Whether scintigraphy or CTA should be the preferred imaging technique remains a controversially debated topic. Already the PIOPED I trial showed that more than 60% of V/Q imaging is non-diagnostic and additional diagnostic studies might be pursued, as the probability of PE is still considerable. This may result in delay and more radiation exposure, which is not desirable in pregnancy [
31,
42]. However, a substantial reduction in the proportion of non-diagnostic scintigraphy studies has been achieved since PIOPED [
43,
44]. In a recent publication, lung scintigraphy had a lower diagnostic inadequacy rate than CTA in pregnant patients [
45], probably due to a transient interruption of contrast material by unopacified blood from the inferior vena cava in the CTA studies. Still, today, the standard assumption in radiological practice remains that work-up of suspected LE in pregnant women should be performed by scintigraphy because of the lower quantity of radiation administered to the fetus.
International recommendations
In the literature, even international recommendations remain unclear as to whether to use scintigraphy or CTA for pregnant patients.
Several national and international societies, such as the Fleischner Society or the PIOPED II investigators, recommend D-dimer assessment and the use of ultrasound instead of CT or scintigraphy as the first-line imaging test for the evaluation of pregnant patients [
20,
46,
47]. According to the guidelines of the German Society of Radiology, CT is the preferred technique because of the lower radiation dose to the uterus, but clinical risk assessment and combined D-dimer testing is recommended before imaging strategies are attempted [
46].
If imaging with ionising radiation is necessary, both CT angiography and ventilation-perfusion lung imaging can provide useful information; however, CT might be the preferred technique because of exposure of the conceptus to lower doses [
48].
The British Thoracic Society guidelines give no specific recommendations for imaging pregnant patients for suspected PE, but declare CT to be the initial lung imaging technique in the general patient. Isotope lung imaging may be considered if several quality criteria are fulfilled [
47].
In a statement by the Fleischner Society, strategies for pregnant patients were briefly discussed, but with no direct recommendations being given [
20]. However, even among the PIOPED II investigators the discussion remained controversial. Most of the PIOPED II investigators recommended D-dimer assessment and ultrasound before perfusion scintigraphy for suspected pulmonary embolisms in pregnant patients [
15,
48].
Fetal radiation dose
Many methods for the estimation of fetal dose in pregnant patients undergoing CT examinations assumed early term pregnancy in a single-size patient model with an average, uniform maternal anatomy. These dose estimates did not take into account maternal anatomy variances, natural variations, such as fetal presentation, and gestational age. Differences in these attributes can cause failures in estimation of fetal dose of up to 100% at radiological examinations [
49,
50]. The fetal dose will increase during pregnancy both as the fetus grows in size and as it moves closer to the imaging volume [
23].
In the first trimester of pregnancy, the absorbed dose to the uterus may be used as a substitute for the absorbed dose to the embryo. Similarly, the absorbed dose to the fetus from radioactive substances without placental transfer is expected to be within the same range as the dose to the uterus. In the case of radioactive substances with placental transfer, the absorbed dose to organs and tissues of the mother may, as a first approximation, be taken as representative of the absorbed dose to the corresponding organs and tissues of the fetus [
51].
In CTA, the fetus is only exposed to scatter radiation assuming appropriate planning of the examination. Inadvertent irradiation of a fetus most frequently occurs during the early post-conception period, when the woman is unaware of her pregnancy. In early pregnancy, the distance from the directly irradiated region at the base of the lung to the location of the embryo is generally at least 20 cm, where the scattered radiation level would be no more than 1% of the chest dose [
25].
The risks of causing a range of different radiation effects depend on the gestational age [
52]. In fact, in the pre-implantation embryo, there is no measurable risk of malformation regardless of the amount of radiation exposure, and the greatest concern is death of the embryo.
Within the first 2 weeks of embryonic age, there is a 2% risk of the blastocyst failing to implant, causing death of the embryo when the irradiation dose is greater than 0.1 Gy. If the embryo survives there is likely to be no increased risk [
53,
54].
