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Biomedical subjects

H I Amols

Publications and source records attributed to H I Amols.

At least 19 recordsLinked to original sources

Operator-free, film-based 3D seed reconstruction in brachytherapy.

In brachytherapy implants, the accuracy of dose calculation depends on the ability to localize radioactive sources correctly. If performed manually using planar images, this is a time-consuming and often error-prone process-primarily because each seed must be identified on (at least) two films. In principle, three films should allow automatic seed identification and position reconstruction; however, practical implementation of the numerous algorithms proposed so far appears to have only limited reliability. The motivation behind this work is to create a fast and reliable system for real-time implant evaluation using digital planar images obtained from radiotherapy simulators, or mobile x-ray/fluoroscopy systems. We have developed algorithms and code for 3D seed coordinate reconstruction. The input consists of projections of seed positions in each of three isocentric images taken at arbitrary angles. The method proposed here consists of a set of heuristic rules (in a sense, a learning algorithm) that attempts to minimize seed misclassifications. In the clinic, this means that the system must be impervious to errors resulting from patient motion as well as from finite tolerances accepted in equipment settings. The software program was tested with simulated data, a pelvic phantom and patient data. One hundred and twenty permanent prostate implants were examined (105 125I and 15 103Pd) with the number of seeds ranging from 35 to 138 (average 79). The mean distance between actual and reconstructed seed positions is in the range 0.03-0.11 cm. On a Pentium III computer at 600 MHz the reconstruction process takes 10-30 s. The total number of seeds is independently validated. The process is robust and able to account for errors introduced in the clinic.

Algorithms↗

An independent dose-to-point calculation program for the verification of high-dose-rate brachytherapy treatment planning.

PURPOSE: We describe computer software that performs, quickly and accurately, secondary dose calculations for high-dose-rate (HDR) treatment plans, including those employed for prostate treatments. METHODS: The program takes as primary input the data file used by the HDR remote afterloader console for treatment. Dosimetric calculations are performed using the Meisberger polynomial and the anisotropy table for the HDR Iridium-192 source. For standard applicators, treatment geometry is automatically reconstructed and the dose is calculated at relevant reference point(s). Template-based treatment plans (e.g., prostate) require additional user input; the dose calculation is then performed at user-selected reference points. A total dwell time calculation for volume and planar implants using the Manchester tables was also implemented. RESULTS: For fixed-geometry HDR procedures, secondary dose calculations are within 2% of the treatment plan, and results are available for review instantly. For more general applications, the calculated and planned doses are typically within 3% at the prescription isodose line. The Manchester-based dwell time calculation is within 10% of the planned time.

Algorithms↗

Treatment planning for prostate implants using magnetic-resonance spectroscopy imaging.

PURPOSE: Recent studies have demonstrated that magnetic-resonance spectroscopic imaging (MRSI) of the prostate may effectively distinguish between regions of cancer and normal prostatic epithelium. This diagnostic imaging tool takes advantage of the increased choline plus creatine versus citrate ratio found in malignant compared to normal prostate tissue. The purpose of this study is to describe a novel brachytherapy treatment-planning optimization module using an integer programming technique that will utilize biologic-based optimization. A method is described that registers MRSI to intraoperative-obtained ultrasound images and incorporates this information into a treatment-planning system to achieve dose escalation to intraprostatic tumor deposits. METHODS: MRSI was obtained for a patient with Gleason 7 clinically localized prostate cancer. The ratios of choline plus creatine to citrate for the prostate were analyzed, and regions of high risk for malignant cells were identified. The ratios representing peaks on the MR spectrum were calculated on a spatial grid covering the prostate tissue. A procedure for mapping points of interest from the MRSI to the ultrasound images is described. An integer-programming technique is described as an optimization module to determine optimal seed distribution for permanent interstitial implantation. MRSI data are incorporated into the treatment-planning system to test the feasibility of dose escalation to positive voxels with relative sparing of surrounding normal tissues. The resultant tumor control probability (TCP) is estimated and compared to TCP for standard brachytherapy-planned implantation. RESULTS: The proposed brachytherapy treatment-planning system is able to achieve a minimum dose of 120% of the 144 Gy prescription to the MRS positive voxels using (125)I seeds. The preset dose bounds of 100-150% to the prostate and 100-120% to the urethra were maintained. When compared to a standard plan without MRS-guided optimization, the estimated TCP for the MRS-optimized plan is superior. The enhanced TCP was more pronounced for smaller volumes of intraprostatic tumor deposits compared to estimated TCP values for larger lesions. CONCLUSIONS: Using this brachytherapy-optimization system, we could demonstrate the feasibility of MRS-optimized dose distributions for (125)I permanent prostate implants. Based on probability estimates of anticipated improved TCP, this approach may have an impact on the ability to safely escalate dose and potentially improve outcome for patients with organ-confined but aggressive prostatic cancers. The magnitude of the TCP enhancement, and therefore the risks of ignoring the MR data, appear to be more substantial when the tumor is well localized; however, the gain achievable in TCP may depend quite considerably on the MRS tumor-detection efficiency.

