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Cardiovascular
PET-CT
Ahmed Tawakol, M.D.
Cardiology Division
Massachusetts General Hospital &
Harvard Medical School
Positron Emission Tomography
Just the basics…
b +
b -
511 keV
511 keV
PET Physics
Positron
Emission
b +
Annihilation
511 keV
511 keV
b -
b +
Annihilation
Detector Crystals
and PMT
Positron Emission Tomography
Coincidental photons
registere...
b -
b +
Annihilation
Detector Crystals
and PMT
Positron Emission Tomography
Scattered photons
rejectedrejected
Arrives
fir...
Common PET Perfusion Tracers
• Rubidium (t1/2= 76 sec)
– 82-Rubidium
• Oxygen (t1/2= 2 min)
– Water
• Nitrogen (t1/2= 10 m...
PET Flow Measurements
Correlate Well with µSPHRS
PET_MBF (K1)
0.00
1.00
2.00
3.00
4.00
5.00
0.00 2.00 4.00 6.00 8.00 10.00...
CFR vs. Stenosis MLD
Gould KL - AJC 1974; 33:87-94
0 25 50 75 100
% Stenosis
CoronaryFlowReserve
1
3
2
4
5
PET 13
NH3 MBF Methods:
• Compare MBF at rest and during
adenosine either qualitatively or
quantitatively
• Coronary Flow ...
Accuracy of PET
Rest Stress Rest Stress
Di Carli et al Circulation 1995
Accuracy of PET
Comparison w SPECT
Sensitivity and specificity higher with PET
Go et al, J Nucl Med 1990
Coronary CT Angiography
Complements PET
CT Coronary Angiography
Potential applications:
-detect coronary stenoses
-detect coronary anomalies
-determine bypass pat...
Prerequisites forPrerequisites for
Successful Cardiac CTSuccessful Cardiac CT
II
Temporal ResolutionTemporal Resolution
Sp...
64-slice MSCT
• Simultaneous acquisition of 64 slices/rotation
• Rotation 330 ms  temporal resolution <165 ms
• Slice wid...
Prerequisites forPrerequisites for
Successful Cardiac CTSuccessful Cardiac CT
IIII
• Appropriate Breath HoldAppropriate Br...
Axial Source Images
Thin MIP 3D VRT Curved MPR
Post Processing
Comprehensive Cardiac CTComprehensive Cardiac CT
ExaminationExamination
Diagnostic Accuracy of EBCT, 4 -Diagnostic Accuracy of EBCT, 4 -
and 16 - slice MDCTand 16 - slice MDCT
Assessable
Segment...
n Sens. Spec. n.e.
Ropers ACC 2005 84 91% 93% 7%
Leschka Eur Heart J 2005 67 94% 97% --
Raff JACC 2005 70 86% 95% 12%
Diag...
Maximum Intensity Projection RCA 3D VRT LCX and RCA
RCA StenosisRCA Stenosis
Occlusion 1st
diagonal
branch
Multiplanar Reconstruction
Chest Pain StudyChest Pain Study
early risk stratification in the EDearly risk stratification in the ED
decision to admit ...
Patient without ACSPatient without ACS
43 year old female, 3 hours of substernal chest pain
radiating to the back, negativ...
• Patient with crushing chest pain
• Relieved with NTG SL
• Borderline ST- Elevation
• No biomarker elevation
Patient with...
Perfusion Defect
Test Raw Data Overall
Sensitivity 5/5 1 (0.49, 1)
Specificity 26/35 0.74 (0.57,0.88)
Accuracy 31/40 0.78 (0.62, 0.89)
PPV ...
Potential Impact onPotential Impact on
Decision MakingDecision Making
Pre-test
Probability
Post-test
Probability
P-value
A...
Anomalous Right Coronary
Artery
• High sensitivity and specificity for arterial conduits
and venous grafts
• Limitations: distal Anastomosis in small vess...
Limitations
TECHNICAL
-- Calcium
- Motion - Heart Rate
CONCEPTUAL
- Contrast, X-ray
- Sinus rhythm
- No intervention
How Do PET and CT
complement each other?
