NUCLEAR CARDIOLOGY AND

ADVANCED VASCULAR IMAGING

Joel Kahn, MD, FACC

Short History Nuclear Cardiology

Hermann blumgart-1927-injected radon to measure

circulation time

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

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, similar to potassium

Half life 73 hours, emits 80keV photons, 85% first

pass extraction

Peak myocardial concentration in 5 min, rapid

clearance from intravascular compartment

Redistribution of thallium-begins in 10-15 min

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

Technetium-99m labelled tracers

Half life 6 hrs, 140keV photons, 60% extraction

Uptake by passive distribution by gradient and

trapped in myocardial cell

Minimal redistribution-require two separate

injections-one at peak stress and one at rest

Single day study-first injected dose is low

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

Pharmacologic Stress

Dipyridamole infusion for 4 min-isotope injection 3

min after infusion

Adenosine infusion for 6 min-isotope given 3 min

into infusion

Regadenoson (Lexiscan) infusion for 6 mins

Dobutamine progressive infusion to increase HR

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)

Ant

Inf

Lat Sep

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

Lat Sep

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

Gated SPECT (Like a MUGA)

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.

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

PET imaging of the heart

PET

Radiotracers labelled with positron emitting isotopes

Perfusion tracers-Rb82 and n13 ammonia

Metabolic tracer-F18 FDG

Beta decay-positron emission

PET scanner detects opposing photons in

coincidence-spatial and temporal resolution

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

*

PET Viability

Scan Patterns

Contractility Perfusion Metabolism

Normal N N N

Stunning - N N -

Hibernation

Scar

Cardiac PET/CT: The Ultimate

PET/CT Scanners: The Ultimate

ADVANCED IMAGING OF

THE VULNERABLE PLAQUE

The Old Friend: Angiography

Angiography: the good and the

bad

Good

Extensively used > 60 years

Entire coronary anatomy, including small and distal vessels

Excellent PPV

Validated QCA

Helpful in clinical decision making

Bad

Relative % stenosis

Reference segment assessment

Eccentricity

Post PTCA/dissections

Limited correlation with physiology

Pitfall: lesion eccentricity

Vascular Remodelling (Glagov’s phenomenon)

Plaque Pathogenesis

Morphologic traits

associated with

rupture prone

plaques are found

in thin-cap

fibroatheromas.

Intravascular Assessment of Plaque

Vulnerability

IVUS

IVUS-RF (Virtual Histology)

Palpography

Optical coherence tomography

Near-infrared spectroscopy

Intravascular MR

Angioscopy

Thermography

Intravascular Ultrasound

Real-time cross-sectional tomographic images in the short axis.

Backscatter signal is processed into gray scale with spatial resolution of 150 µm and frame rate of 10 to 30 frames/sec.

Plaque vulnerability features include: Eccentric pattern

Echolucent core

Positive remodeling

Presence of thrombi

Plaque length

Lumen narrowing

Spotty calcifications.

IVUS: the good and the bad

Good

Tomographic views

Vessel wall + lumen visualization

Excellent NPV+PPV

Validated quantitative software

Plaque characterization

Bad

Need to instrument vessels

Limited to proximal segments

Cost

Not as well validated for clinical decision making

Limited correlation with physiology

Not always perpendicular to vessel axis

IVUS Imaging

2D Cross-Sectional

Imaging

Distal LMT

Fibrous Soft

Superficial Ca Deep calcification

IVUS: Potentially unstable coronary

lesion

Echolucent

Intravascular Coronary Ultrasound

Angio remains the most widely and conveniently used coronary imaging modality

IVUS has helped better use/understand angiography

Not IVUS vs Angio, more Angio ± IVUS

Need to understand the pitfalls of each technique and use them appropriately

IVUS-RF (Virtual Histology)

Mathmatical autoregression modeling of each line in

the radiofrequency signal is performed on a region

of interest and averaged over that region.

Results are displayed as a color-coded map

superimposed on gray scale IVUS images.

Sensitivity, specificity, and PPV to detect necrotic

cores in initial ex-vivo and in vivo studies were 67%,

93%, and 88% respectively.

IVUS-RF

Limitations:

Unable to distinguish thrombi from other plaque

components

Limited spatial resolution (equivalent to IVUS),

precludes fibrous cap thickness

Conflicting data regarding assessment of necrotic cores

IVUS - Palpography

Measures the mechanical properties of tissue through

RF-ultrasound signals recorded at different pressures

i.e. measures the local rate of plaque deformation

(strain) in response to the pulsating force of blood

pressure.

