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Quantitative NMR imaging and its applications in vivo Stewart, Wendy Anne 1985

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QUANTITATIVE  NMR  IMAGING AND  ITS APPLICATIONS J_N VI  t>y  WENDY ANNE B.Sc,  University  STEWART o f Dundee,  1982  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  in THE FACULTY OF GRADUATE  STUDIES  (Department o f C h e m i s t r y )  We a c c e p t t h i s  t h e s i s as conforming  t o t h e required standard.  THE UNIVERSITY OF BRITISH COLUMBIA NOVEMBER, 1985 (c) Wendy Anne S t e w a r t , 1985  In  presenting  requirements of  British  it  freely  agree for  this f o r an  available  that  I agree  understood  that  that  may  be  copying  n o t be  CIM  1 Q \  \ I A  I  study.  copying by  allowed  4  £j\\  The University of British 2075 W e s b r o o k P l a c e Vancouver, Canada V6T 1W5  Date  University  and  or publication  shall  ALU  Columbia  of the  shall  granted  permission.  of  at the  make  further  of this  t h e head  h i s or her representatives.  f i n a n c i a l gain  Department  fulfilment  the Library  f o r extensive  purposes  o r by  degree  f o r reference  permission  scholarly  in partial  advanced  Columbia,  department  for  thesis  thesis  of  my  It i s  of this without  thesis my  written  ABSTRACT  The a  field  p r o b l e m o f q u a n t i f y i n g NMR  p a r a m e t e r s , measured a t  s t r e n g t h o f 0.15 T e s l a u s i n g a w h o l e body  Instrument,  and t h e i r  potential  u s e j_n v i vo,  Imaging  have b e e n  i nvest i gated. The with  spin-lattice  relaxation  times  ( T j ) o f water  various concentrations o f paramagnetic  determined  Tj obtained data.  from  from a t h r e e parameter e x p o n e n t i a l  values o f Tj obtained, Tj values  computational  method w h i c h  instruments.  inversion-recovery  imaging  obtained  This  f i t of the  c o n d i t i o n s on t h e  were a l s o e x a m i n e d .  compared w i t h  Intensity  images a s a f u n c t i o n o f t a u a n d  The e f f e c t s o f v a r y i n g  imaging  s p e c i e s were  u s i n g t h e i n v e r s i o n - r e c o v e r y method.  was m e a s u r e d d i r e c t l y  doped  using a  The r e s u l t s  two-point  i s a v a i l a b l e on many  commercial  involves taking the ratio  image a n d a s p i n - e c h o  were  o f an  image, w h i c h  e l i m i n a t e s t h e d e p e n d e n c e o f t h e images on t h e e q u i l i b r i u m magnetization times  and t h e r e p e a t  (T£) were d e t e r m i n e d  water doped w i t h species  from  using the spin-echo  T^.  Intensities  method, o f  were a g a i n  images a s a f u n c t i o n o f 2 t a u a n d  f r o m a two p a r a m e t e r e x p o n e n t i a l effects of diffusion examined.  The s p i n - s p i n r e l a x a t i o n  t h e same c o n c e n t r a t i o n s o f p a r a m a g n e t i c  used t o study  directly  time.  f i t o f the data.  on t h e v a l u e s o f 1^ o b t a i n e d  The v a l u e s were compared w i t h ii  those  obtained obtained The were a l s o  obtained  from  a two-point two T  2  computational  spin-echo  images w i t h  d a t a were a l s o  The  field  with those  literature  literature,  with acceptable e r r o r s  the  range the  Experimental animal  model  have shown t h a t  of  these  and  obtained no  range  can  effects  allergic  of diffusion  become  less. important.  (EAE),  induced  in  an  in a  Macaca  the development o f the d i s e a s e  a powerful  NMR tool  imaging. in the  ms,  imaging  be o b t a i n e d  encephalomyelitis was  100-600  was  This technique s t u d y o f EAE  has  in  since the progression of the disease i s  accompanied that  values of  using quantitative  primates,  in the  for multiple sclerosis,  been shown t o be  Tj  i t is possible  w h i c h have e r r o r s o f ± 1 5 % o r  f a s c i c u 1 a r i s monkey, and followed  values  (±127.) u n d e r v a r i a b l e  Reproducible  r a n g e 40-200 ms,  Above t h i s  The  of  s t u d i e s , w h i c h compare f a v o u r a b l y  to obtain reproducible values of T  conditions.  tau-times.  ratio  present.  of these  in the  the  spectroscopic c o n d i t i o n s , with  gradients  results  different  compared w i t h  under c o n v e n t i o n a l magnetic  method, w h i c h t a k e s  by  changes  changes w i l l  inflammation  and  i n T j and  T • 2  The  indications  allow discrimination  o t h e r s which c o n t a i n  i ii  between  are areas  demye1ination.  CONTENTS Page Abstract  i i  List  of Tables  vi  List  of Figures  x  List  of Abbreviations  xv  G l o s s a r y o f Terms  xvii  Acknow 1 edgements  xx  Introduction  1  Chapter i  24  Evaluation  o f t h e Instrument  a.  Magnetic F i e l d  b.  Spatial  24  Inhomogeneity  24  Resolution  28  c. A t t e n u a t i o n  30  d.  32  Phasing  and R e c o n s t r u c t i o n  Chapter 2  45  Q u a n t i t a t i o n o f NMR a.  Parameters  45  Spin-lattice Relaxation  ...45  ( i)  Definition  45  (ii)  Measurement  (iii)  Computed  (iv)  Effects  o f a S p i n - e c h o Readout  54  (v)  Effects  o f Proton  55  (vi)  Multiexponential  o f Tj  48  T  52  iv  Density Relaxation  Behaviour...57  (vii)  Discussion  b. S p i n - s p i n  Chapter  60  Relaxation  62  ( i)  Definition  62  (ii)  Measurement o f 1^  63  (iii)  Computed T"  67  (iv)  Effects of Diffusion  69  (vi )  Discussion  70  2  3  72  Applications  o f Q u a n t i t a t i v e NMR  (i )  Background  (i i )  I n d u c t i on o f EAE NMR  (i i i)  Development NMR  72 72  Imaging  using  Imaging  and  Protocol of  74  EAE  Imaging  (iv)  Q u a n t i t a t i o n o f NMR  (v)  Discussion  76 Parameters  79 81  Conclusions  84  F u t u r e Work  86  References  88  Appendix  93  I  v  L I S T OF  TABLES Page  Table  1:  Intensities  f r o m two s p i n - e c h o  images c o m p a r i n g automatic  cm  2  and  setting of the  attenuation. given  manual  Intensities are  a s t h e mean v a l u e s  p l u s o r minus  deviation, vials.  from  2.6  standard  at the centre o f the  Two  values  each s o l u t i o n different  32  are given f o r  corresponding  positions  t o two  in the  receiver coi1.  Table  II:  Tj values  f o r various  concentrations  o f CuS0  solutions obtained  51 4  a t 20  and M n C l  2  (± i)°C  using the inversion-recovery method.  Two  values  are given f o r  each c o n c e n t r a t i o n t o two d i f f e r e n t rece1ver  Table  I I I : Computed  corresponding  positions  In t h e  co i 1 .  Tj values  concentrations  f o r various  o f CuSO^ a n d M n C l £  vi  53  solutions  obtained  Two v a l u e s  are  given  concentration, two  different  recei ver  Table  IV:  Tj  at  for  1)°C.  each  positions  in  to the  coi1.  values  for  various  55  concentrations  of  MnC^ solution,  obtained  (±  i)°C using  at  spin-echo Computed readout  20  readout Tj  are  Two v a l u e s  are  Tj  values  with for  given  and  the  ms.  comparison. for  each  corresponding positions  in  to the'  coi1.  for  various  56  of  MnCl^  obtained  (±  i)°C using  at  20  solution,  inversion-recovery  method,  slice  2 0 mm.  thickness  values  a  same  concentrations  Tj  the  T = 20  with  given  two d i f f e r e n t recei ver  method,  values  concentration,  Va:  (±  corresponding  inversion-recovery  Table  20  are  of  given  comparison.  vi 1  for  the  and  a  Computed  Table  Vb:  T  values  for  various  57  concentrations  of  obtained  (± 1 ) ° C u s i n g  at  20  MnCl  solution,  2  the  inversion-recovery  method,  slice  5 mm. C o m p u t e d  Tj  thickness  values  are  of  given  and  a  for  compar i s o n .  Table  VI:  T^ v a l u e s  for  various  concentrations  CuS0  solution,  obtained  using  spin-echo  values  the are  different rece i ver  at  given for  concentration  Table  of  MnCl  (±  i)°C  method.  Two  20  2  each  in  to  two  the  coi1.  2  values  concentrations  of  for  obtained  Two  are  values  concentration  various  CuSO^ a n d  solutions,  recei ver  and  4  corresponding  positions  V I I : Computed T  different  66  at  in  coi1.  vi 1 i  2  each  corresponding  positions  MnCI  (± 1 ) ° C .  20  given for  68  the  to  two  Table  VIII:  Computed T  values  2  concentrations  of  MnCl  obtained  (±  i)°C  at  various  20  combinations  Two v a l u e s  are  concentration different recei ver  Table  IX:  for  Tj  as  a  (WM) a n d  which  using  of  -[-times. each  corresponding in  to  two  the  function  induction of  matter  solutions,  2  given for  positions  69  coiI.  values  after  various  appear  of time  EAE, for  grey  normal,  white  matter and  79  (GM)  the  1es i o n .  Table  X:  T  values  2  after  as  a  function  induction of  matter which  (WM) a n d appear  of time  EAE, for  grey  normal  white  matter  and  80  (GM)  the  1es i o n .  Table  XI:  Tj  v  a  i  u  e  f  s  r o  slice  images  death  for  grey  five  different  immediately p r i o r  white  matter  normal,  m  matter  (GM) w h i c h  and the  lesion. ix  (WM) a n d appear  81 to  L I S T OF F I G U R E S Page Figure  1:  Single projections  for  back  projection  4  i mag i n g .  Figure  2:  a.  Application  of  gradient  G^  b.  Application  of  gradient  G  c.  Application  of  G  Two d i m e n s i o n a l and  gradient  plus G  Fourier transform  3:  Slice  Figure  4 :  Selective radiofrequency  Figure  5:  the  domain and  6:  diagrams  effects  pulse Figure  selection  Vector  Plot  recovery 7:  8:  of  9:  Sagittal using  a  Fourier  in the  11  spin-system.  versus for  tau,  an  the  12  inversion-  sequence. sequence.  intensity pulse  8  transform.  Schematic  showing formation o f the  spin-echo Figure  pulse  inversion-recovery  delay,  Spin-echo pulse  Plot  5  7  demonstrating  o f an  pulse  diagrams Figure  imaging.  its  intensity  inter-pulse  Figure  in  sequence on a of  pulse  sequence.  Figure  time  y  versus  2 tau  for  13  echo. a  15  sequence.  image o f a spin-echo  human h e a d  pulse  x  obtained  sequence.  17  Figure  10:  Fourier transform  Figure  11:  single  projection  20  in back Fourier  projection imaging. transform of a single  projection  21  in  projection  back  of a  imaging showing  phase  errors. Figure  12:  Diagram o f  parallel  studying magnetic Figure  13:  Free  Induction  gradient Figure  14:  Figure  15:  Plot of  Figure  16:  the  of  xz  of  field  Decay  phantom  for  25  inhomogeneity.  (FID) p u l s e  and  26  sequence.  F I D image in  tube  parallel  tube  phantom  26  plane.  intensity  distance  as  along  the  Inversion-recovery  a  function  27  x-direction.  pulse  and  image  of  gradient  28  capillary  29  sequence. Figure  17:  Inversion-recovery tube  phantom.  Figure  18:  Diagram o f  Figure  19:  Spin-echo  Figure  20:  Phantom  Figure  21:  i n Tj  a.  Plot  b.  image o f  used  and  •  resolution  and of  4.96  Plot of •  for  4.96  T  2  resolution  studying  magnitude  phantom.  attenuation  versus  O 0.99  intensity mM a n d  29 30 31  measurements.  intensity mM a n d  phantom.  34  4  tau  for  mM C u S 0  reconstruction. xi  for  mM C u S C > .  versus  O 0.99  tau  4 ?  34 with  Figure  22:  Phantom  used  for  ambiguities  studying  intensity  A = 4.96  mM C u S 0  B = 0.99  mM CuSC-  35  4  4 Figure  23:  Inversion-recovery intensity  Figure  24:  - 50 ms  b.  X  =  100 ms  c.  X  =  150 ms  d.  X  =  2 5 0 ms  e.  X  =  300  ms  f.  X  =  4 0 0 ms  g.  X  =  500  ms  h.  X  =  6 0 0 ms  i .  X  Plot  1000 of  ms  intensity  4.96  a.  in signal  mM C u S 0  to  b.  T h e same magnitude  26:  Plot  of  image  2.54  X 2.54  Figure  27:  a.  mM C u S 0  mM C u S 0  image o f  4  phantom  42  intensity  x = 200 in a.  ms.  after  versus  tau  relaxation 4  &  0.99  mM C u S C K + 0 . 9 9 4  versus  38  42  reconstruction.  intensity  Plot of  showing  sign.  O 0.99  4  at  mu1tiexponentia1 O  tau  demonstrate  ambiguities  Figure  versus  Inversion-recovery used  37  ambiguities.  X  • 25:  demonstrating  a.  fluctuations  Figure  images  spin-lattice concentration  so 1ut i o n s . xi i  showing  59  behaviour.  mM C u S 0  4  CuSO. 4 relaxation for  Cu50  4  rate  60  b.  O  IR  A  Computed  Plot  data  of  versus  data  spin-lattice  relaxation  concentration  rate  60  for MnC^  solutions. O IR  data  A Computed Figure  28:  a.  Plot of versus  data  spin-spin  relaxation  concentration  for  rate  71  CuSO,  4 so 1ut i o n s . O SE  data  A Computed b.  Plot  of  versus  data  spin-spin  relaxation  concentration  for  rate  MnCl  71  2  solutions O SE  data  A Computed  data  Figure  29:  Diagram o f  Figure  30:  Diagram showing the  Figure  31:  nerve  monkey  in the  slices  being  Transverse brain, the of  cell. position of  instrument  the  76  monkey's  77  and  the  obtained.  SE image  showing the  left  72  of  the  abnormal  hemisphere.  image). xi i i  (Right  area side  in  Figure  32:  Series  of  three  spin-echo  obtained  from  the  a.  16.25  days  after  inoculation  b.  16.75  days  after  inoculation  c.  18.42  days  after  inoculation  The  light  areas  monkey's  images  are  xiv  brain.  abnormal.  78  LIST  OF  adenosine static  ABBREVIATIONS  triphosphate  magnetic  field  radiofrequency Bohr  field  magneton  cent imetre computed  tomography  copper(II) decibels, degrees static  sulphate measure o f  celcius magnetic  radiofrequency  field field  inhomogeneity inhomogeneity  n o n - 1 i near i t y  grad i ent diffusion  coefficient  experimental free  attenuation  allergic  induction  encephalomyelitis  decay  magnetic  field  gradient  along  the  x-direction  magnetic  field  gradient  along  the  y - d i r e c t i on  magnetic  field  gradient  along  the  z - d i r e c t i on  grey  matter  gamma,  of  the  gyromagnet i c  brain rat i o  hertz nuclear  spin  intensity  i n an  intensity  in a  inversion-recovery spin-echo xv  image  image  IR  inversion-recovery  mM  millimo1ar  mm  millimeter  MnCl  2  manganese(I I)  chloride  MS  multiple  M  e q u i 1 i b r i um m a g n e t i z a t i o n  Q  sclerosis  My,  magnetization  in the  xy  M^  magnetization  along the  v  nu,  NMR  nuclear  u  omega, Larmor p r e c e s s i o n per sec  Larmor p r e c e s s i o n magnetic  plane z - d i r e c t i on  frequency  in  hertz  resonance frequency  in  radians  31 P % PET RF  phosphorous-31 percent positron  emission  tomography  radiofrequency  p  rho,  spin  density  S T  electron tau, the  T. c  correlation  Tj  spin-lattice  T^  spin-spin relaxation  TR  r e p e a t t i m e , the time between successive reapplication of a pulse sequence  2DFT  two d i m e n s i o n a l  WM  white matter  spin interpulse  delay  time relaxation  time  Fourier  of the  xvi  time  transformation  brain  G L O S S A R Y OF TERMS  Central  nervous  spinal Cerebral  system:  constituting upper  a  the  or  the  brain  the  portion  the  cranial or  pair of  of  and  the  structures brain,  Haemorrhagic  removal  Inflammation  of  the  myelin  Diseased  individual  cells,  areas,  to  That  minute  i n v o l v i n g both  tissues  Death  groups o f  department  v i s i b l e to  of tissue,  rupturing  structure,  tissues.  