The role of thermal conduction in hyperthermia

The role of thermal conduction in hyperthermia has been studied by developing mathematical models that were based on a numerical solution of the partial differential heat conduction equation. Models were developed to study (a) the efficiency of thermal conduction as a heating modality, (b) the effect of heat conduction out of the heated region, and (c) the effect of conduction in equalizing the temperature distribution produced by a non-uniform heating source. Thermal conduction is an efficient form of heating for certain tissue sizes: guidelines have been given indicating this for various tissues and tissue geometries. Conduction of heat out of a uniformly heated region reduces the effective treatment volume. In addition, if the temperature monitoring device (used as a feedback control of power input) is in a position which is influenced by thermal conduction, the temperature within the tissue may rise above the desired value. Non-uniformities in temperature distribution are smoothed out by thermal conduction, however, over only limited distances.     

Thermal radiosensitization of human tumour cell lines with different sensitivities to 41.1oC

While much work on radiosensitization by hyperthermia in the 43oC and higher temperature range has been done, relatively little work has been done at temperatures in the 41-42oC range. In this moderate hyperthermia range there are dramatic differences in the resistance of mammalian cells to hyperthermia. Therefore, thermal radiosensitization was measured in two human colon adenocarcinoma cell lines, one that expresses chronic thermotolerance and proliferates at 41.1oC, NSY 42129 (NSY) cells and one that is slowly killed at 41.1oC, HCT15 cells. Heat-resistant NSY cells were found to be more radioresistant than heatsensitive HCT15 cells. Hyperthermia at 41.1oC enhanced the radiation sensitivity in NSY cells, but no significant induction of heat-induced radiosensitization was observed in HCT15 cells. The radiation sensitivity induced by 41.1oC in NSY cells appeared to be related to both intrinsic heat-induced radiosensitization (HIR) and cell-cycle redistribution at 41.1oC. Incidentally, cells incubated at 41.1oC for between 8-16h displayed an identical radiosensitivity to those heated for 24h. This result implies that modest hyperthermia for 2h or more can have a radiosensitizing effect in heat-resistant cells.     

Predictions of blood flow from thermal clearance during regional hyperthermia

In order to provide a method for estimation of regional blood flow during hyperthermia, a mathematical model has been developed which employs thermal clearance to measure this physiologic parameter. Limbs of mongrel dogs were heated with 2450 megaHertz microwaves to temperatures of 43 degrees C, 45 degrees C, or 47 degrees C and thermal washout was measured at five minute intervals throughout each treatment period. Calculated blood flow indicates that in response to heat challenge, normal tissue compensates by increasing regional blood flow within the treatment volume. This increase in blood flow continues to a maximum value after which the blood flow begins to decrease. Data indicate that the time for maximum increase in blood flow (induction time) decreases as treatment temperature increases. These induction times were 40 minutes, 25 minutes, and 15 minutes for treatment temperatures of 43 degrees, 45 degrees, and 47 degrees C, respectively. The data also show that the calculated value of peak blood flow is directly related to treatment temperature. Calculated peak blood flow values reached 37.8, 59.0, and 183.0 ml/minute/100 grams of tissue during 43 degrees, 45 degrees, and 47 degrees C, hyperthermia, respectively. It is suggested that a therapeutic advantage could be gained by treating tumors for a specific length of time during which the blood flow in adjacent normal tissues continues to increase. This would take maximum advantage of normal tissue's ability to compensate for increased temperature, and would exploit any decreased ability of tumor tissue to perform this same function.     

Edta Clearance in Monitoring Cisplatin Dose Escalation in Patients with Bulky Metastatic Germ Cell Tumors of the Testis

A fast cisplatin clearance may reduce exposure time of tumor cells to the drug, and thus impair the expected effects of dose escalation. This hypothesis was tested in 23 patients with bulky metastatic germ cell tumors of the testis, treated with etoposide, bleomycin and high-dose cisplatin (60 mg/m²/24 h×4). The daily dose was retrospectively calculated in mg/1 EDTA clearance/24 h. A daily dose of 60 mg/m² of cisplatin in a person with a body surface of 1.7 m² and EDTA clearance of 100 ml/min was equivalent to 0.69 mg cisplatin/l EDTA clearance/24 h. In the whole group, 10 patients had complete remission (CR), 10 partial response (PR) and 3 progressive disease (PD). The mean daily cisplatin dose (×) in the whole group was 0.86 mg/1 EDTA clearance/24 h (range 0.35-2.00). For patients with CR, × × SD was 1.00±0.46, for those with PR 0.80±0.44, and for those with PD only 0.61±0.07. A cisplatin dose over 0.86 mg/1 EDTA clearance/24 h × 4 was obtained in 6/10 patients with CR versus 2/13 patients with PR + PD. Patients with PD received a significantly lower cisplatin dose than the whole group (0.61 versus 0.86 mg cisplatin/l EDTA clearance/24 h × 4.) The difference between the average toxicity grade after cisplatin dose over and below 0.69 mg/l EDTA clearance/24 h × 4 was significant only for leukocytes (WHO grade 2.17 versus 1.36). Thus, the effective escalated dose of cisplatin should preferably be calculated not per m² body surface but per 1 liter EDTA clearance. The 'ideal' escalated dose might be about 0.86-1.0 mg cisplatin/l EDTA clearance 24 h × 4.     

