Biomedical subjects

E G Moros

Publications and source records attributed to E G Moros.

49 records · Page 3Linked to original sources

PubMedDate not supplied

Radiosensitization of heat resistant human tumour cells by 1 hour at 41.1 degrees C and its effect on DNA repair.

The present study was undertaken to determine if short duration (1-2 h), moderate hyperthermia (41.1 degrees C) could radiosensitize human tumour cells. It was found that moderate hyperthermia (41.1 degrees C), for as little as 1 h, can radiosensitize heat resistant human adenocarcinoma cells, NSY42129 (NSY), provided the cells are irradiated 15 min prior to the end of the heat exposure. Analysis of the survival data showed a 2.5-3-fold increase in the alpha parameter with no significant change in the beta parameter of the survival curve, implying that the cells had become more susceptible to killing by single radiation energy deposition events as opposed to lethal events that require an interaction between two separate energy deposition events. 41.1 degrees C hyperthermia did not affect the induction or repair of alkaline labile DNA damage in a way that correlated with radiosensitivity. In contrast, heat-induced changes in the induction of micronuclei by radiation correlated with changes in cell killing. Therefore, the effect of 41.1 degrees C hyperthermia on the intracellular localization of the DNA double strand break repair protein, Mre11, was measured using in situ immunofluorescence and immunoblotting of soluble and insoluble cellular fractions. The results showed that Mre11 delocalizes from the nucleus as a function of time at 41.1 degrees C. It was then determined if 41.1 degrees C hyperthermia altered the association of Mre11 with its functional partner, Rad50. A significant decrease in the amount of Rad50 recovered with Mre11 occurred under the experimental conditions that produced significant radiosensitization. These results are consistent with the possibility that the heat-induced perturbation in Mre11 localization and its radiation-induced association with Rad50 contributes to an increase in radiosensitivity.

Cell Nucleus↗

PubMedDate not supplied

A multi-user networked database for analysis of clinical and temperature data from patients treated with simultaneous radiation and ultrasound hyperthermia.

A database was developed using commercially available development software that allows the entry of clinical data and automatically analyses temperature and power data from a commercial ultrasound hyperthermia system. The database can be accessed via network connections by more than one authorized user, thus facilitating the entry, management, and analysis of clinical data. The software automatically estimates ultrasound induced temperature artifacts and calculates thermal dose parameters such as T90s, equivalent minutes at 43 degrees, and time at or above index temperatures using the corrected temperatures. These parameters also become part of the database. Digital photographs of treatment setup, probe placement, and tumour or normal tissue response can be included in the database for documentation and reference. Ultrasound diagnostic images that document the depth and reproducibility of probe placement can be scanned into the PC and included in the database as well. This short communication documents experiences developing this tool that may be useful to other investigators.

Combined Modality Therapy↗

PubMedDate not supplied

Simultaneous superficial hyperthermia and external radiotherapy: report of thermal dosimetry and tolerance to treatment.