& ’Brigham Women s Hospital& ’Brigham Women s Hospital
-Patient 1 Rubidium Study-Patient 1 Rubidium Study
. : ’Complements of M Di Carli Brigham and Women s Hospital. : ’Complements of M Di Carli Brigham and Women s Hospital
Pat...
/ :Cardiac PET CT Patient 2/ :Cardiac PET CT Patient 2
-Non calcified-Non calcified
plaqueplaque
stentstent
calcifiedcalci...
’Brigham and Women s Hospital’Brigham and Women s Hospital
/ :Cardiac PET CT Patient 2/ :Cardiac PET CT Patient 2
Future of PET-CT:
Detection of Vulnerable Plaques
Introduction to the Vulnerable Plaque
• Vulnerable Plaques (VP) = rupture-prone
plaques
• Autopsy studies : majority of ca...
Falk E., Shak P.K., Fuster V. Circulation 1995
Most Ruptured Plaque Caused Insignificant
Luminal Narrowing Prior to Ruptur...
Technologies that detect luminal
narrowing are not useful for the
detection of vulnerable plaques.
Novel methods to detect...
Which Targets?
Vascular inflammation is an
attractive target for the detection
of vulnerable plaques.
Inflammatory Markers Predict Coronary Events
Ridker PM et al. N Engl J Med 2000;342:836
4
3
2
1
1
RelativeRiskofFuture
Cor...
From: Libby P. Nature 2002,:420, 868 - 874
Inflammation and Plaque
Progression
Inflammation is an Important Participant in
All Phases of Atherothrombotic Disease
• Lesion initiation
• Lesion progressio...
Imaging technologies that
characterize plaque inflammation
may prove useful for assessment of
risk of an ischemic event.
Nuclear Methods to
Image Inflammation
• Nuclear probes long been used to non-invasively
localize inflammation in humans.
•...
FDG Uptake Reflects Glycolysis
Adapted from: Hughes: Thorax, Volume 51(2S) 16S-22S
K1
18
FDG 18
FDG 18
FDG
K2
18
FDG-6-pho...
Metabolic Basis for Using FDG-PET
for Macrophage Imaging
• Macrophages:
– Have high basal metabolic rates,
– Rely on exter...
Increased FDG Uptake has
been Observed in Human
Atherosclerotic Plaques
Increased FDG Uptake in Vascular
Inflammatory Diseases
Increased FDG uptake has been reported in:
-Takayasu's arteritis,
-...
Increased FDG Uptake Observed in
Symptomatic Carotid Disease
Symptomatic
CarotidStenosis
Asymptomatic
CarotidStenosis
PET ...
Can FDG uptake, (PET), be used
to measure vascular inflammation?
-Animal study
PET-FDG Methods
Histology3 hr
PET
ImagingFDG administered
(IV) to balloon-
injured,
cholesterol-fed
atherosclerotic
rabbit...
Rabbit Model: Gross Pathology
Rabbit Model: Histopathology
H&E Trichrome RAM-11
InflamedFibrous
Tawakol, JNC 2005
Co-Registered Control Rabbit Aorta ImagesPETCT
AxialSagittal
Co-Registered Atherosclerotic Rabbit Aorta Images
Axial
PETCT
Axial
P<0.001, r=0.79
FDG Uptake vs. Inflammation in Atherosclerotic Rabbits
Vessel Inflammation
(% RAM-11 Staining)
FDGUptake
(...
P<0.0001,
r =0.93
PET - SUV vs. Inflammation in Atherosclerotic Rabbits
Inflammation
(% RAM-11 Staining)
0 10 20 30
FDGUpt...
Plaque inflammation can
be characterized with
FDG-PET
Can FDG-PET be used to
measure vascular
inflammation in humans?
Carotid PET Study
Histologic
correlationCEA
10 patients
w carotid
stenosis
scheduled
for CEA
FDG-
PET
Merged
with MRI
or CT
Results: Subject Characteristics
Characteristic Mean (± SEM)
Age (yr) 73 ± 3
Gender (M/F) 4/6
Symptoms (%) 20
Diabetes (%)...
Patient 1: Low FDG Uptake
Trichrome
Collagen-rich plaque
Thick Fibrous Cap
Low lipid content
CD68
<1% plaque area
composed of
inflammatory cells
Pat...
