Characterization of a flexible a-Si:H detector for in vivo dosimetry in therapeutic x-ray beams.

BACKGROUND: The increasing use of complex and high dose-rate treatments in radiation therapy necessitates advanced detectors to provide accurate dosimetry. Rather than relying on pre-treatment quality assurance (QA) measurements alone, many countries are now mandating the use of in vivo dosimetry, whereby a dosimeter is placed on the surface of the patient during treatment. Ideally, in vivo detectors should be flexible to conform to a patient's irregular surfaces. PURPOSE: This study aims to characterize a novel hydrogenated amorphous silicon (a-Si:H) radiation detector for the dosimetry of therapeutic x-ray beams. The detectors are flexible as they are fabricated directly on a flexible polyimide (Kapton) substrate. METHODS: The potential of this technology for application as a real-time flexible detector is investigated through a combined dosimetric and flexibility study. Measurements of fundamental dosimetric quantities were obtained including output factor (OF), dose rate dependence (DPP), energy dependence, percentage depth dose (PDD), and angular dependence. The response of the a-Si:H detectors investigated in this study are benchmarked directly against commercially available ionization chambers and solid-state diodes currently employed for QA practices. RESULTS: The a-Si:H detectors exhibit remarkable dose linearities in the direct detection of kV and MV therapeutic x-rays, with calibrated sensitivities ranging from (0.580 ± 0.002) pC/cGy to (19.36 ± 0.10) pC/cGy as a function of detector thickness, area, and applied bias. Regarding dosimetry, the a-Si:H detectors accurately obtained OF measurements that parallel commercially available detector solutions. The PDD response closely matched the expected profile as predicted via Geant4 simulations, a PTW Farmer ionization chamber and a PTW ROOS chamber. The most significant variation in the PDD performance was 5.67%, observed at a depth of 3 mm for detectors operated unbiased. With an external bias, the discrepancy in PDD response from reference data was confined to ± 2.92% for all depths (surface to 250 mm) in water-equivalent plastic. Very little angular dependence is displayed between irradiations at angles of 0° and 180°, with the most significant variation being a 7.71% decrease in collected charge at a 110° relative angle of incidence. Energy dependence and dose per pulse dependence are also reported, with results in agreement with the literature. Most notably, the flexibility of a-Si:H detectors was quantified for sample bending up to a radius of curvature of 7.98 mm, where the recorded photosensitivity degraded by (-4.9 ± 0.6)% of the initial device response when flat. It is essential to mention that this small bending radius is unlikely during in vivo patient dosimetry. In a more realistic scenario, with a bending radius of 15-20 mm, the variation in detector response remained within ± 4%. After substantial bending, the detector's photosensitivity when returned to a flat condition was (99.1 ± 0.5)% of the original response. CONCLUSIONS: This work successfully characterizes a flexible detector based on thin-film a-Si:H deposited on a Kapton substrate for applications in therapeutic x-ray dosimetry. The detectors exhibit dosimetric performances that parallel commercially available dosimeters, while also demonstrating excellent flexibility results.

A brief history of contact X-ray brachytherapy 50 kVp.

Contact X ray brachytherapy 50 kVp was initiated in the 1930s with the Siemens unit and popularized with the Philips unit in the 1950s. A renaissance was seen in the early 2000s with the Intrabeam™ unit for breast IORT. Presently the Papillon™ systems thanks to its high dose rate (>10Gy/mn) can be used to treat breast (IORT), skin, eyelid and rectal cancers. Future developments are expected to consolidate the place of contact radiotherapy as a safe and efficient treatment for accessible early tumors.

Synchrotron X-Ray Boost Delivered by Microbeam Radiation Therapy After Conventional X-Ray Therapy Fractionated in Time Improves F98 Glioma Control.

