Correspondence Perfusion Computed Tomography: An Imaging Biomarker for Brain Tumors’ Grading erfusion computed tomography (CT) is a modern imaging technique that has been successfully applied to the clinical management of patients with ischemic stroke and aneurysmal subarachnoid hemorrhage (4). The literature has shown that perfusion CT has other important clinical applications in various neurosurgical conditions, especially concerning the assessment of brain tumors (4, 10).
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Using modern multidetector row CT, a small quantity of iodinated contrast medium is injected, and a limited number of CT sections are rapidly performed on the region of interest. In this way, the first “intravascular” passage of contrast medium is traced, many perfusion parameters can be evaluated, and quantitative maps are generated. A Patlak algorithm allows tracking of the progressive extravasation of contrast material out of the vessels into the interstitium, by mathematical comparison (deconvolution) of a parenchymal time-signal curve (where there is extravasation) and a reference arterial curve (where extravasation is assumed to be not significant) (2). Cerebral blood flow (CBF) (mL/100 g tissue/min), cerebral blood volume (CBV) (mL/100 g tissue), mean transit time (MMT seconds), and permeability surface area-product (PS) are the main available CT perfusion parameters. Perfusion CT has numerous advantages compared with perfusionweighted magnetic resonance imaging (MRI) (3, 10). The main advantage is the linear relation between density changes and tissue concentration of the contrast agent, such as to make reliable the quantification of perfusion CT parameters (3, 10). Other significant advantages of perfusion CT are the absence of susceptibility artifacts generated by hemorrhage or various mineral deposits, which can create diagnostic concerns on perfusion-weighted MRI examination, and the lack of sensitivity to flow and the high spatial resolution (3). Limitations of CT compared with MRI for evaluation of the microvasculature are the exposure to ionizing radiation, the potential risk for adverse reaction to the contrast agent, and the limited anatomic coverage (3). The radiation dose can be reduced to that of noncontrast head CT scan (2 mSV) through the use of appropriate technical parameters (80 kVp and 100 mAs); increased z-axis coverage can be obtained using a modern CT scanner, which offers whole-brain coverage, or by “toggling table” technique, in which the CT table moves back and forth alternating between 2 different locations (4). Perfusion techniques such as perfusion CT and perfusion-weighted MRI have been used primarily to assess cerebral ischemia;
Key words Brain tumors - Contrast enhancement - Perfusion computed tomography - Perfusion MRI - Tumour grading -
Abbreviations and Acronyms CBF: Cerebral blood flow CBV: Cerebral blood volume CT: Computed tomography MRI: Magnetic resonance imaging PS: Permeability surface area-product
WORLD NEUROSURGERY 82 [6]: e831ee844, DECEMBER 2014
however, the range of perfusion applications has progressively increased, including the diagnostic field of cerebral tumors. Conventional MRI provides important anatomic information, but it is insufficient to determine tumors’ grading preoperatively (2). Contrast enhancement on MRI depicts areas of blood-brain barrier breakdown, which is often associated with high-grade tumors; however, contrast enhancement is not always accurate in predicting tumors’ grading (2). Even in high-grade gliomas with pathologic contrast enhancement, the enhancement may not reflect the areas of neovascularity and angiogenesis. Malignant gliomas are characterized by neovascularity and increased angiogenic activity, with higher proportion of immature and hyperpermeable vessels (2, 10). For this reason, perfusion CT appears to be the ideal technique, for accuracy and speed, to obtain “in vivo” assessment of neoplastic grading. In a group of 23 patients with treatment-naïve gliomas, Jain et al. (6) demonstrated a significant positive correlation with