Nuclear Cardiology Practice in Asia: Analysis of Radiation Exposure and Best Practice for Myocardial Perfusion Imaging　― Results From the IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS) ―

Abstract

Background: This paper examines the current status of radiation exposure to patients in myocardial perfusion imaging (MPI) in Asia.

Methods and Results: Laboratories voluntarily provided information on MPI performed over a 1-week period. Eight best practice criteria regarding MPI were predefined by an expert panel. Implementation of ≥6 best practices (quality index [QI] ≥6) was pre-specified as a desirable goal for keeping radiation exposure at a low level. Radiation effective dose (ED) in 1,469 patients and QI of 69 laboratories in Asia were compared against data from 239 laboratories in the rest of the world (RoW). Mean ED was significantly higher in Asia (11.4 vs. 9.6 mSv; P<0.0001), with significantly lower doses in South-East vs. East Asia (9.7 vs. 12.7 mSv; P<0.0001). QI in Asia was lower than in RoW. In comparison with RoW, Asian laboratories used thallium more frequently, used weight-based technetium dosing less frequently, and trended towards a lower rate of stress-only imaging.

Conclusions: MPI radiation dose in Asia is higher than that in the RoW and linked to less consistent use of laboratory best practices such as avoidance of thallium, weight-based dosing, and use of stress-only imaging. Given that MPI is performed in Asia within a diverse array of medical contexts, laboratory-specific adoption of best practices offers numerous opportunities to improve quality of care.

It has been estimated that half of the world’s burden of cardiovascular diseases is carried by the Asia-Pacific region,^1,2 underscoring the critical role of the diagnosis, prevention, and treatment of cardiovascular disease in this region.³ Nuclear myocardial perfusion imaging (MPI) is extensively used for the evaluation of known or suspected coronary artery disease (CAD), with an estimated 15–20 million procedures performed annually worldwide.⁴ It has been proven as a cost-effective tool for the evaluation and management of cardiac patients, often playing a decisive role in diagnosis, prognosis, risk stratification, as well as guidance of therapy.^5–7 Clinical scenarios in which nuclear cardiology (NC) can be helpful are continuously expanding.

Concomitantly, radiation exposure due to medical practices, to which cardiac imaging contributes,⁸ is a growing concern, with its several-fold increase in the last 3 decades.⁹ In some populations now, MPI is the procedure contributing most to radiation doses.^10,11 Several steps have been taken to address this problem, such as emphasizing lower-dose protocols, and the introduction of technological approaches such as gamma-cameras with solid state detectors,^12,13 and more efficient image reconstruction algorithms.^14,15 The American Society of Nuclear Cardiology (ASNC) established a series of recommendations with the aim of reducing median radiation effective dose (ED) to ≤9 mSv.¹⁶

Pursuant to its mission, the International Atomic Energy Agency (IAEA) has long played a focal role in the dissemination and promotion of nuclear medicine,^17,18 with a special focus on applications in cardiology throughout its Member States. This has been accomplished by means of educational and training initiatives, such as regional training courses supported by the IAEA Technical Cooperation Program,¹⁹ as well as through fellowships provided to nuclear medicine or cardiology practitioners who want to improve their clinical competence in the field of NC.

Given that radiation exposure due to medical practices, to which cardiac imaging contributes,¹² is a growing concern, the IAEA Nuclear Cardiology Protocols Study (INCAPS) was launched with the aim of characterizing NC practice worldwide, with a focus on MPI and radiation exposure to patients undergoing this procedure. This paper provides a snapshot of the practice of NC in Asia, presenting INCAPS results in Asia, and identifies areas of possible intervention to optimize patient radiation exposure due to NC procedures.

Methods

Study Design and Focus

This study was conceptualized following expert and stakeholder meetings organized by the IAEA since February 2012 (participant list given in Appendix 1) aimed at improving NC practice worldwide. INCAPS was designed as a study with a specific focus on the current status of NC practice worldwide and an emphasis on MPI and the corresponding radiation exposure.

A survey instrument was emailed to all nuclear medicine centers performing NC MPI registered in the IAEA database,²⁰ as well as to the entire database of local and international nuclear medicine, cardiology and related professional organizations and INCAPS coordinators. Voluntary in nature, it asked respondents to provide information on patients undergoing MPI between the weeks beginning 19 March and 22 April 2013 (inclusive), and answer questions related to tracer utilization, dosage/doses used and the technology available. Data received from responders worldwide were checked for accuracy of information and, if necessary, clarifications were made. Potential participants were approached and provided with data collection forms. Active participants were not pre-selected but rather voluntarily agreed to contribute to the study.

Data collection included demographics; weight; radiopharmaceutical(s) used; radiopharmaceutical dosage; and type of study protocol (i.e., single-day/2-day or stress-only protocol for ^99mTc99 compounds). All data were collected in compliance with the Columbia University Institutional Review Board, which approved this study, deeming it exempt from the requirements of US federal regulations for the protection of human subjects (Code of Federal Regulations, Title 45, Part 46) because no individually identifiable health information was collected. Worldwide, a total of 308 laboratories responded, and ED estimates, and adherence to best practice in NC, were the main parameters measured to establish comparisons of variations in NC between the 69 participant laboratories from Asia and the remaining 239 from the rest of the world (RoW).

ED Estimation

ED (in mSv) is defined by the International Commission on Radiological Protection as “the weighted sum of the equivalent doses in all specified tissues and organs of the human body and [which] represents the stochastic health risk to the whole body, which is the probability of cancer induction and genetic effects, of ionising radiation.”²¹ Radiation dose was calculated according to models of the International Commission on Radiological Protection.²² Following the ASNC recommendation to attain a median ED ≤9 mSv by 2014,¹⁶ we considered the proportion of patients and laboratories achieving this goal as a benchmark for best practice.

