preface - bücher.de · 2020-05-15 · he practice of stereotactic radiosurgery has developed from...

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Preface

The practice of stereotactic radiosurgery has developed from an unprecedented degree of collaboration among practitioners of neurosurgery, radiation oncology, and medical physics. Because the patients and the diseases that we treat are at the intersection of

surgery, radiation, and medical therapy, we felt that a full description of this fi eld required a comprehensive and global approach to the subject. Not only would we discuss the main diseases that comprise the typical intracranial radiosurgery practice, such as brain metastases and AVMs, we would also cover the fast-growing fi eld of extracranial radiosurgery, as well as more unusual indications such as epilepsy and psychiatric disease. We also wanted to avoid a bias toward Gamma Knife radiosurgery, which tends to dominate most publications. There-fore, we made sure that all major stereotactic radiosurgery techniques were represented. In selecting contributing authors, we felt it critical to enlist the help of our international col-leagues who have been at the vanguard of expanding radiosurgery indications. After all, stereotactic radiosurgery was invented by a Swedish neurosurgeon.

We organized this book into fi ve main sections, with the fi rst few providing important background for the rest of the book. Part One covers the history of radiosurgery, basics of neuroimaging, and a general overview of key concepts in radiosurgery. Part Two concen-trates on the principles of radiation physics and radiobiology that explain the noninvasive, yet powerful, nature of stereotactic radiation treatments. Other topics covered include treat-ment planning and the designing of a radiosurgery unit. We think this portion of the book will be of particular interest to medical physicists, as it is intended to be a practical guide for the running and maintenance of a radiosurgery center. Part Three contains reviews of the major techniques of stereotactic radiosurgery by physicians who are considered by most to be the leading fi gure in their disciplines. We hope you fi nd their insights as valuable to your practice as we did.

Part Four includes eighteen chapters that describe the major disease types treated by practitioners of stereotactic radiosurgery. In each chapter, we asked the authors to provide case reports of actual patients that illustrated the approach, treatment plan, and outcome of their treatment, thus providing a blueprint to follow for those new to the specialty. One of the more unusual aspects of this book is the inclusion of “perspective” chapters that follow a main topic chapter. We felt that having minichapters written by experts in the fi eld who might have a differing viewpoint would provide the most balanced approach to diseases that often have more than one effective treatment.

The last part of this book presents topics related to patient care and the often ignored but critical socioeconomic side of stereotactic radiosurgery. The diverse subjects tackled include complication management, cost-effectiveness and quality of life, building a radiosur-gery practice, and nursing issues. We also included a few topics that have controversial aspects: regulatory and reimbursement issues, medicolegal pitfalls, and radiosurgery seman-tics. In these chapters, the reader will fi nd that some author opinion is unavoidable but does not necessarily refl ect the views of the editors and the publisher.

Our mantra for this book was to be comprehensive and balanced, but we recognize that there will always be disagreements on many of the topics discussed in this book. We hope that this book will be informative but also stimulate a healthy and constructive dialog among its readers. We must continually examine our results in this critical manner to provide the best care for our patients.

This book has been the culmination of several years of planning and execution by a large number of very talented individuals. First, we are indebted to the authors of the individual chapters, who provided their time and expertise in the creation of this project. We would like to thank the editors and staff at Springer who brought dedication and excellence to this project: Beth Campbell, Paula Callaghan, Barbara Lopez-Lucio, and Brad Walsh. We thank Barbara Chernow who rounded this book into its fi nal form. We thank our assistants Debbie

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Redmon, Yvette Green, and Michele Murphy who kept our practices humming while dealing with manuscripts, contributors, editors, and Fed-Ex. Our professional lives owe a debt to the mentors who brought us into neurosurgery, radiation oncology, and the world of radiosur-gery, Buz Hoff, Martin Weiss, Michael Apuzzo, Steven Giannotta, Howard Eisenberg, Simon Kramer, Larry Kun, and Jay Loeffl er. Most importantly, we thank our wives Rita and Julie, along with our children, and the rest of our family and friends for their constant love and support. Lastly, we thank our patients, colleagues, trainees, and students who provided the inspiration for this book.

Lawrence S. Chin, MD William F. Regine, MD

v i i i preface

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9

Neuroimaging in Radiosurgery Treatment

Planning and Follow-up Evaluation

Clark C. Chen, Paul H. Chapman, Hanne Kooy, and Jay S. Loeffl er

2

Introduction

Radiosurgery refers to the precise delivery of a large, single dose of radiation to a focal target. The focal dose distribution allows for a positive therapeutic gain. Because of the opacity of the cranial vault, target volume defi nition relies entirely on the ana-tomic accuracy of the available imaging modalities. The need for accurate anatomic visualization is magnifi ed by the use of higher radiation dose delivered in radiosurgery as compared with radiotherapy. To achieve maximal spatial accuracy in radiosur-gical planning, an understanding of the basic principles underly-ing neuroimaging as well as the limitations associated with each imaging modality is mandatory. Additionally, the optimal man-agement of patients after radiosurgery requires knowledge of the expected neuroimaging changes as they relate to clinical outcome. These issues will be reviewed in this chapter.

Imaging Modalities

Since its inception with the discovery of X-rays in 1895, radiol-ogy has played a pivotal role in the diagnosis and treatment of various neurosurgical lesions. The advent of computed tomo-graphy (CT) imaging in the 1970s marked a major step forward in the application of imaging in radiotherapeutic planning by allowing improved anatomic resolution as well as calculation of electron density maps. Improved soft tissue resolution was achieved with the introduction of magnetic resonance imaging (MRI), a technique based on differential nuclear interaction rather than differential density. Advances made in computa-tional technology in the past decade have enabled the superpo-sition of CT and magnetic resonance (MR) images in order to maximize anatomic deline ation. More recently, signifi cant strides in functional imaging have further refi ned target defi ni-

tion in radiosurgical planning (Fig. 2-1). The following section will review the basic principles underlying the various neuroim-aging modalities as well as limitations associated with each modality.

Computed Tomography Imaging

Computed tomography provides cross-sectional images of the body using mathematical reconstructions based on X-ray images taken circumferentially around the subject. In practice, X-ray transmissions through the subject from a rotating emitter are detected and digitally converted into a grayscale image. Because CT images are ultimately a compilation of X-ray transmissions, the physical principles underlying the two modalities are identi-cal; that is, structural discrimination is made based on the rela-tive atomic composition, and therefore the electron density, of the tissue imaged. CT images, however, offer improved ana-tomic resolution because each image represents the synthesis of information from multiple X-ray images (Fig. 2-1a).

Besides improved anatomic delineation, CT imaging aids radiosurgical planning in another way. Because the pixel inten-sity on a CT image refl ects the electron density of the tissues imaged, the pixel intensity can be mathematically converted into electron density maps (electrons per cm3). This information can be used to defi ne isodose lines in radiosurgical planning. Without this information, actual radiation dose delivered can deviate from the desired dose by as much as 20% as a result of tissue inhomogeneity [1].

