Perfusion CT and perfusion MRI combined study in patients treated for glioblastoma multiforme: a pilot study

Transcription

1 Perfusion CT and perfusion MRI combined study in patients treated for glioblastoma multiforme: a pilot study Poster No.: C-0789 Congress: ECR 2012 Type: Scientific Paper Authors: P. AMATUZZO, S. Zizzari, F. Fabbiano, M. Peveroni, G. Chiarelli, A. Cassarà, M. Krengli, A. Stecco, A. Carriero; Novara/IT Keywords: Neuroradiology brain, CT, MR-Diffusion/Perfusion, Diagnostic procedure, Neoplasia DOI: /ecr2012/C-0789 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 17

2 Purpose High grade gliomas are extremely aggressive and it is important to quantify angiogenesis and neoangiogenesis in order to assess the grade and predict their ability to growth and diffusion. Microvascular density and increased vascular permeability have been associated with tumour grading: greater vascular permeability is associated with a higher grade tumours. Computed Tomography (CT) and Magnetic Resonance (MR) advanced techniques, such as perfusion imaging, are now widely used to characterise brain tumours, and to predict the transformation and recurrence of gliomas. The purposes of this study are: - to compare the diagnostic capacity of Perfusion CT (PCT) and Perfusion-Weighted Imaging MR (PWI-MR) in predicting the tumoral infiltration of brain tissue in patients with surgically treated glioblastoma - to assess the accuracy of the parameter Cerebral Blood Volume (CBV) obtained with PCT and PWI-MR colour-map and correlate these results with the two techniques of imaging. Methods and Materials Subjects Between May 2009 and December 2010, we enrolled five patients with a mean age of 60 years surgically treated, and with adjuvant radio- and chemotherapy, for WHO grade IV Central Nervous System glioma (glioblastoma multiforme). Their Eastern Cooperative Oncology Group (ECOG) performance status was < 3 and they were not clinically compromised. This study was approved by our Institutional Review Board, and all of the patients gave their informed consent. Technique: CT perfusion imaging PCT was performed using a 64-detector-row scanners. A non-contrast enhanced CT head scan was used to localise the Region of Interest (RoI) before obtaining a perfusion scan, for which 50 ml of non-ionic contrast (370 mgi/ml) Page 2 of 17

3 was injected at a rate of 4 ml/s through a 20G intravenous line. Five seconds after the injection, a continuous CINE scan was started using the following parameters: 80 kvp, 100 mas and 1 second/rotation for a duration of 45 seconds. In post-processing, on a specific workstation with a software of perfusion analysis, CBV colour-coded maps were generated, sampling the artery with the greatest peak and slope on time-attenuation curves, as the arterial input function, and the superior sagittal sinus, as the output venous function (Figure 1). None of the patients experienced any adverse reaction to the contrast medium. Technique: PWI-MR Perfusion MR pulses were acquired by a superconductive magnet, operating at 1.5 Tesla (T) with updated gradients. DSCE (Dynamic Susceptibility Contrast-Enhanced) - PWI has been performed using a gradient-echo T2* pulse acquired dynamically during contrast medium injection (Gadolinium 0,5 molar) at a dose of 20 ml and at a rate of 5 ml/sec with a 20 Gauge intravenous line positioned in an antecubital vein. PWI raw data were analyzed by mean of a software of neuro-perfusion analysis calculating the CBV colour map by using the Arterial Input Funcion (AIF), sampling the Middle Cerebral Artery (MCA) to localise RoIs (Figure 2). None of the patients experienced any adverse reaction to the contrast medium. Image analysis The patients underwent CT and MR (before and after contrast medium injection) one month after surgery (time T0, baseline) and then every three months after radiotherapy until tumour recurrence (time T1), defined as an increase in the area of residual enhancement or as the appearance of nodular or diffuse enhancement on the resection margins. In post-processing data were analyzed on two separate workstations for CT and MR by using specific softwares of perfusion analysis. The retrospective RoI-based analysis was conducted by two expert radiologists in consensus. Starting with the examination performed at time T1 (when tumour recurrence occurs), the radiologists manually drew two groups of RoI for CBV data set as summarized below (Figures 3,4) on both CT and MR images: Page 3 of 17

4 - one on the solid enhancing tumoral area (ENH) as seen in CT and MR T1-weighted images, - the second on the corresponding area on controlateral hemisphere (ENH-CL) by mean of a mirroring system. Similar measurements were repeated at time T0 retrospectively (after surgery and before radiotherapy) on the same corresponding areas in all patients in the normal appearing cerebral tissue (Figures 5,6). Two separate RoI measurements were obtained and the maximum value was recorded (Tables 1, 2 and figure 7). Statistical analysis We conducted a work with preliminary results in order to carry out a further study with a more statistically significant number of patients, designed on the findings of our pilot analysis. Data were analyzed with three independent statistical tests. - The T-student test was performed at a P value < 0,05. - Pearson and Spearman tests were applied in order to verify the correlation between PCT and PWI-MR. The statistical data obtained with these independent tests were compared with each other in order to assess the statistically appropriate information. Images for this section: Page 4 of 17

5 Fig. 1: Generation of CBV colour-map sampling the artery and the vein with the greatest peak and slope on time-attenuation curves. Page 5 of 17

