X-ray microbeams: Tumor therapy and central nervous system research

Abstract

Irradiation with parallel arrays of thin, planar slices of X-ray beams (microplanar beams, or microbeams) spares normal tissue, including the central nervous system (CNS), and preferentially damages tumors. The effects are mediated, at least in part, by the tissue's microvasculature that seems to effectively repair itself in normal tissue but fails to do so in tumors. Consequently, the therapeutic index of single-fraction unidirectional microbeam irradiations has been shown to be larger than that of single-fraction unidirectional unsegmented beams in treating the intracranial rat 9L gliosarcoma tumor model (9LGS) and the subcutaneous murine mammary carcinoma EMT-6. This paper presents results demonstrating that individual microbeams, or arrays of parallel ones, can also be used for targeted, selective cell ablation in the CNS, and also to induce demyelination. The results highlight the value of the method as a powerful tool for studying the CNS through selective cell ablation, besides its potential as a treatment modality in clinical oncology.

Fig. 1

Schematic view of irradiating a tumor with an array of parallel microbeams. The figure indicates the sparing effect of microbeams in normal tissue, and their preferential tumoricidal effect.

Fig. 2

Monte Carlo simulations of the dose distribution from an array of parallel microbeams in a cylindrical water phantom using the EGS4 code of photon- and electron-transport. The figure represents the dose distribution for one complete period of the array.

Fig. 3

Path of a microbeam in the cerebellum 3 h post-irradiation seen as darkened cerebella granular cells (400 ×).

Fig. 4

Microbeam’s path seen in the cerebellum 2 d post-irradiation (400 ×).

Fig. 5

Microbeam’s path in the cerebellum 4 d post-irradiation. Some neurons have disappeared (400 ×).

Fig. 6

Microbeam pattern of banding seen in the cerebellum 16 d post-irradiation. Almost all neurons had disappeared, leaving a strong white band (arrows) (200 ×).

Fig. 7

Similar to Fig. 6, but also showing two undamaged capillary blood vessels crossing the microbeam-induced tracks (arrows) (200 ×).

Fig. 8

Microbeam pattern of banding seen in the cerebrum 3 weeks post-irradiation (arrows) (200 ×).

Fig. 9

Schematic horizontal section of the rat brain showing the position of the microbeam just lateral to the midsaggital sulcus. Loss of putative oligodendrocytes (APC+) and astrocytes (glial fibrillary acidic protein, GFAP+) one week after exposure to a 270 μm wide, 650 Gy microbeam in the white matter of the rat brain (midsaggital sulcus) (work carried out in collaboration with John McDonald et al., Washington University).