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Principles of nuclear cardiology
History
• Hermann blumgart-1927-injected radon to
measure circulation time
• Liljestrand-1939-normal blood volume
• Myron prinzmetal-1948- radiolabelled
albumin
• Hal anger-1952-gamma camera-beginning of
clinical nuclear cardiology
• 1976-thallium201-two dimensional planar
imaging
• 1980s-SPECT using rotating anger camera
• 1990-technetium99m based agents and gated
SPECT
• 90% of SPECT in U.S use technetium and 90%
are gated SPECT
SPECT
single photon emission computed tomography
Basic concept
• Intravenously injected radiotracer distributes
to myocardium proportional to blood flow
• Gamma camera captures the photons,
converts to digital data and displays it as a
scintillation event
• Parallel hole collimator-better localisation of
source
• Photomultiplier tubes-conversion of signals
• Final result-multiple tomograms of radiotracer
distribution
SPECT image display
• Short axis images-perpendicular to long axis of
the heart,displayed from apex to base
• Vertical long axis-parallel to long axis of heart
and parallel to long axis of body
• Horizontal long axis-parallel to long axis of
heart,perpendicular to VLA slice
SPECT
SPECT perfusion tracers
• Thallium 201
• Technetium–99m
– Sestamibi (Cardiolyte)
– Tetrafosmin (Myoview)
– Teboroxime
• Dual Isotope
– Thallium injected for resting images
– Tech -99m injected at peak stress
Thallium-201
• Monovalent cation,property similar to
potassium
• Half life 73 hours,emits 80keV photons,t½
73hrs,85% first pass extraction
• Peak myocardial concentration in 5 min, rapid
clearance from intravascular compartment
• Redistribution of thallium-begins 10-15
min.after ,related to conc.gradient of thallium
between myocyte and blood
• Differential washout-clearance is more rapid
from normal myocardium
• Hyperinsulinemic states reduce blood
conc.&slow redistribution.so fasting
recommended
• Thallium protocols-
– Stress protocols-injected at peak stress and
images taken at peak stress and at 4 hrs,24hrs
– Reversal of a thallium defect marker of reversible
ischemia
– Rest protocols-thallium defect reversibility from
initial rest images to delayed redistribution images
reflect viable myocardium with resting
hypoperfusion
– Initial defect persists-irreversible defect
• Stress/redistribution/reinjection method
commonly used
• Reinjection if fixed defects seen at 4 hrs
• Timing of stress image-early
• Rest redistribution image for resting
ischemia/viability
Technetium-99m labelled tracers
• Half life 6 hrs,140keV photons,60% extraction
• Uptake by passive distribution by gradient
• Minimal redistribution-require two separate
injections-one at peak stress and one at rest
• Single day study-first injected dose is low
• Two day study-higher doses injected both rest
and stress-optimise myocardial count rate-
larger body habitus
• Tc99m tracers bound by mitochondria.limiyed
washout occurs.so imaging can commence
later and can be repeated
• 2 day image protocol better for image quality
• Most common-same day low dose rest/high
dose stress-disadvantage is reduction in stress
defect contrast.
