Studies have shown that x-rays delivered as arrays of parallel microplanar beams (microbeams), 25-to 90-m thick and spaced 100 -300 m on-center, respectively, spare normal tissues including the central nervous system (CNS) and preferentially damage tumors. However, such thin microbeams can only be produced by synchrotron sources and have other practical limitations to clinical implementation. To approach this problem, we first studied CNS tolerance to much thicker beams. Three of four rats whose spinal cords were exposed transaxially to four 400-Gy, 0.68-mm microbeams, spaced 4 mm, and all four rats irradiated to their brains with large, 170-Gy arrays of such beams spaced 1.36 mm, all observed for 7 months, showed no paralysis or behavioral changes. We then used an interlacing geometry in which two such arrays at a 90°angle produced the equivalent of a contiguous beam in the target volume only. By using this approach, we produced 90-, 120-, and 150-Gy 3.4 ؋ 3.4 ؋ 3.4 mm 3 exposures in the rat brain. MRIs performed 6 months later revealed focal damage within the target volume at the 120-and 150-Gy doses but no apparent damage elsewhere at 120 Gy. Monte Carlo calculations indicated a 30-m dose falloff (80 -20%) at the edge of the target, which is much less than the 2-to 5-mm value for conventional radiotherapy and radiosurgery. These findings strongly suggest potential application of interlaced microbeams to treat tumors or to ablate nontumorous abnormalities with minimal damage to surrounding normal tissue.

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.

Microbeam radiation therapy is an experimental modality using parallel arrays of thin (<100 micro m) slices of synchrotron-generated X rays (microplanar beams, microbeams). We used EMT-6 murine mammary carcinoma subcutaneously inoculated in the hind legs of mice to compare the therapeutic efficacies of single-fraction, unidirectional (1) "co-planar" microbeams (an array of vertically oriented microplanar beams), (2) "cross-planar" microbeams (two arrays of parallel microbeams propagated in the same direction, one with vertically and the other with horizontally oriented microplanar beams), and (3) seamless (broad) beams from the same synchrotron source. The microbeams were 90 micro m wide and were spaced 300 micro m on center; the median energy in all beams was 100 or 118 keV. Tumor ablation rates were 4/8, 4/8 and 6/7 for a 410-, 520- and 650-Gy in-slice cross-planar microbeam dose, respectively, and 1/8, 3/8, 3/7 and 6/8 for a 23-, 30-, 38- and 45-Gy broad-beam dose, respectively. When the data were pooled from the three highest doses (same average tumor ablations of 50-60%), the incidences of normal-tissue acute toxicity (moist desquamation and epilation) and delayed toxicity (failure of hair regrowth) were significantly lower for cross-planar microbeams than broad beams (P < 0.025). Furthermore, for the highest doses in these two groups, which also had the same tumor ablation rate (>75%), not only were the above toxicities lower for the cross-planar microbeams than for the broad beams (P < 0.02), but severe leg dysfunction was also lower (P < 0.003). These findings suggest that single-fraction microbeams can ablate tumors at high rates with relatively little normal-tissue toxicity.

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Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.

There is growing interest in evaluating microbeam radiation therapy as a potential clinical modality. Microbeam radiation therapy uses arrays of parallel, microscopically thin (<100 microm) planes of synchrotron-generated X rays (microplanar beams, or microbeams). Due to the relatively low beam energies involved in microbeam radiation therapy (a median beam energy of 120 keV was used in the present study), the dose penetration of microbeams in tissue is lower than that used in conventional radiotherapy. This lower energy necessitates using a significantly elevated dose to the skin's surface during clinical microbeam therapy to ensure an adequate dose distribution in the target tumor. The findings of the present study, using a rat skin model, indicated that the skin had an extremely high tolerance to microbeam radiation at doses considerably in excess of those that were therapeutically effective in preclinical studies. A histological study was undertaken to evaluate the biological mechanisms underlying this high tolerance. The irradiation configuration employed single-exposure, unidirectional microbeams 90 microm wide, with 300 microm beam spacing on-center. The in-beam skin-surface absorbed doses were in the range 835-1335 Gy. Monte Carlo simulations of the dose distribution indicated that the "valley" dose, i.e. the radiation leakage between adjacent microbeams, was about 2.5% of the in-beam dose. The high tolerance of the rats' skin to microbeams and the rapid regeneration of the damaged segments of skin were attributed to the surviving clonogenic cells situated between the adjacent microplanar beams. In the epidermis, clonogenic cells in the hair follicular epithelium appeared to play a key role in the regeneration process.

We present EGS4 Monte Carlo calculations of the spatial distribution of the dose deposited by a single x-ray pencil beam, a planar microbeam, and an array of parallel planar microbeams as used in radiation therapy research. The profiles of the absorbed dose distribution in a phantom, including the peak-to-valley ratio of the dose distribution from microbeam arrays, were calculated at micrometer resolution. We determined the dependence of the findings on the main parameters of photon and electron transport. The results illustrate the dependence of the electron range and the deposited in-beam dose on the cut-off energy, of the electron transport, as well as the effects on the dose profiles of the beam energy, the array size, and the beam spacing. The effect of beam polarization also was studied for a single pencil beam and for an array of parallel planar microbeams. The results show that although the polarization effect on the dose distribution from a 3 cm x 3 cm microbeam array inside a water phantom is large enough to be measured at the outer side of the array (16% difference of the deposited dose for x-ray beams of 200 keV), it is not detectable at the array's center, thus being irrelevant for the radiation therapy purposes. Finally we show that to properly compare the dose profiles determined with a metal oxide semiconductor field emission transistor detector with the computational method predictions, it is important to simulate adequately the size and the material of the device's Si active element.

A bent Laue monochromator and a conventional x-ray tube were used to produce a fan beam that was parallel in the plane perpendicular to the plane of the fan. The x-ray fan beam was tunable in energy and had about 12% energy bandwidth at a slice height of 5 mm when tuned to 50 keV. The beam's energy was slightly coupled to the vertical position on the beam's height. The slice height could be varied from 1 to 10 mm. The flux at 50 keV was approximately 2x10(6) photons/mm2/s with a rotating anode tungsten x-ray tube operating at 120 kVp and 100 mA. The narrow energy bandwidth of the beam produced is advantageous over a conventional divergent polychromatic beam for all radiography applications, while the parallelism of the beam enhances its intensity by about threefold and offers some advantages for computed tomography.