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

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. 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. Dr Michael Hofman
Fever, shortness of breath, chest pain, productive cough
?PE

4. Dr Michael Hofman


What does the perfusion
look like?

5. Planar V/Q

6. Dr Michael Hofman
99mTc-MAA 68Ga-MAA
SPECT PET

7. Dr Michael Hofman
PET/CT: major improvement in image accuracy

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. 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. 68Ga eluted from onsite generator
(IBD Holland)
Dr Michael Hofman
Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfusion
4D PET

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. 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. 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. Galligas
inhalation
Ventilation
PET/CT
GaMAA
iv
Perfusion
PET
Dr Michael Hofman
68Ga-macroaggregated albumin (GaMAA) PET

15. Galligas
inhalation
Ventilation
4D PET/CT
GaMAA
iv
Perfusion
4D PET
Dr Michael Hofman

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. Dr Michael Hofman
Multiple segmental
unmatched perfusion defects
HofmanMSetal,JNM2011,52(1)
Pulmonary embolism

18. Extrinsic compression of RUL
Dr Michael Hofman
PET/CT perfusion (Q)
PET/CT ventilation (V)
“High probability”but not PE

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. 4D

21. Respiratory Gated 4D V/Q PET/CT

22. Gated CT and Gated PET

23. Dr Michael Hofman
Phase Matched CT attenuation correction
each PET time bin corrected with corresponding CT time bin

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. Planar V/Q & CTPA purport high accuracy of
>90-95% V/Q
Dr Michael Hofman

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. Overdiagnosis in CTPA & D-Dimer era
Dr Michael Hofman
Segard T, Macdonald BG MJA 2013, 198(2)
CTPA
PE diagnoses
no Δ deaths

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. Dr Michael Hofman
PET/CT V/Q = High Resolution V/Q
New applications

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. Dr Michael Hofman
Radiotherapy planning using V/Q

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.  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. 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. 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. Dr Michael Hofman

37. 4D CT: additional information

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. 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. 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. 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. Dr Michael Hofman
Pre-operative regional lung quantification
“Zonar” function
…for real ??

43. Dr Michael Hofman
Lobar function
Pre-operative regional lung quantification

44. Dr Michael Hofman

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.  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. Dr Michael Hofman
Thank-you
Peter MacCallum Cancer Centre
Melbourne, Australia
michael.hofman@petermac.org