• Viability assessment improved by NTG prior to
rest study
Dual isotope protocol
• Anger camera can collect image in different
energy windows
• Thallium at rest followed by Tc 99m tracer at
peak stress
• If there is rest perfusion defect,redistribution
imaging taken either 4 hrs prior or 24hrs after
Tc99m injection
Radionuclide Properties
Property Thallous Chloride Tc-Sestamibi
Chemistry +1 cation, hydrophilic +1 cation, lipophilic
half life 73 hrs 6 hours
Photon energy 68-80 keV 140 keV
Uptake Active: Na-K ATPase
pump
Passive diffusion (if
intact membrane
potentials)
Extraction fraction 85% 66%
Heart uptake 4% 1.2%
Redistribution Redistributes Fixed
Stress protocols
• Dipyridamole infusion for 4 min-isotope
injection 3 min after infusion
• Adenosine infusion for 6 min-isotope given 3
min into infusion
Interpretation and reporting
• Myocardium devided into 17 segments on the
basis of 3 short axis and a long axis slice
• Perfusion graded from 0(normal perfusion) to
4(no uptake)
• SSS-summed stress score-stress perfusion
abnormality
• SRS –summed rest score-extent of infarction
• SDS-summed difference score-stress induced
ischemia
Visual Analysis of Perfusion SPECT
• 0-normal uptake,
• 1-mildly reduced uptake,
• 2-moderately reduced uptake,
• 3-severely reduced uptake, and
• 4-no uptake
• bull̒s eye polar plot-two dimensional
compilation of all three dimensional short axis
perfusion data
Ant
Inf
LatSep
Apex  Base
Ant
Inf
Apex
Septum  Lateral
Apex
Sep Lat
Inferior  Anterior
Stress
Stress
Stress
Rest
Rest
Rest
Normal
Ant
Inf
LatSep
Apex  Base
Ant
Inf
Apex
Septum  Lateral
Apex
Sep Lat
Inferior  Anterior
Stress
Stress
Stress
Rest
Rest
Rest
Reversible Ischeamia, defect appears
at stress and disappears during rest
Ant
Inf
LatSep
Apex  Base
Ant
Inf
Apex
Septum  Lateral
Apex
Sep Lat
Inferior  Anterior
Stress
Stress
Stress
Rest
Rest
Rest
Fixed Scar, defect is seen in both stress and rest
Interpretation of the Findings-SPECT
Stress Rest Interpretation
• No defects No defects Normal
• Defect No defect Ischemia
• Defect Defect Scar/
hibernating
• Defect location (anterior, posterior, lateral, or septal wall),
size (small, medium, or big), severity (mild, moderate,
absent), degree of reversibility at rest (completely
reversible, partially reversible, irreversible)
• Regional wall motion, EDV, ESV, EF
(Stress-induced
ischemia)
Additional signs
• Lung uptake of thallium
• Transient ischemic dilatation of left ventricle
Thallium-201 Lung Uptake
• ↑ lung uptake of thallium following stress -marker of severe
CAD,elevation of PCWP,↓EF
• ↑PCWP-slow pulmonary transit-more extraction
• Minimal splanchnic uptake,early image after stress-lung
uptake more apparent in thallium
• More liver uptake,delayed imaging-lung uptake missed with
Tc99m
TID: transit Ischemic Dilation (Stress
induced LV Cavity Dilation)
• Severe, extensive CAD (usually with classic ischemic defect)
Left Main
Prox LAD
MVD
diffuse subendocardial ischemia
Variations
• Dropout of the upper septum
• Apical thinning
• Lateral wall may appear brighter than septum
• Minimised by review of series of normal
volunteers
Technical artifacts
• Breast attenuation-
– Minimised by Tc99m agents,ecg gated SPECT
– Presence of preserved wall motion and thickening
• Inferior wall attenuation
– Diaphragm overlapping inferior wall
– Minimised by gated SPECT,prone position
• Extracardiac tracer uptake
– Repeat imaging,drink cold water to clear tracer
from visceral organs
• LBBB-
– isolated reversible perfusion defects of septum
– Heterogeneity of flow b/w LAD &LCx due to
delayed septal relaxation
– Reduced O2 demand due to late septal
contraction,when wall stress is less
• HCM-
– due to ASH,appearance of lateral perfusion defect
• Combined SPECT/CT or PET/CT scanners-
complementary anatomical and functional
information
Gated SPECT
• Simultaneous assessment of LV function and
perfusion
• Each R-R interval is devided into prespecified
number of frames
• Frame one represent end diastole,middle
frames end systole
• An average of several hundred beats of a
particular cycle length acquired over 8-15 min.
