1 Introduction

Four photon-energy radiosurgery devices have been competitive in the market due to their uniqueness and specific advantages over the other systems (see Chap. 2). In the near future, these systems will compete with the evolution of non-photon delivery systems, such as proton beam systems. Inexpensive proton beam systems have been on the radar for many years. Now, one such device still five times more expensive than the photon delivery systems is making its way into the market and may be successful due to potentially better dose distributions (Kjellberg et al. 1983). However, the intrinsic advantage of the proton beam with its Bragg peak delivery has yet to match the current developments of the photon beam exploitations, such as multiple beams (200+ gamma beams), continuous beam delivery with shaping and modulation (LINACs), 150+ non-isocentric nodes of the Cyberknife® (Accuray Inc, Sunnyvale, CA), or the tomographic capabilities of Tomotherapy® (TomoTherapy, Madison, WI). Systems combining all the predicates of these four systems are also likely to gain market share. An example is the VERO™ (Brainlab AG, Feldkirchen, Germany), already in use in Europe.

Little has improved on the generation of energy; what has improved is the capability of beam manipulation. This became possible with the integration of fast computer calculation of radiation dosimetry (see Chap. 5). It made possible the introduction of three-dimensional imaging to treatment planning, relaying this information to smart robotic machines capable of delivering intricate plans, including shaping and modulation of the radiation beam. As the advances of this field continue depending on the image capabilities, we will discuss the landmarks of imaging integration and speculate the impact of the imaging development in the future of stereotactic radiation.

2 Three- and Four-Dimensional Imaging

Stereotactic radiosurgery was initiated with anteroposterior and lateral X-rays (Leksell 1951). These two projections were able to give precision to the stereotactic technique, allowing calculation of X, Y, and Z coordinates of a point inside of the stereotactic space. It also allowed calculation of the volume of an ellipsoid projection to the two 2D planes (Bova and Friedman 1991). This depended on collimator size to obtain the functional lesion desired, as envisioned by Leksell, which was then possible with the radiofrequency technique. Therefore, at the inception of radiosurgery, Leksell was trying to mimic a radio­frequency heat lesion for functional procedures in the brain. When radiosurgery started to be applied to ablate arteriovenous malformations, the need for better definition of the volume of radiation came into demand (Friedman and Bova 1989). Rough approximation of the lesion volume was then initially tried (De Salles et al. 1987), however the integration of computed tomography to treatment planning brought the revolution capable of tumor volume definition with the possibility to integrate the radiation delivery with the true lesion volume. This brought about the proposal of modulation of the radiation beam as the next step, allowing the treatment of previously difficult to treat pathologies (Fig. 1.1). Now the possibility of registering the movement of lesions for moving targets, such as those in the liver and lung, has brought into reality radiosurgery of lesions throughout the body, revolutionizing the field of radiation therapy with stereotactic body radiation therapy (SBRT) and demanding 4D treatment planning, competing with gated radiation delivery (see Chaps. 24–26).

Fig. 1.1
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Skull sarcoma planned with Rapid Arc. Axial (a), Coronal (b), and Sagittal (c)

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3 Image Fusion

The desire to merge images of different modalities was initiated to bring the high definition of 3D visualization of lesions on magnetic resonance imaging (MRI) and computed tomography (CT) scans into the radiosurgery planning. This effort required the transport of the information obtained by MRI and CT into the stereotactic space (De Salles et al. 1987). The need to fuse images was further stimulated by the identification of distortions of the MRI, hampering the quality of the stereotactic calculations. Fusion of MRI and CT of the same patient allowed for the MRI distortions correction (Alexander et al. 1995), improving visualization of the lesions and still maintaining the stereotactic exquisite precision. This advance permitted the delivery of effective single dose of radiation to targets in the brain and now in the whole body (De Salles et al. 1997; De Salles et al. 2004).

