Pearls and Pitfalls of MR Diffusion

in Clinical Neurology Dr.  Alberto  Bizzi  Neuroradiology  Unit  Fondazione  IRCCS  Istituto  Neurologico  Carlo  Besta  Milan,  Italy  Email:  alberto_bizzi@fastwebnet.it  

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  

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.  

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  

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  

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  

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.  

 

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