Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200-1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size  ≈  4  ×  10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM  =  246  ±  32 µm; center-to-center  =  926  ±  23 µm; peak-to-valley dose ratio  =  24.35  ±  2.10; collimator relative output factor  =  0.84  ±  0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP  =  glioblastoma; B16-F10  =  melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p< 0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.

Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based X-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board X-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 μm measured directly from the histology (537 μm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors.

A new imaging technology has emerged that uses carbon nanotubes (CNT) as the electron emitter (cathode) for the X-ray tube. Since the performance of the CNT cathode is controlled by simple voltage manipulation, CNT-enabled X-ray sources are ideal for the repetitive imaging steps needed to capture threedimensional information. As such, they have allowed the development of a gated micro-computed tomography (CT) scanner for small animal research as well as stationary tomosynthesis, an experimental technology for large field-of-view human imaging. The small animal CT can acquire images at specific points in the respiratory and cardiac cycles. Longitudinal imaging therefore becomes possible and has been applied to many research questions, ranging from tumor response to the noninvasive assessment of cardiac output. Digital tomosynthesis (DT) is a low-dose and low-cost human imaging tool that captures some depth information. Known as three-dimensional mammography, DT is now used clinically for breast imaging. However, the resolution of currently-approved DT is limited by the need to swing the X-ray source through space to collect a series of projection views. An array of fixed and distributed CNT-enabled sources provides the solution and has been used to construct stationary DT devices for breast, lung, and dental imaging. To date, over 100 patients have been imaged on Institutional Review Board-approved study protocols. Early experience is promising, showing an excellent conspicuity of soft-tissue features, while also highlighting technical and post-acquisition processing limitations that are guiding continued research and development. Additionally, CNT-enabled sources are being tested in miniature X-ray tubes that are capable of generating adequate photon energies and tube currents for clinical imaging. Although there are many potential applications for these small field-of-view devices, initial experience has been with an X-ray source that can be inserted into the mouth for dental imaging. Conceived less than 20 years ago, CNT-enabled X-ray sources are now being manufactured on a commercial scale and are powering both research tools and experimental human imaging devices.