Patient 2: High FDG Uptake
CD68 Stain
20-30% plaque area
composed of
inflammatory cells
Trichrome
Thin Fibrous Cap
(50 microns)
Large necrotic core
P...
Carotid FDG Uptake
FDGUptake(T/B)
Macrophage Staining (% plaque area)
Inflammation vs. FDG Uptake (PET)
N=10
P<0.0001
r=0.82
J
J J
JJJ
JJJJJJ...
Macrophage Staining (% plaque area)
Inflammation vs. FDG Uptake (PET)
Individual Patient Data
0 2 4 6 8 10 12 14
MeanT/B
0...
FDGUptake(T/B)
Collagen Staining (% plaque area)
Collagen vs. FDG Uptake (PET)
J
J
J
J
J
J
J
J
JJ
J
J
0.5
1
2
3
50 60 70 8...
Smooth Muscle Cell Staining (%)
0 10 20 30 40 50
FDGUptake(T/B)
0.5
1.0
1.5
2.0
2.5
3.0
3.5
P=NS
Smooth Muscle Cells vs. F...
Carotid FDG uptake
correlates with histological
evidence of inflammation.
Implications
• FDG-PET may be useful for non-invasive characterization of
vascular inflammation
• Technique has promise:
–...
Structural Imaging (CT or
MR) needed for PET
measurements
CT is also useful for plaque
detection
Detection of Plaque
Source Image LAD in Cross Section
Detection of Plaque
Non-diseased segment (LAD) Diseased segment (LAD)
16-slice MSCT
MPR of LAD in Cross SectionThin MIP
Detection of Plaque
Sensitivity 82%, Specificity 88%
Achenbach et al. Circulation 2004
r = 0.64, p < 0.001
Moselewski et al. AJC 2004
Plaque Area
Potential to detect and quantify coronary plaque
Plaque CompositionPlaque Composition
Potential to discriminate calcified and non- calcified
plaque
Leber et al JACC
MDCT Plaque Remodeling:
0.34 cm² 0.43 cm²
PET-CT Imaging of Other
Large Vessels?
Left Iliac
Shoulder of AAA
Rapidly Expanding AAA:
Coronal Images
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Sagittal CT Coronal PET
Are we ready for coronary plaque imaging?
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
•Myocardial uptake of FDG
•...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
•Myocardial uptake o...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
•Myocardial uptake o...
Suppression of Myocardial FDG Uptake
• Relatively simple
• Healthy myocardium prefers lipids to
glucose
• High fat, low gl...
Suppression of Myocardial FDG Uptake
after Atkins-Type Diet for 24 Hrs
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
•Myocardial uptake o...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
•Myocardial uptake o...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
•Myocardial uptake o...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
•Myocardial uptake o...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
Myocardial uptake of...
Novel Tracers
Potential Targets:
– Inflammation
• FDG
• Scavenger receptor
• P2 purine receptors
• others
– Apoptosis
– Th...
Purine Receptor Imaging
18
F-Meth-Ap4A
Sagittal
Aorta
Transverse
Aorta
Coronal
Spine
Aorta
Micro-PET
P<0.001
r=0.87
AP4AUptake
(%ID/cc)
0.00
0.02
0.04
0.06
0.08
0.10
0-7 8-16 >16
Plaque Inflammation
(% Ram-11 Staining)
Ap4A...
Annexin V
Kietselaer BL, NEJM 2004
ConjugatedF
FreeF
ConjugatedF
FreeF
0
10
20
30(molce6equivalent/gmtissuex10-10
)
FlurochromeConcentration
Inflamed Ao
Cont...
Detection of Coronary Plaques:
Additional Technical Challenges
•Cardiac and respiratory motion
Gating
Myocardial uptake of...
Improved Instrumentation
• Intravascular positron detectors
• Improved PET and PET-CT
• PET-MRI
Volume CT System
Canine heart
150 micron isotropic resolution
VCT Lab in Bldg 149
Detector
Tube
Crossflex 3 x 18 mm
Stent
VCT MDCT
150 x 150 x 150µ 650 x 650 x 1250µ
Courtesy of HW Strauss
Visualization of Coronary Plaque
FDG with PET-CT
Future of Cardiac PET-CT:
• Location of stenoses
• Perfusion map (rest and adenosine stress)
• Flow reserve map (correlate...
