Update in Nuclear Imaging of Amyloidosis and Sarcoidosis
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1 Update in Nuclear Imaging of Amyloidosis and Sarcoidosis Balaji Tamarappoo MD, PhD, Cedars-Sinai Heart Institute and Biomedical Imaging Research Institute Cedars-Sinai Medical Center Los Angeles, CA, USA.
2 Outline Amyloidosis General considerations Nuclear imaging methods Role of MRI Diagnostic algorithm Sarcoidosis General concepts Nuclear imaging methods Complementary imaging with MRI Diagnostic algorithm
3 Cardiac Amyloid Amyloidosis-major types: ATTR and Light Chain How do we distinguish between the subtypes with nuclear imaging? Tc-99m-Pyrophosphate (Tc-99m-PYP) scanning Significance of assessment of Tc99m-PYP uptake SPECT Improved localization over planar Dual isotope imaging
4 Cardiac Amyloid ATTR ATTR includes senile ( Wild-type ) (95%) and hereditary/familial types (5%) Senile type: tends to be an older male with LVH 25% of men over 85 have it (may include patients with AS-low flow low gradient or patients with HFPEF) Biopsy: Congo red stain positive Immunohistochemistry stain positive for kappa or lambda light chains Medical therapy (tafamidis, Diflunisal, small interfering RNA)
5 ATTR Amyloidosis: Prognosis and Treatment Median overall survival for ATTR WT is 3.6y Tafamidis improves survival compared to non-treatment Sultan et al. Clin Med Insights Cardiol. 11:
6 Cardiac Amyloid AL is a systemic disorder Characterized by monoclonal gammopathy Immunoglobulin light chain produced by a clonal cell population Lambda chain predominant Biopsy Congo red staining with infiltration Bone marrow biopsy and presence of circulating light chains Treatment consists of chemotherapy and stem cell transplantation Cardiac transplantation
7 AL Survival with SCT Cardiac AL Non-cardiac AL D Souza et al. Journal of Clinical Oncology 33,
8 CMR: Usual initial imaging test Diffuse late gadolinium enhancement (LGE): high sensitivity Does not distinguish between ATTR and AL
9 99m Tc-PYP in Cardiac Amyloidosis Nuclear Medicine for Cardiac Amyloid Tc-99m pyrophosphate Bone imaging tracer since 1970 s High specificity for ATTR SPECT increasing utilization F-18 Florbetapir FDA approved 2012 (brain) Images the amyloid protein itself AL>ATTR uptake
10 99m Tc-PYP in Cardiac Amyloidosis We propose that the scintigraphic pattern of intense, diffuse, biventricular uptake of Tc- 99m PYP may be highly specific for the diagnosis of amyloid cardiomyopathy.
11 99m Tc-PYP in Cardiac Amyloidosis Sporadic use early on due to apparent low sensitivity We propose that the scintigraphic pattern of intense, diffuse, biventricular uptake of Tc- 99m PYP may be highly specific for the diagnosis of amyloid cardiomyopathy.
12 99m Tc-PYP in Cardiac Amyloidosis Planar Imaging 99m Tc-PYP 20mci Planar and SPECT acquisition (30min) 0 3h Standard approach: Recommended by ASNC guidelines Can distinguish patients with strong uptake and absence of uptake
13 99m Tc-PYP in Cardiac Amyloidosis Tc-99m-PYP SPECT Semiquantitative Assessment of PYP Uptake
14 99m Tc-PYP in Cardiac Amyloidosis Quantification of Tc99m PYP Uptake
15 99m Tc-PYP in Cardiac Amyloidosis Limitation of Planar Imaging
16 99m Tc-PYP in Cardiac Amyloidosis Simultaneous Dual Isotope Imaging with Tl-201/Tc99m-PYP SPECT 99m Tc -PYP 201 Tl 99m Tc -PYP 201 Tl
17 99m Tc-PYP in Cardiac Amyloidosis Tc-99m-PYP SPECT Tl-201 SPECT 17
18 99m Tc-PYP in Cardiac Amyloidosis Simultaneous Dual Isotope Imaging with Tl-201/Tc99m-PYP SPECT 201 Tl 99m Tc -PYP Tl-201 allows unequivocal demonstration of the absence of myocardial Tc99m-PYP uptake 18
19 99m Tc-PYP in Cardiac Amyloidosis Myocardial Tc99m-PYP counts with and without the use of Tl-201 for processing of raw images and for quantification
20 99m Tc-PYP in Cardiac Amyloidosis Prediction of ATTR by Tc-99m PYP SPECT with and without the use of Tl-201
21 Clinical Approach to the Use of Imaging in Diagnosis of Cardiac Amyloidosis Clinical Suspicion CMR for myocardial infiltration Light chains in serum and urine + plasma cells in bone marrow YES NO Tc99m-PYP SPECT YES Systemic Amyloidosis -AL NO YES ATTR WT Or Mutation NO Alternate etiology