Best Practice

In an attempt to identify the best approach to individual dose optimization in NC, experts, including physicians and medical physicists, convened for an IAEA meeting, to identify and define 8 best practices in NC. Based on a review of published guidelines,^23–27 the panel determined best practice as follows. (1) Avoidance of ²⁰¹Tl stress; (2) avoidance of dual isotope imaging; (3) avoidance of too much ^99mTc; (4) avoidance of too much ²⁰¹Tl; (5) performance of stress-only imaging; (6) use of camera-based dose-reduction strategies; (7) use of weight-based dosing for ^99mTc; and (8) avoidance of inappropriate dosing that can lead to “shine-through” artefact (Table 1).²⁸ More details regarding these practices are reported elsewhere.²⁹ Those criteria were included in the study design, before its launch, as well as a quality index (QI) score, equal to the number of best practices adhered to by a laboratory. Implementation of at least 6 of those 8 best practices (QI ≥6) was pre-specified as a desirable goal for keeping radiation exposure low. Best practices and the quality score were considered at the individual laboratory level.

Table 1. Base for Recommendation of the 8 Best Practices

No.	Best practice	Basis
1	Avoid 201Tl stress	SPECT with 201Tl is associated with a considerably higher radiation dose to patients than 99mTc.11 This practice excludes 201Tl viability studies and stress redistribution-reinjection stress-and-viability studies
2	Avoid dual isotope imaging	Dual isotope imaging is associated with the highest radiation dose of any protocol11
3	Avoid use of too much 99mTc	1,332 MBq is the highest recommended activity in guidelines,12 and 15 mSv is a very high radiation dose for 99mTc
4	Avoid use of too much 201Tl	The expert committee maintained that 129.5 MBq should be the upper threshold for 201Tl activity
5	Perform stress-only imaging	If stress images are completely normal, subsequent rest imaging can be omitted
6	Use camera-based dose-reduction strategies	Each of these approaches reduces the activity needed and facilitates performance of stress-only imaging
7	Use weight-based dosing for 99mTc	Tailoring the activity to patient weight offers an opportunity to reduce radiation dose
8	Avoid inappropriate dosing that can lead to “shine-through” artefact	Shine-through occurs in 1-day 99mTc when residual radioactivity from the first injection interferes with the images following the second injection. To avoid shine-through, guidelines recommend that the activity of the second injection should be 3–4-fold higher than that of the first injection.12 A second injection with an activity <3-fold the activity of the first injection can lead to shine through.13

Adapted from Lindner et al.²⁸ SPECT, single-photon emission computed tomography.

Statistical Analysis

For the purpose of this study, data have been extracted from the overall INCAPS study and analyzed for the Asia region overall, as well as for subregions, in accordance with the United Nations Geoscheme.³⁰ These subregions are West Asia (Israel, Kuwait, Saudi Arabia, Turkey, United Arab Emirates), South Asia (Bangladesh, India, Iran, Pakistan, Sri Lanka), East Asia (China, Japan, South Korea) and South-East Asia (Indonesia, Philippines, Singapore, Thailand, Vietnam). Practice variables and ED, at both the patient and laboratory level, are compared with the RoW.

The full description of statistical methods has been published previously.²⁹ Briefly, statistical analysis focused on the calculated patient ED and the corresponding adherence to identified best practice and the QI score differences between the Asian regions and subsequently with the RoW. Continuous variables were compared using Student’s t-test or analysis of variance for calculated means, and Kruskal-Wallis test for calculated medians. The comparison of mean ED among Asian regions, and between Asia and the RoW was adjusted for patient weight using analysis of variance. Chi-squared test was used to compare categorical variables. All analysis was performed using Stata/SE 13.1 (StataCorp, College Station, TX, USA), and P<0.05 was considered statistically significant.

Results

Demographics

Out of a total of 308 laboratories participating in this study worldwide, 69 labs from Asia reported on a total of 1,469 patients (Figure 1). Mean age was 61.8±12.5 years, significantly lower for Asia compared with the RoW (P<0.0001). Out of those patients 559 were female (38%), 482 (33%) were from the West subregion, 310 (21%) from the South-East, 272 (18.5%) from the East, and the remaining 405 (27.5%) were from the South (Table 2).

Figure 1.

Geographical distribution of participating centers in Asia and corresponding patient contribution. Dot size reflects the total number of patients, across all centers, in a specific geographical area.

Table 2. (A) Asia vs. RoW, and (B) Asia Subregions^†

(A)	Asia Total vs. RoW
	Asia total	RoW	P-value
Laboratories n (% in Asia)	69	239
Patients n (% in Asia)	1,469	6,442
Female, n (%)	559 (38)	2,695 (42)	0.008
Age (years)
Mean	61.8	64.7	<0.0001
SD	12.5	11.8
Weight
Mean	71.6	82.2	<0.0001
SD	15.7	18.8
Patients per laboratory
Mean	21.3	27	0.19
SD	23.9	33.4
Median	15	16	0.10
IQR	6–29	9–34
(B)	South Asia	East Asia	South-East Asia	West Asia	P-value
Laboratories n (% in Asia)	16 (23)	16 (23)	20 (29)	17 (25)
Patients n (% in Asia)	405 (28)	272 (19)	310 (21)	482 (33)
Female, n (%)	124 (31)	128 (47)	114 (37)	193 (40)	<0.01
Age (years)
Mean	58.1	68	62	61.2	<0.0001
SD	12.2	11	12.1	12.4
Weight
Mean	70.1	63.7	67.4	80.2	<0.0001
SD	12.2	11.7	14.4	16.8
Patients per laboratory
Mean	25.3	17	15.5	28.4	0.31
SD	18.1	13.2	34.8	19.6
Median	27	14.5	5	23	0.01
IQR	6.5–38.5	8–21.5	3.5–13	11–39

RoW, rest of the world. ^†West Asia: Israel, Kuwait, Saudi Arabia, Turkey, United Arab Emirates; South Asia: Bangladesh, India, Iran, Pakistan, Sri Lanka; East Asia: China, Japan, South Korea; South-East Asia: Indonesia, Philippines, Singapore, Thailand, Vietnam.