Despite yielding improved anatomic resolution as well as electron density information, delineation of soft tissue struc-tures by CT imaging is suboptimal, even with the aid of intra-venous contrast agents. For the most part, delineation of soft tissue structures is achieved by the use of MRI, especially for targets in the cranial base.

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10 c .c . chen et al .

Magnetic Resonance Imaging

The human body consists primarily of fat and water, both having a high content of hydrogen atoms. MRI exploits the nuclear spin property of these hydrogen atoms as a means to attain soft tissue resolution. In MRI, a radiofrequency pulse is applied to the imaged subject. As a result, the nuclear spin states of these atoms shift from that of equilibrium to that of excitation. To return to their equilibrium state, the law of energy conservation dictates that an energy equal to that absorbed must be emitted. The energy release between nuclear spin state transitions can be measured and analyzed. Because the process of energy absorption and emission is affected by the local chemical environment, hydrogen atoms in soft tissues of varying chemical composition will absorb and emit differential energy. Mathematical transformation of this information yields fi ne-resolution maps of soft tissue structures (Fig. 2-1c, d). Because tumor and normal tissues often differ in chemical com-position [2], the same principle allows delineation of these tissue types.

Because of the complexity of the nuclear interactions involved in MRI, the modality is subject to many sources of error, resulting in distortion of the image obtained. One such

source of error involves the imperfection of the input magnetic fi eld. The input magnetic fi eld in MRI is produced by electric currents passing through sets of mutually orthogonal coils. Ideally, the magnetic fi eld generated should be uniform such that a linear relationship between space and resonance fre-quency can be established [3]. However, such uniform fi elds cannot be easily achieved in practice. This phenomenon is referred to as gradient fi eld nonlinearity and tends to escalate with increasing distance from the central axis of the main magnet. For the most part, gradient fi eld nonlinearity can be corrected computationally. Prior to correction, gradient fi eld nonlinearity can induce spatial distortions as large as 4 mm. After computational correction, the distortion is minimized to <1 mm [4].

A more complex MR distortion that is more diffi cult to correct computationally involves electromagnetic interactions between the imaged tissue and the input magnetic fi eld. This distortion is often referred to as resonance offset. Resonance offset occurs because hydrogen atoms carry with them an inher-ent magnetic fi eld. Thus, placement of hydrogen-bearing tissues in a magnetic fi eld necessarily induces a perturbation in the input magnetic fi eld. This perturbation disrupts the linear rela-tionship between space and resonance frequency as to produce

FIGURE 2-1. CT, MR, and MRS images from a patient with a left cerebellar tumor. (a) CT imaging without intravenous contrast shows a poorly defi ned left cerebellar mass with effacement of the fourth ven-tricle and displacement of the brain stem. (b) Intravenous contrast administration improves the anatomic resolution of the left cerebellar mass, revealing a densely enhancing mass with surrounding edema. (c) The same lesion is visualized using T1-weighted MRI. (d) MRI after gadolinium administration reveals a heterogeneously enhancing mass. The homogeneously enhancing tissue on CT is further resolved into tissues of varying intensity on MRI, demonstrating the superiority of MRI over CT in soft tissue resolution. The numbered grid corresponds with the MR spectral arrays shown in (e). The grid is placed over

normal-appearing tissue. (e) The various chemical peaks are as indi-cated in box 9. The thick arrow indicates the choline peak. The arrow-head represents the creatine peak. The thin arrow designates the N-acetylaspartate (NAA) peak. The MRS in box 9 is typical of normal tissue, with comparable choline and creatine peaks and a notable NAA peak. (f) The numbered MRS grid is placed over the diseased tissue. The MRS is shown in (g). (g) The various chemical peaks are labeled in box 1. The diseased tissue shows an elevated choline peak (thick arrow) relative to a diminished creatine peak (arrowhead). The NAA peak is also decreased (thin arrow) relative to normal tissue. The accu-mulation of lactate (double arrow) is another signature of diseased tissue.


2 . neuro imag ing in rad iosurgery planning and evaluat ion 11

geometric distortions. The physics of this perturbation is complex because it depends on the inherent magnetic proper-ties as well as the volume and shape of the imaged object. Reso-nance offset distortions tend to be largest at the interface of materials that differ in magnetic properties, such as at the air-water interface. In anatomic imaging, this translates into large distortions at the air-bone or air-tissue interfaces. Studies reveal that distortions at these interfaces can be as large as 2 mm [3, 5, 6].

Although the development of higher-strength magnets has allowed for improved resolution of soft tissue structures as well as minimization of geometric distortions related to gradient fi eld nonlinearity, higher-strength magnets do not address the issue of resonance offset. Because resonance offset is a product of the input magnetic fi eld and the local fi eld imposed by the imaged tissue, increasing the strength of the input magnetic fi eld will magnify the effects of resonance offset [7].

The accuracy of MR as a stand-alone imaging modality has been determined by a number of investigators [8–12]. Most investigators report a localization uncertainty of 2 to 3 mm [8–11], but maximal absolute errors of 7 to 8 mm have also been reported [12]. These studies reveal that error in fi ducial localiza-tion is amplifi ed by subsequent mathematical transformation. Though the degree of localization uncertainty varies between studies, the reported uncertainty consistently remains greater than 1 mm, failing to achieve the current radiosurgical standard set forth by the American Society of Therapeutic Radiology and Oncology (ASTRO) [13–15].

Another downside of MRI as it pertains to radiosurgical planning is the absence of electron density information (see earlier “Computed Tomography Imaging” section). Contrary to CT imaging where the image is derived based on differential electron density, pixel intensities in MR images bear no correla-tion with electron density. For radiosurgical planning using MR as the only imaging modality, image processing and assignment of hypothetical electron density values are required. Such strat-egies have led to suboptimal radiosurgical plans [16].

Motion artifact is another consideration affecting spatial accuracy in MRI. The prolonged duration required for image acquisition increases the potential for patient movement. Even with a cooperative patient, motion artifact occurs with breath-ing and internal physiologic motions. The resultant motion compromises the accuracy of spatial resolution.

Though MRI is inadequate as a stand-alone modality in radiosurgical planning, combining MR and CT images has led to radiosurgical plans that are superior to plans derived from each modality alone [17–20]. For example, Shuman et al. reported that the incorporation of MR information into CT-based radiotherapy plans resulted in better defi nition of tumor volume in 53% of the cases [18]. These observations have led to the development of algorithms for superimposing MR and CT images.

CT-MR Image Integration

The differences between CT and MRI illustrate the conceptual distinction between geometric and diagnostic accuracy. Although CT imaging is geometrically accurate due to absence of spatial distortion effects, disease tissues are often missed by this modality. As such, CT imaging is diagnostically inaccurate.

On the other hand, due to enhanced soft tissue resolution, MRI affords enhanced diagnostic accuracy; however, the spatial accuracy is limited due to MR distortion effects.

Algorithms have been developed to maximally utilize the different types of information afforded by CT and MRI (Fig. 2-2). Simple approaches to image integration involve manual superposition of equivalent views of MR and CT images, using bony landmarks as correlation points. Such approaches, however, are labor intensive and error-prone with uncertainties of up to 8 mm [21].