BACKGROUND: In vitro and animal studies indicate that a moderate temperature of 41 degrees C maintained for approximately 1 h will provide radiosensitization if radiation (RT) and hyperthermia (HT) are delivered simultaneously, but not with sequential treatment. A minimum tumour temperature of 41 degrees C is a more feasible goal than the goal of >42 degrees C needed for sequential treatment. METHODS AND MATERIALS: Forty-four patients with 47 recurrent superficial cancers received simultaneous external beam radiotherapy and superficial hyperthermia on successive IRB approved phase I/II studies. All lesions had failed previous therapy, 35 were previously irradiated (mean dose 52.7 Gy). Hyperthermia was delivered with 915 MHz microwave or 1-3.5 MHz ultrasound using commercially available applicators. The average dimensions of 19 lesions treated with microwave were 4.7 x 3.6 x 1.7 cm and the average dimensions of 28 lesions treated with ultrasound were 8.0 x 6.1 x 2.9 cm. The most common sites were chest wall (15 cases) and head and neck (21 cases). Temperatures were monitored at an average of six intratumoral locations using multisensor probes. The median number of hyperthermia treatments was three and the median radiation dose 30 Gy. Radiation dose per fraction was 4 Gy with hyperthermia and 2 Gy or 4 Gy (depending on protocol) on non-hyperthermia days. RESULTS: Six different measures of minimum monitored temperature and duration were found to be highly correlated with each other. There was nearly a one-to-one correspondence between minimum tumour time at or above 41 degrees C (Min t41) and minimum tumour Sapareto Dewey equivalent time at 42 degrees C (Min teq42). After four sessions 63% of cases had a per session average Sapareto Dewey equivalent time at 41 degrees C which exceeded 60 min in all monitored tumour locations. The complete and partial response rate in evaluable lesions were respectively 21/41 (51%) and 7/41 (17%) and were best correlated with site (chest wall showing best response). Toxicity consisted of 10/47 (21%) slow healing soft tissue ulcers which healed in all cases but required a median of 7 months. The most important predictors for chronic ulceration were cumulative radiation dose >80 Gy and complete response to treatment. CONCLUSIONS: Minimum tumour temperatures maintained for durations compatible in vitro with thermal radiosensitization (if RT and HT are delivered simultaneously) are clinically feasible and tolerable for broad but superficial lesions amenable to externally applied ultrasound or microwave hyperthermia. The current in-house protocol is evaluating the impact of more than four hyperthermia sessions on the overall thermal dose distribution and toxicity.

Animals↗

PubMedDate not supplied

A two-parameter method for the estimation of ultrasound-induced temperature artifacts.

A two-parameter method for the estimation of ultrasound-induced temperature artifacts was evaluated and compared with other commonly applied methods using analytical solutions to the bioheat equation. The two parameters are the exponent of the assumed temperature decay curve after power is turned off and the baseline temperature. These parameters are found by optimizing the fit of the temperature data from 30 to 60s after power is turned off. The artifact is modelled as a point source at the centre of a Gaussian temperature distribution. The blood flow, baseline temperature, and variance of the Gaussian temperature distribution were varied to simulate different clinical situations. Noise was added to the model to investigate the effects of thermometry resolution and sampling intervals. It was found that for artifacts of < 2 degrees C the two-parameter method had errors of less than 0.25 degrees C, whereas other methods generally had greater errors depending on the conduction rate and blood flow rate. The effects of the temperature sampling interval and resolution on the ability of the methods to estimate the artifact were also investigated, and it was found that the two-parameter method was much more sensitive to these parameters than other commonly applied methods.

Blood Flow Velocity↗

PubMedDate not supplied

Aperture size to therapeutic volume relation for a multielement ultrasound system: determination of applicator adequacy for superficial hyperthermia.

Three-dimensional acoustic and thermal models were developed to simulate superficial hyperthermia treatments using a new multielement planar ultrasonic system. Typical power density and steady-state temperature distributions are presented. A parametric study was performed to determine the relationship between therapeutic volume (volume at and above 42 degrees C) and aperture size (number of active elements). The parameters investigated were: maximum allowable temperature, skin surface temperature, blood perfusion (thermal diffusion length), acoustic absorption, and frequency. Results showed that this device produces well distributed sound beams with lateral dimensions comparable to the aperture size. These simulated results were in agreement with experimental measurements. The simulated temperature distributions were uniform at each depth across the applicator's aperture. The main heating characteristics found were: (1) the therapeutic volume was directly proportional to the aperture size; (2) the lateral dimensions of the therapeutic volume were independent of the parameters studied and remained practically constant with depth for several centimeters, with a very rapid increase near the skin surface and a very rapid fall off at depth; and (3) therapeutic penetration was strongly dependent on maximum allowable temperature, frequency, and acoustic absorption; and weakly dependent on blood perfusion and skin surface temperature. These heating characteristics are new in commercial systems for superficial hyperthermia. Despite the well-distributed beams, it was found that in order to produce adequate hyperthermia with this device the lateral dimensions of tumors must be smaller than the applicator's active aperture and that thermal depth coverage must be monitored during treatments. Guidelines for aperture selection and thermometry strategies are discussed.

