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REORGANIZATION OF FUNCTIONAL CONNECTIVITY MRI IN PATIENTS WITH BRAIN TUMORS

XIX Symposium Neuroradiologicum The World Congress of Neuroradiology Bologna, Italy, 4-9 October 2010. REORGANIZATION OF FUNCTIONAL CONNECTIVITY MRI IN PATIENTS WITH BRAIN TUMORS. Briganti C, Pravatà E*, Mantini D, Sestieri C, Tartaro A, Caulo M

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REORGANIZATION OF FUNCTIONAL CONNECTIVITY MRI IN PATIENTS WITH BRAIN TUMORS

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  1. XIX Symposium Neuroradiologicum The World Congress of Neuroradiology Bologna, Italy, 4-9 October 2010 REORGANIZATION OF FUNCTIONAL CONNECTIVITY MRI IN PATIENTS WITH BRAIN TUMORS Briganti C,Pravatà E*, Mantini D, Sestieri C, Tartaro A, Caulo M Department of Neuroscience and Imaging. University “G. d’Annunzio” Chieti-Pescara - Italy * Department of Radiology, Catholic University - Rome - Italy

  2. Introduction_1 • Pre-surgical cortical brain mapping using functional MRI (fMRI) is a widely diffuse procedure permitting a non-invasive neurosurgical planning in patients with brain tumors • Due to the high social relevance of speech, the accurate mapping of the language functions in the brain and the identification of the dominant hemisphere are crucial for minimizing postoperative neurological deficits

  3. Languageis left lateralized in 92.5% of right-handed individuals (Knecht et al., 2000) Introduction_2 • Right-handed patients with left hemisphere brain tumors show an increased recruitment of homologue regions of the classical language areas in the right hemisphere (Plasticity) (Thiel et al., 2001; Desmurget et al, 2007)

  4. Introduction_3 • The leading roles of language production and comprehension are classically attributed to Broca’s and Wernicke’s cortical areas (Naeser et al, 1989) • More recently, a distributed dynamic model of language organization focuses on the importance of functional correlations between brain regions belonging to the language network (Vigneau et al, 2006)

  5. Introduction_4 • The functional correlation can be evaluated by functional connectivity MRI (fcMRI), a technique that measures the spontaneous and synchronous low-frequency (<0.1 Hz)fluctuations of the BOLD signal between distant brain regions (Biswal, 1995; Fox, 2005; Greicius, 2003) • These brain regions can be considered as a “network” with increased functional synchrony (default network, attention, motor system, language, ….)

  6. Purposes • To evaluate language lateralization in patients with a left hemisphere brain tumor using BOLD fMRI during a block-designed verb-generation task • To investigate potential differences in fcMRI within the language network between patients and controls • To explore variability of fcMRI correlated with the position, the histopathology and the volume of the tumors

  7. Degree of lesion overlap across all patients Subjects and Methods • 39 patients • (21 male and 18 female; mean age 51 ±14 years) with a pathologically confirmed brain glioma of the left hemisphere 13 healthy controls Patients and controls were strongly right-handed as determined by the Edinburgh Handedness Inventory test with a Laterality Index (L.I.) > 80 (Oldfield, 1971)

  8. “anterior” or “posterior” considering their position with respect to the anterior commissure • "in" or "out" depending on their distance from the left Broca and Wernicke areas • “low grade” or “high grade” on the basis of the latest WHO classification Tumors classification Tumors were classified as: The volume of the tumors was calculated in mm3 after a manual segmentation

  9. pen Verb Generation Task fMRI • 1.5 T SIEMENS and PHILIPS scanners • BOLD fMRI: block-designed verb-generation task • fMRI statistical activation maps were generated with a combined Independent Component Analysis – General Linear Model (ICA-GLM) method • The Lateralization Index (L.I.) was calculated for each subject using a formula for the correction of the tumor volume

  10. For each subject, an initial seed ROI was identified as the region with the strongest task-evoked activity within the pars opercolaris of the left inferior frontal gyrus (left Broca) fcMRI_1 • The fcMRI was calculated using a seed-based method • The time-course of the BOLD activitywas extracted from each seed regionof interest (ROI) after the regression of several nuisance variables, including task-evoked activity (Fox et al, 2005; Fair et al, 2006)

  11. Using the whole-brain fcMRI map generated from this ROI, 5 additional seed regions were obtained corresponding to: right Broca area and bilateral Superior Temporal Sulcus (STS) and Temporo-Parietal Junction (TPJ) fcMRI_2 • Pearson’s correlation coefficients(r)between signal time-courses were calculated: • between each seed region and all the voxels of the brain (Whole-Brain FC maps) • between pairs of seed regions (Cross-correlation Matrices and Plots)

  12. Only patients with high grade tumors showed a significant reduction of language lateralization compared to controls(p< 0.05) • The size of the tumors was negatively correlated with lateralization index, so that patients with larger tumors were less left-lateralized Results fMRI • Overall, patients presented a non-significant shift of language lateralization toward the non-dominant hemisphere compared to controls

  13. fcMRI Cross-correlation matrices and plots_1 • In cross-correlation matrices and plots, both patients and controls showed significant functional correlations between all the 6 seed regions • However, patients showed a significant reduction of the fcMRI among the language network (p < 0.01) compared to controls

  14. fcMRI Cross-correlation matrices and plots_2 • The contrast between the functional connectivity of patients and controls demonstrates that the left TPJ is the node showing the greatest reduction of fcMRI

  15. fcMRI • Considering the averaged values of fcMRI in the two hemispheres, patients show a significant reduction of connectivity (p < 0.01) in: • Averaged Left intra-hemispheric fcMRI • Averaged Inter-hemispheric fcMRI • Global fcMRI

  16. fcMRI_subgroups Using a multivariated ANOVA, patients with a posteriortumor showed a significantly greater reduction of the left intra-hemispheric fcMRI compared to patients with an anterior tumor (p <0.05)

  17. Conclusion_1 • Tumor patients present a significant reorganization of the language towards the non-dominant hemisphere • The presence of a brain tumor in the left hemisphere significantly reduces the fcMRI between language-related brain regions, especially when posterior • Modification of the fcMRI is not restricted to the area surrounding the tumor; remote and controlateral areas are also influenced

  18. These findings reinforce the results of some theoretical lesional models (Alstott, 2009) demonstrating that lesion placed in proximity of hub nodes of high centrality, as the TPJ, determine greater changes of FC Conclusion_2 • Tumors located near the TPJ determine the strongest reduction of the fcMRI, demonstrating the central role of the Wernicke area in the language network

  19. Conclusion_3 • The presence of a brain tumor in the left hemisphere determines a cortical and networking reorganization of the language function

  20. Acknowledgments Massimo Caulo MD, PhD Emanuele Pravatà MD Carlo Sestieri PhD Dante Mantini PhD Armando Tartaro MD

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