4 Functional Image Integration

The integration of functional imaging into treatment planning, promises the improvement of stereotactic radiosurgery results. Advanced functional imaging such as functional MRI with fiber tracking can now be used in brain pathologies such as arteriovenous malformation (AVMs) (Hauptman et al. 2008), and implementation of molecular imaging ­such as metionine and fluorodopa scans, as well as with well-established ­fluoro-deoxy-glucose positron emission tomography (PET) are useful tools in treating tumors of the brain (Melega et al. 2010). This likely will lead to a new capability of preserving function from radiation damage and directing radiation to the functional portions of the pathology. Moreover, head and neck cancers and tumors in other locations can now be functionally localized and brought into the treatment planning by computed tomography fused to PET (CT-PET) fusion allowing for more specific delivery of radiation (Fig. 1.2).

Fig. 1.2
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CT fused to fluoro-deoxy-glucose PET (CT-FDG-PET) fusion for stereotactic planning of a head and neck tumor. Notice that the molecular image alone has poor anatomic definition (a), CT alone has poor lesion definition (b), merging both images it is possible to precisely localize the most active portion of the tumor to be treated (c)

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5 Anatomical Integration

5.1 Atlas

Historical atlases have helped neurosurgeons integrate knowledge accumulated by electrophysiology and classic anatomy to advanced imaging techniques. The integration of three-dimensional imaging to historical atlases, pioneered by Talairach and Tournoux (1988), became commonplace in commercial software for neurosurgery. Now it is becoming commonplace for SBRT pioneered by Brainlab technology (see Chap. 3). These robust guidelines for planning radiation delivery have expedited segmentation of structures to be avoided, thereby making this approach readily applicable in clinic without the need of tedious segmentation by a knowledgeable professional. This becomes important with techniques of inverse treatment planning such as intensity modulation radiation therapy (IMRT), volumetric intensity modulated arc therapy (VMAT), and Hybrid Arc delivery (Fig. 1.1).

5.2 Fiber Tracking

Imaging techniques have evolved beyond the ability of the practitioner to use them clinically. Fiber tracking and its integration with localization and treatment planning software is an example of such technical advance over clinical practice. While practitioners are still using almost exclusively anatomical visualization of lesions, fiber tracking could revolutionize dose distribution in neurological applications. Understanding that white matter tracts should be avoided from high exposure of radiation due to the paucity of blood supply to the white matter tracts in the brain and spine leads to preservation of important functional pathways. White matter tracts are served with one fourth of the blood supply available to the gray matter. As much of the permanent damage caused by radiation is secondary to vascular obstruction with ensuing ischemia, avoidance of large dose to these brain-sensitive portions can be achieved with integration of fiber tracking information in relation to lesion locations and functionality of the brain. This is now possible with currently available software used in Novalis® radiosurgery (Brainlab AG, Feld­kirchen, Germany) treatment planning (Fig. 1.3).

Fig. 1.3
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The application of fiber tracking in radiosurgery is still at its infancy. The universe of fibers in the brain is depicted in (a). An AVM imbedded in the right white matter tracks and motor area is shown for planning centered in the cross lines. High dose should be avoided in the medial periphery of the AVM where the fibers are seen in blue (b)

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6 Functional Applications

Accuracy and precision of linear accelerator radiosurgery has been well established by several groups (De Salles et al. 2001; Friedman and Bova 1992; Rahimian et al. 2004; Solberg et al. 2004). This application allows precise and accurate placement of high doses of radiation to specific regions of the brain and spine (Frighetto et al. 2004; De Salles and Medin 2009; Smith et al. 2003), even daring positioning of isocenters close to vital structures such as the brainstem (Gorgulho et al. 2006). Trigeminal neuralgia (De Salles et al. 1997), cluster headaches (De Salles et al. 2006), central pain (Frighetto et al. 2004), epilepsy (Selch et al. 2005), are all functional disorders already proven controlled by stereotactic radiosurgery using the Novalis radiosurgery platform, now also achieved without the stereotactic frame (Agazaryan et al. 2008; Chen et al. 2004). Functional applications will tend to increase as dermatomal benign pain and cancer pain start to be treated with current image-guided radiation therapy (IGRT). As radiation oncologists become confident with precision and applications of this technique to control patient’s pain, the benefits of this advanced technology will likely be exploited. The non-invasiveness and the effectiveness of high-dose radiation to ganglia and spinal nerves overcome invasive techniques to control pain, as it has been shown for trigeminal neuralgia (Gorgulho and De Salles 2006). Even if the final result falls short from what can be obtained with invasive surgery, patients and payers would prefer a less invasive approach. Application to control trigeminal neuralgia is just the tip of the iceberg of what may become commonplace in cancer and benign pain control (See Chaps. 4, 17–20, 28). Manipulation of the radiation strength to achieve functional changes in the neural tissue is still an unexploited field. Radiation may modulate function of cells to profit the patient with functional disorders. An example is the experimental work showing that low dose of radiation, i.e., radiation in the penumbral zone of the high radiation beam, affect cells leading to over production of neurotransmitters and growth factors (De Salles et al. 2001). The latter reaction may be similar to the phenomenon of repair with cellular proliferation and overproduction of collagen type IV material, which occurs in the vasculature of the AVM nidus treated by radiosurgery (Jahan et al. 2006).

