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Danish University Colleges Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches for the evaluation of blood flow and blood volume in human gliomas Thomsen, Henrik; Larsson, Elna-Marie; Steffensen, Elena Published in: Acta Radiologica Publication date: 2012 Document Version Pre-print Link to publication Citation for pulished version (APA): Thomsen, H., Larsson, E-M., & Steffensen, E. (2012). Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches for the evaluation of blood flow and blood volume in human gliomas. Acta Radiologica, 53, 95-101. 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May. 2017 Original article Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches for the evaluation of blood flow and blood volume in human gliomas H Thomsen1,2, E Steffensen3 and E-M Larsson3,4 1 Den Sundhedsfaglige Kandidatuddannelse, Aarhus Universitet Bygning 1264, Århus, Denmark; 2University College Nordjylland, Aalborg, Denmark; 3Aalborg Hospital/Aarhus University Hospital, Department of Radiology, Aalborg, Denmark; 4Uppsala University Hospital, Department of Radiology, Uppsala, Sweden Correspondence to: H Thomsen. Email: [email protected] Abstract Background: Perfusion magnetic resonance imaging (MRI) is increasingly used in the evaluation of brain tumors. Relative cerebral blood volume (rCBV) is usually obtained by dynamic susceptibility contrast (DSC) MRI using normal appearing white matter as reference region. The emerging perfusion technique arterial spin labelling (ASL) presently provides measurement only of cerebral blood flow (CBF), which has not been widely used in human brain tumor studies. Purpose: To assess if measurement of blood flow is comparable with measurement of blood volume in human biopsy-proven gliomas obtained by DSC-MRI using two different regions for normalization and two different measurement approaches. Material and Methods: Retrospective study of 61 patients with different types of gliomas examined with DSC perfusion MRI. Regions of interest (ROIs) were placed in tumor portions with maximum perfusion on rCBF and rCBV maps, with contralateral normal appearing white matter and cerebellum as reference regions. Larger ROIs were drawn for histogram analyses. The type and grade of the gliomas were obtained by histopathology. Statistical comparison was made between diffuse astrocytomas, anaplastic astrocytomas, and glioblastomas. Results: rCBF and rCBV measurements obtained with the maximum perfusion method were correlated when normalized to white matter (r ¼ 0.60) and to the cerebellum (r ¼ 0.49). Histogram analyses of rCBF and rCBV showed that mean and median values as well as skewness and peak position were correlated (0.61 , r , 0.93), whereas for kurtosis and peak height, the correlation coefficient was about 0.3 when comparing rCBF and rCBV values for the same reference region. Neither rCBF nor rCBV quantification provided a statistically significant difference between the three types of gliomas. However, both rCBF and rCBV tended to increase with tumor grade and to be lower in patients who had undergone resection/treatment. Conclusion: rCBF measurements normalized to white matter or cerebellum are comparable with the established rCBV measurements used for the clinical evaluation of cerebral gliomas. Keywords: MR imaging – modalities/techniques, MR diffusion/perfusion, brain/brain stem – structures, tissue characterization – topics Submitted May 8, 2011; accepted for publication October 24, 2011 In brain tumor evaluation, magnetic resonance dynamic susceptibility contrast imaging (DSC-MRI) is presently the most widely used MRI perfusion technique (1), allowing estimation of the cerebral perfusion in terms of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF). Visual evaluation of rCBV and rCBF maps can be supplemented by quantitative measurements of the perfusion values in regions of interest (ROI) placed in tumor tissue. Tumor type and malignancy grade are determined by histopathological investigation. Perfusion MRI allows quantitative characterization of gliomas and can potentially be a diagnostic alternative to histopathological examination, which is invasive Acta Radiologica 2012; 53: 95– 101. DOI: 10.1258/ar.2011.110242 96 H Thomsen et al. ................................................................................................................................................. and may not be possible to perform in some patients. A ROI-based maximum perfusion approach