personalized medicine? Pierre-Yves MARIE Department of Nuclear - - PowerPoint PPT Presentation

Pierre-Yves MARIE Department of Nuclear Medicine CHU-Nancy, FRANCE.

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine?

I - A remaining need of a personalized

functional information

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine?

II - The future:

• new cameras and new tracers
• combining functional and

anatomic information.

I - A remaining need of a personalized

functional information

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine?

II - The future:

• new cameras and new tracers
• combining functional and

anatomic information.

Anatomical information: is not enough for assessing CAD,

Multidetector CT

Coronary angiography

coronary atherosclerosis remains frequently:

• without ischemia,
• uncomplicated.

I - A remaining need of a personalized functional information

Multidetector CT

Coronary angiography

Autopsy studies have determined the rates of high grade coronary atherosclerosis in patients : (i) who were without any history of CAD (ii) who died because of a non-cardiac cause.

• 1. less than 25%
• 2. from 25 to 50%
• 3. more than 50%

What is this rate in > 65 years-old north-american male subjects?

Coronary atherosclerosis in diabetes mellitus A population-based autopsy study.

Tauqir Y. Goraya et al. J Am Coll Cardiol. 2002;40(5):946-53.

Prevalence of high-grade coronary atherosclerosis at autopsy by diabetes and clinical coronary disease status.

No CAD history D- D+ D+ D- CAD history D- D+ D+ D-

Short-axis apical median basal vertical horizontal Exercise

99mTc-sestamibi

Long-axis

Patient with a total occlusion of the right coronary artery, but with a normal exercise-SPECT under beta-blockers

Mechanisms:

• collaterals,
• antianginal medications.

Severe coronary stenoses are not always associated with severe perfusion abnormalities at exercise

I - A remaining need of a personalized functional information

Short-axis apical median basal vertical horizontal Exercise

99mTc-sestamibi

Long-axis

0% 10% 20% 30% 40%

Survival of 442 patients who had exercise SPECT under beta-blockers and their anti-anginal treatment

5 4 3 2 1

P<0.001

Years

Large necrosis (> 20% LV) Ischemia Neither ischemia nor large necrosis

Survival

1.0 .9 .8 .7 .6 .5 J Nucl Cardiol. 2003;10(4): 361-8.

J Nucl Cardiol 2003; 10:361-8.

I - A remaining need of a personalized functional information

Coronary flow insufficiency may occur in the absence of any > 50% stenosis at coronary angiography:

• abnormal flow reserve,
• exercise vasoconstriction.

Severe coronary stenoses are not always associated with severe perfusion abnormalities at exercise

I - A remaining need of a personalized functional information

Gage JE. Circulation. 1986;73:865

In intermediate stenoses, exercise ischemia may involves both:

• a limitation of coronary

flow reserve,

• vasoconstriction of

stenotic coronary segments.

40 patients with: [1] proven CAD (> 50% stenosis at angiography) and [2] positive exercise test

Eur J Nucl Med 2000 ;27(7):788-99.

Exercise Rest- reinjection Short-axis Dipyridamole Vertical long-axis apical mid-vent. basal . 72-year old man, angina and ST depression at exercise . 60 % stenosis on RCA

Exercise SPECT-defects are larger than dipyridamole SPECT- defects when ischemic areas are related to < 70% stenoses

(Eur J Nucl Med 2000 ;27(7):788-99).

Tl-201

Exercise Rest- reinjection Short-axis Dipyridamole Vertical long-axis apical mid-vent. basal . Exercise: angina, ST depression and 73% of maximal heart rate . Coronary angiography: dominant LCx: 80 %, intermediate branch: 90 % . Tl-201

Dipyridamole SPECT-defects are larger than exercise ones in patients with low exercise-increase in heart rate (β-blockers)

Eur J Nucl Med 2000 ;27(7):788-99.