Effective Dose

Looking at Asia as a whole, ED was significantly higher than in the RoW (11.4 vs. 9.6 mSv; P<0.0001). This difference remained after adjustment for patient weight (P<0.0001). There was a statistically significant difference in ED between the Asian subregions, with lower doses noted in South-East Asia (Table 3). Again, this difference was maintained after adjustment for patient weight (P<0.0001). Figures 2,3 show the distribution of ED observed, demonstrating considerable variability in ED in all regions, with modest but significant differences in ED among Asian subregions and between Asia and RoW. Fewer Asian patients and laboratories achieved doses ≤9 mSv compared with the RoW, with differences across Asia, and this goal was achieved more frequently in South-East Asia (Table 3).

Figure 2.

Effective dose from myocardial perfusion imaging vs. region.

Figure 3.

Distribution of myocardial perfusion imaging effective dose vs. Asia subregion.

Table 3. ED and Achievement of Targeted ED ≤9 mSv

	Asia Subregions†					Asia vs. RoW
	South Asia	East Asia	South-East Asia	West Asia	P-value	Asia total	RoW	P-value
Patient-level ED (mSv)
Mean	11.7	12.7	9.7	11.6	<0.001	11.4	9.6	<0.0001
SD	5.5	4.9	4.1	4.3		4.8	4.4
Median	11.4	12.4	10.6	11.5	<0.0001	11.4	9.8	<0.0001
IQR	8.7–14.1	9.9–15.4	7.5–12.2	9.9–13.8		9.2–13.5	6.2–12.5
99mTc only (mSv)
Mean	9.0	11.7	9.1	10.8	<0.0001	10.1	9.9	0.081
SD	3.8	2.5	3.8	3.0		3.5	4.0
Median	10.6	12.3	10.0	10.6	<0.0001	10.8	10.1	0.001
IQR	5.5–11.9	9.9–12.7	7.5–11.6	9.7–12.5		8.5–12.4	7.2–12.5
201Tl (mSv)
Mean	17.1	20.2	14.8	17.1	<0.0001	17.4	17.4	0.997
SD	4.2	2.5	3.0	4.0		4.0	5.1
Median	17.4	19.9	15.7	16.4	<0.0001	16.7	16.8	0.981
IQR	13.2–10.9	19.9–22.8	12.5–16.3	15.5–17.6		15.5–20.5	14.1–20.7
Achievement of targeted ED
Patients (n)	405	272	310	482		1,469	6,442
ED ≤9 mSv, n (%)	102 (25)	49 (18)	126 (41)	81 (17)	<0.001	358 (24)	2,707 (42)	<0.001
ED >9 mSv, n (%)	303 (75)	223 (82)	184 (59)	401 (83)	<0.001	1,111 (76)	3,735 (58)	<0.001
Laboratories	16	16	20	17		69	239
ED ≤9 mSv, n (%)	2 (12)	3 (19)	6 (30)	1 (6)	0.25	12 (17)	79 (33)	0.012
ED >9 mSv, n (%)	14 (88)	13 (81)	14 (70)	16 (94)		57 (83)	160 (67)

^†West Asia: Israel, Kuwait, Saudi Arabia, Turkey, United Arab Emirates; South Asia: Bangladesh, India, Iran, Pakistan, Sri Lanka; East Asia: China, Japan, South Korea; South-East Asia: Indonesia, Philippines, Singapore, Thailand, Vietnam. ED, effective dose.

Protocols

Patients underwent a stress-only protocol more frequently in Asia than in the RoW. Across the region, 272 (18%) underwent this protocol as opposed to 733 (11%) in the RoW (P<0.001). Again there were significant variations among the subregions: South Asia applied this protocol in 78 patients (11%); East Asia in 13 patients (5%); South-East Asia in 76 patients (25%) and West Asia in 105 patients (22%; P<0.001). The use of ²⁰¹Tl was more frequent in Asia than in the RoW (11%, 195/1,469, vs. 1.5%, 98/6,442 in the RoW) whereas the use of positron emission tomography appeared more limited: 52 patients in Asia (3.5%) vs. 418 (6.5%) in the RoW. Among Asian patients, 298 of 1,469 patients had ²⁰¹Tl (e.g., ²⁰¹Tl or dual isotope) vs. 147 of 6,442 in the RoW (P<0.0001). On a laboratory basis, 51 laboratories performed at least 1 study with ²⁰¹Tl, 26 of which were in Asia (26/69 in Asia vs. 25/239 in RoW; P<0.0001).

Best Practices and QI

Use of individual best practices in the 69 Asian laboratories is shown in Table 4. Overall, 18/69 Asian laboratories (26%) achieved QI ≥6 vs. 124/239 (52%) in the RoW (P<0.001).