Enhancement of Blood Stasis and Vascular Permeability in Meth-A Tumors by Administration of Hyperthermia in Combination with Tumor Necrosis Factor

Blood stasis and vascular permeability induced by tumor necrosis factor (TNF) in Meth-A tumors transplanted in BALB/c mice were significantly enhanced by hyperthermia at 40°C for 30 min immediately following TNF administration. A dose-dependent, sustained decline in the intratumoral blood flow rate occurred following the administration of TNF alone (i.v.; 5 × 10³, 5 × 10⁴, or 5 × 10⁵ JRU/kg) and was enhanced by the administration of hyperthermia in combination with the TNF, even though no decline occurred with hyperthermia alone. The combination of TNF at 5 × 10⁵ JRU/kg and hyperthermia resulted in a blood flow ratio (ratio of blood flow after administration to that before) of 0.47 at 1 h compared with a ratio of 0.65 at 1 h after TNF alone. The blood flow in normal skin sites did not decrease in any case. The permeability of the intratumoral vasculature similarly increased in a dose-dependent manner after the administration of TNF alone and was further increased by combination with hyperthermia, even though no increase occurred with hyperthermia alone. The mean permeability in mice receiving TNF alone at 5 × 10⁵ JRU/kg was 1.35 times that in untreated mice. In mice receiving TNF at the same dose together with hyperthermia, the ratio was increased to 1.65. The results suggest that TNF selectively suppresses intratumoral blood flow, that this effect is enhanced by mild hyperthermia, and that the mechanism of the suppression by TNF with or without hyperthermia partly involves an increase in blood vessel permeability.     

Experimental evaluation of the thermal properties of two tissue equivalent phantom materials

Tissue equivalent radio frequency (RF) phantoms provide a means for measuring the power deposition of various hyperthermia therapy applicators. Temperature measurements made in phantoms are used to verify the accuracy of various numerical approaches for computing the power and/or temperature distributions. For the numerical simulations to be accurate, the electrical and thermal properties of the materials that form the phantom should be accurately characterized. This paper reports on the experimentally measured thermal properties of two commonly used phantom materials, i.e. a rigid material with the electrical properties of human fat, and a low concentration polymer gel with the electrical properties of human muscle. Particularities of the two samples required the design of alternative measuring techniques for the specific heat and thermal conductivity. For the specific heat, a calorimeter method is used. For the thermal diffusivity, a method derived from the standard guarded comparative-longitudinal heat flow technique was used for both materials. For the 'muscle'-like material, the thermal conductivity, density and specific heat at constant pressure were measured as: k = 0:31 0:001W(mK)-1, rho = 1026 7kgm-3, and c p = 4584 107J(kgK)-1. For the 'fat'-like material, the literature reports on the density and specific heat such that only the thermal conductivity was measured as k = 0:55W(mK)-1.     

CT与MRI对鞍区常见肿瘤的诊断价值对比分析

目的 比较CT与MRI诊断鞍区常见肿瘤的临床价值,以期为临床鞍区肿瘤的诊断提供参考.方法 收取确诊为鞍区肿瘤的患者81例对其CT及MRI等影像学诊断结果及病理学诊断结果进行比较与分析,判断两种方法的诊断价值.结果 CT诊断鞍区肿瘤肿瘤检出率为71.60％,MRI诊断鞍区肿瘤检出率为82.72％,MRI检查略高于CT检查,无统计学差异(P＞0.05).垂体腺瘤、脑膜瘤的MRI检出率均明显高于CT检查,颅咽管瘤CT检出率明显高于MRI检查,差异有统计学意义(P＜0.05).由于病理类型不同,CT、MRI检查对于鞍区肿瘤均可显示出不同的影像学特征.结论 CT与MRI对鞍区肿瘤临床诊断价值相当,可能与肿瘤具体病理类型密切相关,因此常规使用两种方法进行联合检测可能获得更佳的辅助诊断效果.     