CTA: 3D VOLUME RENDERING
LAD
1st
Diag
LCX
2nd
Diag
LAD - stenosis
1st
Diag
LCX
2nd
Diag
MBF
ml/g/min
Future Cardiac PET-CT Display?
MBF
ml/g/min
Future Cardiac PET-CT Display?
Middle Aged Woman w CP
Could we have intervened and prevented the MI?
What if… we also detected a high degree of plaque inflammation?
Acknowledgements
Cardiology
• Kusai Aziz, MD
• Gregory Bashian, MD
• Henry Gewirtz, MD
• Alex Morss, MD
• James Muller, MD...
Cardiac petct ahmed tawakol
Cardiac petct ahmed tawakol
Cardiac petct ahmed tawakol
Cardiac petct ahmed tawakol
Cardiac petct ahmed tawakol
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Cardiac petct ahmed tawakol

  1. 1. Cardiovascular PET-CT Ahmed Tawakol, M.D. Cardiology Division Massachusetts General Hospital & Harvard Medical School
  2. 2. Positron Emission Tomography
  3. 3. Just the basics…
  4. 4. b + b - 511 keV 511 keV PET Physics Positron Emission b + Annihilation
  5. 5. 511 keV 511 keV b - b + Annihilation Detector Crystals and PMT Positron Emission Tomography Coincidental photons registered as true events
  6. 6. b - b + Annihilation Detector Crystals and PMT Positron Emission Tomography Scattered photons rejectedrejected Arrives first Arrives late
  7. 7. Common PET Perfusion Tracers • Rubidium (t1/2= 76 sec) – 82-Rubidium • Oxygen (t1/2= 2 min) – Water • Nitrogen (t1/2= 10 min) – Ammonia • Carbon (20 min) – Acetate
  8. 8. PET Flow Measurements Correlate Well with µSPHRS PET_MBF (K1) 0.00 1.00 2.00 3.00 4.00 5.00 0.00 2.00 4.00 6.00 8.00 10.00 uSPHRS (ml/min/g) PET_13NH3 r=0.97
  9. 9. CFR vs. Stenosis MLD Gould KL - AJC 1974; 33:87-94 0 25 50 75 100 % Stenosis CoronaryFlowReserve 1 3 2 4 5
  10. 10. PET 13 NH3 MBF Methods: • Compare MBF at rest and during adenosine either qualitatively or quantitatively • Coronary Flow Reserve (CFR) = MBFadenosine / MBFrest
  11. 11. Accuracy of PET Rest Stress Rest Stress Di Carli et al Circulation 1995
  12. 12. Accuracy of PET Comparison w SPECT Sensitivity and specificity higher with PET Go et al, J Nucl Med 1990
  13. 13. Coronary CT Angiography Complements PET
  14. 14. CT Coronary Angiography Potential applications: -detect coronary stenoses -detect coronary anomalies -determine bypass patency -assess LV function -assess myocardial perfusion
  15. 15. Prerequisites forPrerequisites for Successful Cardiac CTSuccessful Cardiac CT II Temporal ResolutionTemporal Resolution Spatial ResolutionSpatial Resolution Volume CoverageVolume Coverage
  16. 16. 64-slice MSCT • Simultaneous acquisition of 64 slices/rotation • Rotation 330 ms  temporal resolution <165 ms • Slice width .6 mm  spatial resolution (0.6 mm)3 • Scan time 10 seconds • ECG-gating  multi-phasic reconstruction
  17. 17. Prerequisites forPrerequisites for Successful Cardiac CTSuccessful Cardiac CT IIII • Appropriate Breath HoldAppropriate Breath Hold exact instructions (mid inspiration)exact instructions (mid inspiration) exercise and observe heart rateexercise and observe heart rate Low heart rate, NSR (<65 bpm)Low heart rate, NSR (<65 bpm) Beta Blocker PO/IVBeta Blocker PO/IV
  18. 18. Axial Source Images
  19. 19. Thin MIP 3D VRT Curved MPR Post Processing
  20. 20. Comprehensive Cardiac CTComprehensive Cardiac CT ExaminationExamination