Fibrous plaques are less elastic than lipid rich

plaques.

Validated ex vivo, in pig models, and in small in vitro

studies.

IVUS - Palpography

Limitations:

Has worse spatial and temporal resolution than

conventional IVUS or IVUS-RF (~200 µm).

Cardiac motion and pullback of catheter can create

artifacts.

J Am Coll Cardiol, 2006; 47:86-91

Optical coherence tomography

Uses optical scattering to generate an ultra-high

resolution (4 to 20 µm) 2-dimensional image.

Limited tissue penetration due to use of light to

create the image.

Attenuated by blood.

Compares favorably with IVUS for plaque

characterization.

Eur Heart J (2008) 29 (16): 2023

Near-infrared spectroscopy

Based on absorbance of light of organic molecules. NIRS allows for the chemical characterization of biological tissues – can be used to assess lipid and protein content in plaques.

Resultant image termed a “chemogram.”

Validated against histologic hallmarks of plaque vulnerability – lipid pool, thin cap, and inflammatory cells.

NIRS

Limitations

Limited tissue penetration on par, or slightly worse than,

OCT

Cardiac motion artifact

Detection by Near-Infrared Spectroscopy of Large Lipid

Core Plaques at Culprit Sites in Patients With Acute ST-

Segment Elevation Myocardial Infarction

We performed NIRS within the culprit vessels of 20 patients with acute

STEMI and compared the STEMI culprit findings to findings in nonculprit

segments of the artery and to findings in autopsy control segments. Culprit

and control segments were analyzed for the maximum lipid core burden

index in a 4-mm length of artery (maxLCBI4mm).

MaxLCBI4mm was 5.8-fold higher in STEMI culprit segments than in 87

nonculprit segments of the STEMI culprit vessel and 87-fold higher than in

279 coronary autopsy segments free of large LCP by histology . Within the

STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit

segments. Conclusions

The present study has demonstrated in vivo that a maxLCBI4mm >400, as

detected by NIRS, is a signature of plaques causing STEMI.

Madder R et al. JACC Intevent July 17, 2013

Detection by Near-Infrared Spectroscopy of Large Lipid

Core Plaques at Culprit Sites in Patients With Acute ST-

Segment Elevation Myocardial Infarction

Intravascular Magnetic Resonance

Pulsed field MRI has been used to calculate the water diffusion coefficient in atherosclerotic plaques.

Water diffusion is less in lipid-rich than fibrous plaques.

In ex vivo studies, correlation between MRI and histology was good, with a sensitivity of 100% and specificity of 89% for lipid cores.

IV MRI

Limitations:

Requires hybrid lab or transport to MRI suite

Catheter-coil needs to be stabilized with occlusive

balloon

Gadolinium contrast utilization

Atherosclerosis; 196; 2; 916-25

Angioscopy

Direct visualization of the surface of plaque.

Number of yellow plaques is a strong predictor of

ACS

Subjective, needs blood displacment, factual

accuracy per patient is poor

Angioscopy

Cover of JACC intervention 2/1/2008

Thermography

Based on assumption that plaque inflammation and neoangiogenesis produce heat that can be measured by dedicated catheter.

Temperature difference of up to 1.5 °C between plaque and healthy vessel in ACS has been shown in human subjects.

Major limitation is blood flows’ cooling effect, requiring interruption of flow.

JACC; 57, 20, 2011 1961-79

Noninvasive Assessment of Plaque

Vulnerability

Multidetector Computed Tomography

Magnetic Resonance Imaging

Nuclear Imaging

Contrast-enhanced Ultrasonography

Multidetector CT

MDCT can detect features associated with plaque

vulnerability including positive remodeling, spotty

calcification, lower plaque density, intra-plaque dye

penetration, and ulceration.

Currently considered a first-line method in detecting

vulnerable plaque.

Circulation: Cardiovascular Imaging. 2010;3: 351-59

Magnetic Resonance Imaging

Due to cardiac motion, MRI best suited for study of

large, static arteries.

Lipid and fibrotic plaque components have been

accurately quantified on T2 weighted imaging.

T2 weighted imaging has also been utilized to

measure fibrous cap thickness, ruptures, and

intraplaque hemorrhages.

MRI

Limitations:

Clinical utility remains to be determined

Technical improvements still needed prior to better

visualization of coronary arteries.

http://www.erasmusmc.nl

Conclusions

Detection of plaque vulnerability is becoming a

reality.

More evidence needed for many of the imaging

modalities correlating to clinical events.

Further research into the morphologic, molecular,

biologic, and mechanical features of vulnerable

plaques is needed.