Blood flow and intravascular volume of mammary adenocarcinoma 13726a and normal tissues of rat during and following hyperthermia

The effects of hyperthermia on blood flow and intravascular volume were studied in mammary adenocarcinoma 13762A growing subcutaneously in the leg of Fischer F344 rats. The blood flow was determined using microspheres labelled with ¹²⁵I, and the blood volume was determined using red blood cells labelled with ⁵¹Cr. At the end of heating with water bath at 43.5°C for 1 hour, there was a marked elevation of ⁵¹Cr in tumor. The 1251 content in tumor also was mildly elevated. Histologically there was a greater number of patent blood vessels per unit area, and they were dilated and hyperemic. In addition, widespread and diffuse hemorrhage could be seen. It appeared, therefore, that the increased ⁵¹Cr and ¹²⁵I label in the tumors immediately after heating was, at least in part, a result of leakage of the labels to extravascular space in addition to possible vasodilation and increased blood flow. At 1 and 5 hours after heating, tumor blood flow was considerably reduced, and at 16 hours both tumor blood flow and blood volume were considerably reduced. Histological examination demonstrated that the tumor blood vessels remained dilated and hyperemic after heating. The effect of heat on blood flow and blood volume in the skin and muscle adjacent to the tumors was also investigated. Blood flow and blood volume in the surrounding normal tissues were significantly elevated at the end of heating. Blood flow was relatively unchanged at 1, 5 and 16 hours after heating, but blood volume was reduced to about one balf. These findings indicate that hyperthermia may induce greater damage to vasculature of tumors than normal tissues, and that vascular damage in tumors may take some time to express itself following moderate hyperthermia.     

Measurement of the thermal conductivity of polyacrylamide tissue-equivalent material

The purpose of this work was to measure the thermal conductivity of polyacrylamide (PAG) and compare it with previously reported values. Polyacrylamide phantoms play an important role in the development of hyperthermia and high-temperature thermal therapies based on electromagnetic (EM) radiation by providing a material that mimics the electrical and thermal properties of human tissue. The thermal properties of PAG have, up until now, not been thoroughly investigated and at least two significantly different values have been published. In this study, the thermal conductivity of polyacrylamide was measured from the steady state temperature drop across samples exposed to a known heat flux. The measured conductivity was 0.56 &#45 0.047 W m &#109 1 °C &#109 1 . To validate the correct set of thermal properties for polyacrylamide, simple heating experiments were performed in a PAG phantom and then simulated using a finite element numerical model that incorporated the measured thermal conductivity along with literature values for specific heat and density. Temperature predictions from the model agreed with average temperatures measured in the phantom to within 1 SD of the measured temperatures.     

彩色多普勒超声对良恶性骨肿瘤的诊断价值

目的 探讨彩色多普勒超声对良恶性骨肿瘤的诊断价值.方法 选取了130例拟诊骨肿瘤患者,根据病情程度分为良性组和恶性组.通过观察患者的血流分级、血流动力学参数、骨皮质连续性、周围软组织浸润情况、超声诊断的准确性,评价彩色多普勒超声对于良恶性骨肿瘤的诊断效果.结果 2组总体血流分级比较,差异具有统计学意义(P<0.05),良性组血流分级多为0级,而恶性组血流分级分布在Ⅱ~Ⅲ级.与恶性组相比,良性组RI和PI值明显较高(P<0.05).与恶性组相比,良性组骨皮质连续性优于恶性组(P<0.05),良性组周围软组织无浸润的情况优于恶性组(P<0.05).超声诊断恶性骨肿瘤符合率95.1%,准确率97.7%.结论 彩色多普勒超声对良、恶性骨肿瘤具有较高的诊断准确度,能清晰地观察到良、恶性骨肿瘤中血流动力学特征及血流分布情况,是良恶性骨肿瘤的首选诊断方式.     