PURPOSE: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly collimated synchrotron beam into arrays of parallel microbeams depositing several hundred grays. It appears relevant to combine MRT with a conventional treatment course, preparing a treatment scheme for future patients in clinical trials. The efficiency of MRT delivered after several broad-beam (BB) fractions to palliate F98 brain tumors in rats in comparison with BB fractions alone was evaluated in this study. METHODS AND MATERIALS: Rats bearing 106 F98 cells implanted in the caudate nucleus were irradiated by 5 fractions in BB mode (3 × 6 Gy + 2 × 8 Gy BB) or by 2 boost fractions in MRT mode to a total of 5 fractions (3 × 6 Gy BB + MRT 2 × 8 Gy valley dose; peak dose 181 Gy [50/200 µm]). Tumor growth was evaluated in vivo by magnetic resonance imaging follow-up at T-1, T7, T12, T15, T20, and T25 days after radiation therapy and by histology and flow cytometry. RESULTS: MRT-boosted tumors displayed lower cell density and cell proliferation compared with BB-irradiated tumors. The MRT boost completely stopped tumor growth during ∼4 weeks and led to a significant increase in median survival time, whereas tumors treated with BB alone recurred within a few days after the last radiation fraction. CONCLUSIONS: The first evidence is presented that MRT, delivered as a boost of conventionally fractionated irradiation by orthovoltage broad x-ray beams, is feasible and more efficient than conventional radiation therapy alone.

Evaluation of UVA emission from x-ray megavoltage-irradiated tissues and phantoms.

RECA (Radiotherapy enhanced with Cherenkov photo-activation) is a proposed treatment where the anti-cancer drug psoralen is photo-activated in situ by UVA (Ultraviolet A, 320-400 nm) Cherenkov light (CL) produced directly by the treatment beam itself. In this study, we develop a UVA-imaging technique to quantify relative UVA CL produced by bulk tissues and other phantoms upon clinical x-ray megavoltage irradiation. UVA CL emission (320-400 nm) was quantified in tissue samples of porcine and poultry and in two kinds of solid waters (SW): brown (Virtual Waters, Standard Imaging, WI) and white (Diagnostic Therapy, CIRS, VA), and in 1% agarose gels variously doped with absorbing dye. Quantification was achieved through cumulative imaging of the samples placed in a dark, light-blocking chamber during irradiation on a Varian 21 EX accelerator. UVA imaging required a specialized high-sensitivity cooled camera equipped with UVA lenses and a filter. At 15 MV, white SW emitted [Formula: see text], [Formula: see text] and [Formula: see text] less UVA than chicken breast, pork loin and pork belly, respectively. Similar under-response was observed at 6 MV. Brown SW had [Formula: see text] less UVA emission than white SW at 15 MV, and negligible emission at 6 MV. Agarose samples (1% by weight) doped with 250 ppm India ink exhibited equivalent UVA CL emission to chicken breast (within 8%). The results confirm that for the same absorbed dose, SW emits less UVA light than the tissue samples, indicating that prior in vitro studies utilizing SW as the CL-generating source may have underestimated the RECA therapeutic effect. Agarose doped with 250 ppm India ink is a convenient tissue-equivalent phantom for further work.

A Novel Radiotherapy Approach for Keloids with Intrabeam.

BACKGROUND: Keloids are hard nodules or plaques formed by excessive proliferation of connective tissue. Radiotherapy, widely used in various benign and malignant skin diseases, is an effective treatment for keloids. This work evaluates Intrabeam photon radiotherapy in the management of keloids. METHODS: Fourteen patients who have undergone Intrabeam radiotherapy for a total of 15 sites of keloids were followed up. Twelve cases were first onset and the other two had recurrent diseases. Thirteen patients underwent surgical resection of keloids before radiotherapy. One relapsing patient received only 2 rounds of radiation therapy as she could not be reoperated. Radiotherapy was divided into 2 sessions on days 0 and 3 after surgery. The dose was 4 or 5 Gy each time for 3 min 14 s to 12 min 1 s. In addition, we compared our data to the recurrence of keloids in fourteen patients who had previously been exposed to electron beam using conventional accelerators. RESULTS: We analyzed the treatment for adverse reactions and recurrence. In the Intrabeam group, one patient developed superficial skin ulcers a month after treatment. No one experienced wound rupture, bleeding, infection, skin contractures, or obvious hyperpigmentation. None of the fourteen cases showed any recurrence so far after on median 22.5 months of follow-up. Five patients in the electron beam group relapsed 3 to 10 months after treatment. CONCLUSION: Here, Intrabeam photon radiotherapy was shown to be an effective treatment for keloid scars and it is therefore recommended for management of this disease.