Advances in computational technology have allowed for the development of automated algorithms for superposition of CT and MR images in three-dimensional space. One way of integrating CT and MR images requires that the patient be placed in an immobilization device, such as the stereotactic frame. The immobilization device minimizes motion artifacts and ensures that the images are acquired in a predetermined manner. Fiduciary markers are used to establish the spatial relationship between the target and the head frame. Addition-ally, they serve as coregistration points between the MR and CT images. Because image acquisition and correlative points are fi xed in space in a predetermined way, this mode of image fusion is sometimes referred to as prospective image coregistra-tion [14].

Alternatively, image coregistration can be done with images that are not acquired in a predetermined manner. This mode of image fusion is also known as retrospective coregistration. Ret-rospective image coregistration relies on matching correspond-ing anatomic landmarks instead of fi duciary markers. The CT and MR images are integrated on the basis of aligning these anatomic landmarks [22]. Various computational techniques, including point matching [23], line matching, and iterative matching [24], have been developed for retrospective image superposition. Whether one method is superior to another remains an area of research. In general, with proper training and quality control, most current algorithms will coregister MR and CT images to an uncertainty of 1 to 2 mm using prospective registration and of 2 to 3 mm using retrospective registration [14].

Contrast Administration

Contrast administration takes advantage of the observation that disease processes, such as tumor growth, often result in vascular encroachment or faulty angiogenesis [2]. These pro-cesses allow contrast material to escape the vasculature and preferentially accumulate in the diseased tissue. The accumula-tion of contrast material can be easily visualized on CT or MRI (Fig. 2-1b, d). In malignant gliomas for instance, contrast enhancement correlates with diseased tissue. Kelly et al. evalu-ated 195 brain tumor biopsies acquired from various locations relative to the contrast-enhancing regions of CT or MRI scans and showed that the regions of contrast enhancement best cor-related with regions of tumor burden [25].

Because contrast-enhancing volumes are used for radio-surgery target defi nition, diseased tissues without contrast enhancement often escape therapy. Investigators have used various functional imaging modalities to address this issue. Although these modalities hold tremendous promise, they are limited by poor anatomic resolution. As such, functional imaging



is most useful in conjunction with traditional anatomic imaging modalities. In many instances, the clinical applications of func-tional imaging remain investigational.

Positron Emission Tomography and Single-Photon-Emission Computed Tomography

One type of functional imaging relies on visualizing tracer mol-ecules that preferentially accumulate in diseased tissues. This type of imaging includes positron emission tomography (PET) and single-photon-emission computed tomography (SPECT). PET is designed to detect the preferential accumulation of posi-tron-emitting radioactive tracer compounds in the diseased tissue. The emitted positron collides with an electron to yield opposing gamma rays. These emissions are detected by a gamma-ray camera, thereby generating images of regional radioactivity (Fig. 2-3). Similarly, SPECT is designed to detect the preferential accumulation of tracer compounds bearing photon-emitting isotopes. Photon emission is detected by a rotating gamma camera detection system and reconstructed into three-dimensional tomographic images.

In tumor neuroimaging, the enhanced metabolic state of the tumor cells is often exploited to achieve preferential tracer accumulation in these tissues. For instance, 18-fl uorodeoxyglu-cose (18F-FDG), a commonly used PET tracer, is preferentially transported into tumor cells relative to normal cells due to an

intense upregulation of glucose metabolism in tumor cells. Once inside the cell, 18F-FDG undergoes phosphorylation to yield an intermediate that cannot undergo further metabolic processing or cellular export. The phosphorylated intermediate is, therefore, preferentially transported into tumor cells and trapped there [26].

Studies investigating the use of 18F-FDG in guiding radio-surgery for treatment of gliomas yielded mixed results. Tralins et al. reported a series of 27 patients who underwent conven-tional MR or CT scanning as well as 18F-FDG PET. In this study, a multivariate analysis revealed 18F-FDG PET fi ndings as the only variable that retained statistical signifi cance in pre-dicting time to tumor progression and overall survival. More-over, the 18F-FDG PET defi ned target volumes differing from those defi ned by MR or CT imaging by at least 25% in all patients [27]. Gross et al., on the other hand, reported that regions of 18F-FDG abnormal uptake closely correlated with regions of contrast enhancement in their 18 patients. In a minor-ity of patients, 18F-FDG PET did affect target volume defi ni-tion. These changes, however, were not associated with improved survival when compared with historical controls [28]. Likewise, Prado et al. reported that the inclusion of PET scan data minimally altered radiation planning in most patients [29].

These confl icting data can, in part, be attributed to the vari-ability and subjectivity involved in PET image interpretation.

FIGURE 2-2. Fusion of MR and CT images in radiosurgical planning. (a) CT image of a patient with left frontal metastatic lesion. The image is selected to illustrate the continuity of the ventricular contour and the cranial vault as landmarks to gauge the spatial discrepancy when com-paring MR and CT images. The lesion is not shown in (a). (b) Equiva-lent T1-weighted MR image of the CT image shown in (a). Again, note the continuity of the ventricular contour and the cranial vault. (c) Superposition of (a) and (b) without correction of MR distortion shows spatial discrepancy as evidenced by the discontinuity of ventricular contour and the cranial vault at the transition point. The CT-derived image is shown on the top-half panel. The MR image is shown on the

bottom-half panel. (d) After computational correction of MR distor-tion, continuity of the transition point is restored and various anatomic landmarks are coregistered. (e) Three-dimensional view of the meta-static lesion in relation to the stereotactic frame and a surface rendering of the patients head. The lines interconnecting the small red, green, and yellow spheres indicate the planes through which radiation is delivered. (f) Axial, (g) sagittal, and (h) coronal views of the lesion on MRI after correcting for MR distortion effects. The colored lines represent the various isodose contours. The magnitude of the radiation delivered is shown in the right lower corner of each panel.



Because normal gray matter exhibits high physiologic uptake of 18F-FDG, the distinction between normal gray matter and tumor is sometimes subjective, especially in cases of signifi cant anatomic distortion secondary to mass effect. Additionally, regions known to be at high risk for tumor infi ltration, such as regions of edema, often display increased 18F-FDG uptake. In many instances, different thresholds are used for defi ning abnormal 18F-FDG uptake [27–30].

Despite their differences, the various studies suggest that, in selected patients, the inclusion of PET or SPECT can aid in the defi nition of target volumes in radiosurgery for gliomas. The extent of clinical benefi t and the criteria for patient selec-tion await future investigations. The likelihood of routine PET or SPECT for radiosurgical planning should increase with the development of tracer compounds that exhibit high specifi city to diseased tissues.

Magnetic Resonance Spectroscopy

Another type of functional imaging capitalizes on the ability of MRI to measure the levels of biochemical metabolites. Three metabolites commonly used to distinguish tumor and healthy tissue include choline, creatine, and N-acetylaspartate (NAA) (Fig. 2-1d–g; Fig. 2-4). Choline is an essential component of the cell membrane. The level of choline refl ects the rapidity of membrane turnover and is increased in rapidly proliferating tumors. Creatine is a metabolic intermediate for the synthesis of phosphocreatine, an energy source for cellular metabolism. The level of creatine corresponds with the level of cellular energy reserve, which is decreased in tumor tissues. NAA is a marker for neuronal differentiation and is decreased in tumors [2].

