Aimo A.

Gimelli A.

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J A C C : C A R D I O V A S C U L A R I M A G I N G VO L . - , N O . - , 2 0 2 0ª 2 0 2 0 B Y T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y F O UN DA T I O NP U B L I S H E D B Y E L S E V I E REDITORIAL COMMENTThe Relativity of Reference Values forMyocardial Perfusion Imaging*Alessia Gimelli, MD,a Alberto Aimo, MDbM yocardial perfusion imaging (MPI) has ac-quired a crucial role in the diagnosis andmanagement of chronic coronary syn-drome, as acknowledged by the latest European Soci-ety of Cardiology Guidelines (1). An estimated 15 to 20million procedures are performed annually world-wide, and diffusion of technology and expertise hasled to its progressive adoption in developing coun-tries as well (2). The downside is that MPI accountsfor a substantial proportion of the radiation expo-sures every person gets per year from all medicalsources (3). For example, nuclear cardiology accountsfor more than one half of all nuclear medicine proced-ures and 26% of the overall medical exposure of pa-tients in the United States (4). Cardiologists andnuclear medicine specialists, then, have the responsi-bility to avoid unjustified and nonoptimized use ofradiation.The risk of cancer attributable to radiation expo-sure has been estimated as 1 in 100 subjects (andranging from 1 in 30 to 1 in 300) following exposure to100 mSv, which roughly corresponds to 20 single-photon emission computed tomography (SPECT)scans with 99mtechnetium (Tc)-labeled tracers (2,3).Although these estimates are extremely imprecise, itis indisputable that the risk of radiation-related can-cer increases with the radiation dose and, therefore,can be reduced by limiting radiation exposure.ISSN 1936-878X/$36.00*Editorials published in JACC: Cardiovascular Imaging reflect the views ofthe authors and do not necessarily represent the views of iJACC or theAmerican College of Cardiology.From the aFondazione Toscana Gabriele Monasterio, Pisa, Italy; and thebInstitute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy. Bothauthors have reported that they have no relationships relevant to thecontents of this paper to disclose.The authors attest they are in compliance with human studiescommittees and animal welfare regulations of the authors’ institutionsand Food and Drug Administration guidelines, including patientconsent where appropriate. For more information, visit the JACC:Cardiovascular Imaging author instructions page.Following the “as low as reasonably achievable”principle, MPI needs to be performed with a radiationdose as low as possible (2). Additionally, the activityof a radiopharmaceutical to be administered must bedetermined in agreement with national legislationand the European Council Directive Euratom 2013/59.Diagnostic reference levels (DRLs) for radiopharma-ceuticals are a crucial element of this legislation.DRLs correspond to levels of activity for broadlydefined types of equipment and groups of standard-sized patients, not to be exceeded for standardprocedures, and derive from distributions of actualpatient examinations (5). DRLs are reference valuesthat are useful for identifying outliers, whose in-struments and protocols can then be re-evaluated (5).Their implementation as a dose-reduction strategy iswidely endorsed by professional societies and na-tional agencies for radiological protection and isrequired by the International Safety Standards (5).The achievable administered activity (AAA), anothermeasure proposed more recently, is calculated as themedian of a dose distribution, and it provides a goalthat laboratories should strive to achieve even whenthey fall below DRLs.Tracer activity is, in general, a compromise be-tween image quality and radiation exposure. Thehigher the activity administered, the better the imagequality and the higher the radiation exposure to thepatient and staff (6). The activity to administer de-pends on the type of equipment (a single-head ormultiple-head scintillation camera or a camera basedon a cadmium-zinc-telluride detector), patient char-acteristics (body weight), acquisition protocol (1-dayor 2-day protocols, imaging time, pixel size, andgated acquisition), and the radiopharmaceutical(99mTc compounds or 201thallium [Tl] chloride) (6).The reconstruction method may also be of impor-tance, that is, filtered back-projection versus iterativereconstruction. When a 1-day 99mTc protocol is used(i.e., 2 administrations of activity on 1 day), the ac-tivity for the second examination has to be 3 timeshttps://doi.org/10.1016/j.jcmg.2020.06.028Gimelli and Aimo J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . - , N O . - , 2 0 2 0Reference Values for MPI - 2 0 2 0 :- –-2higher than the first administered activity. Further-more, if the stress examination is performed first andthe findings are reported as normal, the rest exami-nation can be omitted (6).Technological advances in scanner, hardware, andsoftware equipment for image acquisition andreconstruction have led to a dramatic improvement inthe efficiency and quality of MPI, allowing a pro-gressive reduction of radiation doses (2). In parallel, avariety of best practices have been developed todecrease radiation exposure. These have been sum-marized as follows: avoid Tl stress, avoid dualisotope, avoid too much Tc or Tl, perform stress-onlyimaging when possible, use camera-based dose-reduction strategies, and use weight-based doses ofTc (7). The International Atomic Energy AgencyNuclear Cardiology Protocols Cross-Sectional Study(INCAPS) has represented the first attempt to eval-uate technologies, best practices, and the resultingradiation exposure on a worldwide scale (7). A total of308 nuclear cardiology laboratories from 65 countrieswere asked to provide data regarding consecutive MPIstudies performed during a single week in 2013. Theworldwide median laboratory radiation dose fromMPI was 10.9 mSv, ranging over an order of magni-tude (2.2 to 24.4 mSv) depending on the