On the use of the pion stopping distribution and the lesion additivity concept for the calculation of effective doses in pion treatment planning

The large spatial variation in LET, and hence in RBE, is one of the main obstacles in the development of routine treatment planning of charged particle beams. Since the biological effect distribution of plans cannot be realistically measured for each patient, a simple scheme of relating effect to basic empirical physical measurement is required. For the case of a pion beam, the high LET dose distribution is correlated with that of the pion stopping density, which can be indirectly measured using several techniques. A scheme based on this spatial correlation has been developed. In this method, after partitioning the local dose into a high and a low LET fraction, the local effective dose is computed using a simple formula extracted from a recent analysis of radiobiological results for mixtures of radiations of different LET. This simple formula can also be derived from a mechanistic model of mixed radiation action developed using the hypothesis of additivity of common intermediate lesions. In this paper, the concept of spatial correlation between the high LET dose and the pion stars is merged with the concept of lesion additivity for mixed radiation, from which a simple computational scheme is formulated for the calculation of effective doses in the treatment planning of pions. Similar schemes can also be developed for other charged particle beams.     

Neutron doses in negative pion radiotherapy

Absorbed neutron doses in regions outside the treatment volume from negative pion radiotherapy are presented, based on neutron spectral measurements for pions stopping in a tissue-equivalent target. A Monte Carlo neutron transport computer code was developed and used to calculate the absorbed dose as a function of the distance from the centre of the treatment volume. The Monte Carlo code, which is a modification of a neutron detector efficiency code, follows neutrons and gamma rays as they interact with either hydrogen or oxygen nuclei in a phantom. The code includes neutron elastic scattering on both hydrogen and oxygen as well as five inelastic nuclear reactions on oxygen. The recoil charged particles which provide the absorbed dose are considered until the neutron escapes the phantom or its kinetic energy falls below 1 ke V. Calculations of absorbed dose are compared with earlier dose calculations and measurements. Measurements of the neutron spectrum from a tissue-equivalent target indicate that the total kinetic energy carried away by neutrons is about 76 MeV, which is a significantly higher value than that used in earlier estimates of the neutron dose. The calculations presented here suggest that the neutron dose outside large treatment volumes may limit the use of negative pions for some therapeutic applications.     

Developing aspects of radiation oncology

Both physics and radiobiology provide growing points in modern radiotherapy. Better physical dose distributions appear to be still worth achieving and can be obtained from beams of protons, heavy ions, or negative pi mesons because a peak region of high dose is deposited at depth in tissue. The heavier ion and pions also have biological properties of high LET radiation which could be important: the radioresistance of hypoxic cells in tumors is less, and tissues which are proliferating fast may be relatively more vulnerable. Although fast neutrons provide ordinary physical dose distributions, their high LET properties are similar to those of ions as heavy as neon. Drugs which specifically radiosensitize hypoxic cells offer a way of determining with certainty how important hypoxic cells are in radiotherapy. Hyperthermia is in its early stages but promises to damage just those cells poor in nutrients which are relatively resistant to ionizing radiation. Radioprotecting drugs, which depend upon poor uptake in tumors but high uptake in normal tissues, are also being tested.     

Volume-of-change cone-beam CT for image-guided surgery

C-arm cone-beam CT (CBCT) can provide intraoperative 3D imaging capability for surgical guidance, but workflow and radiation dose are the significant barriers to broad utilization. One main reason is that each 3D image acquisition requires a complete scan with a full radiation dose to present a completely new 3D image every time. In this paper, we propose to utilize patient-specific CT or CBCT as prior knowledge to accurately reconstruct the aspects of the region that have changed by the surgical procedure from only a sparse set of x-rays. The proposed methods consist of a 3D-2D registration between the prior volume and a sparse set of intraoperative x-rays, creating digitally reconstructed radiographs (DRRs) from the registered prior volume, computing difference images by subtracting DRRs from the intraoperative x-rays, a penalized likelihood reconstruction of the volume of change (VOC) from the difference images, and finally a fusion of VOC reconstruction with the prior volume to visualize the entire surgical field. When the surgical changes are local and relatively small, the VOC reconstruction involves only a small volume size and a small number of projections, allowing less computation and lower radiation dose than is needed to reconstruct the entire surgical field. We applied this approach to sacroplasty phantom data obtained from a CBCT test bench and vertebroplasty data with a fresh cadaver acquired from a C-arm CBCT system with a flat-panel detector. The VOCs were reconstructed from a varying number of images (10-66 images) and compared to the CBCT ground truth using four different metrics (mean squared error, correlation coefficient, structural similarity index and perceptual difference model). The results show promising reconstruction quality with structural similarity to the ground truth close to 1 even when only 15-20 images were used, allowing dose reduction by the factor of 10-20.     