22 99m Tc-PYP in Cardiac Amyloidosis Summary ATTR best diagnosed by Tc-99m-PYP SPECT Myocardial Tc-99m-PYP uptake is usually absent in AL Quantification may be important for assessment of progression/effects of therapy Quantification is improved by simultaneous dual isotope imaging with Tl-201
23 18 F-FDG PET in Cardiac Sarcoidosis Sarcoidosis Clinical features Nuclear imaging for inflammation (F18-FDG) Quantification of FDG uptake Potential benefits of quantitative assessment
24 18 F-FDG PET in Cardiac Sarcoidosis Sarcoidosis Systemic disease of unknown cause Pulmonary> skin > eye > bone Cardiac involvement recognized in only a small % of cases Nearly 25% of patients with extracardiac sarcoid have cardiac involvement (autopsy findings) Cardiac sarcoid Heart block VT Heart failure Atrial arrhythmias
25 18 F-FDG PET in Cardiac Sarcoidosis Diagnosis of Cardiac Sarcoid HRS Criteria Cardiac biopsy positive OR Extracardiac biopsy positive AND
26 18 F-FDG PET in Cardiac Sarcoidosis Diagnostic and Therapeutic Strategy in Cardiac Sarcoidosis Indications for screening Diagnosed extracardiac sarcoidosis Unexplained 2 or 3 AV block age <55 y Unexplained monomorphic VT Non ischemic dilated cardiomyopathy Routine screening Physical, ECG, Echo, Holter Advanced screening CMR PET (F18-FDG has replaced Ga67) Invasive EP study J Nucl Med 2014; 55:
27 18 F-FDG PET in Cardiac Sarcoidosis CMR for Sarcoid Imaging Post-contrast cine image shows difference in signal intensity Delayed gadolinium image dark myocardium (without fibrosis) and enhancement (in regions of fibrosis) Assessment of inflammation for treatment decisions is made with PET imaging
28 F18-FDG PET Imaging for Inflammation Bokhari et al., FDG-PET is a Superior Tool in the Diagnosis and Management of Cardiac Sarcoidosis, ACC Expert analysis Apr 10, 2017
29 18 F-FDG PET in Cardiac Sarcoidosis Practical Concerns F18-FDG for detection of myocardial inflammation Myocardial glucose uptake suppression is the goal F18-FDG uptake indicates inflammation CSMC pre- test preparation protocol: HFLC dietary preparation 24-48hr Prolonged fast hours Heparin iv at 45 min and 15 min pre F18-FDG* Diabetic patients Early morning zero carbohydrate meal * There is evolving consensus regarding the use of heparin. 29
30 18 F-FDG PET in Cardiac Sarcoidosis Perfusion and FDG PET Rest Rb82 and F18-FDG cardiac PET Key concept: FDG uptake in inflamed myocardium but suppressed in healthy tissue which utilizes free fatty acid How do you measure disease burden?
31 18 F-FDG PET in Cardiac Sarcoidosis Is There a Need to Measure FDG Uptake and How to Quantify? SUV (standard uptake value): Uptake of FDG activity in a lesion normalized on the basis of a distribution volume. Useful to measure disease activity and monitor treatment
32 18 F-FDG PET in Cardiac Sarcoidosis FDG Uptake and Response to Treatment Yokoyama et al., Quantitative analysis of myocardial 18F-fluorodeoxyglucose uptake by PET/CT for detection of cardiac sarcoidosis International Journal of Cardiology, Volume 195, 2015,
33 18 F-FDG PET in Cardiac Sarcoidosis Quantitative Measurement of FDG Uptake for Prognostication 63 patients out of 203 suffered adverse events over a mean followup of 1.8y Sperry et al., Prognostic Impact of Extent, Severity, and Heterogeneity of Abnormalities on 18 F-FDG PET Scans for Suspected Cardiac Sarcoidosis JACC Imag 2017
34 Diagnostic Imaging in Sarcoidosis Extracardiac Sarcoidosis, Abnormal heart rhythm or Sudden death ECG and Echocardiography CMR with T1 and T2 and DE imaging Abnormal Equivocal Abnormal FDG PET Positive Sarcoidosis Assessment of Inflammation Positive Steroid Negative No Steroids
35 18 F-FDG PET in Cardiac Sarcoidosis PET-MRI for Sarcoid Imaging MRI PET Perfusion PET FDG Eur Heart J. 2013;35(5):312
36 18 F-FDG PET in Cardiac Sarcoidosis Cardiac Imaging in Sarcoidosis Diagnosis: MRI/PET Prognosis: MRI/PET Quantification of FDG uptake can be useful for guiding therapy and monitoring response PET-MRI combines the best of both modalities
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