sheath  the  brain  and  „  necrosis:  due  occupying  cavity.  cord.  pathology:  Histology:  of  nerves.  Encephalomyelitis:  Gross  of  of  main  Destruction  nerve  spinal  Either  part  Demye1ination: of  consists  cord.  hemisphere:  the  This  of  cells blood  Histopathology:  and  the  usually or  naked  eye.  as  in small  localized  vessels.  o f anatomy,  composition  the  which deals function  histology  of  with  of  the  the  diseased  tissue. Inflammation: injury  or  destroy, and  the  complex  A localized protective destruction dilute, injured series  arterioles, permeability  or  of  wall  of  and  blood  both  which and  flow.  elicited  which serves the  include  venules,  it  agent  involves  dilation  with  by  to  injurious  Histologically,  events  capillaries  tissue, off  tissue.  response  of  increased  a  Intradermal: skin of  Within  deep t o  vascular  Ketamine  the  the  dermis,  which  epidermis,  connective  2-methy1 aminocyc1ohexanone rapid acting  be a d m i n i s t e r e d  the  tuberculosis.  formation  of  outer  consisting of  name  layer  a dense  of  bed  (±)-2-o-chlorophenyl-  hydrochloride. general  Species  and  which  can  intramuscularly.  of micro-organism  The d i s e a s e  tubercles  A non-  anaesthetic  intravenously or  M y c o b a c t e r i um t u b e r c u 1 o s i s : causes  the  tissue.  h y d r o c h l o r i d e : Chemical  barbiturate,  is  is  which  characterized  caseous  necrosis  in  by the  t i ssues. Myelin:  The  nerve Neuron:  lipid  substance  system.  the  conducting  A typical  containing  the  nucleus  short  and  long process  one  Chemical  name,  administered  the  around  (axon)  the of  central a  cell  surrounding  processes  a n d may h a v e  certain  which  known as terminates  branches  along  nervous body,  cytoplasm; dendrites, in its  twigcourse.  2-(2,6-dimethylphenylamino)-4H-5,6-  dihydro-1,3-thiazine. be  consists  and  radiating  branches,  cells of  neuron  several  Rompun:  sheath  fibers.  Any o f  like  forming a  Potent  intravenously  xv i i i  sedative, or  hypnotic.  intramuscularly.  Can  Synapse:  The a n a t o m i c a l  another;  the  two a d j a c e n t impulse  is  r e l a t i o n o f one  region of neurons,  transmitted  nerve  j u n c t i o n between forming from  xix  the  one  place  cell  to  processes where a  neuron t o  of nervous  another.  ACKNOWLEDGEMENTS  I would support  and  like  to  encouragement  I would a l s o D.W.  Paty,  thank  for  collaborative  like  his  Professor throughout  to  express  support  research.  and  Research  and  Cleveland, I thesis, its  give  has  for  special  and f o r  her  their thanks  patience  work.  enthusiasm throughout  our  been  helpful to  go t o  Mr. D.  Picker  the  International,  discussions. for  and encouragement  xx  Aikins,  i n v a l u a b l e , and t o  Anneke Rees  preparation.  his  Dr.  Development group at  Ohio,  this  for  my a p p r e c i a t i o n t o  Thanks a l s o  whose e n g i n e e r i n g e x p e r t i s e  L . D . Hall  typing  this  throughout  Ded i c a t i on  To P r o f e s s o r Roy  XXI  Foster  INTRODUCTION  The  phenomenon  of  nuclear  magnetic  an  d i s c o v e r e d b y P u r e e 11 a n d  important  analytical  phys i c i ans. NMR s p e c t r o s c o p y elucidation  of  and  proteins,  the  study  few  examples  of  tool  has  Bioch  for  been  used  complex chemical in reaction  '  both  in  1946,  scientists  and  such  in  now  complexes,  the  as  steroids  characterization,  electron-donor-acceptor  is  and  by s c i e n t i s t s  structures,  product  (NMR) w a s  2  1  first  resonance  and  to  in  name  a  3 technical  from  organic  improvements  biological  studies  chemistry.  With  progressive  i n NMR i n s t r u m e n t a t i o n ,  have  also  become  many  possible.  1971,  In  4  Damadian tissue,  carried and  behaviour  of  the  used  to  evidence  between  be  and  the  from  chemical  work o f  Henderson,  C o s t e l l o and  resonances  from  tissue.  NMR s i g n a l s  could  and  diseased  that  detailed  Moon a n d  inorganic the  be  states.  extended 31  In  when  P  phosphate  intraerythro-  study  6  R i c h a r d s was  , who a l s o  triphosphate  1  relaxation  intraerythrocytic  a  rat  of  the  shift.  Omachi  adenosine  the  on  cancerous  m e d i c i n e was  the  demonstrated  deduced  phosphate  1974,  between  that  normal  NMR t o  detected  They a l s o  c y t i c pH c o u l d inorganic  5  NMR s t u d i e s  2 , 3 - d i p h o s p h o g 1 y c e r a t e and  of  blood.  In  i n normal  application of Richards  resonances from  first  discriminate  the  differences  protons  provided the  Moon a n d  jjn v i t r o p r o t o n  demonstrated  This  1973,  out  extended  detected  (ATP) i n  the  human  31  by P  erythrocytes. 3  the  1  P  NMR s i g n a l s  phosphate is  the  could  same y e a r ,  from  in the  inorganic  3  1  body.  P  could  be  from  Its  is  radiation,  showed  every  for  the  metabolic disorders  could  ATP  both  therefore  first  not  inorganic  transfer  involves  In a d d i t i o n ,  n o n - i n v a s i v e and does  that  samples.  energy  phosphocreatine;  followed  and  muscle  regeneration  NMR s p e c t r o s c o p y .  technique  e_£ a j _ .  intact  in v i r t u a l l y  phosphate and  metabolism  Hoult  ATP, phosphocreatine  be o b t a i n e d  key m e t a b o l i t e  process  using  In t h e  time  j_n v i v o  since  the  require  be  ionizing  followed  over  time  8 9 and t h e  effects  decade a been  large  number  1.  .  Over the  a n d many m o r e a r e  in  past  studies  have 4  progress.'  Methods  Back  Projection  In most study  monitored  o f J_n v i v o s p e c t r o s c o p i c  carried out^  Imaging  the  of therapy  is  conventional  placed  equilibrium  perturbed  in a  NMR e x p e r i m e n t s  uniform static  magnetization  in the  by a p p l i c a t i o n o f a  the  magnetic  sample field,  z - d i r e c t i on  radiofrequency  under B  Q  , and  is  (RF) p u l s e  at  15  the  resonance  work is  is  frequency  concerned  with  g i v e n by e q u a t i o n  of  appropriate  proton  NMR.  nucleus  The r e s o n a n c e  .  This  frequency  1, »  where  the  y = gyromagnetic  o  -  y B  ratio  2  (1)  o  o f the  proton.  The a b i l i t y t o using  the  NMR s i g n a l s  by L a u t e r b u r  in  In t h e applied,  imaging  to  If  the  1 6  sample  encoded was  information  first  demonstrated  .  experiment,  magnetic  in frequency  distance  gradient.  spatially  from a  1973  resulting  respect  obtain  along  the  applied  field  labelling of  direction  gradient  (G  of  gradients  the  the  for  are  sample  with  applied  example)  is  X  linear,  then  equation  1 becomes ca  x  where  is  during  the  - vB + ' o  resonance  application  of  (2)  G x x  Y  frequency  gradient  of  nuclei  at  position  G . X  Cons i der  a  same s o l u t i o n magnetic  field,  gradient  is  pulse,  then  signal  has  the  water  frequencies  samp1e compr i s i ng two  (for as  the the  form o f  in the  two  along  the  y-axis  has to  during  Now t h e frequency,  twice  intensity  data  and  in a  1.  a  If  1 7  of  the  different  the  acquisition  a  x  9 0 ° RF  domain  in Figure  of of  the a  and  la;  has  a  single  profile  from a  single  tube.  the is  If  tubes  gradient  subsequent  projection  tubes  G  resonance  application  in both  3  time  positions  the  after  shown  the  static  linear  acquisition  provides  water  c o n t a i n i ng  placed  projection  Similarly,  resonance the  the  tubes  transformation lb.  data  transform  corresponding x-axis.  water)  in Figure  during  Fourier  the  Figure  shown  applied  along  Fourier  example,  tubes  shown  in  same  obtained linear  with  x  combinations effective may b e  the  linear  obtained  example,  rotated'  are  at  1°  x - and  gradient at  4 5 ° , as  projections %  of  y-gradients is  obtained,  any a n g l e  shown  with  in Figure  obtained, intervals.  with  are  used,  and  hence  respect lc).  the  to  simple  projections  the  Usually,  composite  a  y-axis 180  gradient  The F o u r i e r t r a n s f o r m s  of l ft  projection carried  out  are to  then  " f i l t e r e d " and  provide the  final  "back  projection"  image.  y  a /N  /is  ~) o  o  Bo *  Figure  1:  Single projections i mag i n g .  for  back  projection  a.  Application  of  gradient  b.  Application  of  gradient  c.  Application  of  G plus G x y  G  (for  each  2.  Two-Dimensional The  idea of  introduced imaging  Fourier Transformation  u s i n g F o u r i e r methods  by Kumar,  is a  Welti  and  Ernst  in  in  (2DFT)  i m a g i n g was  1975  s p e c i f i c example o f a broader  1 9  .  2DFT  class  o f NMR  20 techniques pulse in  and  known as gradient  Figure 2.  used,  the  2DFT s p e c t r o s c o p y sequence  I f the  used  for  imaging method  experiment  begins  with  . 2DFT  the  a  shown  selection  application of  is  a  «5*»  I  RF - J l "  imaging is  of plane  180*  W  An example o f  — ~ ~ < J f ~  1  Slice Select Gradient  Read  1  Gradient  \  J  \  Phase Encoding. Gradient  Data  Figure  2:  selective gradient  Two d i m e n s i o n a l F o u r i e r t r a n s f o r m and g r a d i e n t sequence.  9 0 ° RF p u l s e (see  During which  as  the  together  page 6 f o r  data  with  the  "read"  sample  spatia 1 information; this  gradients  used  a  in the  select  slice  selection).  gradient  under  study  functions  Lauterbur  pulse  slice  description of  acquisition, a  frequency-encodes  provides  1_  Collect  is and  in the  method.  In  applied, thus same way addition,  a  phase e n c o d i n g  first,  and i t s amplitude  excitation. chosen (see 256  gradient  1).  f o r each s u c c e s s i v e increments  and t h u s t h e r e s o l u t i o n  In a l l images o b t a i n e d f o r t h i s i n c r e m e n t s were u s e d .  thesis,  The o b s e r v e d  S ( t ) c a n be w r i t t e n a s S(t)  where s ( r , t ) d x d y volume a v e r a g e d p(r)  i s incremented  t h e 2D m a t r i x s i z e  phase e n c o d i n g  signal  perpendicular to the  The number o f t h e s e p h a s e e n c o d i n g  determines  Chapter  i s applied,  i s the contribution over t h e s l i c e  i s the spin  pixel.  - J/p(r)8(r,t)dxdy  density.  The 2DFT o f S ( t )  (3)  from t h e a r e a  thickness,  The a r e a dxdy  dxdy,  at position i s referred  x  (  y  4  )  that S(u>) - J/S(t)exp(-iu)t)dt dt x  For  t o as a  i s g i v e n by  S(w) = S ( w , a ) )  such  r , and  further  details,  the reader  (5)  y  is referred  t o M a n s f i e l d and  • 21 Morris Imaging methods may a l s o depending time  22  on whether t h e y  , from  a  be d i v i d e d  receive  23 1ine , o r from  signal  t h e whole  into from  groups one p o i n t  sample  at a  24  SI i c e S e l e c t i o n The  two i m a g i n g  discrimination object  methods d e s c r i b e d  a l o n g t h e x, y - a x e s  of finite  length,  of the object.  the resultant  6  above p r o v i d e  spatial  F o r an  image r e p r e s e n t s t h e  projection  of  all  spin-densities  Clearly,  it  necessary  to  have  slice  known t h i c k n e s s  at  any  of This  is  the  technique  of  selection  was  first  proposed  Mansfield  in  1974  Consider perpendicular B  Q  (Figure  applied  pulse  excite  3).  of  B  q  a  o n l y the  position  excitation  plane.  selecting  within  by Garroway,  a  of a thin  direction of linear  in this narrow  desired  the  magnetic  direction,  position  containing  nominal  or  the  a  object.  slice  Grannel1  and  .  the If  a  a means f o r  selective  irradiation  to  in the  function a  the  2 5  onto  the  field  absorption  of  7  magnetic  gradient  as  is  Irradiation  shown  will  area field,  frequency  frequencies  cross-section  Narrow band of RF  static  direction. band  cross-sectional  is  a  with then  in Figure  3.  It  is desirable  slice  that  the physical  be r e c t a n g u l a r  rectangular sample;  in cross  envelope of  in t u r n ,  this  domain o f  section.  frequencies  requires  To  the  excited  implement  this,  must be a p p l i e d t o  use o f  a  the  a sinc-shaped pulse  in  t h e t i me doma i n . In p r a c t i c e , it  extends  distortion  to  the  sine  infinity.  in the  function  The r e s u l t  must be t r u n c a t e d of  frequency-envelope.  this  is  some  These d i s t o r t i o n s  be m i n i m i z e d by w e i g h t i n g t h e t i m e domain w i t h a function, pulse  typically  a Gaussian f u n c t i o n .  shape u s e d f o r  together  Figure  with  4:  its  Fourier  d e s c r i b e d as f o l l o w s . nuclei  imaging  is  shown  can  damping  The r e s u l t i n g in Figure  RF  4,  transform.  S e l e c t i v e r a d i o - f r e q u e n c y pulse in the t i m e domain a n d i t s F o u r i e r t r a n s f o r m .  The r e s p o n s e o f  the  NMR  since  (B ^^) e  is  the  nuclei  within  The e f f e c t i v e  field  g i v e n by e q u a t i o n  8  this  6.  slice  c a n be  experienced  by  B  In t h e a b s e n c e  e  f  f  -  B  x  o f the gradient  (6)  GZ  +  and a s s u m i n g  i n t e n s e B j , -the n u c l e a r moments w o u l d However, due different fields.  positions along B This  results  pulse that  approximately  in a  pulse.  this  will  Q  linear,  However,  and t h u s p h a s e reversal  approximately h a l f that  o f the  sequence 2.  The  o f events f o r s l i c e slice  the magnetic bandwidth  thickness field  gradient  system o f P i c k e r  1982,  shown f o r a  coherence can  for a  of the  Imaging  CT X - r a y s c a n n e r and  be  length o f time  irradiating  pulse.  