laboratory,and fewer than a third of laboratories achieved themedian effective dose of #9 mSv recommended inprofessional society guidelines (8). Radiation expo-sure differed between world regions, being lowest inEurope and highest in Latin America. Adherence tobest practices was higher in Europe, and adherence tothe best practices listed here was associated with asignificantly lower ED (7).So far, DRL and AAA values have been establishedat the local or national level. In this issue the iJACC,the INCAPS investigators propose DRLs and AAAvalues for SPECT imaging, calculated on a worldwidescale and for geographic regions (Africa, Asia, Europe,Latin America, North America, and Oceania) (9). Forexample, the investigators report that worldwideDRLs for rest/stress or stress/rest studies using 99mTc-labeled tracers were 11.2 mCi (first dose) and 32.0 mCi(second dose) for 1-day protocols and 23.0 mCi (firstdose) and 24.0 mCi (second dose) for multiday pro-tocols. The corresponding AAAs were 10.1 mCi (firstdose) and 28.0 mCi (second dose) for 1-day protocolsand 17.8 mCi (first dose) and 18.7 mCi (second dose)for multiday protocols. DRL and AAA valueswere clearly lower for stress-only protocols. The in-vestigators also considered examinations using 201Tlor dual isotopes, which were still used in a non-negligible proportion of studies in Europe, Asia,Oceania, and Latin America. DRL and AAA values foreach protocol displayed wide variations (up to 14 mCifor DRLs and 15 mCi for AAAs) across regions, whichwas evidently explained by different technologiesand an uneven adoption of best practices, as previ-ously demonstrated in the same INCAPS cohort (7).It is unfortunate that these results, based on MPIexaminations dating back to 2013, were publishedjust before the start of INCAPS 2. Nonetheless,Hirschfeld et al. (9) should be congratulated even justfor introducing the notion that DRLs and AAAs shouldbe established for the entire world and single conti-nents. The availability of these reference values mayrepresent a major step toward the standardization ofMPI practices and a general decrease of the activityadministered. On the other hand, targeting uniformDRLs and AAAs is still not the best we can do toreduce global radiation exposure. Indeed, DRLs andAAAs are calculated from real-world data and arenecessarily higher than values achievable throughstate-of-the-art technology and rigorous adoption ofbest practices. Therefore, the next step will be topursue the minimal activity needed to have aninterpretable examination in standard conditions.This activity should be defined for each tracer, ex-amination protocol, and technology by an indepen-dent regulatory board, and it would represent the realoptimal target to pursue. Defining minimal activitiesfor each technology would also stimulate competitionamong the producers of SPECT cameras, who wouldtry to progressively reduce the doses needed.In summary, Hirschfeld et al. (9) has the greatmerit of proposing, for the first time, internationalDRLs and AAAs. Although these are useful targets forSPECT laboratories, they are suboptimal compared to“ideal” minimal doses, which are yet to be estab-lished. Understanding the relativity of referencevalues could represent important progress toward thereduction of radiation exposure from MPI.ADDRESS FOR CORRESPONDENCE: Dr. AlessiaGimelli, Fondazione Toscana Gabriele Monasterio,Via Moruzzi, 1, 56124-Pisa, Italy. E-mail: gimelli@ftgm.it.J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . - , N O . - , 2 0 2 0 Gimelli and Aimo- 2 0 2 0 :- –- Reference Values for MPI3RE F E RENCE S1. Knuuti J, Wijns W, Saraste A, et al. 2019 ESCGuidelines for the diagnosis and management ofchronic coronary syndromes. Eur Heart J 2020;41:407–77.2. Gimelli A, Achenbach S, Buechel RR, et al.Strategies for radiation dose reduction in nuclearcardiology and cardiac computed tomographyimaging: a report from the European Associationof Cardiovascular Imaging (EACVI), the Cardio-vascular Committee of European Association ofNuclear Medicine (EANM), and the European So-ciety of Cardiovascular Radiology (ESCR). EurHeart J 2018;39:286–96.3. Picano E, Vano E, Rehani MM, et al. Theappropriate and justified use of medical radiationin cardiovascular imaging: a position document ofthe ESC Associations of Cardiovascular Imaging,Percutaneous Cardiovascular Interventions andElectrophysiology. Eur Heart J 2014;35:665–72.4. Mettler FA Jr., Bhargavan M, Faulkner K, et al.Radiologic and nuclear medicine studies in theUnited States and worldwide: frequency, radiationdose, and comparison with other radiation sour-ces—1950-2007. Radiology 2009;253:520–31.5. Alessio AM, Farrell MB, Fahey FH. Role ofreference levels in nuclear medicine: a report ofthe SNMMI Dose Optimization Task Force. J NuclMed 2015;56:1960–4.6. Verberne HJ, Acampa W, Anagnostopoulos C,et al. EANM procedural guidelines for radionuclidemyocardial perfusion imaging with SPECT andSPECT/CT: 2015 revision. Eur J Nucl Med Mol Im-aging 2015;42:1929–40.7. Einstein AJ, Pascual TN, Mercuri M, et al.Current worldwide nuclear cardiology practicesand radiation exposure: results from the 65country IAEA Nuclear Cardiology ProtocolsCross-Sectional Study (INCAPS). Eur Heart J2015;36:1689–96.8. Cerqueira MD, Allman KC, Ficaro EP, et al.Recommendations for reducing radiation exposurein myocardial perfusion imaging. J Nucl Cardiol2010;17:709–18.9. Hirschfeld CB, Dondi M, Pascual TNB, et al.Worldwide diagnostic reference levels for singlephoton emission computed tomographymyocardial perfusion imaging: findings from theIAEA Nuclear Cardiology Protocols Study(INCAPS). J Am Coll Cardiol Img 2020:XX:XXX–XXX.KEY WORDS diagnostic reference values,myocardial perfusion scintigraphy, radiation dose,SPECT

The Relativity of Reference Values for Myocardial Perfusion Imaging

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The Relativity of Reference Values for Myocardial Perfusion Imaging

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