Effects of Synchrotron X-Ray Micro-beam Irradiation on Normal Mouse Ear Pinnae.

PURPOSE: To analyze the effects of micro-beam irradiation (MBI) on the normal tissues of the mouse ear. METHODS AND MATERIALS: Normal mouse ears are a unique model, which in addition to skin contain striated muscles, cartilage, blood and lymphatic vessels, and few hair follicles. This renders the mouse ear an excellent model for complex tissue studies. The ears of C57BL6 mice were exposed to MBI (50-µm-wide micro-beams, spaced 200 µm between centers) with peak entrance doses of 200, 400, or 800 Gy (at ultra-high dose rates). Tissue samples were examined histopathologically, with conventional light and electron microscopy, at 2, 7, 15, 30, and 240 days after irradiation (dpi). Sham-irradiated animals acted as controls. RESULTS: Only an entrance dose of 800 Gy caused a significant increase in the thickness of both epidermal and dermal ear compartments seen from 15 to 30 dpi; the number of sebaceous glands was significantly reduced by 30 dpi. The numbers of apoptotic bodies and infiltrating leukocytes peaked between 15 and 30 dpi. Lymphatic vessels were prominently enlarged at 15 up to 240 dpi. Sarcomere lesions in striated muscle were observed after all doses, starting from 2 dpi; scar tissue within individual beam paths remained visible up to 240 dpi. Cartilage and blood vessel changes remained histologically inconspicuous. CONCLUSIONS: Normal tissues such as skin, cartilage, and blood and lymphatic vessels are highly tolerant to MBI after entrance doses up to 400 Gy. The striated muscles appeared to be the most sensitive to MBI. Those findings should be taken into consideration in future micro-beam radiation therapy treatment schedules.

Monte Carlo simulations of a kilovoltage external beam radiotherapy system on phantoms and breast patients.

