Aprico, A.

Armitage, J.A.

Assemat, P.

Ching-Dusting, J.

Contreras, K.

Dart, A.

Hough, J.

Hourigan, K.

Siu, K.K.W.

English

Engineering Conferences International

Engineering Conferences InternationalECI Digital ArchivesComputational Fluid Dynamics (CFD) in MedicineAnd Biology in Conjunction With the SeventhInternational Biofluid Mechanics SymposiumProceedingsSpring 3-28-2012Blood Flow Through the Aorta in a Mouse Modelof AtherosclerosisJ. HoughMonash UniversityP. AssematMonash UniversityK.K.W. SiuMonash UniversityJ.A. ArmitageMonash UniversityK. ContrerasMonash UniversitySee next page for additional authorsFollow this and additional works at: http://dc.engconfintl.org/cfdmedicinePart of the Biomedical Engineering and Bioengineering CommonsThis Conference Proceeding is brought to you for free and open access by the Proceedings at ECI Digital Archives. It has been accepted for inclusion inComputational Fluid Dynamics (CFD) in Medicine And Biology in Conjunction With the Seventh International Biofluid Mechanics Symposium by anauthorized administrator of ECI Digital Archives. For more information, please contact franco@bepress.com.Recommended CitationJ. Hough, P. Assemat, K.K.W. Siu, J.A. Armitage, K. Contreras, A. Aprico, A. Dart, J. Ching-Dusting, and K. Hourigan, "Blood FlowThrough the Aorta in a Mouse Model of Atherosclerosis" in "Computational Fluid Dynamics (CFD) in Medicine And Biology inConjunction With the Seventh International Biofluid Mechanics Symposium", D. Elad, Tel Aviv Univ.; D. Bluestein, Stony BrookUniv.; D. Dooly, Imperial College London; M. Gharib, California Inst. Of Technology; P. Hunter, The Univ. of Auckland; M.Engelman, ANSYS, Inc. Eds, ECI Symposium Series, (2013). http://dc.engconfintl.org/cfdmedicine/2AuthorsJ. Hough, P. Assemat, K.K.W. Siu, J.A. Armitage, K. Contreras, A. Aprico, A. Dart, J. Ching-Dusting, and K.HouriganThis conference proceeding is available at ECI Digital Archives: http://dc.engconfintl.org/cfdmedicine/21	  Blood	  Flow	  Through	  the	  Aorta	  in	  a	  Mouse	  Model	  of	  Atherosclerosis	  	  J.	  Hough1,	  P.	  Assemat1,	  K.	  K.	  W.	  Siu2,3,	  J.	  A.	  Armitage4	  ,	  K.	  Contreras1,	  A.	  Aprico5,	  A.	  Dart5,	  	  J.	  Chin-­‐DusIng5,	  K.	  Hourigan1	  	  	  1Department	  of	  Mechanical	  and	  Aerospace	  engineering	  &	  	  Division	  of	  Biological	  Engineering,	  Monash	  University,	  Melbourne,	  Australia	  2Monash	  Biomedical	  Imaging,	  Monash	  University,	  Clayton,	  Australia	  3Australian	  Synchrotron,	  Clayton	  Australia	  4Department	  of	  Anatomy	  and	  Developmental	  Biology,	  Monash	  University,	  	  	  	  	  	  	  	  Melbourne,	  Australia	  5Baker	  IDI	  Heart	  and	  Diabetes	  InsHtute,	  Melbourne,	  Australia	  	  	  	  	  ECI	  Conference	  on	  ComputaHonal	  Fluid	  Dynamics	  (CFD)	  in	  Medicine	  and	  Biology	  /	  Seventh	  InternaHonal	  Biofluid	  Mechanics	  Symposium	  March	  25-­‐30,	  2012,	  Crowne	  Plaza	  Dead	  Sea,	  Ein	  Bokek,	  Dead	  Sea,	  Israel	  	  2	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ3	  Organigram	  • Nanopar+cles	  • Wenlong	  • Nanopar+cles	  • Wenlong	  • Baker	  • Jaye	  Tony,	  Andreas	  • Synchrotron	  • Karen	  • Histology	  • James/	  Karla	  • Jillian	  • Numerical	  	  	  Study	  • AFM	  • Ninnuja	  • Nicholas	  • Tuncay	  • Theory	  • Gwenael	  • ∑	  • Model	  stenosis	  • Xiang	  Ning	  • Aor+c	  arch	  • Jillian	  • Simple	  model	  • Gwenael	  • Ac+va+on	  cells	  • Xiang	  Ning	  • Josie	  • Pump	  • PIV	  • Ming	  • Josie	  • 3D	  • images	  • Jillian	  4	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ5	  www.lancastria.net	  www.coastalcimt.com	  Sequence	  of	  progression	  of	  atherosclerosis	  Biomolecular	  acIvity	  in	  atherosclerosis	  Caplice,	  N.	  &	  Mar+n,	  K.,	  ,	  J.	  Am.	  Coll.	  Cardiol.,	  	  3	  (1	  2)	  ,	  2010	  www.vp.org	  6	  Refer	  to	  review	  paper:	  	  Stabilisa+on	  of	  atherosclero+c	  plaques	  Posi+on	  Paper	  of	  the	  European	  Society	  of	  Cardiology	  (ESC)	  Working	  Group	  on	  Atherosclerosis	  and	  Vascular	  Biology	  Thrombosis	  and	  Haemostasis	  2011;	  106:	  1–19	  Seppo	  Ylä-­‐Herauala;	  Jacob	  Fog	  Bentzon;	  Mat	  Daeme;	  Erling	  Falk;	  Hector	  M.	  Garcia-­‐Garcia;	  Joerg	  Herrmann;	  Imo	  Hoefer;	  J.	  Wouter	  Jukema;	  Rob	  Krams;	  Brenda	  R.	  Kwak;	  Nikolaus	  Marx;	  Marek	  Naruszewicz;	  Andrew	  Newby;	  Gerard	  Pasterkamp;	  Patrick	  W.	  J.	  C.	  Serruys;	  Johannes	  Waltenberger;	  Chris+an	  Weber;	  Lale	  Tokgözoglu	  7	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ8	  From	  PIV	  to	  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  PIV:	  Laser	  Based	  X-­‐rays:	  opaque	  and	  small	  	  objects	  Experimental	  setup	  for	  CTXV	  Phase	  contrast	  imaging	  increases	  signal	  from	  weakly	  absorbing	  objects	  Phase	  retrieval	  algorithm	  allows	  for	  recovery	  of	  projected	  thickness	   Pre-­‐processing	  improves	  images	  for	  analysis	  Raw	  Image	  Average	  Image	  Subtrac+on	  Phase	  Retrieval	  PIV	  with	  laser	  light	  9	  From	  PIV	  to	  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  (ctd)	  The	  cross-­‐correla+on	  contains	  VOLUMETRIC	  mo+on	  informa+on	  Non-­‐linear	  itera+ve	  algorithm	  is	  to	  reconstruct	  the	  3D	  velocity	  profile	  from	  the	  2D	  cross-­‐correla+ons	  Forward	  projec+on	  es+mates	  cross-­‐correla+on	  func+on	  Dubsky,	  S.,	  Jamison,	  R.,	  Higgins,	  S.,	  Siu,	  K.,	  Hourigan,	  K.	  &	  Fouras,	  A.,	  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  for	  simultaneous	  3D	  measurement	  of	  velocity	  and	  geometry	  in	  opaque	  vessels,	  Experiments	  in	  Fluids,	  2012,	  52:543–554.	  	  10	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ11	  X-­‐ray	  PIV	  (2D)	  measurement	  of	  flow	  in	  a	  syntheIc	  stenosed	  vessel	  Jamison,	  R.A.,	  Dubsky,	  S.,	  Siu,	  K.W.,	  Hourigan,	  K.,	  Fouras,	  A.,	  X-­‐ray	  velocimetry	  and	  haemodynamic	  forces	  within	  a	  stenosed	  femoral	  model	  at	  physiological	  flow	  rates,	  Annals	  of	  Biomedical	  Engineering,	  39	  (6),	  1643-­‐1653,	  2011.	  12	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ13	  The	  evoluIon	  of	  thrombi	  geometry	  14	  Tolouei,	  E.,	  Butler,	  C.J.,	  Fouras,	  A.,	  Ryan,	  K.,	  Sheard,	  G.J.	  &	  Carberry,	  J.	  (2011)	  Effect	  of	  hemodynamic	  forces	  on	  thrombi	  geometry.	  Annals	  of	  Biomedical	  Engineering.	  39	  (5),	  1403-­‐1413.	  Measurement	  of	  platelet	  aggrega+on	  geometries	  using	  bright	  field	  scanning	  microscopy	  and	  image	  reconstruc+on	  Average centroid height (zc) of mature platelet aggregations increases with shear rate	  The	  three-­‐dimensional	  profiles	  for	  the	  average	  platelet	  aggrega+ons	  at	  each	  shear	  rate	  	  Local shear rate distribution around a representative mature platelet aggregation	  Varia+on	  of	  average	  cross-­‐sec+onal	  area	  with	  exposure	  +me	  Effect	  of	  haemodynamic	  forces	  on	  thrombi	  geometry	  	  15	  Par+cle	  Image	  Velocimetry	  Extending	  to	  3-­‐Dimensional	  analysis	  of	  in	  vivo	  flows	  Small,	  bea+ng,	  compliant,	  non-­‐Newtonian	  blood	  Zebra	  fish	  heart:	  +ssue,	  blood	  2d	  -­‐>	  3d	  velocity	  fields	  16	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ17	  CFD	  in	  idealised	  stenosed	  vessels	  –	  see	  Poster	  by	  Griffith	  et	  al.	  • D• r	  • d	  • R	  Steady	  inflow	   Eccentric	  stenosis	  Pulsed	  inflow	  Griffith,	  M.D.,	  Leweke,	  T.,	  Thompson,	  M.C.	  &	  Hourigan,	  K.	   	  2008	   	  Steady	  inlet	  flow	  in	  steno+c	  geometries:	  convec+ve	  and	  absolute	  instabili+es.	  Journal	  of	  Fluid	  Mechanics	  616,	  111-­‐133.	  Griffith,	  M.D.,	  Leweke,	  T.,	  Thompson,	  M.C.	  &	  Hourigan,	  K.	  	  2009	  	  Pulsa+le	  flow	  in	  steno+c	  geometries:	  flow	  behaviour	  and	  stability.	  Journal	  of	  Fluid	  Mechanics	  622,	  291-­‐320.	  Griffith,	  M.D.,	  Thompson,	  M.C.,	  Leweke,	  T.	  &	  Hourigan,	  K.	   	  2010	   	  Convec+ve	  instability	  in	  steady	  steno+c	  flow:	  op+mal	  transient	  growth	  and	  experimental	  observa+on.	  Journal	  of	  Fluid	  Mechanics	  655,	  504-­‐514.	  18	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ19	  Two-­‐dimensional	  slice	  in	  Avizo	  showing	  a	  secIon	  of	  the	  aorIc	  arch	  of	  an	  Apo	  E-­‐deficient	  mouse.	  The	  image	  has	  been	  segmented,	  vessel	  (blue),	  plaque	  (green)	  and	  lumen	  (brown).	  	  	  CFD	  in	  the	  model	  from	  a	  mouse	  Mouse	  aorta	  geometry.	  	  Mouse	  aorta	  geometry	  20	  • AA	  • BCA	  • LCC	  • LS	  • DA	  The	  lumen	  of	  the	  vessel	  which	  has	  been	  segmented	  and	  cropped,	  ready	  for	  meshing	  in	  ICEM	  CFD.	  	  Ascending	  Aorta	  (AA)	  Brachiocephalic	  Artery	  (BCA)	  Leq	  Common	  Caro+d	  Artery	  (LCC)	  Leq	  Subclavian	  Artery	  (LS)	  Descending	  Aorta	  (DA)	  Diameter,	  D	  (mm)	  0.83	   0.56	   0.33	   0.38	   0.82	  Flow	  Rate,	  Q	  (mL/min)	  [7]	  12.02	   1.87	   1.35	   1.06	   7.74	  Reynolds	  Number,	  Re	  95	   22	   27	   18	   62	  Dimensions	  of	  the	  aorta	  and	  its	  main	  branches	  measured	  from	  the	  reconstructed	  three-­‐dimensional	  geometry.	  The	  flow	  rates	  used	  as	  boundary	  condiIons	  were	  obtained	  from	  Huo	  et	  al.	  (2008).	  	  Vessel	  geometry:	  CAD	  21	  SecIon	  of	  the	  ApoE-­‐deficient	  mouse	  aorta	  demonstraIng	  the	  locaIon	  of	  the	  plaques	  (green)	  on	  the	  inner	  curvature	  of	  the	  aorta	  and	  on	  the	  upstream	  side	  of	  the	  three	  main	  branch	  points.	  	  a)	  Histology	  of	  a	  cross-­‐secIon	  of	  the	  AA	  and	  BCATwo	  plaques	  are	  visible,	  one	  with	  a	  well	  defined	  fibrous	  cap	  (provided	  by	  J.	  Armitage).	  b)	  Related	  two-­‐dimensional	  slice	  in	  Avizo	  with	  the	  wall	  and	  plaque	  segmented.	  	  Plaque	  locaIons	  22	  Surface	  pressure	  Plaque	  present	   Plaque	  “removed”	  Wall	  shear	  stress	  23	  Wall	  shear	  stress	  (exaggerated	  contours)	  Plaque	  present	   Plaque	  “removed”	  c.f.	  plaque	  loca+ons	  24	  Outline	  of	  the	  PresentaIon	  •  Context	  of	  current	  research	  •  Atherosclerosis	  overview	  •  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  	  SyntheIc:	  Stenosis	  	  In	  vitro:	  Thrombi	  	  In	  vivo:	  Heart	  •  CFD	  	  Idealised	  stenoses	  	  Mouse	  aorta	  •  Conclusions	   ñ25	  Conclusions	  • 	   	  X-­‐ray	  CT	  Velocimetry	  +	  CFD	  can	  be	  used	  to	  determine	  +ssue	  geometries,	  blood	  flow	  velocity	  fields,	  WSS,	  etc	  •  	   In	   accordance	   with	   the	   literature,	   plaques	   were	   found	   to	  develop	   on	   the	   inner	   curvature	   of	   the	   aor+c	   arch	   and	   the	  upstream	  side	  of	  the	  main	  branches	  in	  Apo	  E-­‐deficient	  mice	  	  • 	   	  The	  WSS	  results	  are	  consistent	  with	  those	  found	  by	  others	  in	  arteries	  without	  plaque	  	  • 	  	  As	  an	  extension	  to	  previous	  work,	  the	  flow	  around	  plaque	  has	  been	  inves+gated,	  with	  altered	  WSS	  distribu+ons	  observed	  	  • 	   	  Work	  is	  in	  progress	  looking	  at	  the	  deforma+on	  of	  the	  arterial	  wall	   and	  plaque	  by	   incorpora+ng	   the	   elas+c	  proper+es	  of	   the	  materials	  (coupled	  solver,	  AFM,	  Biodynamic	  tester)	  • 	   X-­‐ray	   CT+Velocimetry	   +	   in	   vivo,	   func+onal	   nanopar+cles	  will	  also	  be	  inves+gated	  	  •  	   Part	   of	   a	   broader	   program	   in	   lung/brain/cardiovascular,	  imaging,	  cfd,	  nanotechology,	  drug	  delivery,	  devices,	  ….	  26	  Acknowledgements	  Swiss	  Light	  Source	  27	  MulIdisciplinary	  research	  –	  one	  needs	  to	  wear	  many	  hats	  28	  29	  Microvessels	  in	  atherosclerosis	  as	  important	  entry	  pathways	  for	  leukocytes	  to	  lesions.	  Wikipedia	  • 	  Results	  from	  the	  interrup+on	  of	  blood	  supply	  to	  a	  part	  of	  the	  heart,	  causing	  heart	  cells	  to	  die	  • 	  Most	  commonly	  due	  to	  occlusion	  (blockage)	  of	  a	  coronary	  artery	  following	  the	  rupture	  of	  a	  vulnerable	  atherosclero+c	  plaque	  • vulnerable	  plaque	  rupture	  causes	  as	  many	  as	  85%	  of	  all	  heart	  aaacks.	  Eriksson, Circulation 2011, 124:2129-2138	  Myocardial	  InfarcIon	  • As	  cholesterols	  are	  absorbed	  by	  the	  artery,	  proteins	  called	  "cytokines"	  are	  released.	  The	  cytokines	  cause	  inflamma+on	  and	  make	  the	  arterial	  wall	  s+cky,	  resul+ng	  in	  the	  aarac+on	  of	  immune-­‐system	  cells	  to	  the	  area.	  The	  immune-­‐system	  cells	  are	  called	  "monocytes.”	  • When	  the	  monocytes	  enter	  the	  arterial	  wall,	  they	  differen+ate	  into	  "macrophage"	  cells	  and	  begin	  to	  absorb	  fat	  droplets.	  Over	  +me,	  these	  fat-­‐filled	  cells	  form	  a	  plaque	  –	  what	  researchers	  now	  call	  "vulnerable	  plaque.	  30	  Computed	  Tomographic	  X-­‐ray	  Velocimetry	  of	  Biofluid	  Flows	  Kim	  GB,	  Lee	  SJ	  (2006)	  X-­‐ray	  PIV	  measurements	  of	  blood	  flows	  without	  tracer	  parHcles.	  Exp	  Fluids	  41:195-­‐2006	  2D	   Axisymmetric	  Im	  KS,	  Fezzaa	  K,	  Wang	  YJ,	  Liu	  X,	  Wang	  J,	  Lai	  MC	  (2007)	  ParHcle	  tracking	  velocimetry	  using	  fast	  X-­‐ray	  phase-­‐contrast	  imaging.	  Appl	  Phys	  Lea	  90:	  Artn	  091919	  Fouras	  A,	  Dus+ng	  J,	  Lewis	  R,	  Hourigan	  K	  (2007)	  Three-­‐dimensional	  synchrotron	  X-­‐ray	  parHcle	  image	  velocimetry.	  J	  Appl	  Phys	  102:	  Artn	  064916	  3D,	  planar	  symmetry	  assumed	  Irvine	  SC,	  Paganin	  DM,	 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Blood Flow Through the Aorta in a Mouse Model of Atherosclerosis

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Blood Flow Through the Aorta in a Mouse Model of Atherosclerosis

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