The  full  in Figure  u s e d , and t h e f r e q u e n c y RF  pulse.  t h e p r o t o t y p e w h o l e body NMR was  installed  in the  Care Unit o f the H e a l t h S c i e n c e s Centre H o s p i t a l  part  90°  with z i s  s e l e c t i o n a r e shown  International  University of British  local  i s d e t e r m i n e d by t h e m a g n i t u d e o f  o f the s e l e c t i v e  In December  at  coherence a t the  i t c a n be  i n phase  r e c o v e r e d by z - g r a d i e n t  nuclei  experience d i f f e r e n t  l o s s o f phase  variation  sufficiently  p r e c e s s i n phase.  t o the presence o f the gradient,  end o f t h e 9 0 ° RF RF  a  Columbia  (UBC)  campus.  This  Research C e n t r e , which a l s o Positron  on  Extended the system i s  includes  E m i s s i o n Tomograph.  i m a g i n g s y s t e m c o n s i s t s o f an O x f o r d  imaging  The  a NMR  Instruments  s u p e r c o n d u c t i n g magnet, w i t h a room t e m p e r a t u r e b o r e o f 1 metre, Tesla  operating at a static (proton  magnetic  r e s o n a n c e f r e q u e n c y , 6.4  9  field MHz).  strength of The  0.15  system i s  interfaced software  with  is  a  Perk in Elmer  written  for  more d e t a i l s ) .  has  been  systems  have  not  plane  available  to  user  been  approved as  been  of  Picker  since  NMR i m a g i n g tools  in  imaging  software  package  technique image;  software  for  of  however imaging  transformation.  pulse  International  research  o f the  the  I  scientific  o b t a i n i n g an  Fourier  different  use  contained  Appendix  diagnostic  The f i r s t  contained  (see  basis,  makes  operational  clinical  available for  for  also  two-dimensional  on the  only  projection  packages  A number  sequences are system,  for  available  for  example:  Inversion-recovery (180 For  o _  direction, takes  T-90°-Data  this  equilibrium  = - M  2  Q  .  along the  Figure 5).  magnetization  Q  (  s  tau  e  e  ( i ) after  along z  in the  by e q u a t i o n  the  into the  receiver  used  to  invert  z-axis to  the  Spin-lattice relaxation  M  time  given  M  M  is  magnetization along z  pulse  signal  1 8 0 ° RF p u l s e  and the  to  at  sequence a  i.e.  place  acquisition-De1 ay-)n  magnetization,  restored  a  volunteer  selection.  the  back  subsequent  1.  scanning for  on a  also  and al1  International  T h e UBC i n s t r u m e n t  method o f  filtered  yet  Time has  research.  use  Patient  c a r r i e d out  Canada.  using  by P i c k e r  computer,  coll,  is  Application 180° pulse x'y' the  plane,  the  -z-  then  gradually of a  will which  90° then will  amplitude o f which  R  F  tip  any  induce is  7. I  - yi-^xpC-T/T^)  10  (7)  i  Bo  'A  r  A j:Bo  c  Bo  2  b  d  3  r  180V  BO  s.  90V  Duringt  41*  •A Figure  5:  Vector the  curve  The  actual  t h e w h o l e body  i  g i v e s an e x p o n e n t i a l  i n F i g u r e 6.  The r e t u r n o f  t o i t s e q u i l i b r i u m s t a t e i s d e p e n d e n t on relaxation  giving  i n more d e t a i l  spin-system.  versus  l i k e t h a t shown  spin-lattice  interactions  o f an i n v e r s i o n - r e c o v e r y  amplitude  the magnetization the  demonstrating  s e q u e n c e on a  of signal  recovery  diagrams  effects  pulse  A plot  X  rise  i n Chapter  time,  to this  T  .  The m a g n e t i c  relaxation  2.  inversion-recovery pulse imaging  are considered  system  1 1  s e q u e n c e u s e d on  i s g i v e n by e q u a t i o n  8.  -Mo  F i g u r e 6:  P l o t o f i n t e n s i t y versus t a u , the i n t e r - p u l s e d e l a y , f o r an i n v e r s i o n - r e c o v e r y p u l s e sequence.  (-180°-T-90°-t-180-t-Data a q u i s i t i o n - )  The  reasons  f o r having  implications  2.  are d e a l t with  Spin-echo At t h i s  t h e second  (8)  n  1 8 0 ° RF p u l s e a n d i t s  i n Chapter  2.  (90°—t-180°—r.-Data Acqu i s i t i on-De l a y - ) n  juncture  i t seems a p p r o p r i a t e t o i n t r o d u c e t h e  27 concept again  o f the spin-echo  i n Chapter The  After  plane  pulse  along  a l s o be  considered  sequence  i s more  clearly  by c o n s i d e r i n g t h e v e c t o r d i a g r a m s  t h e 9 0 ° RF p u l s e  reference)  It will  2.  use o f t h i s  understood  .  (along x ' i n the r o t a t i n g  the magnetization y'.  in Figure  M  Q  i s turned  i.e. the individual 12  7.  frame o f  i n t o t h e x'y'  protons  precess  about  z  At time 2t after 90* x  Figure  7:  Spin-echo pulse sequence. Schematic diagrams showing formation o f the echo.  13  in t h e xy p l a n e o f t h e l a b o r a t o r y frame o f r e f e r e n c e ( F i g u r e 7b).  The p r o t o n s  the magnetic  then  field  inhomogeneities  Some p r o t o n s w i l l  (Figure  7c).  dephase r e l a t i v e  precess faster  The s p i n - s p i n  magnetization after  application  is applied protons  were r o t a t i n g  clockwise  and hence t h e decay o f  x after  i n t h e x'y' plane I f a 1 8 0 ° RF p u l s e  the 90° pulse, the  180° about  versa  x' a n d t h o s e  (Figure 7d).  t h e 180° p u l s e , t h e i n d i v i d u a l  this  decay  in the receiver  the protons  will  coil  (this  A further will  will  The  build  magnetic  inhomogeneity  way t h e a m p l i t u d e  spin-echo the  and i n t h i s  a n d x.  i s d e p e n d e n t o n l y on  spin-echo  f o r a given t-value R  (2T)  If,  however, m o l e c u l a r  and  180  p u l s e s , then  =  Z  of the  The a m p l i t u d e o f  i s shown  in equation  9.  (9)  2  2  diffusion  after  field  o P<- */T ) ex  up  inverting  180° p u l s e c a n c e l s o u t a n y s t a t i c effects  time  cross  i s t h e "echo"),  c o n t i n u e t o dephase.  that  rotate  protons  t h e -y' a x i s t o g e t h e r , and a n e g a t i v e s i g n a l and  slower  1^, d e s c r i b e s  i n t h e x'y' plane w i l l  c o u n t e r c l o c k w i s e and v i c e x after  time,  o f t h e 9 0 ° RF p u l s e .  now be r o t a t e d  relaxation.  u a n d some o  direction  a l o n g x' a t a t i m e  will  than  system  in a particular  o t h e r due t o  and s p i n - s p i n  relaxation  t h e p h a s e memory o f t h e s p i n  t o each  t a k e s p l a c e between t h e 9 0 °  t h e echo a m p l i t u d e  will  be a f f e c t e d by  28  the d i f f e r e n t protons  magnetic  a s t h e y move.  fields  experienced  The e c h o a m p l i t u d e  e q u a t i o n 10, 14  by  individual  i s then  g i v e n by  I  where  G is  diffusion  the  a  exponential  3.  In  o  e x  2 T  plot  e x  2  of  In t h e  echo  like  -  that  2  2  field  gradient  absence o f  amplitude shown  this  pulse  Decay  magnetization,  and  almost  sampled  by e q u a t i o n  after  M , Q  immediately.  is  and  D is  effects  2t g i v e s  in Figure  (90°-Data  sequence,  the  versus  P l o t of i n t e n s i t y versus 2 tau spin-echo pulse sequence.  Induction  (10)  3  P < I Y G Dx )  magnetic  equilibrium  given  T  P<- / )  spatial  plot  8:  Free  X  coefficient.  diffusion,  Figure  (2T)  the  of  an  8.  for  a  acquisition-De1 ay-)n the  9 0 ° RF p u l s e  turned The  into the  signal  the  x'y'  amplitude  plane is  11. 1=1  o  (l-exp(-TR/T.))  J-  15  (11)  For between  all  three  pulse  successive  referred  to  as  reapplications  the  repeat  The a p p e a r a n c e o f number  of  parameters  relaxation density pulse  (p),  an  weighted  of  (Tj),  used  image  one  object;  (D) a n d obtain  of  of  the  the  is  the  time  sequence  dependent  namely,  flow.  It  is  displayed  time  a  (T ),  spin-  2  depends on  which  is  to  is  For  provides  the  chosen  intensity  parameters.  sequence  on  spin-lattice  also  image,  object  inversion-recovery pulse  entire  relaxation  the  the  above,  (TR).  spin-spin  to  described  NMR i m a g e  the  in which  towards  time  the  diffusion  sequence  provide  the  time  sequences  an  example,  image  29 which  is  Tj  different  areas  difference  t and  weighted o f the  in their  the  object  contrast  observed  i s m a i n l y due  Tj-values.  T h i s can be  to  between  the  explained  as  f o l l o w s : f o r a g i v e n t - v a l u e , areas o f d i f f e r e n t Tj w i l l have r e c o v e r e d d i f f e r e n t magnitudes o f z - m a g n e t i z a t i o n : t h u s o * when t h e 90 sampling pulse is applied to observe the signals,  areas  intensity. sequence  of  As a  different second  provides  an  T  will  example,  image w h i c h  have  the  different  Free  Induction  is m a i n l y dependent  Decay on  the  30 spin  density  present  i n any  explained,  or  part  since  equilibrium data  » p,  of  this  the  long for  words,  sample.  the  This  sequence merely  z-magnetization.  a c q u i s i t i o n and  sufficiently  in other  all  protons 16  to  is  i f the the  relax  of  protons  easily  samples  However,  reapp1icat ion of  number  the delay  90° pulse back  to  between is  not  equilibrium, Tj  then  dependence.  the  also In  image w i l l  and data  has  a dependence  on  can  detail  (Figure 9).  Figure  S a g i t t a l image o f using a spin-echo  goal  is to quantify  hope  that  they  characterization  of  appear  occur  between  i n an  image  this  with  exquisite  achieved,  the  next  a human h e a d o b t a i n e d pulse sequence.  NMR p a r a m e t e r s  measured  j_n v i v o ,  in the  tissue  32 '  .  of quantitative  differentiating  which  With  can p r o v i d e a method o f 31  In a d d i t i o n ,  measurements  between  visually  identical  it  that  different  17  of  T_.  now b e o b t a i n e d  anatomical  help  d i s p l a y some d e g r e e  acquisition, resulting  v i v o NMR i m a g e s  9:  also  S p i n - s p i n r e l a x a t i o n may a l s o  90° pulse  which  the  is  there  types  on t h e  only  of  with  i s any  the chance  pathology  NMR i m a g e .  Thesis 1.  Objectives  To d e t e r m i n e  the  spin-lattice  have  acceptable  experiment. on t h e  whether  relaxation errors,  obtained  To d e t e r m i n e  2. the  spin-spin  have  errors,  which  the  also it  is  time, under  to are  obtain  be  of  imaging  the  of and  Imaging  conditions  examined.  possible which  the  values  reproducible  conditions  varying the  will  whether  possible  time,  of  relaxation  acceptable  is  under  The e f f e c t s  values  it  to  are  obtain  values  reproducible  conditions  of  the  of  and  imaging  experiment. 3.  To a p p l y  whether  it  relaxation appears  is  quantitative feasible  times  to  visually  introduce 1.  (Bj).  these  the  field  of  the  spin-lattice  of  static  are  times,  determine  and  spin-spin  pathology  which  NMR i m a g e .  the  sources  inhomogeneities  relaxation  between  problems  imaging, the  inhomogeneities  range o f  usual  possible  In  the  on t h e  conditions  further  means t h a t  a  the  Inhomogeneity  RF f i e l d  If  to  use  differentiate  similar  In a d d i t i o n measurements,  to  NMR i m a g i n g j_n v i v o a n d  of  imaging of  use  of  are  since  experiment  error,  magnetic  large,  q u a n t i t a t i v e NMR  namely:  field  large  they  Q  bore  difficult they  (B )  would  to  field  overcome.  non-linearity.  This  rise  dependent. 2.  Magnetic f i e l d  distortion  in the  gradient image.  18  the  magnets  give  are  and  causes  to  3.  Slice  selection.  a v e r a g i n g which 4.  Spatial  resolution.  6.  diagnostic Methods  of  appearance o f observed  in d e t a i l  This  Software  have  limits,  Reconstruction.  the  image a n d  Limitations.  These can a f f e c t  time.  the  introduce ambiguities  Certain  unexpectedly  the  strategy of t h i s  measurements on s i m p l e  difficult  expended t o o b t a i n transformation sets  task.  spacially  in  the  encoded  projections  (Figure  10) o f  vials  was t h a t  the  of  TR)  accurate  signal  f r o m any s u b s e q u e n t  expected that  if  the  proved t o  x  using  from back  sulphate from of  T  projection doped  w o u l d be o b s e r v e d ,  with  without  J t  and  The  these  imaging o p e r a t i o n .  positive  Fourier  (CuSO^).  inversion-recovery pulse  19  then  be an  spectra'  calculation  carry  much t i m e was  intensities  as d e s c r i b e d e a r l i e r ,  intensities  systems,  c o n t a i n i n g water  copper(II)  c o u l d be u s e d f o r  then,  (such as  work was t o  Initially,  single  * spectra' artefacts  This  of  concentrations  intention  parameters  t h e outcome o f  p r o g r e s s t o more complex o n e s .  signal  over  to  measurements.  quantitative  used,  smallest  measurements a r e  u s e t h e y must be r e p r o d u c i b l e  At t h e o u t s e t ,  various  2.  determine the  If q u a n t i t a t i v e  which can a f f e c t  quantitative  data  will  in Chapter  volume  intensities.  7.  out  the problem o f  studied.  Reproducibility.  be o f  introduces  is discussed  a r e a w h i c h c a n be 5.  This  It  was  s e q u e n c e was negative  d e p e n d i n g on  the  Figure  10:  Fourier transform of a single in back p r o j e c t i o n imaging.  relaxation t-value. was  time  the was  for  became  of  apparent  phasing These  these  is  and  also  could  solutions that  the  are  could of  which  observed  affect  explain,  doped w i t h phenomena  11.  arose  20  other  implied the  value  null of  Tj  solutions signs  errors  In an  were  attempt  manufacturers, various  CuSO^ were  in detail the  the  phase  studied.  from the  employed by P i c k e r  some o f  around  in signal  and  of  signal  This  different  the  choice  concentration  positive.  in Figure  not  considered  evaluates  the  observed  shown  reconstruction  problems  chapter  were  the  single  fluctuations  phenomena,  International,  combinations  and  and  intensities  when s e t s  solutions  a  be  signal  doubt,  An example  understand  Picker  sign of  simultaneously,  individual  study  i-values,  found t o  In a d d i t i o n ,  studied  apparent. to  range o f  in serious  under  in practice  always  absolute  obtained. were  were  sample  when  using a  intensities  point  the  However,  studied  that  of  projection  methods  It of  International.  in Chapter sources  of  1.  