Using elevated choline and decreased NAA as criteria, Pirzkall et al. compared the magnetic resonance spectroscopy (MRS)-defi ned tumor volume to that defi ned by contrast-enhanced MRI for malignant gliomas. The authors report that the MRS-defi ned volume extended outside of the MRI-defi ned volume by <2 cm in 88% of the patients [31]. In another study

of 46 patients with malignant gliomas, patients with MRS abnormality outside of the MR-defi ned target volume showed decreased median survival relative to those with MRS abnor-mality inside the MR-defi ned tumor volume (10.7 months vs. 17.4 months, p = 0.002) [32]. Other studies have confi rmed the correlation between untreated MRS abnormality and worse prognosis [33–37]. These studies suggest that MRS data should be taken into consideration in target volume determination for the treatment of gliomas.

MR Perfusion Imaging

Like levels of biochemical metabolites, perfusion parameters such as cerebral blood volume (CBV) can be measured using MRI techniques (Fig. 2-5). CBV is measured by monitoring the transit of a rapid bolus of contrast with respect to time. This parameter is an indirect measure of tissue vascularity, a prop-erty often associated with tumor burden. It is, therefore, not surprising that MR-derived measurements of cerebral blood volume correlate with tumor grading and clinical outcome. In a series of 28 patients with gliomas, pretreatment high CBV intensity was associated with shorter median survival [2, 38, 39].

The use of CBV in radiosurgical planning is limited by several factors. CBV values in tumor volumes are often greater than CBVs of normal white matter but comparable with CBVs of normal gray matter. Thus, distinguishing tumor and cortex is problematic, especially in the context of anatomic distortion caused by large tumors. Additionally, regions of increased CBV correlate well with regions of contrast enhancement. As such, incorporation of CBV information will only alter radiosurgical plans in a subpopulation of patients.

MR Diffusion Weighted Imaging

The white matter in a normal cerebrum is organized into tracts that allow communication between cortical neurons. As a result of this high degree of organization, water molecules in the

FIGURE 2-3. Use of 18F-FDG PET in neuroimaging. (a) A left parietal-occipital mass (arrow) that shows gadolinium enhancement on T1-weighted MR imaging. (b) The same lesion shows increased 18F-FDG accumulation on PET imaging (arrow). The signal intensity of the lesion on 18F-FDG PET imaging is comparable with those of the gray matter. (c) Bilateral gadolinium enhancement in a patient undergoing treatment for malignant glioma on a T1-weighted MR sequence. (d)

PET imaging showed preferential 18F-FDG accumulation in the right hemispheric lesion (arrow). Biopsy specimen of this lesion reveals recurrent glioma. (From Davis WK, Boyko OB, Hoffman JM, et al. [18F] 2-fl uoro-2deoxyglucose-positron emission tomography correla-tion of gadolinium-enhanced MR imaging of central nervous system neoplasia. AJNR 1993; 14:515–523. Copyright by American Society of Neuroradiology.)



FIGURE 2-5. Application of MR perfusion imaging in tumor diag-nosis. (a) T1-weighted MRI shows a heterogeneous right temporal lesion. (b) Gadolinium administration reveals peripheral enhancement and septation of the lesion. A nodular enhancing region is seen in the

right lower corner of the lesion. (c) MR perfusion shows increased cerebral blood volume (CBV) correlating with the contrast-enhancing rim, septation, and nodule. Biopsy of the lesion reveals a grade IV glioma.

FIGURE 2-4. MRS images from a patient with high-grade glioma. (a) T1-weighted MRI reveals an area of hypointensity in the basal frontal lobe involving the anterior limb of the internal capsule. (b) The lesion does not enhance with gadolinium administration but shows increased signal intensity on a (c) FLAIR sequence. (d) The numbered MRS grid is placed over normal-appearing tissue. The MRS is shown in (e). (e) The various chemical peaks are as indicated in box 1. The

MRS shown is typical of normal tissue, with comparable choline (thick arrow) and creatine peaks (arrowhead) and a notable NAA peak (thin arrow). (f) The numbered MRS grid is placed over the diseased tissue. The MRS is shown in (g). (g) The various chemical peaks are labeled in box 10. The diseased tissue shows an elevated choline peak (thick arrow) relative to a diminished creatine peak (arrowhead). The NAA peak is also decreased (thin arrow) relative to normal tissue.

cerebral cortex diffuse in a highly directional manner. The extent of this directional diffusion can be estimated using spe-cialized MR techniques and is referred to as apparent diffusion coeffi cient (ADC) (Fig. 2-6). Because gliomas often distort cerebral architecture, regions with altered ADC are expected to correlate with tumor burden. This expectation was demon-strated in several studies [40–42]. These studies revealed that

patients with lower ADC values in the tumor volume showed shorter median survival than patients with normal or near-normal ADC values (12 months vs. 21.7 months). These studies suggest that ADC maps may be helpful in guiding radiosurgical planning, especially in cases where conventional MRI and ADC maps yield discordant information with regard to tumor volume.



Combined Imaging Modality

Given the complexity of physiology and pathology underlying tumor biology, it is unlikely that any single imaging modality will allow perfect defi nition of the diseased volume [43]. The failure to precisely defi ne tumor volume will result in inade-quate or excessive radiation treatment and suboptimal clinical outcomes. Precise tumor volume defi nition likely requires a synthesis of information obtained from contrast-enhanced CT or MRI, PET, SPECT, MRS, CBV, and ADC in a meaningful way. The optimal algorithm for the synthesis of this information remains an area of active research.

Cerebral Angiography

The primary application of cerebral angiography in radiosurgi-cal planning lies in the treatment of cerebral arteriovenous malformations (AVMs). AVMs represent abnormal communi-cations between vessels of disproportionately unbalanced hydrodynamic stress. The region of abnormal communication is referred to as the nidus. Due to increased hydrodynamic stress, the nidus in an AVM is at high risk for rupture, causing intracranial hemorrhage. The goal of AVM treatment is to eliminate this risk by obliterating the AVM nidus. Estimates of the annual risk for hemorrhage secondary to AVM rupture lie in the range 2.2% to 4.0%, with an associated fatality of roughly 10%. Whereas surgical resection is the treatment of choice for AVMs, radiosurgical treatment is often performed in cases of surgical inaccessibility, patient preference, or severe preopera-tive morbidity.

The risks associated with surgical resection of AVMs are graded by the Spetzler-Martin scale, which refl ects the impor-tance of AVM size, location, and venous drainage. Higher grades are associated with increased postoperative morbidity and mortality. In most series, complete surgical resection of grade I or II AVMs is associated with minimal surgical compli-cations (0 to 10%). Resection of grade IV or V AVMs is associ-ated with complication rates exceeding 40% [44].

