Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

Zhang, Lei; Yuan, Hong; Burk, Laurel; Inscoe, Christina R.; Hadsell, M; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, S; Zhou, Otto

doi:10.1088/0031-9155/59/5/1283

Cited by 23 publications

(29 citation statements)

References 55 publications

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“…Our compact microbeam system is different from the synchrotron irradiation system, since it electronically controls the radiation and thus allows real-time gated radiation delivery using respiratory or cardiac signals to accurately deliver the radiation under organ motions (15). An image-guided MRT protocol has been established for mouse brain tumor treatment, where magnetic resonance images were registered to the on-board X-ray radiography images of mouse brain to guide the delivery of microbeam radiation to the brain tumor with an average 450 µm accuracy (16). The current study used the same image-guided MRT protocol reported earlier, and aimed to evaluate radiobiological effects from MRT.…”

Section: Introductionmentioning

confidence: 99%

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

et al. 2015

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Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 µm wide and spaced at 900 µm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

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Section: Introductionmentioning

confidence: 99%

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

et al. 2015

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“…[10][11][12][13] The purpose of the compact x-ray tube based system is not to match the exquisite MRT dosimetry from the massive synchrotron facility based MRT systems. Our hypothesis is that the compact MRT system, especially future generation systems, can produce similar radiobiology response as the synchrotron-based MRT system.…”

Section: A Microbeam Radiation Therapymentioning

confidence: 99%

“…The five segments of electron source array are focused onto the surface of a common tungsten-rhenium anode with an energy 160 kVp. 12,13 The resulting reflective x-ray focal line, created by the five aligned linear electron beams bombarding the tungsten anode, was 142 µm by 160 mm after projection into an angle of 8…”

Section: A Compact Microbeam X-ray Systemmentioning

confidence: 99%

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

et al. 2015

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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.

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“…Targeted delivery of the microbeam to the brain tumor site in mouse has been demonstrated using a combined MRI and onboard x-ray projection imaging procedure. 20 Using the compact microbeam irradiator with an inevitably lower dose rate compared to what is used in synchrotron MRT experiments, it is necessary to minimize physiological motion induced microbeam blurring. MRT research so far is mainly focused on the brain tumors.…”

Section: B Compact Image Guided Mrt System For Small Animal Treatmentmentioning

confidence: 99%

“…20 The gate mesh, which is directly above the CNT substrates on the cathodes, is grounded, the anode is set to 160 kVp, and the cathodes are pulsed from ground to a negative voltage using a pulse generator to produce x rays at scheduled intervals. In regular experiments where gating is not used, the tube is operated at an 8% duty cycle using 500 μs width pulses.…”

Section: A Desktop Mrt Systemmentioning

confidence: 99%

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

et al. 2014

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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 c 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...

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Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

Cited by 23 publications

References 55 publications

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

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

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

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