5.3.1 Comparing the volume results to other methods and studies
For the 19 participants included in this study, it has been found that the mean volume for placentas with a gestational age of 25-27 weeks was 464.45 ± 92.25 cm3. Since placenta volume varies throughout gestational age, the study has only been compared to other studies with the same gestational age available. Therefore, there is only one US and MRI study used for comparison. Volume data from an US study showed that the placental volume’s 90th percentile was between 361.0 and 398.7 cm3, and that the 50th percentile was between 243.1 to 267.7 cm3, at gestational weeks 25-27 (29). A limitation of the US study was that volumes were only available in percentiles, so it has only been possible to compare percentiles. This study’s 90th and 50th percentiles were 630.86 cm3 and
445.36 cm3 respectively, which is a lot higher. In an earlier study, MRI measurements showed that placental volume at gestational age 25-27 was 460.8 ± 89.3 cm3 (31). The same study observed that US significantly underestimated placental volume after the first trimester. The mean and standard deviation of the MRI measurements in that earlier study are very close to those in this study, and both studies observed that US
measurements were significantly lower. Given this good alignment with the earlier MRI study, it seems reasonable to conclude that the volume findings of this study are valid despite the small sample size.
In this study placenta location was split into three locations anterior, posterior, or both anterior and posterior placement, in order to describe distribution. Their means were respectively 476.42 cm3, 459.63 cm3 and 434.2 cm3. Furthermore, the number of
placentas in each location category were ten (52.6%) anteriorly, six (31.6%) posteriorly and three (15.8%) anteriorly and posteriorly placed. Placenta location categories varied between studies. One study divided placenta location into anterior, posterior and fundal.
Fundal is placentas placed at the top of the uterus (and therefore stretch from anterior to posterior). Of the three anteriorly and posteriorly placed placentas included in this study, one of them was lower-lying and more laterally placed in the uterus, and can therefore not be considered fundal. So comparison between this study’s anterior and posterior category and the other study’s fundal category was therefore limited. However, the anterior and posterior placentas could be compared. The same study found anterior location in 28%, posterior in 26% and fundal in 46% of the women (65). This differs from results found in this study, which show that more placentas are placed anterior and posterior than fundal. Placental volumes were not mentioned, and can therefore not be compared. Another study had four categories, and they found anterior location in 44.8%, posterior in 35.7%, fundal in 12.3% and lateral in 7.1% of women (29). This is in better agreement with the findings of this study. However, the comparison cannot be
completely trusted since there is no lateral or fundal category in this study. Again, no data was provided about volumes based on placental location. The sample size in this study was small, with few placentas in each category, which can indicate that the results for each placenta location do not necessarily represent the population. Also, the studies used for comparison were not in agreement with each other, neither in regards to use of categories nor percentages of placentas in each category. Furthermore, none of the
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studies used for comparison had volume measurements. It can therefore not be concluded whether the findings of this study are in agreement with other studies, or whether they are a good representation of placental location distribution. Furthermore, comparison between studies is complicated since volume varies throughout pregnancy, which makes it is necessary to have the same gestational age available for comparison.
5.3.2 Comparing the IVIM results to other methods and studies
D for this study was 277.46 ± 36.23×10-5 mm2/s at gestational week 25-27, which is higher than D found in other studies (19, 24). There were two articles that were relevant for comparison. They found that D was 157 ± 3×10-5 mm2/s at gestational age 20-40 (19) and 176×10-5 mm2/s at gestational week 18-40 (24). Articles report conflicting results in whether D is correlated with gestational age or not. One study reports that there is no correlation (19), while another says there is a negative correlation between gestational age and D (24). To avoid differences in gestational age affecting comparison between studies, this study has only compared results of D with studies that include gestational weeks 25-27. However, the other studies have a wider gestational age span, which could influence their mean D. This could be part of the reason why this study’s D is higher. Furthermore, D has been shown to be the most repeatable IVIM parameter, and has been shown to be twice as reproducible as f and D*, which is thought to be due to several and high b-values often being used when estimating the mono-exponential component (17). Higher b-values were however not part of this study, which could also have influenced the results for D, and possibly explain why they were higher.
This study’s pseudodiffusion coefficient D* was 739.54 ± 211.15×10-5 mm2/s at
gestational week 25-27, which is lower than other studies (19, 20, 24). The other studies found D* to be 3170 ± 310×10-5 mm2/s at gestational week 20-40 (19),
3680×10-5 mm2/s at gestational week 18-40 (24), and 9217×10-5 mm2/s at week 24-38 (20). It is possible to see that two of the studies are in close agreements with each other, while the last has a substantially higher D*. Unlike D, studies are in agreement that D* is not correlated with gestational age (19, 24), and therefore variations in gestational age should not affect comparisons of results from studies with other gestational ages. Despite this, it is possible to see that D* varies greatly between studies, both this one and others. This coincides with findings that state that the
variability of D* was shown to be high. From this study’s results it is also possible to see that D* varied greatly: the lowest mean was 495.69 and the highest was 1398.31.
Furthermore, the D* standard deviation was a lot higher than D’s, which could also reflect the variability. It has been theorized that D* should be sensitive to movement of blood within placental villi and intervillous spaces, and therefore could potentially act as a pathology marker. However, a study found this not to be the case, because the
variability makes it hard to use for discriminating between healthy and pathologic placentas (19). The variability of D* may influence why there are variations between study results. In addition, perhaps the lower number of b-values used may have been part of the reason.