The effi cacy of radiosurgery in AVM treatment has been demonstrated in a number of studies [45–53]. For instance, Pollock et al. reported the results of stereotactic Gamma Knife radiosurgery for 65 patients with Spetzler-Martin grade I or II AVMs who opted not to undergo surgery. The series reported a cure rate of 84% and a complication rate of 7.7% [52]. As was

demonstrated by other studies, AVM obliteration occurred 2 to 3 years after radiosurgical treatment. The risk of hemorrhage during this latency interval was the same as that seen in untreated AVMs [45–53].

Radiosurgical treatment of AVMs requires a precise defi ni-tion of the nidus in three-dimensional space. This precise defi ni-tion can be achieved only by the combination of MRI, CT imaging, and cerebral angiography. Whereas MR and CT images afford anatomic resolution, they cannot discriminate between the AVM nidus and the feeding arteries and draining veins [54]. This distinction is crucial because the goal of AVM treatment lies in the obliteration of the former while sparing the latter.

On the other hand, cerebral angiography offers a limited defi nition of the nidus margin without the corresponding MR and CT imaging, especially in cases of irregularly shaped AVMs (Fig. 2-7). Conventional angiographic studies yield two-dimen-sional projections of the AVM nidus, a three-dimensional lesion. The spatial information lost as a result of dimensional reduction represents a source of inaccuracy in nidus defi nition [48, 55–57]. For instance, angiographic projections may outline different AVM nidus margins depending on the angle of projec-tion and the nidus geometry [54, 56]. Not surprisingly, studies examining the value of incorporating CT and MR information into conventional angiography–based radiosurgical plans yielded data supporting the superiority of the combined approach. In one study, inclusion of CT imaging in angiogra-phy-based plans resulted in a mean isocenter shift of 3.6 mm in 44 of 81 (54%) patients and changes in the diameter of collima-tor beam in an equal number of patients [55]. Other studies have reported similar fi ndings [57].

CT- and MR-based angiograms are proposed alternatives to conventional angiogram in radiosurgical planning (Fig. 2-8); however, the spatial accuracy and the resolution of vessel archi-tecture afforded by CT and MR angiograms are insuffi cient as stand-alone modalities [58, 59]. Tanaka et al. compared AVM resolution by MR angiography (MRA), CT angiography (CTA), and conventional angiogram in terms of feeding vessel and draining vein visualization [59]. In this study, only 20% to 30% of feeding vessels and draining veins detected by conventional angiogram were identifi ed by MRA or CTA. Combined use of CTA and MRA did not further improve AVM resolution. The work by Aoyama et al. further illustrated the inadequacy of CT and MR angiograms as stand-alone modalities in radiosurgery

FIGURE 2-6. MR diffusion imaging in tumor assessment. (a) T1-weighted MRI shows a heterogeneous right temporal lesion. (b) Gado-linium administration reveals a multicystic lesion with a central region

of enhancement. (c) MR diffusion imaging shows decreased apparent diffusion coeffi cient (ADC) signal in the region of central enhance-ment. Biopsy of the lesion reveals a grade IV glioma.



FIGURE 2-8. Comparison of CTA, MRA, and conventional angiog-raphy in AVM resolution. (a) Axial CTA image of a patient who pre-sented with a left parietal-occipital intracranial hemorrhage. An AVM nidus is visualized on the superoposterior aspect of the hematoma. (b) Axial image reconstruction affords improved anatomic resolution of the AVM nidus, demonstrating feeder vessels from the middle cerebral artery and the posterior cerebral artery. (c) Sagittal reconstruction of the CTA images shows venous drainage of the AVM into the superior sagittal sinus. (d) Three-dimensional reconstruction of the CTA images

allows visualization of the spatial geometry of the AVM nidus. (e) Cranial-caudal view of an MRA demonstrating the left parietal-occipital hematoma as well as an enlarged, left middle cerebral artery branch. The AVM nidus is poorly visualized. (f) Anterior-posterior and (g) lateral views of the AVM during the mid–arterial phase of a conventional angiogram (left internal carotid artery injection) show detailed view of the arterial feeders and venous drainage of the AVM. The resolution afforded by conventional angiogram in this regard is superior to that of CTA or MRA.

FIGURE 2-7. MRI as an adjunct to conventional angiography in defi ning AVM nidus. (a) Anterior-posterior and (b) lateral views of an AVM during mid–arterial phase (right internal carotid artery injection) revealed a large AVM in the right parietal temporal region supplied by distal right middle cerebral artery, posterior cerebral artery, and external carotid artery branches. (c) Coronal T2-weighted and (d) axial T1-weighted images further refi ne the anatomic geom-etry of this complex AVM.



planning for AVM treatment [58]. These authors investigated the spatial discrepancy between AVM targets as defi ned by MRA, CTA, and conventional stereotactic angiogram. The authors reported a mean discrepancy of 2 to 3 mm in the center of the target volume when MRA and CTA targets were compared with conventional angiography–defi ned targets. Dis-crepancies were noted in the left-right, anterior-posterior, and cranio-caudal directions. Independent of the size of the AVM, the discrepancy was greater than 5 mm in one-third of the cases.

Despite their limitations, CT and MR angiograms allow for a more precise defi nition of the AVM nidus when used in con-junction with conventional angiography [48, 55–57]. In a series of 28 patients, Kondziolka et al. reported that MR angiography provided information on irregularly shaped AVMs that was not visualized by conventional angiography alone. The utility of MR angiography was especially evident in situations where conventional angiography showed different superior and infe-rior nidus margins on different projections. The improved nidus defi nition resulted in modifi cation of treatment plans in 16 of 28 (55%) cases [56]. Others have reported similar results [48, 55, 57].

Conventional angiography for the purpose of radiosurgical planning is generally done by placing the patient in an immo-bilizing stereotactic head frame in order to ensure maximal spatial accuracy. Recent advances in image acquisition and ret-rospective image coregistration techniques have raised ques-tions about the necessity of such practice. Three-dimensional rotatory angiography is an imaging technique that combines the principles of CT with those of conventional angiography. As the contrast material is injected through the cerebral vascula-ture, X-ray transmissions from a rotating emitter are detected and digitally converted into a high-resolution view of the cere-bral architecture in three dimensions. Radiosurgical planes derived using nonstereotactic three-dimensional angiography have been compared with those derived from conventional ste-reotactic angiography. In one study, this comparison revealed target coordinate discordance in 5 of the 20 patients. Coordi-nate discordance ranged from 0.3 to 1 mm with a mean of 0.7 mm [54].

Today, the gold standard for radiosurgical treatment of AVMs remains a combination of stereotactic cerebral angio-graphy, CT-based or MR-based imaging, (including CTA and MRA), and three-dimensional angiography. The resultant information enables a detailed geometric reconstruction of nidus anatomy that is required in complex treatment strategies [60]. With improvement in algorithms for image acquisition and coregistration, nonstereotactic three-dimensional angiography may supplant the need for stereotactic angiography in radiosur-gical planning for selected patients.

