Perturbations due to the use of catheters with non-perturbing thermometry probes

Perturbations due to the use of catheters with non-perturbing thermometry probes were investigated in static phantom at 915 MHz. Fibre optic probes for the Luxtron and Clini-Therm thermometry systems, and Vitek probes for the BSD hyperthermia systems, were inserted in closed-end catheters at depths up to 2 cm in the phantom and exposed parallel to the E-field. The probes alone produced 0-12 per cent changes in heating and catheters alone were 0-20 per cent. When the probes were inserted in catheters, perturbations were 0-12 per cent at the surface and 1 cm depth, and 5-15 per cent at 2 cm depth. Even with non-perturbing probes it is important to place catheters perpendicular to the E-field during microwave hyperthermia.     

Perturbations due to the use of catheters with non-perturbing thermometry probes

Perturbations due to the use of catheters with non-perturbing thermometry probes were investigated in static phantom at 915 MHz. Fibre optic probes for the Luxtron and Clini-Therm thermometry systems, and Vitek probes for the BSD hyperthermia systems, were inserted in closed-end catheters at depths up to 2 cm in the phantom and exposed parallel to the E-field. The probes alone produced 0-12 per cent changes in heating and catheters alone were 0-20 per cent. When the probes were inserted in catheters, perturbations were 0-12 per cent at the surface and 1 cm depth, and 5-15 per cent at 2 cm depth. Even with non-perturbing probes it is important to place catheters perpendicular to the E-field during microwave hyperthermia.     

The use of implanted closed-tip catheters for the introduction of thermometry probes during local hyperthermia treatment series

In the past two and a half years custom-made closed-tip catheters have been used to allow extensive temperature monitoring with multi-junction thermocouple probes during local hyperthermia. Data from animal experiments indicate that the use of thermometry probes within such a catheter provides reliable temperature measurements. In order to reduce stress to the patient the catheters were fixed so that they could stay in place during the total treatment series. The catheters, outer diameter 1.22 mm, were introduced through hollow needles under sterile conditions before the first hyperthermia session, and fixed using Histo-acryl (tissue adhesive) and Tegaderm (transparent adhesive). Recently, the data concerning the first 180 catheters placed in 74 treatment areas were evaluated. In one patient, an abscess developed 10 days after removal of the (3) catheters, which required surgical intervention, but it was not clear whether these problems had developed as a result of catheter placement. There were no problems with 139 of the remaining 177 catheters (79 per cent) and in 50 treatment fields (68 per cent), respectively, for a duration of 9-55 (mean 23) days. Ten catheters (6 per cent) were lost during the treatment series after 1-22 (mean 10) days. With 28 catheters (16 per cent) infection was observed, 14-27 (mean 19) days after insertion, which necessitated catheter removal before the last treatment session in 11 cases (6 per cent). The complication rate decreased with increasing experience; from 29 per cent (25/85) in the early period to 14 per cent (13/92) in the later period. We conclude that the use of closed-tip catheters under proper control generally causes few, if any, problems. This results in the acquisition of a substantial amount of reliable temperature data at reproducible sites, and it is well tolerated by the patient.     

Automated mechanical thermometry probe mapping systems for hyperthermia.

In order to better assess temperature distribution patterns in patients, tissue equivalent phantoms, and experimental animals, mechanical devices and automated control systems for positioning temperature probes in implanted catheters and catheters laid on the skin surface have been developed. They employ stepper motor actuated roller and idler wheel drives to move the probes. Two devices incorporate positive positioners in addition to the drive rollers in order to obtain higher positioning accuracy where significant probe to catheter friction is present. Automated systems have been constructed which can simultaneously position, record and display data from up to 10 temperature sensors in a colour-coded position versus temperature format to produce a real time two-dimensional colour-coded pseudo isotherm display. These thermal mapping devices have been used for characterizing the power deposition patterns of several large area microwave applicators (on the surface and at depth within tissue equivalent phantoms), for intraorgan temperature mapping in experimental animals, and for surface and subcutaneous temperature mapping during clinical treatments.     

Treatment monitoring and thermometry for therapeutic focused ultrasound.