That error  W W Figure  11: F o u r i e r t r a n s f o r m o f a s i n g l e p r o j e c t i o n in back p r o j e c t i o n imaging showing phase errors.  mentioned phantoms  previously,  c o n t a i n i n g water  Once t h e quantitative these  such as  behaviour Tj  a n c  j  values  analyses  inhomogeneity,  doped w i t h  o f the  was  on a l 1 t h e  c a r r i e d out  goal  o f the  studies  quantitative  NMR m e a s u r e m e n t s  1.  a  if  of  reasons  The mammalian c e l l  complex and 2.  number  Water there  Is  Is  not  exists  on  imaging c o n d i t i o n s complete  of  error  course,  The a b i l i t y  j_n v i v o for  was,  is a  to  carry  difficult  out  task.  this:  c o m p o s i t i o n and  environment  Is  very  static. i n more t h a n  slow exchange  contributions  understood,  results.  a p p l i c a t i o n s J_n v i v o .  are  and  was  ions.  c a r r i e d out  o f the  quantitative  There  were  studied,  using  paramagnetic  instrument  The e f f e c t  obtained  The u l t i m a t e  Q  measurements  simple systems.  on t h e  B  one  on the  may come f r o m 21  each  state  within  NMR t i m e  scale,  separate  state  cells  3  giving  4  ,  and  rise  contributions  may c o m e  from each  separate  state  giving  rise  35 to  multiexponential  the  resultant  intensities  behaviour  •  can  the  sum o f  signal  compartments  having  different  intensity various  properties.  This  is  be  considered  T h i s means  i n more  that  detail  in  2.  Mobile  3.  signal from the  relaxation Chapter  relaxation  fat  again  giving  since  the  protons  may c o n t r i b u t e  rise  to  multiexponential  protons  of  fat  relaxation  rates,  frequencies  at  but  the  and  water  virtually  low m a g n e t i c  to  the  NMR s i g n a l ,  relaxation  behaviour  t y p i c a l l y have  identical field  different  resonance  strength  used  in  i mag i n g . These describes the  obstacles the  first  development  (EAE),  a wel1  of  present use  of  a  real  challenge.  quantitative  Experimental 36  documented  3  NMR i m a g i n g t o  Allergic  animal  Chapter  model  study  Encephalomyelitis for  Multiple  37 Sclerosis  (MS)  ,  in primates.  f a s c i c u 1 a r i s monkey, followed rise  to  using  are  These  abnormal  and  dark  elevation  areas  measurements  from the  central  observed  appear  1^ a n d  day o f  of  NMR i m a g i n g .  in the  those  induced  development  bright  inversion-recovery  in their  Quantitative brain  areas  s i m i l a r to  on an  the  quantitative  abnormal  which  and  EAE was  Tj  d e t e c22 tion  The d i s e a s e  nervous  system  was  gives (CNS)  i n humans w i t h M S . spin-echo 39  image  , due  to  38 image3  the  respectively.  carried of  Macaca  disease  on a  values  were  the  in a  the  out  on the  disease  monkey's  until  death.  mortem,  and  already  s h o w n NMR i m a g i n g t o  of  the  Tj  a  EAE In p r i m a t e s ,  extrapolating  the  n  d  and  j  £  v a  iues.  the  findings  be  These  a powerful  future to  23  studies  the  looks study  tool  have in the  promising of  MS  in  study  for  humans.  CHAPTER 1  E V A L U A T I O N OF T H E INSTRUMENT  In  preparation  measurements  on t h e  is  that  important  for  c a r r y i n g out  w h o l e b o d y NMR i m a g i n g i n s t r u m e n t ,  its  mode o f o p e r a t i o n  understood;  the  following  Information  for  measuring the  this  effects  images o b t a i n e d provided  a  of  the  object  which  referred  automatic phasing  NMR p a r a m e t e r s  of  could as  value for  be the  Within  spatial  of the  thereby  the  necessary  Interest  In  on t h i s  usual  Field  This  volume a t  this  volume, the  smallest  determined.  resolution.  used  on t h e  useful  methods  instrument were  evaluation  This  of  of  were  identified  quantitative  and  measurements  chapter  in detail.  Inhomogeneity  and  Inhomogeneity  fields  24  for  studying the  the  This  The e f f e c t s  and the  Introduced  method adopted  of these  examined.  homogeneous  instrument.  Magnetic F i e l d  Rad1 o f r e g u e n c y  distribution  of  quality of  the  attenuator,  allowing  process  were  I d e n t i f i e d was t h e n  The p r o b l e m s t h e y  Static  The  instrument  reconstruction  c a r r i e d out  describes  1nhomogeneity on the  field  magnet.  to  and  explained,  a.  fully  evaluation provided the  using the  setting  studied.  be  of  numerical  centre  to  be  it  work. The  is  q u a n t i t a t i v e NMR  spatial  i n v o l v e s p l o t t i n g them on  a  point  by p o i n t  therefore an  basis,  decided  indication of  field  which  to the  1 cm d i a m e t e r  CuS0 ,  as  4  A B , and q  shown  the  phantoms  glass  tubes 12.  which  the  It  static  consisted  the  provide  magnetic  of  field equally  c o n t a i n i n g water  Using  was  could  radiofrequency  These  in Figure  consuming.  phantoms  distribution of  AB j .  spaced  time  construct  inhomogeneity,  inhomogeneity,  is  doped  with  instrument  U~  r-  Figure  12:  coil,  20 mm s l i c e  Induction were  —r-  20  1  40  cm  30 o Diagram o f p a r a l l e l tube phantom f o r studying magnetic f i e l d inhomogeneity.  transmitter and  i  10  which images  is were  Decay sequence  obtained  using  a  256  taken  in the  in a l l  xz plane,  used  obtained  (FID)  three  x 256 d a t a  also  shown  for  body  using the  Free  in Figure  13.  orientations,  xy,  matrix.  An e x a m p l e  of  is  in Figure  14.  shown  25  imaging,  x z and these  10 mm  Images yz, images,  Distortions  90*  Slice Select Gradient  Read Gradient  Phase Encoding Gradient  Data Collect  Figure  13:  in the  images o f t h e g l a s s t u b e s  gradient  Figure  F r e e I n d u c t i o n Decay g r a d i e n t sequence.  non-linearity,  14:  AG.  The  FID image o f p a r a l l e l i n t h e xz p l a n e .  26  (FID)  pulse  represent  and  AB  distortions  tube  phantom  Q  and/or  are observed  on  the  periphery  and  AB  the  coil  of  become  Q  in a  image. distance the  along  intensity  larger  V a r i a t i o n in the information  variation  Figure  image w h i c h shows  significantly  centre.  image p r o v i d e s result  the  15  is  the  in  as  a plot  of  one  in that  it  expected,  moves  away  across  imperfect  intensity  x - d i r e c t i on;  as  intensity  on A B j .  intensity  that,  as  a  from the  pulses  region  will  of  the  function  demonstrates  AG  of  clearly  how  varies.  1—z—i—»  s~  7  Distance (cm)  Figure  15:  P l o t o f i n t e n s i t y as a f u n c t i o n along the x - d i r e c t i o n .  Examination a  volume o f  12100  homogeneous, consistent length  and  these  cm^ a t  the  images centre  should provide  quantitative  across  processing.  o f al1  this  Outside  this  can  be  region  o f the  27  indicates  coil  good q u a l i t y  images  for  that  is  Variations  corrected the  distance  together  measurements.  region  of  and  in  in the  homogeneity  pulse data  deteriorates, be o b t a i n e d magnet  and a l t h o u g h out  axis,  to  q u a l i t a t i v e l y useful  4 5 cm i n d i a m e t e r  intensity  and  spatial  and o f  images  can  4 5 cm a l o n g  distortions  are  the  both  preva1ent.  Spat i a 1  b.  Resolut ion  A s i m p l e phantom spatial  resolution of  was  constructed  the  instrument  180'  determine  used.  It  the  consisted  of  IBCf 18 0*  7  J  RF  to  1  8*o» Select Gradient  Read Gradient  P n a s e CncodinQ Gradient  J  Data Collect  Figure  16:  Inversion-recovery sequence.  melting-point solutions in  of  vials of  were given  then  pulse  c a p i l l a r y tubes CuS0  4 ?  r j . 9 9 mM a n d  2 cm d i a m e t e r .  obtained  In F i g u r e  16.  filled 2.54  and  gradient  with  two  As can  28  different  mM, r a n d o m l y  10 mm h o r i z o n t a l  using the  seen  In t h e  arranged  slice  inversion-recovery be  L  Image  Images  sequence In  Figure  17,  it  appears  identified  17:  1  than and  one is  Figure  '  «  However,  tube.  shown  c a p i l l a r y tubes  can  1 mm r e s o l u t i o n  is  1  •  4  it  in a  in Figure  Diagram o f  is  image o f  possible  single  A second  pixel  phantom  18;  ' 8  1  6  Inversion-recovery tube phantom.  observed  18:  that  1  2  attainable. intensity  individual  which suggests  I 0  Figure  that  all  cm  the  signal  arising  therefore  dimensions  resolution  29  was  1  capillary  that is  1  be  phantom.  are  from  more  constructed, as  indicated.  In t h e  image  resolution  shown  in Figure  the  1 mm p e r s p e x  of  19,  the  wall  arrow  indicates  between  two o f  the the  XL Figure  19:  areas.  Spin-echo  This demonstrates  resolvable  and  the  less  than  c.  Attenuation The  that  image o f  it  that  1 mm i s  maximum r e s o l u t i o n  phantom.  indeed  easily  possible  is  somewhat  this.  instrument  used  automatically  receiver  resolution  in order  This  implies that  with  a  range o f  to for  in these  changes  the  maximize the a  -t-values  series (where  30  of t  studies  is  input  gain  signal  to  designed of be  the  RF  digitized.  inversion-recovery = pulse  such  interval),  images the  attenuation directly manual  will  the  Figure  be  comparable.  setting  thesis,  not  20:  constant  The  o f the  and  instrument,  attenuator.  attenuation  the  was  set  Intensities  however,  For a l l  based  also  studies  on t h e  not allows in  signal  this  from  the  Phantom used f o r s t u d y i n g a t t e n u a t i o n and f o r c a r r y i n g out Tj and T measurements. 2  sample  using a  spin-echo  sequence w i t h  2t  = 2 6 ms a n d  TR = 5  sec. In o r d e r attenuation setting, shown  a  to  provides  was  obtained  setting  20,  placed  The f i r s t of  the  same  the  which  in the  using the  = 5 sec.  whether  simple experiment  in Figure  CuSO^,  check  manual  intensities was  receiver  three  coil  which  31  gave  the  automatic The  phantom  solutions  and  sequence w i t h  image was o b t a i n e d  attenuator,  as  of  carried out.  contained  spin-echo  setting  with  two  of  images  Zi = 2 6 ms a n d TR automatic  26 d e c i b e l s  (dB).  The  second  image was t h e n  attenuation solution  Table  to  are  I:  obtained  26 d B .  given  The  manual  2  plus  centre each  or  g i v e n as  vials.  in the  123 t 7.6  Manual  122  i  133  7.6  It  6.1  131 t 5.9  intensities  identical.  mean  receiver  i  comparing attenuation.  values  from  are  two  given  for  different  coil.  all  if)  0.99 i  6.5  154  7.4  146  i  9.7  139 • 6.6  133  J  6.5  152 • 7.6  145  i  7.9  in both  images  be assumed  provide  images  that with  i  are  virtually  manual the  setting  correct  i ntens i t f es.  d.  Phas i n g and  Reconstruct ion  As<^previous 1 y c o n s i d e r e d , images o f an o b j e c t values, sequence  obtained 12,  which  using the  is.dependent  has  the  contrast  regions  observed  of different  i n v e r s i o n - r e c o v e r y (IR) on the  32  2.6  the  134  observed  will  each  6.5  140  can t h e r e f o r e  attenuation  for  deviation, at  Two v a l u e s  2.54 i  images  o f the  the  standard  4.96 i n  Autoaatic  the  setting  solution corresponding to  Attenuation  of  two s p i n - e c h o  minus  of the  positions  The  from  are  obtained  the  I.  and automatic  Intensities cm  intensities  in Table  Intensities  by manually s e t t i n g  intrinsic  In  Tj pulse  difference  (-180°-T-90 -Data a c q u i s i t i o n - )  (12)  0  n between within  the the  spin-lattice different  relaxation  spatial  intensity  changes which are  interval,  i .  sample  shown  is  A typical  domains. a  21  for  of  This  function  situation  in Figure  rates  for  of  the leads  the  a two  two  protons to  pulse compartment  solutions  of  CuSO. 4  (see  Chapter  single  2).  The  compartment  at  signal a  intensity  particular  observed  value  from  T is  of  a  given  by  40  equation  13: I  - I {l-[l-rW(l-exp(-k/T )]exp(-T/T )}  x  where  1  o  I  =  Q  k  intensity  T >>  at  W = correction  Although signals  associated many  the  between with the  the  mode".  time  positive.  the  factor  the  phase  180°  for  all  In t h o s e  and  magnetization can  180°  signal  and  signals  necessary  shown  that  are  rectified the  after  signals  become  form o f  in  21a, the  acquisition  Fourier to  to  in Figure  NMR s i g n a l s  subsequent  circumstances,  33  is  produces  negative-going  plot  and  pulse.  Itself  o n l y produce means  acqu i s i t i on  pulse  information  positive  What t h i s  domain  transformation,  of  data  NMR d a t a - a c q u i s i t i o n  imaging p r o t o c o l s  "absolute of  the  w h i c h have  distinguish  Tj  = wa i t i n g p e r i o d b e t w e e n reapplication  (13)  1  the  inversion-recovery  intensity  magnitude  21b,  and  the  *high  reconstructed long  Tj  as  occurrence used  image  from one of  in this  this study  reconstruction, numbers, employed. from  as  curve  could  signals  which  short  the  Tj. the  systems,  reconstruction  it  introduced  in  a  In o r d e r  to  minimize  software  of  the  when a n  was  p o s i t i v e or  IR p u l s e to  observed  additional  instrument  that  negative  sequence  obtain  values  this  problems.  of  the  "rea1-intensity"  either  However, d u r i n g attempts  various  Figure  come f r o m a r e g i o n  option of  provides  appropriate,  observed  equally well  ambiguity, has  to  reconstruction.  intensity'  of  corresponds  is of  method  Tj of  In o r d e r  to  simple  phantoms  Figure  22:  Illustrate were  the  phenomenon o b s e r v e d ,  constructed,  each  consisting of a  (Figure at  vial 22).  accurately  and  located  spot'  p.60).  4  i n s i d e a beaker  The two aqueous  values  of  As assembled,  and phantom-B t o  a  of  solutions  known c o n c e n t r a t i o n s  h a v i n g known T j  (see  2 0 mm  Phantom used f o r s t u d y i n g i n t e n s i t y a m b i g u i t i e s A = 4 . 9 6 mM C u S 0 , B = 0 . 9 9 mM C u S 0 4  diameter  two  of  70 mm d i a m e t e r contained  4 . 9 6 mM a n d  117 ms a n d  4  2  0 . 