PURPOSE: To determine the most suitable lesion size and depth for radiotherapy treatments with a prototype kilovoltage x-ray arc therapy (KVAT) system through Monte Carlo simulations of the dose delivered to lesion, dose homogeneity, and lesion-to-skin ratio. METHODS: Monte Carlo simulations were used to calculate dose distributions generated by a novel low-energy kilovoltage x-ray system to a variety of clinically relevant lesion sizes and depths in phantoms and for hypothetical partial breast irradiations of patients in supine and prone positions. The treatments by 200 kV KVAT system were modeled for four sizes of tumor (1-4 cm diameter) at three depths (superficial, middle, and deep) in two sizes of cylindrical water phantoms (16.2-cm and 32.2-cm diameter). In addition, treatments of 3-cm and 4-cm diameter lesions were modeled for two breast patients in prone and supine positions. Dose distributions were calculated using the EGSnrc/DOSXYZnrc code package. Phantom study metrics included lesion-to-skin ratio, dose delivered to isocenter (cGy/min), dose homogeneity, dose profiles, and cumulative dose volume histograms. Lesion-to-skin ratio, lesion-to-rib ratio, dose profiles, and cumulative dose volume histograms were used to evaluate simulated breast patient treatments. Supine breast irradiations were compared to 6-MV VMAT plans. The criterion applied to evaluate the dose distributions was derived from NSABP-B39/RTOG 0413 for accelerated partial breast irradiation. Skin dose was limited to a maximum of 250 cGy for a prescribed lesion dose of 385 cGy per fraction (with the whole treatment being delivered in 10 fractions). This produced the minimum lesion-to-skin dose ratio of 1.5 that served as the main guideline, along with other metrics, for evaluation of future clinical viability of treatments. RESULTS: Phantom dose distributions in the centrally located lesions treated with 360-degree KVAT were found to be superior to dose distributions in off-center lesions with the exception of isocenter dose, which was highest for lesions located closer to the phantom surface. Dose metrics were more favorable for smaller lesions, suggesting that KVAT might be most suitable for treatment of lesions of 1-2 cm in diameter down to depths of 8.1 cm along with 3 cm lesions at depths from 3 cm to 8.1 cm. In addition, treatments of 4-cm lesions were found to be acceptable down to the depths of 4.1 cm (in the 16.2-cm phantom) and 8.1 cm (in the 32.2-cm phantom). At depths from 8.1-cm to 16.1-cm, treatments of 1-cm to 4-cm lesions are possible at the cost of decreased dose rate. KVAT breast treatments in the supine patient position demonstrated that increasing the arc angle and decreasing lesion size improved lesion-to-skin ratio and lesion-to-rib ratio. Supine breast data indicate that 3-cm lesions are treatable at a minimum depth of 3 cm. The 6-MV VMAT plan resulted in lower doses to the ipsilateral lung and the body, but a higher heart dose compared to the KVAT plans. Dose distributions for the prone breast phantoms were superior to the supine cases due to the increased treatment angle of 360-degrees. CONCLUSIONS: Although nonoptimized KVAT dose distributions presented here were of inferior quality to VMAT plans, this work has demonstrated the feasibility of delivering low-energy kilovoltage x-rays to lesions up to 4 cm in diameter to depths of 8.1 cm while sparing surrounding tissue.

Trans-oral miniature X-ray radiation delivery system with endoscopic optical feedback.

PURPOSE: Surgery, chemo- and/or external radiation therapy are the standard therapy options for the treatment of laryngeal cancer. Trans-oral access for the surgery reduces traumata and hospitalization time. A new trend in treatment is organ-preserving surgery. To avoid regrowth of cancer, this type of surgery can be combined with radiation therapy. Since external radiation includes healthy tissue surrounding the cancerous zone, a local and direct intraoral radiation delivery would be beneficial. METHODS: A general concept for a trans-oral radiation system was designed, based on clinical need identification with a medical user. A miniaturized X-ray tube was used as the radiation source for the intraoperative radiation delivery. To reduce dose distribution on healthy areas, the X-ray source was collimated by a newly designed adjustable shielding system as part of the housing. For direct optical visualization of the radiation zone, a miniature flexible endoscope was integrated into the system. The endoscopic light cone and the field of view were aligned with the zone of the collimated radiation. The intraoperative radiation system was mounted on a semi-automatic medical holder that was combined with a frontal actuator for rotational and translational movement using piezoelectric motors to provide precise placement. RESULTS: The entire technical set-up was tested in a simulated environment. The shielding of the X-ray source was verified by performing conventional detector-based dose measurements. The delivered dose was estimated by an ionization chamber. The adjustment of the radiation zone was performed by a manual controlling mechanism integrated into the hand piece of the device. An endoscopic fibre was also added to offer visualization and illumination of the radiation zone. The combination of the radiation system with the semi-automatic holder and actuator offered precise and stable positioning of the device in range of micrometres and will allow for future combination with a radiation planning system. CONCLUSIONS: The presented system was designed for radiation therapy of the oral cavity and the larynx. This first set-up tried to cover all clinical aspects that are necessary for a later use in surgery. The miniaturized X-ray tube offers the size and the power for intraoperative radiation therapy. The adjustable shielding system in combination with the holder and actuator provides a precise placement. The visualization of radiation zone allows a targeting and observation of the radiation zone.

