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Morphological and functional MRI, MRS, perfusion and diffusion changes after radiosurgery of brain metastasis
European Journal of Radiology 72 (2009) 370–380
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Morphological and functional MRI, MRS, perfusion and diffusion changes after radiosurgery of brain metastasis Tae Wook Kang a,1 , Sung Tae Kim a,∗ , Hong Sik Byun a,1 , Pyoung Jeon a,1 , Keonha Kim a,1 , Hyungjin Kim a,1 , Jung II Lee b,1 a b
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea
a r t i c l e
i n f o
Article history: Received 22 May 2008 Received in revised form 11 August 2008 Accepted 11 August 2008 Keywords: Radiosurgery Magnetic resonance imaging Brain Metastasis
a b s t r a c t Radiosurgery is a noninvasive procedure where spatially accurate and highly conformal doses of radiation are targeted at brain lesions with an ablative intent. Recently, radiosurgery has been established as an effective technique for local treatment of brain metastasis. After radiosurgery, magnetic resonance (MR) imaging plays an important role in the assessment of the therapeutic response and of any complications. The therapeutic approach depends on the imaging findings obtained after radiosurgery, which have a role in the decision making to perform additional invasive modalities (repeat resection, biopsy) to obtain a definite diagnosis and to improve the survival of patients. Conventional MR imaging findings are mainly based on morphological alterations of tumors. However, there are variable imaging findings of radiation-induced changes including radiation necrosis in the brain. Radiologists are sometimes confused by radiation-induced injuries, including radiation necrosis, that are seen on conventional MR imaging. The pattern of abnormal enhancement on follow-up conventional MR imaging closely mimics that of a recurrent brain metastasis. So, classifying newly developed abnormal enhancing lesions in follow-up of treated brain metastasis with correct diagnosis is one of the key goals in neuro-oncologic imaging. To overcome limitations of the use of morphology-based conventional MR imaging, several physiological-based functional MR imaging methods have been used, namely diffusion-weighted imaging, perfusion MR imaging, and proton MR spectroscopy, for the detection of hemodynamic, metabolic, and cellular alterations. These imaging modalities provide additional information to allow clinicians to make proper decisions regarding patient treatment. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Radiosurgery has been widely used to treat meningiomas, schwannomas, pituitary adenomas, metastatic brain tumors, malignant gliomas and other neurological diseases as an alternative method in place of surgical resection [1–7]. Follow-up imaging studies are needed to assess the results of radiosurgery and to detect any complications. The introduction of magnetic resonance (MR) imaging has revolutionized the clinical effectiveness of radiosurgery by improving the identification and characterization of
∗ Corresponding author. Tel.: +82 2 3410 6458; fax: +82 2 3410 0084. E-mail addresses: [email protected] (T.W. Kang), [email protected] (S.T. Kim), [email protected] (H.S. Byun), [email protected] (P. Jeon), [email protected] (K. Kim), [email protected] (H. Kim), [email protected] (J.I. Lee). 1 Tel.: +82 2 3410 2507; fax: +82 2 3410 2559. 0720-048X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2008.08.009
target tissues by precisely characterizing treatment response. The role of MR imaging in assessing the response to radiosurgery in post-treatment has been studied for variable diseases [8–13]. Conventional MR imaging is an anatomy-based procedure and morphologic alterations are the key to resolve abnormal findings on follow-up imaging studies after radiosurgery. However, the histological response of brain normal tissue and tumors to radiosurgery has confounded correct follow-up evaluations. Recurrent tumors and radiation-induced changes often appear at the same location within or near the region of the irradiated area, and both occurrences resemble contrast-enhancing, expansile brain lesions surrounded by edema. It is difficult with the use of conventional MR imaging to assess abnormal imaging findings after radiosurgery as lesions that are related to a residual or recurrent brain tumor, or as lesions that are related to non-tumorous, radiation-induced changes [14]. Thus, an accurate diagnosis of radiation-induced changes on MR imaging has been challenging. If a lesion deviates from usual conventional MR imaging findings on follow-up,
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Fig. 1. Schematic representation of histological changes after radiosugery. In the central part (gray circle) of the area treated by radiosurgery, a decrease of the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls are seen. In the peripheral part (white circle) of the area treated by radiosurgery, some tumors contain viable cells intermingled with blood vessels that have been seen with endothelial and pericytic proliferation.
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additional information is required to make a correct diagnosis using functional MR imaging. Currently, diffusion-weighted imaging (DWI), perfusion-weighted imaging, and proton MR spectroscopy are used as physiological-based functional MR imaging methods. Diffusion-weighted imaging (DWI) is based on the detection of changes in the random motion of protons in water, and its use enables the characterization of tissues and pathological processes at a microscopic level [15,16]. Perfusion-weighted imaging is an important tool to measure the degree of brain tumor angiogenesis and capillary permeability, both of which are major biological markers of malignancy, grading, and prognosis, especially for gliomas [17–20]. MR spectroscopy can provide a noninvasive window to analyze neurometabolism. Pattern analysis of MR spectroscopy data can be successfully applied to detect metabolic alterations of brain tumors and other non-neoplastic lesions [21,22]. This review provides a comprehensive overview of the radiation biology to understand MR imaging changes. In addition, this review evaluates conventional and functional MR imaging after radiosurgery of metastatic brain tumors in order to obtain more accurate follow-up results and ultimately to improve patient clinical outcome. 2. Materials and methods Written informed consent was obtained from every patient prior to treatment. From January 2004 to October 2007, 429 patients with
Fig. 2. Typical conventional MR imaging after radiosurgery for brain metastasis in a 60-year-old female. (A) Axial post-contrast T1-weighted MR image before radiosugery demonstrates well-defined enhancing mass in left parietal lobe. (B and C) After radiosurgery, axial T2-weighted and post-contrast T1-weighted MR image from 3-month followup shows progressive cavitation with capillary proliferation surrounding the necrotic center representing rim enhancement and perilesional edema. (D) After radiosurgery, axial post-contrast T1-weighted MR image from 6-month follow-up shows decrease in size of tumor and loss of enhancement with time.
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Fig. 3. Serial change of edema on conventional MR imaging after radiosurgery for brain metastasis in a 55-year-old-male. FLAIR = fluid attenuated inversion recovery. (A and B) Axial post-contrast T1-weighted and FLAIR MR image before radiosurgery shows well enhancing mass with perilesional edema in right frontal lobe. (C) After radiosurgery axial FLAIR MR image from 3-month follow-up after demonstrates slightly decrease in size of tumor and perilesional edema. (D and E) After radiosurgery axial FLAIR MR image from 6- and 15-month follow-up shows markedly decrease in size of tumor and perilesional edema without tumor progression.