microvessel density antigen (CD34), whereas PS showed a significant positive correlation with microvascular cellular proliferation, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels. Ellika et al. (2) demonstrated the usefulness of normalized perfusion CT parameters in assessing the grade of treatment-naïve gliomas comparing perfusion CT data with conventional MRI features (10). Perfusion CT was performed in 19 patients with gliomas (14 high-grade and 5 low-grade gliomas). For normalized CBV, the cut point of 1.92 was selected to identify high-grade tumors (85.7% sensitivity and 100% specificity); for normalized CBF, the cut point of 1.48 was selected to identify high-grade tumors (71.4% sensitivity and 100% specificity); and, finally, for normalized mean transit time, the cut point of 1.94 was selected to identify high-grade tumors (92.9% sensitivity and 40% specificity) (2). Schramm et al. (9) performed perfusion CT in 43 patients with a previous diagnosis of intraaxial brain tumor (4 low-grade gliomas, 31 glioblastomas, 8 intracerebral lymphomas) to identify elements capable of characterizing such lesions. Presurgical characterization appears to be crucial because high-grade gliomas and cerebral lymphomas require different therapeutic management and differ in prognosis. The authors showed that lymphomas can be differentiated from high-grade gliomas by comparing CBV and CBF parameters using perfusion CT. Both histopathologic entities showed significantly higher permeability values compared with normal brain parenchyma, but only high-grade gliomas showed significantly higher values of regional CBV and CBF parameters than those of normal cerebral parenchyma (9). Low-grade gliomas exhibited no different perfusion parameters compared with normal parenchyma (9). Another important application of perfusion CT is the demarcation between normal tissue and tumor. Di Nallo et al. (1) performed a quantitative analysis of the perfusion CT maps of 22 patients with gliomas or metastases, demonstrating a significant predictive value of PS and Patlak Rsquare for differentiating between malignant and normal surrounding tissue. In patients with treated gliomas, perfusion CT appears to be particularly effective in differentiating recurrent or progressive tumor from treatment-induced necrosis (5, 7). In particular, recurrent tumors showed higher CBV and CBF and lower MTT compared with radiation necrosis (5). Also, PS is significantly increased in recurrent or progressive tumors (7).
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Using perfusion CT technique to evaluate meningiomas’ grading also appears to be of interest. Ren et al. (8) reported their experience in a group of 17 patients with extraaxial neoplasms studied by perfusion CT. The values of CBV and PS in parenchyma of hemangiopericytomas were significantly higher compared with benign meningiomas (8). Francesco Tomasello1, Concetta Alafaci1, Francesca Granata2 From the Departments of Neurosurgery1 and Neuroradiology2, University of Messina, Messina, Italy To whom correspondence should be addressed: Francesco Tomasello, M.D. [E-mail: [email protected]] Published online 4 May 2014; http://dx.doi.org/10.1016/j.wneu.2014.05.001.
REFERENCES 1. Di Nallo AM, Vidiri A, Marzi S, Mirri A, Fabi A, Carapella CM, Pace A, Crecco M: Quantitative analysis of CT-perfusion parameters in the evaluation of brain gliomas and metastases. J Exp Clin Cancer Res 28:38, 2009. 2. Ellika SK, Jain R, Patel SC, Scarpace L, Schultz LR, Rock JP, Mikkelsen T: Role of perfusion CT in glioma grading and comparison with conventional MR imaging features. AJNR Am J Neuroradiol 28:1981-1987, 2007. 3. Hoeffner EG, Case I, Jain R, Gujar SK, Shah GV, Deveikis JP, Carlos RC, Thompson BG, Harrigan MR, Mukherji SK: Cerebral perfusion CT: technique and clinical applications. Radiology 231:632-644, 2004. 4. Huang AP, Tsai JC, Kuo LT, Lee CW, Lai HS, Tsai LK, Huang SJ, Chen CM, Chen YS, Chuang HY, Wintermark M: Clinical application of perfusion computed tomography in neurosurgery. J Neurosurg 120:473-488, 2014. 