A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

PURPOSE: To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. METHODS: Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. RESULTS: The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. CONCLUSIONS: The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning technique (E+IMRT) can decrease the normal tissue integral dose compared to a photon-only IMRT plan. Different planning approaches can be enabled by the use of an electron beam directed toward organs at risk distal to the target, which are still spared due the rapid dose fall-off of the electron beam. Examples of such cases are the lateral electron beams in the thoracic region that do not irradiate the heart and contralateral lung, electron beams pointed toward kidneys in the abdominal region, or beams treating brain lesions pointed toward the brainstem or optical apparatus. For brain, electron vertex beams can also be used without irradiating the whole body. Since radiation retreatments become more and more common, minimizing the normal tissue integral dose and the dose delivered to tissues surrounding the target, as enabled by E+IMRT type techniques, should receive more attention.

An EPID response calculation algorithm using spatial beam characteristics of primary, head scattered and MLC transmitted radiation.

We have developed an independent algorithm for the prediction of electronic portal imaging device (EPID) response. The algorithm uses a set of images [open beam, closed multileaf collimator (MLC), various fence and modified sweeping gap patterns] to separately characterize the primary and head-scatter contributions to EPID response. It also characterizes the relevant dosimetric properties of the MLC: Transmission, dosimetric gap, MLC scatter [P. Zygmansky et al., J. Appl. Clin. Med. Phys. 8(4) (2007)], inter-leaf leakage, and tongue and groove [F. Lorenz et al., Phys. Med. Biol. 52, 5985-5999 (2007)]. The primary radiation is modeled with a single Gaussian distribution defined at the target position, while the head-scatter radiation is modeled with a triple Gaussian distribution defined downstream of the target. The distances between the target and the head-scatter source, jaws, and MLC are model parameters. The scatter associated with the EPID is implicit in the model. Open beam images are predicted to within 1% of the maximum value across the image. Other MLC test patterns and intensity-modulated radiation therapy fluences are predicted to within 1.5% of the maximum value. The presented method was applied to the Varian aS500 EPID but is designed to work with any planar detector with sufficient spatial resolution.

An independent dose calculation algorithm for MLC-based radiotherapy including the spatial dependence of MLC transmission.

An analytical dose calculation algorithm was developed and commissioned to calculate dose delivered with both static and dynamic multileaf collimator (MLC) in a homogenous phantom. The algorithm is general; however, it was designed specifically to accurately model dose for large and complex IMRT fields. For such fields the delivered dose may have a considerable contribution from MLC transmission, which is dependent upon spatial considerations. Specifically, the algorithm models different MLC effects, such as interleaf transmission, the tongue-and-groove effect, rounded leaf ends, MLC scatter, beam hardening and divergence of the beam, which results in a gradual MLC transmission fall-off with increasing off-axis distance. The calculated dose distributions were compared to measured dose using different methods (film, ionization chamber array, single ionization chamber), and the differences among the treatment planning system, the measurements and the developed algorithm were analysed for static MLC and dynamic IMRT fields. It was found that the calculated dose from the developed algorithm agrees very well with the measurements (mostly within 1.5%) and that a constant value for MLC transmission is insufficient to accurately predict dose for large targets and complex IMRT plans with many monitor units.

Spatial dependence of MLC transmission in IMRT delivery.

In complex intensity-modulated radiation therapy cases, a considerable amount of the total dose may be delivered through closed leaves. In such cases an accurate knowledge of spatial characteristics of multileaf collimator (MLC) transmission is crucial, especially for the treatment of large targets with split fields. Measurements with an ionization chamber, radiographic films (EDR2, EBT) and EPID are taken to characterize all relevant effects related to MLC transmission for various field sizes and depths. Here we present a phenomenological model to describe MLC transmission, whereby the main focus is the off-axis decrease of transmission for symmetric and asymmetric fields as well as on effects due to the tongue and groove design of the leaves, such as interleaf transmission and the tongue and groove effect. Data obtained with the four different methods are presented, and the utility of each measurement method to determine the necessary model parameters is discussed. With the developed model, it is possible to predict the relevant MLC effects at any point in the phantom for arbitrary jaw settings and depths.

Determination of depth and field size dependence of multileaf collimator transmission in intensity-modulated radiation therapy beams.