Table 4. (A) Best Practices Used, and (B) Laboratory QI

	Asia Subregions†				P-value	Asia total vs. RoW		P-value
	South Asia	East Asia	South-East Asia	West Asia		All of Asia	RoW
(A)
Laboratories	16 (23)	16 (23)	20 (29)	17 (25)		69 (23)	239 (77)
Best practice
Avoid thallium stress	13 (81)	14 (88)	13 (65)	12 (71)	0.44	52 (75)	230 (96)	<0.001
Avoid dual isotope	14 (88)	14 (88)	20 (100)	16 (94)	0.33	64 (93)	234 (98)	0.049
Avoid too much technetium	15 (94)	14 (88)	18 (90)	17 (100)	0.61	64 (93)	199 (83)	0.054
Avoid too much thallium	16 (100)	16 (100)	20 (100)	16 (94)	0.71	68 (99)	238 (100)	0.40
Perform stress-only imaging	4 (25)	0 (0)	3 (15)	9 (53)	0.002	16 (23)	77 (32)	0.15
Use camera-based dose-reduction strategies	11 (69)	12 (75)	15 (75)	10 (59)	0.75	48 (70)	158 (66)	0.59
Weight-based dosing for technetium	1 (6.3)	0 (0)	3 (15)	4 (24)	0.18	8 (12)	80 (33)	<0.001
Avoid “shine through” dosing	5 (31)	6 (38)	9 (45)	6 (35)	0.88	26 (38)	110 (46)	0.22
(B)
Laboratories, n (%)	16 (23)	16 (23)	20 (29)	17 (25)		69 (23)	239 (77)
QI (target ≥6)
Mean±SD	4.9±0.9	4.8±0.9	5.1±1.4	5.3±1.2	0.57	5±1.1	5.5±1.3	0.002
Median	5	5	5	5	NA	5	5	NA
IQR	4–5.5	4.5–5	4–6	4–6		4–6	5–6
QI ≥6, n (%)	4 (25)	2 (12)	6 (30)	6 (35)	0.52	18 (26)	124 (52)	<0.001
QI (0–8), n (%)
2	0	0	0	0		0	2 (1)
3	0	2 (13)	2 (10)	0		4 (6)	11 (5)
4	6 (38)	2 (13)	5 (25)	5 (29)		18 (26)	38 (16)
5	6 (38)	10 (63)	7 (35)	6 (35)		29 (42)	64 (27)
6	3 (19)	2 (13)	4 (20)	3 (18)		12 (17)	70 (29)
7	1 (6)	0	0	2 (12)		3 (4)	35 (15)
8	0	0	2 (10)	1 (6)		3 (4)	19 (8)

Data given as n (%). ^†West Asia: Israel, Kuwait, Saudi Arabia, Turkey, United Arab Emirates; South Asia: Bangladesh, India, Iran, Pakistan, Sri Lanka; East Asia: China, Japan, South Korea; South-East Asia: Indonesia, Philippines, Singapore, Thailand, Vietnam. QI, quality index; RoW, rest of the world.

Discussion

As an independent United Nations intergovernmental organization, the IAEA develops radiation and nuclear safety standards and, based on these standards, promotes the achievement and maintenance of high levels of safety in applications of atomic energy, such as in the protection of human health. One of the means to ensure that patient radiation exposure is kept “as low as reasonably achievable” (ALARA principle) is to foster and promote training and education in fields such as NC, something that the Agency has pursued actively in the last decade (Figure 4). A total of 1,071 participants were trained through 41 regional training courses conducted in NC. Recognition of these efforts and their costs has triggered attempts to measure the outcome of those activities. To this aim, some projects are underway and 1 of these has been the INCAPS study.

Figure 4.

(A) No. nuclear cardiology regional training courses (RTC) run by the International Atomic Energy Agency in different regions from 2005 to 2015; (B) no. participants.

The worldwide analysis of the INCAPS data²⁹ demonstrated variations with regards to adherence to best practices and patient radiation dose. Regional analyses have been also performed for Europe,²⁸ Latin America,³¹ the USA,³² Africa,³³ and Oceania.³⁴ On a laboratory-basis analysis for the Asia region, the proportion of laboratories adhering to ≥6 best practices is 18/69 (26%), significantly smaller than in the RoW, where 124/239 laboratories had QI ≥6 (52%; P<0.001; Table 4). This low proportion in Asia is due mainly to the limited implementation of 2 best practices, namely the avoidance of thallium stress testing in patients <70 years and weight-based dosing for technetium, which are used less frequently than in the RoW. Of note, the practice of using thallium stress in patients <70 years occurs in 25% of laboratories in Asia and is consistent across all Asian subregions with no statistically significant difference. With regards to patient-level ED calculation, the median ED for ²⁰¹Tl was virtually identical between Asia and the RoW, whereas median ED was higher in Asia for ^99mTc (Table 3), notwithstanding the considerably heavier weights of RoW patients, who weighed >10 kg than their Asian counterparts on average (Table 2). These findings probably reflect several factors, including less concern among Asian laboratories regarding avoidance of thallium and dual isotope stress testing, their significantly lower use of weight-based ^99mTc dosing (12% vs. 33%), and a generally less careful approach to dose optimization. This raises a red flag with respect to the potential inappropriate use of this radiopharmaceutical and further confirms its continued use in the laboratories in the region, while it is almost abandoned in the RoW, where only 4% of laboratories still use thallium stress testing (Table 4), probably due to its considerably higher radiation dose and poorer spatial resolution.

Many societal factors likely contribute to the variations in ED and QI observed among Asian countries, which reflect a diverse array of developed and developing societies. Differences in education, human resources, technological resources available, health policy, and medical economy all could contribute to these findings. In terms of education, both the nature of medical training and initiatives for continuous professional development and continuous medical education (CPD/CME) are important. In the absence of updated CPD/CME opportunities, requesting physicians can still refer for ²⁰¹Tl stress, dual isotope imaging and other deviations from the best practices in NC, which contributes to higher patient ED. Adherence to at least 6 of the best practices in NC will significantly reduce unnecessary radiation exposure. Determination of adherence to these best practices provides an opportunity for each laboratory to identify its own areas for potential improvement. Appropriate CPD/CME opportunities focused on the 8 best practices in NC should be made available in order to harmonize or standardize appropriate MPI use.

