SHAPE Society

1. SPECT/CT for Atherosclerosis Imaging: The
Future is Clear
Daniel S. Berman, MD
Director, Cardiac Imaging
Cedars-Sinai Medical Center
Professor of Medicine
David Geffen School of Medicine at UCLA

2. DISCLOSURE
Daniel S. Berman, M.D.
declares the following relationships:
Grant Support: BMS Medical Imaging, Astellas,
GE Amersham, Mallinckrodt-Tyco
Speakers Bureau: Astellas
Consultant: Mallinckrodt-Tyco
Spectrum Dynamics
Royalties: Cedars-Sinai Medical Center
Stockholder: Spectrum Dynamics

3. MDCT Technical Parameters 2005
Four major manufacturers with 64 slice CT
• ~.4-.5 mm3
isotropic voxels
• Temporal resolution: 165-210 ms for 180°
(330-420 ms rotation time)
• Cardiac study in 5-10 beats

4. 76 M #3311-1526
Sx: ASYMPTOMATIC
RISK FACTORS: ↑CHOLESTEROL
RESTING ECG: NORMAL
RESULTS OF EXERCISE:
DURATION: 9:39
HR: 131 (91% MPHR) BP: 134/74 → 150/72
CLINICAL RESPONSE: NONISCHEMIC
ECG RESPONSE: NONISCHEMIC

5. 73 M #3311-1526
EBT RESULTS
Location # Calcified
Lesions
Calcified Plaque
Volume (mm
3
)
Calcium Score
LAD 3 97 126
* 32th percentile

6. 76 M #3311-1526
CTA

7. 76 M 11/3/05 #3311-1526
Stress MIBI
Rest Tl
Stress MIBI
Rest Tl
Stress MIBI
Rest Tl
Stress MIBI
Rest Tl

8. 76 M #3311-1526

9. A B C D
Calcification Soft Plaque
D2
Lesion
76 M #3311-1526

10. Limitations of Anatomic Imaging
Little information regarding disease activity
• Two patients: with mild coronary calcium,
score ~100 discovered on screening 1 yr ago
and placed on statin, ASA, and ACE
• Patient A: recently symptomatic
• Patient B: still asymptomatic
• Both undergo CT coronary angiography, and
are found to have 75% mid LAD stenosis by
CT angio AND extensive non-calcified plaque
by IVUS
• Should the treatment be the same?

11. It will be!

12. Why not catheterize all suspected CAD patients?
Occulo-stenotic reflex*: unnecessary PCI• Immediate Risk
– Death (rare)
– Clinical MI (uncommon)
– Subclinical MI (more frequent)
– Branch occlusion (frequent)
• Late risk
– Possible higher mortality risk than medical therapy in patients without ischemia
• Costs
• Objective measurements of perfusion and function
• Accurate for assessing risk of cardiac death (CD)
• Relationship of degree of abnormality to risk
• Identifies likely to benefit from revascularization
• Proven as cost effective “gatekeeper” to the cath lab
Limitations
• Cannot detect early atherosclerosis
• May underestimate extent of CAD
*Topol

13. Cardiac CT
Limitations
• Densely calcified plaques: nondiagnostic
• Dependence on low HR and regular rhythm
• Radiation, iodinated contrast
• Overestimation of stenosis
• No information regarding plaque “activity”

14. • No Hx CAD
• Known CAD
• Post-PTCA
• Post-CABG
• Men and Women
• Sx and Asx
• DM
• Elderly
SPECT: Risk Increases as a Function of
Stress Perfusion Abnormality
Extent/Severity of Perfusion Defec
Risk*
*Adjusted or unadjusted
Guidelines for Clinical Use of Cardiac Radionuclide Imaging 2003
Data from over 50,000 patients

15. logHazardRatio
0123456
% Myocardium Ischemic
0 12.5% 25% 32.5% 50%
Medical Rx
Revasc
*
*
*p<0.001
Adjusted†
Risk of Cardiac Death vs MPS ischemia
Revascularization vs Medical Rx
Hachamovitch, et al Circulation 2003
†
Adjusted for predictors
of revascularization as well as
clinical, hx, stress SPECT data

16. VISUAL SSS
STANDARD
TPD
stenosis ≥ 50%
1.00.75.50.250.00
1.00
.75
.50
.25
0.00
1 - Specificity
Sensitivity
Changes in Analytic Software
Automatic Total Perfusion Deficit
**
* P < 0.05
Slomka, et al J Nucl Cardiol 2005;12:66-77

17. When was the last fundamental change in the
detector technology?
Nuclear Cardiology: Single Photon Imaging

18. When was the last fundamental change in the
detector technology?
1958: Hal Anger patented the current NaI
(Tl) detector/photomultiplier array
configuration (#3011057)
Nuclear Cardiology: Single Photon Imaging