Intensity-modulated radiation therapy (IMRT) plans for the treatment of large and complex volumes may contain a relatively large contribution from multileaf collimator (MLC) transmission. In such cases, comprehensive characterization of direct and scatter MLC transmission is important. We designed a set of tests (open beam, closed static MLC, and dynamic MLC gap) to determine dosimetric MLC properties as a function of field size and depth at the central axis. We developed a generalized model of MLC transmission to account for direct MLC transmission, MLC scatter, beam hardening, and leaf-end transmission (dosimetric gap). The model is consistent with the beam model used in IMRT optimization. We tested the model for extreme asymmetric fields relevant for large targets and for split IMRT fields. We applied our MLC scatter estimation formula to clinically relevant cases and showed that MLC scatter is contributing an undesired background dose. This contribution is relatively large, especially in low-dose regions. (For instance, a uniform extra dose may dramatically increase normallung toxicity in thorax treatment.) For complex IMRT of large-volume targets, we found direct MLC transmission dose to be as high as 30%, and MLC scatter, up to 10% within the target volume for the selected cases. We identified that the dose discrepancies between the IMRT planning system [Eclipse (Varian Medical Systems, Palo Alto, CA)] and ionization chamber measurements (inside and outside of the field) are attributable to an inadequate model of MLC transmission in the planning system (constant-value model). In the present study, we measured MLC transmission properties for Varian 6EX (6 MV) and 21EXs (6 and 10 MV) linear accelerators; however, the experimental method and theoretical model are more general.

An MLC-based linac QA procedure for the characterization of radiation isocenter and room lasers' position.

We have designed and implemented a new stereotactic linac QA test with stereotactic precision. The test is used to characterize gantry sag, couch wobble, cone placement, MLC offsets, and room lasers' positions relative to the radiation isocenter. Two MLC star patterns, a cone pattern, and the laser line patterns are recorded on the same imaging medium. Phosphor plates are used as imaging medium due to their sensitivity to red light. The red light of room lasers erases some of the irradiation information stored on the phosphor plates enabling accurate and direct measurements for the position of room lasers and radiation isocenter. Using film instead of the phosphor plate as imaging medium is possible, however, it is less practical. The QA method consists of irradiating four phosphor plates that record the gantry sag between the 0 degrees and 180 degrees gantry angles, the position and stability of couch rotational axis, the sag between the 90 degrees and 270 degrees gantry angles, the accuracy of cone placement on the collimator, the MLC offsets from the collimator rotational axis, and the position of laser lines relative to the radiation isocenter. The estimated accuracy of the method is +/- 0.2 mm. The observed reproducibility of the method is about +/- 0.1 mm. The total irradiation/ illumination time is about 10 min per image. Data analysis, including the phosphor plate scanning, takes less than 5 min for each image. The method characterizes the radiation isocenter geometry with the high accuracy required for the stereotactic radiosurgery. In this respect, it is similar to the standard ball test for stereotactic machines. However, due to the usage of the MLC instead of the cross-hair/ball, it does not depend on the cross-hair/ball placement errors with respect to the lasers and it provides more information on the mechanical integrity of the linac/couch/laser system. Alternatively, it can be used as a highly accurate QA procedure for the nonstereotactic machines. Noteworthy is its ability to characterize the MLC position accuracy, which is an important factor in IMRT delivery.

Reducing the low-dose lung radiation for central lung tumors by restricting the IMRT beams and arc arrangement.

To compare the extent to which 7 different radiotherapy planning techniques for mediastinal lung targets reduces the lung volume receiving low doses of radiation. Thirteen non-small cell lung cancer patients with targets, including the mediastinal nodes, were identified. Treatment plans were generated to both 60- and 74-Gy prescription doses using 7 different planning techniques: conformal, hybrid conformal/intensity-modulated radiation treatment (IMRT), 7 equidistant IMRT beams, 2 restricted beam IMRT plans, a full (360°) modulated arc, and a restricted modulated arc plan. All plans were optimized to reduce total lung V5, V10, and V20 volumes, while meeting normal tissue and target coverage constraints. The mean values for the 13 patients are calculated for V5, V10, V20, V(ave), V0-20, and mean lung dose (MLD) lung parameters. For the 74-Gy prescription dose, the mean lung V10 was 42.7, 43.6, 48.2, 56.6, 57, 55.8, and 54.1% for the restricted ±36° IMRT, restricted modulated arc, restricted ±45° IMRT, full modulated arc, hybrid conformal/IMRT, equidistant IMRT, and conformal plans, respectively. A similar lung sparing hierarchy was found for the 60-Gy prescription dose. For the treatment of central lung targets, the ±36° restricted IMRT and restricted modulated arc planning techniques are superior in lowering the lung volume treated to low dose, as well as in minimizing MLD, followed by the ±45° restricted IMRT plan. All planning techniques that allow the use of lateral or lateral/oblique beams result in spreading the low dose over a higher lung volume. The area under the lung dose-volume histogram curve below 20 Gy, V0-20, is proposed as an alternative to individual V(dose) parameters, both as a measure of lung sparing and as a parameter to be minimized during IMRT optimization.

A clinical comparison of patient setup and intra-fraction motion using frame-based radiosurgery versus a frameless image-guided radiosurgery system for intracranial lesions.