Therapeutic ultrasound is currently enjoying increasingly widespread clinical use especially for the treatment of cancer of the prostate, liver, kidney, breast, pancreas and bone, as well as for the treatment of uterine fibroids. The optimum method of treatment delivery varies between anatomical sites, but in all cases monitoring of the treatment is crucial if extensive clinical acceptance is to be achieved. Monitoring not only provides the operating clinician with information relating to the effectiveness of treatment, but can also provide an early alert to the onset of adverse effects in normal tissue. This paper reviews invasive and non-invasive monitoring methods that have been applied to assess the extent of treatment during the delivery of therapeutic ultrasound in the laboratory and clinic (follow-up after treatment is not reviewed in detail). The monitoring of temperature and, importantly, the way in which this measurement can be used to estimate the delivered thermal dose, is dealt with as a separate special case. Already therapeutic ultrasound has reached a stage of development where it is possible to attempt real-time feedback during exposure in order to optimize each and every delivery of ultrasound energy. To date, data from MR imaging have shown better agreement with the size of regions of damage than those from diagnostic ultrasound, but novel ultrasonic techniques may redress this balance. Whilst MR currently offers the best method for non-invasive temperature measurement, the ultrasound techniques under development, which could potentially offer more rapid visualisation of results, are discussed.     

Cytotoxic T-cells as imaging probes for detecting glioma

Tumor vaccination using tumor-associated antigen-primed dendritic cells (DCs) is in clinical trials. Investigators are using patients' own immune systems to activate T-cells against recurrent or metastatic tumors. Following vaccination of DCs or attenuated tumor cells, clinical as well as radiological improvements have been noted due to migration and accumulation of cytotoxic T-cells (CTLs). CTLs mediated tumor cell killing resulted in extended survival in clinical trails and in preclinical models. Besides administration of primed DCs or attenuated or killed tumors cells to initiate the generation of CTLs, investigators have started making genetically altered T-cells (CTLs) to target specific tumors and showed in vivo migration and accumulation in the implanted or recurrent tumors using different imaging modalities. Our groups have also showed the utilization of both in vivo and in vitro techniques to make CTLs against glioma and used them as imaging probes to determine the sites of tumors. In this short review, the current status of vaccination therapy against glioma and utilization of CTLs as in vivo imaging probes to determine the sites of tumors and differentiate recurrent glioma from radiation necrosis will be discussed.     

Nitroaryl compounds as potential fluorescent probes for hypoxia. I. Chemical criteria and constraints

Cellular reduction of nitroaryl compounds is efficiently inhibited by oxygen, and detection of products characteristic of reduction could form the basis for diagnostic tests for the presence of hypoxic cells in tumors. The criteria for suitable compounds include a high sensitivity and selectivity of detection response between oxic and hypoxic cells, which can be provided using fluorescence detection and suitable nitroaryl compounds which have very low fluorescence until reduced. Examples described include a nitroacridine and nitronaphthalimides. Although the intercalating ability of these ring systems lead to high sensitivity for detection of reduced metabolites in vitro by flow cytometry, poor bioavailability is an unwanted consequence of intercalation. The application of several model reducing systems for reduction of potential fluorescent probes for hypoxia is described, and the absorption and fluorescence spectral characteristics of other examples of structures which could form the basis for useful probes are outlined.     

Radiofrequency capacitive hyperthermia for deep-seated tumors. I. Studies on thermometry

The thermometry results of radiofrequency (RF) capacitive hyperthermia for 60 deep-seated tumors in 59 patients are reported. Hyperthermia was administered regionally using two RF capacitive heating equipments which the authors have developed in cooperation with Yamamoto Vinyter Company Ltd., (Osaka, Japan). Intratumor temperatures were measured by thermocouples inserted through angiocatheters which were placed 5 cm to 12 cm deep into the tissues. Tumor center temperatures were measured for 307 treatments in all tumors; thermal distributions within tumors and surrounding normal tissues were obtained for 266 treatments of 53 tumors by microthermocouples. Thermometry results obtained were summarized as follows. A maximum tumor center temperature greater than 43 degrees C and 42 degrees C to 43 degrees C was obtained in 23 (38%) and 14 (23%) of the 60 tumors respectively. The time required to reach 43 degrees C in the tumor center was within 20 minutes after the start of hyperthermia in 87% of tumors heated to more than 43 degrees C. Temperature variations within a tumor exceeded 2 degrees C in 81% of tumors heated to more than 43 degrees C. The lowest tumor temperature greater than 42 degrees C was achieved in six of the 53 tumors (11%). Of 42 tumors in which temperatures of the subcutaneous fat, surrounding normal tissues, and the tumor center were compared, 24 (57%) showed the highest temperature in the tumor center and ten (24%) in the subcutaneous fat. When the heating efficacy was assessed in terms of a maximum tumor center, it great deal depended on the treatment site, tumor size, thickness of subcutaneous fat, and tumor type. Tumors in the head and neck, thorax, lower abdomen, and pelvis could be heated better than tumors in the upper abdomen. Greater heating efficacy was shown in patients with large, hypovascular tumors, and with the subcutaneous fat measuring less than 15 mm thick. The predominant limiting factor for power elevation was pain associated with heating. Systemic signs including increases in pulse rate and body temperature were not serious and seldom became limiting factors for power elevation. Our thermometry results indicate that the advantages of deep RF capacitive heating are its applicability to various anatomic sites and negligible systemic effects. The disadvantages are that its primary usefulness is limited to patients with thin subcutaneous fat and with large or hypovascular tumors.     

