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Invited bizzi


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Invited bizzi

  1. 1. Pearls and Pitfalls of MR Diffusion in Clinical NeurologyDr.  Alberto  Bizzi  Neuroradiology  Unit  Fondazione  IRCCS  Istituto  Neurologico  Carlo  Besta  Milan,  Italy  Email:   Diffusion   Tensor   Imaging   (DTI)(1)   measures   the   effects   of   tissue  microstructure   on   the   random   walks   (brownian   motion)   of   water   molecules   in  the   brain.   In   tissues   with   an   orderly   oriented   microstructure,   such   as   the  cerebral  white  matter,  the  measured  diffusivity  of  water  varies  with  the  tissue’s  orientation   (anisotropic   diffusion).   Water   diffuses   fastest   along   the   principal  direction   of   the   fibers,   and   slowest   along   the   cross-­‐sectional   plane.   The   DTI  model   provides   the   required   information   to   construct   a   diffusion   ellipsoid   in  each   voxel   of   an   imaging   volume.   DTI   measures   the   diffusivities   of   water  molecules   along   the   three   orthogonal   axes   of   the   ellipsoid   (eigenvalues)   and  their   average   (mean   diffusivity).   Fractional   anisotropy   is   a   measure   of  eccentricity  of  the  displacement  of  water  molecules.  In  the  healthy  human  brain  probably  the  most  relevant  factor  affecting  fractional  anisotropy  is  the  intravoxel  orientation  coherence  of  white  matter  fibers(2).   There   are   three   main   imaging   output   of   DTI   MR   imaging:   quantitative  parametric  maps  displayed  in  gray  scale  (i.e.  fractional  anisotropy  maps),  color  maps   showing   the   principal   orientation   of   diffusion   for   each   voxel   and   3  dimensional  maps  showing  virtual  dissection  of  tracts  with  streamline  tracking  methods.   In   the   interest   of   time   in   the   oral   presentation   we’ll   focus   on   diffusion  MR   Tractography   and   its   clinical   application   in   brain   tumors,   stroke,   multiple  sclerosis,   prion   disorders   and   neurodegenerative   diseases   (Alzheimer,  Amyotrophic  Lateral  Sclerosis).  The  aim  of  MR  Tractography  or  fiber  tracking  is  to   infer   the   three-­‐dimensional   trajectories   of   white   matter   bundles   by   piecing  
  2. 2. together   discrete   estimates   of   the   underlying   continuous   fiber   orientation   field  measured  non-­‐invasively  with  DTI  data(3,  4).     Fiber   tracking   algorithms   can   be   broadly   classified   into   two   types:  deterministic  and  probabilistic.  Few  DTI  Tractography  atlases  for  virtual  in  vivo  dissection   of   the   principal   human   white   matter   tracts   using   a   deterministic  approach   have   been   recently   published(5-­‐7).   Few   limitations   of   fiber   tracking  performed   with   the   deterministic   approach   motivated   the   development   of  probabilistic  tracking  algorithms(5).  It  is  very  important  to  understand  well  the  inherent   limitations   of   all   methods   of   DTI-­‐based   virtual   dissections   and  measurements.  One  important  limitation  is  that  in  each  voxel  the  eigen  vector  is  the  average  of  the  orientation  of  all  bundles  included  in  the  voxel.  In  volumes  of  white   matter   with   many   crossing   bundles,   as   in   the   frontal   and   parietal  paraventricular   white   matter,   fractional   anisotropy   is   low   and   the   degree   of  uncertainty  in  the  estimation  of  bundle  orientation  increases.  An   attempt   to   overcome   the   limitation   of   crossing   fibers   has   been   addressed  with  the  development  of  more  sophisticated  imaging  acquisition  schemes  using  high  angular  resolution  diffusion  imaging  (HARDI)(6).   It   is   important   to   emphasize   that,   given   the   relative   size   differences  between   the   individual   axons   (1–5   micron)   and   voxels   (2–3   mm)   size,   it   is  possible  to  observe  white  matter  anatomy  only  from  a  macroscopic  point  of  view  with   MR   Tractography.   Notwithstanding,   the   anatomic   detail   provided   by   MR  Tractography  with  10-­‐15  min  of  MR  acquisition  is  unparalleled.   Encouraging  results  with  DTI  have  been  reported  in  several  neurological  disorders:   brain   tumors,   stroke,   multiple   sclerosis,   amyotrophic   lateral   sclerosis,  Alzheimer   disease   and   other   dementias.   In   the   interest   of   time   we’ll   focus   on   the  application   that   is   probably   closer   to   become   of   clinical   use:   diffusion   MR  Tractography  in  presurgical  planning.   The   integration   of   functional   data   acquired   with   fMRI   and   MEG   into   the  navigational  data  sets  has  improved  quick  identification  of  eloquent  cortex  with  intraoperative   ESM   in   the   operating   room.   To   avoid   postoperative   neurological  deficits,   however,   it   is   also   necessary   to   preserve   the   white   matter   tracts  connecting  eloquent  cortex.  