has been used in several studies to grade gliomas (2–4). Other studies have used histogram-based analyses, obtaining a larger number of the parameters characterizing the tumor region (5–7). Clinically established methods for quantitative perfusion measurements usually include normalization of the mean or maximum perfusion values in the tumor region in relation to mean values in normal appearing white matter. Normalized rCBV measurements are considered to be the clinical standard (8, 9). However, white matter is often affected by treatment and/or edema or may be invaded by diffuse tumor growth. When perfusion is measured with other techniques (e.g. O15-PET, SPECT, and arterial spin labelling [ASL] MRI) the cerebellum has often been used as a reference region (10 –12). These techniques measure CBF but usually not CBV. Thus the measurement of rCBF values by DSC-MRI perfusion in tumors with the cerebellum as a reference region needs to be evaluated (12). The aim of this study was to assess if measurement of blood flow is comparable with measurement of blood volume in human biopsy-proven gliomas obtained by DSC-MRI using two different regions for normalization and two different measurement approaches. Material and Methods Patients This is a retrospective study of patients with cerebral gliomas who had undergone DSC-MRI examination at the Department of Radiology of our hospital during the period October 1, 2006 to September 30, 2008. Seventy-five patients were enrolled in the study using the following inclusion criteria: the diagnosis was a cerebral glioma, DSC-MRI of the brain had been performed, and histopathological diagnosis based on tissue from needle biopsy or surgical resection had been obtained. Subsequently, 14 patients were later excluded because of technical reasons: artifacts in images and inadequate histopathological diagnoses. The final study population consisted of 61 patients, 31 men and 30 women. Twenty-three patients had DSC-MRI at baseline before the start of treatment and 38 patients after the start of treatment. Each patient was only assessed on one occasion in this study. The National Danish Board of Health and the Danish Data Protection Agency approved this study. MR imaging and postprocessing MRI protocol: MRI was performed on 3T and 1.5T systems (Signa HDx; GE Healthcare, Milwaukee, WI, USA) with morphological sequences (transverse T2-weighted fast spin echo [FSE], transverse T1-weighted fluid attenuated inversion recovery [FLAIR] before and after contrast injection, coronal T1-weighted spin echo [SE] after contrast injection), transverse diffusion-weighted imaging (DWI) and transverse DSC perfusion imaging. The DSC imaging was performed with a single-shot gradient echo planar imaging (EPI) sequence with TR/TE ¼ 1400/29 msec, matrix 128 128, acceleration factor ¼ 2, FOV 24 cm, slice thickness 5 mm with 1 mm inter-slice gap, 24 slices, scan time 1.5 min. Gadolinium-based contrast agent (Gadovist; Bayer Schering Pharma AG, Berlin, Germany), 0.1 mmol/kg, was injected intravenously at 5 mL/s. Postprocessing: rCBV and rCBF maps were calculated using an established tracer kinetic model applied to firstpass data (13, 14) (NordicIce NordicImagingLab, Bergen, Norway) (15). Deconvolution of the measured signal-time curves was performed using singular value decomposition with arterial input function of about 5 pixels retrieved from the middle cerebral artery branches in the hemisphere contra lateral to the tumor. Correction for contrast agent leakage in the tumor due to blood –brain barrier disruption was also included in the postprocessing (16). Quantitative image analysis Tumor tissue was identified on T1-weighted contrastenhanced images and/or T2-weighted images and simultaneously on the perfusion images. ROIs were placed in tumor tissue with maximum signal intensity on rCBF maps, and in normal-appearing white matter and cerebellum as reference regions. (Fig. 1). Care was taken to avoid edema and blood vessels by comparison with T2-weighted images at the corresponding slice positions. All ROIs were drawn by a technician and subsequently checked and corrected if needed by an MRI-physicist with experience in image postprocessing and an experienced neuroradiologist. In addition, ROIs representing a substantial part of the tumor for histogram analyses were drawn over three slices on rCBF maps. All ROIs was copied to rCBV images. The size of the ROIs varied from 0.25– 1.19 cm2 for the small ROIs and from 3.3 –86 cm2 for the large ROIs used for histogram