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Fig. 4. Serial change of lesion enhancement on conventional MR imaging after radiosurgery for brain metastasis in a 66-year-old-male. (A) Axial post-contrast 3D spoiled gradient recalled (SPGR) MR image for planning before radiosurgery shows heterogenous enhancing mass around third ventricle. (B and C) After radiosurgery axial postcontrast T1-weighted MR image from 5 and 10 months follow-up shows decrease in size of enhancing mass. After radiosurgery blurring marginal enhancement (arrow) can be shown without tumor recurrence by radiation-induced change. (D) After radiosurgery axial post-contrast T1-weighted MR image from 15 months follow-up shows slightly disappearance of blurring marginal enhancement. If there is no aggravation of tumor, the blurring marginal enhancement changes may become more discrete with time.
brain metastasis were treated with 566 radiosurgery procedures at our institution. The mean age of patients was 56.4 years (range: 30–83 years). There were 208 men and 221 women. The primary tumor was lung cancer (n = 267), breast cancer (n = 61), renal cell carcinoma (n = 41), colorectal cancer (n = 23), gynecologic cancer (n = 12), and others (25), respectively. For the evaluation of treatment response, All MR images were obtained with a MR scanner, 3-T Achieva (Philips medical systems, BEST, Netherland), using a eight-channel sense head coil. Patients were assigned to the specific MR imaging protocols for brain tumors at our institution. This protocol consisted of pre- and post-contrast axial and sagittal T1-weighted imaging (TR/TE: 500/10), axial fat suppressed T2-weighted imaging (TR/TE: 2200/70), axial fluid attenuated inversion recovery (FLAIR) imaging (TR/TI/TE: 11000/2800/125), diffusion-weighted imaging (single shot spin echo EPI sequence, TR/TE: 3000/46, b factor: 1000, matrix: 128 × 128), and perfusion weighted imaging (single shot EPI gradient sequence, TR/TE: 1510/35, flip angle: 40◦ , matrix: 128 × 128, 50 dynamic, one dynamic scan time: 1.5 s). These sequences were obtained with following parameters (field of view: 24, slice thickness: 5 mm, slice gap: 2 mm). MR spectroscopic data were acquired from single voxel proton spectroscopy with press technique (TR/TE: 2000/40, 128 acqusition).
3. Biological effects 3.1. Radiation biology Radiosurgery utilizes ionizing radiation. When ionizing radiation interacts with a cell, it can interact with water, lipids, proteins, carbohydrates and nucleotides. Deoxyribonucleic acid (DNA) is most likely the critical target for cellular radiation effects. Damage to DNA creates permanent cell injury or death. Injuries of other intracellular molecules such as lipids or proteins can also play a role in the cellular effects of radiation. Radiation may indirectly lead to cell death mediated by apoptotic cascade or other damaging cellular events [23,24]. 3.2. Histological changes From the time of irradiation to the development of brain tissue injury, there is a dose-related variable latency period that can last from months to years [25,26]. Delayed vascular injury after radiation is dependent on dose, volume, and time after treatment [26]. Within the brain adjacent to necrosis, astrocytosis, endothelial cell degeneration, shrunken neurons, vessel wall thickening, edema, and microhemorrhages are observed after radiation [27].
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Fig. 5. Serial change of perilesional signal on conventional MR imaging after radiosurgery for brain metastasis in a 66-year-old-male. (A) Axial FLAIR MR image before radiosurgery shows irregular margin and heterogenous signal intensity mass around third ventricle. (B and C) Axial FLAIR MR image obtained 5 and 10 months later shows interval decrease in extent of abnormal high signal intensity area around mass. Perilesional signal change usually shows decrease in extent with time representing glial scar change. (D) Axial FLAIR MR image at 15 months follow-up after radiosurgery shows more decrease in size of the mass with perilesional signal change. And mild hydrocephalus with transependymal edema is newly developed.
In the central part of the area treated by radiosurgery, a decrease of the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls are seen. In the peripheral part of the area treated by radiosurgery, some tumors contain viable cells intermingled with blood vessels that have been seen with endothelial and pericytic proliferation (Fig. 1) [28,29]. 4. Conventional MR imaging The temporal biological effects of radiosurgery on normal brain tissue have been classified into three stages: (i) an early stage, with edema in the central region of the area treated by radiosurgery showing a swelling of the lesion and perilesional edema; (ii) an intermediate stage, with progressive cavitation and capillary proliferation surrounding the necrotic center, an occurrence compatible with ring enhancement and minute perilesional edema; (iii) a late stage, with central necrosis and a glial scar that represents peripheral enhancement without perilesional edema seen on MR imaging [29,30]. In brain tumors, sequential changes identified on MR imaging show temporary exacerbation of a lesion, central loss of contrast enhancement, growth arrest, and regression or obliteration (Fig. 2) [31].
After radiosurgery, a lesion shows perilesional edema, rim-like enhancement at 2–6 months and central hypointensity on T2weighted imaging (Fig. 3). This perilesional edema is known as vasogenic edema. The absence of blood–brain barrier and presence of fenestrations in the capillary wall of tumor vessels are probably important in the formation of vasogenic edema associated with brain metastasis. Blurring marginal enhancement can be demonstrated without tumor progression. With time, the blurring marginal enhancement changes become more discrete (Fig. 4) [29,31]. A perilesional signal change usually decreases in extent with time representing a glial scar change (Fig. 5). Furthermore, the tumor volume usually tends to decrease with time (Fig. 6) [10,11,13,32]. 5. Functional MR imaging The radiological differentiation of radiation-induced changes from recurrence or progression after radiosurgery for brain tumor remains a challenge despite improvement of morphologicalbased conventional MR imaging. Although a lesion shows an increase in the degree of enhancement and the size of perilesional edema in addition to a blurred margin of a lesion on
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Fig. 6. Serial change of tumor size on conventional MR imaging after radiosurgery for brain metastasis in a 64-year-old-male. (A and B) Axial post-contrast T1-weighted and FLAIR MR image before radiosurgery demonstrates well defined enhancing mass with extensive perilesional edema in right parietal lobe. (C and D) Axial post-contrast T1-weighted and FLAIR MR image at 7 months follow-up after radiosurgery shows markedly decrease in size of tumor with surrounding edema in right parietal lobe. After radiosurgery, the tumor volume usually tends to decrease with time.
Fig. 7. Serial change of diffusion weighted MR imaging after radiosurgery for brain metastasis in a 55-year-old-male. ADC = Apparent diffusion coefficient. (A) Axial postcontrast T1-weighted MR image before radiosurgery shows well enhancing mass with central necrosis in right frontal lobe (left). The diffusion restriction on ADC map shows in the region coincident with peripheral enhancing solid component of mass (right). (B) Axial post-contrast T1-weighted MR image at 3 months follow-up after radiosurgery shows interval decrease in size of enhancing mass (left). There is no abnormal diffusion restriction in area of previous radiosurgery site on ADC map (right). (C) After radiosurgery, blurring marginal enhancement and minimal increase in size is shown in axial post-contrast T1-weighted MR image at 6 months follow-up (left). But still there is no abnormal diffusion restriction in area of previous radiosurgery site on ADC map (right). This result of diffusion weighted MR imaging may suggest the radiation induced change rather than tumor recurrence. (D) Axial post-contrast T1-weighted MR image at 16 months follow-up after radiosurgery shows interval decrease in size of enhancing mass without tumor progression (left) and abnormal diffusion restriction on ADC map (right).