One of the possible explanations for the persistence of inappropriate ²⁰¹Tl studies in Asia compared with the RoW could be that the nomenclature “stress thallium” is still embedded into referring physician culture as a synonym for MPI, and laboratories do not question this referral. Another possible explanation could be that, particularly in remote areas, availability of ^99mTc (or reliability of generator arrival) may be an issue and as such, thallium protocols may be an easier default. In a survey conducted by the IAEA in 2011,¹⁷ operating nuclear medicine centers worldwide were asked to rate the efficiency of their centers in responding to requests from referring physicians. The Asian region was found to have maximum efficiency, translated into more procedures performed per referring physician request. The longer physical half-life of thallium (73 h vs. 6 h for ^99mTc), while resulting in higher radiation dose, may facilitate its availability, reflected by this better availability of nuclear imaging services in some Asian centers. In any event, the reasons why thallium stress testing is used more frequently in Asia than elsewhere should be further investigated, to fulfil the twin goals of facilitating best practice use and minimizing radiation dose in NC.

With regards to scaling patient dose to weight, this practice is also not widely implemented in Asia. This is done in only 11% of centers, evenly distributed in the 4 subregions, as opposed to 33% worldwide. One reason could be that most laboratories in Asia receive their radiopharmaceuticals as unit doses from commercial centralized radiopharmacies, which tend to dispense unit doses with predefined activities (i.e., 10–15 mCi for rest and 30–40 mCi for stress studies). A laboratory where tests are performed may not proceed further to dose adjustment before the test is done, perhaps due to lack of equipment, skill or simply for practicality or convenience Insurance regulations in some countries of Asia, which request fixed doses rather than weight-based dosing, is another possible reason. This deviation in best practice should be further investigated in order to plan appropriate and adequate interventions to improve NC practice.

This is all reflected in the higher radiation exposure for Asian patients, who receive a 2 mSv higher dose on average compared with the RoW, notwithstanding being lighter than patients elsewhere. This higher radiation exposure is linked to a greater usage of dual isotope and thallium stress protocols, as well as more limited implementation of weight-based dosing when ^99mTc is utilized as discussed here. There is, however, a significant variation within the region, in that the number of patients in South-East Asia (Indonesia; Philippines; Singapore; Thailand; Vietnam) who have received >9 mSv is significantly smaller (P<0.001) than in the other subregions, while those from East Asia (China; Japan; South Korea) receive on average 12.7 mSv. This offsets the finding that Asian patients are more likely to undergo a stress-only ^99mTc protocol, which in principle should carry with it a lower ED because the rest injection is not given. Again, in the wide Asian region there are significant differences between the subregions, with patients from the East region being the least likely to undergo a stress-only protocol. One possible explanation is that this is simply due to fewer patients with a low likelihood of CAD being studied in the East. Between the Asian subregions, aside from the other deviations from the best practices noted, variation in the average ED might also be attributed to differences in the level of enforcement of existing directives geared towards radiation exposure due to medical reasons. Unlike Europe, the Asian region as a whole lacks a common directive approach, such as the Directive 2013/59/Euratom of 5 December 2013,³⁵ which is binding in European member states and reflected in the lower ED (8.7 mSv) there.²⁹

Overall, the INCAPS study clearly shows that ED to patients is linked to QI. Indeed, in Asia QI is lower than in the RoW, and the ED patients receive is higher. This is further supported by the finding that the number of centers reaching QI ≥6 in East Asia is only 2, and this is in the subregion where ED to patients is higher than in the other 3, due to 2 best practices, viz. “perform stress-only imaging” and “weight-based dosing for technetium”, being least used. Stress-only imaging, in particular, has been shown to reduce radiation exposure, as reflected in a study looking at stress-only imaging in the INCAPS population.³⁶

Finally, considering the long-lasting efforts of the IAEA on training activities in NC in 2005–2015 (Figure 4), there is clearly a need to provide greater focus on best practice to improve the quality of cardiac imaging and minimize radiation exposure to patients.^28–34,36

Study Limitations

Several limitations exist in this study. Due to the voluntary nature of the survey, 308 laboratories were enrolled in the study worldwide, 69 of which were from Asia, a number that is far lower than the actual number of Asian clinics performing MPI. Given, however, that the exact number of clinics is unknown, it would be difficult to predict to what extent these centers are representative of current MPI practice. Although the modest number of centers studied here may limit the generalizability of the findings, they provide the baseline and a framework for further research involving more centers and patients in individual Asian countries. Building on this research, successive initiatives can include more participants and provide a more complete picture of the nature of nuclear practice.

Crucial socioeconomic factors such as the economic and technological resources available, health policy, nature of medical training and initiatives for CPD/CME, are all likely to have an influence on variation in medical practice in general and NC practice in particular. The present study did not collect data to assess the impact of such factors on NC practices, but their further investigation is needed in future research.

Additionally, while the countries and subregions are geographically close, they are nevertheless very different and do not share language, resources or educational opportunities. The lumping of countries by regions, although a practical necessity, dilutes the significant variations that may exist even among neighbors in the same region and within individual countries. Finally, given that the focus was on radiation exposure, other important aspects of MPI practice were not investigated, including, but not limited to, justification/appropriateness and quality of imaging.

Conclusions

In this study of MPI practice in Asia and worldwide, we observed marked variation in radiation dose and in the use of best practices impacting radiation dose. In comparison with the RoW, Asian laboratories were characterized by higher average radiation dose despite lower patient weight, more frequent use of thallium, less use of weight-based technetium dosing, and a trend towards a lower rate of stress-only imaging. Although involving a diverse array of societies, significant differences were noted between regions of Asia. Laboratory-specific identification of best practices non-adherence, and interventions targeted at implementing best practices, offer Asian laboratories numerous opportunities to improve the quality of NC care across the continent.