• Normal regional systolic function-brightening
of wall during systole
• Quantitative analysis of LV function-three
dimensional display representing global LV
function created by information from all
tomographic slices-EF and LV volumes
calculated
Radionuclide ventriculography
• MUGA scanning-multiple gated acquisition
– Tc 99m labelled r.b.c or albumin
– Image constructed over an average cardiac cycle
by e.c.g gating,16-32 frames /cycle
– Image acquired in antr.,LAO, left lateral
projections
– Size of chambers,RWMA,LV function
– Time activity curve-LV volumes
• First pass RVG-i.v injected radioactive tracer
passes through rt.chambers-lungs-lt.chambers
• Tc99m DTPA preferred
• RAO projection
• 2-5 cycles summed for RV phase,5-7 for LV
phase
• Time activity curves generated-quantitative
analysis
PET
• Radiotracers labelled with positron emitting
isotopes
• Perfusion tracers-Rb82 and n13 ammonia
• Metabolic tracer-F18 FDG
• Beta decay-positron emission
• Annihilation-collide with electron-give two
gamma rays of 511keV-travel in opp.direction
• PET scanner detects opposing photons in
coincidence-spatial and temporal resolution
Perfusion tracers
• Diffusible tracers-O-15-accumulate and wash
out.
• Non diffusible-Rb82,N13ammonia
• Rb82-generator produced,t½76s.
Advantage of PET
• Higher spatial resolution
• Improved attenuation correction
• Quantification regional blood flow
– SPECT may fail to detect balanced ischemia in multivessel
CAD
– ↓blood flow reserve by PET –early identification of CAD
• Higher sensitivity and specificity(95%)for detection
of CAD
Limitations
• High cost
• Requirement of cyclotron
• Short half life-pharmacological stress only
Metabolic tracers
• C-11 palmitate
• I-123 BMIPP-Ischemic memory-fatty acid
metabolism suppressed for longer time after
an ischemic event
• F18 FDG-imaging myocardial glucose
utilisation with PET
– Phosphorylated and trapped in myocardium
– Uptake may be increased in hibernating but viable
myocardium
• FDG uptake in regions with reduced blood
flow at rest –marker of hibernation
• FDG studies performed after 50 to 75 gm
glucose loading 1-2 hrs prior to injection
– ↑glucose metabolism,FDG uptake and improves
image quality
• Enhanced FDG uptake relative to blood flow
referred to as PET mismatch pattern indicative
of viable myocardium
Viability PET Study
• Traditionally the gold standard
• Two sets of resting images to detect viable and
hibernating myocardium:
– Perfusion image (usually with N-13 ammonia or
rubidium-82)
– Glucose metabolic image (with F-18
fluorodeoxyglucose = FDG)
*
PET Viability
Scan Patterns
Contractility Perfusion Metabolism
Normal N N N
Stunning - N N -
Hibernation
Scar
Guidelines
• Acute syndromes
– Assessment of patients presenting to ED with
chest pain
– Diagnosis of AMI when other measures non
diagnostic-Tc99m
– Risk assessment,prognosis in AMI
– Risk assessment,prognosis in NSTEMI/UA
Chronic syndromes-
recommendations
Class1-
• Exercise SPECT for identifying location ,severity of
ischemia in pts without baseline ECG
abnormalities that interfere with ST seg.analysis
• Adenosine SPECT for LBBB,paced rhythem,unable
to exercise
• To assess functional significance of an
intermediate coronary lesion(25-75%)
• Intermediate duke TMT score
• Rpt.MPI for recent change of symptoms
• Class 2a-
– 3-5 yrs after revascularisation in asymptomatic
patients
– As initial test in high risk patients(>20% 10yr risk)
• Class 2 b-
– Pts with cor.calcium score more than 75 percentile
– Asymptomatic pts.high risk occupation
Indications for PET for risk stratification of patients
with intermediate likelihood of CAD
CLASS1-
– SPECT study equivocal
• Class 2a-
– As initial test in patients unable to exercise
– As initial test in pts. With baseline ECG
abnormalities
Risk Stratification
• Normal perfusion imaging after adequate
stress: very low cardiac event rate < 1%
• Small fixed defect with normal global LV
function: good prognosis
• High risk: (reversible defects) more than
one territory, LAD (most important coronary
artery), post-stress LV (left ventricular)
dysfunction (LV dilatation, abnormal wall
motion, decreased LVEF, lung uptake)

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Principles of nuclear cardiology

  • 2. History • Hermann blumgart-1927-injected radon to measure circulation time • Liljestrand-1939-normal blood volume • Myron prinzmetal-1948- radiolabelled albumin • Hal anger-1952-gamma camera-beginning of clinical nuclear cardiology • 1976-thallium201-two dimensional planar imaging
  • 3. • 1980s-SPECT using rotating anger camera • 1990-technetium99m based agents and gated SPECT • 90% of SPECT in U.S use technetium and 90% are gated SPECT
  • 4. SPECT single photon emission computed tomography
  • 5. Basic concept • Intravenously injected radiotracer distributes to myocardium proportional to blood flow • Gamma camera captures the photons, converts to digital data and displays it as a scintillation event • Parallel hole collimator-better localisation of source • Photomultiplier tubes-conversion of signals • Final result-multiple tomograms of radiotracer distribution
  • 6.