9 9 mM  5 3 4 ms r e s p e c t i v e l y  phantom-A c o r r e s p o n d s  *cold-spot'  CuS0 .5H 0  in terms  of  to  a  * hot-  relative  Tj  va1ues. The t w o phantoms receiver of  coil  used  for  were head  30 cm, a n d h o r i z o n t a l  obtained  placed side imaging,  (xz)  which  10 mm t h i c k  simultaneously through  35  by s i d e  both.  has  In  the  an  aperture  slice-images  IR i m a g e s  were  were  obtained  with  sec  T.  plus  t-values  The r e s u l t a n t  The p o s i t i o n s o f t h e experiments magnitudes white of  of  each  cursor,  Figure  line  and the  the  each  trace  below  23c where t h e inner  it,  outer-component  negative.  36  reversed  the  as  o f the  23. and  unchanged.  the  The  position  corresponding shows  can be  o f the  4  signal  image shows t h e  intensity trace  component  in Figure  relative  s o l u t i o n were  through  The  shown  were t h e n  and n e g a t i v e - g o i n g s i g n a l s ,  phantom and t h e both  expected,  particular  intensity-projection. positive  as  5 0 - 1 0 0 0 ms a n d TR o f  images a r e  two phantoms  repeated;  horizontal  the  r a n g i n g from  clearly  seen  the  in  right-hand  left-hand  phantom  are  F i g u r e 23:  I n v e r s i o n - r e c o v e r y images intensity ambiguities. a. c. e. g. i.  i X X 1  X  = 50 ms = 150 ms = 300 ms = 500 ms = 1000 ms  b. d. f. h.  37  x x x x  — — = -  demonstrating  10 0 250 400 600  ms ms ms ms  Since obtain  the  relative the  IR-images  the  shown  traces  24:  case.  The n a t u r e  which  whereas  both  they  that  the  close  to  =  should  be  of  of the  would  two  however,  themselves  the  the  and  employed expect to  as  seen  can  be  plot  of  this  is  not  to  the  solutions  the  in Figure 24,  problem  data  signal  are,  given  i  one  was  follow both  the  P l o t o f i n t e n s i t y versus tau showing fluctuations in signal sign. • 4 . 9 9 mM CuSC© 0 . 9 9 mM C u S O . 4 4  examines  time  each  T shown  versus  Figure  when o n e  of  in Figure 21a;  cursor  intensity  reconstruction  in Figure 23,  intensities  trend  from  phase-sensitive  corresponding  intensities  in fact,  null  point  100 m s ,  all  positive.  i s more  the  signals  In p r a c t i c e  38  to  i  s h o u l d be  positive. of  clearly  4.96  As a  the  = 50 m s ,  example,  solution  4  after  value at  at  negative,  second  mM C u S 0  observed  understood  that t  is  i-time  = 150 ms  is  negative becomes 0.99 at  and  remains  positive.  Conversely, the  mM s o l u t i o n s h o u l d b e  x = 400 ms,  signal  after  which time  Obviously,  these  attempt  quantitative  the  i  at  absolute  serious  becomes  positive  measurements  of the  signal  this  phenomenon  carries  attenuation  out  based  peak.  A global  making  this  signal  signs  a peak  on t h e  phase  then  real  between  made  the 250-  any since  image was  to  become t h e  out,  when i  resulting = 50 m s ,  4 . 9 6 mM s o l u t i o n s a r e coming from the  on t h i s o f the  this it  Is  maximum p o s i t i v e p e a k .  is manually set,  the  reference  this  In t h e the  same  signals  negative, 0.99 peak  The  in  39  instrument set  the  intensity  c a r r i e d out  by  A l l other  peak.  If  it  happens  phase-corrected E v e n when  180°  the  phase c o r r e c t i o n  Is  still  signal-sign fluctuations. from  with  is  has  maximum  both the  the  0.99  maximum  mM s o l u t i o n . and  and  view to  and p o s i t i v e .  then  4 1  2D i m a g e  Is t h e n  relative to  be a n e g a t i v e - g o i n g peak  attenuation  search  correction  maximum p e a k are  view o f a  magnitude  to  as  point  again.  explained  no p h a s e e n c o d i n g g r a d i e n t .  software  The c e n t r e  c a n be  effectively  acts  the  Instead,  in a particular  for.  signal  sign  null  very d i f f i c u l t ,  compensated  Thus,  it  doubt.  However,  carried  its  negative  in signal  time  intensity of  prior to  = 50-150 ms, it  which  become p o s i t i v e .  fluctuations  sign  signal  negative  and t h e r e a f t e r  is p o s i t i v e from  400 ms,  T = 2 5 0 ms a t  so u n t i l  inverted  This  mM a n d  intensity  automatically  180°.  Since  the  signal  from  becomes  the  4 . 9 6 mM s o l u t i o n  positive.  As a n o t h e r  obtained  w h e n T = 150 m s .  the  mM s o l u t i o n s h o u l d b e  0.99  signal from  This  from  the  hence  the  again  In o r d e r  fast  0.99  to  acts to  signs,  as  get  the  the  around the  i-values being used.  reference  peak  of al1  however,  single  signal  and  other  projections  since they  obtained,  the  were t o o  long  Tj  then  the  by t h i s has  a  negative  solution).  4  therefore  the  images  for  from  them d i r e c t l y ,  volume, such as which  40  will  However, a  bath  the  result  as  of use  the  measuring  IR i m a g e s  i m a g e s o b t a i n e d j_n v i v o  a  correct  measured  signal  This  longer p o s s i b l e to  Instead  by  always acted  ensured  back p r o j e c t i o n complex.  and  t  surrounded  One u n f o r t u n a t e  was no  that  fluctuating  study were  method o f p h a s i n g .  large  J  the  peak.  concentration  processed.  affected  It  of  than  longer T  each  subsequently  cases,  Its  the  is  magnitude  for  species  In most  it  intensities  paramagnetic  from  from  larger  too  Image  a n d was a l w a y s p o s i t i v e f o r  signals.  from  the  it  signal  reverse  problem o f  consequently  was t h a t  the  and t h a t  still  ( ~ 1 0 mM C u S 0  range o f  Tj,  most  bath  the  the  that  is  under  the  this,  fact  reference  solutions  r e l a x i n g water  phasing  negative,  mM s o l u t i o n  provided  the  t-value  in practice the  same s i g n ,  consider  4 . 9 6 mM s o l u t i o n , b y v i r t u e o f  it  signal  i s due  of the  example,  At t h i s  4 . 9 6 mM s o l u t i o n p o s i t i v e ; observed.  Is  were  of and  not  i f a  fluid-filled  be  region of cyst,  s h o u l d be o b s e r v e d from  this  region  on an  Inversion-recovery  The r e a s o n  for  become t h e  maximum p o s i t i v e p e a k .  course, also  this  is that  the  i n v e r t e d and  problem which  is  the  image  signals  have  the  signal  the  manufacturer  a  paired  Although  method it  longer  imaging time.  total  A further in the  consists  of  does  the  t  = 2 0 0 ms  this be  two s i g n a l s  shown  in the  following  image  magnitude  The b a n d i n g instrument 20  it  Identical  is  from  from the  with.  of  of  a  and  is  which  entire of  results,  approximately equal  to  intensity  having  number  0.99  is  reference.  the  the  are  a  companies  a  instrumental  i n F i g u r e 25b as  phantoms. occasions  ruling  out  problem.  4.96  mM s a m p l e  mM n e g a t i v e . magnitudes  absolute  That is  intensities  reconstruction.  c a n be  carries  image,  Instrument  have  deal  to  of  regions  was o b s e r v e d  large  180°  clearly  in Figure 25a,  on a  signal  p o s i t i v e and t h a t  these  to  possibility  bands a c r o s s  with  the  have  is  disadvantage  of a transient  t-value,  It  image a s  IR-image  positive.  of this,  surrounding  aberration  was r e p e a t e d  possibility  should  will  the  the  l i g h t and dark  a p e r i o d o f months  At  the  have  instrumental  The measurement over  the  employed by o t h e r  removes  ambiguities,  shown  The r e s u l t  saturation-recovery  this  In f a c t ,  phase c o r r e c t e d  wrong s i g n .  One m e t h o d o f p h a s i n g use  from  is  is.  out  explained its  peak  unable  to  e f f e c t i v e l y sees  41  4 1  as  search  find  follows: on t h e  when  centre  a maximum p e a k .  no s i g n a l  due  to  the  the view  of  The intensities  having the time  equal  but  opposite  echo p o s i t i o n , t h a t domain s i g n a l .  Figure  25: a .  b.  sign.  is,  This  This  there  c a n be  is  results a time  represented  in a  shift in  shift of  in  the  the  I n v e r s i o n - r e c o v e r y image o f phantom u s e d t o d e m o n s t r a t e i n t e n s i t y a m b i g u i t i e s a t i = 200 ms. The same i m a g e i n a . reconstruct i on.  42  after  magnitude  following the  way:  function  derivation  In time, gets the  f(t-a)  of  f(t-a)e-  i ( J t  dt  words,  results  u.  shift  following IR  pulse  180° and to  =  a  a )  e-  i u a  time  domain s i g n a l  remains factor  identical  which  proportional  phase  shifts  2  .  The  to  the  (14)  is  shifted  except  varies  observed  proof  the  that  time  which  banding  domain s i g n a l  experiment. sequence  the  As  used  indicated  on t h i s  time  in  that  linearly  in the  is applied at  time  c o l l e c t the  echo  at  must  be  encoding  identical  the  If  spin-echo of  used.  If  gradients to  the  above  this  those time  =  of  for  data  image  it  with  shift,  a  the  echo  position  substitution  gave  rise  to  has  in the banded  43  due  p r o v i d e d by  t  the  for  has  after  an  the  echo at correct then the  a. in  data  with  actual  additional 90°  2t.  pulse In  read  the  time  domain  images  like  order  and  acquisition  left  those  = 20 m s ,  a  the  sequence  is  to  gradient  the  spin-echo  acquisition  2t  is  p r e v i o u s l y , the  the  substituted  that  was  13 m s ,  required  used  gradients  sequence  time, t  observed  instrument  acquisition of  shift  4  - e^FCa.)  d(t-a)  data  26 m s .  and  is  -  subsequent  sequence  are  of  pulse  phase  1 u a  then  25a.  Additional time  i w ( t  phase  and  in the  F(w)e~  F(u)»  straightforward:  i f the  by a  Fourier transform  transform  Fourier transform  frequency,  Figure  is  the  the  - /f(t-a)e-  multiplied  This  has  has  this  other  its  i f f(t)  with  unchanged,  required result  is  signal. that  2T  shown  for a This in  Figure which give  25a. causes  rise It  using was  It  no  to  was  the  a  fast  from these  In t i m e  phase  also  of  shifts  possible  to  any  signals  correct  required  to  44  any  factor  domain  signal,  on t h e s e  images.  will  these  phase  shifts  water  bath,  since  there  the  data  that  for  from the  This allowed useful T-values  time  observed  possibility of  the  studies  the  r e l a x i n g background  misinterpreting  range o f  clear  shift  the  longer  studied.  is  to  instrument solutions be  determine  being  obtained T,.  for  the  CHAPTER  2  Q U A N T I T A T I O N OF NMR P A R A M E T E R S  than  The  appearance  one  parameter.  images whose and  which  identification and  normal  pulse  discrimination;  Tj'and  T2 values.  Tj  T  and  _  using the  2  instrument. of  a.  the  Both  measurement  conditions and  This  and  in turn  chapter  Picker  T^ o b t a i n e d a r e  Relaxation  o f the  spins  return  lattice  after  perturbation.  lattice  most  relative  measurement  of  imaging  d e f i n e d and the  methods  imaging values  of  Tj  (Tp  to  process  nuclear  exchange  The optimum  whole body  of  Tj  examined,  s p i n - l a t t i c e relaxation time  an  In  on the  l i m i t a t i o n s on the  The  involves  parameter,  for  the  The e f f e c t s  Definition  constant  provide  provides the  describes  are  more  p r o v i d e d by  depends  (i)  time  one  important.  International  described.  instrument  tissue  one w h i c h  time constants  are  Spin-Lattice  most  is the  this  chosen to  The c o n t r a s t  the  on  differences  and d i s e a s e d  sequence  tissue  are  necessary  images a r e  dependent  weighted towards  of pathology.  T2~weighted  choice of  are  provide the  between  Is  P u l s e sequences  intensities  also  intensity  o f a n NMR I m a g e  thermal  and o c c u r s due t o  equilibrium form  between  Interaction  45  c a n be d e f i n e d  whereby an  This  o f energy  (Tj)  of the  ensemble with  of  their  relaxation spin  between  and  the  the  as  fluctuating those  field  generated  nuclei.  These  different 1.  generated  in the  by t h e  lattice  interactions  processes  magnetic  4 3  ,  shift  rotation  is  aqueous  solutions  paramagnetic unpaired  species.  times  greater  water  protons,  and  hence  4 4  they  relaxation  o f the  the  and the  a  If  the  bulk  exchange  to  magnetic  moments o f species  m a g n e t i c moments o f  the  larger  ion  solvent o f the  relaxation  4 5  .  species,  case  water)  The bound  have d i f f e r e n t water the  3  fields,  unpaired electrons  two phases  the will on  the  water  relaxation  molecules and  the  gives  rise  time.  random f l u c t u a t i n g magnetic  46  local  10  water.  (In t h i s  o f the  metal  the £a.  much  All  contained  are  nuclei  molecules within  single observed  magnetic  r e l a x a t i o n o f the  effects  molecules  o f the  section  paramagnetic  nuclear  solvent  sphere o f the  protons  in t h i s  give rise  solvation  Rapid  fluctuating  s o l u t i o n o f a paramagnetic  be d o m i n a t e d by t h e  times.  interactions  to  Since the  dominate the  In a d i l u t e  rise  in these  than  interactions  a p o s s i b l e r e l a x a t i o n mechanism.  studied  electrons  of  interactions.  fields  nucleus  number  interactions  gives  a  a  magnetic  interactions  anisotropy  Any m e c h a n i s m w h i c h at  and  namely:  4. s c a l a r - c o u p l i n g 5. s p i n  involve  dipole-dipole  chemical  nuclei  by movement o f o t h e r  can  2. e l e c t r i c q u a d r u p o l e 3.  precessing  fields  at  the  site  to  of  the  the  paramagnetic  solvent  induces  a  protons  nuclear  The T j o f given  by t h e  a  species  occur  then  relaxation  T.  at  spin transition nucleus  following  from  bound t o  equation  the  a  Larmor frequency  can o c c u r , I  -1/2  =  i.e. to  paramagnetic  of  it  +1/2.  site  is  :  + The f i r s t between is  terms  the  arise  called which  Bohr  nuclear  b y oi^ a n d wj , y j magneton,  distance  Hz.  and  is  S  between  the  dipole-dipole and the  correlation the  nuclear-electron  characterized  electronic given  by the  S,  from modulation o f  isotropic is  from the  electron-spin,  characterized  terms  A/fi  arise  is the  the  time, scalar  the  nucleus  times  electron and  the  are  interaction  defined  (often  interaction) The  t  frequencies ratio,  spin,  r  are  8 is  is  the  the ion,  coupling constant as  which  second  paramagnetic  hyperfine  I,  The  i  time,  gyromagnetic  total  spin,  spin-exchange  Larmor p r e c e s s i o n  electron-nucleus  The c o r r e l a t i o n  nuclear  by c o r r e l a t i o n  is  interaction  and in  follows:  (16)  47  where  T.