analyses. For the histogram analyses, slices through the central largest portion of the tumor were chosen to minimize partial volume effects. Postoperative cavities were avoided, whereas central necrosis was included as a part of the large ROI for the histogram analyses when they were present on the slices with the most substantial part of the tumor. This method was chosen to keep the methodology of the histogram ROI drawing as simple and operator independent as possible (Fig. 1). Patients with small residual tumors after treatment (less than 3 cm2) were not included in the histogram analyses. In low grade gliomas, small ROIs were defined by the experienced radiologist according to the most prominent tumor signal on CBF images, whereas the large ROIs were drawn according to morphological MR images. The perfusion values of normal appearing white matter and cerebellum were used to obtain normalized maximum rCBF and rCBV calculated as ratios of mean perfusion values in tumor ROI with maximum perfusion to mean values in reference regions. Histograms were normalized to the total number of pixels in the ROIs and to the mean values in reference regions; the Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches 97 ................................................................................................................................................. Fig. 1 Example of the ROI placement on rCBF and rCBV maps together with T1-weighted post-contrast images for tumor delineation. The upper row depicts ROI placed in a region with maximum rCBF; the second row includes an example of the larger ROI drawing used for histogram analyses placed on rCBF images and reference ROIs for the cerebellum. The last row presents choice of the ROI for the reference regions number of histogram bins was 108 as proposed by Emblem et al. (7). The following histogram metrics were used for analyses: mean, median, standard deviation (SD), peak position (PP), peak height (PH), skewness, and kurtosis. Statistical analysis The analysis of results obtained with the maximum perfusion ROI approach included descriptive statistics, logarithmic transformation of data in cases of non-normal distribution, and one-way analysis of variance ANOVA. Stratification into groups of untreated and treated tumors and correlation analysis for CBF and CBV measurements were made to compare the influence of the choice of reference region on results assessed by maximum perfusion ROI approach and the histogram method. Results The histopathological diagnoses of the majority of the 61 gliomas investigated in our study were glioblastomas (n ¼ 38), diffuse astrocytomas (n ¼ 8), and anaplastic astrocytomas (n ¼ 8). Oligodendrogliomas, anaplastic oligodendrogliomas, and gangliogliomas were the smallest groups, the number of tumors being n ¼ 4, n ¼ 2, and n ¼ 1, respectively. Tumor types, WHO grades, number of patients, mean age of patients, rCBF, and rCBV values calculated with white matter tissue and cerebellum tissue as reference are summarized in Table 1. Table 1 shows higher perfusion values for glioblastoma than for diffuse and anaplastic astrocytomas. The results of comparison of median perfusion values for diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma are shown in Table 2. The stratified analysis of untreated and treated tumor groups did not show any statistically significant difference in perfusion values between these tumor groups; however, Table 2 shows lower values of rCBF and rCBV for tumors undergoing treatment. Figs. 2 and 3 illustrate the correlation between rCBF and rCBV measurements in the maximum enhancement perfusion tumor region for both reference ROIs in white matter and cerebellum (Pearson correlation coefficient r ¼ 0.60 and r ¼ 0.49, respectively). Mean values for histogram metrics for rCBF and rCBV measurements in tumor regions normalized to cerebellum and white matter for all tumors included in our study are presented in Table 3. Pearson correlation coefficients for comparison between rCBF and rCBV measurements with different normalization regions are shown in Table 4. 