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Fig. 8. Diffusion weighted MR imaging after radiosurgery for brain metastasis in a 61-year-old-male. ADC = Apparent diffusion coefficient. (A) Axial post-contrast T1-weighted MR image before radiosurgery shows a small enhancing mass with perilesional edema in left parietal lobe. (B) Axial post-contrast T1-weighted MR image at 3 months followup after radiosurgery shows interval decrease in size of a small enhancing mass with perilesional edema in left parietal lobe. (C) Axial post-contrast T1-weighted MR image obtained 7 months after radiosurgery shows interval increase in size of enhancing component and perilesional edema (left). The diffusion restriction on ADC map is appeared in the region coincident with left lateral aspect of enhancing solid component of the mass (right). This result of diffusion weighted MR imaging may suggest the tumor recurrence rather than radiation induced injury. (D) Axial post-contrast T1-weighted MR image obtained 11 months after radiosurgery shows more aggravation about mass size and perilesional edema. At that time, the lesion was surgically removal, and the pathologic examination revealed recurrent tumor. If appearance of diffusion restriction in enhancing component of the mass after radiosurgery appears on follow-up MR imaging, this finding may be considered indicative of tumor recurrence.
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Fig. 9. Perfusion MR imaging after radiosurgery for brain metastasis in a 60-year-old female. rCBV = relative cerebral blood volume. (A) Axial post-contrast T1-weighted MR image before radiosugery demonstrates well-defined enhancing mass in left parietal lobe. (B and C) After radiosurgery, post-contrast T1-weighted MR image from 3 and 6 months follow-up shows central necrosis, peripheral rim enhancement and decrease in size with time (left). There is no abnormal increment of rCBV in area of previous radiosurgery site in perfusion MR imaging. This result of perfusion MR imaging may suggest the radiation induced change (right).
follow-up MR imaging after radiosurgery, these imaging findings are not always compatible for tumor recurrence [14,33]. [Radiation-induced changes can mimic these variable image findings that resemble tumor recurrence.] However, a therapeutic approach including the use of invasive modalities (repeat resection, biopsy) depends on the imaging findings after radio-
surgery, and an accurate diagnosis is important to improve clinical outcome. To overcome the limitation of morphologybased conventional MR imaging, several physiological-based functional MR imaging methods have been used. These methods provide additional information for proper decision making [34].
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Fig. 10. Perfusion MR imaging after radiosurgery for brain metastasis in a 54-year-old-male. rCBV = relative cerebral blood volume. (A) Axial post-contrast T1-weighted MR image before radiosurgery demonstrates a well enhancing mass with central necrosis in right frontal lobe. (B) Axial post-contrast T1-weighted MR image obtained 3 months after radiosurgery shows interval decrease in size of mass with enhancement degree (left). But the rCBV in perfusion MR imaging is increased in the region coincident with peripheral aspect of enhancing solid component of the mass (right). This result of perfusion MR imaging may suggest the tumor recurrence rather than radiation induced injury. At that time, the lesion was surgically removal, and the pathologic examination revealed recurrent tumor.
Fig. 11. MR spectroscopy after radiosurgery for brain metastasis in a 63-year-old-male. (A) Axial post-contrast T1-weighted MR image before radiosurgery demonstrates well enhancing mass without edema in left cerebellum. (B) Axial post-contrast T1-weighted MR image obtained 6 months after radiosurgery shows more irregular marginal enhancement compared with pre-treatment. (C) At that time, MR spectroscopy shows no abnormal peaks of metabolites including choline (gray arrow), creatine, and Nacetylaspartate (white arrow). The result of MR spectroscopy may suggest radiation induced change rather than tumor recurrence. (D) Axial post-contrast T1-weighted MR image obtained 14 months after radiosurgery shows more decrease in size of lesion with discrete margin representing no tumor recurrence.
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5.1. Diffusion-weighted imaging Diffusion-weighted imaging (DWI) is an important physiological-based imaging method that measures differences in the apparent diffusion coefficient (ADC) caused by water proton mobility alterations. The principle of DWI to quantify cellularity is based on the premise that water diffusivity within the extracellular compartment is inversely related to the content of the constituents of the intracellular space [34]. The use of DWI has several clinical applications to identify tumor grade, cellularity, post-operative injury, peritumoral edema, and the integrity of the white matter tract in brain tumors [35,36]. One of clinical applications of DWI is to assess radiation injury and tumor recurrence in brain tumors after radiosurgery. Higher cellularity represents a greater volume of intracellular space; a lower the ADC value results from decreased water diffusivity caused by a relative reduction in the extracellular space for the proton to move about. Thus, higher cellularity in a recurrent tumor contributes to the lower ADC values as compared to radiation necrosis [15,16]. This useful functional imaging finding tool is helpful to diagnose the difference between a recurrent tumor and radiation necrosis on a follow-up MR imaging study after radiosurgery (Figs. 7 and 8). 5.2. Perfusion MR imaging The most widely used technique for a perfusion study is to evaluate the relative cerebral blood volume (rCBV) from dynamic susceptibility-weighted contrast enhanced MR imaging [34]. MR imaging measurements of tumor hemodynamics are very useful to characterize tumors as tumor aggressiveness and growth are associated with both endothelial hyperplasia and neovascularization [37]. With an increment of vascularity in tumors, new vessels and damaged mature vessels are permeable to contrast agents, unlike vessels in the normal brain. Measurement of the rCBV reliably correlates with tumor grade and histological findings of increased tumor vascularity, particularly in gliomas [20,38–40]. Variable lesions of the brain, such as radiation necrosis, subacute infract, demyelinating lesion, and infectious or inflammatory lesions can mimic a brain tumor on conventional images [41–44]. These lesions sometimes demonstrate contrast enhancement on post-contrast T1-weighted images due to leakage of contrast material into the interstitial space through a disruption of the blood–brain barrier. rCBV can be used to differentiate between a radiation-induced change and tumor recurrence by estimating the regional cerebral blood volume after radiosurgery. A decrease of rCBV values indicates a tumor response to therapy regardless of increases in tumor volume, which might be due to radiation-induced edema and blood–brain barrier disruption necrosis as seen on a followup MR imaging study after radiosurgery. If increment of rCBV in enhancing component of the mass after radiosurgery appears on follow-up MR imaging, this finding may be considered indicative of tumor recurrence (Figs. 9 and 10) [41]. 5.3. Proton MR spectroscopy MR spectroscopy is a noninvasive imaging technique that offers unique metabolic information on brain tumor biology that is not available from the use of conventional MR imaging. MR spectroscopy is intrinsically a multiparameter method, yielding simultaneous information about a variety of metabolites. It is an effective tool to overcome the limitations of conventional MR imaging by enabling detection of altered levels of biochemical tissue compounds such as choline, lipid and lactate. This biochemical pattern analysis of MR spectroscopy data can be successfully applied to detect metabolic signatures of brain lesions. After radiosurgery
Fig. 12. MR spectroscopy after radiosurgery for brain metastasis in a 61-year-oldmale. (A) Axial T2-weighted MR image obtained 7 months after radiosurgery shows small mass lesion (arrow) with extensive perilesional edema. (B) At that time, MR spectroscopy shows abnormal pattern of metabolite such as slightly elevated choline (gray arrow) and lipid–lactate complex (white arrow) representing tumor recurrence. The lesion was surgically removal, and the pathologic examination revealed recurrent tumor.