^  = life-time of a  t  = rotational  R  (ii)  Measurement  of  study, carry  relaxation  of  o f measurement, the  out  method the  described  bound  time.  i n NMR s p e c t r o s c o p y ,  is  well  known a s  including  - 5  documented^ *}  #  i n v e r s i o n - r e c o v e r y was on t h e  aqueous  In  this  used  solutions,  to  and  is  sequence  given  intensity  used  in the  inversion-recovery  below:  at  a particular  t-value  -)  is  (12)  g i v e n by  equation  7 ,  = I (l-2exp(-T/T ))  I  which  is  obtained  describing  decay  o  by  (7)  1  integration  of the  Bioch  equation  of M , z  dM  —5- - -(M -M )/T. dt  where  M  q  is  below.  (-180°-T-90°-Data a c q u i s i t i o n  The  the  Tj  measurements  The p u l s e method  of  site  Tj  The u t i l i z a t i o n methods  time  bound  ion  = electron-spin  g  in the  correlation  paramagnetic i  nucleus  = thermal  N  z  o  equilibrium value  48  (18)  1  of  M ,  The  intensity  i s measured  over  may b e o b t a i n e d  from an  semi-log  The r e p e t i t i o n  long  plot.  (5Tj)  to  equilibrium In  the  observable the  a l l o w the  state  before  magnetization  being  studied.  magnetization  can  fitting  the  factor,  W, f o r  data  I  where  I  o  field  be to  the  T  their  of  at  180°  z-component  be  fully  of  the  data  due  to  large  inversion of  which  the  inverted  over  in the  pulse.  the processing  includes  a  was  correction  ,  between of  180°  factor  data  acquisition  for  180°  2 cm d i a m e t e r  filled  as  shown  CuSO^ a n d m a n g a n e s e ( I I)  solutions,  Tj  measurements were  49  vials  placed  in Figure  with accurately  of  method.  and  pulse.  concentrations  inversion-recovery  (13)  l  pulse  constructed  The v i a l s were  by  x >> T , 1  consisting of  dish  and  the  1  W = correction  (p.31).  a  to  for  4 0  or  return  Incomplete  pulse  data  sufficiently  inhomogeneity  13,  the  Tj  be  the  may n o t  of  then  must  reapplication  o  reapplication  petri  to  t-values,  - I {l-[l-W(l-exp(-k/T )]exp(-x/T )}  k = waiting period  large  nuclei  equation  = intensity  A phantom  fit  time  corrected  180°  range o f  exponential  imaging experiment  radiofrequency  volumes  a  out  20  known  chloride  carried  in  (MnC^)  using  the  a  Copper(II)  Sulphate  Solutions  Inversion-recovery obtained  with  sec  x.  of the  plus the  t-values T h e mean  v i a l s were  cursor  exponential  in the  slice  50-1000  over  2.6  and a  c a r r i e d out  images  were  ms a n d a cm  d i r e c t l y from the  instrument  was  (xz)  range  intensities  obtained  on t h e fit  horizontal  2  at  TR of" 4  the  images  centre using  three-parameter  on t h e  data  using  equation  13.  Manganese(11)  Chloride Solutions  Inversion-recovery values  in the  intensities vials,  and  range  were  processed  on a l l  standard  results,  deviations,  were  obtained  1 0 - 1 0 0 0 ms a n d TR o f  obtained  A 957. a c c u r a c y out  images  once  in the linear and are  again  regression Tj  given  50  3 sec  from the  same way a s  the  as  the  in Table  plus II.  plus  or  4  was  x-  with t.  centres  CuS0  analysis  values,  before  The of  the  data. carried  minus  two  Table  I I : T j values f o r v a r i o u s c o n c e n t r a t i o n s o f CuS0 MnCl  2  4  and  s o l u t i o n s o b t a i n e d a t 20 (± 1)°C u s i n g the  i n v e r s i o n - r e c o v e r y method.  Two values a r e g i v e n  f o r each c o n c e n t r a t i o n corresponding t o two d i f f e r e n t p o s i t i o n s i n the r e c e i v e r c o i l .  So 1ut f on  Concentration  CuSC4  MnCl  2  51  (mM)  Tj  (ms)  4.96  108 ± 10  4.96  126 ± 4  2.54  245 ± 6  2.54  243 ± 13  0.99  519 ± 4  0.99  548 ± 2  0.67  103 ± 1  0.67  106 ± 1  0.34  189 ± 2  0.34  188 ± 1  0. 16  350 ± 8  0.16  340 ± 8  0.06  659 ± 9  0.06  663 ± 8  (iii)  Computed T j The s o f t w a r e  International,  o f the instrument,  developed  by Picker  has t h e c a p a b i l i t y o f c a r r y i n g o u t Tj  computat i o n s . Two  images  computations: The r e p e a t  must  f o r each  be equal  The r a t i o  image a r e g i v e n  o  I  I R  I  S E  2  i n equations  19 a n d 2 0 .  (19)  from a  (20)  1  l~(2-2 exp(-k/T ) + exp(-x-k/T )exp(-t/T ) 1  1  1  (  n  )  (l-2exp(-k/T ) + exp(-TR/T ) 1  o f these  intensities  eliminates  1  is given  t h e image  look-up table,  TJ computations  containing (ii)  The  + expU-k-O/TpiexpC-t/T^  the equilibrium magnetization  Tj.  images.  image.  - I exp(-2x/T )[l-2exp(-k/T ) + exp^TR/T^ ]  Taking the r a t i o  obtained  out these Tj  i n both  - iMrt-ltflJll-d-Zexpi-VTJ  K  I  on  to carry  an inversion-recovery and a spin-echo  times  intensities  I  are required  were  carried  t h e same p a r a m a g n e t i c  a n d t h e numbers  compared.  Table  III.  The computed  T  value  from 2 . 6 c m a t t h e centre  2  2  52  intensity  and T  which  i n equation 21.  2  , then  is a plot  out on  dependence  T j may b e of S  versus  solutions  Ion c o n c e n t r a t i o n The r e s u l t s  values  Q  as i n  are given in  a r e g i v e n a s t h e mean  of the  vials.  Table I I I : Computed T j values f o r v a r i o u s c o n c e n t r a t i o n s o f CuS0  4  a  n  d  MnCl  2  s o l u t i o n s o b t a i n e d a t 20 (± 1 ) ° C  Two values a r e given f o r each c o n c e n t r a t i o n , c o r r e s p o n d i n g t o two d i f f e r e n t p o s i t i o n s  i n the  receiver coi1.  So1ut i on CuSC4  MnCl  2  Concentration  (mM)  Computed Tj (ms)  4.96  1 17  4.96  123  2.54  245  2.54  235  0.99  556  0.99  548  0.67  83  0.67  98  0.34  192  0.34  188  0. 16  357  0. 16  350  0. 06  678  0.06  679  53  (iv)  Effects After  sequence, Larmor the  not  the  all  the  of  they  the  this,  a  a  short  time  ( 2 6 ms)  after  the  readout.  occur,  which  any  will  t-value  the  T ,  since  }  have  used  in  (ii)  does  T  not  exponential in every  different  spin-echo  T  a  term as  employed.  The d a t a  values; the T,.  MnCl  therefore 2  The r e s u l t s  will  this  solutions, for  t  a  were of  = 13 ms have  T  2  t-value  54  is of  of  the  to  spins  are  in  is  to  applied  as  2t  a  error  spin-  s h o u l d be  used  to  that  since  was o n l y  Tj  2 0 ms  a SE  is two  values were II.  The  on s h o r t  c a r r i e d out  considerably shorter 20 ms a r e  to  it  in Table  effect  at but  possible  and the  given  the  processing  check t h i s ,  13 ms a n d is  in  Tj term  fact  constant,  can  intensity  of data the  more o f an  experiment  where  for  In o r d e r  readouts  due  to  exponential  it  for  source  The method  sequence.  SE r e a d o u t  the  In t h e o r y , 2  is  spin-spin relaxation  into account  Spin-echo t-values  of a  2t,  same  collected  referred  equation  term.  compared.  use  is  the  In o r d e r  spin-echo  further  only  take  employed.  identical  a  the  not 2  detected.  This  at  This  Unless the  not  IR  precess  o f phase.  and the  time  introduce  exponential  the  is  i n an  180° refocusing pulse  ( 1 3 ms)  an  treat  be o u t  will  gradient.  second  also  is  spins  90° pulse.  may of  readout  will  field  During  measurement  9 0 ° RF p u l s e  nuclear  xy magnetization  around  echo  Readout  a p p l i c a t i o n o f the  presence  after  Spin-echo  frequency;  phase, get  of a  shown  in  T  on than  Table  2  IV,  together  with  the  computed  Tj  values  using the  same  readout.  Table  IV:  Tj  values  for  solution,  various  obtained  inversion-recovery readout the  are  MnCl  (v)  2  Effects The  not  on t h e  is  referred  This slice  and a  each  the  spin-echo  Computed Tj  given for  values  positions  in  T  (ms)  l  Computed Tj  +  3  78  0.67  107  +  10  73  0.34  191  7  190  0.34  189 ± 5  189  0 . 16  343  0 . 16  335  +  3  346  3  352  the  number as  are  (ms)  Density  i n t e n s i t y o b s e r v e d on an  thicknesses  Two  concentration,  100  to  with  comparison.  two d i f f e r e n t  (mM)  o n l y on the  also  i)°C using  MnCl2  0.67  Proton  signal  dependent but  of  are  to  (±  of  coi1.  Concentration  Solution  20  method,  given for  corresponding recei ver  at  T = 20 m s .  with  same r e a d o u t  values  concentrations  NMR i m a g e  relaxation times  o f protons  giving  the  density.  proton  available for  55  use  of  rise  the to  is protons  the  A number  on t h e  signal. of  imaging  instrument.  Varying  further  source  changes  the  of  the  error  proton  slice thickness in the  density  may  measurement  introduce  of  contribution to  a  T j , since  the  it  observed  signal . If, is  for  a  series  applied for  the  proton  using  each  density  factor  it as  a  The  results  shown  are  computed  Va:  Tj  images  values  Tj  were  in Tables with  values  solution,  for  the  possible  constant. of  as  various at  on the before  (±  method,  treat by  2 0 mm a n d  MnCl and  2  the  with  thickness.  concentrations 20  to  5 mm a n d  Vb, together  same s l i c e  thickness  T h i s was t e s t e d  experiments  Va and  obtained  same s l i c e  s h o u l d be  processed  inversion-recovery of  the  s l i c e thicknesses  i n v e r s i o n - r e c o v e r y Tj  solutions.  Table  IR i m a g e s ,  image,  two a d d i t i o n a l  running  of  of  i)°C using and  2 0 mm. C o m p u t e d T^ v a l u e s  MnCl  2  the  a  slice  thickness  are  given  for  compar i s o n .  So1ut1 on  MnCl  2  Concentration  (mM)  T  l  (ms)  Computed Tj  0.34  198  +  2  174  0.34  182  +  5  178  0 . 16  330  +  1 1  349  0 . 16  350  6  338  0.06  630  13  682  0.06  689  22  675  56  (ms)  Table  Vb:  values  for  solution,  various  obtained  at  inversion-recovery of  5 mm. C o m p u t e d  concentrations 20  (±  method, Tj  of  i)°C using and  values  a  are  MnCl  2  the  slice given  thickness for  compar i s o n .  So 1ut i o n  MnCl  (vi)  for  Concentration  2  T  (ms)  l  Computed  183  4  187  0.34  186 ± 3  184  0 . 16  349  +  2  333  0 . 16  346  +  1  337  0.06  662  +  12  650  0.06  696  4  683  Relaxation  Behaviour  Mu1tiexponential  relaxation  behaviour  an  isotropic  water,  i f proton  sources  scale. give  these,  image thick.  solution  characteristics,  NMR t i m e  can  In an  rise  to  this  containing such  as  does  not  may b e  protons  a mixture occur  or  imaging measurement,  Is  the  most  by s e l e c t i v e l y  thickness  compartments or  there  of  oil  is  s l o w on  57  and the  additional  exciting a  in different  different  behaviour;  significant.  may b e  (ms)  observed  with  mu11iexponentia 1 r e l a x a t i o n  obtained  Within  different  exchange  volume a v e r a g i n g be  Tj  0.34  Multiexponential  physical  of  (mM)  water  types  of  slice  An 10 mm  protons tissue.  in  which  are  proton  not  source  sequence  used  intensity  will  of  obtain  to  The its  excite  the  pixel  is  through  the  the the  due two  to  the  signals  images.  the  by  than  equation  the  (  T  )  of  description experimental Computer  they  are  to  times  Consider exchange,  water  give  behaviour,  for  of  and  a  T  rise  since 2  and  used  the  mobile  is  present,  particular  to  to  those  decay  fat  difference  than  and  1  -  2  E  P(-^  T 1  ±  of  t-value  fat  water. the  is  given  of  taking  the  data,  accuracy, are  available  having Tj  f i t  and thus  contributing  to  values  simultaneously  58  for  an  into  adequate  account  .  programs  data,  22  < >  ))  required  two compartments,  excited  X  exponentials  These the  ^ i *  I  -  programs  data.  exponentials relaxation  signals  22.  n = number  relaxation  NMR i m a g i n g  also  exponential  image  For proton  low m a g n e t i c  Tj  each  signal  field  observed  I  where  the  at  This could  one  intensity  the  resulting  shift  a different  signal  sum o f  from  pulse  n e g l i g i b l e chemical  protons  more  on the  The  slice.  relaxation  may h a v e  contribution  volume and slice.  multiexponential  If  signal  mammalian t i s s u e s ,  overlap  between  depends on  i n each  contributions studies  exchanging.  for a  chosen  provide  the  of  number  the  of  different  signal.  between of  analysis  which  2 4 5 ms a n d  in the  there  is  519 ms.  same s l i c e ,  no If  then  the  observed  signal  intensity  inversion-recovery intensities  for  magnetization each Tj  26:  the  compartment. together  are  t-value  g i v e n by t h e  given  The  with  the  in Figure  T h i s means t h a t  O  2.54  mM C u S 0  4  X  2.54  mM C u S 0  4  observed  source. result  intensity  is  a given  the  in  sum o f  an the  resultant individual 26,  and  computed  plots  the  Tj  for  observed  images  can  P l o t of Intensity versus tau demonstrating multiexponential relaxation behaviour.  provide  their is  plot,  338 ms.  Figure  only  each  compartment,  is  image  for  must  A  0.99  +0.99  Tj-values,  In o r d e r  to  measured  CuS0  giving  determine  of multiexponentiaI be  as  59  a  mM C u S 0 4  no  i n d i c a t i o n as  whether  relaxation  function  4  the  observed  behaviour,  of t .  to T the  (vii)  D i s c u s s i on The T j  show t h a t 100-600  useful  ms.  encompass those of  Figure  data  summarized  the  a.  Tj-values grey  and  is  can  not  a  be made large  o f many t i s s u e s ,  white matter  27.  of  the  The  range, and  IP  results  in the  in  it  range does  particular  brain.  Plot of spin-lattice relaxation rate c o n c e n t r a t i o n f o r CuSO^ s o l u t i o n s . O  Comparison  versus  data  A Computed b.  in Figure  Tj measurements  Although this  the  27:  are  data  Plot of spin-lattice relaxation rate concentration for MnCl solutions. 2  O  IR  data  &  Computed  data  60  versus  of  the  with  Tj data  that  within are  from  107..  not  the  computed  useful,  than  the  possible to  extract  using the  The v a l u e s  therefore  rapidly  obtained  i n v e r s i o n - r e c o v e r y method  images  obtained  since  gives  from  they  a  the  correlation computed  c a n be o b t a i n e d  Inversion-recovery data. make e r r o r  estimates  more  However,  on t h e s e  i n f o r m a t i o n on m u l t i e x p o n e n t i a l  Images  it  is  numbers,  or  to  relaxation  behaviour. Taking together  into account  with  reproducible  the  effects  values  cases  the  trend  was o b s e r v e d  echo  errors  read  time  the  of  were  of  Tj  data  and a g a i n  for  under  correlation  of  demonstrates to  treat  obtained  and  less  57. b e t w e e n  than  over  the  Tj  range  within  affecting 127. o f  the  The  obtained  shows  a  results.  