Early Phase Tumor Accumulation of Macromolecules: A Great Difference in Clearance Rate between Tumor and Normal Tissues

The objective of this study was to investigate the molecular weight (MW) and time-dependence of the phenomenon termed "the enhanced permeability and retention"(EPR) effect in solid tumor, in particular to determine and define the early phase accumulation of macromolecules in tumor and normal tissues and the relationship between blood concentration and tissue clearance. As a model, radioiodinated N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers of MW ranging from 4.5 K to 800 K were administered i.v. to mice bearing sarcoma 180 tumor. Within 10 min all HPMA copolymers accumulated effectively in the tumor regardless of MW (1.0–1.5% of injected dose per g of tumor). However, higher MW copolymers (>50 K) showed significantly increased tumor accumulation after 6 h, while the lower MW copolymers (<40 K) were cleared rapidly from tumor tissue due to rapid diffusion back into the bloodstream. Blood clearance was also MW-dependent; the lower MW copolymers displayed rapid clearance, with kidney radioactivity of the copolymers of MW <20 K representing 24% of injected dose per g kidney at 1 min after i.v. administration. Within 10 min these copolymers passed through the kidney and were excreted in the urine. Higher MW copolymers consistently showed kidney levels of 3–5% dose per g kidney in the early phase with no time-dependent accumulation in kidney. There was also no progressive accumulation in muscle or liver, regardless of polymer MW. These results suggest the "EPR effect" in solid tumor primarily arises from in the difference in clearance rate between the solid tumor and the normal tissues after initial penetration of the polymers into these tissues.     

淋巴细胞清除并血浆置换术治疗多发性骨髓瘤的疗效观察

 目的　了解淋巴细胞清除并血浆置换术降低多发性骨髓瘤 (MM )异常免疫球蛋白的作用与疗效。方法　用CS30 0 0 plus血细胞分离机对 2 8例MM患者行淋巴细胞清除并血浆置换术 ,观察淋巴细胞清除并血浆置换术后血沉 (ESR)、球蛋白 (GLB)的下降情况及临床症状的缓解效果。结果　每次淋巴细胞清除并血浆置换术后 ,患者ESR下降 4 1.5± 12 .6mm/h ,GLB下降 16 .9± 7.6g/L ,临床症状得以明显缓解。结论　淋巴细胞清除并血浆置换术能迅速有效地降低MM患者的GLB、ESR水平 ,并具有明显改善临床症状的优点.     

多层螺旋CT三维重建技术在肋骨转移瘤放疗定位中的应用

目的 探讨多层螺旋CT三维重建技术在肋骨转移瘤放疗定位中的应用价值.方法 对50例ECT骨扫描诊断为肋骨转移瘤的患者,行多层螺旋CT扫描并三维重建,根据三维重建图像确定肋骨转移瘤的具体部位和范围,并在模拟定位机下精确定位后实施放疗.结果 50例患者的99处经ECT骨扫描诊断的肋骨转移瘤中,有86处经多层螺旋CT扫描并三...     

聚焦超声高温热疗在治疗实体瘤方面的临床研究

目的　研究聚焦超声高温热疗对实体瘤的治疗效应。方法　用高强可控圆阵聚焦超声 (highintensitycontrolfocusultrasoundHICFU)肿瘤治疗机对入选的 30例进行治疗 ,同时在非该机治疗的另外 2 8例进行对照。结果　HICFU组 :完全缓解 (CR) 5例 ,部分缓解 (PR) 9例 ,好转 (MR) 16例 ,总缓解率 (OR) 46 67% ;KPS评分提高 2 0例 ,稳定 8例 ,下降 2例。对照组 :CR 0例 ,PR 2例 ,MR 14例 ,PD 12例 ,OR 7 14 % ;KPS评分提高 5例 ,稳定 11例 ,下降 12例。两组OR(CR +PR)差异非常显著 (P <0 .0 1)。结论　高强聚焦超声肿瘤治疗机在临床应用过程中具有以下优点 :( 1)技术先进 ,性能优越。 ( 2 )安全、有效。 ( 3)无明显副作用。 ( 4)适用于所有经机载B超可以观察到病灶全貌的良、恶性肿瘤病人。是肿瘤治疗领域里的一种新手段 ,值得推广应用     

机载影像系统分析体部肿瘤放疗摆位误差的临床观察

目的通过直线加速器机载影像系统分析体部肿瘤放疗期间产生的摆位误差,测量临床靶体积(CTV)到计划靶体积(PTV)边界的大小。方法应用直线加速器治疗55例体部肿瘤。放疗前获取锥形束CT(CBCT)图像,将该图像与计划CT图像相匹配,计算平移和旋转误差。结果胸部肿瘤平移误差在左右(x)方向、头脚(y)方向、前后(z)方向分别为(-0.309 8±3.706 7)mm、(0.500 1±5.958 7)mm、(0.161 0±4.512 6)mm;腹部肿瘤分别为(-0.392 7±2.601 2)mm、(0.872 1±5.600 1)mm、(0.110 3±3.297 8)mm;旋转误差在胸部和腹部肿瘤分别为(0.218 3±1.502 8)°、(-0.198 9±1.596 6)°。结论 CTV到PTV胸部肿瘤外放边界值在x方向、y方向、z方向分别为7 mm、11 mm、8 mm为宜;腹部肿瘤分别为5 mm、10mm、6 mm为宜,可以包括90%的摆位误差。     