Acoustics↗

PubMedDate not supplied

Pre-focal plane high-temperature regions induced by scanning focused ultrasound beams.

A steady-state, three dimensional, bioheat transfer equation-based simulation program has been developed and used with single and multiple transducer arrangements to investigate the effects of spherical transducer characteristics (frequency and f-number) and scanning patterns on treatment temperature distributions. Results for uniformly perfused tissues show that: (1) a single circular scan induces radially non-uniform temperature distributions at the focal depth and undesirable pre-focal high temperature regions; and (2) multiple circular scans spaced by the focal diameter of the ultrasound beam and using feedback control can induce uniform temperature distributions in the focal plane, but still cause undesirable pre-focal plane high temperatures. These two results apply both to a single transducer scanned with its axis normal to the skin and to multiple tilted transducers with overlapping foci. The extent and magnitude of this pre-focal high-temperature region increases as frequency increases (from 0.5 to 2.0 MHz) and as the f-number increases (from 1.0 to 2.0). Finally, (3) when four tilted transducers with overlapping foci are used with multiple circular scans spaced by the focal diameter, if the transducer closest to the central axis of the scans is turned off (every transducer is turned off periodically) the pre-focal high-temperature region can be eliminated. From the results of this parametric study and practical considerations, a reasonable compromise of transducer choice for general use is one with a low f-number (about 1.0) and a frequency of about 1.0 MHz. For multiple tilted transducers with overlapping foci the choice of frequency is also 1.0 MHz and the f-number should be as low as possible.

Body Temperature↗

PubMedDate not supplied

Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit choroidal melanoma model.

Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an episcleral plaque to give concurrent hyperthermia and irradiation for enhanced tumour destruction. A Greene melanoma cell line was utilized to study the interaction between these treatment modalities. We attached five FM thermoseeds (with an operating temperature of 48 degrees C) in parallel with alternating rows of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some rabbits were then placed within a heating coil, and their eye tumours were warmed rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while the temperature of normal conjunctiva across the globe did not exceed 38.5 degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local control rate after 125I with concurrent FM hyperthermia. Thus, a thermal enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour response rate, but responses were only temporary. We conclude that FM thermoseeds can be used to deliver biologically effective hyperthermia concurrently with radiation, thereby reducing the dose of radiation needed for tumour control.

Animals↗

PubMedDate not supplied

Optimization of temperature distributions in scanned, focused ultrasound hyperthermia.

Scanned, focused ultrasound systems (SFUS) have considerable flexibility in shaping the power deposition field during hyperthermia treatments. When utilizing this adaptability many complicated, interacting decisions must be made to obtain an optimal steady-state temperature distribution. This optimization problem is studied using a 3-D, radially symmetric simulation program which searches for a set of optimal scan parameters. The conjugate-gradient optimization technique with a golden section search was used to obtain the optimal temperature distributions attainable with a single circular scan of a tumour. The variable scan parameters of the single transducer heating system optimized (and under the control of the therapist) are: transducer tilt and rotation angles, focal depth, output acoustical power, and scan radius. This single scan study includes the effects of tumour and normal tissue blood perfusions, tumour depth, skin temperature boundary condition, as well as tumour size and shape. A similar, but less comprehensive, study was done for larger tumours using two concentric circular scans. The results show that (1) the optimization process can produce a set of scan parameters that give a considerably better temperature distribution than could be obtained ad hoc, and (2) the optimal scan parameter configuration obtained produces a close-to-ideal tumour temperature distribution for a wide variety of clinically relevant conditions. Thus, when extended to include data from individual patients such optimization should be a very useful tool in patient treatment planning, and should enhance the present capabilities of clinical scanned, focused ultrasound systems.

Body Temperature↗

PubMedDate not supplied

Experimental evaluation of two simple thermal models using hyperthermia in muscle in vivo.