of brain tumors, MR spectroscopy has a promising role, and evaluation of metabolic changes with MR spectroscopy can improve tissue discrimination and provide a correlation with histological findings [45]. MR spectroscopy may be able to distinguish lesions composed of predominantly tumor recurrence from lesions containing predominantly radiation-induced changes, based on a change in the cellular metabolites including choline/creatine level. Changes in the choline/creatine level and lipid–lactate complex peak are indicative of abnormal levels of the metabolites at the cellular level after radiosurgery. An increase in the level of choline correlates with a poor radiological response and suggests tumor recurrence (Figs. 11 and 12) [21,22]. 6. Prognostic factors in MR imaging With conventional MR imaging, an abnormal enhancing lesion after brain metastatic tumor radiosurgery shows a decrease in perilesional edema, the degree of enhancement, and a decrease of mass
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size with a more discrete margin, representing good prognosis as seen on serial follow up imaging studies. With functional MR imaging, an abnormal enhancing lesion after brain metastatic tumor radiosurgery shows diffusion restriction by diffusion-weighted imaging, and an increase in the value of the rCBV in perfusion MR imaging. A high elevation of abnormal metabolites detected by MR spectroscopy represents a poor prognosis. 7. Summary Conventional MR imaging is a useful tool for follow-up of a brain metastatic tumor after radiosurgery. However, radiologists are sometimes confused by radiation-induced changes including radiation necrosis seen on conventional MR imaging. To overcome these limitations, the use of functional MR imaging can lead to more accurate follow-up findings and ultimately to an improved patient clinical outcome. References [1] Friedman DP, Goldman HW, Flanders AE, Gollomp SM, Curran Jr WJ. Stereotactic radiosurgical pallidotomy and thalamotomy with the gamma knife: MR imaging findings with clinical correlation–preliminary experience. Radiology 1999;212:143–50. [2] Ulm 3rd AJ, Friedman WA, Bradshaw P, Foote KD, Bova FJ. Radiosurgery in the treatment of malignant gliomas: the University of Florida experience. Neurosurgery 2005;57:512–7, discussion 517. [3] Bindal AK, Bindal RK, Hess KR, et al. Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg 1996;84:748–54. [4] Kondziolka D, Lunsford LD, Coffey RJ, Flickinger JC. Stereotactic radiosurgery of meningiomas. J Neurosurg 1991;74:552–9. [5] Flickinger JC, Kondziolka D, Niranjan A, Lunsford LD. Results of acoustic neuroma radiosurgery: an analysis of 5 years’ experience using current methods. J Neurosurg 2001;94:1–6. [6] Izawa M, Hayashi M, Nakaya K, et al. Gamma knife radiosurgery for pituitary adenomas. J Neurosurg 2000;93(Suppl. 3):19–22. [7] Suh JH, Vogelbaum MA, Barnett GH. Update of stereotactic radiosurgery for brain tumors. Curr Opin Neurol 2004;17:681–6. [8] Nakamura H, Jokura H, Takahashi K, Boku N, Akabane A, Yoshimoto T. Serial follow-up MR imaging after gamma knife radiosurgery for vestibular schwannoma. AJNR Am J Neuroradiol 2000;21:1540–6. [9] Shinoda J, Yano H, Ando H, et al. Radiological response and histological changes in malignant astrocytic tumors after stereotactic radiosurgery. Brain Tumor Pathol 2002;19:83–92. [10] Peterson AM, Meltzer CC, Evanson EJ, Flickinger JC, Kondziolka D. MR imaging response of brain metastases after gamma knife stereotactic radiosurgery. Radiology 1999;211:807–14. [11] Tung GA, Noren G, Rogg JM, Jackson IM. MR imaging of pituitary adenomas after gamma knife stereotactic radiosurgery. AJR Am J Roentgenol 2001;177:919–24. [12] Friedman DP, Morales RE, Goldman HW. MR imaging findings after stereotactic radiosurgery using the gamma knife. AJR Am J Roentgenol 2001;176:1589–95. [13] Meijer OW, Weijmans EJ, Knol DL, et al. Tumor-volume changes after radiosurgery for vestibular schwannoma: implications for follow-up MR imaging protocol. AJNR Am J Neuroradiol 2008;29:906–10. [14] Mullins ME, Barest GD, Schaefer PW, Hochberg FH, Gonzalez RG, Lev MH. Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis. AJNR Am J Neuroradiol 2005;26:1967–72. [15] Asao C, Korogi Y, Kitajima M, et al. Diffusion-weighted imaging of radiationinduced brain injury for differentiation from tumor recurrence. AJNR Am J Neuroradiol 2005;26:1455–60. [16] Hein PA, Eskey CJ, Dunn JF, Hug EB. Diffusion-weighted imaging in the followup of treated high-grade gliomas: tumor recurrence versus radiation injury. AJNR Am J Neuroradiol 2004;25:201–9. [17] Boxerman JL, Schmainda KM, Weisskoff RM. Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. AJNR Am J Neuroradiol 2006;27:859–67. [18] Lee SJ, Kim JH, Kim YM, et al. Perfusion MR imaging in gliomas: comparison with histologic tumor grade. Korean J Radiol 2001;2:1–7.
