Validation of a precision radiochromic film dosimetry system for quantitative two-dimensional imaging of acute exposure dose distributions.

We present an evaluation of the precision and accuracy of image-based radiochromic film (RCF) dosimetry performed using a commercial RCF product (Gafchromic MD-55-2, Nuclear Associates, Inc.) and a commercial high-spatial resolution (100 microm pixel size) He-Ne scanning-laser film-digitizer (Personal Densitometer, Molecular Dynamics, Inc.) as an optical density (OD) imaging system. The precision and accuracy of this dosimetry system are evaluated by performing RCF imaging dosimetry in well characterized conformal external beam and brachytherapy high dose-rate (HDR) radiation fields. Benchmarking of image-based RCF dosimetry is necessary due to many potential errors inherent to RCF dosimetry including: a temperature-dependent time evolution of RCF dose response; nonuniform response of RCF; and optical-polarization artifacts. In addition, laser-densitometer imaging artifacts can produce systematic OD measurement errors as large as 35% in the presence of high OD gradients. We present a RCF exposure and readout protocol that was developed for the accurate dosimetry of high dose rate (HDR) radiation sources. This protocol follows and expands upon the guidelines set forth by the American Association of Physicists in Medicine (AAPM) Task Group 55 report. Particular attention is focused on the OD imaging system, a scanning-laser film digitizer, modified to eliminate OD artifacts that were not addressed in the AAPM Task Group 55 report. RCF precision using this technique was evaluated with films given uniform 6 MV x-ray doses between 1 and 200 Gy. RCF absolute dose accuracy using this technique was evaluated by comparing RCF measurements to small volume ionization chamber measurements for conformal external-beam sources and an experimentally validated Monte Carlo photon-transport simulation code for a 192Ir brachytherapy source. Pixel-to-pixel standard deviations of uniformly irradiated films were less than 1% for doses between 10 and 150 Gy; between 1% and 5% for lower doses down to 1 Gy and 1% and 1.5% for higher doses up to 200 Gy. Pixel averaging to form 200-800 microm pixels reduces these standard deviations by a factor of 2 to 5. Comparisons of absolute dose show agreement within 1.5%-4% of dose benchmarks, consistent with a highly accurate dosimeter limited by its observed precision and the precision of the dose standards to which it is compared. These results provide a comprehensive benchmarking of RCF, enabling its use in the commissioning of novel HDR therapy sources.

A simple technique for alignment of perineal needle template to ultrasound image grid for permanent prostate implants.

Proper alignment of a needle template and ultrasound software grid is required to accurately deliver permanent prostate seed implants optimized using pretreatment volume studies. Correct alignment may also reduce tissue edema, morbidity, and the time and labor required to deliver permanent prostate seed implants. A technique has been developed to rapidly assess (and, if necessary, improve) the alignment using a custom-designed water phantom. Verification of needle positions can be conducted within 1 mm and requires less than ten minutes. We have instituted the technique as a part of our periodic quality assurance program.

Production and manipulation of elevated temperatures in pig abdomen with a three-electrode capacitive heating device.

The ability of a three-electrode capacitive heating device operating at 13.56 MHz to produce and effect spatial redistribution of hyperthermic temperatures is demonstrated through abdominal heating studies conducted with 80 kg female and 65 kg male pigs. Temperature-time profiles over the respective heating periods were obtained in anterior and posterior superficial tissue and in selected abdominal organs. At selected times during heating, spatial redistribution of elevated temperatures was effected through adjustment of power settings for one or more of the three electrodes, i.e. through manipulation of the specific absorption rate (SAR) in-vivo.

Design and dosimetric characteristics of a high dose rate remotely afterloaded endocavitary applicator system.