  21. 21. Diagnostic Accuracy of EBCT, 4 -Diagnostic Accuracy of EBCT, 4 - and 16 - slice MDCTand 16 - slice MDCT Assessable Segments Pooled Sensitivity   97.5% CI     Pooled Specificit y 97.5% CI All CT 83% 80.6%-85.3% 94% 93.2%- 94.6% MSCT 83% 79.8%-85.7% 96% 95.1%- 96.5% 4- and 8-slice 82% 78.3%-85.2% 96% 95.0%- 96.6% 16-slice 86% 80.3%-91.4% 96% 94.4%- 97.1% All Segments       All CT 72% 69.5%-74.3% 84% 83.3%- 84.9% MSCT 72% 71.4%-73.2% 88% 87.9%- 88.7%
  22. 22. n Sens. Spec. n.e. Ropers ACC 2005 84 91% 93% 7% Leschka Eur Heart J 2005 67 94% 97% -- Raff JACC 2005 70 86% 95% 12% Diagnostic Accuracy of 64- slice MDCT
  23. 23. Maximum Intensity Projection RCA 3D VRT LCX and RCA
  24. 24. RCA StenosisRCA Stenosis
  25. 25. Occlusion 1st diagonal branch
  26. 26. Multiplanar Reconstruction
  27. 27. Chest Pain StudyChest Pain Study early risk stratification in the EDearly risk stratification in the ED decision to admit to hospitaldecision to admit to hospital MDCTMDCT standard clinical care (blinded to MDCT)standard clinical care (blinded to MDCT)
  28. 28. Patient without ACSPatient without ACS 43 year old female, 3 hours of substernal chest pain radiating to the back, negative initial Troponin and CK-MB, ECG: sinus bradycardia
  29. 29. • Patient with crushing chest pain • Relieved with NTG SL • Borderline ST- Elevation • No biomarker elevation Patient with ACSPatient with ACS
  30. 30. Perfusion Defect
  31. 31. Test Raw Data Overall Sensitivity 5/5 1 (0.49, 1) Specificity 26/35 0.74 (0.57,0.88) Accuracy 31/40 0.78 (0.62, 0.89) PPV 5/14 0.38 (0.13, 0.65) NPV 26/26 1 (0.87, 1) DOR 286 Overall Diagnostic Accuracy of MDCT (>50% stenosis) vs. ACS outcome
  32. 32. Potential Impact onPotential Impact on Decision MakingDecision Making Pre-test Probability Post-test Probability P-value ACSACS 0.44±0.39 0.79±0.28 0.03 NoNo ACSACS 0.28±0.21 0.05±0.07 0.0001 Decrease average LOS in patients without ACS by 22 hours per patient
  33. 33. Anomalous Right Coronary Artery
  34. 34. • High sensitivity and specificity for arterial conduits and venous grafts • Limitations: distal Anastomosis in small vessels, metallic clips Martuscelli Circulation 2004 Bypass Graft Patency
  35. 35. Limitations TECHNICAL -- Calcium - Motion - Heart Rate CONCEPTUAL - Contrast, X-ray - Sinus rhythm - No intervention
  36. 36. How Do PET and CT complement each other?
  37. 37. & ’Brigham Women s Hospital& ’Brigham Women s Hospital -Patient 1 Rubidium Study-Patient 1 Rubidium Study
  38. 38. . : ’Complements of M Di Carli Brigham and Women s Hospital. : ’Complements of M Di Carli Brigham and Women s Hospital Patient 1Patient 1 LMLM AoAo LMLM AoAo LVLV AoAo LMLM LADLAD LADLAD LCXLCX LVLV
  39. 39. / :Cardiac PET CT Patient 2/ :Cardiac PET CT Patient 2 -Non calcified-Non calcified plaqueplaque stentstent calcifiedcalcified plaqueplaque
  40. 40. ’Brigham and Women s Hospital’Brigham and Women s Hospital / :Cardiac PET CT Patient 2/ :Cardiac PET CT Patient 2
  41. 41. Future of PET-CT: Detection of Vulnerable Plaques
  42. 42. Introduction to the Vulnerable Plaque • Vulnerable Plaques (VP) = rupture-prone plaques • Autopsy studies : majority of cases of sudden death are associated with an underlying ruptured plaque
  43. 43. Falk E., Shak P.K., Fuster V. Circulation 1995 Most Ruptured Plaque Caused Insignificant Luminal Narrowing Prior to Rupturing 68% 18%
  44. 44. Technologies that detect luminal narrowing are not useful for the detection of vulnerable plaques. Novel methods to detect vulnerable plaques are needed.