The beginning of using X-rays and the evolution of equipment for the treatment of ocular cancer.

Until the early 20thcentury enucleation of the eyeball or its partial excision were the basic treatments for ocular cancer. The discovery of X-rays by Wilhelm Conrad Röntgen (1845-1923) offered new possibilities to the treatment of ocular cancer either as mono or as adjuvant therapy. Nowdays this treatment is more sophisticated.

Feasibility of external beam radiation therapy to deep-seated targets with kilovoltage x-rays.

PURPOSE: Radiation therapy to deep-seated targets is typically delivered with megavoltage x-ray beams generated by medical linear accelerators or 60 Co sources. Here, we used computer simulations to design and optimize a lower energy kilovoltage x-ray source generating acceptable dose distributions to a deep-seated target. METHODS: The kilovoltage arc therapy (KVAT) x-ray source was designed to treat a 4-cm diameter target located at a 10-cm depth in a 40-cm diameter homogeneous cylindrical phantom. These parameters were chosen as an example of a clinical scenario for testing the performance of the kilovoltage source. A Monte Carlo (MC) model of the source was built in the EGSnrc/BEAMnrc code and source parameters, such as beam energy, tungsten anode thickness, beam filtration, number of collimator holes, collimator hole size and thickness, and source extent were varied. Dose to the phantom was calculated in the EGSnrc/DOSXYZnrc code for varying treatment parameters, such as the source-to-axis distance and the treatment arc angle. The quality of dose distributions was quantified by means of target-to-skin ratio and dose output expressed in D50 (50% isodose line) for a 30-min irradiation in the homogeneous phantom as well as a lung phantom. Additionally, a patient KVAT dose distribution to a left pararenal lesion (~1.6 cm in diameter) was calculated and compared to a 15 MV volumetric modulated arc therapy (VMAT) plan. RESULTS: In the design of the KVAT x-ray source, the beam energy, beam filtration, collimator hole size, source-to-isocenter distance, and treatment arc had the largest effect on the source output and the quality of dose distributions. For the 4-cm target at 10-cm depth, the optimized KVAT dose distribution generated a conformal plan with target-to-skin ratio of 5.1 and D50 in 30 min of 24.1 Gy in the homogeneous phantom. In the lung phantom, a target-to-skin ratio of 7.5 and D50 in 30 min of 25.3 Gy were achieved. High dose conformity of the 200 kV KVAT left pararenal plan was comparable to the 15 MV VMAT plan. The volume irradiated to at least 10% (<240 cGy) of the prescription dose was 2.2 × larger in the 200 kV KVAT plan than in the 15 MV VMAT plan, but considered clinically insignificant. CONCLUSIONS: This study demonstrated that conformal treatments of deep-seated targets were achievable with kilovoltage x-rays with dose distributions comparable to MV beams. However, due to the larger volumes irradiated to clinically tolerated low doses, KVAT x-ray source usage for deep-seated lesions will be further evaluated to determine optimal target size.

Acceptance, commissioning and clinical use of the WOmed T-200 kilovoltage X-ray therapy unit.

OBJECTIVE: The objective of this work was to characterize the performance of the WOmed T-200-kilovoltage (kV) therapy machine. METHODS: Mechanical functionality, radiation leakage, alignment and interlocks were investigated. Half-value layers (HVLs) (first and second HVLs) from X-ray beams generated from tube potentials between 30 and 200 kV were measured. Reference dose was determined in water. Beam start-up characteristics, dose linearity and reproducibility, beam flatness, and uniformity as well as deviations from inverse square law were assessed. Relative depth doses (RDDs) were determined in water and water-equivalent plastic. The quality assurance program included a dosimetry audit with thermoluminescent dosemeters. RESULTS: All checks on machine performance were satisfactory. HVLs ranged between 0.45-4.52 mmAl and 0.69-1.78 mmCu. Dose rates varied between 0.2 and 3 Gy min(-1) with negligible time-end errors. There were differences in measured RDDs from published data. Beam outputs were confirmed with the dosimetry audit. The use of published backscatter factors was implemented to account for changes in phantom scatter for treatments with irregularly shaped fields. CONCLUSION: Guidance on the determination of HVL and RDD in kV beams can be contradictory. RDDs were determined through measurement and curve fitting. These differed from published RDD data, and the differences observed were larger in the low-kV energy range. ADVANCES IN KNOWLEDGE: This article reports on the comprehensive and novel approach to the acceptance, commissioning and clinical use of a modern kV therapy machine. The challenges in the dosimetry of kV beams faced by the medical physicist in the clinic are highlighted.

