Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Impaired myocardial function does not explain reduced left ventricular filling and stroke volume at rest or during exercise at high altitude

Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end-diastolic volume was ∼19% lower at rest (P = 0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (∼17%; 60 ± 10 vs. 70 ± 8 ml) despite higher LV twist (43%), apical rotation (115%), and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely because of the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, although hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted. during initial exposure to hypobaric hypoxia at high altitude (HA), cardiac output for a given absolute workload is increased to compensate for a lower arterial oxygen content before returning to baseline levels with acclimatization (8). However, after 2-5 days of acclimatization, the required cardiac output is generated through a lower stroke volume (SV) and higher heart rate (38). The reduced SV is suggestive of either lower ventricular filling, potentially caused in part by an impaired myocardial relaxation, or impaired ejection secondary to systolic contractile dysfunction. There is, however, a paucity of data in humans supporting a direct effect of hypoxia on myocardial function at HA (25, 41). The suggestion that hypoxia may impair myocardial systolic function during exercise was proposed nearly 50 years ago (3) and has been revisited more recently (27–29). Negative inotropic effects of hypoxia (arterial oxygen tension of 44 mmHg) have been shown in intact animal models (39) and isolated myocardial fibers under severe hypoxia (1% O2) (33). Exercise training under hypobaric hypoxia is also associated with altered mechanical properties at a cellular level in rodents (9), although chronic hypoxia alone did not decrease myofilament sensitivity to calcium. However, in contrast to animal studies, data in humans indicate that systolic function is maintained or enhanced at HA. For example, Suarez et al. (37) reported the maintenance of systolic function after gradual decompression to a barometric pressure of 282 mmHg, a finding that was subsequently confirmed by numerous investigations during acute and prolonged hypoxic exposure (6, 10, 12, 23, 31). However, of these studies, only Suarez et al. (37) investigated systolic function during light exercise (60 W), where function appeared to be maintained. It is not known whether systolic function is maintained at higher exercise intensities. It has also been speculated that reduced oxygen availability may impair diastolic relaxation at HA (15, 18) and thus explain the decreased left ventricular (LV) end-diastolic volume (EDV) commonly observed (2, 6, 18). However, despite numerous studies reporting a decrease in plasma volume and altered transmitral filling patterns (2, 6, 20), myocardial relaxation was only previously investigated during hypoxia in dogs (15), and no data exist examining LV relaxation during exercise at high altitude. By using sensitive, noninvasive imaging techniques (two-dimensional speckle tracking), it is now possible to examine the LV deformation mechanics (strain, twist, and untwist velocity) that underpin LV systolic and diastolic function. LV strain and twist have been shown to be sensitive measures of global and regional myocardial function, and reveal subclinical dysfunction in patients where ejection fraction is unchanged (16, 22). In addition, diastolic LV untwist velocity correlates well with invasive measures of LV stiffness and provides a temporal link between relaxation and the development of intraventricular pressure gradients (30, 43). Therefore, examination of LV mechanics at HA may determine whether the decreased SV observed at HA is dependent on impaired myocardial relaxation and/or myocardial contractile dysfunction or confirm previous findings of preserved ventricular function during exercise (37). We therefore assessed systolic and diastolic ventricular mechanics during incremental exercise at sea level and HA to examine whether impaired myocardial relaxation or systolic dysfunction explains the previously reported reduction in SV at HA. We hypothesized that at HA, 1) ventricular filling would be lower at rest and during exercise and would be accompanied by a reduction in untwist velocity and 2) systolic mechanics would be impaired during exercise at HA

Quality assurance guidelines for superficial hyperthermia clinical trials: II. Technical requirements for heating devices

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle

Resting pulmonary haemodynamics and shunting: a comparison of sea-level inhabitants to high altitude Sherpas