The predictions from two simple field equation models for calculating temperature distributions in tissue, namely, the Pennes' bioheat transfer equation (BHTE) and an effective thermal conductivity equation (ETCE), were compared to in vivo experimental temperature measurements made under hyperthermic conditions generated by scanned focused ultrasound. The models were kept simple (i.e. homogenous isotropic properties, no separate blood vessels included) in order to concentrate attention on the predictive abilities of these field equations using a minimum number of free parameters. Simulated results were fitted to the experimental data (multiple, linear temperature profiles in the thigh muscles of greyhound dogs) by minimizing a performance index using a golden section searth. This search determined a value for the single free parameter in each model (blood perfusion in the BHTE, and effective thermal conductivity in the ETCE) which minimized the square error difference between the experimental and simulated temperatures. The results showed that (a) the simple BHTE model could qualitatively reproduce the major features of the temperature patterns seen experimentally better than the ETCE model could, and (b) the simple BHTE model produced better quantitative fits to the experimental data than did the simple ETCE model. In addition, blood perfusion predictions from the BHTE model compared well to measurements done with coloured microspheres. Finally, the experimental results showed that individual, large blood vessels appeared to have a major influence in producing asymmetries in the experimental data in 21% of the measured temperature profiles.

Animals↗

PubMedDate not supplied

Clinical system for simultaneous external superficial microwave hyperthermia and cobalt-60 radiation.

A system for simultaneous thermoradiotherapy was devised to investigate the possible benefits and/or complications of thermal radiosensitization in human superficial tumours. The system combines the well-known treatment modalities of external 915 MHz microwave hyperthermia and cobalt-60 teletherapy. Single waveguide applicators are utilized either attached to blocking trays, so that the gamma beam travels through a waveguide and into the patient (en face setup), or in a conventional way with the microwave propagation vector orthogonal to the gamma beam (orthogonal setup). With these setups a radiation fraction can be delivered in the middle of a 60-min, non-interrupted hyperthermia treatment. Temperatures and power level are remotely monitored and recorded outside the Cobalt room. Extensive measurements and testing showed that the operation of the hyperthermia system (generator, applicators, thermometry unit and temperature sensors) was not disrupted by irradiation and that the microwaves were confined to the treatment room and did not interfere with the operation of the Cobalt unit, of an adjacent linear accelerator or of an adjacent radiotherapy simulator. For the en face setup the dose distributions induced in solid water phantoms were uniform with the exception of a narrow (< 0.5 cm) region under the applicators' internal probes where 10-18% reduction exists. This dose defect is clinically smoothed using feathering techniques. The system has been successfully used without technical problems in 51 treatments in 15 patients (18 lesions) in a phase I/II clinical trial. An analysis of the thermal data showed that the temperature distributions achieved during simultaneous delivery have the same general characteristics of those achieved in conventional sequential hyperthermia with microwaves, and that the steady state distributions are maintained during the time of simultaneous irradiation. The tests performed in addition to the preliminary clinical experience clearly indicate that this type of combined therapy is technically feasible and safe. Here the system for simultaneous, external, superficial thermoradiotherapy and the implementation tests performed are described in detail. Preliminary clinical experience and results are also reported.

Cobalt Radioisotopes↗

PubMedDate not supplied

Phase stability of a clinical phased array system for deep regional hyperthermia.

Measurements were performed on the amplifiers of a phased array system to evaluate the dependence of phase on frequency. The power from the amplifiers was terminated into a 50 ohm load at the point of connection to the antennas of the applicator, and the power was sampled to determine the phase relation between amplifier channels. It was found that the measured phase difference between two amplifier channels can: (1) change by as much as 20 degrees with frequency; (2) be as much as 12 degrees different than the prescribed phase; and (3) be as much as 30 degrees different than the phase measured and displayed by the system. Previous studies indicate that in order to accurately plan and deliver treatments with this type of device, it is necessary to know the phase relationship of the array to within at least 20 degrees. Since the differences as great as 20 degrees were obtained under ideal loading conditions, greater differences could result during normal (clinical) loading conditions, and these may not be compensated by the operator because of the inaccurate values reported by the system itself. These findings should be of concern to investigators using these devices since they could result in SAR distributions different from those planned and/or optimized for a particular patient. It is therefore recommended that the measurements such as those reported here also be performed on similar clinical devices as a standard quality assurance procedure so that the power steering capabilities of these systems can be utilized effectively and safely.