Commissioning a 50-100 kV X-ray unit for skin cancer treatment.

This study provides the authors' experience along with dosimetric data from the commissioning of two Sensus SRT-100 50-100 kV X-ray units. Data collected during the commissioning process included: a) HVL, b) output (dose rate), c) applicator cone factors, and d) percentage depth dose. A Farmer-type chamber (PTW-N23333), and a thin-window parallel plate ion chamber (PTW-N23342) were used for dose rate measurements and dose profiles were measured with EBT3 GafChromic film. The average HVL values for 50, 70, and 100 kV of the two treatment units were found to be 0.52, 1.15, and 2.20 mm Al, respectively. The HVL's were 5%-9% lower when measured with the Farmer chamber, as compared to measurements with the parallel plate chamber, for energies of 70 and 100 kV. Dose rates were also measured to be 3%-4% lower with the Farmer chamber. The dose rate variation between the two units was found to be 2%-9% for 50, 70, and 100 kV. The dose uniformity over a circle of 2 cm diameter was within 4% in four cardinal directions; however, the dose profiles for the 5 cm applicator were nonuniform, especially in the cathode-anode direction. Measurements indicated as much as 15% lower dose for the 50 kV beam at field edge on the anode side, when normalized to the center. The crossline profile was relatively more symmetric, with a maximum deviation of 10% at the field edge. All ion chamber readings agreed with film measurements within 3%. The nonuniform profile produced by these units may introduce uncertainty in dose rate measurements, especially for larger applicators. Since there is no intrinsic tool (crosshair or field light) for alignment with the beam axis, the user should take care when positioning the chamber for output measurements. The data obtained with a Farmer-type chamber should be used cautiously and as a reference only for the SRT-100 X-ray treatment unit.

Early effects comparison of X-rays delivered at high-dose-rate pulses by a plasma focus device and at low dose rate on human tumour cells.

A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications.

Fiber-optic detector for real time dosimetry of a micro-planar x-ray beam.

PURPOSE: Here, the authors describe a dosimetry measurement technique for microbeam radiation therapy using a nanoparticle-terminated fiber-optic dosimeter (nano-FOD). METHODS: The nano-FOD was placed in the center of a 2 cm diameter mouse phantom to measure the deep tissue dose and lateral beam profile of a planar x-ray microbeam. RESULTS: The continuous dose rate at the x-ray microbeam peak measured with the nano-FOD was 1.91 ± 0.06 cGy s(-1), a value 2.7% higher than that determined via radiochromic film measurements (1.86 ± 0.15 cGy s(-1)). The nano-FOD-determined lateral beam full-width half max value of 420 µm exceeded that measured using radiochromic film (320 µm). Due to the 8° angle of the collimated microbeam and resulting volumetric effects within the scintillator, the profile measurements reported here are estimated to achieve a resolution of ∼0.1 mm; however, for a beam angle of 0°, the theoretical resolution would approach the thickness of the scintillator (∼0.01 mm). CONCLUSIONS: This work provides proof-of-concept data and demonstrates that the novel nano-FOD device can be used to perform real-time dosimetry in microbeam radiation therapy to measure the continuous dose rate at the x-ray microbeam peak as well as the lateral beam shape.