6 Fig. 2: CBV colour-map calculated with the Arterial Input Function to localise RoIs. Page 6 of 17

7 Fig. 3: CT image at T1 after contrast medium and the corresponding CBV colour-map with two RoIs (ENH and ENH-CL). In the image after contrast medium the red arrow shows the enhancing tumoral lesion (recurrence); on the CBV map the RoIs were positioned on the recurrence (3) ENH and on the controlateral side (4) ENH-CL. Fig. 4: MR image T1-weighted after contrast medium at time T1 and the corresponding CBV colour-map with two RoIs (ENH and ENH-CL). In the dynamic image the red Page 7 of 17

8 arrow shows the enhancing tumoral lesion (recurrence); the RoIs were positioned on the recurrence (pink) ENH and on the controlateral side (white) ENH-CL in order to register CBV values. Fig. 5: CT image at T0 after contrast medium and the corresponding CBV colour-map with two RoIs (ENH and ENH-CL). In the image after contrast medium the red arrow shows the margin of resection; on the CBV map the RoIs were positioned on these margins (3) ENH and on the corresponding area on the controlateral side (4) ENH-CL. Page 8 of 17

9 Fig. 6: MR image T1-weighted after contrast medium at time T0 and the corresponding CBV colour-map with two RoIs (ENH and ENH-CL).In the dynamic image the red arrow shows the margins of resection; the RoIs were positioned on these margins (pink) ENH and on the corresponding area on the controlateral side (white) ENH-CL in order to register CBV values. Table 1: Values of CBV measured in the RoIs (PCT) at time T0 and T1. Page 9 of 17

10 Table 2: Values of CBV measured in the RoIs (PWI-MR) at time T0 and T1. Page 10 of 17

11 Fig. 7: Representation of CBV values at time T1 and T0 for all patients with a bar graphic. Page 11 of 17

12 Results - T- Student test shows that, in the comparison between PCT and PWI-MR, there are no statistically significant differences at time T0 (p = 0,802) while at time T1 there is a slight difference between the two techniques of imaging (p = 0,045) (Table 3). - Pearson and Spearman test show a positive correlation between the two methods with regard to the CBV values at time T1 (Pearson correlation=0,887 and Spearman correlation=0,900) (Tables 4,5), while there is no correlation at time T0 (Pearson correlation=-0,156 and Spearman correlation=0) (Tables 6,7) - the correlation tests show a greater sensitivity of PWI-MR technique compared to PCT, relative to CBV parameter at time T1 (1,388 Vs 1,207) (Table 4). Images for this section: Table 3: T-Student test at time T1 and T0. Page 12 of 17

13 Table 4: Pearson test at time T1 for CBV values (PCT and PWI-MR). Sig.= Statistical Significance Table 5: Spearman test at time T1 for CBV values (PCT and PWI-MR). Sig.= Statistical Significance Page 13 of 17

14 Table 6: Pearson test at time T0 for CBV values (PCT and PWI-MR). Sig.= Statistical Significance Page 14 of 17

15 Table 7: Spearman test at time T0 for CBV values (PCT and PWI-MR). Sig.= Statistical Significance Page 15 of 17

16 Conclusion 1. The comparison of the different statistical tests applied demonstrates that the parameter CBV does not substantially differ with the two techniques of perfusion analysis. 2. Our results show a positive correlation at time T1 which instead cannot be demonstrated at time T0. 3. PWI-MR seems relatively more effective than PCT in the identification of changes in CBV parameter. 4. The correlation between the two methods at time T1 appears retrospectively statistical significant of the internal comparability among the five subjects evaluated. Preliminary results from our pilot study suggests the need to make some changes to the original design of the study. This could consist in the assumption of a different T0 (chronometric or clinical aspect to be defined) to no more than one month after surgery, when there are still changes in vascular bed related to recent surgery and likely to affect the value of the parameter CBV, but, for example, when surgical stabilization occurred after radiation treatment. References Schramm P, Xyda A, Klotz E, et al. Dynamic CT perfusion imaging of intraaxial brain tumours: differentiation of high grade gliomas from primary CNS lymphomas. Eur Radiol 2010; 20: Stecco A, Pisani C, Quarta R, et al. DTI and PWI analysis of peri-enhancing tumoral brain tissue in patients treated for glioblastoma. J Neurooncol 2011; 102: Gossmann A, Okuhata Y, Shames DM, et al. Prostrate cancer tumour grade differentiation by dynamic contrast enhanced MR imaging in the cat: comparison of macromolecular and small-molecular contrast media preliminary experience. Radiology 1999; 213: Yuan F, Salehi HA, Boucher Y, et al. Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. Cancer Res 1994; 54: Pham CD, Roberts TP, Van Bruggen N, et al. Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor. Cancer Invest 1998; 16: Page 16 of 17

17 6. Cianfoni A, Colosimo C, Basile M, et al. Brain Perfusion CT: principles, technique and clinical applications. Radiol Med 2007 ; 112 : Cao Y, Shen Z, Chenevert TL, et al. Estimate of vascular permeability and cerebral blood volume using Gd DTPA contrast enhancement and dynamic T2*-weighted MRI. J Magn Reson Imaging 2006; 24: Rizzo L, Crasto SG, Moruno PG, et al. Role of diffusion and perfusion weighted MR imaging for brain tumour characterisation. Radiol Med 2009; 114(4): Law M, Young RJ, Babb JS, et al. Gliomas: Predicting Time to Progression or Survival with Cerebral Blood Volume Measurements at Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging. Radiology 2008; 247 (2): Oken M.M., Creech R.H.,TormeyD.C., Horton, J.,Davis, T.E., McFadden, E.T., Carbone, P.P. Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: Personal Information Page 17 of 17