PURPOSE: An applicator is described for endocavitary treatment of rectal cancers using a high dose rate (HDR) remote afterloading system with a single high-intensity 192Ir source as an alternative to the 50 kVp x-ray therapy contact unit most frequently used in this application. METHODS AND MATERIALS: The applicator consists of a tungsten-alloy collimator with a 45 degree beveled end, placed in a protoscope with an elliptical cross-section. The resultant 3 cm diameter circular treatment aperture, located in the beveled face of the proctoscope, is irradiated by circular array of dwell positions located about 6.5 mm from the applicator surface. This beveled end allows patients with posterior wall tumors to be treated in the dorsal lithotomy position. The dose-rate distributions about the applicator were determined using a combination of thermoluminescent dosimetry (TLD-100 detectors) and radiochromic film dose measurement techniques along with Monte Carlo dosimetry calculations. TLD-100 (3 x 3 x 0.9 mm3 chips) measurements were used to measure the distribution of dose over the proctoscope surface as well as the central axis dose-rate distribution. Relative radiochromic film measurements were used to measure off-axis ratios (flatness and penumbra width) within the treatment aperture. These data were combined with Monte Carlo simulation results to obtain the final dose distribution. RESULTS: The tungsten collimator successfully limits the dose to the tissue in contact with the proctoscope walls to less than 12% of the prescribed dose. These results indicate that the HDR applicator system has slightly more penetrating depth-dose characteristics than the most widely used contact therapy x-ray machine. Flatness characteristics of the two treatment delivery systems are comparable, although the HDR endocavitary applicator has a significantly wider penumbra. Finally, the HDR applicator has a lower surface dose rate (1.5-4 Gy/min of dwell time) compared to 9-10 Gy/min for the x-ray unit. CONCLUSIONS: An applicator system has been developed for endocavitary treatment of early stage rectal carcinoma that uses a single-stepping source HDR remote afterloading system as a radiation source. The advantages of the HDR-based system over x-ray therapy contact units currently used in this clinical application are (a) enhanced flexibility in applicator design and (b) widespread availability of single-stepping source HDR remote afterloading systems.

Theory and design of "shortened" multiantenna microwave applicators with controllable SAR patterns.

A "shortened" multiantenna hyperthermia applicator has been designed and tested at the Mallinckrodt Institute of Radiology at Washington University School of Medicine. By shortening the distance from antenna to aperture, an applicator is obtained that produces an SAR pattern that is essentially the same as produced by a monopole antenna. By placing several properly spaced probe antennas into the same "shortened" applicator, an applicator is obtained that produces a SAR distribution that is essentially a composite of small overlapping SAR patterns produced by weakly interacting incoherently driven antennas. Such a design significantly improves the applicator's lateral heating efficiency and allows the independent control of temperatures in certain tumor areas by changing the input power to the respective antennas.

Potential for localized, adjustable deep heating in soft-tissue environments with a 30-beam ultrasonic hyperthermia system.

Initial heating rates (degrees C/min) along parallel tracks at depths of 1-14 cm in a static, muscle-like phantom were determined from time-temperature profiles obtained with 'Helios', a 30-beam ultrasonic hyperthermia system developed by Varian Associates. Data were taken at a single operating frequency of 556 kHz, for different sets of focal plane ring diameters of the four-ring array applicator, different levels of transducer driving power and two different focal plane depths, 6 cm and 9 cm. In each experiment, at each point of temperature measurement, analysis of temperature versus time data over a 2 min heating interval permitted separation of the desired phantom heating from artefactual heating resulting primarily from absorption of transverse (shear) waves produced at phantom-metal probe catheter interfaces. The results of the studies conducted suggest that in a non-translating carriage mode, Helios can produce axially and laterally localized deep heating in soft tissues for tissue volumes of lateral dimension up to a minimum of 4 cm and tissue depths of at least 11 cm. The results obtained also suggest that Helios can produce laterally localized heating to tissue depths of at least 11 cm without excessive heating of superficial soft-tissue layers, for tissue volumes of lateral dimension up to a minimum of 8 cm. The methodology used in the phantom studies was applied to the production of localized heating in the right lobe of the liver of adult pigs. Temperature versus time profiles obtained in the in vivo studies indicated that, for the set of system parameters employed, concentration of ultrasonic power at greater depths in the liver (e.g. 10.5 cm versus 5 cm) could be achieved, suggesting that Helios should be able to produce localized heating of targeted hepatic volumes when its operating parameters are selected in accordance with effective treatment planning techniques.

Results of a preliminary study of the potential of vasodilators for improving thermotherapy of deep-seated tumours [printed with original paging at end of 2(2); omitted from Int J Hyperthermia 1986 Jan-Mar;2(1)].