  45. 45. Which Targets?
  46. 46. Vascular inflammation is an attractive target for the detection of vulnerable plaques.
  47. 47. Inflammatory Markers Predict Coronary Events Ridker PM et al. N Engl J Med 2000;342:836 4 3 2 1 1 RelativeRiskofFuture CoronaryEvents Quartile of Inflammatory Marker hs-CRP 2 3 4 SAA IL-6 sICAM-1
  48. 48. From: Libby P. Nature 2002,:420, 868 - 874 Inflammation and Plaque Progression
  49. 49. Inflammation is an Important Participant in All Phases of Atherothrombotic Disease • Lesion initiation • Lesion progression • Plaque Rupture • Thrombosis
  50. 50. Imaging technologies that characterize plaque inflammation may prove useful for assessment of risk of an ischemic event.
  51. 51. Nuclear Methods to Image Inflammation • Nuclear probes long been used to non-invasively localize inflammation in humans. • Examples: – 67 Ga citrate, – 111 In- or 99m Tc-labeled leukocytes, – 111 In-labeled IgG. • Perhaps the best clinically available method is FDG- PET
  52. 52. FDG Uptake Reflects Glycolysis Adapted from: Hughes: Thorax, Volume 51(2S) 16S-22S K1 18 FDG 18 FDG 18 FDG K2 18 FDG-6-phosphate Glycogen Glycolysis Hexokinase K3 Vessel Cell transporter protein x x
  53. 53. Metabolic Basis for Using FDG-PET for Macrophage Imaging • Macrophages: – Have high basal metabolic rates, – Rely on external glucose source as fuel (macrophages do not store glycogen) – Increase glucose consumption further when activated. • FDG uptake by inflamed tissues is 10-20 times that of most other tissues. • FDG uptake is often higher in inflammatory tissue than in tumor cells.
  54. 54. Increased FDG Uptake has been Observed in Human Atherosclerotic Plaques
  55. 55. Increased FDG Uptake in Vascular Inflammatory Diseases Increased FDG uptake has been reported in: -Takayasu's arteritis, -Giant cell arteritis, -Polymyalgia rheumatica and -Nonspecific aortitis -Patients with atherosclerosis
  56. 56. Increased FDG Uptake Observed in Symptomatic Carotid Disease Symptomatic CarotidStenosis Asymptomatic CarotidStenosis PET CT Co-Registered Image J.H.F. Rudd et al,. Circulation 2002
  57. 57. Can FDG uptake, (PET), be used to measure vascular inflammation? -Animal study
  58. 58. PET-FDG Methods Histology3 hr PET ImagingFDG administered (IV) to balloon- injured, cholesterol-fed atherosclerotic rabbits +/- 16s CT Angiography
  59. 59. Rabbit Model: Gross Pathology
  60. 60. Rabbit Model: Histopathology H&E Trichrome RAM-11 InflamedFibrous Tawakol, JNC 2005
  61. 61. Co-Registered Control Rabbit Aorta ImagesPETCT AxialSagittal
  62. 62. Co-Registered Atherosclerotic Rabbit Aorta Images Axial PETCT Axial
  63. 63. P<0.001, r=0.79 FDG Uptake vs. Inflammation in Atherosclerotic Rabbits Vessel Inflammation (% RAM-11 Staining) FDGUptake (%ID/gm*103 ) 0 20 40 60 80 100 120 140 0 >0-5 >5-15 >15Blood Activity
  64. 64. P<0.0001, r =0.93 PET - SUV vs. Inflammation in Atherosclerotic Rabbits Inflammation (% RAM-11 Staining) 0 10 20 30 FDGUptake (SUV) 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6
  65. 65. Plaque inflammation can be characterized with FDG-PET
  66. 66. Can FDG-PET be used to measure vascular inflammation in humans?