  3. 3. Diffusion   MR   Tractography  has  recently  emerged  as  potentially  valuable  clinical   tool   for   presurgical   planning(7-­‐9)   and   intraoperative   imaging-­‐guided  navigation   in   the   operating   room(10).   Diffusion   MR   Tractography   can   provide  the   neurosurgeon   with   additional   information   about   brain   anatomy,   pathology  and  architecture  that  conventional  MRI  methods  cannot.      Fig.   1   -­‐   Directionally   encoded   color   maps   in   a   65   years   old   male   with  glioblastoma  multiforme  in  the  left  dorsolateral  prefrontal  region.  The  mass  has  infiltrated   the   superior   longitudinal   fasciculus,   including   the   arcuate   fasciculus  (displayed  in  green,  see  cursor).     The   directionally   encoded   color   maps,   with   hues   reflecting   tensor  orientation   and   intensity   weighted   by   fractional   anisotropy,   provides   an  aesthetic   and   informative   synthesis   of   tissue   microstructure   and   architecture.  The   color   maps   are   a   promising   tool   for   delineation   of   tumor   extent   and  infiltration.  DTI  color  maps  indicate  whether  a  mass  is  displacing,  infiltrating  or  destroying   the   main   white   matter   tracts(11).   MR   Tractography   can   be   used   to  virtually   dissect   functionally   critical   white   matter   tracts,   such   as   the  corticospinal   tract   and   the   arcuate   fasciculus   (AF),   enabling   the   neurosurgeon   to  identify  and  preserve  the  tract  during  resection(12).   It  has  been  shown  that  acquisition  of  DTI  color  maps  is  feasible  also  in  the  operating  room  with  intraoperative  1.5  Tesla  MR  scanners.  Intraoperative  DTI  can   depict   shifting   of   major   white   matter   tracts   that   may   occur   during   surgical  removal  of  the  mass.  It  has  been  shown  that  shifting  of  brain  structures  may  be  
  4. 4. unpredictable,   therefore   intraoperative   updating   of   the   navigation   system   is  strongly  recommended(10).      Fig.  2  –  Streamlines  of  the  three  segments  of  the  left  arcuate  fasciculus  (AF:  long  segment   in   red,   anterior   in   green,   posterior   in   yellow)   are   displied   on   the  diffusion-­‐weighted   image   at   the   level   of   a   mass   in   the   left   posterior   mesial  temporal  lobe.  In   this   70   years-­‐old   male   with   glioblastoma   multiforme,   MR   Tractography   was  essential   to   demonstrate   that   the   mass   had   not   destroyed   but   only   displaced   the  AF   posteriorly   and   laterally.     Streamlines   of   the   AF   confirmed   that   most   of   the  fasciculus  was  intact.     Three   dimensional   objects   of   preoperative   virtually   dissected   tracts   can  be   reliably   integrated   into   a   standard   neuronavigation   system,   allowing   for  intraoperative   visualization   and   localization   of   the   main   tracts(13).   MR  Tractography   may   show   the   relationship   of   the   mass   to   the   virtually   dissected  AF.   Virtual   dissection   of   the   three   segments   of   the   AF   may   show   whether   the  mass   has   partially   interrupted   or   only   displaced   each   of   the   three   segments   of  the  AF.  Display  of  MR  Tractography  results  may  also  be  useful  in  the  operating  room   when   the   neurosurgeon   is   approaching   an   important   bundle   and   he   wants  to   reinforce   his   anatomical   orientation   in   the   operating   field   and   consider  