IVIM parameters f and (1-f) are related, since they are opposite fractions, and one is calculated from the other. This is probably the reason that few studies state their findings for (1-f). Following this practice, f and (1-f) will be discussed together, with the main focus on f. In this study the mean perfusion fraction f was 14.2 ± 2.7%, which is lower than f found in other studies (12, 17, 19). This study found the mean diffusion of the extravascular space fraction (1-f) to be 88.4 ± 2.8%. Since f in this study appears to be
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lower than others, it could indicate that (1-f) was overestimated in the same way. Other studies found f to vary between 26% and 36% during pregnancy (12), and 26.2% at week 20 and 18.8% at week 40 (19). A different study from 21 to 36 weeks showed that f was 28 ± 10.5% at the central part of the placenta, and that there was a tendency towards higher perfusion near the basal layer (17). Unlike D*, f is correlated with
gestational age and its value decreases with gestational age (12, 19). Since f varies with gestational age, it complicates comparison to other studies, because it is dependent on the studies gestational ages overlapping. Taking into consideration that f of this study is measured relatively early, it further emphasizes that this study’s f is lower than others.
Furthermore, the lowest mean value for a placenta in this study was 9.8% and the highest was 19.7%, which also confirms that the results of this study are lower than the others. Only the 95th (35.0%) and 75th (19.4%) percentiles fall within the range of the other studies. A reason as to why the perfusion fraction was lower in this study could be patient positioning. An ASL study examined whether lateral or supine positioning during placental/fetal MRI influenced placental perfusion. It demonstrated a significant
difference between the two patient positions, where lateral positioning had a perfusion of 207 ± 39 ml/100g/min and supine had 171 ± 32 ml/100g/min. The lower perfusion in supine positioning was likely disturbed by the weight of the pregnant uterus. The
perfusion was more stable in the lateral position during advanced gestational age, while it was progressively decreased in the supine position, likely due to the increased weight of the uterus (55). In this study all patients were positioned supine, which could have affected the measurements. The first study, with f between 26 and 36%, does not specify the patient position as it is based on several studies (12), while the study with f between 18.8 and 26.2%, had lateral patient positioning (19). This being said, it should be noted that comparisons between ASL and IVIM should be made with caution, because ASL only reflects blood that has been labelled outside the voxels of interest, while IVIM reflects all randomly flowing blood within each voxel (38). Perhaps future studies and examinations with IVIM of the placenta should use the lateral position as a standard, to avoid this potential problem.
The chosen cut-off threshold could possibly explain why all IVIM parameters differed from other studies. When using a too high threshold D and D* values become lower, and f values become higher, and vice versa (64). Going under the assumption that this study has chosen the wrong threshold compared to other studies it has been compared to, it could indicate that a too low threshold was used, because this study’s results showed D to be higher, and D* and f to be lower. In theory D* should also be higher, but that deviation might be due to D* variability. On the other hand, if this study’s threshold was correct, it could indicate that other studies’ thresholds were too high. Unfortunately, none of the studies used for comparisons have stated their cut-off threshold, so it cannot be determined whether a too high or low threshold was used or not. It seems likely that the cut-off threshold could be a main reason for results differing between studies. This can however not be shown due to lack of data from other studies. Assuming that the cut-off value was the problem, differences between results would be explained and could easily be remedied using an optimal cut-off threshold.
The IVIM results from this study differed compared to other studies. D and (1-f) appeared higher, while D* and f appeared lower. Since f of this study was lower than other studies, it is not unexpected that D* could be influenced by this and also be lower, since both f and D* are related to perfusion. f reflects the percentage of a voxel occupied by capillaries, while D* reflects the movement of blood within the intervillous space and in the fetal capillaries within the villi. Likewise, D of this study was higher, and perhaps it
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can be expected that (1-f) would also be higher. This is because both D and (1-f) are linked to diffusion, not to mention that f and (1-f) are opposite fractions. The amount of diffusion present in the placenta can be reflected by D, while (1-f) reflects the percentage of a voxel occupied by diffusion in the extravascular space. Additionally, it is visualized that f and (1-f) are opposite fractions of each other, in Figure 21 the f histogram is heavily weighted at the low end of the scale, while (1-f) is weighted at the top end.
Furthermore, D* is higher than D as expected, which is in agreement with previous research and literature (13, 19): perfusion is higher than diffusion. This is also consistent with the placenta being a highly perfused organ. In previous research the most promising IVIM parameters for use in pathology differentiation appeared to be D and f (12), while D* was less promising. Results from this study are partly in agreement with this, since D and f deviate less from other studies than D* does. Furthermore, D* has a larger
standard deviation than the other IVIM parameters, and has been shown to have a higher variability (19).
It may seem surprising that the percentages of f and (1-f) add up to 102.6% rather than 100% when (1-f) is calculated directly from f. This is likely because the numbers are calculated as the mean of a set of 19 means (one for each placenta), and there are small rounding errors in the calculation of each of the means. The rounding errors grow when added in calculating the overall mean. Furthermore, it is possible to see that D has a smaller standard deviation than D*, and that f and (1-f) have similar standard
deviations. The standard deviation of f and (1-f) should be the same, but the difference is likely due to the same rounding errors. These findings coincide with the lowest and highest means, showing that D, f and (1-f) have a smaller range than D*.
5.3.3 Comparing correlation results to other studies
This study found no correlation between volume and IVIM measurements using the Pearson test. This is in line with expectations. Only one previous study was found to compare results with, and it only checked if volume correlated with f and D (66). The study found no correlations between volume and the two IVIM parameters. A search was conducted to try to identify other studies that have checked correlation between
placental volume and IVIM measurements, but none were found. It is unknown if a larger sample size would affect these findings. The fact that the data did not show perfect homoscedasticity could possibly affect the results of the test.