[19] Maia Jr AC, Malheiros SM, da Rocha AJ, et al. MR cerebral blood volume maps correlated with vascular endothelial growth factor expression and tumor grade in nonenhancing gliomas. AJNR Am J Neuroradiol 2005;26:777–83. [20] Law M, Yang S, Babb JS, et al. Comparison of cerebral blood volume and vascular permeability from dynamic susceptibility contrast-enhanced perfusion MR imaging with glioma grade. AJNR Am J Neuroradiol 2004;25:746–55. [21] Graves EE, Nelson SJ, Vigneron DB, et al. Serial proton MR spectroscopic imaging of recurrent malignant gliomas after gamma knife radiosurgery. AJNR Am J Neuroradiol 2001;22:613–24. [22] Schlemmer HP, Bachert P, Herfarth KK, Zuna I, Debus J, van Kaick G. Proton MR spectroscopic evaluation of suspicious brain lesions after stereotactic radiotherapy. AJNR Am J Neuroradiol 2001;22:1316–24. [23] Crompton NE. Programmed cellular response to ionizing radiation damage. Acta Oncol 1998;37:129–42. [24] Hallahan DE, Virudachalam S, Kuchibhotla J, Kufe DW, Weichselbaum RR. Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction. Proc Natl Acad Sci U S A 1994;91:4897–901. [25] Calvo W, Hopewell JW, Reinhold HS, Yeung TK. Time- and dose-related changes in the white matter of the rat brain after single doses of X rays. Br J Radiol 1988;61:1043–52. [26] Munter MW, Karger CP, Reith W, Schneider HM, Peschke P, Debus J. Delayed vascular injury after single high-dose irradiation in the rat brain: histologic immunohistochemical, and angiographic studies. Radiology 1999;212:475–82. [27] Oh BC, Pagnini PG, Wang MY, et al. Stereotactic radiosurgery: adjacent tissue injury and response after high-dose single fraction radiation. Part I. Histology, imaging, and molecular events. Neurosurgery 2007;60:31–44, discussion 45. [28] Kamada K, Mastuo T, Tani M, et al. Effects of stereotactic radiosurgery on metastatic brain tumors of various histopathologies. Neuropathology 2001;21:307–14. [29] Uematsu Y, Fujita K, Tanaka Y, et al. Gamma knife radiosurgery for neuroepithelial tumors: radiological and histological changes. Neuropathology 2001;21:298–306. [30] Blatt DR, Friedman WA, Bova FJ, Theele DP, Mickle JP. Temporal characteristics of radiosurgical lesions in an animal model. J Neurosurg 1994;80:1046–55. [31] Lunsford LD, Kondziolka D, Maitz A, Flickinger JC. Black holes, white dwarfs and supernovas: imaging after radiosurgery. Stereotact Funct Neurosurg 1998;70(Suppl. 1):2–10. [32] Kondziolka D, Nathoo N, Flickinger JC, Niranjan A, Maitz AH, Lunsford LD. Longterm results after radiosurgery for benign intracranial tumors. Neurosurgery 2003;53:815–21, discussion 821-822. [33] Kumar AJ, Leeds NE, Fuller GN, et al. Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 2000;217:377–84. [34] Cha S. Update on brain tumor imaging: from anatomy to physiology. AJNR Am J Neuroradiol 2006;27:475–87. [35] Kono K, Inoue Y, Nakayama K, et al. The role of diffusion-weighted imaging in patients with brain tumors. AJNR Am J Neuroradiol 2001;22:1081–8. [36] Lam WW, Poon WS, Metreweli C. Diffusion MR imaging in glioma: does it have any role in the pre-operation determination of grading of glioma? Clin Radiol 2002;57:219–25. [37] Burger PC. Malignant astrocytic neoplasms: classification, pathologic anatomy, and response to treatment. Semin Oncol 1986;13:16–26. [38] Shin JH, Lee HK, Kwun BD, et al. Using relative cerebral blood flow and volume to evaluate the histopathologic grade of cerebral gliomas: preliminary results. AJR Am J Roentgenol 2002;179:783–9. [39] Sugahara T, Korogi Y, Kochi M, et al. Correlation of MR imaging-determined cerebral blood volume maps with histologic and angiographic determination of vascularity of gliomas. AJR Am J Roentgenol 1998;171:1479–86. [40] Wong JC, Provenzale JM, Petrella JR. Perfusion MR imaging of brain neoplasms. AJR Am J Roentgenol 2000;174:1147–57. [41] Essig M, Waschkies M, Wenz F, Debus J, Hentrich HR, Knopp MV. Assessment of brain metastases with dynamic susceptibility-weighted contrast-enhanced MR imaging: initial results. Radiology 2003;228:193–9. [42] Morgenstern LB, Frankowski RF. Brain tumor masquerading as stroke. J Neurooncol 1999;44:47–52. [43] Schwartz RB, Carvalho PA, Alexander 3rd E, Loeffler JS, Folkerth R, Holman BL. Radiation necrosis vs high-grade recurrent glioma: differentiation by using dual-isotope SPECT with 201TI and 99mTc-HMPAO. AJNR Am J Neuroradiol 1991;12:1187–92. [44] Zagzag D, Miller DC, Kleinman GM, Abati A, Donnenfeld H, Budzilovich GN. Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis. Am J Surg Pathol 1993;17:537–45. [45] Rabinov JD, Lee PL, Barker FG, et al. In vivo 3-T MR spectroscopy in the distinction of recurrent glioma versus radiation effects: initial experience. Radiology 2002;225:871–9.