Measurement of ionizing radiation using carbon nanotube field effect transistor

Single-walled carbon nanotubes (SWNTs) are a new class of highly promising nanomaterials for future nano-electronics. Here, we present an initial investigation of the feasibility of using SWNT field effect transistors (SWNT-FETs) formed on silicon-oxide substrates and suspended FETs for radiation dosimetry applications. Electrical measurements and atomic force microscopy (AFM) revealed the intactness of SWNT-FET devices after exposure to over 1 Gy of 6 MV therapeutic x-rays. The sensitivity of SWNT-FET devices to x-ray irradiation is elucidated by real-time dose monitoring experiments and accumulated dose reading based on threshold voltage shift. SWNT-FET devices exhibit sensitivities to x-rays that are at least comparable to or orders of magnitude higher than commercial MOSFET (metal-oxide semiconductor field effect transistor) dosimeters and could find applications as miniature dosimeters for microbeam profiling and implantation.     

Optimisation in fluoroscopy

Optimisation of radiation protection in fluoroscopy is important since the procedure could lead to relatively high absorbed doses both in patients and personnel resulting in acute radiation injury. Optimisation procedures include adjustment of the fluoroscopy equipment such as exposure factors as well as proper use of automatic brightness control and pulsed fluoroscopy. It is also important to gain the benefits of image processing and the higher sensitivity of flat panel detectors as compared to image intensifier-TV systems.Proper positioning of the patient with respect to detector and X-ray tube is of fundamental importance to image quality and radiation dose to the patient. Both image quality and radiation dose are also affected by the methodology used with parameters such as magnification factor, increased filtration, use of last-image-hold and the use of a grid.There is a direct relation between patient dose and the absorbed dose to the personnel since this is mostly due to scattered radiation from the patient. If the correct methodology and the correct radiation protection devices are used, the absorbed dose to the personnel could be minimised to acceptable levels even for those working with complex procedures.In order to have an organised review of all aspects of optimisation, it is recommendable to have an active quality system at the department. This system should define responsibilities and tasks for persons involved.     

Radiation doses and detriment from chest x-ray examinations

Radiation dose distributions for chest x-ray examinations have been measured in a Rando phantom for three views (AP, PA and lateral) as a function of kVp. On the basis of these data, the relationship between the surface dose, energy imparted and the effective dose equivalent have been determined. The mean energy imparted in a typical chest examination (PA + lateral views at 100 kVp) is 1.7 mJ and the corresponding value of the effective dose equivalent, HE, is 42 muSv. The measured radiation doses associated with chest x-rays were compared with the predictions of Monte Carlo calculations. The average difference between Monte Carlo and measured data for the HE was only about 16%. Demographic features (age/sex) of patients undergoing chest x-rays were investigated, and a population irradiation factor (PIF) introduced to estimate the radiation detriment to this population. The probability of expressed radiation-induced detriment to the patient population from chest x-ray examinations was computed to be about one half of that expected for a normal adult (working) population receiving the same dose. The radiation risk associated with chest x-ray examinations for this population was estimated to be less than 0.3 fatal cancers plus serious genetic disorders in the first two generations per million patient examinations.     

Measurement of stopping power ratios for 60 MeV positive or negative pions.

