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									                        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
                      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
                                   Introduction_2


• Language is left lateralized in
  92.5% of right-handed
  individuals (Knecht et al., 2000)




• 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)
                          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)
                       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, ….)
                            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
                       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
                                                 Degree of lesion overlap across all patients




  Patients and controls were
  strongly right-handed as
  determined by the Edinburgh
  Handedness Inventory test
  with a Laterality Index
  (L.I.) > 80 (Oldfield, 1971)
Tumors classification
                       LOCATION                       HISTOLOGY
          Anterior   Posterior   “In”   “Out”   High Grade   Low Grade

           n=22        n=17      n=9    n=30      n=22         n=17


Tumors were classified as:

•    “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

    The volume of the tumors was calculated in mm3 after a manual
    segmentation
fMRI                                                   Verb Generation Task




• 1.5 T SIEMENS and PHILIPS scanners
                                                                  pen


• 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
fcMRI_1
• The fcMRI was calculated using a seed-based method

• The time-course of the BOLD activity was extracted from each seed
  region of interest (ROI) after the regression of several nuisance
  variables, including task-evoked activity
  (Fox et al, 2005; Fair et al, 2006)




• 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_2

• 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)


• 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)
                             Results
fMRI
• Overall, patients presented a non-
  Only patients with high grade tumors
  significant significant reduction of
  showed a shift of language lateralization
  toward the non-dominant hemisphere
  language lateralization compared to
  compared to controls
  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
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
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
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
fcMRI_subgroups




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


• 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_3




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

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

								
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