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Morphological and functional MRI, MRS, perfusion and diffusion changes after radiosurgery of brain metastasis Tae Wook Kang a,1 , Sung Tae Kim a,∗ , Hong Sik Byun a,1 , Pyoung Jeon a,1 , Keonha Kim a,1 , Hyungjin Kim a,1 , Jung II Lee b,1 a b
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea
a r t i c l e
i n f o
Article history: Received 22 May 2008 Received in revised form 11 August 2008 Accepted 11 August 2008 Keywords: Radiosurgery Magnetic resonance imaging Brain Metastasis
a b s t r a c t Radiosurgery is a noninvasive procedure where spatially accurate and highly conformal doses of radiation are targeted at brain lesions with an ablative intent. Recently, radiosurgery has been established as an effective technique for local treatment of brain metastasis. After radiosurgery, magnetic resonance (MR) imaging plays an important role in the assessment of the therapeutic response and of any complications. The therapeutic approach depends on the imaging findings obtained after radiosurgery, which have a role in the decision making to perform additional invasive modalities (repeat resection, biopsy) to obtain a definite diagnosis and to improve the survival of patients. Conventional MR imaging findings are mainly based on morphological alterations of tumors. However, there are variable imaging findings of radiation-induced changes including radiation necrosis in the brain. Radiologists are sometimes confused by radiation-induced injuries, including radiation necrosis, that are seen on conventional MR imaging. The pattern of abnormal enhancement on follow-up conventional MR imaging closely mimics that of a recurrent brain metastasis. So, classifying newly developed abnormal enhancing lesions in follow-up of treated brain metastasis with correct diagnosis is one of the key goals in neuro-oncologic imaging. To overcome limitations of the use of morphology-based conventional MR imaging, several physiological-based functional MR imaging methods have been used, namely diffusion-weighted imaging, perfusion MR imaging, and proton MR spectroscopy, for the detection of hemodynamic, metabolic, and cellular alterations. These imaging modalities provide additional information to allow clinicians to make proper decisions regarding patient treatment. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Radiosurgery has been widely used to treat meningiomas, schwannomas, pituitary adenomas, metastatic brain tumors, malignant gliomas and other neurological diseases as an alternative method in place of surgical resection [1–7]. Follow-up imaging studies are needed to assess the results of radiosurgery and to detect any complications. The introduction of magnetic resonance (MR) imaging has revolutionized the clinical effectiveness of radiosurgery by improving the identification and characterization of
∗ Corresponding author. Tel.: +82 2 3410 6458; fax: +82 2 3410 0084. E-mail addresses: [email protected] (T.W. Kang), [email protected] (S.T. Kim), [email protected] (H.S. Byun), [email protected] (P. Jeon), [email protected] (K. Kim), [email protected] (H. Kim), [email protected] (J.I. Lee). 1 Tel.: +82 2 3410 2507; fax: +82 2 3410 2559. 0720-048X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2008.08.009
target tissues by precisely characterizing treatment response. The role of MR imaging in assessing the response to radiosurgery in post-treatment has been studied for variable diseases [8–13]. Conventional MR imaging is an anatomy-based procedure and morphologic alterations are the key to resolve abnormal findings on follow-up imaging studies after radiosurgery. However, the histological response of brain normal tissue and tumors to radiosurgery has confounded correct follow-up evaluations. Recurrent tumors and radiation-induced changes often appear at the same location within or near the region of the irradiated area, and both occurrences resemble contrast-enhancing, expansile brain lesions surrounded by edema. It is difficult with the use of conventional MR imaging to assess abnormal imaging findings after radiosurgery as lesions that are related to a residual or recurrent brain tumor, or as lesions that are related to non-tumorous, radiation-induced changes [14]. Thus, an accurate diagnosis of radiation-induced changes on MR imaging has been challenging. If a lesion deviates from usual conventional MR imaging findings on follow-up,
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Fig. 1. Schematic representation of histological changes after radiosugery. In the central part (gray circle) of the area treated by radiosurgery, a decrease of the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls are seen. In the peripheral part (white circle) of the area treated by radiosurgery, some tumors contain viable cells intermingled with blood vessels that have been seen with endothelial and pericytic proliferation.
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additional information is required to make a correct diagnosis using functional MR imaging. Currently, diffusion-weighted imaging (DWI), perfusion-weighted imaging, and proton MR spectroscopy are used as physiological-based functional MR imaging methods. Diffusion-weighted imaging (DWI) is based on the detection of changes in the random motion of protons in water, and its use enables the characterization of tissues and pathological processes at a microscopic level [15,16]. Perfusion-weighted imaging is an important tool to measure the degree of brain tumor angiogenesis and capillary permeability, both of which are major biological markers of malignancy, grading, and prognosis, especially for gliomas [17–20]. MR spectroscopy can provide a noninvasive window to analyze neurometabolism. Pattern analysis of MR spectroscopy data can be successfully applied to detect metabolic alterations of brain tumors and other non-neoplastic lesions [21,22]. This review provides a comprehensive overview of the radiation biology to understand MR imaging changes. In addition, this review evaluates conventional and functional MR imaging after radiosurgery of metastatic brain tumors in order to obtain more accurate follow-up results and ultimately to improve patient clinical outcome. 2. Materials and methods Written informed consent was obtained from every patient prior to treatment. From January 2004 to October 2007, 429 patients with
Fig. 2. Typical conventional MR imaging after radiosurgery for brain metastasis in a 60-year-old female. (A) Axial post-contrast T1-weighted MR image before radiosugery demonstrates well-defined enhancing mass in left parietal lobe. (B and C) After radiosurgery, axial T2-weighted and post-contrast T1-weighted MR image from 3-month followup shows progressive cavitation with capillary proliferation surrounding the necrotic center representing rim enhancement and perilesional edema. (D) After radiosurgery, axial post-contrast T1-weighted MR image from 6-month follow-up shows decrease in size of tumor and loss of enhancement with time.
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Fig. 3. Serial change of edema on conventional MR imaging after radiosurgery for brain metastasis in a 55-year-old-male. FLAIR = fluid attenuated inversion recovery. (A and B) Axial post-contrast T1-weighted and FLAIR MR image before radiosurgery shows well enhancing mass with perilesional edema in right frontal lobe. (C) After radiosurgery axial FLAIR MR image from 3-month follow-up after demonstrates slightly decrease in size of tumor and perilesional edema. (D and E) After radiosurgery axial FLAIR MR image from 6- and 15-month follow-up shows markedly decrease in size of tumor and perilesional edema without tumor progression.
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Fig. 4. Serial change of lesion enhancement on conventional MR imaging after radiosurgery for brain metastasis in a 66-year-old-male. (A) Axial post-contrast 3D spoiled gradient recalled (SPGR) MR image for planning before radiosurgery shows heterogenous enhancing mass around third ventricle. (B and C) After radiosurgery axial postcontrast T1-weighted MR image from 5 and 10 months follow-up shows decrease in size of enhancing mass. After radiosurgery blurring marginal enhancement (arrow) can be shown without tumor recurrence by radiation-induced change. (D) After radiosurgery axial post-contrast T1-weighted MR image from 15 months follow-up shows slightly disappearance of blurring marginal enhancement. If there is no aggravation of tumor, the blurring marginal enhancement changes may become more discrete with time.
brain metastasis were treated with 566 radiosurgery procedures at our institution. The mean age of patients was 56.4 years (range: 30–83 years). There were 208 men and 221 women. The primary tumor was lung cancer (n = 267), breast cancer (n = 61), renal cell carcinoma (n = 41), colorectal cancer (n = 23), gynecologic cancer (n = 12), and others (25), respectively. For the evaluation of treatment response, All MR images were obtained with a MR scanner, 3-T Achieva (Philips medical systems, BEST, Netherland), using a eight-channel sense head coil. Patients were assigned to the specific MR imaging protocols for brain tumors at our institution. This protocol consisted of pre- and post-contrast axial and sagittal T1-weighted imaging (TR/TE: 500/10), axial fat suppressed T2-weighted imaging (TR/TE: 2200/70), axial fluid attenuated inversion recovery (FLAIR) imaging (TR/TI/TE: 11000/2800/125), diffusion-weighted imaging (single shot spin echo EPI sequence, TR/TE: 3000/46, b factor: 1000, matrix: 128 × 128), and perfusion weighted imaging (single shot EPI gradient sequence, TR/TE: 1510/35, flip angle: 40◦ , matrix: 128 × 128, 50 dynamic, one dynamic scan time: 1.5 s). These sequences were obtained with following parameters (field of view: 24, slice thickness: 5 mm, slice gap: 2 mm). MR spectroscopic data were acquired from single voxel proton spectroscopy with press technique (TR/TE: 2000/40, 128 acqusition).