98 H Thomsen et al. ................................................................................................................................................. Table 1 Patients (n), age, and mean relative perfusion values obtained with maximum perfusion ROI approach for different tumor types Histopathological diagnosis Diffuse Astrocytoma WHO grade II Patients (n) 8 Age (mean years) (sd) 37.2 (9.6) White matter as reference tissue Mean rCBV (sd) 2.90 (1.47) Mean rCBF (sd) 5.08 (4.25) Cerebellum as reference tissue Mean rCBV (sd) 1.81 (1.29) Mean rCBF (sd) 2.51 (2.06) Anaplastic Astrosytoma Glioblastoma Oligodendroglioma Anaplastic Oligodendroglioma Ganglioglioma III 8 45.8 (13.8) IV 38 55.5 (12.7) II 4 55.1 (26.0) III 2 57.9 (16.7) I 1 41 3.73 (1.83) 4.53 (2.57) 6.35 (5.05) 6.72 (3.48) 3.65 (1.45) 4.10 (1.91) 7.97 (2.73) 7.66 (2.12) 4.72 3.51 2.79 (2.29) 2.21 (1.72) 2.99 (2.02) 2.70 (1.36) 2.62 (1.85) 2.03 (1.04) 3.24 (2.18) 2.64 (1.34) 1.78 1.23 Table 2 Medians for diffuse astrocytoma WHO II, anaplastic astrocytoma WHO III, and glioblastoma WHO IV divided into groups of untreated and treated patients All tumors WHO (n) White matter as reference tissue rCBV II 8 III 8 IV 38 rCBF II 8 III 8 IV 38 Cerebellum as reference tissue rCBV II 8 III 8 IV 38 rCBF II 8 III 8 IV 38 Untreated tumor Treated tumor Median (95% CI) (n) Median (95% CI) (n) Median (95% CI) 2.66 3.69 4.51 3.66 3.75 5.81 (1.39 –5.09) (1.93 –7.08) (3.34 –6.08) (2.28 –5.85) (2.34 –6.00) (4.68 –7.21) 2 4 12 2 4 12 4.40 4.13 5.75 9.71 3.89 6.90 (1.24 –15.65) (1.80 –9.46) (3.14 –10.52) (2.20 –42.80) (1.62 –9.33) (4.85 –9.81) 6 4 26 6 4 26 2.25 3.30 4.08 2.64 3.61 5.41 (1.08 – 4.67) (1.44 – 7.56) (2.78 – 6.01) (1.12 – 6.22) (1.51 – 8.67) (4.33 – 6.78) 1.39 2.19 2.17 1.69 1.68 2.34 (0.72 –2.70) (1.13 –4.24) (1.60 –2.94) (1.03 –2.77) (1.03 –2.76) (1.87 –2.94) 2 4 12 2 4 12 2.14 2.23 2.61 4.14 1.67 3.00 (0.49 –9.30) (0.86 –5.81) (1.46 –4.66) (0.79 –21.98) (0.57 –4.90) (2.16 –4.14) 6 4 26 6 4 26 1.21 2.16 1.99 1.25 1.70 2.10 (0.52 – 2.83) (0.83 – 5.58) (1.35 – 2.97) (0.18 – 3.25) (0.58 – 5.05) (1.68 – 2.61) The highest correlation was observed for mean values (histogram metric) with white matter as reference region (r ¼ 0.93); the lowest correlation was observed for kurtosis and peak height (r ¼ 0.3). Our study has shown that CBF measurements with cerebellum and normal-appearing white matter as reference region are correlated with the established rCBV measurements used for quantification of relative tumor perfusion. The correlation was slightly higher when normal-appearing white matter was used as reference region. Thereby methods that only provide CBF measurements, such as the increasingly used ASL perfusion technique, can potentially replace the DSC perfusion for evaluation of gliomas. ASL is useful particularly in patients with renal failure or previous adverse effects after injection of gadolinium-based contrast agents. Cerebellum has previously been used as Fig. 2 Scatterplot showing rCBF and rCBV in tumor tissue normalized to normal-appearing white matter in diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma. Pearson correlation coefficient is 0.60 Fig. 3 Scatterplot showing rCBF and rCBV in tumor tissue normalized to cerebellum in diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma. Pearson correlation coefficient is 0.49 Discussion Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches 99 ................................................................................................................................................. Table 3 Mean values and standard deviations in parentheses of histogram metrics for CBF and CBV analyses for all tumors in the study Median Mean SD Peak position Mean values (SD) of histogram metrics for CBF analyses in tumour with different reference regions White matter as reference region 2.38 (1.63) 3.00 (1.81) 2.55 (1.74) 1.61 (1.33) Cerebellum as reference region 0.93 (0.52) 1.17 (0.57) 0.99 (0.50) 0.65 (0.54) Mean values (SD) of histogram metrics for CBV analyses in tumor with different reference regions White matter as reference region 2.58 (1.93) 3.21 (2.14) 2.68 (1.58) 1.62 (1.73) Cerebellum as reference region 1.22 (0.72) 1.54 (0.80) 1.31 (0.70) 0.79 (0.76) reference region in a few studies (11, 12) when comparing CBF measurement assessed by different techniques. We did not find statistically significant differences between the perfusion parameters for the different tumor types: diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma. A comprehensive review of studies performed during the last 5 years showed that some studies found a statistically significant difference between tumor groups (2 – 4, 17, 18), and others did not (8, 19). The results of our study are in accordance with the theory of tumors: tumor development and angiogenesis showing increasing perfusion of tumor tissue with higher tumor grade (20 – 23). Table 2 shows that there is a trend towards increasing