During the first two trimesters the fetus is most susceptible to deterministic teratogenic effects, but it is assumed that the fetus is not at risk if the irradiation dose does not exceed a threshold dose [
55]. None of the studies analysed explicitly reported fetal doses when applying dose reduction measures such as lead shielding or automatic exposure control (AEC), only relative changes in percentage. Therefore, the absolute fetal dose using recent imaging technology including dose reduction strategies must be estimated to be lower than those reported.
Meeting the threshold for inducing deterministic effects as malformations or reduction in intelligence is not likely with the expected doses in CT or in V/P imaging either; thus, the most important consideration is induction of childhood cancer. As in all examinations in radiology, there is always a stochastic risk of carcinogenesis, and also in the fetus after in utero irradiation, regardless of the dose. Despite the fact that fetal radiation dose for both CTA and scintigraphy examinations in suspected pregnancy-related PE must be seen to be very low, further reduction must be aimed at during pregnancy. The risks of low-level radiation are difficult to quantify and the risk of malignancy is known to be increased in persons that have been exposed to radiation in utero [
56]. However, many effects of radiation-induced childhood cancer still remain controversial [
57].
The fetal doses in CTA reported in the literature are well below the 100-mGy threshold reported to be relevant for deterministic effects [
29]. The fetal dose of 50 mGy is considered as the limit below which there is no harm from deterministic effects and the risk of stochastic effects is <1% [
58]. There is no evidence that the pattern of cancer induction varies with gestational age and the risk is likely to be constant over the entire pregnancy [
59]. The number of excess malignancy cases up to the age of 15 years following irradiation in utero is considered to be 1 in 16,000 per mSv [
59]. This equates to an additional risk of malignancy of 1 in 560,000 following half-dose perfusion scintigraphy and 1 in 1,000,000 after CT pulmonary angiography [
28]. Other publications report the excess risk of the induction of childhood cancer to be 1 in 33,000 per mGy [
52]. In addition, the excess relative risk of developing childhood cancer has been estimated to be approximately 0.28 at 1.0 mGy in the first trimester, 0.03 at 1.0 mGy in the third trimester, and overall 0.037 at 1.0 mGy during pregnancy [
59]. A recent paper reports the probability of giving birth to a healthy baby decreases by only 0.5% even when performing routine dose level biphasic CT of the abdomen [
60]. The fetal dose level for chest CT is far beyond these estimated dose values [
60]. Fetal threshold doses and risks in different gestational periods have been outlined extensively [
61].
The natural background radiation dose to the fetus during pregnancy is approximately 1 mGy [
57]. By comparison, exposure of at least 100 mGy is necessary before pregnancy termination is considered [
42].
In chest CT, the fetal doses reported for specified trimesters range between 0.003 and 0.47 mGy in the first trimester [
21,
23,
24,
26]. Two studies determined fetal dose measurements in the second trimester of pregnancy to be 0.0079–0.66 mGy [
21,
23]. A variance of a factor of about 80 could be observed. For the third trimester, a wide variety of fetal doses was reported, such as 0.051–1.2 mGy, differing by a factor of nearly 30 [
22,
23,
27].
Similarly the high fetal doses reported by Hurwitz et al. [
21] must be reviewed critically. These were the only authors using a tube current of 140 kV, together with a high tube current product of 380 mAs for the imaging of pregnant patients. Therefore, we attribute the high reported fetal dose of 0.24–0.66 mGy in the first trimester to the selection of technical parameters for both tube current and tube voltage, which were above recent recommendations.
Conversely, Winer-Muram et al. [
23] calculated very low fetal doses. Fetal and uterus dimensions were precisely measured in 23 pregnant women, who formed the basis for the dose calculations. The imaging parameters used were reasonable (120 kV, 100 mAs, pitch 1), but the imaging distance was described as 11 cm from just inferior to the xiphoid process to the aortic arch. We do not estimate this image length to be sufficient to rule out maternal PE properly. Using commercial dosimetry tools [
62], the image length to cover the whole lungs is around 24 cm. Even reducing the basal image length, as has been proposed in the literature, results in an image length of 19 cm [
22]. The amount of fetal radiation in the calculations might not reflect the scatter radiation in routine chest CT examinations for suspected PE. Therefore, we think that the fetal doses reported from Winer-Muram and co-workers cannot be associated with an image length covering the whole lungs.