measured  The  it  is  with  as The  measured no  data  possible  Tj-values.  values  conditions,  spin-  was  errors  studied,  most same  longer  imaging experiment  literature  spectroscopic  the  coil,  In  thickness  imaging c o n d i t i o n s  that  conventional  this.  using a  slice  the  ± 12%.  different  without  are  than  mean v a l u e s  many c o n d i t i o n s o f t h e  constants values  less  when t h e  Comparison o f the  data  inhomogeneity across  somewhat  for  In t h e  can be o b t a i n e d  varied. data  random e r r o r  Tj  under  magnetic  51 field  gradients These  literature corrections  present  findings by Rosen, must  .  contradict Pykett  b e made t o  61  and T.  those  reported  Brady rjata  5 2  for  ,  in  the  who s t a t e the  effects  that of  slice  selection  and  a  spin-echo  Multiexponential volume a v e r a g i n g to  be aware  of  is a  it  readout.  relaxation  behaviour  arising  problem  imaging.  It  T^ — a 1 u e s may a r i s e  however,  the  values  Chapter  3.  b.  c a n be  (1)  studies.  90° pulse,  for  x'y'  This  M ,,  inhomogeneities result also  in a  cause  time  the  the  type;  same s l i c e  considered  M , to  constant  spins  again  is in  T * which (equation  on  The T  2  In  field,  with in  one  the  addition, AB , will 0  My- d e c r e a s e s  i  In t h e  -  which  to  the  zero  with  field  **o  — T 2  +  (23) 2  T  x,  y and  z directions  all  have  T „ 2  2  by the  of a  nucleus  following  bound t o  equation  62  a  paramagnetic 4  24. ^  a  nuclei  frequencies  for  by  23).  2  fields  T .  includes a term  2  energy  magnetization  magnetic  Overall  perturbed  individual  exchange  Larmor p r e c e s s i o n  decay.  been  o f the  constant  static  i  Fluctuating  has  o f the  a time  in the  system  begin to  — * T  given  is  tissue  2  decay  with  range o f  inhomogeneity  effect  i f the  one  The  (T )  spin  They then  leading to  plane,  a  example,  in phase.  another  important  Definition  Immediately after  a  compared  Spin-spin Relaxation  are  f r o m more t h a n  V  in serial  is  w h e n a p p l y i n g NMR I m a g i n g J_n v i v o .  observed  excited  in  from  site  is  an  1  1  Y  2 \&  2 2 S(S+1)B  15  r  13x  c  2 +  2  6  1+U) X T  x  h  3  parameters  equation  (p.47)  interactions  (i i )  are  equivalent  and the  as  those  Measurement As  the  terms  described  not  only  inhomogeneity. measure  of  from  for  e  + x  in the  the  same  e  Tj types  of  Tj.  of  p r e v i o u s l y mentioned,  dependent  of those  arise  (24)  2  l+0) T o  + ls(S+l)  The  c  2  on T ,  but  2  It  is  the  magnetization  on t h e  therefore  not  static  decay  magnetic  possible to  use  is field  T  as  2  a  T^. 27  In method  1950, to  Hahn  overcome the  inhomogeneity. was  shown  magnetic  o f the  the  is  of  dephase pulse  for  about  are  all  the  o f any not  they  63  nuclear  with  nuclei  field,  I f the  followed  x-axis,  the  the  will  and the  spins  field  spin-echo  inhomogeneity  all  external  spins. x,  all  spin-echo  o f the  Immediately  precess.ing  that  same  a time the  of the  effect  13.  90° pulse,  means  experiencing dephasing  page  The p r e s e n c e  field  use  The p r i n c i p l e b e h i n d t h e  i.e.'they  frequency.  the  dephasing  i n F i g u r e 6,  application phase,  proposed  are  after spins same  refocus  or  are  in  Larmor  in the  static  be result  of  allowed  to  by a p p l i c a t i o n o f a  will  technique  this  180°  come b a c k  into  phase at is  time  measured by  as  a  when t h e y function  c a r r y i n g out  exponential  f i t .  sufficiently successive of  2t,  the  diffusion  either  to  pulses,  a  allow  be  Zx,  The  time  for  the  return  to  IR T j  in the  method  is  limited  during the in a  intensity  providing a  logarithmic plot  as  resulting  detected.  thus  just  may o c c u r  magnetization  of  The r e p e a t  long  spin-echo  can  or  value  of  must  be  an  sequence  equilibrium  between  experiment.  however,  refocusing  reduction  since  of  The  use  molecular  the  in the  echo  28 amplitude. diffusion spatial  Carr on a  occur.  It  P u r e e 11  spin-echo  magnetic  coefficient  and  field  I  experiment  gradients  (D) a n d t h e is  have  time  I  " o  e x  is  the  dependent  (G), the  effect  on  of  the  diffusion  during which  g i v e n by e q u a t i o n (2T)  shown t h a t  diffusion  can  10.  2  P ( - * / T ) exp (- | 2  2 Y  G D-c ) 2  (10)  3  3 The be of  x  dependence  much more diffusion  the  means  that  spin-echo  given  effects  pronounced f o r large values c a n be o v e r c o m e , t o a g r e a t 29  C a r i — P u r e e 11 m e t h o d  Hahn  the  method.  in equation  , which  Is  of  o f T^. extent,  method  and  has  will  The e f f e c t s by u s i n g  a modification of  T h e C a r i — P u r e e 11 p u l s e  the  sequence  is  25,  (90°-T-180°—c-[echo]-T-180°-x-[echo]-  Positive  diffusion  negative  echoes  two advantages:  it  64  are  alternately  saves  time  and  )  formed.  (25)  This  by m a k i n g x  short  the  effects  One d r a w b a c k incomplete sequence  is  of diffusion  that  pulse  rephasing  is  not  may b e  virtually  imperfections  of the  spins  a v a i l a b l e on the  may  resulting instrument  eliminated.  cause in error. used  for  This these  studies. The same p h a n t o m was a l s o slice  used  images  for were  1 3 - 1 6 0 ms a n d solutions. from  the  carried  images out  the  to  3 sec  and an  standard  T  2  plus  Tj  for again fit  measurements  Horizontal  i-values  t,  were  the  the  in the CuS0  4  obtained to  I  and  deviations  MnCl  2  equation  9  was  T , 2  = equilibrium  linear  ( 9 >  magnetization.  regression  obtained, are  SE  directly  X  values  (xz)  range  (2T) " o - P C - ^ ' V  A 957. a c c u r a c y on a l 1  with  exponential  determine  where  for  measurements.  2  intensities  X  out  T  obtained,  TR o f  The  constructed  given  65  and  analysis  values  in Table V I .  plus  was or  carried minus  two  Table VI: T  2  values f o r v a r i o u s c o n c e n t r a t i o n s o f CuS0  MnCl  2  4  and  s o l u t i o n , o b t a i n e d a t 20 (± 1)°C u s i n g the  spin-echo method.  Two values a r e g i v e n f o r each  c o n c e n t r a t i o n corresponding t o two d i f f e r e n t positions  Solution  CuSO. 4  MnCl  in the receiver  Concentration  coil.  (mM)  T  2  (ms)  4.96  1 16 ± 4  4.96  116 ± 4  2.54  194 ± 10  2.54  191 ± 15  0.99  313 ± 22  0.99  354 ± 26  0.67  46  ± 2  0.67  46  ± 3  0.34  78  ±3  0.34  78  ± 5  0.16  136 ± 7  0. 16  136 ± 4  0.06  244 ± 14  0.06  248 ± 9  2  66  (i i i)  Computed Two s p i n - e c h o  computation software. different  images  using the These  echo  Picker  images  of  the  look-up table,  solutions 40 m s ,  these  image  just  26.  T  as  in  and the  to  carry  International  must  have  equal  intensities  intensity  out  a  1^  Instrument  repeat  2  as  for  7  computations (fi),  results  .  is  2  is  times  were  given  taken, on  then  The r a t i o  and  is  thus  the obtained given  c a r r i e d out  using spin-echo are  then  dependence  and T j . J  equilibrium magnetization  equation  required  times.  The r a t i o eliminating  are  a  in  on the  t-times of  from  2 0 ms  same and  in Table V I I .  SE. ( l - Z e x p C - k . / T . ) + exp(-TR/T ) exp(2x /T ) i = — I ( l - 2 e x p ( - k / T ) + exp(-TR/T ) e x p ( 2 T / T )  I  S  S E  2  1  67  1  2  2  (26)  Table  V I I : Computed T CuS0 (±  4  and  2  values  MnCl  positions  Solution  are  in the  receiver  Concentration  4  2  68  concentrations  obtained  given for  corresponding  CuSC*  MnCl  various  solutions,  2  1 ) ° C . Two v a l u e s  concentration  for  to  two  at  20  each different  coll.  (mM)  T  2  (ms)  4.96  120  4.96  131  2.54  219  2.54  221  0.99  522  0.99  548  0.67  43  0.67  44  0.34  77  0.34  78  0 . 16  135  0 . 16  137  0.06  414  0.06  443  of  The e f f e c t resultant  T  Table  varying the  values  2  measurements different  of  were  carried  i-times,  VIII:  was a l s o  and  Computed T MnCl  2  various given  values  (iv)  the  for  each  2  Computed  MnCl^  are  of  at  positions  (mli)  using VIII.  concentrations  20  (±  1)°C  Two v a l u e s  receiver  t-times  of  using  corresponding  in the  the  2  in Table  i-times.  concentration  T  on  solutions,  given  various  obtained  t-time  are to  coil.  (ms)  20,40  20,60  0.67  43  43  44  0.67  44  43  46  0.34  77  77  71  0.34  78  71  69  0 . 16  135  124  123  0 . 16  137  129  122  Effects  of  SE method  whole body  imaging  expected,  values,  the  40,60  Diffusion  Only the  As T  for  combinations  two d i f f e r e n t  Concentration  on the  results  solutions,  2  examined.  out  the  combination of  is  available  measuring  T  2  using  instrument.  when a t t e m p t s  effects  for  of  were  diffusion  69  made t o resulted  measure in  long  abnormally  low  values  of  T^.  A maximum v a l u e  measured.  The e f f e c t s  values  minimized  are  result, than  above  T  of  diffusion  because a  = 2 0 0 ms t h e  2  those obtained  of  2 0 0 ms c o u l d  on t h e  ratio  Is  computed  using the  computed  taken  T  and,  values  exponential  be  as  are  fits  2  a  higher  to  the  SE  data.  (v)  Discussion The T  in  the  data  data  2  range  provide  T  images  2  a quick  of  ms,  computed  minimize the study  summarized  40-200  and the  computed  is  are  difference  values  2  useful,  is  longer  T . 2  2  not _  v  a  as  with  range o f  one  CuS0  above  and  range  5  3  j  S  200 ms,  using the  G i l l  would  4  Comparison field  to  make e r r o r  t, t  they  they  u  also  allowing the  the  computed  estimates  or  relaxation  Tj to  behaviour  numbers.  Above t h e  gets  possible  for  i n f o r m a t i o n on m u l t i e x p o n e n t i a l  doped  e  as  extract  Increase,  u  However,  just  The  o n l y can  thereby  it  these  ]  values  2  spin-echo  less.  of diffusion,  values,  from  not  T  For T  between  15% o r  since  Indication o f the  effects  is  T  the  in Figure 28.  ,  40-200  to  literature  a  the  unity,  70  and  data  values method,  correlation of a  ms.  effects  The T J / T  spin-echo  Carr-Purcel1  shows  ms,  expect.  close the  of  40-200  2  5 1  as  ratio  once  does  of  the  not  diffusion  for  water  T  value  2  reflect  obtained  at  the  m o d i f i e d by  few p e r c e n t  for  this. same  Meiboom the  Although lie  within  this  i s a n a r r o w r a n g e , many t i s s u e  i t , i n p a r t i c u l a r those o f brain  i  " 3 '  5  *  I  Concent rat ion (mM)  F i g u r e 28: a . P l o t  of spin-spin  concentration  tissue.  oS  oTi oTT^  Concent ration (mM)  rate  versus  f o r CuSO. 4  solutions.  b.  O  SE d a t a  &  Computed  Plot  data  of spin-spin  versus  relaxation  concentration  solutions O SE d a t a A Computed  data  71  T2~values  rate  f o r MnC^  CHAPTER  Applications  This  chapter  application is  of Quantitative  describes  In d e t a i l  of quantitative  Introduced  to  and the  diseases  diseases  affect  the  the  NMR I m a g i n g  an  experimental  NMR i m a g i n g j_n v i v o .  structure  of  3  interest central  o f the in this  nervous  b r a i n and study.  system  The  reader  spinal  cord,  How t h e s e is  also  exp1 a i n e d .  (i)  Background The  nerve  cord  consist  29.  It  and the  is  cells,  df  cell  along the  axons  or  neurons  bodies  and axons,  axon t h a t  of different  o f the  the  neurons  b r a i n and as  nerve  shown  spinal  in Figure  impulses  travel,  communicate w i t h  one  dendrites  axon Figure  29:  another  at  surrounded  Diagram o f  junctions  nerve  cell.  known a s  by a m y e l i n  sheath,  72  synapses. which  Many a x o n s  Increases  the  are rate  at  which the  axon  can  is  known a s  is  by a m i x t u r e o f  well  as  conduct  saltatory  conduction.  cable  by c h e m i c a l  impulses.  this  decrease along (>  in the  the  One o f that  for of  but  the  MS h a v e  in  the  their must  which a  the  one  of  detect  the  be  as  resulting  They can  Is  in the  in order  the  to  protons  study  areas  73  since  the  is  mortem,  by  of  animal  the models  mechanism is  (EAE).  a  for  which  are  serially  the  result  protons.  they  o f MS  stage.  the  no known r i s k t o  the  in  One s u c h model  The  subject.  of  changes  molecular  in turn  is these molecular  charted,  post  reason,  lesion.  changes,  It  course  pathology  p r o v i d e d an o p p o r t u n i t y  of  large  occur  chronic  Encephalomyelitis  abnormal  travel  matter.  For t h i s  EAE w i t h  a  predominantly  i n mapping the  early  in  i n MS a r e  a v a i l a b l e o n humans  the  Sclerosis  impulse can  system,  grey  problems  developed  NMR p r o p e r t i e s . eventually  nerve  type.  nervous  disease.  of  Multiple  of abnormality  NMR c h a r a c t e r i s t i c s  environment  such as  known a b o u t  MS a n d  to  fibres,  is  NMR i m a g i n g h a s  The a b i l i t y  nerve  little  Allergic  both  o f the  usually  development  studying  conduction  Is  been  Experimental  where  disease  of  what  is  broken down,  in the  only data  stages  the  also major  means t h a t  early  at  central  the  the  which time This  is  a n d o f more t h a n  white matter  Is  sheath  The a r e a s  In t h e  allows  mechanisms.  speed  axon.  3 mm),  anywhere  myelin  This  properties  In d e m y e l i n a t i n g d i s e a s e s , (MS),  The m y e l i n  affects  changes  that  responsible  for  the  c h a n g e s o b s e r v e d a s g r o s s p a t h o l o g y and  images. EAE  This  was  the basis  the  NMR  f o r undertaking these studies  of  in primates. It  i s known t h a t  the f i r s t  l e a d i n g t o haemorrhagic is a l s o that  present.  