Main parameters:  Exercise testing parameters

(maximal work load and heart rate, positive test)

 Normal stress-SPECT  Extent of stress defects  Extent of reversible stress

defects

 Post-stress LV ejection fraction

(<45%) and end-systolic volume (>70 mL)

 Reversible wall motion

abnormalities

Short-axis apical median basal Long-axis vertical horizontal

Function Exercise Rest Exercise Rest

Prognostic stratification using exercise MPI

Perfusion

Hachamovitch R, Circulation, 2003 Cardiac death rate (% per year)

Help in therapeutic decision according to the amount of ischemic area

Patients with prior MI (n=3,216)

% total myocardium ischemic Hazard ratio % total myocardium ischemic Hazard ratio

Patients with <10% MI (n=11,880)

Help in therapeutic decision according to the amount of ischemic area

Hachamovitch R, et al. Eur Heart J 2011;32:1012-1024: 13 969 patients followed at >7 years for all-cause death after stress SPECT (65% exercise) Hazard ratio for revascularization vs. medical therapy as a function of %myocardium ischaemic

Help in therapeutic decision according to the amount of ischemic area

Medical therapy Early revascularization % total myocardium ischemic Log Hazard ratio

Hachamovitch R, et al. Eur Heart J 2011;32:1012-1024: 13 969 patients followed at >7 years for all-cause death after stress SPECT (65% exercise) Log hazard ratio for revascularization vs. for medical therapy as a function of %myocardium ischaemic in patients with <10% necrotic myocardium

Cine-MRI Perfusion

Septal ischemia

• No radiation
• Highly accurate assessments of contractility and of MI areas
• Perfusion assessment with pharmacologic tests

I - A remaining need of a personalized functional information: is MRI a better choice than SPECT?

• specificity

(58% → 87%)

Klem I. et al. Improved detection of CAD by stress perfusion cardiovascular MR with the use of delayed enhancement infarction imaging. J Am Coll

• Cardiol. 2006;47:1630-8.

Delayed-enhancement imaging for increasing:

• sensitivity

(84% → 89%)

+ +

• Delayed

enhancement Stress perfusion Rest perfusion Coronary angiography

I - A remaining need of a personalized functional information: is MRI a better choice than SPECT?

Stress perfusion Abnormal Ischemia Rest perfusion Abnormal Normal DCE analysis Infarction Normal Abnormal No CAD (artifact)

Detection of CAD by perfusion-MRI with DCE analysis

Stress perfusion Rest perfusion Function (G.SPECT)

Detection of CAD by perfusion-SPECT with G.SPECT

Abnormal Ischemia Abnormal Normal Infarction Normal Abnormal No CAD (artifact)

Vi Viab able In Inte term rmediat ate Non vi viab able

(> 80% of further improvement) (≈ 50% of further improvement) (< 20% of further improvement )

0% 50% 100%

SPECT-tr trac acers rs ± nitrates % of

• f u

upta take > 60% 40-60% < 40% MRI : delayed retention Tra ransmura ral e exte tent < 25% 25-50% >50%

Viability assessment

I - A remaining need of a personalized functional information: is MRI a better choice than SPECT?

But MRI < SPECT for assessing stress ischemia:

• no assessment at exercise
• less safe
• more complex to perform and to analyze
• No radiation
• Highly accurate assessments of contractility and of MI areas
• Perfusion assessment with pharmacologic tests

II - The future:

• new cameras and new tracers
• combining functional and

anatomic information.

• ...

I - A remaining need of a personalized

functional information Physiological information on myocardial ischemia at exercise. Help in therapeutic decision.

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine?

II - The future:

• new cameras and new tracers
• combining functional and

anatomic information.

• ...

I - A remaining need of a personalized

functional information Physiological information on myocardial ischemia at exercise. Help in therapeutic decision.

Is myocardial-SPECT still a reference technique for CAD patients in the era of personalized medicine?