The fetal doses reported for perfusion scintigraphy are all very consistent for all trimesters [
21,
24,
28,
29,
38]. Reducing administered activity of
99mTc-MAA to 25% equally reduces the fetal dose calculated. Therefore, possible dose reduction can be performed easily and straightforwardly. However, a minimum of 60,000 particles is required [
34]; thus, there are clearly limits in further fetal dose reduction.
Exclusion of the CTA data discussed above leaves us with only the data published by Nijkeuter et al. [
24] and, therefore, CTA mean fetal doses of 0.013 mGy in the first trimester using recent multislice technology. For the second trimester no data remain to be discussed. However, as fetal size increases, the dose must be assumed to be somewhere between the first and third trimester data. In the third trimester at least two studies remain to give an average fetal dose of 0.06–0.14 mGy [
22,
26]. These data are consistent with the average doses reported for the whole pregnancy, which range between 0.01 and 0.06 mGy [
28‐
30].
Taking into account recent recommendations to perform perfusion scintigraphy with “half dose” activity, perfusion scintigraphy resulted in mean fetal doses of 0.177 mGy (SD 0.095) for all trimesters based on the data analysed [
24,
28].
Ventilation imaging can and should be avoided in pregnant women if perfusion imaging is within normal limits. The fetal radiation dose strongly depends on the substances used for inhalation. Noble gases such as 81mKr and 133Xe should be preferred over 99mTc-aerosols.
There is a reported overall excess relative risk of childhood cancer of 0.037 at 1 mGy of fetal radiation during pregnancy [
59]. In the mother, a risk of radiation-induced breast cancer of 0.005% for 1 mSv of radiation is reported [
42]. This reflects an absorbed solitary dose of 8.3 mGy calculated with the new tissue weighting factors for breasts that have been raised from 0.05 to 0.12 [
63]. These calculations were performed using a recent imaging protocol to detect suspected PE using a 16-row system and commercial dosimetry software [
62,
64]. For the CT protocol applied by Nijkeuter et al. [
59] we calculated a breast dose of 11 mGy or 1.32 mSv respectively, associated with a 0.017 mGy fetal dose in the first trimester. Therefore the maternal breast cancer risk was 0.0066 and the fetal excess risk of childhood cancer around 0.000476 in early pregnancy using the numbers of the ICRP. Based on the numbers by Doshi et al. [
22], we calculated for the same image length and late pregnancy a breast dose of 10 mGy or 1.2 mSv respectively, associated with 0.1 mGy fetal dose. Therefore, the maternal breast cancer risk was 0.006 and the fetal excess risk of childhood cancer was around 0.003.
Based on the data analysed for perfusion-only scintigraphy the absorbed breast dose is around 0.044 mSv for low-dose perfusion scintigraphy (74 MBq) and 0.12 mSv for normal dose scintigraphy (200 MBq). This leads to a maternal breast cancer risk of 0.0002–0.0006 (74–200 MBq). For early/late pregnancy a fetal dose of 0.11–0.6 mGy (74–200 MBq 99mTc-MAA)/0.8 mGy (200 MBq 99mTc-MAA) could be observed. This results in a fetal excess risk of childhood cancer of around 0.0031–0.17 (74–200 MBq 99mTc-MAA) in early and 0.024 (200 MBq 99mTc-MAA) in late pregnancy.
Maternal breast tissue
Although still debated controversially, radiation dose to the breast tissue seems to be of critical importance, especially in girls and young women. Just recently, tissue weighting factors for breast tissue have more than doubled, taking into account recent research implying possible elevated radiosensitivity [
63]. However, CT radiation risks for breast tissue still remain unclear [
77].
