Major Cardiac Imaging Advances in Last 5 Years: Nuclear (Imaging Technology) Advances Youngho Seo, PhD
Technical Advances in Major Cardiac Imaging Areas using SPECT or PET Information we (can) get from nuclear imaging techniques Myocardial perfusion nuclear myocardial perfusion imaging Ejection fraction radionuclide ventriculography or gated MPI Myocardial viability radionuclide viability study (e.g., FDG-PET) Sympathetic innervation radioactive norepinephrine analogue (e.g., mibg) Myocardial blood flow Dynamic PET (and SPECT) Coronary flow reserve Stress dynamic PET (and SPECT) Research areas to advance nuclear cardiac imaging Improve quantitation of the above parameters accuracy, ease, dose reduction, speed of acquisition, etc. Dedicated nuclear cardiac imaging Small footprint, mobile, compact, etc. (not that much going on lately) Dedicated cardiac SPECT collimators (improving existing systems) New general-purpose scanner (e.g., PET/MRI) New radiopharmaceuticals Better flow agent (improved PET (e.g., F-18) and SPECT perfusion agents) Better norepinephrine analogue imaging agent (e.g., mfbg or other analogues) New applications Coronary flow reserve (by PET and SPECT), myocardial efficiency, inflammation, etc.
General-Purpose SPECT(/CT) Systems for Cardiac Imaging Newer scanner technologies have been introduced to improve both qualitative and quantitative SPECT imaging Quantification - Siemens xspect (2013), GE Q.Metrix (2014) provides measurements in Bq/ml (activity concentration) PET-like quantitative accuracy Improve resolution by improving reconstruction algorithm - Siemens IQ-SPECT (2011), UltraSPECT Wide-Beam reconstruction (correcting PSF variability, 2006) Improve resolution and sensitivity by improving collimator geometry Siemens IQ- SPECT (2011) New detector technology (e.g., CZT) for general-purpose SPECT GE Discovery NM/CT 670 CZT (2016)
Examples: Confocal Collimators & PSF Model Recon https://usa.healthcare.siemens.com/molecular-imaging/iq-spect-technology http://ultraspect.com/products/xpress-cardiac/half-dose-cardiac-imaging/
Dedicated Cardiac SPECT Systems D-SPECT (Spectrum Dynamics) introduced in 2005 (a while ago) GE NM 530c and NM/CT 570c introduced in 2009 (also a while ago) Both systems use new solid-state detectors, CdZnTe (CZT) instead of NaI(Tl) crystals. Evidence of the advantage of doing scans with dedicated scanners is coming more lately. Erlandsson K, et al. Phys Med Biol. 2009;54:2635
One of Benefits of Using Dedicated Cardiac SPECT Dynamic Cardiac SPECT data acquisition is simpler than rotational SPECT. Allowing further analysis of the data when SPECT data are acquired dynamically. Ben-Haim S, et al. J Nucl Med. 2013;54:873
General-Purpose PET(/CT) Systems for Cardiac Imaging Not that much specialized hardware improvement for cardiac applications But, technologies like time-of-flight (TOF), PSF model in reconstruction, large axial FOV (better sensitivity and better/easier whole-heart coverage) all contribute to improved cardiac PET imaging. More efforts for new PET radiotracer development The workhorse is Rb-82 (generator produced). 13 N-NH 3 is better (shorter positron range), but less used because of logistics (onsite cyclotron requirement) and poorer production control. The biggest latest effort is F-18 labeled PET myocardial perfusion imaging agent development High throughput, best-possible radionuclide (F-18) for PET imaging (shortest positron range) First Phase 3 trial of 18 F-flurpiridaz (binding to mitochondrial complex 1, MC-1) did not meet the expected end points, flurpiridaz F 18 far exceeded SPECT for sensitivity but did not meet the non-inferiority threshold for specificity (May 4, 2015) Press Release from Lantheus The second Phase 3 study with different end points has been designed (according to Lantheus). However, this trial has not started yet though.