Acknowledgments

This paper is dedicated in memory of our friend and colleague Dr. Ravi Kashyap, for all of his efforts at advancing nuclear medicine, in India and throughout the world. The authors gratefully acknowledge funding from the International Atomic Energy Agency (IAEA), the Margaret Q. Landenberger Research Foundation (in memory of Professor A. Donny Strosberg), and the Irving Scholars Program. We are grateful to the INCAPS Investigators Group members (Appendix 2) and their institutions for efforts in collecting the data, and to the cooperating professional societies, including the American Society of Nuclear Cardiology, the Asian Regional Cooperative Council for Nuclear Medicine, Australian and New Zealand Society of Nuclear Medicine, British Nuclear Medicine Society/British Nuclear Cardiology Society, Comissão Nacional de Energia Nuclear, European Association of Nuclear Medicine, European Council of Nuclear Cardiology, IAEA, and the Intersocietal Accreditation Commission.

Disclosures

A.J.E. has received research grants to Columbia University for other investigator-initiated studies from GE Healthcare, Philips Healthcare, and Toshiba America Medical Systems; the other authors declare no conflict of interest.

Appendix 1

List of Participants in the IAEA Meeting

Maurizio Dondi, IAEA, Vienna, Austria; Thomas N.B. Pascual, IAEA, Vienna, Austria; Diana Paez, IAEA, Vienna, Austria; Ravi Kashyap, IAEA, Vienna, Austria; Madan Rehani, IAEA, Vienna, Austria; Andrew Einstein (chairman), New York City, USA; John Mahamarian, Houston, USA; Nathan Better, Melbourne, Australia; Vikram Lele, Mumbai, India; Salaheddine Bouyoucef, Algiers, Algeria; Ganesan Karthikeyan, New Delhi, India; Klaus Bacher, Ghent, Belgium; Joao Vitola, Curitiba, Brazil.

Appendix 2

Members of the INCAPS Investigators Group

Executive Committee

A.J. Einstein (chair), T.N.B. Pascual (IAEA project lead), D. Paez (IAEA section head), M. Dondi (IAEA section head); (alphabetically) N. Better, S.E. Bouyoucef, G. Karthikeyan, R. Kashyap, V. Lele, V.P.C. Magboo, J.J. Mahmarian, M. Mercuri, F. Mut, M.M. Rehani, J.V. Vitola.

Regional Coordinators (alphabetically)

E. Alexánderson (Latin America), A. Allam (Africa/Middle East), M.H. Al-Mallah (Middle East), N. Better (Oceania), H. Bom (East Asia), S.E. Bouyoucef (Africa), A. Flotats (Europe), S. Jerome (United States), P.A. Kaufmann (Europe), V. Lele (South Asia), O. Luxenburg (Israel), J. Mahmarian (North America), L.J. Shaw (North America), S.R. Underwood (United Kingdom), J. Vitola (Latin America).

Members (alphabetical order, by region)

Africa W. Amouri, H. Essabbah, S.S. Gassama, K.B. Makhdomi, G.I.E. El Mustapha, N. El Ouchdi, N. Qaïs, N. Soni, W. Vangu.

Asia R.M. Abazid, B. Adams, V. Agarwal, M.A. Alfeeli, N. Alnafisi, L. Bernabe, G.G. Bural, T. Chaiwatanarat, J.M. Chandraguptha, G.J. Cheon, I. Cho, A.S. Dogan, M. Eftekhari, A. Frenkel, I. Garty, S. George, P. Geramifar, H. Golan, S. Habib, R. Hussain, H. Im, H-J. Jeon, T. Kalawat, W.J. Kang, F. Keng, A. Klaipetch, P.G. Kumar, J. Lee, W.W. Lee, I. Lim, C.M.M. Macaisa, G. Malhotra, B.R. Mittal, M.H. Mohammad, P. Mohan, I.D. Mulyanto, D. Nariman, U.N. Nayak, K. Niaz, G. Nikolov, J.M. Obaldo, E. Ozturk, J.M. Park, S. Park, C.D. Patel, H.K. Phuong, A.P. Quinon, T.R. Rajini, Y. Saengsuda, J. Santiago, H.B. Sayman, A.S. Shinto, V. Sivasubramaniyan, M.H. Son, P. Sudhakar, G.M.S. Syed, N. Tamaki, K. Thamnirat, T. Thientunyakit, S. Thongmak, D.N. Velasco, A. Verma, U. Vutrapongwatana, Y. Wang, K.S. Won, Z. Yao, T. Yingsa-nga, R. Yudistiro, K.T. Yue, N. Zafrir.

Europe S.C. Adrian, D. Agostini, S. Aguadé, G. Armitage, M. Backlund, M. Backman, M. Baker, M.T. Balducci, C. Bavelaar, M. Berovic, F. Bertagna, R. Beuchel, A. Biggi, G. Bisi, R. Bonini, A. Bradley, L. Brudin, I. Bruno, E. Busnardo, R. Casoni, A. Choudhri, C. Cittanti, R. Clauss, D.C. Costa, M. Costa, K. Dixon, M. Dziuk, N. Egelic, I. Eriksson, G. Fagioli, D.B. de Faria, L. Florimonte, A. Francini, M. French, E. Gallagher, I. Garai, O. Geatti, D. Genovesi, L. Gianolli, A. Gimelli, E. del Giudice, S. Halliwell, M.J. Hansson, C. Harrison, F. Homans, F. Horton, D. Jędrzejuk, J. Jogi, A. Johansen, H. Johansson, M. Kalnina, M. Kaminek, A. Kiss, M. Kobylecka, M. Kostkiewicz, J. Kropp, R. Kullenberg, T. Lahoutte, O. Lang, Y.H. Larsson, M. Lázár, L. Leccisotti, N. Leners, O. Lindner, R.W. Lipp, A. Maenhout, L. Maffioli, C. Marcassa, B. Martins, P. Marzullo, G. Medolago, C.G. Mendiguchía, S. Mirzaei, M. Mori, B. Nardi, S. Nazarenko, K. Nikoletic, R. Oleksa, T. Parviainen, J. Patrina, R. Peace, C. Pirich, H. Piwowarska-Bilska, S. Popa, V. Prakash, V. Pubul, L. Puklavec, S. Rac, M. Ratniece, S.A. Rogan, A. Romeo, M. Rossi, D. Ruiz, N. Sabharwal, B.G. Salobir, A.I. Santos, S. Saranovic, A. Sarkozi, R.P. Schneider, R. Sciagra, S. Scotti, Z. Servini, L.R. Setti, S-Å. Starck, D. Vajauskas, J. Veselý, A. Vieni, A. Vignati, I.M. Vito, K. Weiss, D. Wild, M. Zdraveska-Kochovska.