Cadmium zinc telluride (CZT) solid-state detectors

• - much higher myocardial count rate
• - much higher energy resolution
• - higher spatial resolution
• - smaller size

GE Medical Systems Spectrum Dynamics

II - The future: solid-state detectors

++ ++++ ++ +

Performances of High-Sensitivity Cameras Imbert L. et al. 2012

II - The future: solid-state detectors

Discovery

• NM 530c

DSPECT IQSPECT Conventional

• SPECT

Phantom study Long-axis Short-axis

Comparison:

• between Discovery-NM530c and DSPECT CZT-cameras, and

Anger cameras with astigmatic or parallel-hole collimator,

• on SPECT images from phantoms and from normal subjects.

Clinical study Horizontal long-axis Median short-axis

Phantom study Clinical study

Sharpness index (cm-1) Spatial resolution (mm)

c r t

DSP NM IQ Conv DSP NM IQ Conv

*

c r t c r t c r t

* *

Performances of High-Sensitivity Cameras Imbert L. et al. 2012

II - The future: solid-state detectors

Comparison:

• between Discovery-NM530c and DSPECT CZT-cameras, and

Anger cameras with astigmatic or parallel-hole collimator,

• on SPECT images from phantoms and from normal subjects.

Spatial resolution

DSP NM IQ Conv DSP NM IQ Conv

* * * *

Contrast / noise ratio Contrast / noise ratio

Phantom study Clinical study

*

Performances of High-Sensitivity Cameras Imbert L. et al. 2012

Contrast

II - The future: solid-state detectors

Comparison:

• between Discovery-NM530c and DSPECT CZT-cameras, and

Anger cameras with astigmatic or parallel-hole collimator,

• on SPECT images from phantoms and from normal subjects.

Count sensitivity (count.sec-1.MBq-1) DSP NM IQ Conv

* * *

Phantom study Clinical study

DSP NM IQ Conv Normalized activity (count.sec-1.MBq-1)

Performances of High-Sensitivity Cameras Imbert L. et al. 2012

Count sensitivity

II - The future: solid-state detectors

Comparison:

• between Discovery-NM530c and DSPECT CZT-cameras, and

Anger cameras with astigmatic or parallel-hole collimator,

• on SPECT images from phantoms and from normal subjects.

Stress 2 min Rest 4 min Stress 11.5 min Rest 14 min Semi-conductors

Cadmium zinc telluride (CZT) solid-state detectors

•  6 to 10 fold increase in myocardial count rate

31

Inferior ischemia

For shortening recording times, up to 2 min for high injected activities,

Herzog BA et al. J Nucl Med. 2010;51:46-51 Gambhir SS, et al. J. Nucl. Med. 2009; 50(4):635–43. Sharir T, et al. JACC Cardiovasc

• Imaging. 2008;1(2):156–63.

Sharir T, al. J. Am. Coll. Cardiol. 2010; 55(18):1965–74.

High concordance with results from Anger cameras

II - The future: solid-state detectors

Conventional

Cadmium zinc telluride (CZT) solid-state detectors

•  6 to 10 fold increase in myocardial count rate
• -  image quality and  low-count artifacts
• especially in obese patients (A. Verger et al. 2012)

D.SPECT (4 min) Conventional (10 min)

Apical-SA Median-SA Basal-SA HLA VLA

Sestamibi SPECT in an obese patient

II - The future: solid-state detectors

for reducing injected activities, up to 110 MBq for

99mTc tracers,

Recording (2-3 min) Recording (7-10 min) 110 MBq of

99mTc tracer

330 MBq of

99mTc tracer

Stress / Rest Rest / Stress ~3 mSv for 99mTc tracer in non obese patients (≤ 1 mSv for only stress acquisition)

Cadmium zinc telluride (CZT) solid-state detectors

•  6 to 10 fold increase in myocardial count rate

Mouden M, et al. Eur J Nucl Med Mol Imaging. 2012

• Higher image quality and fewer equivocal results vs. Anger camera

Duvall WL, et al. J Nucl Cardiol. 2011;18(5):847-857. Gimelli A, et al. Eur J Nucl Med Mol Imaging. 2012; 39(1):83-90 Duvall WL, et al.J Nucl Cardiol. 2012;19(1):19-27.