  67. 67. Carotid PET Study Histologic correlationCEA 10 patients w carotid stenosis scheduled for CEA FDG- PET Merged with MRI or CT
  68. 68. Results: Subject Characteristics Characteristic Mean (± SEM) Age (yr) 73 ± 3 Gender (M/F) 4/6 Symptoms (%) 20 Diabetes (%) 40 Smoking (%) 40 Statin Rx (%) 60 Aspirin Rx (%) 100 SBP (mm Hg) 135 ± 7 DBP (mm Hg) 69 ± 3 LDL Chol (mg/dL) 113 ± 13 CRP 3.9 ± 1.8
  69. 69. Patient 1: Low FDG Uptake
  70. 70. Trichrome Collagen-rich plaque Thick Fibrous Cap Low lipid content CD68 <1% plaque area composed of inflammatory cells Patient 1 Histology
  71. 71. Patient 2: High FDG Uptake
  72. 72. CD68 Stain 20-30% plaque area composed of inflammatory cells Trichrome Thin Fibrous Cap (50 microns) Large necrotic core Patient 2 Histology
  73. 73. Carotid FDG Uptake
  74. 74. FDGUptake(T/B) Macrophage Staining (% plaque area) Inflammation vs. FDG Uptake (PET) N=10 P<0.0001 r=0.82 J J J JJJ JJJJJJJ JJJ JJ JJJ J JJJ JJJ J J J JJ JJ J JJJ JJ JJ J J J J JJJ J J JJ J JJ JJ J J J J J J J J J J J J J J 0.5 1 2 3 0 5 10 15 20 25
  75. 75. Macrophage Staining (% plaque area) Inflammation vs. FDG Uptake (PET) Individual Patient Data 0 2 4 6 8 10 12 14 MeanT/B 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 P<0.0001 r=0.96
  76. 76. FDGUptake(T/B) Collagen Staining (% plaque area) Collagen vs. FDG Uptake (PET) J J J J J J J J JJ J J 0.5 1 2 3 50 60 70 80 90 100 P<0.01 r=-0.76
  77. 77. Smooth Muscle Cell Staining (%) 0 10 20 30 40 50 FDGUptake(T/B) 0.5 1.0 1.5 2.0 2.5 3.0 3.5 P=NS Smooth Muscle Cells vs. FDG Uptake
  78. 78. Carotid FDG uptake correlates with histological evidence of inflammation.
  79. 79. Implications • FDG-PET may be useful for non-invasive characterization of vascular inflammation • Technique has promise: – for targeting therapies to patients at potentially higher risk for stroke – as an end-point for drug testing – to identify event-causing carotid plaques • Findings warrant further verification in a larger patient population.
  80. 80. Structural Imaging (CT or MR) needed for PET measurements
  81. 81. CT is also useful for plaque detection
  82. 82. Detection of Plaque Source Image LAD in Cross Section
  83. 83. Detection of Plaque Non-diseased segment (LAD) Diseased segment (LAD) 16-slice MSCT
  84. 84. MPR of LAD in Cross SectionThin MIP Detection of Plaque Sensitivity 82%, Specificity 88% Achenbach et al. Circulation 2004
  85. 85. r = 0.64, p < 0.001 Moselewski et al. AJC 2004 Plaque Area Potential to detect and quantify coronary plaque
  86. 86. Plaque CompositionPlaque Composition Potential to discriminate calcified and non- calcified plaque Leber et al JACC
  87. 87. MDCT Plaque Remodeling: 0.34 cm² 0.43 cm²
  88. 88. PET-CT Imaging of Other Large Vessels?
  89. 89. Left Iliac Shoulder of AAA Rapidly Expanding AAA: Coronal Images
  90. 90. Sagittal CT Coronal PET
  91. 91. Sagittal CT Coronal PET
  92. 92. Sagittal CT Coronal PET
  93. 93. Sagittal CT Coronal PET
  94. 94. Sagittal CT Coronal PET
  95. 95. Sagittal CT Coronal PET
  96. 96. Sagittal CT Coronal PET
  97. 97. Sagittal CT Coronal PET
  98. 98. Sagittal CT Coronal PET
  99. 99. Sagittal CT Coronal PET
  100. 100. Sagittal CT Coronal PET
  101. 101. Are we ready for coronary plaque imaging?
