediately after thawing. Pathologic changes in exposed tissues were studied by histology. Streptokinase treatment and rapid rewarming both resulted in less tissue damage at all freezing temperatures. Streptokinase was most beneficial when given 12 hr after freezing, but was effective even when treatment was delayed up to 48 hr.     

Initial experience of percutaneous renal cryosurgery under the guidance of a horizontal open MRI system

OBJECTIVE: The aim of this study was to obtain preliminary results of cryoablation of renal tumors by using a percutaneous approach guided by a horizontal open MRI system, and to assess the safety and efficacy of this procedure. MATERIALS AND METHODS: Four patients with renal tumors underwent percutaneous cryosurgery with local anesthesia using a horizontal open MRI system (AIRIS II, Hitachi Medical Corp., Tokyo, Japan). The size of the mass was radiographically documented as 4 cm or less in diameter. A 2- or 3-mm cryoprobe was advanced into the renal mass under real-time MR monitoring. Growth of the iceball during cryoablation was monitored by two-dimensional MR images. Follow-up dynamic CT and physical examination were done after two weeks and six weeks. RESULT: MR imaging demonstrated the iceballs as sharply marginated regions of signal loss that expanded and engulfed the renal mass with clear contrast between the iceball and surrounding tissue. Cryoablated tumors resolved, and there were no serious complications and no clinically significant changes during the procedures and follow-up study. CONCLUSION: In this limited clinical trial of percutaneous renal tumor surgery, cryoablation demonstrated its feasibility with minimal morbidity. Intraprocedual MR-guided cryosurgery can be used as a safe modality, although further studies are necessary to determine the long-term efficacy of this procedure.     

Improved slice selection for R2* mapping during cryoablation with eddy current compensation

PURPOSE: To improve the slice profile and image quality of R2* mapping in the iceball during cryoablation with ultrashort echo time (UTE) imaging by compensating for eddy currents induced by the selective gradient when half-pulse radiofrequency (RF) excitation is employed to achieve UTEs. MATERIALS AND METHODS: A method to measure both B0 and linear eddy currents simultaneously is first presented. This is done with a least-square fitting process on calibration data collected on a phantom. Eddy currents during excitation are compensated by redesigning the RF pulse and the selective gradient accordingly, while that resultant from the readout gradient are compensated for during image reconstruction. In vivo data were obtained continuously during the cryoablation experiments to calculate the R2* values in the iceball and to correlate them with the freezing process. RESULTS: Image quality degradation due to eddy currents is significantly reduced with the proposed approaches. R2* maps of iceball throughout the cryoablation experiments were achieved with improved quality. CONCLUSION: The proposed approaches are effective for compensating eddy currents during half-pulse RF excitation as well as readout. TEs as short as 100 microsec were obtained, allowing R2* maps to be obtained from frozen tissues with improved quality.     

Effect of altitude acclimatization on thermoregulation efficiency of man

A study has been conducted on 20 sojourners (SJs) at a high altitude (HA) of 3500 m to evaluate the changes in thermoregulation efficiency (ThE) during acclimatization for 3 weeks, by observing the rate and pattern of rewarming of palm skin temperature (Tsk) after dipping the hand in water of 10 +/- 1 degrees C for 2 min (Tromp's water bath test). The ThE of the SJs was compared to that of 10 acclimatized lowlanders (ALs) staying at the same altitude for about 1 year and 10 high-altitude natives (HANs). In SJ, at sea level (SL), the effect of seasonal variation and ambient temperature on ThE was also studied. The initial Tsk of the palm (29.9 degrees C) was lower at altitude as compared to SL value (32.2 degrees C) in SJs inspite of similar ambient temperature (21 +/- 1 degrees C). There was a prolongation of rewarming time in all the subjects during stay at altitude. The rewarming curve showed a shift towards the right, indicating slower rewarming. The rewarming response of ALs and SJs was comparable at altitude. In HANs, the rewarming at altitude was faster and resembled those of SJs at SL. The rewarming improved in the season following cold months, and at higher ambient temperature in the same season, on the plains. It may be concluded that thermoregulation efficiency of man deteriorates at high altitude, and the peripheral vascular responses to local cold stress do not reach the level attained by natives even after 1 year of acclimatization. General cold acclimatization improves the rewarming response.     

An improved method for inducing hypothermia and rewarming.

A hypothermia and rewarming system combining body surface and ventilatory heat exchange is described. The method utilizes body surface heat exchange through conduction, convection, and black body radiation, and ventilatory heat exchange across the lung surface through conduction, convection, and water evaporation. The system consisted of a chamber in which the temperature was maintained at a desired level (+/- 2.5 degrees C) using a refrigeration-heat pump unit. Chamber temperatures during cooling and rewarming were -15.5 +/- 2.7 degrees C and 43.2 +/- 2.3 degrees C, respectively. Inhalate temperatures during cooling were -8.2 +/- 6.5 degrees C and during rewarming they were 41.5 +/- 0.3 degrees C. Helium (100%) was supplied to the chamber, while the animal was ventilated with 20% O2 + 80% He. Under these conditions, the cooling and rewarming rates were 0.33 +/- 0.06 degrees C/min and 0.20 +/- 0.04 degrees C/min, respectively, at 38--21 degrees C. The system provided for rapid cooling and rewarming with no evidence of any untoward effects.     

Frostbite: experimental assessment of tissue damage using Tc-99m pyrophosphate. Work in progress

We designed an experimental model using a new method of freezing to study the pathogenesis and treatment of frostbite. Frostbite was simulated in a manner that closely resembles that which occurs in a natural environment. We used a radionuclide imaging technique to monitor the evolution and extent of tissue damage relative to temperature, rate of freezing, and controlled rewarming. Characteristic sequential changes were demonstrated on sequential nuclear scans. Nonperfusion, followed by perfusion, and finally again by nonperfusion occurred in all areas in which necrosis developed. The reappearance of nonperfusion corresponded to vascular injury and thrombosis evidenced at pathologic examination. We determined that lack of tissue perfusion corresponded to tissue injury. We believe that our experimental model provides an effective means of evaluating potential therapeutic regimens.