Introduction: Non-invasive thermometry for thermotherapy

Cancer of the cervix is the second most common cancer in women worldwide and the fourth leading cause of cancer mortality in women. Early cervical cancer stage IB1 includes a broad range of disease from clinically undetectable microinvasive cancer to bulky tumours that infiltrated the entire cervix. This article reviews the literature about risk factors and surgical radicality and fertility-sparing surgery in early cervical cancer. The review evaluates selection criteria, preoperative management and the most frequent surgical procedures used for individually tailored surgery for cervical cancer.     

Nitroaryl compounds as potential fluorescent probes for hypoxia. II. Identification and properties of reductive metabolites

Nitroakridin 3582 (NA) and a nitronaphthalimide (DM113), which fluoresce only upon reduction, have been studied by HPLC. V79-379A cells incubated with NA under 20% or 2% O2 and N2 gave increasing amounts of the fluorescent amine with an hypoxic:oxic differential of 160. Measurement of the uptake of NA showed that it was concentrated within the cell by over 1000-fold. Studies in 3 different cell lines of reduction under hypoxia showed a 7-fold range in amine production. DM113 yields more than one fluorescent product, which show different absorption and fluorescence spectra. Chemical reduction of NA or DM113 using a variety of methods gave, depending on conditions, amine and/or (what was presumed to be) hydroxylamine; the latter was non-fluorescent. In vivo, NA is toxic at greater than 0.19 mumol g-1. At this dose much of the drug is found in the liver and kidneys. Plasma levels at 30 minutes are only 2 microM while tumor concentrations are 10 microM compared to 600 microM in the liver. However, the half life is greater than 1 hr and amine was detectable in these tumors.     

Total implants for hyperthermia application and thermometry

Tests have been performed in saline phantoms on a 6.78 MHz hyperthermia applicator designed for complete implantation; no conductors would penetrate the skin following the implant procedure. Energy is coupled across the skin from an external to an internal loop antenna: the latter is connected by transmission line to conventional r.f. tissue electrodes which are typically either parallel plates or arrays of cylindrical pins. In phantoms the technique produces deep, localized heating at a selected site without significant hearing at the 'subdermal' receiving antenna near the surface. In addition, the hyperthermia applicator may have potential as an indicator of temperature for the tissue volume at the deep site, since complex impedance at the external antenna is a function of tissue resistivity/temperature at the electrodes. Specifically, temperature at the deep site can be controlled effectively by regulation of the phase angle between voltage and current at the external antenna. A separate passive implantable electromagnetic-reflectance thermometer, energized by external electromagnetic fields, has been designed. This device, also tested in gel and water phantoms, is energized and interrogated by external r.f. fields and tracks a thermocouple to within +/- 0.1 degree C over the range of interest in clinical hyperthermia. The intended application for these devices is repeated, long-term hyperthermic treatment and thermometry of deep-seated malignant tumours following a single invasive procedure.     

半导体量子点荧光探针在恶性肿瘤中的应用

半导体量子点（或称半导体纳米微晶体）与传统的有机荧光标记物相比,具有独特的光谱特性和良好的光化学稳定性.近年来随着水溶性量子点制备技术、纳米技术和生物技术的飞速发展,基于半导体量子点发展起来的生物亲和性功能化的纳米荧光探针,提供了对体内活细胞或活细胞内多种生物分子“编码”标记后同时进行多通道原位实时动态研究的技术平台.现综述半导体量子点荧光探针的光谱特性及其在活细胞生理条件下用于恶性肿瘤的研究进展和发展前景.     

半导体量子点荧光探针在恶性肿瘤中的应用

半导体量子点(或称半导体纳米微晶体)与传统的有机荧光标记物相比,具有独特的光谱特性和良好的光化学稳定性.近年来随着水溶性量子点制备技术、纳米技术和生物技术的飞速发展,基于半导体量子点发展起来的生物亲和性功能化的纳米荧光探针,提供了对体内活细胞或活细胞内多种生物分子"编码"标记后同时进行多通道原位实时动态研究的技术平台.现综述半导体量子点荧光探针的光谱特性及其在活细胞生理条件下用于恶性肿瘤的研究进展和发展前景.     

