Michael Hofman, MBBS, FRACP, FANNMS
Molecular Imaging, Centre for Cancer Imaging
Peter MacCallum Cancer Centre / The Unive...
Acknowledgements
Centre for Cancer Imaging
 Prof. Rod Hicks
 Mr. Jason Callahan
 Mr. Peter Eu
 Dr. Shankar Siva
No Con...
Dr Michael Hofman
Fever, shortness of breath, chest pain, productive cough
?PE
Dr Michael Hofman


What does the perfusion
look like?
Planar V/Q
Dr Michael Hofman
99mTc-MAA 68Ga-MAA
SPECT PET
Dr Michael Hofman
PET/CT: major improvement in image accuracy
 Local release of inflammatory mediators result in failure of reflex vasoconstriction
 shunting & hypoxia1
 Histologic ...
WHY do we need PET/CT V/Q?
Dr Michael Hofman
Superior image quality
 fully tomographic
  accuracy
  reproducibility
...
68Ga eluted from onsite generator
(IBD Holland)
Dr Michael Hofman
Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfu...
Dr Michael Hofman
Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfusion
4D PET
Substitute 68Ga instead of 99mTc  G...
Dr Michael Hofman
Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfusion
4D PET
uSv/hr vs Norm KCPS
R2
= 0.803
0
1
2...
Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfusion
4D PET
Dr Michael Hofman
PETSPECT
BorgesJBetalJNM2011,
52(2)
...
Galligas
inhalation
Ventilation
PET/CT
GaMAA
iv
Perfusion
PET
Dr Michael Hofman
68Ga-macroaggregated albumin (GaMAA) PET
Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfusion
4D PET
Dr Michael Hofman
Dr Michael Hofman
PET SPECT
Ventilation
Perfusion
Acute shortness of breath & pleuritic chest pain
V/Q PET/CT versus V/Q S...
Dr Michael Hofman
Multiple segmental
unmatched perfusion defects
HofmanMSetal,JNM2011,52(1)
Pulmonary embolism
Extrinsic compression of RUL
Dr Michael Hofman
PET/CT perfusion (Q)
PET/CT ventilation (V)
“High probability”but not PE
Dr Michael Hofman
Hofman MS et al, J Nuc Med 2011 Oct;52(10):1513-9
n=10
Superior image quality with PET
4D
Respiratory Gated 4D V/Q PET/CT
Gated CT and Gated PET
Dr Michael Hofman
Phase Matched CT attenuation correction
each PET time bin corrected with corresponding CT time bin
Insp PET/CT
DICE = 0.81
FB PET/CT
DICE = 0.83
FB PET/Ave-CT
DICE = 0.84
Exp PET/CT
DICE = 0.84
Expiratory bin: best PET-CT...
Planar V/Q & CTPA purport high accuracy of
>90-95% V/Q
Dr Michael Hofman
Planar V/Q & CTPA purport high accuracy
>90-95% V/Q?
Dr Michael Hofman
Modest agreement ≠ high accuracy
 Many false posit...
Overdiagnosis in CTPA & D-Dimer era
Dr Michael Hofman
Segard T, Macdonald BG MJA 2013, 198(2)
CTPA
PE diagnoses
no Δ dea...
Only when new superior modality comes
along do you realize how bad the
“gold standard” is !
Dr Michael Hofman
PET
Perfusio...
Dr Michael Hofman
PET/CT V/Q = High Resolution V/Q
New applications
Dr Michael Hofman
Radiotherapy planning using V/Q
 Current RT planning assumes all lung functions equally
- “one size fit...
Dr Michael Hofman
Radiotherapy planning using V/Q
Functional adapted
radiotherapy
Dr Michael Hofman
Hypothetical functional lung : - ‘any perfusion’ and ‘high perfusion’ co...
 14 consecutive patients with RT plans adapted to perfusion PET/CT
 Optimised 3D conformal and IMRT plans showed an impr...
RT planning field CT @ 4 weeks: no ΔPET V 4 weeks PET Q
Radiation pneumonitis
Can early PET V/Q Δ predict?
Advantage of hi...