  • 7.
  • 8. SPECT image display • Short axis images-perpendicular to long axis of the heart,displayed from apex to base • Vertical long axis-parallel to long axis of heart and parallel to long axis of body • Horizontal long axis-parallel to long axis of heart,perpendicular to VLA slice
  • 10. SPECT perfusion tracers • Thallium 201 • Technetium–99m – Sestamibi (Cardiolyte) – Tetrafosmin (Myoview) – Teboroxime • Dual Isotope – Thallium injected for resting images – Tech -99m injected at peak stress
  • 11. Thallium-201 • Monovalent cation,property similar to potassium • Half life 73 hours,emits 80keV photons,t½ 73hrs,85% first pass extraction • Peak myocardial concentration in 5 min, rapid clearance from intravascular compartment • Redistribution of thallium-begins 10-15 min.after ,related to conc.gradient of thallium between myocyte and blood
  • 12. • Differential washout-clearance is more rapid from normal myocardium • Hyperinsulinemic states reduce blood conc.&slow redistribution.so fasting recommended
  • 13.
  • 14.
  • 15. • Thallium protocols- – Stress protocols-injected at peak stress and images taken at peak stress and at 4 hrs,24hrs – Reversal of a thallium defect marker of reversible ischemia – Rest protocols-thallium defect reversibility from initial rest images to delayed redistribution images reflect viable myocardium with resting hypoperfusion – Initial defect persists-irreversible defect
  • 16. • Stress/redistribution/reinjection method commonly used • Reinjection if fixed defects seen at 4 hrs • Timing of stress image-early • Rest redistribution image for resting ischemia/viability
  • 17.
  • 18. Technetium-99m labelled tracers • Half life 6 hrs,140keV photons,60% extraction • Uptake by passive distribution by gradient • Minimal redistribution-require two separate injections-one at peak stress and one at rest • Single day study-first injected dose is low • Two day study-higher doses injected both rest and stress-optimise myocardial count rate- larger body habitus
  • 19. • Tc99m tracers bound by mitochondria.limiyed washout occurs.so imaging can commence later and can be repeated
  • 20.
  • 21. • 2 day image protocol better for image quality • Most common-same day low dose rest/high dose stress-disadvantage is reduction in stress defect contrast. • Viability assessment improved by NTG prior to rest study
  • 22. Dual isotope protocol • Anger camera can collect image in different energy windows • Thallium at rest followed by Tc 99m tracer at peak stress • If there is rest perfusion defect,redistribution imaging taken either 4 hrs prior or 24hrs after Tc99m injection
  • 23.
  • 24. Radionuclide Properties Property Thallous Chloride Tc-Sestamibi Chemistry +1 cation, hydrophilic +1 cation, lipophilic half life 73 hrs 6 hours Photon energy 68-80 keV 140 keV Uptake Active: Na-K ATPase pump Passive diffusion (if intact membrane potentials) Extraction fraction 85% 66% Heart uptake 4% 1.2% Redistribution Redistributes Fixed
  • 25.
  • 26.
  • 28.
  • 29.