Algorithms↗

A language for generating tomographic images of mathematical phantoms.

A computer language is presented that can be used to generate image files, as if the images are created with a CT or a MR scanner. The language defines objects in the "scanner's" coordinate system, as sets of quadratic inequalities. Each of these objects, e.g., an ellipsoid or a half-plane or a cylinder, has its own density. Objects can be superimposed and collections of objects are allowed to translate and rotate. The language allows for a concise way of describing complex objects with precisely defined geometries and densities. An implementation of the language can be used for testing, developing, and analyzing diagnostic software, treatment planning systems, etc. A software module that is based on the language can be made available. The utility of the module for acceptance testing of radiation therapy treatment planning systems is described.

Algorithms↗

Practical considerations in using calculated healthy-tissue complication probabilities for treatment-plan optimization.

PURPOSE: Healthy and neoplastic tissues are generally exposed nonuniformly to ionizing radiation. It is thus useful to develop algorithms that predict the probability of tumor control or normal tissue complication probability (NTCP) for any given spatial pattern of dose delivery. The questions addressed here concern: (a) the sensitivity of the NTCP predictions to the actual model used for extrapolation from uniform irradiation (where some clinical data exist) to nonuniform exposures, (b) its dependence on tissue type, and (c) consequences for treatment-plan optimization. METHODS AND MATERIALS: Two (of several possible) NTCP formulations are used here: the Lyman model and a binomial equation. The effective volume-reduction scheme of Kutcher and Burman is used to obtain the NTCP for an arbitrary distribution of dose. NTCP was calculated for seven organs by postulating a dose distribution of maximum nonuniformity. RESULTS: Both models fit available NTCP data well, but have very different extrapolations for exposures of small tissue volumes and very low values of NTCP (e.g., < 5%) where no data exist. Organs with pronounced volume effects (lung, kidneys) show substantial NTCP differences between the two models. Even in organs where the volume effect is small (e.g., spinal cord, brain), differences in NTCP due to the model selected may still have serious clinical consequences, as an actual example (for the spinal cord) indicates. CONCLUSIONS: NTCP calculations based on extrapolations to volume fractions and/or NTCP levels for which reliable data do not exist depend on the model used to fit the data and the degree of dose nonuniformity. If NTCP is to be used in treatment-plan optimization, the prudent approach is to design plans that reproduce the conditions under which available dose-volume data were taken (e. g., uniform dose distributions).

Algorithms↗

Intracoronary radiation for prevention of restenosis: dose perturbations caused by stents.