PET V 4 weeks PET QRT planning field
Radiation pneumonitis
4 Week PET Q 3 month CT
Δ function before Δ anatomy
may enable ...
Dr Michael Hofman
4D CT: additional information
We use a “mechanical” definition of ventilation:
Regional gas exchange is proportional to changes in regional volume.
(i) ...
Validating of 4D-CT Ventilation
Kipritidis J et al AAPM 2013
4D-CT (DVFs from exhale)PET-Ga (gated)
Activity
Respiratory g...
Validating of 4D-CT Ventilation
Kipritidis J et al AAPM 2013
4D-CTPET-Ga
Activity
 Low degree of voxel-wise correlation (...
Dr Michael Hofman
Pre-operative regional lung quantification
Lets get serious... Does
anyone really believe this is
satisf...
Dr Michael Hofman
Pre-operative regional lung quantification
“Zonar” function
…for real ??
Dr Michael Hofman
Lobar function
Pre-operative regional lung quantification
Dr Michael Hofman
Dr Michael Hofman
50 years since Wagners’ first 99mTc-MAA
perfusion scan
I was taught that the way of progress
was neither...
 Attractive in the context of recent shortages in 99mTc generators
 Superior image quality and faster acquisition
 Quan...
Dr Michael Hofman
Thank-you
Peter MacCallum Cancer Centre
Melbourne, Australia
michael.hofman@petermac.org
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Advantages of Ga-68 4D PET/CT Ventilation Perfusion (V/Q) Imaging

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Talk given at Society of Nuclear Medicine 2013 Scientific Meeting by Dr Michael Hofman. Galligas and GaMAA.

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  • Planar/SPECT will still have a role but the balance will shift to PET
  • Planar/SPECT will still have a role but the balance will shift to PET
  • PET/CT imaging is incredible: high radiotracer sensitivity, vastly superior spatial & temporal resolution, fully tomographic, fast, non-invasive quantitation, multi-slice CT correlationPET is our strength: we should embrace it to further improve clinical diagnosis and direct appropriate managementCost base has reduced substantially and in real terms is certainly cheaperWe now perform a whole range of routine studies, from renal, V/Q to Indium on our PET scannersUnfortunately we can’t access the same rebateUrgent need for substitutional funding
  • Ge: 270 day half life: excellent source for positron emitting radionuclide 68Ga (68 min half life)
  • Approximately 50 MBq of 68Ga in the form of gallium chloride was placed in the carbon crucible of the synthesis unit
  • Ge: 270 day half life: excellent source for positron emitting radionuclide 68Ga (68 min half life)
  • Porcine modelUppsala Univeristy
  • MIP images
  • Another way of presenting the dataCT component particularly helpful in a cancer hospital
  • PET quality equivalent or superior to SPECT in all patients, with more homogeneous radiotracer distributionSimilar number of matched & unmatched defects
  • Varian
  • eg. 111In-Octreotide vs68Ga-DOTATATE
  • eg. 111In-Octreotide vs68Ga-DOTATATE
  • eg. 111In-Octreotide vs68Ga-DOTATATE
  • Deemed non-diagnostic on conventional scintigraphy
  • Rod HicksOliverNeelsPeter EuDavid BinnsJason CallahanVal
  • Advantages of Ga-68 4D PET/CT Ventilation Perfusion (V/Q) Imaging

    1. 1. Michael Hofman, MBBS, FRACP, FANNMS Molecular Imaging, Centre for Cancer Imaging Peter MacCallum Cancer Centre / The University of Melbourne michael.hofman@petermac.org Lung Imaging - From Planar to SPECT and PET with CT Advantages of PET/CT V/Q Scanning with 68Ga
    2. 2. Acknowledgements Centre for Cancer Imaging  Prof. Rod Hicks  Mr. Jason Callahan  Mr. Peter Eu  Dr. Shankar Siva No Conflicts of Interest or Disclosure to Declare Dr Michael Hofman
    3. 3. Dr Michael Hofman Fever, shortness of breath, chest pain, productive cough ?PE
    4. 4. Dr Michael Hofman   What does the perfusion look like?