values for glioblastoma (WHO IV) in comparison with diffuse astrocytoma (WHO II), which is in agreement with other studies (18, 24). As seen from Table 5, several studies report higher values of rCBV in gliomas of high grade than gliomas of low grade (2 – 4, 17, 18, 24– 27). Normalized rCBV values in our study are in agreement with the values found in the literature (Tables 3 and 5). The stratified analysis of patients groups with untreated and treated tumors did not show any statistically significant difference between the two strata with our ROI methods. However, in general, lower median values were observed for rCBF and rCBV in the group with treated tumors. It can be seen from Fig. 2 that for the majority of tumors higher values of rCBF corresponded to higher values of rCBV for calculations performed using both reference regions. The Pearson correlation coefficient was r ¼ 0.60 in the case of normalization to white matter and r ¼ 0.49 when the cerebellum was used. The lower correlation coefficients observed in our study in comparison with r ¼ 0.65 in Jarnum et al. (12) and r ¼ 0.75 in Senturk et al. (28) can be explained by a more homogeneous tumor population in our study. We did not observe extremely high values for normalized perfusion using cerebellum as reference region. From our experience and taking into account the discussion above, it is difficult to recommend one of the investigated reference regions; both white matter and cerebellum Peak height Skewness Kurtosis 0.08 (0.04) 2.18 (0.95) 5.06 (5.65) 0.08 (0.03) 2.09 (0.84) 4.44 (4.35) can be used for relative measurements of perfusion values in cerebral gliomas. However, the white matter perfusion may potentially more often be affected by, for example, radiation therapy and tumor invasion than the cerebellum. In some of the patients, we have observed abnormally low values in the white matter compared with the rest of the patients resulting in higher rCBF values. The maximum perfusion ROI approach has been reported to have an ability to differentiate between different tumor types (2–4), but it also has been reported to suffer from observer bias (7). To increase reproducibility of the measurements, placement of up to four ROIs in different parts of the tumor has been proposed (5, 6). In our study, we have instead used three experts with technical, image postprocessing, and neuroradiological skills to agree on maximum perfusion tumor region on perfusion images to verify our ROI measurements. The histogram analysis method has been found to be less observer-dependent (5, 7), and we have used 108 bins for ROI histogram visualization and analyses, as recommended by Emblem et al. (7). Histogram metrics (mean, median, SD, and PP) were calculated for histograms normalized to both white matter and cerebellum. As skewness, PH, and kurtosis do not depend on choice of reference region, these parameters were calculated with only normalization to the total number of pixels. The mean values for histogram metrics obtained in our study are comparable with calculations performed by other groups. Emblem et al. (7) gives PH values from 0.07– 0.16 for high and low-grade gliomas, respectively; another study (29) shows values from 0.024 – 0.12, which is in good agreement with a PH of about 0.08 (Table 3) in our study. The mean values for median, mean, SD, and PP, as well as skewness, kurtosis, and PH can be found in, for example, Law et al. (5). While there is a good correspondence between median (from 1.14 + 0.49 to 2.72 +0.68, depending on tumor grade (5) versus 2.38 + 1.63 in our study), mean (from 1.24 + 0.47 to 2.83 + 0.68 (5) and 2.55 + 1.74 in our study), SD values (from 0.49 + 0.32 to 2.32 + 0.29 and 3.34 + 1.75 in our study), and PP (from Table 4 Pearson correlation coefficients for different histogram metrics for CBF and CBV analyses for all tumors presented in the study Median Mean SD Pearson correlation coefficients for rCBF versus rCBV White matter as reference region 0.91 0.93 0.88 Cerebellum as reference region 0.80 0.76 0.69 Pearson correlation coefficients for white matter versus cerebellum reference rCBF 0.82 0.79 0.80 rCBV 0.80 0.76 0.73 Calculation performed for histograms without normalization to reference region NC ¼ not calculated Peak position 0.76 0.72 region 0.90 0.90 Peak height Skewness Kurtosis 0.30 0.43 0.3 NC NC NC NC NC NC 100 H Thomsen et al. ................................................................................................................................................. Table 