Pion stopping power ratios are essential parameters for pion radiotherapy treatment planning. The validity of scaling proton stopping powers to pions is called into question since the pion mass is intermediate between the electron and proton masses. Direct measurements of stopping power ratios with respect to water were made for 60 MeV pions of both charges in Teflon, Plexiglas, nylon, paraffin, gelatine, tissue-equivalent plastic (Shonka A150), graphite, aluminium, steel and copper. Corrections for multiple scattering and energy dependence of the stopping power are applied. Measured stopping power ratios at an accuracy of 0.6% are in agreement to within the limits of experimental error with stopping power ratios calculated from the Bethe-Bloch equation using elemental I-values and Bragg additivity.     

Variable versus fixed modulation of proton beams for treatments in the cranium

Dose distributions in the cranium with fixed and with variably modulated proton beams were compared. The variable modulation was designed to tailor the proximal high-dose region of each field to the target volume surface whereas the fixed modulation beams had a constant modulation determined by the greatest extent of the target. Dose-volume histograms of normal tissues were compared, as were the estimated complication probabilities. Twelve patients with chordomas or chondrosarcomas of the base of skull who had been treated to approximately 70 cobalt Gray equivalent (CGE) were evaluated. Dose distributions of the actual treatments were compared to those which would have been delivered had the proton beams been variably modulated; two patients for whom x-ray plans were available were also evaluated. The greatest difference in dose between the variable and fixed modulation proton beams, averaged over all the patients, was 13.8 CGE (8.0-18.0 CGE range). Much of this reduction occurred in the brain, particularly the temporal lobes. In those temporal lobes receiving significant doses, variable modulation reduced the volume receiving more than 54 CGE by 3.0 cc; all temporal lobes had at least a 5 CGE difference to some portion, half had more than 10 CGE and three more than 15 CGE difference to some portion. The optic structures, brainstem and spinal cord received from 1 to 3 CGE less dose with the variability modulated beams. Eight of the parotid glands received more than 20 CGE to more than half their volume with the fixed modulation beams; in these, variable modulation reduced the mean dose by 5.3 CGE. The reduction in integral dose with variable as compared to fixed modulation was in the range 3 to 12%; this gain was considerably less than the gain for uniformly modulated proton beams over x-rays in the two patients for whom x-ray plans were available.     

Radiation treatment of brain tumors: concepts and strategies

Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.     

Calculation of radiation dose enhancement factors for dose enhancement therapy of brain tumours.

When brain tumours are loaded with iodinated contrast media (CM) and exposed to x-rays, the photoelectrons, Auger electrons and fluorescent x-rays from the iodine enhance the radiation dose absorbed by the tumour. A modified CT scanner, the CTX, can be used to localize the tumour and to deliver the dose enhancement therapy. Monte Carlo calculations are presented here of the central-axis radiation depth dose in a brain containing a tumour loaded with an iodine concentration of 5 mg ml-1 and irradiated with the CTX operated at various kV settings. The dose enhancement factor (DEF) is also calculated for various field sizes and for 5 mg ml-1 of gadolinium in the tumour when the CTX is operated at 140 kV. The calculated values of the DEF are close to published experimental results.     

Estimation of tumour dose enhancement due to gold nanoparticles during typical radiation treatments: a preliminary Monte Carlo study

A recent mice study demonstrated that gold nanoparticles could be safely administered and used to enhance the tumour dose during radiation therapy. The use of gold nanoparticles seems more promising than earlier methods because of the high atomic number of gold and because nanoparticles can more easily penetrate the tumour vasculature. However, to date, possible dose enhancement due to the use of gold nanoparticles has not been well quantified, especially for common radiation treatment situations. Therefore, the current preliminary study estimated this dose enhancement by Monte Carlo calculations for several phantom test cases representing radiation treatments with the following modalities: 140 kVp x-rays, 4 and 6 MV photon beams, and 192Ir gamma rays. The current study considered three levels of gold concentration within the tumour, two of which are based on the aforementioned mice study, and assumed either no gold or a single gold concentration level outside the tumour. The dose enhancement over the tumour volume considered for the 140 kVp x-ray case can be at least a factor of 2 at an achievable gold concentration of 7 mg Au/g tumour assuming no gold outside the tumour. The tumour dose enhancement for the cases involving the 4 and 6 MV photon beams based on the same assumption ranged from about 1% to 7%, depending on the amount of gold within the tumour and photon beam qualities. For the 192Ir cases, the dose enhancement within the tumour region ranged from 5% to 31%, depending on radial distance and gold concentration level within the tumour. For the 7 mg Au/g tumour cases, the loading of gold into surrounding normal tissue at 2 mg Au/g resulted in an increase in the normal tissue dose, up to 30%, negligible, and about 2% for the 140 kVp x-rays, 6 MV photon beam, and 192Ir gamma rays, respectively, while the magnitude of dose enhancement within the tumour was essentially unchanged.     