The incidence of blood flow through intracardiac shunt and intrapulmonary arteriovenous anastomoses (IPAVA) may differ between Sherpas permanently residing at high altitude (HA) and sea-level (SL) inhabitants as a result of evolutionary pressure to improve gas exchange and/or resting pulmonary haemodynamics. To test this hypothesis we compared sea-level inhabitants at SL (SL-SL; n = 17), during acute isocapnic hypoxia (SL-HX; n = 7) and following 3 weeks at 5050 m (SL-HA; n = 8 non-PFO subjects) to Sherpas at 5050 m (n = 14). inline image, heart rate, pulmonary artery systolic pressure (PASP) and cardiac index (Qi) were measured during 5 min of room air breathing at SL and HA, during 20 min of isocapnic hypoxia (SL-HX; inline image = 47 mmHg) and during 5 min of hyperoxia (inline image = 1.0; Sherpas only). Intracardiac shunt and IPAVA blood flow was evaluated by agitated saline contrast echocardiography. Although PASP was similar between groups at HA (Sherpas: 30.0 ± 6.0 mmHg; SL-HA: 32.7 ± 4.2 mmHg; P = 0.27), it was greater than SL-SL (19.4 ± 2.1 mmHg; P < 0.001). The proportion of subjects with intracardiac shunt was similar between groups (SL-SL: 41%; Sherpas: 50%). In the remaining subjects, IPAVA blood flow was found in 100% of subjects during acute isocapnic hypoxia at SL, but in only 4 of 7 Sherpas and 1 of 8 SL-HA subjects at rest. In conclusion, differences in resting pulmonary vascular regulation, intracardiac shunt and IPAVA blood flow do not appear to account for any adaptation to HA in Sherpas. Despite elevated pulmonary pressures and profound hypoxaemia, IPAVA blood flow in all subjects at HA was lower than expected compared to acute normobaric hypoxia

Clinical Feasibility of a High-Resolution Thermal Monitoring Sheet for Superficial Hyperthermia in Breast Cancer Patients

Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature distribution. The influence of the TMS on applicator performance was investigated, feasibility and ability to reliably monitor the temperature distribution were evaluated in a clinical study. Methods: Phantom experiments were performed to determine the influence of the TMS on power deposition patterns, applicator efficiency, and heat transfer of the water bolus for 434 and 915 MHz applicators. Clinical feasibility was evaluated in 10 women with locoregional recurrent breast cancer. Skin surface temperatures during consecutive treatments were monitored alternatingly with either standard Amsterdam UMC thermometry or TMS. Treatments were compared using (generalized) linear mixed models. Results: The TMS did not significantly affect power deposition patterns and applicator efficiency (1&ndash;2%), the reduced heat transfer of the water boluses (51&ndash;56%) could be compensated by adjusting the water bolus flow. Skin surface temperatures were monitored reliably, and no alteration of thermal toxicity was observed compared to standard Amsterdam UMC thermometry. Conclusion: Clinical application of the TMS is feasible. Power deposition patterns and applicator efficiency were not affected. Surface temperatures were monitored reliably

Modelling curved contact flexible microstrip applicators for patient-specific superficial hyperthermia treatment planning

This paper describes a method to reconstruct bendable superficial hyperthermia applicators for routine clinical patient-specific treatment planning. The reconstruction uses a CT scan with a flexible silicone dummy applicator positioned on the patient. The curvature was approximated by two second-degree polynomial functions. A realistic treatment series was mimicked using a standard Alderson radiation therapy phantom and a treatment planning model was reconstructed from a CT scan. The variation among treatment curvatures was compared to the modelled curvature. The mathematical approximation of the applicator curvature was validated for this phantom experiment, as well as for clinical treatments. The average maximum variation among the successive mimicked sessions was 3.67 ± 0.69 mm (range 2.98–4.60mm). The maximum deviation between the treatment curvature and the modelled curvature was 4.35 mm. Comparing the treatment and approximated curvature yielded a maximum deviation between 2.98 mm and 4.12 mm. For clinical treatments the maximum deviation of the treatment and approximated curvature varied between 0.48 mm and 1.98 mm. These results allow adequate reconstruction of bendable hyperthermia applicators for treatment planning, which can further improve treatment quality, for example by optimizing the water bolus temperature for patient-specific tumor depths. Predictive parameters for hyperthermia treatment outcome can easily be evaluated and compared for various input parameters

Technical and Clinical Evaluation of the ALBA-4D 70MHz Loco-Regional Hyperthermia System

Hyperthermia, increasing tumor temperatures to 39-43°C for 1 h, enhances the effectiveness of radiotherapy and chemotherapy. Deep seated pelvic tumors are usually heated by arrays of radiofrequency or microwave antennas placed around the patient, capable of focussing power onto the tumor. The AMC developed the AMC 4 loco-regional hyperthermia system with 4 rectangular 70 MHz waveguide antennas for heating deep-seated pelvic tumors. This system has been commercialized as the ALBA4D utilizing the same geometric layout and the same waveguides. Goal of this study was to evaluate the performance of the ALBA4D system. We compared electric field (E-field) distributions in a patient-mimicking phantom and confirmed that phase control of the focal point is similar to the AMC 4, thus ensuring similar clinical performance