Treatment monitoring and thermometry for therapeutic focused ultrasound

Therapeutic ultrasound is currently enjoying increasingly widespread clinical use especially for the treatment of cancer of the prostate, liver, kidney, breast, pancreas and bone, as well as for the treatment of uterine fibroids. The optimum method of treatment delivery varies between anatomical sites, but in all cases monitoring of the treatment is crucial if extensive clinical acceptance is to be achieved. Monitoring not only provides the operating clinician with information relating to the effectiveness of treatment, but can also provide an early alert to the onset of adverse effects in normal tissue. This paper reviews invasive and non-invasive monitoring methods that have been applied to assess the extent of treatment during the delivery of therapeutic ultrasound in the laboratory and clinic (follow-up after treatment is not reviewed in detail). The monitoring of temperature and, importantly, the way in which this measurement can be used to estimate the delivered thermal dose, is dealt with as a separate special case. Already therapeutic ultrasound has reached a stage of development where it is possible to attempt real-time feedback during exposure in order to optimize each and every delivery of ultrasound energy. To date, data from MR imaging have shown better agreement with the size of regions of damage than those from diagnostic ultrasound, but novel ultrasonic techniques may redress this balance. Whilst MR currently offers the best method for non-invasive temperature measurement, the ultrasound techniques under development, which could potentially offer more rapid visualisation of results, are discussed.     

A thermometry system for quality assurance and documentation of whole body hyperthermia procedures.

Since December 2001, the Department of Oncology and Medical Physics, Haukeland University Hospital, Norway has been conducting whole body hyperthermia (WBH) studies, treating patients with either ovarian carcinoma or non-Hodgkin lymphomas. Accurate and reliable thermometry instrumentation is important in all types of hyperthermia procedures, particularly in WBH, where the target patient body temperature is 41.8 degrees C. Reliable documentation of side-effects in clinical studies is also dependent on precise temperature monitoring, since in this temperature range even small, but systematic, inaccuracies (0.1-0.2 degrees C) in the temperature monitoring is expected to affect the amount of side effects. Readily available heating and temperature data from previous treatment sessions of the same patient is also valuable for precise temperature control in future treatment sessions. The WBH thermometry system implemented at Haukeland University Hospital is described. It is based on commercially available components, including standard medical thermistor probes, and includes a temperature calibration and verification facility. The thermometry system is accurate, reliable, easy to use, comfortable for the patient and relatively inexpensive. By implementing the Steinhart-Hart polynomial fit to standard medical thermistor probe data, it is shown that the WBH treatment thermometers used can measure the patient body temperatures with a short- and long-term accuracy of +/- 0.01 degrees C.     

基于适配子的分子探针在肿瘤分子影像学中的应用

理想的分子影像探针应具有一定的特异性、敏感性、安全性。适配子是可与靶分子高特异性和高亲和力结合的单链 DNA 或 RNA 分子,具有靶分子广泛、分子小、易生产和修饰、免疫原性低、渗透性强等特点,是一种新型的分子影像探针。目前基于适配子的肿瘤分子影像学研究越来越多,为肿瘤的诊断和治疗提供了新的技术和工具。     

A feasibility study for non-invasive thermometry using non-linear ultrasound

Purpose: High intensity focused ultrasound (HIFU) is used during hyperthermia cancer treatment to increase the tumour temperature. For an adequate and safe application it is important to measure the temperature in the heated region, preferably in a non-invasive manner and by the same modality as used for heating. The goal of this feasibility study is two-fold; first, it is investigated whether the acoustic non-linearity parameter B/A is most suitable for measuring temperature changes, second, a non-invasive thermometry method based on B/A is proposed and demonstrated.

Material and methods: Water is used to confirm that B/A is a sensitive acoustic medium parameter that is practically applicable for non-invasive thermometry. Next, a thermometry method is proposed that employs the ratios between the fundamental and the higher harmonic frequency components of a non-linear acoustic wave. The method determines these ratios for a measured acoustic pulse that has traversed a certain medium, and compares these with temperature dependent reference ratios for the same medium. The method is demonstrated using simulated measurements of an acoustic plane wave propagating in glycerol.

Results: Results obtained for water show that B/A is more sensitive for temperature changes than other practical acoustic parameters. For a combination of 16 simulated measurements, it is demonstrated that temperature can be predicted non-invasively with zero bias and a standard deviation of 2°C if the noise level does not exceed ?40?dB.

Conclusion: The suitability of B/A as a basis for non-invasive thermometry is confirmed, and a non-invasive thermometry method based on B/A is proposed and successfully demonstrated.