BACKGROUND AND PURPOSE: A comparison of patient positioning and intra-fraction motion using invasive frame-based radiosurgery with a frameless X-ray image-guided system utilizing a thermoplastic mask for immobilization. MATERIALS AND METHODS: Overall system accuracy was determined using 57 hidden-target tests. Positioning agreement between invasive frame-based setup and image-guided (IG) setup, and intra-fraction displacement, was evaluated for 102 frame-based SRS treatments. Pre and post-treatment imaging was also acquired for 7 patients (110 treatments) immobilized with an aquaplast mask receiving fractionated IG treatment. RESULTS: The hidden-target tests demonstrated a mean error magnitude of 0.7mm (SD=0.3mm). For SRS treatments, mean deviation between frame-based and image-guided initial positioning was 1.0mm (SD=0.5mm). Fusion failures were observed among 3 patients resulting in aberrant predicted shifts. The image-guidance system detected frame slippage in one case. The mean intra-fraction shift magnitude observed for the BRW frame was 0.4mm (SD=0.3mm) compared to 0.7mm (SD=0.5mm) for the fractionated patients with the mask system. CONCLUSIONS: The overall system accuracy is similar to that reported for invasive frame-based SRS. The intra-fraction motion was larger with mask-immobilization, but remains within a range appropriate for stereotactic treatment. These results support clinical implementation of frameless radiosurgery using the Novalis Body Exac-Trac system.

Temperature-dependent studies of NO recombination to heme and heme proteins.

The rebinding kinetics of NO to the heme iron of myoglobin (Mb) is investigated as a function of temperature. Below 200 K, the transition-state enthalpy barrier associated with the fastest (approximately 10 ps) recombination phase is found to be zero and a slower geminate phase (approximately 200 ps) reveals a small enthalpic barrier (approximately 3 +/- 1 kJ/mol). Both of the kinetic rates slow slightly in the myoglobin (Mb) samples above 200 K, suggesting that a small amount of protein relaxation takes place above the solvent glass transition. When the temperature dependence of the NO recombination in Mb is studied under conditions where the distal pocket is mutated (e.g., V68W), the rebinding kinetics lack the slow phase. This is consistent with a mechanism where the slower (approximately 200 ps) kinetic phase involves transitions of the NO ligand into the distal heme pocket from a more distant site (e.g., in or near the Xe4 cavity). Comparison of the temperature-dependent NO rebinding kinetics of native Mb with that of the bare heme (PPIX) in glycerol reveals that the fast (enthalpically barrierless) NO rebinding process observed below 200 K is independent of the presence or absence of the proximal histidine ligand. In contrast, the slowing of the kinetic rates above 200 K in MbNO disappears in the absence of the protein. Generally, the data indicate that, in contrast to CO, the NO ligand binds to the heme iron through a "harpoon" mechanism where the heme iron out-of-plane conformation presents a negligible enthalpic barrier to NO rebinding. These observations strongly support a previous analysis (Srajer et al. J. Am. Chem. Soc. 1988, 110, 6656-6670) that primarily attributes the low-temperature stretched exponential rebinding of MbCO to a quenched distribution of heme geometries. A simple model, consistent with this prior analysis, is presented that explains a variety of MbNO rebinding experiments, including the dependence of the kinetic amplitudes on the pump photon energy.

Rapid timescale processes and the role of electronic surface coupling in the photolysis of diatomic ligands from heme proteins.

We have observed coherent oscillations of the heme protein myoglobin (Mb) following femtosecond laser excitation and photodissociation of the CO, O2, and NO bound ligands. Use of a novel methodology, involving "wavelength selective modulation" of the pump and/or probe laser pulse train, allows us to discriminate between coherences created by pump fields of differing wavelength within the laser pulse versus signals that arise from the decay of either vibrational or electronic populations. The population driven signals appear when pump field interactions having the same optical frequency are allowed to contribute to the signal detection channel. One surprising result, which will be stressed in the discussion, is the observation of a distinct product state vibrational coherence (the iron-histidine stretching vibration of deoxy Mb at 220 cm(-1)) that depends upon the presence of pump field interactions having a wavelength mismatch that is equal to the 220 cm(-1) vibrational frequency. This observation is surprising because the iron-histidine mode is not observed in the resonance Raman measurements on the six-coordinate reactant species. Thus, the pump-pulse laser excitation between the ground and excited state, which leads to the ligand dissociation, is evidently able to create a "field driven" vibrational coherence of a resonance Raman inactive mode that extends into non-vertical regions of the reactive excited state potential energy surface. Non-radiative electronic surface crossing, followed by the rapid development of new electronic forces on the nuclei, appears to be ruled out as a source of the coherent signals (the random phase of the optically uncoupled modes is one possible explanation for this observation). The extremely rapid timescale (<< 150 fs) for the development of the (S = 2) high-spin product state of the iron atom from the initial unphotolyzed state (S = 0) is worthy of further theoretical discussion because of the spin forbidden nature of such a transition. Excited state admixtures of the iron spin states are presumably involved, and the mixing of these states, along with the unpaired electron on NO, may help to explain the ultrafast time scales and large amplitudes that characterize the NO geminate recombination in comparison to CO.