Radiologic Considerations in Radiosurgical Planning

The following section will review pertinent radiologic features that affect radiosurgical planning, including size of lesion and proximity to critical neuroanatomic structures. Nonradiologic factors that affect radiosurgical planning are reviewed else-where [61, 62].

Size of the Lesion

The size of the lesion treated remains an important criterion for determining the appropriateness of radiosurgery versus radio-therapy. As the size of the irradiated target volume increases, undesired radiation of the surrounding nontarget tissue increases in an exponential manner. The clinical impact of this geometric inevitability is magnifi ed by the higher doses of radia-tion delivered in radiosurgery. Generally, single-dose irradia-tion of normal cerebral parenchyma should be restricted to <12 to 15 Gy, because doses exceeding this range are associated with increased risks of neurologic defi cits [63]. As a result of this dose restriction, lesions with sizes >4 cm are usually not treated radiosurgically.

Critical Neuroanatomic Structures

Radiosurgery may be contraindicated for the treatment of lesions in the immediacy of highly radiosensitive neuroana-tomic structures. For instance, because of the radiosensitivity of cranial nerve II, radiosurgery is contraindicated in the treatment of lesions in the proximity of or intrinsic to the optic nerve, chiasm, or tracts. The distance between the tumor margin and the optic apparatus should be at least 4 mm before radiosurgery is considered [64, 65]. The dose delivered to the optic apparatus should be restricted to less than 10 Gy to mini-mize the risk of optic neuropathy. Like cranial nerve II, cranial nerves VII and VIII are more radiosensitive than other neu-roanatomic structures [66]. Detailed delineation of these structures on neuroimaging is required for radiosurgical planning.

Lesion localization relative to regional cerebral anatomy is another consideration in radiosurgical planning because this spatial relationship is a major predictor for posttreatment com-plications. Flickinger et al. reviewed 332 patients with AVMs treated with radiosurgery and correlated the risk of posttreat-ment neurologic injury to the location of the lesion. The risk for neurologic defi cit is maximal when the lesions are located in the deep gray matters (thalamus, basal ganglia) and brain stem (pons/midbrain). Minimal risk for defi cit was seen in the lesions located in the frontal and temporal lobe [63]. Thus, depending on lesion location, radiation doses should be adjusted to minimize the risk of posttreatment neurologic defi cit.

Evaluation of Treatment Effi cacy

Radiation can induce imaging changes that are unrelated to the underlying disease process. Misinterpretation of these imaging results can lead to inappropriate treatment. For instance, radia-tion induces cytotoxicity and also disrupts cerebral vascular architecture. These changes, often referred to as radiation necrosis, can lead to imaging fi ndings that are indistinguishable from tumor recurrence on contrast-enhanced MRI. As another example, radiation can induce infl ammatory changes, causing a temporary increase in the volume of contrast enhancement that is unrelated to tumor regrowth [67, 68]. Thus, optimal patient management requires an understanding of the imaging fi ndings as they relate to clinical outcome. This issue will be addressed



in the following section. Means of distinguishing radiation necrosis from tumor recurrence will be discussed in the context of malignant gliomas and intracranial metastasis. Temporary increases in the volume of contrast enhancement will be reviewed in the context of vestibular neuroma. The utility of serial MR in the management of trigeminal neuralgia will also be discussed. Finally, the complexity of posttreatment manage-ment after AVM radiosurgery will be reviewed.

Malignant Gliomas and Metastatic Disease

For malignant gliomas, radiosurgery represents a second-line treatment option, usually offered in the context of recurrence after primary therapy or as adjuvant therapy. In contrast, radio-surgery is a fi rst-line treatment option for intracranial metasta-sis without signifi cant mass effect. In both diseases, typical follow-up regimens include neurologic examination and con-trast-enhanced MRI 6 to 8 weeks after radiosurgery and then at roughly 3-month intervals. More frequent imaging is per-formed with neurologic deterioration or with interval enlarge-ments of the treated lesion [67, 68].

For both malignant gliomas and metastatic diseases, response to radiosurgery is radiologically defi ned by a decrease in the size of the contrast-enhancing volume on conventional MRI [67, 68]. Complete and partial responses are generally defi ned as the complete disappearance or a partial decrease in the size of the enhancing lesion, respectively. No change in the contrast-enhancing volume is usually referred to as stable disease. Using these defi nitions, Ross et al. described the imaging fi ndings after radiosurgery for malignant gliomas and intracranial metastasis. Based on imaging obtained roughly 3 months after radiosurgery, 17% of the patients with malignant glioma showed partial or complete response; 10% showed stable disease, and 73% showed an increase in the size of con-trast enhancement. In patients with intracranial metastasis, images obtained in the same time frame revealed 51% complete or partial response, 27% stable disease, and 22% contrast-enhancement size increase [67]. Comparable results are reported by other studies [69–72].

The use of corticosteroids is common in the treatment of cerebral edema in both malignant gliomas and intracranial metastasis. Questions are often raised as to whether corticoste-roid administration affects MRI fi ndings after radiosurgery. Case series addressing this issue revealed that whereas cortico-steroids reduced the extent of peritumoral edema on T2-weighted MRI, their administration did not alter the size of the contrast-enhancing volume [67].

The physiology underlying increased contrast uptake is complex and cannot be equated with treatment failure in all cases. Two independent series that detailed the imaging changes after radiosurgical treatment of intracranial metastatic disease revealed that 6% to 12% of all radiosurgically treated lesions displayed a transient increase in contrast uptake [67, 68]. This transient increase occurred at 3 months after treatment (range, 2 to 10 months) and resolved after an additional 6 months (range, 2 to 6 months). Microsurgical resection of these con-trast-enhancing volumes revealed hyalinized thrombosis, tumor necrosis, and granulomatous changes [73]. Genuine treatment failures, documented by surgical biopsy and enlargement of

contrast-enhancing volume, on the other hand, were more likely to occur at 6 months after treatment (range, 3 to 24 months). Thus, although contrast-enhancing volume represents an important predictor for therapeutic effi cacy [67], it must be interpreted with caution.

Another caveat in equating increased contrast uptake with radiosurgical failure involves the phenomenon of radiation necrosis. Radiation necrosis is a term used to describe radiologic changes (primarily visualized in the form of increasing size of contrast-enhancing volume) resulting from radiation-induced cytotoxicity that is unrelated to the underlying disease process. Some reports suggest that radiation necrosis is more likely to produce a fuzzy, indiscrete pattern of enhancement in contrast with the discrete pattern of enhancement seen in tumor recur-rence [68]; however, 10% to 20% of post-radiosurgery patients develop radiologic fi ndings indistinguishable from tumor recur-rence [74].

The functional imaging modalities described earlier have been employed as a means to better distinguish radiation necro-sis from tumor recurrence. Early results are promising in this regard. In general, whereas functional imaging modalities exhibit high degrees of sensitivity for detecting tumor recur-rence, the specifi city remains somewhat poor. For instance, Tusyuguchi et al. compared the methionine PET fi ndings in eight cases of biopsy-proven glioma recurrence with six cases of biopsy-proven radiation necrosis. They calculated the ratio of methionine accumulation in the regions of contrast enhance-ment relative to regions of normal gray matter. They found this ratio elevated in cases of tumor recurrence when compared with cases of radiation necrosis. In this study, the sensitivity and specifi city of methionine PET for tumor recurrence detection were 100% and 60%, respectively [75]. Comparable results are reported for thallium 201 SPECT [76].