  102. 102. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion •Myocardial uptake of FDG •Smaller volume of coronary plaques.
  103. 103. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating
  104. 104. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating •Myocardial uptake of FDG
  105. 105. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Suppression of myocardial FDG uptake
  106. 106. Suppression of Myocardial FDG Uptake • Relatively simple • Healthy myocardium prefers lipids to glucose • High fat, low glucose diet results in suppression of myocardial FDG uptake
  107. 107. Suppression of Myocardial FDG Uptake after Atkins-Type Diet for 24 Hrs
  108. 108. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques.
  109. 109. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Are we limited by PET’s spatial resolution?
  110. 110. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Not necessarily- With PET, it’s about target-to-background ratio
  111. 111. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating •Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Not necessarily- With PET, it’s about target-to-background ratio Lighthouse effect
  112. 112. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Higher target to background •More specific tracers
  113. 113. Novel Tracers Potential Targets: – Inflammation • FDG • Scavenger receptor • P2 purine receptors • others – Apoptosis – Thrombus – Neovascularization – Others
  114. 114. Purine Receptor Imaging 18 F-Meth-Ap4A Sagittal Aorta Transverse Aorta Coronal Spine Aorta Micro-PET
  115. 115. P<0.001 r=0.87 AP4AUptake (%ID/cc) 0.00 0.02 0.04 0.06 0.08 0.10 0-7 8-16 >16 Plaque Inflammation (% Ram-11 Staining) Ap4A uptake vs. Inflammation
  116. 116. Annexin V Kietselaer BL, NEJM 2004
  117. 117. ConjugatedF FreeF ConjugatedF FreeF 0 10 20 30(molce6equivalent/gmtissuex10-10 ) FlurochromeConcentration Inflamed Ao Control Ao Targeting Scavenger Receptor-A: Increased Uptake By Inflamed Plaques P<0.001
  118. 118. Detection of Coronary Plaques: Additional Technical Challenges •Cardiac and respiratory motion Gating Myocardial uptake of FDG Requires suppression •Smaller volume of coronary plaques. Higher target to background More specific tracers •Improved instrumentation
  119. 119. Improved Instrumentation • Intravascular positron detectors • Improved PET and PET-CT • PET-MRI
  120. 120. Volume CT System Canine heart 150 micron isotropic resolution VCT Lab in Bldg 149 Detector Tube
  121. 121. Crossflex 3 x 18 mm Stent VCT MDCT 150 x 150 x 150µ 650 x 650 x 1250µ
  122. 122. Courtesy of HW Strauss Visualization of Coronary Plaque FDG with PET-CT
  123. 123. Future of Cardiac PET-CT: • Location of stenoses • Perfusion map (rest and adenosine stress) • Flow reserve map (correlate of ischemia) • Relationship between stenotic lesions and flow reserve • Detection of vulnerable plaques
  124. 124. CTA: 3D VOLUME RENDERING LAD 1st Diag LCX 2nd Diag LAD - stenosis 1st Diag LCX 2nd Diag
  125. 125. MBF ml/g/min Future Cardiac PET-CT Display?
  126. 126. MBF ml/g/min Future Cardiac PET-CT Display?
  127. 127. Middle Aged Woman w CP
  128. 128. Could we have intervened and prevented the MI? What if… we also detected a high degree of plaque inflammation?
  129. 129. Acknowledgements Cardiology • Kusai Aziz, MD • Gregory Bashian, MD • Henry Gewirtz, MD • Alex Morss, MD • James Muller, MD • Raymond Migrino, MD • Jane Sherwood, RN • Jeffrey Swanson, BS Neurology • Karen Furie, MD Radiology • Suhny Abbara, M.D. • Nathaniel Alpert, PhD • Ali Bonab, PhD • Thomas Brady, MD • Ricardo Curry, MD • Maros Ferencik, MD • Alan Fischman, MD, PhD • Denise Hinton, PhD • Udo Hoffmann, MD • Koen Nieman, MD Pathology • James Stone, MD • Stuart Houser, MD

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