**5.1 Histopathological response**

Radiation induces endothelial damage (lasting biochemical changes and apoptosis), thrombocyte aggregation/development of fibrin microthrombi, and subendothelial/ perivascular spindle cell proliferation (contractile myofibroblasts formed in vascular walls and AVM connective tissue—stroma) [23, 82, 83]. Both degenerative and proliferative changes are dose- and time-dependent. Degeneration expressions are tissue granulation and inflammatory cell presence in the stroma followed by type IV collagen-producing fibroblasts and fibrocytes and eventually hyaline phenotypics and obliterated vessels. Proliferation is expressed by the formation and accumulation of myofibroblasts (neointima) assumed as the canonical shrinking and occlusion factor in irradiated AVMs [23, 82, 83]. Importantly, normal vessels do not exhibit propensity to obliterate. Apparently, due to the connective tissue (stroma) surrounding the AVM nidus, pathological vessels playing a key role in the obliteration process [23, 84]. Obliteration is often followed by new vessel formation, occasionally visible on MRI [23, 82]. Radiation-induced necrosis, neural loss, myelin fragmentation, and gliosis have been detected in the surrounding brain tissue 1–10 mm from the lesion

#### **Figure 5.** *Schematic illustration of a stereotactic radiosurgery procedure [© Mayo clinic].*

*Advocating Intraluminal Radiation Therapy in Cerebral Arteriovenous Malformation Treatment DOI: http://dx.doi.org/10.5772/intechopen.89662*

#### **Figure 6.**

*Top: SRS treatment planning (dosimetry). Using imaging scans and specialized software, the treatment team determines the best combination of radiation beams to target the lesion [© Mayo clinic]. Bottom: marginal dose versus efficacy (following [81]).*

border [23]. Histopathology is typically elicited and efficacy-controlled by focused irradiation of marginal doses of ~10–35 Gy (median ~20) (**Figure 6**)—delivered in a single or fractionated (higher doses) protocol [81, 82]. It has become a consensus that a better understanding of irradiation response physiology may facilitate the targeting of individual enzyme systems and open up new SRS opportunities [84].

#### **5.2 Widely used systems**

**Gamma-knife systems** consist of up to ~200 cobalt-60 sources arranged in circular arrays within a spherical mechanism [79]. The arrays' geometry and source strength (typically ~30 curies each) result in a 3D energy field of isodoses at any defined volume within the sphere. While each source beam dose is very low, the converged irradiation at any pre-chosen focus position adds up to clinical values. The targeted volume can be varied using different sized collimators. These systems

traditionally required complete patient immobilization—which involves direct mechanical fixation of patients' skulls using a stereotactic frame. The fixation is an invasive procedure that can be highly painful and stressful. Newer models can perform frameless treatment (thermoplastic mask for immobilization and advanced imaging for stereotactic orientation), thus supporting a less invasive patient experience. **Gantry and robotic arms systems** employ gantry-mounted linear accelerators ("LINACS") to generate the energy beam and rely on either fixed circular or multi-leaf collimators (MLCs) for its shaping. This allows a conformal scheme which aids in treating irregular nidus geometries. Alternatively, the system can be mounted on a robotic platform (arm vs. gantry) that adds mechanical degrees of freedom. Patient positioning can also be achieved using imaging (cone beam CT) or laser systems, so frame-based immobilization systems are becoming obsolete. Less common are **proton beam systems** that accelerate protons (using a synchrotron or cyclotron) in order to generate the therapeutic beam. An advantage of proton treatment is the minimal target-exiting dose safeguarding the lesion surrounding tissue. The proton beam is typically delivered to the target volume via a gantry mechanism. Patient immobilization can be achieved invasively and non-invasively. Proton systems' main disadvantage is that they are scarce and expensive.