Latin America R.N. Agüro, N. Alvarado, C.M. Barral, M. Beretta, I. Berrocal, J.F. Batista Cuellar, T-M. Cabral Chang, L.O. Cabrera Rodríguez, J. Canessa, G. Castro Mora, A.C. Claudia, G.F. Clavelo, A.F. Cruz Júnior, F.F. Faccio, K.M. Fernández, J.R. Gomez Garibo, U. Gonzalez, P. González E., M.A. Guzzo, J. Jofre, M. Kapitán, G. Kempfer, J.L. Lopez, T. Massardo V., I. Medeiros Colaco, C.T. Mesquita, M. Montecinos, S. Neubauer, L.M. Pabon, A. Puente, L.M. Rochela Vazquez, J.A. Serna Macias, A.G. Silva Pino, F.Z. Tártari Huber, A.P. Tovar, L. Vargas, C. Wiefels.

North America A. Aljizeeri, R.J. Alvarez, D. Barger, W. Beardwood, J. Behrens, L. Brann, D. Brown, H. Carr, K. Churchwell, G.A. Comingore, J. Corbett, M. Costello, F. Cruz, T. Depinet, S. Dorbala, M. Earles, F.P. Esteves, E. Etherton, R.J. Fanning Jr., J. Fornace, L. Franks, H. Gewirtz, K. Gulanchyn, C-L. Hannah, J. Hays, J. Hendrickson, J. Hester, K. Holmes, S. Jerome, A. Johnson, C. Jopek, H. Lewin, J. Lyons, C. Manley, J. Meden, S. Moore, W.H. Moore, V. Murthy, R. Nace, D. Neely, L. Nelson, O. Niedermaier, D. Rice, R. Rigs, K. Schiffer, E. Schockling, T. Schultz, T. Schumacker, B. Sheesley, A. Sheikh, B. Siegel, A.M. Slim, J. Smith, M. Szulc, N. Tanskersley, P. Tilkemeier, G.D. Valdez, R. Vrooman, D. Wawrowicz, D.E. Winchester.

Oceania A. Alcheikh, B. Allen, E. Atkins, J. Bevan, C. Bonomini, J. Christiansen, L. Clack, E. Craig, H. Dixson, I. Duncan, S. Fredericks, S. Gales, R. Hampson, T. Hanley, K. Hartcher, J. Hassall, B. Kelley, S. Kelly, T. Kidd, T. de Kort, G. Larcos, W. Macdonald, C. McGrath, E. Murdoch, S. O’Malley, M. O’Rourke, M. Pack, R. Pearce, R. Praehofer, S. Ramsay, L. Scarlett, K. Smidt, F. Souvannavong, K. Taubman, G. Taylor, K. Tse, S. Unger, J. Weale.