5 rCBV measurements in four studies with calculated weighted common estimates Reference/ study Gliomas of low grade Gliomas of high grade Hakyemez et al. (4) Fan et al. (26) Law et al. (5) Costanzo et al. (2) Hakyemez et al. (4) Fan et al. (26) Law et al. (5) Costanzo et al. (2) n rCBV estimate sd 11 1.69 0.51 0.15 42.29 71.47 7 31 11 1.09 1.51 2.00 0.26 0.64 1.50 0.10 0.11 0.45 103.55 75.68 4.89 112.87 114.28 9.78 26 5.76 3.35 0.66 2.32 13.34 8 31 25 3.27 5.54 4.30 1.54 2.37 1.20 0.54 0.43 0.24 3.37 5.52 17.36 11.03 30.58 74.65 se † ‡ w Estimate w Common estimate§ (95% CI) sdf common estimate sef common estimate†† 1.36 (1.23 –1.49) 0.86 0.07 4.54 (4.17 –4.9) 2.27 0.19 Given estimate from reference/study p se ¼ sd/ n w ¼ 1/se2 P P § Common estimate ¼ (Estimatei wi)/ (wi) p 2 2 2 2 sdf ¼ ((sd1 þ sd2 þ sd3 þ sd4)/4) p †† sef ¼ 1/ w1 þ w2 þ w3 þ w4 † ‡ 1.10 + 0.61 to 3.34 + 1.75 and 1.61 + 1.33 in our study), the remaining histogram metrics are difficult to compare due to the different number of histogram bins used. Due to a good correlation for rCBF and rCBV histogram metrics calculated with different reference regions (correlation coefficients 0.73 r 0.90, Table 4), we suggest that both reference ROIs can be used for histogram analyses of brain tumors. Low correlations for kurtosis, skewness, and PH parameters comparing unnormalized rCBF and rCBV measurements reflect the fact that rCBF and rCBV distributions in tumor have different shapes (Figs. 4 and 5). However, the typical differences in histogram shapes for CBV for different tumor types (5) are accompanied by differences in shapes for CBF measurements. Potentially, rCBF could be used in the same manner as rCBV to train radiologist to recognize histogram shape patterns for different tumors (7). The main limitation of our study is the relatively small number of samples, which contributes to the statistical uncertainty and could be the reason for the statistically nonsignificant results. This presumption is supported by the sample size calculation. Table 5 shows rCBV measurements in four studies with calculated weighted common estimates used for sample size calculations. Although DSC-MRI is in widespread clinical use, tumor studies with this technique often include a relatively small number of patients, from 10 to up to 92 patients (3, 5). Our study is based on clinical data collected during 2 years at our hospital. Since gliomas have a relatively low incidence (20), the number of patients was relatively small. The sample size calculations for this study estimated sample sizes between 20 and 75, and only the glioblastoma group met this requirement. To obtain a reasonable sample size, we have included both untreated and treated patients in our study. The sample size and inclusion of both treated and untreated patients was also the main reason for not performing statistical analyses for histograms Fig. 4 Example of CBV distribution for glioblastoma (in yellow) and anaplastic astrocytoma (in blue). CBV values are normalized to cerebellum Fig. 5 Example of CBF distribution for glioblastoma (in yellow) and anaplastic astrocytoma (in blue). CBF values for the same patients as in Fig.4 normalized to cerebellum Perfusion MRI (dynamic susceptibility contrast imaging) with different measurement approaches 101 ................................................................................................................................................. metrics and no attempts to provide classification based on visual inspection of histograms. Another limitation is the fact that our patients had been examined at two different field strengths. Field strength affects tissue characteristics and image quality. Improved quality of the calculated parametric perfusion maps may be seen at higher field strength due to higher signal-to-noise ratio. However, as we compared patients on the individual basis and used normalized values of CBF and CBV we could disregard the impact of this factor compared, for example, to inclusion of both treated and untreated patient in the study. In conclusion, rCBF values may be used as an alternative to rCBV values for MRI evaluation of perfusion in gliomas. Comparison of the results obtained with cerebellum and white matter as reference regions shows that the cerebellum can be used as a valid reference region for the calculation of relative perfusion values. Conflict of interest: None. REFERENCES 1 Lacerda S, Law M. Magnetic resonance perfusion and permeability imaging in brain tumors. Neuroimaging Clin