    5. 5. Planar V/Q
    6. 6. Dr Michael Hofman 99mTc-MAA 68Ga-MAA SPECT PET
    7. 7. Dr Michael Hofman PET/CT: major improvement in image accuracy
    8. 8.  Local release of inflammatory mediators result in failure of reflex vasoconstriction  shunting & hypoxia1  Histologic correlate: red hepatisation phase of lobar pneumonia 1 Light RB et al, J Appl Physiol 1981. Li DJ et al, Clin Nucl Med 1994
    9. 9. WHY do we need PET/CT V/Q? Dr Michael Hofman Superior image quality  fully tomographic   accuracy   reproducibility  quantitative  faster  respiratory gating  “CTPA capable” Advantages of 68Ga  generator produced  short t½  flexible protocols  mSv  99mTc shortages  cost effective Improved diagnostic algorithms for patients with PE Whole range of new indications
    10. 10. 68Ga eluted from onsite generator (IBD Holland) Dr Michael Hofman Galligas inhalation Ventilation 4D PET/CT GaMAA iv Perfusion 4D PET
    11. 11. Dr Michael Hofman Galligas inhalation Ventilation 4D PET/CT GaMAA iv Perfusion 4D PET Substitute 68Ga instead of 99mTc  Galligas Technegas Generator (Cyclopharm Australia) 1Kotzerke J et al, EJNMMI 2010, 37(1). 2Borges JB et al JNM 2011, 52(2). 3Hofman MS et al, JNM 2011, 52(1)
    12. 12. Dr Michael Hofman Galligas inhalation Ventilation 4D PET/CT GaMAA iv Perfusion 4D PET uSv/hr vs Norm KCPS R2 = 0.803 0 1 2 3 4 5 6 7 8 9 0 2 4 6 8 uSv/hr KCPS Close correlation between Geiger counter measurement and camera count rate
    13. 13. Galligas inhalation Ventilation 4D PET/CT GaMAA iv Perfusion 4D PET Dr Michael Hofman PETSPECT BorgesJBetalJNM2011, 52(2) normal lobar obstruction diffuse obstruction PET provided more detailed V distribution images & better appreciation of ventilation heterogeneity
    14. 14. Galligas inhalation Ventilation PET/CT GaMAA iv Perfusion PET Dr Michael Hofman 68Ga-macroaggregated albumin (GaMAA) PET
    15. 15. Galligas inhalation Ventilation 4D PET/CT GaMAA iv Perfusion 4D PET Dr Michael Hofman
    16. 16. Dr Michael Hofman PET SPECT Ventilation Perfusion Acute shortness of breath & pleuritic chest pain V/Q PET/CT versus V/Q SPECT/CT
    17. 17. Dr Michael Hofman Multiple segmental unmatched perfusion defects HofmanMSetal,JNM2011,52(1) Pulmonary embolism
    18. 18. Extrinsic compression of RUL Dr Michael Hofman PET/CT perfusion (Q) PET/CT ventilation (V) “High probability”but not PE
    19. 19. Dr Michael Hofman Hofman MS et al, J Nuc Med 2011 Oct;52(10):1513-9 n=10 Superior image quality with PET
    20. 20. 4D
    21. 21. Respiratory Gated 4D V/Q PET/CT
    22. 22. Gated CT and Gated PET
    23. 23. Dr Michael Hofman Phase Matched CT attenuation correction each PET time bin corrected with corresponding CT time bin
    24. 24. Insp PET/CT DICE = 0.81 FB PET/CT DICE = 0.83 FB PET/Ave-CT DICE = 0.84 Exp PET/CT DICE = 0.84 Expiratory bin: best PET-CT match
    25. 25. Planar V/Q & CTPA purport high accuracy of >90-95% V/Q Dr Michael Hofman
    26. 26. Planar V/Q & CTPA purport high accuracy >90-95% V/Q? Dr Michael Hofman Modest agreement ≠ high accuracy  Many false positives and negatives with V/Q & CTPA  Only modest inter-observer agreement (Ƙ=0.47 for 3mm CTPA)1  25% false positive rate in cohort of 322 patients with CTPA2 1 Chartrand-Lefebvre C et al, AJR Am J Roentgenol 1999; 172:107-112 2 Ranji SR et al, J Hosp Med 2006; 1:81-87
    27. 27. Overdiagnosis in CTPA & D-Dimer era Dr Michael Hofman Segard T, Macdonald BG MJA 2013, 198(2) CTPA PE diagnoses no Δ deaths