References

• 1.   Martiniuk ALC, Lee CMY, Lawes CMM, Ueshima H, Suh I, Lam TH, et al. Hypertension: Its prevalence and population-attributable fraction for mortality from cardiovascular disease in the Asia-Pacific region. J Hypertens 2007; 25: 73–79.
• 2.   Sasayama S. Heart disease in Asia. Circulation 2008; 118: 2669–2671.
• 3.   Ohira T, Iso H. Cardiovascular disease epidemiology in Asia. Circ J 2013; 77: 1646–1652.
• 4.   Vitola JV, Shaw LJ, Allam AH, Orellana P, Peix A, Ellmann A, et al. Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world. J Nucl Cardiol 2009; 16: 956–961.
• 5.   Bourque JM, Beller GA. Stress myocardial perfusion imaging for assessing prognosis: An update. JACC Cardiovasc Imaging 2011; 4: 1305–1319.
• 6.   Berman DS, Hachamovitch R, Shaw LJ, Friedman JD, Hayes SW, Thomson LE, et al. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: Noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease. J Nucl Med 2006; 47: 1107–1118.
• 7.   Jaarsma C, Leiner T, Bekkers SC, Crijns HJ, Wildberger JE, Nagel E, et al. Diagnostic performance of noninvasive myocardial perfusion imaging using single-photon emission computed tomography, cardiac magnetic resonance, and positron emission tomography imaging for the detection of obstructive coronary artery disease: A meta-analysis. J Am Coll Cardiol 2012; 59: 1719–1728.
• 8.   Einstein AJ, Moser KW, Thompson RC, Cerqueira MD, Henzlova MJ. Radiation dose to patients from cardiac diagnostic imaging. Circulation 2007; 116: 1290–1305.
• 9.   National Council on Radiation Protection and Measurements. NCRP Report No. 160, Ionizing Radiation Exposure of the Population of the United States. Bethesda, MD: National Council on Radiation Protection and Measurements, 2009.
• 10.   Fazel R, Krumholz HM, Wang Y, Ross JS, Chen J, Ting HH, et al. Exposure to low-dose ionizing radiation from medical imaging procedures. N Engl J Med 2009; 361: 849–857.
• 11.   Einstein AJ, Weiner SD, Bernheim A, Kulon M, Bokhari S, Johnson LL, et al. Multiple testing, cumulative radiation dose, and clinical indications in patients undergoing myocardial perfusion imaging. JAMA 2010; 304: 2137–2144.
• 12.   Garcia EV, Faber TL, Esteves FP. Cardiac dedicated ultrafast SPECT cameras: New designs and clinical implications. J Nucl Med 2011; 52: 210–217.
• 13.   Slomka PJ, Berman DS, Germano G. New cardiac cameras: Single-photon emission CT and PET. Semin Nucl Med 2014; 44: 232–251.
• 14.   Davidsson A, Olsson E, Engvall J, Gustafsson A. Influence of reconstruction algorithms on image quality in SPECT myocardial perfusion imaging. Clin Physiol Funct Imaging, doi:10.1111/cpf.12354.
• 15.   Miao TL, Kansal V, Glenn Wells R, Ali I, Ruddy TD, Chow BJ. Adopting new gamma cameras and reconstruction algorithms: Do we need to re-establish normal reference values? J Nucl Cardiol 2016; 23: 807–817.
• 16.   Cerqueira MD, Allman KC, Ficaro EP, Hansen CL, Nichols KJ, Thompson RC, et al. Recommendations for reducing radiation exposure in myocardial perfusion imaging. J Nucl Cardiol 2010; 17: 709–718.
• 17.   Dondi M, Kashyap R, Paez D, Pascual T, Zaknun J, Bastos FM, et al. Trends in nuclear medicine in developing countries. J Nucl Med 2011; 52(Suppl 2): 16S–23S.
• 18.   Dondi M, Andreo P. Developing nuclear medicine in developing countries: IAEA’s possible mission. Eur J Nucl Med Mol Imaging 2006; 33: 514–515.
• 19.   Casas-Zamora JA, Kashyap R. The IAEA technical cooperation programme and nuclear medicine in the developing world: Objectives, trends, and contributions. Semin Nucl Med 2013; 43: 172–180.
• 20.   International Atomic Energy Agency. Nuclear Medicine Database. https://nucleus.iaea.org/Pages/nuclear-medicine-db.aspx (accessed January 24, 2016).
• 21.   The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103. Ann ICRP 2007; 37: 1–332.
• 22.   Cousins C, Miller DL, Bernardi G, Rehani MM, Schofield P, Vano E, et al. Radiological protection in cardiology: ICRP Publication 120. Ann ICRP 2013; 42: 1–125.
• 23.   International Atomic Energy Agency. Nuclear Cardiology: Guidance and Recommendations for Implementation in Developing Countries. IAEA Human Health Series No. 23. Vienna: International Atomic Energy Agency, 2012.
• 24.   Hesse B, Tagil K, Cuocolo A, Anagnostopoulos C, Bardies M, Bax J, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology. Eur J Nucl Med Mol Imaging 2005; 32: 855–897.
• 25.   Verberne HJ, Acampa W, Anagnostopoulos C, Ballinger J, Bengel F, De Bondt P, et al. EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT: 2015 revision. Eur J Nucl Med Mol Imaging 2015; 42: 1929–1940.
• 26.   Henzlova MJ, Cerqueira MD, Mahmarian JJ, Yao SS. Stress protocols and tracers. J Nucl Cardiol 2006; 13: e80–e90.
• 27.   Henzlova MJ, Duvall WL, Einstein AJ, Travin MI, Verberne HJ. ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. J Nucl Cardiol 2016; 23: 606–639.
• 28.   Lindner O, Pascual TN, Mercuri M, Acampa W, Burchert W, Flotats A, et al. Nuclear cardiology practice and associated radiation doses in Europe: Results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries. Eur J Nucl Med Mol Imaging 2016; 43: 718–728.
• 29.   Einstein AJ, Pascual TN, Mercuri M, Karthikeyan G, Vitola JV, Mahmarian JJ, et al. Current worldwide nuclear cardiology practices and radiation exposure: Results from the 65 country IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS). Eur Heart J 2015; 36: 1689–1696.
• 30.   United Nations Department of Economic and Social Affairs. Composition of macro geographical (continental) regions, geographical sub-regions, and selected economic and other groupings. http://millenniumindicators.un.org/unsd/methods/m49/m49regin.htm#asia (accessed July 4, 2016).
• 31.   Vitola JV, Mut F, Alexánderson E, Pascual TN, Mercuri M, Karthikeyan G, et al. Opportunities for improvement on current nuclear cardiology practices and radiation exposure in Latin America: Findings from the 65-country IAEA Nuclear Cardiology Protocols cross-sectional Study (INCAPS). J Nucl Cardiol, doi:10.1007/s12350-016-0433-3.
• 32.   Mercuri M, Pascual TNB, Mahmarian JJ, Shaw LJ, Rehani MM, Paez D, et al. Comparison of radiation doses and best-practice use for myocardial perfusion imaging in US and non-US laboratories: Findings from the IAEA (International Atomic Energy Agency) Nuclear Cardiology Protocols Study. JAMA Int Med 2016; 176: 266–269.
• 33.   Bouyoucef SE, Mercuri M, Pascual TNB, Allam AH, Vangu M, Vitola JV, et al. Nuclear cardiology practices and radiation exposure in Africa: Results from the IAEA Nuclear Cardiology Protocols Study (INCAPS). Cardiovasc J Africa 2017 (in press).
• 34.   Biswas S, Better N, Pascual TN, Mercuri M, Vitola JV, Karthikeyan G, et al. Nuclear cardiology practices and radiation exposure in the Oceania region: Results from the IAEA Nuclear Cardiology Protocols Study (INCAPS). Heart Lung Circ 2017; 26: 25–34.
• 35.   European Union. Council Directive 2013/59/Euratom of 5 December 2013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives 89/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom. Official Journal of the European Union 2014; 57: 1–73.
• 36.   Mercuri M, Pascual TNB, Mahmarian JJ, Shaw LJ, Dondi M, Paez D, et al. Estimating the reduction in the radiation burden from nuclear cardiology through use of stress-only imaging in the United States and worldwide. JAMA Int Med 2016; 176: 269–273.