5. Jain R: Perfusion CT imaging of brain tumors: an overview. AJNR Am J Neuroradiol 32:1570-1577, 2011. 6. Jain R, Gutierrez J, Narang J, Scarpace L, Schultz LR, Lemke N, Patel SC, Mikkelsen T, Rock JP: In vivo correlation of tumor blood volume and permeability with histologic and molecular angiogenic markers in gliomas. AJNR Am J Neuroradiol 32:388-394, 2011. 7. Jain R, Narang J, Schultz L, Scarpace L, Saksena S, Brown S, Rock JP, Rosenblum M, Gutierrez J, Mikkelsen T: Permeability estimates in histopathology-proved treatment-induced necrosis using perfusion CT: can these add to other perfusion parameters in differentiating from recurrent/progressive tumors? AJNR Am J Neuroradiol 32:658-663, 2011. 8. Ren G, Chen S, Wang Y, Zhu R, Geng D, Feng X: Quantitative evaluation of benign meningioma and hemangiopericytoma with peritumoral brain edema by 64-slice CT perfusion imaging. Chin Med J 123:2038-2044, 2010. 9. Schramm P, Xyda A, Klotz E, Tronnier V, Knauth M, Hatmann M: Dynamic CT-perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CSN lymphomas. Eur Radiol 20: 2482-2490, 2010. 10. Wintermark M, Sincic R, Sridhar D, Chien JD: Cerebral perfusion CT: technique and clinical applications. J Neuroradiol 35:253-260, 2008.
Can Excision of Meningiomas Be Limited to Resection of Tumor and Radiologically Abnormal Dura Mater? Neuronavigation-Guided Biopsies of Dural Tail and Seemingly Normal Dura Mater, with a Review of the Literature LETTER: account for almost 35% of all central nervous M eningiomas system tumors (7). Dural attachment with dural thickening in
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continuity with a meningioma may be seen on contrast-enhanced T1-weighted magnetic resonance imaging (MRI). In 1990, this dural thickening was described as the dural tail sign (DTS), with the following criteria: 1) presence on at least 2 consecutive slices through the tumor at the same site and in more than 1 imaging plane, 2) greatest thickness adjacent to the tumor and tapering away from it, and 3) enhancement greater than that of the tumor mass itself (9). With current imaging, because image slices tend to be
P
Using modern multidetector row CT, a small quantity of iodinated contrast medium is injected, and a limited number of CT sections are rapidly performed on the region of interest. In this way, the first “intravascular” passage of contrast medium is traced, many perfusion parameters can be evaluated, and quantitative maps are generated. A Patlak algorithm allows tracking of the progressive extravasation of contrast material out of the vessels into the interstitium, by mathematical comparison (deconvolution) of a parenchymal time-signal curve (where there is extravasation) and a reference arterial curve (where extravasation is assumed to be not significant) (2). Cerebral blood flow (CBF) (mL/100 g tissue/min), cerebral blood volume (CBV) (mL/100 g tissue), mean transit time (MMT seconds), and permeability surface area-product (PS) are the main available CT perfusion parameters. Perfusion CT has numerous advantages compared with perfusionweighted magnetic resonance imaging (MRI) (3, 10). The main advantage is the linear relation between density changes and tissue concentration of the contrast agent, such as to make reliable the quantification of perfusion CT parameters (3, 10). Other significant advantages of perfusion CT are the absence of susceptibility artifacts generated by hemorrhage or various mineral deposits, which can create diagnostic concerns on perfusion-weighted MRI examination, and the lack of sensitivity to flow and the high spatial resolution (3). Limitations of CT compared with MRI for evaluation of the microvasculature are the exposure to ionizing radiation, the potential risk for adverse reaction to the contrast agent, and the limited anatomic coverage (3). The radiation dose can be reduced to that of noncontrast head CT scan (2 mSV) through the use of appropriate technical parameters (80 kVp and 100 mAs); increased z-axis coverage can be obtained using a modern CT scanner, which offers whole-brain coverage, or by “toggling table” technique, in which the CT table moves back and forth alternating between 2 different locations (4). Perfusion techniques such as perfusion CT and perfusion-weighted MRI have been used primarily to assess cerebral ischemia;