3. Biological effects 3.1. Radiation biology Radiosurgery utilizes ionizing radiation. When ionizing radiation interacts with a cell, it can interact with water, lipids, proteins, carbohydrates and nucleotides. Deoxyribonucleic acid (DNA) is most likely the critical target for cellular radiation effects. Damage to DNA creates permanent cell injury or death. Injuries of other intracellular molecules such as lipids or proteins can also play a role in the cellular effects of radiation. Radiation may indirectly lead to cell death mediated by apoptotic cascade or other damaging cellular events [23,24]. 3.2. Histological changes From the time of irradiation to the development of brain tissue injury, there is a dose-related variable latency period that can last from months to years [25,26]. Delayed vascular injury after radiation is dependent on dose, volume, and time after treatment [26]. Within the brain adjacent to necrosis, astrocytosis, endothelial cell degeneration, shrunken neurons, vessel wall thickening, edema, and microhemorrhages are observed after radiation [27].
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Fig. 5. Serial change of perilesional signal on conventional MR imaging after radiosurgery for brain metastasis in a 66-year-old-male. (A) Axial FLAIR MR image before radiosurgery shows irregular margin and heterogenous signal intensity mass around third ventricle. (B and C) Axial FLAIR MR image obtained 5 and 10 months later shows interval decrease in extent of abnormal high signal intensity area around mass. Perilesional signal change usually shows decrease in extent with time representing glial scar change. (D) Axial FLAIR MR image at 15 months follow-up after radiosurgery shows more decrease in size of the mass with perilesional signal change. And mild hydrocephalus with transependymal edema is newly developed.
In the central part of the area treated by radiosurgery, a decrease of the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls are seen. In the peripheral part of the area treated by radiosurgery, some tumors contain viable cells intermingled with blood vessels that have been seen with endothelial and pericytic proliferation (Fig. 1) [28,29]. 4. Conventional MR imaging The temporal biological effects of radiosurgery on normal brain tissue have been classified into three stages: (i) an early stage, with edema in the central region of the area treated by radiosurgery showing a swelling of the lesion and perilesional edema; (ii) an intermediate stage, with progressive cavitation and capillary proliferation surrounding the necrotic center, an occurrence compatible with ring enhancement and minute perilesional edema; (iii) a late stage, with central necrosis and a glial scar that represents peripheral enhancement without perilesional edema seen on MR imaging [29,30]. In brain tumors, sequential changes identified on MR imaging show temporary exacerbation of a lesion, central loss of contrast enhancement, growth arrest, and regression or obliteration (Fig. 2) [31].
After radiosurgery, a lesion shows perilesional edema, rim-like enhancement at 2–6 months and central hypointensity on T2weighted imaging (Fig. 3). This perilesional edema is known as vasogenic edema. The absence of blood–brain barrier and presence of fenestrations in the capillary wall of tumor vessels are probably important in the formation of vasogenic edema associated with brain metastasis. Blurring marginal enhancement can be demonstrated without tumor progression. With time, the blurring marginal enhancement changes become more discrete (Fig. 4) [29,31]. A perilesional signal change usually decreases in extent with time representing a glial scar change (Fig. 5). Furthermore, the tumor volume usually tends to decrease with time (Fig. 6) [10,11,13,32]. 5. Functional MR imaging The radiological differentiation of radiation-induced changes from recurrence or progression after radiosurgery for brain tumor remains a challenge despite improvement of morphologicalbased conventional MR imaging. Although a lesion shows an increase in the degree of enhancement and the size of perilesional edema in addition to a blurred margin of a lesion on
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Fig. 6. Serial change of tumor size on conventional MR imaging after radiosurgery for brain metastasis in a 64-year-old-male. (A and B) Axial post-contrast T1-weighted and FLAIR MR image before radiosurgery demonstrates well defined enhancing mass with extensive perilesional edema in right parietal lobe. (C and D) Axial post-contrast T1-weighted and FLAIR MR image at 7 months follow-up after radiosurgery shows markedly decrease in size of tumor with surrounding edema in right parietal lobe. After radiosurgery, the tumor volume usually tends to decrease with time.
Fig. 7. Serial change of diffusion weighted MR imaging after radiosurgery for brain metastasis in a 55-year-old-male. ADC = Apparent diffusion coefficient. (A) Axial postcontrast T1-weighted MR image before radiosurgery shows well enhancing mass with central necrosis in right frontal lobe (left). The diffusion restriction on ADC map shows in the region coincident with peripheral enhancing solid component of mass (right). (B) Axial post-contrast T1-weighted MR image at 3 months follow-up after radiosurgery shows interval decrease in size of enhancing mass (left). There is no abnormal diffusion restriction in area of previous radiosurgery site on ADC map (right). (C) After radiosurgery, blurring marginal enhancement and minimal increase in size is shown in axial post-contrast T1-weighted MR image at 6 months follow-up (left). But still there is no abnormal diffusion restriction in area of previous radiosurgery site on ADC map (right). This result of diffusion weighted MR imaging may suggest the radiation induced change rather than tumor recurrence. (D) Axial post-contrast T1-weighted MR image at 16 months follow-up after radiosurgery shows interval decrease in size of enhancing mass without tumor progression (left) and abnormal diffusion restriction on ADC map (right).
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Fig. 8. Diffusion weighted MR imaging after radiosurgery for brain metastasis in a 61-year-old-male. ADC = Apparent diffusion coefficient. (A) Axial post-contrast T1-weighted MR image before radiosurgery shows a small enhancing mass with perilesional edema in left parietal lobe. (B) Axial post-contrast T1-weighted MR image at 3 months followup after radiosurgery shows interval decrease in size of a small enhancing mass with perilesional edema in left parietal lobe. (C) Axial post-contrast T1-weighted MR image obtained 7 months after radiosurgery shows interval increase in size of enhancing component and perilesional edema (left). The diffusion restriction on ADC map is appeared in the region coincident with left lateral aspect of enhancing solid component of the mass (right). This result of diffusion weighted MR imaging may suggest the tumor recurrence rather than radiation induced injury. (D) Axial post-contrast T1-weighted MR image obtained 11 months after radiosurgery shows more aggravation about mass size and perilesional edema. At that time, the lesion was surgically removal, and the pathologic examination revealed recurrent tumor. If appearance of diffusion restriction in enhancing component of the mass after radiosurgery appears on follow-up MR imaging, this finding may be considered indicative of tumor recurrence.