N Am 2009;19:527– 57 2 Di Costanzo A, Pollice S, Trojsi F, et al. Role of perfusion-weighted imaging at 3 Tesla in the assessment of malignancy of cerebral gliomas. Radiol Med (Torino) 2008;113:134 –43 3 Rollin N, Guyotat J, Streichenberger N, et al. Clinical relevance of diffusion and perfusion magnetic resonance imaging in assessing intra-axial brain tumors. Neuroradiology 2006;48:150 –9 4 Hakyemez B, Erdogan C, Bolca N, et al. Evaluation of different cerebral mass lesions by perfusion-weighted MR imaging. J Magn Reson Imaging 2006;24:817 –24 5 Law M, Young R, Babb J, et al. Histogram analysis versus region of interest analysis of dynamic susceptibility contrast perfusion MR imaging data in the grading of cerebral gliomas. Am J Neuroradiol 2007;28:761 – 6 6 Young R, Babb J, Law M, et al. Comparison of region-of-interest analysis with three different histogram analysis methods in the determination of perfusion metrics in patients with brain gliomas. J Magn Reson Imaging 2007;26:1053 – 63 7 Emblem KE, Nedregaard B, Nome T, et al. Glioma grading by using histogram analysis of blood volume heterogeneity from MR-derived cerebral blood volume maps. Radiology 2008;247:808 – 17 8 Jenkinson MD, Smith TS, Joyce KA, et al. Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours. Neuroradiology 2006;48:703 –13 9 Zhang H, Rodiger LA, Shen T, et al. Preoperative subtyping of meningiomas by perfusion MR imaging. Neuroradiology 2008;50:835 –40 10 Carvalho PA, Schwartz RB, Alexander E 3rd, et al. Detection of recurrent gliomas with quantitative thallium-201/technetium-99m HMPAO single-photon emission computerized tomography. J Neurosurg 1992;77:565 –70 11 Arbab AS, Aoki S, Toyama K, et al. Brain perfusion measured by flow-sensitive alternating inversion recovery (FAIR) and dynamic susceptibility contrast-enhanced magnetic resonance imaging: comparison with nuclear medicine technique. Eur Radiol 2001;11:635 – 41 12 Jarnum H, Steffensen EG, Knutsson L, et al. Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial spin labeling and dynamic susceptibility contrast imaging. Neuroradiology 2010;52:307 –17 13 Ostergaard L, Weisskoff RM, Chesler DA, et al. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn Reson Med 1996;36:715 – 25 14 Rosen BR, Belliveau JW, Vevea JM, et al. Perfusion imaging with NMR contrast agents. Magn Reson Med 1990;14:249 –65 15 Wu O, Ostergaard L, Sorensen AG. Technical aspects of perfusion-weighted imaging. Neuroimaging Clin N Am 2005;15:623 –37, xi 16 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. Am J Neuroradiol 2006;27:859 –67 17 Cha S, Tihan T, Crawford F, et al. Differentiation of low-grade oligodendrogliomas from low-grade astrocytomas by using quantitative blood-volume measurements derived from dynamic susceptibility contrast-enhanced MR imaging. Am J Neuroradiol 2005;26:266 –73 18 Hakyemez B, Erdogan C, Ercan I, et al. High-grade and low-grade gliomas: differentiation by using perfusion MR imaging. Clin Radiol 2005;60:493 –502 19 Fayed N, Davila J, Medrano J, et al. Malignancy assessment of brain tumours with magnetic resonance spectroscopy and dynamic susceptibility contrast MRI. Eur J Radiol 2008;67:427 – 33 20 Louis DN, Ohgaki H, Wiestler OD, et al. WHO Classification of the Central Nervous System. 4th edn. Lyon: International Agency for Research on Cancer (IARC), 2007 21 Folkman J. Angiogenesis. Annu Rev Med 2006;57:1 –18 22 Naumov GN, Akslen LA, Folkman J. Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch. Cell Cycle 2006;5:1779 –87 23 Folkman J. Fundamental concepts of the angiogenic process. Curr Mol Med 2003;3:643 – 51 24 Cho SK, Na DG, Ryoo JW, et al. Perfusion MR imaging: clinical utility for the differential diagnosis of various brain tumors. Korean J Radiol 2002; 3:171 –9 25 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. Am J Roentgenol 2002;179:783 – 9 26 Knopp EA, Cha S, Johnson G, et al. Glial neoplasms: dynamic contrastenhanced T2 -weighted MR imaging. Radiology 1999;211:791 –8 27 Aronen HJ, Gazit IE, Louis DN, et al. Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. Radiology 1994;191:41 –51 28 Senturk S, Oguz KK, Cila A. Dynamic contrast-enhanced susceptibility-weighted perfusion imaging of intracranial tumors: a study using a 3T MR scanner. Diagn Interv Radiol 2009;15:3– 12 29 Emblem KE, Scheie D, Due-Tonnessen P, et al. Histogram analysis of MR imaging-derived cerebral blood volume maps: combined glioma grading and identification of low-grade oligodendroglial subtypes. Am J Neuroradiol 2008;29:1664 –70