  5. 5. whether   to   use   subcortical   ESM   to   test   the   functional   relevance   of   a   specific  tract(14).      Fig.  3  –  Streamlines  of  the  left  inferior  frontal  occipital  fasciculus  (IFOF)  and  fMRI  (sentence   comprehension   task)   are   overlaid   on   FLAIR   images,   neuronavigator-­‐ready  for  guiding  surgery  in  the  operating  room.  In   this   62   years-­‐old   woman   with   fibrillary   astrocytoma   in   the   left   temporal   pole,  MR   Tractography   demonstrated   that   the   mass   had   partially   interrupted   the  uncinate  fasciculus  (UF,  not  shown),  while  the  IFOF  (in  pink)  appears  intact.  Note  the  close  relationship  of  the  left  IFOF  with  the  hyperintense  mass  in  the  temporal  pole.     Modern   cognitive   models   of   language   have   shown   that   there   is   a   lot   of  redundancy   in   the   language   network.   It   is   of   paramount   importance   to   identify  those  bundles  that  if  severed  may  cause  permanent  language  deficits.  Definition  of   which   bundles   are   functionally   eloquent   and   have   to   be   absolutely   spared  during  resection  remains  an  important  issue.   There  is  a  long  list  of  important  limitations(15).  Few  are  inherent  to  the  DTI   and   the   MR   Tractography   technology   and   they   must   be   well   understood  
  6. 6. before   the   results   of   presurgical   MR   Tractography   dissections   can   be   safely  exported   to   the   operating   room.   It   is   not   yet   established   whether   resection   of  fibers   apparently   infiltrated   by   the   tumor   that   appear   to   be   interrupted   or  destroyed  on  diffusion  MR  Tractography  will  result  in  permanent  postoperative  neurologic   deficits(15).   Nevertheless,   it   should   be   established   whether   resection  of  fibers  that  on  MR  Tractography  appear  to  be  interrupted  within  the  tumor  will  cause   permanent   postoperative   deficits.   On   the   contrary,   it   has   been   shown  many   times   that   severing   of   the   pyramidal   tract   will   cause   hemiplegia.     Whether  severing  of  one  of  the  many  language  connections  will  cause  aphasia  is  currently  a  controversial  issue(16).     In  conclusion,  diffusion  MR  Tractography  has  emerged  as  a  valuable  tool  in   the   evaluation   of   motor   and   language   pathways   both   in   healthy   individuals  and   in   patients   with   neurological   disorders.   In   healthy   subjects   they   are  contributing  to  refine  current  cognitive  and  anatomic  models.  Not  only  they  have  confirmed  several  theories  about  language  processing,  but  they  have  also  raised  unexpected   important   questions.   In   patients   with   brain   tumors   they   have  obtained  recognition  as  valuable  presurgical  clinical  tools  in  the  determination  of  hemispheric  dominance  and  in  the  selection  of  candidates  who  may  benefit  from  awake  craniotomy.    