Key words Brain tumors - Contrast enhancement - Perfusion computed tomography - Perfusion MRI - Tumour grading -
Abbreviations and Acronyms CBF: Cerebral blood flow CBV: Cerebral blood volume CT: Computed tomography MRI: Magnetic resonance imaging PS: Permeability surface area-product
WORLD NEUROSURGERY 82 [6]: e831ee844, DECEMBER 2014
however, the range of perfusion applications has progressively increased, including the diagnostic field of cerebral tumors. Conventional MRI provides important anatomic information, but it is insufficient to determine tumors’ grading preoperatively (2). Contrast enhancement on MRI depicts areas of blood-brain barrier breakdown, which is often associated with high-grade tumors; however, contrast enhancement is not always accurate in predicting tumors’ grading (2). Even in high-grade gliomas with pathologic contrast enhancement, the enhancement may not reflect the areas of neovascularity and angiogenesis. Malignant gliomas are characterized by neovascularity and increased angiogenic activity, with higher proportion of immature and hyperpermeable vessels (2, 10). For this reason, perfusion CT appears to be the ideal technique, for accuracy and speed, to obtain “in vivo” assessment of neoplastic grading. In a group of 23 patients with treatment-naïve gliomas, Jain et al. (6) demonstrated a significant positive correlation with microvessel density antigen (CD34), whereas PS showed a significant positive correlation with microvascular cellular proliferation, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels. Ellika et al. (2) demonstrated the usefulness of normalized perfusion CT parameters in assessing the grade of treatment-naïve gliomas comparing perfusion CT data with conventional MRI features (10). Perfusion CT was performed in 19 patients with gliomas (14 high-grade and 5 low-grade gliomas). For normalized CBV, the cut point of 1.92 was selected to identify high-grade tumors (85.7% sensitivity and 100% specificity); for normalized CBF, the cut point of 1.48 was selected to identify high-grade tumors (71.4% sensitivity and 100% specificity); and, finally, for normalized mean transit time, the cut point of 1.94 was selected to identify high-grade tumors (92.9% sensitivity and 40% specificity) (2). Schramm et al. (9) performed perfusion CT in 43 patients with a previous diagnosis of intraaxial brain tumor (4 low-grade gliomas, 31 glioblastomas, 8 intracerebral lymphomas) to identify elements capable of characterizing such lesions. Presurgical characterization appears to be crucial because high-grade gliomas and cerebral lymphomas require different therapeutic management and differ in prognosis. The authors showed that lymphomas can be differentiated from high-grade gliomas by comparing CBV and CBF parameters using perfusion CT. Both histopathologic entities showed significantly higher permeability values compared with normal brain parenchyma, but only high-grade gliomas showed significantly higher values of regional CBV and CBF parameters than those of normal cerebral parenchyma (9). Low-grade gliomas exhibited no different perfusion parameters compared with normal parenchyma (9). Another important application of perfusion CT is the demarcation between normal tissue and tumor. Di Nallo et al. (1) performed a quantitative analysis of the perfusion CT maps of 22 patients with gliomas or metastases, demonstrating a significant predictive value of PS and Patlak Rsquare for differentiating between malignant and normal surrounding tissue. In patients with treated gliomas, perfusion CT appears to be particularly effective in differentiating recurrent or progressive tumor from treatment-induced necrosis (5, 7). In particular, recurrent tumors showed higher CBV and CBF and lower MTT compared with radiation necrosis (5). Also, PS is significantly increased in recurrent or progressive tumors (7).