    28. 28. Only when new superior modality comes along do you realize how bad the “gold standard” is ! Dr Michael Hofman PET Perfusion +/- CTPA Is this PE? PET Ventilation if uncertain Quantify burden with PET Anticoagulate if significant Improve outcomes Algorithm proposal
    29. 29. Dr Michael Hofman PET/CT V/Q = High Resolution V/Q New applications
    30. 30. Dr Michael Hofman Radiotherapy planning using V/Q  Current RT planning assumes all lung functions equally - “one size fits all”  Functionally adapted RT enables intensification or de-escalation based on an individuals regional lung function Prospective study assessing PET V/Q at multiple time points during RT
    31. 31. Dr Michael Hofman Radiotherapy planning using V/Q
    32. 32. Functional adapted radiotherapy Dr Michael Hofman Hypothetical functional lung : - ‘any perfusion’ and ‘high perfusion’ contours New treatment plan based on PET Functionally adapted radiotherapy
    33. 33.  14 consecutive patients with RT plans adapted to perfusion PET/CT  Optimised 3D conformal and IMRT plans showed an improvement in mean lung dose (MLD) of 1.4Gy (p=0.03) and 2.1Gy (p=0.02), respectively Shankar S et al, RANZCR 2013
    34. 34. RT planning field CT @ 4 weeks: no ΔPET V 4 weeks PET Q Radiation pneumonitis Can early PET V/Q Δ predict? Advantage of high resolution 4D PET/CT clear
    35. 35. PET V 4 weeks PET QRT planning field Radiation pneumonitis 4 Week PET Q 3 month CT Δ function before Δ anatomy may enable RT intensification or de-intensification
    36. 36. Dr Michael Hofman
    37. 37. 4D CT: additional information
    38. 38. We use a “mechanical” definition of ventilation: Regional gas exchange is proportional to changes in regional volume. (i) Acquire paired images (4D-CT) high low (ii) Deformable Image Registration (DIR) (iii) Analyze deformation vector field (DVF) Guerrero et al. (IJROBP 2005) Can 4D CT alone assess ventilation?
    39. 39. Validating of 4D-CT Ventilation Kipritidis J et al AAPM 2013 4D-CT (DVFs from exhale)PET-Ga (gated) Activity Respiratory gated PET-CT (using Galligas) overcomes many experimental validation issues
    40. 40. Validating of 4D-CT Ventilation Kipritidis J et al AAPM 2013 4D-CTPET-Ga Activity  Low degree of voxel-wise correlation (r=0.14) but moderate degree for lowest (25th percentile) function (DICE=0.29).  Large improvement by applying linear scaling of DVF-Jacobian by the CT voxel values (r = 0.24, d = 0.38).
    41. 41. Dr Michael Hofman Pre-operative regional lung quantification Lets get serious... Does anyone really believe this is satisfactory? Surgeons want real lobar function not zonar function !
    42. 42. Dr Michael Hofman Pre-operative regional lung quantification “Zonar” function …for real ??
    43. 43. Dr Michael Hofman Lobar function Pre-operative regional lung quantification
    44. 44. Dr Michael Hofman
    45. 45. Dr Michael Hofman 50 years since Wagners’ first 99mTc-MAA perfusion scan I was taught that the way of progress was neither swift nor easy. Marie Curie
    46. 46.  Attractive in the context of recent shortages in 99mTc generators  Superior image quality and faster acquisition  Quantitative imaging, respiratory gating  Cost effective in centers with PET  More flexible acquisition protocols possible  High resolution V/Q: new applications Dr Michael Hofman 68Ga V/Q PET/CT: feasible now
    47. 47. Dr Michael Hofman Thank-you Peter MacCallum Cancer Centre Melbourne, Australia michael.hofman@petermac.org

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