The physics of cancer therapy with negative pions

The introduction of negative pions into cancer therapy has required the construction of large new proton accelerators together with special magnetic systems to form and direct the pion beam to a patient. A summary is presented of the fundamental properties of pions and of the methods used to study the therapeutic beams. The dosimetry of these beams requires the use of the older techniques as well as new methods for determining the different LET components. The data for a number of beams is given and the utilization of this data in treatment planning is reviewed. An important problem for therapy is the behavior of inhomogeneities in the pion beam, and experimental methods are described which illuminate this problem. The studies of the effects of inhomogeneities in a beam point the way toward fruitful comparisons with the computerized treatment planning codes known as PION-1 and PIPLAN. A useful step in treatment is the verification of doses in patients during therapy. For this purpose the new methods for measuring the high LET doses in patients are described as well as a timing measurement for checking the stopping effect of the tissues as obtained from the CT scans.     

Comment on 'implications on clinical scenario of gold nanoparticle radiosensitization in regard to photon energy, nanoparticle size, concentration and location'

A recent paper by Lechtman et al (2011 Phys. Med. Biol. 56 4631-47) presented Monte Carlo modelling of gold nanoparticle dose modification. In it, they predict that the introduction of gold nanoparticles has the strongest effect with x-rays at kilovoltage energies, and that negligible increases in dose are expected at megavoltage energies. While these results are in agreement with others in the literature (including those produced by our group), the conclusion that ‘(gold nanoparticle) radiosensitization using a 6 MV photon source is not clinically feasible’ appears to conflict with recently published experimental studies which have shown radiosensitization using 6 MV x-ray sources with relatively low gold concentrations. The increasing disparity between theoretical predictions of dose enhancement and experimental results in the field of gold nanoparticle radiosensitization suggests that, while the ability of gold nanoparticles to modify dose within a tumour volume is well understood, the resulting radiosensitization is not simply correlated with this measure. This highlights the need to validate theoretical predictions of this kind against experimental measurements, to ensure that the scenarios and values being modelled are meaningful within a therapeutic context.     

Operational characteristics of a prototype x-ray needle device

A prototype x-ray needle, which emits 62.5 kVp x-rays at the tip of a 20 cm long, 4 mm diameter steel needle, has been developed by Titan Pulse Sciences Incorporated (PSI) (Albuquerque, NM) and was tested for its suitability in brachytherapy applications in comparison with a similar device by the Photoelectron Corporation. The depth dose profiles were also compared with those of two common brachytherapy sources (125I and 192Ir). The depth dose characteristics of the radiation were comparable with the two brachytherapy sources with a slightly reduced attenuation gradient. The dose rate from the x-ray needle tip was relatively isotropic at the needle tip and was continuously adjustable over the range of 0 cGy min(-1) to upwards of 62 cGy min(-1) at a reference distance of 1 cm in air. We detected a significant proportion of x-rays generated along the needle shaft, and not at the needle tip, as intended. The energy spectrum emitted from this device had a peak intensity at 21 keV and an average energy of 28 keV. The beam was attenuated in both aluminium (the first half-value layer being less than 0.1 mm) and in water (50% dose at approximately 2 mm). These studies confirm that although there is potential for a system similar to this one for clinical applications, the simplistic electron guidance used in this particular prototype device limits it to research applications. Further optimization is required in focusing and steering the electron beam to the target, improving x-ray production efficiency and using x-ray target cooling to achieve higher dose rates.     