In the case of chest CT, it is clear that the maternal organ at greatest risk is the female breast. In particular, the proliferating breast tissue in pregnancy seems likely to be at increased risk. Breast doses have been estimated to be 20–60 mGy for a CT examination performed for pulmonary embolism [
78‐
80]. For these breast doses reported, the authors used technical parameters that should not be applied in pregnancy, such as tube voltage of 140 kV [
79,
80] and a tube current product of a maximum of 304 mAs [
80]. Applying a reasonable tube voltage of 120 kV results in breast doses of a maximum of 26 mGy based on the technical parameters reported.
Conversely, injection of
99mTc-MAA results in an absorbed maternal breast dose of 0.005 mGy/MBq per unit of activity administered [
81]. Dose-reduced perfusion imaging therefore results in an absorbed breast dose of 0.2–0.37 mGy, assuming administered activity of 40–74 MBq. Normal dose perfusion imaging with 200 MBq
99mTc-MAA accounts for 1 mGy of breast radiation.
For breast cancer, an associated risk of 0.005% has been reported for 1 mSv of radiation exposure. Considering the baseline risk that approximately 23% of the population will develop cancer at some point in their lives, the increased risk due to CT is very small [
42]. Also, some authors try to push the discussion back to reason and point out that many clinicians underestimate the risk of radiation, but equally others massively overestimate the risk [
82].
Breast bismuth shields have been evaluated in the literature to reduce the dose to the female/maternal breast and are reported to be an effective measure [
60,
83]. However, their radiological value still seems to be controversial, as other authors do not recommend the use of breast shielding because of the impact on image noise. If an increase in image noise is accepted, reduction of the tube current is proposed as an easier and more efficient dose reduction strategy [
84]. Recent articles also promote the use of AEC for significant breast dose reduction [
85].
Value of SPECT scintigraphy
Single photon emission computed tomography (SPECT) further increases the diagnostic accuracy of the scintigraphy images using two main methods [
32]. One method sums projections over a limited angular range, while another uses reconstructed SPECT data projected through an attenuation map to generate count-rich reprojected planar images [
93]. Bajc et al. [
94] identified 53% more mismatched regions with SPECT. In a study by Collart et al. [
95], V/P
SPECT increased the specificity for PE from 78% to 96% at similar sensitivities to CT. Reinartz et al. [
96] found a sensitivity and specificity of 0.76 and 0.85, respectively, with V/P
PLANAR compared with 0.97 and 0.91 with V/P
SPECT.
In summary, CTA for PE has the advantage that the fetus is not directly exposed, but only to scatter radiation. The estimated radiation exposure is low for CT when the fetus is outside the field of view.
In perfusion scintigraphy, the need for intravenous injection of the radionuclide tracer will lead to perfusion-dependent and bladder-reservoir-related direct fetal exposure. In particular, in the first trimester fetal exposure with CTA is therefore lower than exposure with perfusion scintigraphy, even if a half-dose scintigraphic technique is used [
24,
28].
For chest CT, most of the studies cited reported mean fetal dose estimates to be lower by a factor of 10 than the comparable dose-reduced perfusion scintigraphy protocols. These estimates did not take into account the different dose reduction measures possible in CTA. Thus, fetal dose must be estimated as being substantially lower for chest CT than for the scintigraphy pathway.
Based on the data analysed, there is an increased risk of childhood cancer induction in early pregnancy when using perfusion scintigraphy of a factor of about 7; even in late pregnancy the risk is still increased by a factor of about 8 compared with the estimated risk calculated for CTA.
The maternal breast cancer risk was calculated to be increased about tenfold in CTA compared with perfusion scintigraphy over the whole pregnancy.
These risk estimates are applied for normal dose perfusion scintigraphy and CTA without dose reduction measures.
With CTA, dose reduction measures such as abdominal lead shielding, reduced tube current, AEC, reduced tube voltage and reduced image length the maternal and especially the fetal dose can be expected to be further reduced substantially.
In perfusion scintigraphy, dose reduction is directly related to the activity administered. However, the breast dose reduction that can be estimated by reducing the activity administered in perfusion scintigraphy seems to be far more than can be expected from CT dose reduction measures.