Measurement of cerebral blood volume (CBV) on MRI represents another proxy for tumor recurrence [38, 39, 77]. Essig et al. described their experience with 18 patients imaged at 6 weeks and 3 months after radiosurgery for solitary metas-tasis. In this study, a decrease in the CBV of the radiosurgically treated volume at 6 weeks predicted treatment outcome with a sensitivity of 97% and a specifi city of 71% [77].

Perhaps the most promising imaging modality for determin-ing radiation necrosis versus tumor recurrence involves the use of MRS. As previously described, choline is a cell membrane component that refl ects the extent of membrane turnover. Ele-vated levels of choline are associated with rapidly proliferating tumors and poor clinical outcomes [2]. The level of creatine is a proxy for cellular metabolism and is decreased in tumor cells. Using measurements of choline and creatine as guides, Rabinov et al. were able to distinguish recurrent tumor from radiation necrosis in 13 of 14 cases [74]. Others have reported similar fi ndings [35, 78].

Future imaging evaluation after radiosurgery likely will involve the synthesis of information obtained from different imaging modalities. The development of algorithms for data integration requires clinical-imaging correlation. To date, most studies carried out for such purpose are retrospective in design and involve a small number of patients. Ultimately, prospective and randomized studies will be required for the purpose of correlating imaging fi ndings with clinical outcomes.



Benign Lesions: Acoustic Neuroma

Imaging fi ndings after radiosurgical treatment for acoustic neuromas are discussed as a review of the basic principles un -derlying the management of benign intracranial lesions after radiosurgery.

Acoustic neuromas, also known as vestibular schwannomas, are rare, benign tumors that arise from the Schwann cells asso-ciated with the eighth cranial nerve. Their incidence is approxi-mately 1 in 100,000 in the general population. Historically, surgical resection has been the treatment of choice. Two impor-tant goals of acoustic neuroma surgery are facial nerve and hearing preservation. The likelihood of achieving these goals is largely a function of the tumor size.

In recent years, radiosurgery has emerged as an alternative to microsurgical treatment for small acoustic neuromas (<2 cm). In the largest series reported to date (827 patients over a span of 10 years at the University of Pittsburgh), radiosurgical administration of 12 to 20 Gy to the schwannoma achieved local control in 97% of the cases after 10 years [79]. Other series have reported similar fi ndings [80–84]. After radiosurgery, the rate of House-Brackman grade I/II facial nerve function preserva-tion ranged from 70% to 95%; Robertson-Garner serviceable hearing preservation ranged from 13% to 40% [80–84]. In mul-tiple retrospective comparisons of radiosurgery and microsurgi-cal resections, no statistically signifi cant difference was observed in the rate of tumor recurrence, facial nerve preservation, or hearing preservation [82, 85].

Currently, MRI with contrast enhancement is the gold stan-dard for the evaluation of treatment response [86, 87]. Typi-cally, follow-up neuroimaging and clinical examinations are performed at 6 and 12 months during the fi rst year and every 12 months thereafter. In the largest clinical series to date, Naka-mura et al. reported their experiences with serial MRI after Gamma Knife radiosurgery for vestibular schwannoma. They classifi ed the changes in the posttreatment contrast-enhancing volume into four categories. The fi rst category consisted of schwannomas that showed initial enlargement followed by sus-tained regression (25/78, or 32%). This temporary enlargement peaked in roughly 1 year and regressed within an additional 2 years. In many cases, the schwannoma doubled in size before regression. The tumor may not have regressed to the size of the initial lesion. Instead, many tumors regressed to an intermedi-ate size and remained stable at that size. The second category consisted of tumors that showed repeated enlargement fol-lowed by regression (8/78, or 9%). Many of these tumors were cystic schwannomas (5/8), with size fl uctuations resulting from enlargement or collapse of the cystic component. Size fl uctua-tions in noncystic schwannomas also occurred (3/8). Again, the size enlargement could reach a doubling of the initial lesion size before regression. The third category consisted of schwanno-mas that remained stable in size or regressed in size (21/78, or 27%). The fourth category consisted of continual tumor enlarge-ment (7/78, or 9%) [87].

Microsurgical resection of tumors that showed radiologic “progression” often revealed hyalinized thrombosis, thickened vascular wall, and granulomatous changes [88, 89]. Thus, some of the cases of radiologic “progression” may have represented infl ammatory changes rather than genuine treatment failure. Because up to 41% (combined category 1 and 2) of schwanno-

mas treated with radiosurgery displayed a temporary increase in the volume of contrast enhancement (sometimes doubling in size), cautious observation may be warranted for at least 2 years after treatment, provided the imaging changes are not associ-ated with clinical deterioration or signifi cant compression of the brain stem.

Similar temporary enlargement of contrast-enhancing vol-umes is seen after radiosurgery for pituitary adenomas and other benign diseases [90]. As such, in the management of patients with benign intracranial lesions after radiosurgery, sur-gical intervention or a second round of treatment should be reserved for cases with continual disease progression after or for cases with neurologic deterioration.

Another radiologic fi nding pertinent to the management of vestibular schwannoma after radiosurgery is that of hydroceph-alus. It is estimated that roughly 10% of patients with vestibular schwannoma develop communicating hydrocephalus after radiosurgical or radiation treatment [91]. In most cases, the hydrocephalus is not associated with tumor enlargement or cerebrospinal fl uid (CSF) fl ow obstruction. The etiology of the hydrocephalus is unclear though many investigators attribute the phenomenon to CSF malabsorption secondary to tumor necrosis. It is also unclear whether radiation contributes to the process, as a comparable percentage of vestibular schwannoma patients without radiation treatment develops communicating hydrocephalus [92]. Regardless of the etiology, prompt identi-fi cation of ventricular enlargement on imaging and clinical fi nd-ings associated with hydrocephalus are needed in order to ensure timely neurosurgical intervention.

Trigeminal Neuralgia

Imaging fi ndings after radiosurgical treatment for trigeminal neuralgia are reviewed to illustrate a clinical scenario where routine, serial MRI is not warranted.

Trigeminal neuralgia is a facial pain syndrome consisting of paroxysmal, lancinating pain occurring in the distribution of cranial nerve V. Most patients with trigeminal neuralgia are successfully treated with anticonvulsives, antidepressants, neu-roleptics, or opioids. Options available for the treatment of medically resistant trigeminal neuralgia include microvascular decompression, thermal, chemical, or radiofrequency ablative procedures, and radiosurgery [93]. In most studies, excellent responses to radiosurgery are reported in 70% to 90% of patients after treatment [94, 95].