Administration of the vasodilator hydralazine to a single mongrel dog with a transplanted, superficial transmissible venereal tumour in the abdomen permitted tumour-adjacent normal tissue temperature differences produced in local hyperthermia to be enhanced by nearly 2 degrees C. A preliminary study of tumour and normal tissue perfusion rate in the dog, employing the 15O-labelled water-positron emission tomography technique, suggested that administration of the vasodilator led to a significant reduction in the tumour perfusion rate, consistent with the observed tumour temperature enhancement. Computational studies with a multi-layer, one-dimensional cylindrical model of deep-tumour heating suggest that vasodilator-induced reductions of tumour perfusion rates could significantly increase deep tumour-superficial normal tissue temperature differences produced in deep-tumour thermotherapy.

Correlations between 31P NMR spectroscopy and 15O perfusion measurements in the RIF-1 murine tumor in vivo.

The tumor physiological environment is one of the least understood and most important factors in determining the response of solid tumors to cancer therapy. To examine several important characteristics of the tumor physiological environment we have used in situ photon activation-15O decay measurements (perfusion characteristics) and 31P surface coil-NMR spectroscopy (metabolic characteristics) to observe in vivo subcutaneous RIF-1 tumors grown in female C3H/Anf mice. The following correlations between the 15O perfusion characteristics and the 31P NMR metabolic characteristics in individual tumors were observed: a negative correlation between pH, as measured by NMR (pHNMR), and the inorganic phosphate to nucleosides triphosphate peak height ratio (Pi:NTP); for the well-perfused fraction of the tumor there is a positive correlation with both pHNMR and the phosphocreatine to nucleosides triphosphate peak height ratio (PCr:NTP), and a negative correlation with Pi:NTP. These correlations are interpreted as evidence for a direct relationship between the distribution of cellular physiological environments and the tumor metabolic state. Because these physiological characteristics affect tumor response to various therapeutic modalities and both measurements can be made on humans, it is suggested that these techniques may be of prognostic value in the clinical management of human cancer.

Interstitial thermoradiotherapy in the treatment of recurrent/residual malignant tumors.

From October 1981-November 1983, a total of 31 recurrent and/or persistent tumors in 29 patients were treated with interstitial radiotherapy in combination with interstitial hyperthermia. All patients had undergone extensive previous treatments by surgery and/or radiation therapy. In the present series, radiation used was administered by iridium 192 implant, with doses varying from 4000-6000 cGy, delivered at the rate of 1000 cGy +/- 10%/day. Hyperthermia was delivered by radiofrequency (8 lesions) and microwave (25 lesions) in two sessions, each raising tumor temperature to a minimum of 42 degrees C over 60 minutes. Of 26 lesions with at least one satisfactory heating session, there were 18 (69%) complete responses, five (19%) partial responses, and three with less than 50% regression. None of the five lesions with unsatisfactory heating resulted in complete response. Of the total group, two patients developed a cutaneous sinus and one patient developed a fistula. The detailed methodology and results are presented and recommendations for future improvements are discussed.

Quality assessment and assurance in clinical hyperthermia: requirements and procedures.

The ultimate goal of quality assessment and quality assurance in clinical hyperthermia must be the delivery of satisfactorily similar thermotherapy to all patients entered into a given treatment protocol. Therefore, in addition to dealing with performance evaluation and calibration of equipment for heating and thermometry, hyperthermia quality assurance must also address specification, planning, administration, documentation, evaluation, and reconstruction of the clinical treatments themselves.

A practical, modular hyperthermia phantom.

A catheterized, three-component slab phantom has been fabricated for use in mapping specific absorption rate (SAR) distributions from hyperthermia applicators. A planar array of 21 closely spaced catheters, located at one surface of the 1-cm-thick slab, can be positioned at depths of 0-7 cm below the phantom surface, in 1-cm steps, through appropriate placement and orientation of this slab within the three-slab set. Owing to its modular design, the phantom can be prepared, and also purged of degraded material rapidly and without damage to the catheter tracks.

Improved applicator-patient coupling in microwave-induced hyperthermia.