  • 30. • Dipyridamole infusion for 4 min-isotope injection 3 min after infusion • Adenosine infusion for 6 min-isotope given 3 min into infusion
  • 31. Interpretation and reporting • Myocardium devided into 17 segments on the basis of 3 short axis and a long axis slice • Perfusion graded from 0(normal perfusion) to 4(no uptake) • SSS-summed stress score-stress perfusion abnormality • SRS –summed rest score-extent of infarction • SDS-summed difference score-stress induced ischemia
  • 32. Visual Analysis of Perfusion SPECT • 0-normal uptake, • 1-mildly reduced uptake, • 2-moderately reduced uptake, • 3-severely reduced uptake, and • 4-no uptake
  • 33.
  • 34.
  • 35. • bull̒s eye polar plot-two dimensional compilation of all three dimensional short axis perfusion data
  • 36.
  • 37.
  • 38. Ant Inf LatSep Apex  Base Ant Inf Apex Septum  Lateral Apex Sep Lat Inferior  Anterior Stress Stress Stress Rest Rest Rest Normal
  • 39. Ant Inf LatSep Apex  Base Ant Inf Apex Septum  Lateral Apex Sep Lat Inferior  Anterior Stress Stress Stress Rest Rest Rest Reversible Ischeamia, defect appears at stress and disappears during rest
  • 40. Ant Inf LatSep Apex  Base Ant Inf Apex Septum  Lateral Apex Sep Lat Inferior  Anterior Stress Stress Stress Rest Rest Rest Fixed Scar, defect is seen in both stress and rest
  • 41. Interpretation of the Findings-SPECT Stress Rest Interpretation • No defects No defects Normal • Defect No defect Ischemia • Defect Defect Scar/ hibernating • Defect location (anterior, posterior, lateral, or septal wall), size (small, medium, or big), severity (mild, moderate, absent), degree of reversibility at rest (completely reversible, partially reversible, irreversible) • Regional wall motion, EDV, ESV, EF (Stress-induced ischemia)
  • 42. Additional signs • Lung uptake of thallium • Transient ischemic dilatation of left ventricle
  • 43. Thallium-201 Lung Uptake • ↑ lung uptake of thallium following stress -marker of severe CAD,elevation of PCWP,↓EF • ↑PCWP-slow pulmonary transit-more extraction • Minimal splanchnic uptake,early image after stress-lung uptake more apparent in thallium • More liver uptake,delayed imaging-lung uptake missed with Tc99m
  • 44. TID: transit Ischemic Dilation (Stress induced LV Cavity Dilation) • Severe, extensive CAD (usually with classic ischemic defect) Left Main Prox LAD MVD diffuse subendocardial ischemia
  • 45. Variations • Dropout of the upper septum • Apical thinning • Lateral wall may appear brighter than septum • Minimised by review of series of normal volunteers
  • 46. Technical artifacts • Breast attenuation- – Minimised by Tc99m agents,ecg gated SPECT – Presence of preserved wall motion and thickening • Inferior wall attenuation – Diaphragm overlapping inferior wall – Minimised by gated SPECT,prone position • Extracardiac tracer uptake – Repeat imaging,drink cold water to clear tracer from visceral organs
  • 47.
  • 48. • LBBB- – isolated reversible perfusion defects of septum – Heterogeneity of flow b/w LAD &LCx due to delayed septal relaxation – Reduced O2 demand due to late septal contraction,when wall stress is less • HCM- – due to ASH,appearance of lateral perfusion defect
  • 49. • Combined SPECT/CT or PET/CT scanners- complementary anatomical and functional information
  • 50. Gated SPECT • Simultaneous assessment of LV function and perfusion • Each R-R interval is devided into prespecified number of frames • Frame one represent end diastole,middle frames end systole • An average of several hundred beats of a particular cycle length acquired over 8-15 min.
  • 51. • Normal regional systolic function-brightening of wall during systole • Quantitative analysis of LV function-three dimensional display representing global LV function created by information from all tomographic slices-EF and LV volumes calculated
  • 52.
  • 53.
  • 54.
  • 55. Radionuclide ventriculography • MUGA scanning-multiple gated acquisition – Tc 99m labelled r.b.c or albumin – Image constructed over an average cardiac cycle by e.c.g gating,16-32 frames /cycle – Image acquired in antr.,LAO, left lateral projections – Size of chambers,RWMA,LV function – Time activity curve-LV volumes
  • 56.