In t h i s  Furthermore,  project  (ii)  level  ±n  was  induced  weighing  3 k g , by  emulsion  containing  mg  heat  i s inflammation  Eventually serial  demye1ination  studies  have shown  measurement o f T j and  NMR  T^ a s  a  i n d i c a t i o n o f c h a n g e on  a  v i vo.  I n d u c t i o n o f EAE EAE  i n EAE  c a n be f o l l o w e d u s i n g  f u n c t i o n o f t i m e p r o v i d e s an molecular  event  necrosis.  t h e p r o g r e s s i o n o f EAE  imaging.  0.5  on  and  NMR  Protocol  i n a m a l e Macaca f a s c i c u 1 a r i s monkey,  injection  killed  Imaging  15 mg  o f 0.15  mL  of a  water-in-oil  monkey m y e l i n b a s i c  M y c o b a c t e r i um  protein  tubercu1os i s  and  intradermally  54 in the h i n d f o o t Bureau first  pads  of Biologies i n t h e UBC  .  The  animal  Breeding Colony  Animal  Care  was  o b t a i n e d from  i n O t t a w a and  Facility  on S o u t h  then a f t e r  i n d u c t i o n o f t h e d i s e a s e , he was  Acute  Unit  Care NMR  care  w h o l e body  w i t h an a p e r t u r e o f  multi-slice sequences,  s p i n - e c h o and both o f which  on t h e  imaging  system  15 cm.  Data  Campus Road,  moved t o t h e  Picker  using a  receiver  were c o l l e c t e d  inversion-recovery  using  pulse  p r o v i d e d 8 c o n t i g u o u s 5 mm 74  housed  facility.  i m a g i n g d a t a were c o l l e c t e d  International coil  animal  was  the  thick  slices. in  the  the  Echo d e l a y s spin-echo  (2t)  of  sequences.  4 0 ms a n d  A i-time of  i n v e r s i o n - r e c o v e r y sequence,  repeat order  time to  choice  was  allow  of  2 sec. direct  pulse  6 0 ms w e r e  These  and  4 0 0 ms w a s  in a l l  parameters  comparison with  used  sequences  were  human  sequences would a l l o w  employed  chosen  the in  MS d a t a ,  computation  for  and  of  Tj  the and  V rise are  As  indicated  to  multiexponential  obtained  in Chapter  from the  matter  may b e  excited  serial  scanning  were  in the to  be  of  the  slices  be  excited  This  was a c h i e v e d  commercially program, to  the  mm f o r the  volume a v e r a g i n g  relaxation  monkey's  repositioning had t o  2,  brain,  same s l i c e .  head  i n each  set  following  a m o u l d w a s made o f t h e coll.  each  of  monkey  was  set  in the  of  way:  available thermoplastic  receiver  both  comparable,  monkey's  In t h e  behaviour.  then  and  the  images white  results  images using  the  same  obtained. Polyflex-11,  polymer used head,  In t h e  and  scanner  F i g u r e 30 shows and the  obta i ned.  75  slice  the  images  position being  a  PET  fitted  This allowed repositioning within  scans.  of  accurate  essential;  monkey's  give  When  grey If  can  2 of  Figure  (iii)  30:  Diagram showing the p o s i t i o n o f the monkey i n t h e i n s t r u m e n t and t h e s l i c e s being obtained.  Development  of  EAE U s i n g  NMR I m a g i n g  The monkey was a n a e s t h e t i z e d combination of  which  of  ketamine  lasted  every  24  hours  daily  until  which time  1.5-2 for  the he  and  onset  detection  was  of  scanned  matter  of  the  left  signs.  image o b t a i n e d  was  A spin-echo used  abnormal  to  pulse  obtain  area.  the  After  first  cerebral  and  31.  the  the  onset  of  every  Is  an  180° refocusing  76  times scanned  area,  after  hours.  area  in  16 d a y s  shown  in  indicates pulse  the after  clinical  echo-delay  The a r r o w  effects  and  10  any o b v i o u s  sequence w i t h  the  abnormal  abnormal  day  5  0 . 8 mL  the  three  signs^  hemisphere,  on t h a t  image.  ratio)  checked  clinical  a definite  inoculation The  before  (12:1  He w a s of  imaging using  approximately  The monkey d e v e l o p e d white  rompun,  hours.  the  for  is  Figure of  4 0 ms  the applied  In t h e from  spin-echo  the  abnormal  white matter relaxation brighter  Figure  sequence,  due  to  rate.  than  31:  area an  normal  obtained  increase  tissue  than  tn T _ area  on a  intensity  f  that  observed  from  decrease  a  therefore  spin-echo  normal in  its  appears  Image.  T r a n s v e r s e SE image o f t h e m o n k e y ' s b r a i n , showing the abnormal area in the l e f t hemisphere ( r i g h t s i d e of image).  o f the  F i g u r e 32 shows from the  inoculation  signal  greater  The a b n o r m a l  The d e v e l o p m e n t followed.  is  the  are  as  monkey.  disease a  series  could of  The number  Indicated  77  in the  be  easily  spin-echo o f days  caption.  images  after  Figure  32:  Series of three spin-echo from the monkey's b r a i n .  Images  a.  16.25 days  after  inoculation  b.  16.75 days  after  Inoculation  c.  18.42 days  after  Inoculation  The  light areas  are  78  abnormal.  obtained  (iv)  Quantitation Tj  areas  and  from  X contain the  the  day  sample  IX:  NMR P a r a m e t e r s  computations  same s l i c e  Table  of  T  }  of  appearance  series  during  values  of  as  a  until  out  on the  death.  which appear  IX a n d  obtained  of  matter normal,  (Days)  time  after  (WM) a n d and  the  Tj  induction  grey  matter  lesion.  (ms)  WM  GM  Lesion  16.25  370  530  440  16.75  370  530  480  17.12  390  520  500  17.67  380  530  540  1 8 . 04  390  530  570  18.42  370  510  590  18.92  370  520  600  79  from  scanning.  function  white  abnormal  Table  these measurements,  serial  EAE, for  (GM)  Time  of  were c a r r i e d  Table  X:  T^ v a l u e s of  EAE, for  (GM)  Time  as  which  white matter appear  normal  time after  (WM) a n d and  T  the  induction  grey  matter  lesion.  (ms)  2  WM  GM  Lesion  16.25  110  110  150  16.75  110  110  150  17.12  120  140  200  17.67  120  1 10  180  18.04  120  100  220  18.42  100  90  240  18.92  1 10  110  240  obtained  with  function of  (Days)  T a b l e XI c o n t a i n s  These  a  from the  values, the  data  monkey's  together  pathology  Tj  brain  with  found  for  those  post  80  different  slices,  immediately p r i o r to for  mortem.  1^,  were  death.  correlated  Table  XI:  Tj  values  from  immediately  five  different  prior to  and  grey matter  the  lesion.  death  for  (GM) w h i c h  SI i c e  (v)  slice  white matter  appear  Tj  images  normal,  (WM) and  (ms)  WM  GM  Les ion  1  390  490  610  2  390  450  600  3  390  470  650  4  390  470  560  5  400  500  660  Discussion These  that  studies  were based  NMR i m a g i n g c a n b e  development  of  on the  used t o  postulate  detect  EAE i n p r i m a t e s .  and f o l l o w  the  Experimental results  have  56 shown t h i s  to  be  true  EAE c a n be d e t e c t e d clinical the  study  signs of  lesion  clinically, asymptomatic  u s i n g NMR i m a g i n g .  MS i n h u m a n s ;  unaccompanied first  in primates  is  This  in the  symptoms. monkey,  pathologically similar  MS l e s i o n s  Characterization  of  in  has  s o m e MS l e s i o n s  b y new c l i n i c a l observed  before  It  which to  the  onset  of  implications for appear may b e t h a t was  not  the  reflected  clinically  humans.  these  81  asymptomatic  lesions  i n MS  could provide the information necessary chart  the progression of the disease.  topic  f o r further exploration. The  followed  p r o g r e s s o f EAE  u s i n g NMR  individual  imaging.  lesions  whole d i s e a s e p r o c e s s repositioning  This  in primates The t i m e  c o u l d be n o t e d ,  t h e d i s e a s e p o s t mortem.  t o understand  Until  i s an  c a n be  exciting  easily  o f appearance o f  w h i c h a 1 lowed mapping o f  now, t h i s  i n f o r m a t i o n on t h e  h a s been u n o b t a i n a b l e .  is essential,  and  Accurate  s i n c e volume a v e r a g i n g  could  l e a d t o d i s c r e p a n c i e s i n t h e a p p e a r a n c e o f t h e image, a n d i n q u a n t i t a t i v e measurements,  i f more t h a n  contributing to the signal  observed  Comparison o f t h e r e l a x a t i o n prior Tj  t o death  and T  2  initial  pathology reflect  are present.  the molecular  The c h a n g e s  from  respectively) are sizeable 157. f o u n d  paramagnetic  i n T j and T  The i n d i v i d u a l death  of In  lesion by t h e s e  changes  compared w i t h t h e e r r o r s  species, described  later  over  2  time  In C h a p t e r  82  o f 127.  with 2.  This  c a n be d i s t i n g u i s h e d f r o m changes  in Tj  (607. a n d 1407.  i n t h e s t u d i e s on w a t e r d o p e d  the i n i t i a l  occurring  longer  c h a n g e s o c c u r r i n g due t o t h e  detection until  that  immediately  stages o f the disease, not a l l three types o f  and  and  slice.  haemorrhagic n e c r o s i s and d e m y e l i n a t i o n .  o f the disease.  2  data obtained  with the histopathology, r e v e a l s that  progression T  a particular  values a r e a s s o c i a t e d with the presence  inflammation, the  from  one t i s s u e t y p e i s  i n T. a n d T . 9  means  those  In o t h e r  words,  ft  s h o u l d be p o s s i b l e t o  inflammation  (which i s an  demye1ination  (which occurs  disease.)  In a d d i t i o n t o  before  lesion  the  elevation errors  is  is  visible  then  by changes  this  event)  later  this,  reproducible,  involved,  be d e t e c t e d  early  d i s t i n g u i s h between  in the  there  on the  and  is  and areas  large  indicates  i n Tj before  If  the in  is  a  fresh  visible  Tj  this  in comparison to  that it  of  elevation  NMR i m a g e .  of  containing  progress  i s an  areas  lesion on  the can  the  image. The r e s u l t s NMR  imaging has  questions  of this the  regarding  work have  potential  for  shown t h a t  a n s w e r i n g many  EAE i n p r i m a t e s  humans.  83  quantitative  and  pertinent  e v e n t u a l l y MS I n  CONCLUSIONS It  has been shown t h a t  lattice  relaxation  c a n be o b t a i n e d  time  strength of  various  concentrations  0.15  a l s o been shown t h a t and t h e  resultant  Tj  of  paramagnetic  in the Tj  it  method p r o d u c e s  which a r e  addition,  the two-point makes e r r o r  less than  estimates  i n v e r s i o n - r e c o v e r y method c a n a l s o on m u 1 t i e x p o n e n t i a 1 Important  for  are within  field  j_n v i vo s t u d i e s .  127. o f  conventional  time  species.  0.15  in  information which  values  v a l u e s measured  reproducible  (T ) 2  using the  strength of  behaviour, The T j  and  the  The  provide  conditions  with  with  no  is  obtained under magnetic  present.  show t h a t  relaxation obtained  literature  spectroscopic  gradients  Results  relaxation  This  method,  possible.  that  the  consistent  computational  the  observed  using  127..  has  select  in r e s u l t s  values obtained  values  It  has b e e n e s t i m a t e d  is  of  species.  r e a d t i m e do n o t a f f e c t  Using s c a t t e r  at  with  image s l i c e  i n v e r s i o n - r e c o v e r y method  results  spin-  100-600 ms,  T e s l a on w a t e r d o p e d  conditions,  Tj  range  the  i n v e r s i o n - r e c o v e r y method,  spin-echo  under a range o f  values of  in the  changing the  values.  the uncertainty  (Tj),  using the  a field  gradient  reproducible  in the  values of  r a n g e 4 0 - 2 0 0 ms,  s p i n - e c h o method, a t  T e s l a on w a t e r  Above t h i s  range the  84  the  a  doped w i t h effects  of  spin-spin can  be  field paramagnetic diffusion  become T ,  Important,  compared w i t h  2  Carr-Purcel1 The ±  resulting  errors  157. and  values.  literature  estimated f o r T the  The  results  of diffusion  longer than  NMR  imaging  200  can  signs.  2  values  with  are  in the  values method,  and  The  r a t i o o f two  spin-echo  T,-values, which minimizes and  Gill.  literature  estimates possible.  provides r e a l i s t i c  the  values f o r  ms.  d e t e c t Experimental  Encephalomyelitis clinical  127. o f t h e  of  the  r a n g e 40-200 ms  computational  method t a k e s t h e  images w i t h d i f f e r e n t  2  the  n  which a r e c o n s i s t e n t  makes e r r o r  values  Meiboom and  s p i n - e c h o method p r o v i d e s T  computational  T  f  are within  using the two-point  in a d d i t i o n  effects  2  low  values obtained using  method, a s m o d i f i e d by  r a n g e 40-200 ms, obtained  in abnormally  (EAE) The  in primates  technique  can  Allergic before the onset be  used  to  of  follow  t h e d e v e l o p m e n t o f t h e d i s e a s e , w h i c h a l l o w s mapping its  pathological  disease 1407.  i s accompanied  Increase  percentage used  progression.  1n T .  changes  2  by a 607.  The  results  i n T j and  to discriminate  The  T  progression of  the  i n c r e a s e i n T j , and indicate that  of  a  the  taken  t o g e t h e r can  be  between a r e a s o f  inflammation  and  2  o t h e r s w h i c h c o n t a i n demyel1 n a t i o n .  85  FUTURE  NMR a n d a)  EAE i n  WORK  primates  Studies of multiexponential relaxation behaviour  in  v i vo. b)  J_n v i t r o  abnormal  Tj and T  brain tissue.  mu1tiexponentia1 protons c)  at  High  i i)  3  1  2 3  P  than  imaging  and  s p e c t r o s c o p y j_n v i v o  i mag i n g  Na  imaging studies  quantitative  on the  monkey t o  measurements,  correlate  and compare  with  MS i n H u m a n s  Work h a s  a l r e a d y begun on p o s t  tissue  have been  before  5  a n c  fixation,  and a f t e r  made b e t w e e n  pathology ^. Tj  fat  data.  NMR a n d  the  and  field.  Immunological  brain  r e l a x a t i o n behaviour o f water  H i mag i n g  them w i t h  a)  Identification of  *H s p e c t r o s c o p y  iv)  human  and  fat.  field  iii)  on normal  NMR s p e c t r o s c o p y o n m o l e c u l e s o t h e r  and  1  i)  e)  high  J_n v i t r o water  d)  measurements  2  j  T  the  with  values the  fixation.  now b e i n g made  observed post  histopathology.  86  Correlations  NMR i m a g e s a n d t h e  Correlations are 2  m o r t e m NMR s t u d i e s  mortem and  gross between after  The r e s u l t s  of  of  these studies  c a n t h e n be compared w i t h t h o s e f r o m t h e  monkey; t h e u l t i m a t e g o a l different  being the i d e n t i f i c a t i o n o f  t y p e s o f MS p a t h o l o g y  image u s i n g NMR  i n humans o n t h e NMR  parameters.  b) Q u a n t i t a t i o n o f NMR  p a r a m e t e r s jjn v i vo a n d  comparison with primate  87  data.  REFERENCES  1.  2.  P u r e e 1)  E . 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