Absorption spectra variations of EBT radiochromic film from radiation exposure

Gafchromic EBT radiochromic film is one of the newest radiation-induced auto-developing x-ray analysis films available for therapeutic radiation dosimetry in radiotherapy applications. The spectral absorption properties in the visible wavelengths have been investigated and results show two main peaks in absorption located at 636 nm and 585 nm. These absorption peaks are different to many other radiochromic film products such as Gafchromic MD-55 and HS film where two peaks were located at 676 nm and 617 nm respectively. The general shape of the absorption spectra is similar to older designs. A much higher sensitivity is found at high-energy x-rays with an average 0.6 OD per Gy variation in OD seen within the first Gy measured at 636 nm using 6 MV x-rays. This is compared to approximately 0.09 OD units for the first Gy at the 676 nm absorption peak for HS film at 6 MV x-ray energy. The film's blue colour is visually different from older varieties of Gafchromic film with a higher intensity of mid-range blue within the film. The film provides adequate relative absorbed dose measurement for clinical radiotherapy x-ray assessment in the 1-2 Gy dose range which with further investigation may be useful for fractionated radiotherapy dose assessment.     

RBE-dose relations for neutrons and pions.

From cellular radiosensitivity parameters and theoretical particle-energy spectra in tissue, of the secondary particles from neutron and negative pion irradiations, RBE-Dose relations have been calculated. The theoretical results are compared with clinical and radiobiological data for normal tissue, tumours and cells in culture. Formulae for calculation, cellular parameters and the needed properties of equivalent 'track-segment bombardments' are given, for several mammalian cells irradiated with pions and with neutrons of several energies.     

Dose comparison between conventional and quasi-monochromatic systems for diagnostic radiology

Several techniques have been introduced in the last year to reduce the dose to the patient by minimizing the risk of tumour induced by radiation. In this work the radiological potential of dose reduction in quasi-monochromatic spectra produced via mosaic crystal Bragg diffraction has been evaluated, and a comparison with conventional spectra has been performed for four standard examinations: head, chest, abdomen and lumbar sacral spine. We have simulated quasi-monochromatic x-rays with the Shadow code, and conventional spectra with the Spectrum Processor. By means of the PCXMC software, we have simulated four examinations according to parameters established by the European Guidelines, and calculated absorbed dose for principal organs and the effective dose. Simulations of quasi-monochromatic laminar beams have been performed without anti-scatter grid, because of their inherent scatter geometry, and compared with simulations with conventional beams with anti-scatter grids. Results have shown that the dose reduction due to the introduction of quasi-monochromatic x-rays depends on different parameters related to the quality of the beam, the organ composition and the anti-scatter grid. With parameters chosen in this study a significant dose reduction can be achieved for two out of four kinds of examination.     

Dosimetric aspects of film/screen mammography: in-phantom dosimetry with thimble-type ionisation chambers

The characteristics of 0.6 cm3 thimble-type Baldwin-Farmer (BF 2571) ionisation chambers for absorbed dose determinations in-phantom at mammography installations are investigated. The most important aspects for in-phantom dosimetry in mammography concern the conversion from air kerma to absorbed dose in mammary gland tissue, the energy dependence of the sensitivity of the ionisation chamber and the displacement correction factor for measurements in-phantom. Due to the considerable uncertainties in the elemental composition of the mammary glands the conversion from air kerma to absorbed dose in the mammary gland tissue has an uncertainty of the order of +/- 20%. The air kerma calibration factor of the BF-ionisation chamber is about 10% larger at mammography radiation qualities than at 300 kV x-rays or 137Cs gamma rays. For depths in excess of about 15 mm a displacement correction factor of 0.69 +/- 0.06 is derived for measurements with the BF 2571 chamber inside polymethylmethacrylate (PMMA) phantoms irradiated with 30 kV x-rays (first HVL:0.29 mm Al). The previously reported discrepancy between dose measurements with TLD and ionisation chambers at the entrance surface of a phantom for mammography radiation qualities is resolved and could be attributed to attenuation in the TLD encapsulation material.     

New irradiation geometry for microbeam radiation therapy

Microbeam radiation therapy (MRT) has the potential to treat infantile brain tumours when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of x-rays but provides unusual resistance to radioneurotoxicity, presumably from the migration of endothelial cells from 'valleys' into 'peaks', i.e., into directly irradiated microslices of tissues. We present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumour area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumouricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumour in the paths of the arrays.