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Fig. 9. Perfusion MR imaging after radiosurgery for brain metastasis in a 60-year-old female. rCBV = relative cerebral blood volume. (A) Axial post-contrast T1-weighted MR image before radiosugery demonstrates well-defined enhancing mass in left parietal lobe. (B and C) After radiosurgery, post-contrast T1-weighted MR image from 3 and 6 months follow-up shows central necrosis, peripheral rim enhancement and decrease in size with time (left). There is no abnormal increment of rCBV in area of previous radiosurgery site in perfusion MR imaging. This result of perfusion MR imaging may suggest the radiation induced change (right).
follow-up MR imaging after radiosurgery, these imaging findings are not always compatible for tumor recurrence [14,33]. [Radiation-induced changes can mimic these variable image findings that resemble tumor recurrence.] However, a therapeutic approach including the use of invasive modalities (repeat resection, biopsy) depends on the imaging findings after radio-
surgery, and an accurate diagnosis is important to improve clinical outcome. To overcome the limitation of morphologybased conventional MR imaging, several physiological-based functional MR imaging methods have been used. These methods provide additional information for proper decision making [34].
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Fig. 10. Perfusion MR imaging after radiosurgery for brain metastasis in a 54-year-old-male. rCBV = relative cerebral blood volume. (A) Axial post-contrast T1-weighted MR image before radiosurgery demonstrates a well enhancing mass with central necrosis in right frontal lobe. (B) Axial post-contrast T1-weighted MR image obtained 3 months after radiosurgery shows interval decrease in size of mass with enhancement degree (left). But the rCBV in perfusion MR imaging is increased in the region coincident with peripheral aspect of enhancing solid component of the mass (right). This result of perfusion MR imaging may suggest the tumor recurrence rather than radiation induced injury. At that time, the lesion was surgically removal, and the pathologic examination revealed recurrent tumor.
Fig. 11. MR spectroscopy after radiosurgery for brain metastasis in a 63-year-old-male. (A) Axial post-contrast T1-weighted MR image before radiosurgery demonstrates well enhancing mass without edema in left cerebellum. (B) Axial post-contrast T1-weighted MR image obtained 6 months after radiosurgery shows more irregular marginal enhancement compared with pre-treatment. (C) At that time, MR spectroscopy shows no abnormal peaks of metabolites including choline (gray arrow), creatine, and Nacetylaspartate (white arrow). The result of MR spectroscopy may suggest radiation induced change rather than tumor recurrence. (D) Axial post-contrast T1-weighted MR image obtained 14 months after radiosurgery shows more decrease in size of lesion with discrete margin representing no tumor recurrence.
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5.1. Diffusion-weighted imaging Diffusion-weighted imaging (DWI) is an important physiological-based imaging method that measures differences in the apparent diffusion coefficient (ADC) caused by water proton mobility alterations. The principle of DWI to quantify cellularity is based on the premise that water diffusivity within the extracellular compartment is inversely related to the content of the constituents of the intracellular space [34]. The use of DWI has several clinical applications to identify tumor grade, cellularity, post-operative injury, peritumoral edema, and the integrity of the white matter tract in brain tumors [35,36]. One of clinical applications of DWI is to assess radiation injury and tumor recurrence in brain tumors after radiosurgery. Higher cellularity represents a greater volume of intracellular space; a lower the ADC value results from decreased water diffusivity caused by a relative reduction in the extracellular space for the proton to move about. Thus, higher cellularity in a recurrent tumor contributes to the lower ADC values as compared to radiation necrosis [15,16]. This useful functional imaging finding tool is helpful to diagnose the difference between a recurrent tumor and radiation necrosis on a follow-up MR imaging study after radiosurgery (Figs. 7 and 8). 5.2. Perfusion MR imaging The most widely used technique for a perfusion study is to evaluate the relative cerebral blood volume (rCBV) from dynamic susceptibility-weighted contrast enhanced MR imaging [34]. MR imaging measurements of tumor hemodynamics are very useful to characterize tumors as tumor aggressiveness and growth are associated with both endothelial hyperplasia and neovascularization [37]. With an increment of vascularity in tumors, new vessels and damaged mature vessels are permeable to contrast agents, unlike vessels in the normal brain. Measurement of the rCBV reliably correlates with tumor grade and histological findings of increased tumor vascularity, particularly in gliomas [20,38–40]. Variable lesions of the brain, such as radiation necrosis, subacute infract, demyelinating lesion, and infectious or inflammatory lesions can mimic a brain tumor on conventional images [41–44]. These lesions sometimes demonstrate contrast enhancement on post-contrast T1-weighted images due to leakage of contrast material into the interstitial space through a disruption of the blood–brain barrier. rCBV can be used to differentiate between a radiation-induced change and tumor recurrence by estimating the regional cerebral blood volume after radiosurgery. A decrease of rCBV values indicates a tumor response to therapy regardless of increases in tumor volume, which might be due to radiation-induced edema and blood–brain barrier disruption necrosis as seen on a followup MR imaging study after radiosurgery. If increment of rCBV in enhancing component of the mass after radiosurgery appears on follow-up MR imaging, this finding may be considered indicative of tumor recurrence (Figs. 9 and 10) [41]. 5.3. Proton MR spectroscopy MR spectroscopy is a noninvasive imaging technique that offers unique metabolic information on brain tumor biology that is not available from the use of conventional MR imaging. MR spectroscopy is intrinsically a multiparameter method, yielding simultaneous information about a variety of metabolites. It is an effective tool to overcome the limitations of conventional MR imaging by enabling detection of altered levels of biochemical tissue compounds such as choline, lipid and lactate. This biochemical pattern analysis of MR spectroscopy data can be successfully applied to detect metabolic signatures of brain lesions. After radiosurgery
Fig. 12. MR spectroscopy after radiosurgery for brain metastasis in a 61-year-oldmale. (A) Axial T2-weighted MR image obtained 7 months after radiosurgery shows small mass lesion (arrow) with extensive perilesional edema. (B) At that time, MR spectroscopy shows abnormal pattern of metabolite such as slightly elevated choline (gray arrow) and lipid–lactate complex (white arrow) representing tumor recurrence. The lesion was surgically removal, and the pathologic examination revealed recurrent tumor.
of brain tumors, MR spectroscopy has a promising role, and evaluation of metabolic changes with MR spectroscopy can improve tissue discrimination and provide a correlation with histological findings [45]. MR spectroscopy may be able to distinguish lesions composed of predominantly tumor recurrence from lesions containing predominantly radiation-induced changes, based on a change in the cellular metabolites including choline/creatine level. Changes in the choline/creatine level and lipid–lactate complex peak are indicative of abnormal levels of the metabolites at the cellular level after radiosurgery. An increase in the level of choline correlates with a poor radiological response and suggests tumor recurrence (Figs. 11 and 12) [21,22]. 6. Prognostic factors in MR imaging With conventional MR imaging, an abnormal enhancing lesion after brain metastatic tumor radiosurgery shows a decrease in perilesional edema, the degree of enhancement, and a decrease of mass
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