• Accurate identification of patients with coronary stenosis

II - The future: solid-state detectors

for reducing injected activities, up to 50 MBq for 201Tl

Recording (7-10 min) 50 to 80 MBq

• f 201Tl

Stress Rest ~8 to 12 mSv for 201Tl in non obese patients

Cadmium zinc telluride (CZT) solid-state detectors

•  6 to 10 fold increase in myocardial count rate

Songy B, et al. Nucl Med Commun. 2012;33(5):464-9.

• Higher image quality and fewer artefacts vs. Anger camera

Songy B, et al. Nucl Med

• Commun. 2012;33(5):464-9.

Recording (7-10 min) 0 to 20 MBq

• f 201Tl

II - The future: solid-state detectors

for reducing injected activities

• r maximizing spatial and/or temporal resolutions?

Cadmium zinc telluride (CZT) solid-state detectors

•  6 to 10 fold increase in myocardial count rate

Sestamibi (400 MBq) 4 min recording time 16 frames / cycle voxels of 30 mm3

II - The future: solid-state detectors

Cadmium zinc telluride (CZT) solid-state detectors

•  6 to 10 fold increase in myocardial count rate
•  much higher energy resolution

Dual energy recording

Camera recording (10-15 min) Stress

99mTc tracer

• r 201Tl

99mTc tracer

• r 201Tl

Rest Tl-201 Stress Sestamibi Inferior MI

II - The future: solid-state detectors

II - The future: hybrid SPECT/CT imaging

Low-radiation (≤ 2 mSv) CT recording might be useful for providing:

• 1. attenuation correction map (especially in
• bese subjects and in women…),
• 2. calcium score (enhanced prognosis

assessment of patients with normal SPECT),

• 3. coronary angiography (identifying

ischemia-related arteries).

Gaemperli O, Eur Heart J, 2006

CT-angiography for identifying ischemia-related arteries

II - The future: hybrid SPECT/CT imaging

II - The future: hybrid SPECT/CT imaging

M.P. Schenker, et al. Circulation. 2008;117(13):1693-700.

Calcium score for precising patient’s prognosis

risk increases independently according to calcium scores and PET ischemia.

PET+ patients PET- patients

CAC>1000 CAC>1000 CAC<1000 CAC<1000

Freedom from death and MI Freedom from death and MI Days to event

695 patients had stress-rest

82Ru-PET and calcium scoring

• n PET-CT

II - The future: other tracers

Dual 201Tl/123I-MIBG images with CZT-cameras

201Tl 201Tl 123I 123I

MIBG

Sever decrease in MIBG uptake in a diabetic patient (Leguludec D. Hôpital Bichat, Paris)

MIBG

Apoptosis with 99mTc-labeled annexin A5

DCM with rapid deterioration. Annexin uptake in apex and lateral wall.

Kietselaer BL, et al. J Nucl Med. 2007;48:562-7.

II - The future: other tracers

Apoptosis

Imaging of αvβ3 integrin using 18F-RGD in a rat infarct

Higuchi T, et al. Eur J Nucl Med Mol Imaging. 2007;34:S9-19.

Angiogenesis

II - The future: other tracers

MIBG

Apoptosis Angiogenesis Remodeling

Imaging of matrix metalloproteinase (MMP) in a mouse heart infarct.

Sinusas A. Yale University School of Medicine

II - The future: other tracers

MIBG

Apoptosis Angiogenesis Remodeling Inflammation

FDG in activated inflammatory cells

JOLY L et al. Eur J Nucl Med Mol Imaging. 2009;36(6):979.

In progress: many

• ther tracers such

as 18F-LP 17, a small agonist of TREM-1 receptors

II - The future: other tracers

MIBG

2) Promising for the future:

• technological jump related to new CZT cameras,
• combining SPECT information with the

anatomic information from low-dose CT,

• new tracers …

1) Particularly well adapted for providing a

physiological information on ischemia and for guiding treatments

Conclusion : myocardial-SPECT is still a reference technique for CAD patients in the era

• f personalized medicine

routine assessment at physical exercise