  • 57.
  • 58.
  • 59. • First pass RVG-i.v injected radioactive tracer passes through rt.chambers-lungs-lt.chambers • Tc99m DTPA preferred • RAO projection • 2-5 cycles summed for RV phase,5-7 for LV phase • Time activity curves generated-quantitative analysis
  • 60. PET • Radiotracers labelled with positron emitting isotopes • Perfusion tracers-Rb82 and n13 ammonia • Metabolic tracer-F18 FDG • Beta decay-positron emission • Annihilation-collide with electron-give two gamma rays of 511keV-travel in opp.direction • PET scanner detects opposing photons in coincidence-spatial and temporal resolution
  • 61.
  • 62. Perfusion tracers • Diffusible tracers-O-15-accumulate and wash out. • Non diffusible-Rb82,N13ammonia • Rb82-generator produced,t½76s.
  • 63. Advantage of PET • Higher spatial resolution • Improved attenuation correction • Quantification regional blood flow – SPECT may fail to detect balanced ischemia in multivessel CAD – ↓blood flow reserve by PET –early identification of CAD • Higher sensitivity and specificity(95%)for detection of CAD
  • 64. Limitations • High cost • Requirement of cyclotron • Short half life-pharmacological stress only
  • 65. Metabolic tracers • C-11 palmitate • I-123 BMIPP-Ischemic memory-fatty acid metabolism suppressed for longer time after an ischemic event • F18 FDG-imaging myocardial glucose utilisation with PET – Phosphorylated and trapped in myocardium – Uptake may be increased in hibernating but viable myocardium
  • 66. • FDG uptake in regions with reduced blood flow at rest –marker of hibernation • FDG studies performed after 50 to 75 gm glucose loading 1-2 hrs prior to injection – ↑glucose metabolism,FDG uptake and improves image quality
  • 67. • Enhanced FDG uptake relative to blood flow referred to as PET mismatch pattern indicative of viable myocardium
  • 68.
  • 69.
  • 70. Viability PET Study • Traditionally the gold standard • Two sets of resting images to detect viable and hibernating myocardium: – Perfusion image (usually with N-13 ammonia or rubidium-82) – Glucose metabolic image (with F-18 fluorodeoxyglucose = FDG)
  • 71. *
  • 72. PET Viability Scan Patterns Contractility Perfusion Metabolism Normal N N N Stunning - N N - Hibernation Scar
  • 73.
  • 74.
  • 75.
  • 76.
  • 77. Guidelines • Acute syndromes – Assessment of patients presenting to ED with chest pain – Diagnosis of AMI when other measures non diagnostic-Tc99m – Risk assessment,prognosis in AMI – Risk assessment,prognosis in NSTEMI/UA
  • 78.
  • 79.
  • 80.
  • 81. Chronic syndromes- recommendations Class1- • Exercise SPECT for identifying location ,severity of ischemia in pts without baseline ECG abnormalities that interfere with ST seg.analysis • Adenosine SPECT for LBBB,paced rhythem,unable to exercise • To assess functional significance of an intermediate coronary lesion(25-75%) • Intermediate duke TMT score • Rpt.MPI for recent change of symptoms
  • 82. • Class 2a- – 3-5 yrs after revascularisation in asymptomatic patients – As initial test in high risk patients(>20% 10yr risk) • Class 2 b- – Pts with cor.calcium score more than 75 percentile – Asymptomatic pts.high risk occupation
  • 83. Indications for PET for risk stratification of patients with intermediate likelihood of CAD CLASS1- – SPECT study equivocal • Class 2a- – As initial test in patients unable to exercise – As initial test in pts. With baseline ECG abnormalities
  • 84.
  • 85.
  • 86.
  • 87. Risk Stratification • Normal perfusion imaging after adequate stress: very low cardiac event rate < 1% • Small fixed defect with normal global LV function: good prognosis • High risk: (reversible defects) more than one territory, LAD (most important coronary artery), post-stress LV (left ventricular) dysfunction (LV dilatation, abnormal wall motion, decreased LVEF, lung uptake)