The effect on the efficiency of power transfer and microwave leakage of different applicator-load coupling schemes is examined. For a 915-mHz applicator and musclelike phantom separated by 4 cm, it is found that by filling the air gap with dielectric powder or deionized water, the efficiency of power transfer from applicator to load can be raised to levels comparable to that obtained for direct applicator-load contact. For these coupling conditions, it is also found that microwave leakage intensities in the immediate vicinity of the applicator-phantom interface can be reduced to direct contact levels. Employment of such materials and techniques in our clinic, for coupling applicators to patient surfaces in the administration of local hyperthermia to head and neck tumors, has facilitated the reduction of average microwave leakage intensities from more than 15 MW/cm2 to less than 3 MW/cm2 in most cases.

Use of the Clinac-35 for tissue activation in noninvasive measurement of capillary blood flow.

Through adjustment of operating parameters responsible for the acceleration, steering, and focusing of electrons en route to the target, we have extracted a 30-MV x-ray beam from the Clinac-35 linear accelerator that is suitable for use in photon activation -15O decay studies of tissue perfusion. This beam is significantly more efficient than the "standard" 25-MV beam in producing 15O in situ through activation of tissue oxygen, thereby substantially reducing the dose to tissue required to yield a desired initial 15O activity. Production and characteristics of the higher energy beam are discussed, and data obtained from its application to measurement of capillary blood flow in animal tumors are presented and analyzed.

Effects of single-dose irradiation in tumor blood flow studied by 15O decay after proton activation in situ.

A noninvasive technique employing photon activation of tissue oxygen in situ and detection of subsequent 15O positron decay was used to study the effects of single-dose 60Co irradiation on capillary blood flow in transplanted rat rhabdomyosarcomas. Tumor blood flow was measured before irradiation with 16.5, 38.5, or 60.5 Gy and at several intervals afterward (0-72 hr.). Pre-irradiation values of volume-averaged blood flow in the tumor ranged from 7 to 44 ml/min./100 g. Several hours after irradiation, blood flow fell by up to 50% for 60.5 Gy and up to 35% for 16.5 Gy. However, 24 hours after irradiation, tumor blood flow had recovered completely in the 16.5-Gy group and substantially in the others. For smaller doses such as the fractions typically employed in radiotherapy, no changes in tumor blood flow were observed.

Photon activation-15O decay studies of tumor blood flow.

A direct, noninvasive method for measuring absolute values of specific capillary blood flow in living tissue is described. The method is based on the photon activation, in situ, of tissue elements and the measurement of the subsequent decay of the positron activity induced, employing coincidence detection of the photon pairs produced in positron annihilation. Analysis of the time-dependent coincidence spectrum reveals the contribution to the total signal from the decay of 15O, from which the specific capillary blood flow in the imaged, activated volume is ultimately determined. By virtue of its introduction of the radioisotope of interest (15O) directly and uniformly into the tissue volume under investigation, the method described permits both the nonperfused and well perfused fractions of an activated volume to be estimated and hence, the average specific blood flow within imaged tumor volumes to be computed. The model employed to describe and analyze the data is discussed in detail. Results of application of the technique to measurement of specific blood flow in rhabdomyosarcoma tumors grown in WAG/Rij rats are presented and discussed. The method is shown to be reliable and well suited to studies designed to determined the effects of various agents, such as heat, radiation and drugs, on tumor blood flow.

Physiological effects of hyperthermia: response of capillary blood flow and structure to local tumor heating.

Specific capillary blood flow and small-vessel pathology in animal tumors (rhabdomyosarcoma BA-1112) of WAG/Rij rats were examined following local tumor heating to 40-44.5 degrees C. Blood flow in tumors heated to 40-41 degrees C for 40 minutes was reduced initially by about 50%, but returned to near preheating values within 72 hours, consistent with the histopathological observations indicating small-vessel dilation and temporary congestion. The application of hyperthermia greater than 43 degrees C (for 40 minutes) resulted in the virtual elimination of capillary blood flow, consistent with pathological findings of widespread vessel rupture and hemorrhage in this temperature range.

Tissue perfusion rate determined from the decay of oxygen-15 activity after photon activation in situ.

Rates of cerebral perfusion were obtained from measurements of the disappearance (wash-out) of oxygen-15 after in situ tissue activation with 45-million-volt x-rays. In an anesthetized cat, typical values were 90 milliliters per minute per 100 grams of tissue, with 55 percent wash-out. In a specific radiotherapy patient, the value was 65 milliliters per minute per 100 grams of tissue, with 63 percent wash-out of oxygen-15 through incorporation into tissue water.