Physiologically gated microbeam radiation using a field emission x-ray source array.

PURPOSE: Microbeam radiation therapy (MRT) uses narrow planes of high dose radiation beams to treat cancerous tumors. This experimental therapy method based on synchrotron radiation has been shown to spare normal tissue at up to 1000 Gy of peak entrance dose while still being effective in tumor eradication and extending the lifetime of tumor-bearing small animal models. Motion during treatment can lead to significant movement of microbeam positions resulting in broader beam width and lower peak to valley dose ratio (PVDR), which reduces the effectiveness of MRT. Recently, the authors have demonstrated the feasibility of generating microbeam radiation for small animal treatment using a carbon nanotube (CNT) x-ray source array. The purpose of this study is to incorporate physiological gating to the CNT microbeam irradiator to minimize motion-induced microbeam blurring. METHODS: The CNT field emission x-ray source array with a narrow line focal track was operated at 160 kVp. The x-ray radiation was collimated to a single 280 µm wide microbeam at entrance. The microbeam beam pattern was recorded using EBT2 Gafchromic(©) films. For the feasibility study, a strip of EBT2 film was attached to an oscillating mechanical phantom mimicking mouse chest respiratory motion. The servo arm was put against a pressure sensor to monitor the motion. The film was irradiated with three microbeams under gated and nongated conditions and the full width at half maximums and PVDRs were compared. An in vivo study was also performed with adult male athymic mice. The liver was chosen as the target organ for proof of concept due to its large motion during respiration compared to other organs. The mouse was immobilized in a specialized mouse bed and anesthetized using isoflurane. A pressure sensor was attached to a mouse's chest to monitor its respiration. The output signal triggered the electron extraction voltage of the field emission source such that x-ray was generated only during a portion of the mouse respiratory cycle when there was minimum motion. Parallel planes of microbeams with 12.4 Gy/plane dose and 900 µm pitch were delivered. The microbeam profiles with and without gating were analyzed using γ-H2Ax immunofluorescence staining. RESULTS: The phantom study showed that the respiratory motion caused a 50% drop in PVDR from 11.5 when there is no motion to 5.4, whereas there was only a 5.5% decrease in PVDR for gated irradiation compared to the no motion case. In the in vivo study, the histology result showed gating increased PVDR by a factor of 2.4 compared to the nongated case, similar to the result from the phantom study. The full width at tenth maximum of the microbeam decreased by 40% in gating in vivo and close to 38% with phantom studies. CONCLUSIONS: The CNT field emission x-ray source array can be synchronized to physiological signals for gated delivery of x-ray radiation to minimize motion-induced beam blurring. Gated MRT reduces valley dose between lines during long-time radiation of a moving object. The technique allows for more precise MRT treatments and makes the CNT MRT device practical for extended treatment.

The influence of focal spot size, shape, emission profile and position on field coverage in a Gulmay D3300 Kilovoltage X-ray therapy unit.

An important characteristic of kilovoltage therapy is the narrow penumbra obtainable with a well designed collimator system. A graphical illustration of applicator geometry is used to show that undesirable penumbral broadening and consequent reduction of field coverage could result if the upper aperture in an applicator is smaller than a critical size or if the applicator is not sufficiently well aligned with the focal spot. This concept is applied in an investigation of the formation of penumbra in the Gulmay D3300, in which the influence of the focal spot size, shape and emission profile, obtained from an image of the focal spot produced using a pin-hole in a sheet of lead, is elucidated. The effective focal spot of the Varian X-ray tube was observed to be rectangular, significantly longer in the front-back direction (6 mm) than in the anode-cathode direction (3.5 mm) and quite non-uniform in emission intensity over its length, with pronounced hot-spots at each end. It is shown that this results in a penumbra which is slightly broadened in the front-back direction when the alignment is perfect, but significantly broadened asymmetrically even when the alignment just meets the manufacturer's stated tolerance. Consequently the alignment, which is performed with an alignment jig supplied by the manufacturer, needs to be very precise to obtain acceptable field coverage, which needs to be checked following an X-ray tube change.

