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Microbeam radiosurgery using synchrotron-generated submillimetric beams: a new tool for the treatment of brain disorders

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Abstract

Since its advent during the mid-twentieth century, radiosurgery has undergone a steady evolution. Gamma Knife and linear accelerator based systems using rigid frames preceded the development of frameless devices. The present report describes the development of microbeam radiosurgery, a technique which uses submillimetric beams of radiation to treat disease. Typically, the technique is employed using parallel arrays of beams delivered via a high-fluence synchrotron source. Beam widths between 20 and 950 μm have been used with the majority of studies utilizing beam widths less than 100 μm. In addition to its high precision, the technique allows users to take advantage of two unique properties of microbeams. The first is a remarkable tolerance of healthy tissue to microbeams delivered at doses up to several hundred grays, while at the same time, tumors are highly susceptible to the lethal effects of microbeams. Together, these findings allow for a “preferential tumoricidal effect” beyond the typical dose–volume relationship. Although only used in animal experiments so far, we explore the hypothetical clinical role of microbeam radiosurgery which may be feasible in the near future. In addition to the treatment of traditional radiosurgery targets such as malignancies and vascular malformations, microbeams may allow the non-invasive treatment of functional disease such as movement disorders, epilepsy, and mental illness.

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Acknowledgement

We thank Dr. Michel Renier (ESRF) for the kind production of Fig. 3.

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Authors and Affiliations

  1. Comprehensive Epilepsy Center of Long Island, 200 Belle Terre Road, Port Jefferson, NY, 11778, USA

    David J. Anschel

  2. Biomedical Beamline ID17, European Synchrotron Radiation Facility, 6 rue J. Horowitz BP 220, 38043, Grenoble Cedex, France

    Alberto Bravin

  3. Functional Neurosurgery, IRCCS Neuromed, Via Atinense 18, Pozzilli, 86077, IS, Italy

    Pantaleo Romanelli

Authors
  1. David J. Anschel
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  3. Pantaleo Romanelli
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Correspondence to David J. Anschel.

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Comments

Ekkehard M. Kasper, Bosten, USA

In this paper, the authors present the fascinating topic of precise radiosurgery using synchrotron-generated submillimetric beams as a new tool for the treatment of brain disorders. This review deals with the currently available experimental data from literature reporting on the investigative use of such a radiation technique. The intent is to review a topic rather unfamiliar to most clinicians.

This endeavour can be welcomed as an excellent idea, since the available body of literature warrants this project and the authors lucidly present the relevant publications in the field. Before the authors go into detail, a general section addressing the conceptual design/technique is included. Technology of beam generation, geometry, homogeneity, energy and dosing considerations are reviewed. Observed histopathological changes as seen and expected from the dose delivered are shown and the authors report on the experimental options to follow such lesions with modern high-resolution MRI imaging.

The most appealing part of the speculative future applications is in the precision of applying this technique to neurosurgery of superficial lesion (e.g. functional subpial transections) and eventually also to deep-seated lesions (e.g. STN) or other targets in psychiatric settings in which circuitry and hence targeting is currently being worked out. Further studies of the biological effects of this technique are greatly needed to demonstrate the specific tissue response and its preferential tumoricidal effect and to enrich the armatorium of our treatment options. The authors should be congratulated for bringing the results of this technology to the focus of attention of interested readers.

Michael W. McDermott, San Francisco, USA

The article by Anschel et al. presents the concept of microbeam radiation therapy using synchrotron sources. It is another example of the wonder of science potentially providing another window to “improving the therapeutic ratio” when it comes to treating tumors. Since there is no primate or human data available yet, the promise of a benefit remains just that. In the past, we have heard of, and subsequently tried, many different techniques over the past 25 years to improve the results with the use of irradiation techniques in treating brain tumors. I believe we have reached our limit with this “physical” treatment for malignant tumors and the only trade-off for success in terms of tumor control using radiation therapy is radiation necrosis. Many times (e.g. solitary brain metastases, glial tumors in non-eloquent cortex), the trade-off is worth it for patients and families but very few of these long-term radiation therapy survivors live a normal life.

Apart from the limited availability of highly specialized treatment sites, I agree with the authors that another major hurdle before being able to treat patients is the method for patient immobilization and positioning in the microbeam field. System accuracy is one thing; application accuracy is another, which involves the sum of errors of all the steps in the treatment process from imaging, targeting, positioning to delivering the energy. That being said, I see this technique having potential some day for highly specialized functional procedures where the microbeam paths may be used to interrupt association fibers or disturb tiny nuclei without an implanted electrode. I wish all the investigators in microbeam radiation therapy success with their future investigations. I would be delighted to be proven wrong some day!

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Anschel, D.J., Bravin, A. & Romanelli, P. Microbeam radiosurgery using synchrotron-generated submillimetric beams: a new tool for the treatment of brain disorders. Neurosurg Rev 34, 133–142 (2011). https://doi.org/10.1007/s10143-010-0292-3

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