19. Resolution & Contrast - a Comparison
Total counts: 2,500K Total counts: 2,500K
Spectrum-Dynamics
Coronal
Sagittal
Transverse
Net acquisition time: 9 minutes
Frame angle: 3°, positions:60, 9sec per position
Net acquisition time: 1 minute
positions:40, 1.5sec per position
Millennium VG a
Spectrum Dynamics Measured Contrast
Target A: 1.6
Target B: 2.2
Millenium Measured Contrast
Target A: unseen
3:1
2:1

20. Cardiac Phantom
Conventional
• No AC
• Acquisition time 12.5
m
Spectrum Dynamics
• No AC
• Acquisition time 1.25 m
•Tc99m
•Heart : .5mCi
•Background : 2mCi (.19mCi/l)
•Liver : .23mCi
(.19mCi/liter)

21. Cardiac SPECT Improvements
Implications for CHD and Atherosclerosis Testing
• Increased sensitivity: reduced acquisition time
– Dynamic cardiac SPECT:
• time-activity curves for blood and myocardium
• Compartment modeling results in:
– Absolute blood flow (voxel)
– Coronary Flow Reserve: a region compared to itself
– Coronary endothelial function (CPT)
• Increased resolution:
– Potential to directly image plaque
• quantify “activity” of atherosclerosis

22. SPECT/CT
Philips Precedence Siemens Simbia

23. Dynamic SPECT for
Molecular Imaging
• Noninvasive biopsy
• Specific diagnosis
CT for Structure
DynaQ™ hybrid scanner

24. Who needs PET/CT or SPECT/CT
• Equivocal nuclear
• Follow-up studies after initial CT (or
nuclear)
• Why simultaneous: molecular imaging

25. Comparative Spatial Resolution and
Tracer Concentration
SPECT PET ECHO MRI CT
Resolution
(mm)
7-15 3-10 < 1 < 1 < 1
Tracer
Concentration
pM-nM* pM-nM* 10-100
μM
10-100
μM
10-100
μM
*picomolar-nanomolar concentrations employed are
key advantage of the radionuclide methods

26. translocase
death domains
mediated signaling
activation of the
executioner of apoptosis
scramblase
floppase
?
binding followed by
2D-crystallization
Annexin V
Detection of the
apoptotic cell
TNF or
Fas Ligand
TNFR or
CD95
+ +-
Courtesy Chris Reutlingsperger, Maastricht University
Tc-99m Annexin V: Probe for Vulnerable Plaque

27. Old TIA Recent TIA
A B
C D
Transverse
Coronal
ANT
L
Annexin
IHC in
Endarterectomy
Keitselaar, Hofstra, Narula; NEJM 2004
Annexin-V Imaging For ApoptosisAnnexin-V Imaging For Apoptosis

28. Annexin V-Tc99m
autoradiograph
Digital photograph
dissected apoE-/- aorta
H & E
Histological AHA classification
Stage IVa (vulnerable plaque)
Tc-99m Annexin
dissected aorta apoE -/- mouse
C. Mori
Stanford, 2005

29. 99m
Tc-Annexin V SPECT for In Vivo Detection of
Atherosclerotic Lesions in Porcine Coronary Arteries
Johnson et al. J Nucl Med 2005;46:1186-93
Scan positive
Scan negative

30. Imaging of Atherosclerotic Plaques Using a Human
Antibody Against the Extra-Domain B of Fibronectin
Matter et al. Circ Res 2004;95:1225-33
125
I-labeled L19 to
atherosclerotic
plaques in ApoE-/-
mice.

31. OxLDL AB uptake reflects
plaque burden
R=0.95
P<0.001
0.00
0.05
0.10
0.15
0.20
0.25
0 500 1000 1500 2000
Aortic weight (mg)
(%ID)
MDA2
125
I-MDA2 Uptake in Mouse and Rabbit
Atherosclerotic Plaques
Tsimikas J Nucl Cardiol 1999, ATVB 2001

32. IL2 SPECT in 2 pts with bi-lateral carotid plaques
A Annovazzi e A Signore ACC 2005

33. IL2 SPECT: Carotid T/B ratios in patients from
LS before and after 3 month treatment
1
1,5
2
2,5
3
3,5
Before therapy After therapy
99mTc-IL2uptake(C/Bratios)
Atorvastatin
1
1,5
2
2,5
3
3,5
Before diet After diet
Hypocholesterolemic
diet

34. SPECT for imaging vulnerable plaque
Potential to Image Multiple Molecular
Processes Simulaneously
• Apoptosis
• IK-17
• Oxidized LDL
• Interleukin 2
• Thrombus
• Activated platelets
• Neovascularization

35. Molecular Imaging
Needed Developments
• Discovery in molecular biology
• New probes (with FDA approval)
• Multimodality technology
– Structure/function
Post-processing software
• Reimbursement

36. SPECT/CT for Atherosclerosis Imaging
• CT: quantify plaque volume
• SPECT or PET:
– quantify plaque activity
– Potential to quantify rest/stress blood flow
Advantage of SPECT
• Multiple tracers simlutaneously
• Possible wider availability of tracers and cameras
• Potential of SPECT
• Increased sensitivity and resolution need to be realized