BACKGROUND: Intravascular irradiation with beta-emitters has been proposed for inhibition of restenosis in coronary arteries after balloon angioplasty or stent implantation. Previous studies have shown the effectiveness of gamma-radiation to prevent recurrent restenosis, even in the presence of an implanted stent. The limited range of beta-particles compared with gamma-radiation, however, opens the question of whether absorption and scattering of beta-particles by stent struts will cause significant perturbations in the uniformity and magnitude of the radiation dose, which may in turn compromise treatment. METHODS AND RESULTS: Nine different stents were deployed with a balloon filled with a beta-emitting radioactive liquid. Dose distributions were measured with Gafchromic film. Stents varied significantly in their absorption of beta-particles. Some stents, constructed of fine meshed wires, produced minimal dose perturbations. Others, with thicker, high-atomic-number struts, induced cold spots in the dose distribution adjacent to the wires of </=35%. Average dose reduction varied from 4% to 14% in the presence of various stents. CONCLUSIONS: Radiation strategy may have to be tailored to stent design. Stents that minimally perturb the dose distribution may be deployed before irradiation. Those that significantly alter the radiation dose might be better deployed after irradiation. Dose prescriptions may require modification if such perturbations prove clinically significant. Observed dose perturbations, however, decreased rapidly with increasing distance from the stent, which may mitigate the clinical impact of these findings. This, as well as the effects of stents on gamma-dose distributions, requires further investigation.

Angioplasty, Balloon, Coronary↗

A little to a lot or a lot to a little: is NTCP always minimized in multiport therapy?

PURPOSE: We address the question of whether or not, for the same average (or integral) dose, a smaller uniform dose to an entire normal tissue structure always results in a lower normal tissue complication probability (NTCP) than does a proportionally larger dose to a partial volume of the same structure. METHODS AND MATERIALS: A recent compilation of NTCP data and two theoretical formulations of the dependence of NTCP on dose and partial volume irradiated-the Lyman probit equation and the binomial model-are used to examine this question. Both models fit equally well available NTCP data. RESULTS: Empirical data indicate that for lung, kidney, and possibly liver (but not for esophagus, brain, or heart), given a fixed tumor dose and fixed integral dose, NTCP can be minimized by irradiating a partial volume fraction rather than the entire normal organ. The binomial model supports this interpretation, whereas the probit model predicts that for all organs uniform irradiation of the whole organ always results in the lowest possible NTCP. CONCLUSIONS: In contrast to what is commonly believed, this study suggests that for at least two normal tissues, namely lung and kidney, there may be situations where "a lot to a little" (i.e., fewer treatment ports) will result in higher tumor control probability and better treatment plan than "a little to a lot" (i.e., multifield treatment). This finding, which is independent of the binomial or probit models used here, depends only on the accuracy of the empirical NTCP data. It is also interesting to note that: a) lung and kidney are commonly classified as parallel tissues, while the others have more of a serial architecture; and b) the choice of the NTCP model can have a profound impact on treatment planning decisions.

Models, Theoretical↗

Physician/patient-driven risk assignment in radiation oncology: reality or fancy?

PURPOSE: Treatment plan optimization in radiation oncology entails designing multiple x-ray beams to irradiate a tumor to a dose that will achieve locoregional control while minimizing normal tissue complications. For some anatomical sites, it is possible to estimate tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) as a function of radiation dose. Thus, treatment plan optimization can be based on biologic end points rather than on dose calculations alone. Given multiple plans with different NTCPs and TCPs, a tradeoff must be made between maximizing TCP and maintaining an acceptable NTCP. How do physicians reach these decisions? Can the process be quantified? Should patients participate in the process? METHODS AND MATERIALS: Physicians and patients were asked to rank a series of treatment plans having different combinations of TCP and NTCP. Responses were parametrized into a figure of merit (FM) equation which quantifies predilections of TCP and NTCP. RESULTS: Physician-based FM equations are site- and patient-specific. Variations exist among physicians, but treatment plan selection is often conservative in accordance with the primum non nocere dictum. FM equations generated from the responses of patients suggest that some patients may be willing to accept higher treatment toxicity in exchange for increased TCP. CONCLUSION: The term "optimized treatment plan" contains inherently subjective criteria which reflect one's willingness to accept treatment morbidity in exchange for probability of cure. These criteria may differ among patients and/or physicians. A quantifiable FM may permit the design of custom-made treatment plans that include physician and patient input.

Decision Making↗

Predicting optical densitometer response as a function of light source characteristics for radiochromic film dosimetry.