Humans↗

PubMedDate not supplied

Potential for power deposition conformability using reflected-scanned planar ultrasound.

Specialized heating devices for the simultaneous delivery of hyperthermia and ionizing radiation are being developed by several investigators in an effort to increase thermal radiosensitization in clinical treatment. One particular device is the SURLAS (Scanning Ultrasound Refléctor-Linear Array System), which was designed specifically to operate concomitantly with medical linear accelerators. The technical feasibility of the SURLAS has been demonstrated, and a design optimization study has been performed. The main objective of this paper is to demonstrate the potential for power deposition conformability of the SURLAS. This has been done using a thermographic technique which provides qualitative, high spatial-resolution measurements of power deposition distributions. The technique consists of normally insonating one surface of a 1 cm layer of a Polyurethane phantom while the temperature field on the opposite air-exposed surface is recorded using an infrared camera during the first few minutes after power insult. The thermal fields measured in this way are good qualitative estimates of relative power deposition. To demonstrate conformability, a region of 10 cm (the length of the array) by 12 cm (the scanning distance) on the air-exposed phantom surface was divided into 24 sectors (24 subregions with independent power control). Each sector was 2.5 x 2 cm across and long the scanning direction respectively. Several sector insonation patterns were synthesized in an open-loop fashion by properly adjusting power levels to each of the elements of an array as a function of reflector position as the reflector was scanned continuously in a reciprocating fashion at a constant speed. The array was made of a single piezoelectric crystal with resonant frequency of 2.2 MHz and electrically segmented into four 2.5 x 2.5 cm elements. The reflector was made of a 0.5 mm thick Brass plate. Sufficient power was supplied to the array to induce peak temperature elevations of about 10 degrees C in 60s at a scanning speed of 2.4 cm/s. The results show that measured relative power deposition patterns agreed well with programmed insonation patterns demonstrating that the SURLAS possesses great potential for power conformability, and thus, for temperature feedback power deposition control.

Humans↗

PubMedDate not supplied

Numerical and in vitro evaluation of temperature fluctuations during reflected-scanned planar ultrasound hyperthermia.

Temperature fluctuations inside a target volume during reflected-scanned planar ultrasound hyperthermia were investigated numerically and in vitro. The numerical approach consisted of integrating an ultrasonic power deposition model for a scanning ultrasound reflector linear array system (SURLAS) designed for simultaneous thermoradiotherapy, and a three-dimensional transient version of Pennes' bioheat transfer equation. The in vitro approach consisted of delivering hyperthermia to a fixed-perfused canine kidney phantom using a SURLAS prototype. Both approaches allowed the study of temperature fluctuations for several important clinically relevant parameters: scan time, scan distance, perfusion rate and skin cooling. The simulation results showed that the largest temperature fluctuations were located at the opposite ends of the scan window where the scanning reflector comes to a sudden and complete stop and reverses direction. The smallest fluctuations were located at the centre of the scan window. For a given scan distance, the magnitude of the temperature fluctuations increased linearly with increasing scan time, and increased almost linearly as a function of blood perfusion rate. For a scan window of 10 cm x 10 cm and a blood perfusion rate of 5 kg/m3 s, the simulated temperature fluctuations were within +/- 0.5 degree C from the average temperature for scan times less than or equal to 20 s. The in vitro results agreed well with the numerical findings. The measured temperature fluctuations were less than 1.0 degree C for flow rates into the renal artery of less than 200 ml/min and scan times less than 20 s.

Animals↗