7 Stereotactic Brain and Spine Radiation

Radiosurgery has revolutionized the treatment of benign and metastatic brain tumors (See Chaps. 7–15). Single-dose radiation, a novelty for neurosurgeons and radiation oncologists alike, became common practice with the explosion of imaging and precision-oriented radiation technology during the last two decades of the twentieth century. Now, the knowledge of radiation biology accumulated over 100 years is being applied to stereotactic radiotherapy to decrease treatment side effects (see Chap. 6). Challenging short schemes of radiation and taking advantage of the ability to reproduce patient’s positioning in relation to the radiosurgery device without invasive fixation have brought the possibility of hypofractionation to resection cavities (Soltys et al. 2008) and giant AVMs (Xiao et al. 2010). Proven safe schemes of radiation for preservation of specialized sensory structures as optic and cochlear nerves, brainstem, pituitary gland, and spinal cord are used to approach previously untouchable pathologies. For example, preservation and improvement of vision in optic sheath meningiomas, exquisite preservation of the acoustic nerve function in treatment of acoustic neuromas (Selch et al. 2004), preservation of hormonal capabilities in pituitary lesions (Selch et al. 2006), and treatment of intrinsic medullar tumors and AVMs (De Salles et al. 2004; Selch et al. 2009).

8 Stereotactic Body Radiation Therapy

The accuracy required for stereotactic radiosurgery and the effectiveness of single-dose treatment of ­metastatic disease in the brain has spearheaded the development of precision-oriented radiation therapy (De Salles et al. 2008). Stereotactic body radiation therapy (SBRT) became the new and exciting effort in radiation oncology. The ability to exchange number of fractions for precise delivery of high doses has revolutionized the management of malignances in the lung (Fig. 1.4), liver, pancreas, and prostate. This ability may represent not only new more effective treatment of focal disease (Fig. 1.5), but also more comfort for the patient with savings of health dollars. Further development of these applications is the exciting part of stereotactic radiation therapy reflected in the Part III and IV of this book.

Fig. 1.4
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Stereotactic radiosurgery planning for a lesion in the right lung upper lobe. Treatment for this lesion requires tracking of lung movement for gated delivery or 4D imaging capability. (a) Notice the 3D automatic reconstruction of organs at risk, trachea, spinal cord, heart. (b) Coronal, (c) Sagittal and (d) Coronal views of the radiosurgery planning

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Fig. 1.5
figure 5

Hypofractionated intensity modulated radiation therapy plan for a Brachial Plexus AVM presenting with left arm pain (five daily fractions of 6Gy). (a) Axial (b) Coronal and (c) Sagittal views of the radiosurgery plan

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9 Conclusion

A revolution in radiation therapy started with the use of single high-dose delivery using the exquisite accuracy and precision of the work of functional stereotactic ­surgeons. This revolution hinged on the explosion of ­computed imaging technology, initially with the CT followed by the integration of MRI. The application of fiber tracking, functional MRI, and molecular imaging is the next step of the specificity of this revolution. The precision of the stereotactic frame gave way to image-guided technology, and challenged the dogmas established in radiation biology creating room for fewer fractions with high dose, enhanced effectiveness, decreased side effects, more comfort for the patient and likely decrease in health care dollar expenditure. The pages of this text reflect the accomplishments of this revolution.