X-ray microbeam irradiation of the contusion-injured rat spinal cord temporarily improves hind-limb function.

Spinal cord injury is a devastating condition with no effective treatment. The physiological processes that impede recovery include potentially detrimental immune responses and the production of reactive astrocytes. Previous work suggested that radiation treatment might be beneficial in spinal cord injury, although the method carries risk of radiation-induced damage. To overcome this obstacle we used arrays of parallel, synchrotron-generated X-ray microbeams (230 µm with 150 µm gaps between them) to irradiate an established model of rat spinal cord contusion injury. This technique is known to have a remarkable sparing effect in tissue, including the central nervous system. Injury was induced in adult female Long-Evans rats at the level of the thoracic vertebrae T9-T10 using 25 mm rod drop on an NYU Impactor. Microbeam irradiation was given to groups of 6-8 rats each, at either Day 10 (50 or 60 Gy in-beam entrance doses) or Day 14 (50, 60 or 70 Gy). The control group was comprised of two subgroups: one studied three months before the irradiation experiment (n = 9) and one at the time of the irradiations (n = 7). Hind-limb function was blindly scored with the Basso, Beattie and Bresnahan (BBB) rating scale on a nearly weekly basis. The scores for the rats irradiated at Day 14 post-injury, when using t test with 7-day data-averaging time bins, showed statistically significant improvement at 28-42 days post-injury (P < 0.038). H&E staining, tissue volume measurements and immunohistochemistry at day ≈ 110 post-injury did not reveal obvious differences between the irradiated and nonirradiated injured rats. The same microbeam irradiation of normal rats at 70 Gy in-beam entrance dose caused no behavioral deficits and no histological effects other than minor microglia activation at 110 days. Functional improvement in the 14-day irradiated group might be due to a reduction in populations of immune cells and/or reactive astrocytes, while the Day 10/Day 14 differences may indicate time-sensitive changes in these cells and their populations. With optimizations, including those of the irradiation time(s), microbeam pattern, dose, and perhaps concomitant treatments such as immunological intervention this method may ultimately reach clinical use.

Vagus nerve stimulator stability and interference on radiation oncology x-ray beams.

Five different models of Cyberonics, Inc. vagus nerve stimulation (VNS) therapy pulse generators were investigated for their stability under radiation and their ability to change the absorbed dose from incident radiation. X-ray beams of 6 MV and 18 MV were used to quantify these results up to clinical doses of 68-78 Gy delivered in a single fraction. In the first part, the effect on electronic stimulation signaling of each pulse generator was monitored during and immediately afterwards with computer interrogation. In the second part, the effects of having the pulse generators scatter or attenuate the x-ray beam was also characterized from dose calculations on a treatment planning system as well as from actual radiation measurements. Some device models were found to be susceptible to radiation interference when placed directly in the beam of high energy therapeutic x-ray radiation. While some models exhibited no effect at all, others showed an apparent loss of stimulation output immediately after radiation was experienced. Still, other models were observed to have a cumulative dose effect with a reduced output signal, followed by battery depletion above 49 Gy. Absorbed dose changes on computer underestimated attenuation by nearly half for both energies amongst all pulse generators, although the computer did depict the proper shape of the changed distribution of dose around the device. Measured attenuation ranged from 7.0% to 11.0% at 6 MV and 4.2% to 5.2% at 18 MV for x-rays. Processes of back-scatter and side-scatter were deemed negligible although recorded. Identical results from 6 MV and 18 MV x-ray beams conclude no neutron effect was induced for the 18 MV beam. As there were documented effects identified in this research regarding pulse generation, it emphasizes the importance of caution when considering radiation therapy on patients with implanted VNS devices with observed malfunctions consequential.