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e831
CORRESPONDENCE
Using perfusion CT technique to evaluate meningiomas’ grading also appears to be of interest. Ren et al. (8) reported their experience in a group of 17 patients with extraaxial neoplasms studied by perfusion CT. The values of CBV and PS in parenchyma of hemangiopericytomas were significantly higher compared with benign meningiomas (8). Francesco Tomasello1, Concetta Alafaci1, Francesca Granata2 From the Departments of Neurosurgery1 and Neuroradiology2, University of Messina, Messina, Italy To whom correspondence should be addressed: Francesco Tomasello, M.D. [E-mail: [email protected]] Published online 4 May 2014; http://dx.doi.org/10.1016/j.wneu.2014.05.001.
REFERENCES 1. Di Nallo AM, Vidiri A, Marzi S, Mirri A, Fabi A, Carapella CM, Pace A, Crecco M: Quantitative analysis of CT-perfusion parameters in the evaluation of brain gliomas and metastases. J Exp Clin Cancer Res 28:38, 2009. 2. Ellika SK, Jain R, Patel SC, Scarpace L, Schultz LR, Rock JP, Mikkelsen T: Role of perfusion CT in glioma grading and comparison with conventional MR imaging features. AJNR Am J Neuroradiol 28:1981-1987, 2007. 3. Hoeffner EG, Case I, Jain R, Gujar SK, Shah GV, Deveikis JP, Carlos RC, Thompson BG, Harrigan MR, Mukherji SK: Cerebral perfusion CT: technique and clinical applications. Radiology 231:632-644, 2004. 4. Huang AP, Tsai JC, Kuo LT, Lee CW, Lai HS, Tsai LK, Huang SJ, Chen CM, Chen YS, Chuang HY, Wintermark M: Clinical application of perfusion computed tomography in neurosurgery. J Neurosurg 120:473-488, 2014. 5. Jain R: Perfusion CT imaging of brain tumors: an overview. AJNR Am J Neuroradiol 32:1570-1577, 2011. 6. Jain R, Gutierrez J, Narang J, Scarpace L, Schultz LR, Lemke N, Patel SC, Mikkelsen T, Rock JP: In vivo correlation of tumor blood volume and permeability with histologic and molecular angiogenic markers in gliomas. AJNR Am J Neuroradiol 32:388-394, 2011. 7. Jain R, Narang J, Schultz L, Scarpace L, Saksena S, Brown S, Rock JP, Rosenblum M, Gutierrez J, Mikkelsen T: Permeability estimates in histopathology-proved treatment-induced necrosis using perfusion CT: can these add to other perfusion parameters in differentiating from recurrent/progressive tumors? AJNR Am J Neuroradiol 32:658-663, 2011. 8. Ren G, Chen S, Wang Y, Zhu R, Geng D, Feng X: Quantitative evaluation of benign meningioma and hemangiopericytoma with peritumoral brain edema by 64-slice CT perfusion imaging. Chin Med J 123:2038-2044, 2010. 9. Schramm P, Xyda A, Klotz E, Tronnier V, Knauth M, Hatmann M: Dynamic CT-perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CSN lymphomas. Eur Radiol 20: 2482-2490, 2010. 10. Wintermark M, Sincic R, Sridhar D, Chien JD: Cerebral perfusion CT: technique and clinical applications. J Neuroradiol 35:253-260, 2008.
Can Excision of Meningiomas Be Limited to Resection of Tumor and Radiologically Abnormal Dura Mater? Neuronavigation-Guided Biopsies of Dural Tail and Seemingly Normal Dura Mater, with a Review of the Literature LETTER: account for almost 35% of all central nervous M eningiomas system tumors (7). Dural attachment with dural thickening in
e832
www.SCIENCEDIRECT.com
continuity with a meningioma may be seen on contrast-enhanced T1-weighted magnetic resonance imaging (MRI). In 1990, this dural thickening was described as the dural tail sign (DTS), with the following criteria: 1) presence on at least 2 consecutive slices through the tumor at the same site and in more than 1 imaging plane, 2) greatest thickness adjacent to the tumor and tapering away from it, and 3) enhancement greater than that of the tumor mass itself (9). With current imaging, because image slices tend to be