Various forms of GAFChromic (GC) film have been used for several years as radiographic media for measuring dose distributions of brachytherapy sources and small radiation fields. In order to optimize the measurement sensitivity and thus improve precision, we describe a method to calculate the dose response curves (net optical density at a give wavelength or spectrum versus absorbed dose) for different densitometer light sources using measured GC film absorption spectra. Comparison with measurements on the latest version of GC film (model MD-55-2) using four types of densitometers [He-Ne laser, broadband (white light) densitometer, and two LED (red-light) filtered densitometers] confirm the accuracy of this predictive model. The linearity and sensitivity of the dose response curves are found to be highly dependent on the light source spectrum. Initial slope is a function of the average weighted absorbance. Early saturation and decreased linearity of the dose response curves are ascribed to the nonuniform transmission of the light source through the GC film. We found that an LED (red-light) source with a narrow bandpass filter centered at 671 nm near the major absorption peak achieves nearly the maximum possible sensitivity (almost four times more sensitive than He-Ne laser, 632.8 nm) and may be suitable for in vivo dosimetry.

Brachytherapy↗

Dosimetric considerations for catheter-based beta and gamma emitters in the therapy of neointimal hyperplasia in human coronary arteries.

PURPOSE: Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments. METHODS AND MATERIALS: Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied. RESULTS: Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored. CONCLUSIONS: Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Brachytherapy↗

Microdosimetric evaluation of relative biological effectiveness for 103Pd, 125I, 241Am, and 192Ir brachytherapy sources.

PURPOSE: To determine the microdosimetric-derived relative biological effectiveness (RBE) of 103Pd, 125I, 241Am, and 192Ir brachytherapy sources at low doses and/or low dose rates. METHODS AND MATERIALS: The Theory of Dual Radiation Action can be used to predict expected RBE values based on the spatial distribution of energy deposition at microscopic levels from these sources. Single-event lineal energy spectra for these isotopes have been obtained both experimentally and theoretically. A grid-defined wall-less proportional counter was used to measure the lineal energy distributions. Unlike conventional Rossi proportional counters, the counter used in these measurements has a conducting nylon fiber as the central collecting anode and has no metal parts. Thus, the Z-dependence of the photoelectric effect is eliminated as a source of measurement error. Single-event spectra for these brachytherapy sources have been also calculated by: (a) the Monte Carlo code MCNP to generate the electron slowing down spectrum, (b) transport of monoenergetic electron tracks, event by event, with our Monte Carlo code DELTA, (c) using the concept of associated volume to obtain the lineal energy distribution f(y) for each monoenergetic electron, and (d) obtaining the composite lineal energy spectrum for a given brachytherapy source based on the electron spectrum calculated at step (a). RESULTS: Relative to 60Co, the RBE values obtained from this study are: 2.3 for 103Pd, 2.1 for 125I, 2.1 for 241Am, and 1.3 for 192Ir. CONCLUSIONS: These values are consistent with available data from in vitro cell survival experiments. We suggest that, at least for these brachytherapy sources, microdosimetry may be used as a credible alternative to time-consuming (and often uncertain) radiobiological experiments to obtain information on radiation quality and make reliable predictions of RBE in low dose rate brachytherapy.

Americium↗

Dosimetry of a radioactive coronary balloon dilatation catheter for treatment of neointimal hyperplasia.

Recent reports suggest that intraluminal irradiation of coronary arteries in conjunction with balloon angioplasty reduces proliferation of smooth muscle cells and neointima formation, thereby inhibiting restenosis. One possible irradiation technique is to inflate the balloon dilitation catheter with a radioactive solution. This has advantages over other proposed irradiation procedures, in that accurate source positioning and uniform dose to the vessel wall are assured. Several high-energy beta-minus emitters may be suitable for this application. We present experimental measurements and analytical calculations of the dose distribution around a 3-mm-diam by 20-mm-long balloon filled with 90Y-chloride solution. The dose rate at the surface of the balloon is approximately 0.14 cGy/s per mCi/ml (3.78 x 10(-11) Gy/s per Bq/ml), with the dose decreasing to 53% at 0.5 mm, and < 5% at 3.5-mm radial distance. 90Y and other possible isotopes are currently available at specific concentrations > or = 50 mCi/ml (1.85 x 10(9) Bq/ml), which enables the delivery of 20 Gy in less than 5 min. The dosimetric and radiation safety advantages of this system warrant further feasibility studies. Issues of concern include incorporating the beta-emitter into a suitable chemical form, and assessing organ and whole body doses in the (< 1 in 10(3)) event of balloon failure.