Thermal dosimetry of spinal cord heating in the mouse

Three systems for the localized heating of the spinal cord of the mouse have been evaluated by measuring the temperatures in the spinal canal (T_sp); at a reference location dorsal to the spine (T_do), and by numerically calculating temperature distributions throughout two-dimensional transverse cross-sections through the middle of the heated region. The systems assessed were water bath heating alone, water bath-rf combination and rf heating alone with oblique, dorsally located electrodes. It has been established that (1) for all systems ΔT (where ΔT–T_sp) decreased throughout a 1 h heating period–this was attributed to changes in blood flow; (2) there existed a considerable variation in the experimental value of ΔT, particularly for rf heating. The resulting error in the estimation of T_sp from a measured value of T_do can be reduced by making use of the observed correlation between ΔT and the slope of a temperature decay curve measured at the beginning of the heating period; (3) rf alone best spares adjacent visceral and superficial tissues from significant elevation of temperature.     

Optimizing the factors which modify thermal enhancement of melphalan in a spontaneous murine tumor

Background: Hyperthermia enhances the cytotoxicity of some chemotherapeutic agents. Both clinical and laboratory studies suggest melphalan may be an important drug when hyperthermia is added to chemotherapy treatments. Factors that may modify the thermal enhancement of melphalan were studied to optimize its clinical use with hyperthermia. Methods: The tumor studied was an early-generation isotransplant of a spontaneous C3Hf/Sed mouse fibrosarcoma, Fsa-II. All studies were performed under supervision of the Animal Care and Use Committee. Hyperthermia was administered by immersing the tumor-bearing foot into a constant temperature water bath. Four factors were studied: duration of hyperthermia, sequencing of hyperthermia and melphalan, intensity of hyperthermia, and tumor size. To study duration of hyperthermia tumors were treated at 41.5°C for 30 or 90 min immediately after intraperitoneal administration of melphalan. For sequencing of hyperthermia and melphalan, animals received hyperthermia treatment of tumors for 30 min at 41.5°C immediately after drug administration, both immediately and 3 h after administration of drug or only at 3 h after administration of drug. Intensity of hyperthermia was studied using heat treatment of tumors for 30 min at 41.5 or 43.5°C immediately following drug administration. Effect of tumor size was studied by delaying experiments until three times the tumor volume (113 mm³) was observed. Treatment of tumors was for 30 min at 41.5°C immediately following drug administration. Tumor response was studied by the mean tumor growth time. Results: Hyperthermia in the absence of melphalan had a small but significant effect on tumor growth time at 43.5°C but not at 41.5°C. Hyperthermia at 41.5°C immediately after melphalan administration doubled mean tumor growth time at 30 min and caused a threefold increase at 90 min (P=0.0002) when compared to tumors treated with melphalan alone at room temperature. Application of hyperthermia for one-half hour immediately following drug administration was the most effective in delaying tumor growth. No significant difference in mean tumor growth time was observed with an increase in temperature from 41.5 to 43.5°C. For large tumors heat alone and melphalan alone caused a moderate increase in tumor growth delay. These effects in large tumors were greatly increased by a combination of chemotherapy and hyperthermia. Conclusions: From our data it would appear that the administration of intraperitoneal melphalan immediately prior to 90 min of heat at 41.5°C may optimize anti-neoplastic activity. These data may be useful in formulating clinical protocols in which melphalan and heat are combined.     

An investigation into the combined effects of X-irradiation and microwave heating on pig skin

An investigation has been made of the effects of microwave heating in enhancing the radiation response of pig skin following exposure to X-rays. Areas on the flanks of pigs were treated with X-rays alone or with X-rays followed by heating for 90 minutes at either 42°C or 44°C. Treatment was given as either a single dose or as three fractions over six days. Microwave heating was produced by two types of direct contact applicator operating at a frequency of 2450 MHz. Skin temperature was monitored with a liquid crystal thermometer and with thermocouples. The early skin reaction was scored quantitatively up to 16 weeks following treatment. The thermal enhancement ratios (TER's) measured were close to unity for all treatments. For single dose treatments and heating at 42°C for 90 minutes, the TERwas 1.05. For the three fraction treatments, the TER was found to be 1.1 when heat treatment was either 42°C/90 minutes or 44°C/90 minutes. Such TER values are in general agreement with those recommended by the Radiation Therapy Oncology Group (RTOG) in North America.