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 Extraction fraction 85% 66% Heart uptake 4% 1.2% Redistribution Redistributes Fixed Passive diffusion (if intact membrane potentials)
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 (Stress-induced 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
Ant Stress Apex Rest Inf Septum Lateral Stress Apex Rest Sep Lat Inferior Anterior Ant Stress Reversible Ischeamia, defect appears at stress and disappears during rest Rest Sep Lat Inf Apex Base
Ant Stress Apex Rest Inf Septum Lateral Stress Apex Rest Sep Lat Inferior Anterior Ant Stress Rest Sep Inf Lat Fixed Scar, defect is seen in both stress and rest Apex Base
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
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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 Bad Extensively used > 60 years Entire coronary anatomy, including small and distal vessels Excellent PPV Validated QCA Helpful in clinical decision making 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 Bad Tomographic views Vessel wall + lumen visualization Excellent NPV+PPV Validated quantitative software Plaque characterization 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
Soft Fibrous 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 (maxlcbi 4mm ). MaxLCBI 4mm 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 maxlcbi 4mm >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.