18 F-flurpiridaz PET MPI Berman DS, et al. J Am Coll Cardiol. 2013;61:469
Integrated PET-MRI for Cardiac Imaging Cardiac imaging applications that benefit from both PET and MRI Doing both at the same time relieve the logistical challenges at the minimum. Must make sure that the imaging capabilities for both PET and CMR are not compromised. PET Insert PET Insert Siemens mmr (2011) GE SIGNA PET/MR (2015), Image Courtesy of GE Healthcare
Effect of TOF-PET-MRI for Cardiac Imaging A C B D A) Non ECG gated, time-of-flight reconstruction. B) Non ECG gated, non time-of-flight reconstruction C) End diastole, time-of-flight reconstruction D) End diastole, non time-of-flight reconstruction E) 3D Cine MRI at systole F) 3D Cine MRI at diastole. E F Data courtesy of UCSF (K. Ordovas, J. Liu, Y. Seo)
Emerging Radiopharmaceuticals for Nuclear Cardiac Imaging 18 F-labeled perfusion imaging agent for PET e.g., 18 F-flurpiridaz 18 F-labeled sympathetic innervation imaging agent for PET e.g., MFBG (meta-[ 18 F]fluorobenzylguanidine), MFPBG (meta-(3- [ 18 F]fluoropropyl)benzylguanidine), LMI1195 (N-[3-Bromo-4-(3-[18F]fluoro-propoxy)-benzyl]- guanidine) Investigation for cardiac applications is either underway or considered Better flow-extracting 99m Tc-labeled perfusion imaging agent for SPECT 99m Tc-teboroxime could be revived since there are dedicated cardiac SPECT scanners that allow fast imaging suitable for fast washin and washout kinetics of the tracer 123 I-labeled rotenone analogues have been pursued in this direction Imaging fatty acid analogue for fatty acid metabolism (important energy for healthy myocardial activity) 123 I-BMIPP for SPECT 18 F-FTHA for PET
LMI1195 in Rats, Rabbits, and Human Subjects http://www.lantheus.com/pipeline/cna-lmi-1195/ Yu M, et al. Circ Cardiovasc Imaging. 2011;4:435
CMICE-013 ( 123 I-labeled rotenone derivative) Representative CMICE-013 images of porcine heart. R. Glenn Wells et al. J Nucl Med. 2015;56:764
18 F-FDG (glucose), 18 F-FDHROL (rotenol), 18 F-FTHA (fatty acid) in Failing Heart of Rat (Top) PET images corresponding to all electrocardiogram bins summed. (Bottom) PET images corresponding to only diastolic electrocardiogram bins summed. (A) 18 F-FDG images of SHR show almost no liver uptake. (B) 18 F- FDHROL images of SHR show substantial liver uptake. (C) 18 F-FTHA images of SHR again show substantial liver uptake. Andrew M. Hernandez et al. J Nucl Med. 2013;54:1938
New(er) Nuclear Cardiac Imaging Applications Dynamic Cardiac SPECT Imaging Analogous to dynamic cardiac PET imaging Allows SPECT to be used for myocardial blood flow and coronary flow reserve measurements Myocardial Inflammation Imaging (e.g., myocarditis, sarcoidosis, etc.) FDG, choline, somatostatin receptor Myocardial Efficiency Imaging Oxygen consumption, glucose utilization, fatty acid utilization Provided ways to assess the work output (that can be measured by PET only, with MRI strain measurement, etc.)
Dynamic Cardiac SPECT Imaging Data courtesy of UCSF. Shrestha U, et al. J Nucl Cardiol. 2015 (Epub ahead of print)
MBF and CFR in Orthotopic Heart Transplant 5 4 3 2 1 0 LAD 1. basal anterior 2. basal anteroseptal 7. mid anterior 8. mid anteroseptal 13. apical anterior 14. apical septal 17. apex RCA 3. basal inferoseptal 4. basal inferior 9. mid inferoseptal 10. mid inferior 15. apical inferior LCX 5. basal inferolateral 6. basal anterolateral 11. mid inferolateral 12. mid anterolateral 16. apical lateral GLOBAL TOTAL 6 5 4 3 2 1 0 LAD 1. basal anterior 2. basal anteroseptal 7. mid anterior 8. mid anteroseptal 13. apical anterior 14. apical septal 17. apex RCA 3. basal inferoseptal 4. basal inferior 9. mid inferoseptal 10. mid inferior 15. apical inferior LCX 5. basal inferolateral 6. basal anterolateral 11. mid inferolateral 12. mid anterolateral 16. apical lateral GLOBAL TOTAL Data courtesy of UCSF. Shrestha U, et al. J Nucl Cardiol. In Press
Cardiac Efficiency Imaging Using PET/MRI Data courtesy of UCSF (G. Gullberg, U. Shrestha, Y. Seo)
Summary Improved quantitation/quantification techniques accuracy, ease, dose reduction, speed of acquisition, etc. Dedicated nuclear cardiac imaging scanners Small footprint, mobile, compact, etc. (but not that much going on lately) Improved general-purpose scanners (e.g., SPECT/CT, PET/CT, PET/MRI) tuned for cardiac applications (improved cardiac SPECT reconstruction, dedicated cardiac SPECT collimators, MRI combination, etc.) New radiopharmaceuticals Better flow agent (improved PET and SPECT perfusion agents under study) Better sympathetic neuronal activity imaging agents (e.g., MFBG, MFPBG, LMI1195, etc.) New/revisited applications Utility of coronary flow reserve (by PET and SPECT), inflammation, myocardial efficiency