Many institutions obtain a MR contrast-enhanced scan approximately 6 months after radiosurgical treatment. The scan is performed primarily for the purpose of target site verifi cation. In one report, all patients treated with 45 Gy at the 50% isodose line developed contrast enhancement of the target zone within 6 months of treatment [94]. The detection of contrast enhance-ment on cranial nerve V after radiosurgery, therefore, served as a confi rmation of accurate targeting.

Studies correlating clinical responses to contrast enhance-ment of cranial nerve V have yielded mixed results. Some studies suggest that the exact region of enhancement relative to the pontine edge and along the retrogasserian portion of cranial nerve V correlate well with treatment outcome [96–98]. Others report poor correlation between contrast enhancement and clinical response [99]. In many instances, benefi cial clinical



responses or treatment failures are apparent before the onset of contrast enhancement [99].

Despite the lack of consistent correlation between radio-logic fi ndings and clinical response, a case can be made for obtaining a MR contrast-enhanced scan at the 6-month follow-up evaluation, because it allows target confi rmation as well as an assessment of potential brain-stem injuries. Serial MRI in patients without neurologic or radiologic changes at the initial posttreatment scan, however, does not appear warranted. In patients who exhibit good clinical response to radiosurgery without incurring neurologic defi cits, it is also reasonable to forgo the MRI at the 6-month follow-up evaluation, because the imaging fi ndings are unlikely to alter patient management.

Arteriovenous Malformations

Therapeutic effi cacy of radiosurgery for AVMs depends on radiation-induced endothelial cell and mesenchymal cell pro-liferation, causing progressive vasoocclusion [100]. Although it is generally agreed that the peak effect of this process occurs between 2 and 3 years after radiation treatment, the actual time course of AVM obliteration varies widely [45–53]. Com-plete angiographic obliteration, as determined by conventional angiography, remains the gold standard for defi ning treatment success and can occur as early as 4 months or as late as 5 years after treatment [101, 102]. Because of the variable time course in therapeutic response, the frequency and timing of neuro-imaging follow-up evaluation vary widely between institutions [103–105].

Because of the risks associated with conventional cerebral angiography and because most AVMs obliterate between 2 and 3 years after radiosurgery, there is a tendency to delay cerebral angiography until the presumed time of obliteration [103, 105]. Some investigators, however, advocate early cerebral angiogra-phy on grounds that fi ndings on these studies are highly predic-tive of the fi nal treatment outcome. Oppenheim et al. reported their experience with 138 patients radiosurgically treated for AVMs. These patients underwent early angiography 6 to 18 months after treatment. Eighty-four percent of the radiosurgi-cally treated AVMs with evidence of early regression (defi ned as >75% reduction in size at the time of early angiography) eventually developed complete obliteration on subsequent angiograms. On the other hand, only 10% of the AVMs without evidence of early regression (<50% reduction in size on the early angiogram) developed complete obliteration. The authors concluded that the identifi cation of AVMs unresponsive to radiosurgery at a early stage will facilitate planning for subse-quent treatment strategies [104].

To avoid the risks associated with conventional cerebral angiograms, investigators have identifi ed CT and MR imaging fi ndings that correlate well with treatment response. One such fi nding involves contrast enhancement in the region of the AVM nidus after radiosurgery. Contrast enhancement of the AVM nidus on CT imaging was fi rst described in two patients with eventual AVM obliteration after radiosurgery [106]. Sub-sequent studies reported good correlation between nidus enhancement on CT or MR imaging after radiosurgery and therapeutic effi cacy [102, 107]. These studies revealed that the volume of contrast enhancement corresponds with the radio-surgical target volume. The degree of enhancement increases

with time and is correlated with a reduction in the nidus size on conventional angiography. The onset for contrast enhancement is typically 6 to 24 months after radiosurgery. Contrast enhance-ment on CT tends to resolve 1 to 2 years after angiographic demonstration of complete AVM obliteration, whereas enhancement on MRI tends to persist even after disappearance of contrast enhancement on CT [102].

MR and CT angiograms are also used to evaluate cerebral AVMs after radiosurgery. Though the spatial resolution of CT and MR imaging remains poor, AVM changes visualized using these modalities correlate well with those detected using con-ventional angiography [102, 108–110]. As such, serial MR or CT angiograms are often performed for routine monitoring while the defi nitive conventional angiography is postponed until 2 to 3 years after radiosurgery.

Radiosurgery of AVMs inevitably results in irradiation of the surrounding nontarget tissues. It is, therefore, not surprising that an estimated 28% to 50% of the patients undergoing treat-ment develop T2 signal abnormalities in these regions [100, 111]. The onset of these fi ndings occurs between 1 day and 44 months after treatment. Regression of the signal abnormality is seen in 80% to 90% of the cases and tends to occur 5 to 8 months after the initial onset [112]. As previously discussed, the risk of neurologic defi cit expected due to these abnormalities depends on their location. Maximal risk for defi cit is expected in cases of signal abnormalities in the deep gray matters (thala-mus, basal ganglia) and brain stem (pons/midbrain). Minimal risk of defi cit is expected with frontal and temporal lobe abnor-malities [63].

Whereas conventional angiography represents the gold standard for defi ning therapeutic effi cacy for AVM treatment, disappearance of the AVM on angiography after radiosurgery does not always indicate disease eradication. Shin et al. fol-lowed 236 radiosurgery-treated AVMs between 1 and 133 months after angiographic confi rmation of obliteration. The authors identifi ed four patients who developed intracranial hemorrhage between 16 and 51 months after angiographic con-fi rmation. No evidence of residual AVM was found on retro-spective review of the confi rmation angiograms. Two of the patients underwent surgical resection. Histologic analysis of the resection specimen revealed evidence of vasoocclusion as well as small residual AVM vessels. The only radiologic fi ndings associated with these hemorrhages were the persistence of con-trast enhancement on CT and MRI after angiographic evidence of AVM obliteration [113]. Given these fi ndings, yearly follow-up evaluation after angiographic evidence of AVM obliteration may be warranted.

Treatment of patients with AVMs remains one of the most complex and challenging in the fi eld of radiosurgery. Optimal patient management requires an understanding of the patho-physiology, neuroanatomy, as well as the radiologic manifesta-tions after treatment. As such, treatment efforts should involve collaborative inputs from experienced radiation oncologists, neurosurgeons, neuroradiologists, and the patient.

Neuroimaging for Radiation-Associated Secondary Tumors

The probability of secondary tumors arising from radiosurgery is quite low [114]. Thus, once a patient has achieved a positive



result from treatment (e.g., complete obliteration of an AVM documented by angiography), we do not recommend further imaging to look for secondary tumor formation.

Conclusion

There is no doubt that advances in neuroimaging will help to refi ne all aspects of radiosurgery and improve treatment effi -cacy. For many modalities, clinical applications remain poorly defi ned and await further investigation. For radio surgeons and therapists, the challenge lies in understanding the basis and the limitations associated with the various imaging modalities. Ulti-mately, prospective and randomized studies correlating imaging fi ndings and clinical outcomes are required for developing guidelines for optimal patient care.

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preface - bücher.de · 2020-05-15 · he practice of stereotactic radiosurgery has developed from...

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