Angioplasty, Balloon, Coronary↗

Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo.

PURPOSE: Relative biological effectiveness (RBE) values for the high linear-energy-transfer particles produced during boron neutron capture therapy have generally been based on theoretical considerations or in vitro experiments. The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components. METHODS AND MATERIALS: Clonogenic cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an intracerebral tumor. These data were analyzed using the linear quadratic model for cell survival to derive measured RBE values for all beam components and for a number of different boron compounds. RESULTS: In the absence of boron, the combined effects of the protons from the nitrogen capture, 14N(n,p)14C, and the fast neutron scatter, 1H(n,n')p, reactions generated RBEs of 3.7 in vitro and 3.2 in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end point of 1% cell survival. Apparent RBEs for the 10B(n,alpha)7Li reaction products were calculated from cell survival data following reactor irradiations in the presence of the amino acid p-boronophenylalanine, the sulfhydryl dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the 10B(n,alpha)7Li reaction ranged from 1.2 to 9.8 depending on which boron compound was used. RBEs from the in vitro studies were consistently higher than from the in vivo/in vitro studies. Under any conditions, the apparent RBE for the 10B(n,alpha)7Li reaction with p-boronophenylalanine was higher than that with any other boron compound tested. CONCLUSIONS: Generally accepted RBE values for the fast neutron and 14N(n,p)14C reaction components of the total dose are too low. The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei.

Animals↗

Microdosimetry for boron neutron capture therapy.

Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue-equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented.

Boron↗

Enhanced risk from low-energy screen--film mammography X rays.

Modern screen-film mammography with molybdenum-anode X rays results in tissue doses being delivered primarily by photons with an energy of less than 20 keV. Such photons interact with tissue predominantly through the photoelectric effect, producing low-energy electrons that have different patterns of energy deposition at the cellular level compared with those from higher-energy X rays. These differences result in low doses of typical molybdenum-based mammography X rays having an estimated radiobiological effectiveness of approximately 1.3 compared with 80 kVp or 250 kVp X rays, and approximately 2 compared with higher-energy gamma rays. Thus the risk from mammography could be higher, by such factors, than previously estimated. This would result in the optimal age for beginning mammographic screening, derived from risk-benefit ratios, being increased by at least 1-2 years and possibly by as many as 10 years.

Age Factors↗

Acute radiation effects on cutaneous microvasculature: evaluation with a laser Doppler perfusion monitor.

Laser Doppler perfusion monitoring is a noninvasive technique for measuring blood flow in epidermal microvasculature that makes use of the frequency shift of light reflected from red blood cells. Measurements in patients undergoing radiation therapy show increases in blood flow of ten to 25 times baseline at doses above 50 Gy, and increases are observed with doses as low as 2 Gy. Follow-up measurements show rapid decreases in flow levels after completion of therapy, but levels remain elevated even at 1 year.

Blood Flow Velocity↗

Radiobiological effectiveness (RBE) of megavoltage X-ray and electron beams in radiotherapy.

Recent experiments indicate that significant differences exist in the microdosimetric properties (i.e., lineal energy distributions) of megavoltage X-ray and electron beams used in radiation therapy. In particular, dose averaged values of lineal energy for 18 MeV electrons are 10-30% lower than for 10 MeV bremsstrahlung X rays, which in turn are 30-60% lower than for 250 kVp X rays. Differences of this magnitude may manifest themselves in observable radiobiological effectiveness (RBE) differences between these radiations. Cell survival data have been obtained for line DLD-1 human tumor cells on all three of the above radiation sources. Results clearly demonstrate an RBE difference between orthovoltage and megavoltage radiation (P = 0.001). A small difference is also measured in RBE between megavoltage photons and megavoltage electrons, but the difference is not statistically significant (P = 0.25). All biological, dosimetric, and microdosimetric data were obtained under nearly identical geometric conditions. These data raise interesting questions vis à vis the applicability of microdosimetric theories in the interpretation of biological effects.

Cell Line↗