  7. 7. References    1.   Basser  PJ,  Mattiello  J,  LeBihan  D.  MR  diffusion  tensor  spectroscopy  and  imaging.  Biophys   J  1994;  66:259-­‐267.  2.   Pierpaoli  C,  Jezzard  P,  Basser  PJ,  Barnett  A,  Di  Chiro  G.  Diffusion  tensor  MR  imaging  of   the  human  brain.  Radiology  1996;  201:637-­‐648.  3.   Conturo  TE,  Lori  NF,  Cull  TS,  et  al.  Tracking  neuronal  fiber  pathways  in  the  living  human   brain.  Proc  Natl  Acad  Sci  U  S  A  1999;  96:10422-­‐10427.  4.   Mori  S,  Crain  BJ,  Chacko  VP,  van  Zijl  PC.  Three-­‐dimensional  tracking  of  axonal  projections   in  the  brain  by  magnetic  resonance  imaging.  Ann  Neurol  1999;  45:265-­‐269.  5.   Jones  DK.  Studying  connections  in  the  living  human  brain  with  diffusion  MRI.  Cortex   2008;  44:936-­‐952.  6.   Seunarine  KK,  Alexander  DC.  Multiple  Fibers:  Beyond  the  Diffusion  Tensor.  In:  Johansen-­‐ Berg  H,  Behrens  TE,  eds.  Diffusion  MRI:  From  Quantitative  Measurement  to  in  Vivo   Neuroanatomy.  Oxford,  U.K.:  Elsevier,  2009;  55-­‐72.  7.   Clark  CA,  Barrick  TR,  Murphy  MM,  Bell  BA.  White  matter  fiber  tracking  in  patients  with   space-­‐occupying  lesions  of  the  brain:  a  new  technique  for  neurosurgical  planning?   Neuroimage  2003;  20:1601-­‐1608.  8.   Field  AS,  Alexander  AL,  Wu  YC,  Hasan  KM,  Witwer  B,  Badie  B.  Diffusion  tensor   eigenvector  directional  color  imaging  patterns  in  the  evaluation  of  cerebral  white  matter   tracts  altered  by  tumor.  J  Magn  Reson  Imaging  2004;  20:555-­‐562.  9.   Mori  S,  Frederiksen  K,  van  Zijl  PC,  et  al.  Brain  white  matter  anatomy  of  tumor  patients   evaluated  with  diffusion  tensor  imaging.  Ann  Neurol  2002;  51:377-­‐380.  10.   Nimsky  C,  Ganslandt  O,  Hastreiter  P,  et  al.  Intraoperative  diffusion-­‐tensor  MR  imaging:   shifting  of  white  matter  tracts  during  neurosurgical  procedures-­‐-­‐initial  experience.   Radiology  2005;  234:218-­‐225.  11.   Jellison  BJ,  Field  AS,  Medow  J,  Lazar  M,  Salamat  MS,  Alexander  AL.  Diffusion  tensor   imaging  of  cerebral  white  matter:  a  pictorial  review  of  physics,  fiber  tract  anatomy,  and   tumor  imaging  patterns.  AJNR  Am  J  Neuroradiol  2004;  25:356-­‐369.  12.   Laundre  BJ,  Jellison  BJ,  Badie  B,  Alexander  AL,  Field  AS.  Diffusion  tensor  imaging  of  the   corticospinal  tract  before  and  after  mass  resection  as  correlated  with  clinical  motor   findings:  preliminary  data.  AJNR  Am  J  Neuroradiol  2005;  26:791-­‐796.  13.   Nimsky  C,  Ganslandt  O,  Fahlbusch  R.  Implementation  of  fiber  tract  navigation.   Neurosurgery  2006;  58:ONS-­‐292-­‐304.  14.   Bello  L,  Gambini  A,  Castellano  A,  et  al.  Motor  and  language  DTI  Fiber  Tracking  combined   with  intraoperative  subcortical  mapping  for  surgical  removal  of  gliomas.  Neuroimage   2008;  39:369-­‐382.  15.   Bizzi  A.  Presurgical  Mapping  of  Verbal  Language  in  Brain  Tumors  with  Functional  MR   Imaging  and  MR  Tractography.  In:  Pia  Sundgren  M,  ed.  Advanced  Imaging  Techniques  in   Brain  Tumors:  Elsevier,  2009;  573-­‐596.  16.   Bello  L,  Gallucci  M,  Fava  M,  et  al.  Intraoperative  subcortical  language  tract  mapping   guides  surgical  removal  of  gliomas  involving  speech  areas.  Neurosurgery  2007;  60:67-­‐ 82.