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 PropertiesProperty 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

• bul s eye polar plot-two dimensional l̒ �

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, l̒ateral̒, or septal̒ wal̒l̒), size (smal̒l̒, medium, or big), severity (mil̒d,

moderate, absent), degree of reversibility at rest (compl̒etel̒y reversibl̒e, partial̒l̒y reversibl̒e, irreversibl̒e)

• 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 MainProx LADMVDdiffuse 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 MetabolismNormal 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 (l̒eft ventricul̒ar) dysfunction (LV dilatation, abnormal wall motion, decreased LVEF, lung uptake)