To evaluate the volume data’s reliability, the radiographer’s measurements were compared to a radiologist’s, which resulted in means of 464.45 cm3 and 494.16 cm3, respectively. The radiographer’s mean volume was smaller than the radiologist’s, which
5 Discussion
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could indicate that the radiographer’s measurements were slightly underestimated. This can also be visualized in Figure 16. In such a diagram, a “perfect” alignment between the two sets of measurements would mean the all the dots would lie on a diagonal line drawn from the bottom-left to the top-right of the figure. We can see that most of the dots are fairly close to the diagonal, and that most of the discrepancies are towards the bottom-right; this indicates generally good alignment, but with a possible tendency to
underestimation. Despite this, the ICC of this study shows a correlation of 0.956 which indicates excellent reliability. However, the 95% confidence interval for the average measures was 0.667 to 0.988. Therefore the true reliability can be regarded as moderate to excellent (63). The 2-way random effects model was chosen over a 2-way mixed model for the ICC test, since the mixed model is typically used for test/retest and intra-reliability, while this test was for inter-reliability. Furthermore, absolute agreement was chosen over consistency in the test, because it was deemed more important that radiologist’s and radiographer’s measurements were equal to each other.
Perhaps more training with the radiologist could have led to the ICC confidence interval being smaller. Another aspect that could have influenced the results is that self-training was done on placentas from a later gestational age (34-36 weeks), when the placenta is more well developed (6). Since only a few hours of training with the radiologist and physicist led to good ICC results, this can furthermore indicate that the equipment was easy to use and learn.
Since the segmentation of the volume images was in good agreement with the radiologist’s, it is likely that also IVIM segmentation is of similar quality, because the same technique and training was used for both. If the volume measurements were underestimated, the same might apply to IVIM data. It is however unknown if this is the case, since the radiographer was the only one that performed IVIM measurements. A large number of voxels were used for the IVIM measurements of each placenta, which should be sufficient in describing distributional values. Furthermore, the data was checked for optimal cut-off value, and intensity curves were evaluated.
The included bFFE and DWI images were of good quality without artefacts, which was a good foundation for ROI placement and measurements. Several of the participant’s images were too degraded by artefacts (motion, distortion, zebra stripes and
susceptibility) to use them for data collection, and were therefore excluded. The DWI images were more often prone to artefacts than the bFFE images, and were the main reason for excluding participants. The avoidance of degraded images should also help ensure optimal data quality. Both the bFFE and SE EPI (DWI) sequence have a rapid acquisition time and result in fewer motion related artefacts compared to other sequences (5, 33). Short acquisition times combined with few and short breath holds helped combat problems related to image quality. Additionally, the images were checked for pathology prior to inclusion, but the participant’s hospital records were not accessed to confirm the absence of pathology. So there is a possibility that pathology might be present anyway and can affect results of both volume and IVIM.
Another part of checking image quality was to check for large jumps and uneven transitions from one slice to the next. Since all MRI images were acquired with several breath holds per sequence, there is always a chance of leaving a gap or overlapping between breath holds, due to the participants not holding their breath identically each time. This can in turn lead to over- or underestimation of placental volume. However, since the images were acquired in the sagittal plane, it was easy to spot placental movement from the previous slice, and overlapping is less likely from left to right
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compared to head to feet (transverse images) due to diaphragm movement. It would have been possible to acquire all slices in one breath hold, but this would influence the image quality negatively. Several breath holds are therefore seen as beneficial for this study, both in regard to patient comfort and to image quality.
From the above we can conclude that the radiographer’s volume and IVIM measurements can be considered reliable, and that it is safe to use them in further analysis and
discussion.
5.2.1 IVIM specific fators that can influence data quality and results
In this sub-section the focus is on factors that could influence all IVIM measurements in general. One such factor could be the small sample size, leading to an uneven
distribution. Another factor to take into consideration is that IVIM measurements can vary between scanners. It has been demonstrated that there is a larger inter-scanner variability than intra-scanner variability, which means that studies performed on different scanners must be carefully interpreted (17). IVIM quality is dependent on sequence parameters, scanner field strengths and the mathematical models used. Also, repeatability depends greatly on data quality, image post-processing, and fetal and maternal movement. From this it appears that using IVIM in a diagnostic setting can be challenging. Despite this, the placenta should be relatively well suited for MRI perfusion sensitive imaging, because the placenta is large, has a relatively fixed position and is well perfused. About 50% of the placental volume is placental blood (20).
5.2.1.1 IVIM and intensity curves
Another aspect which can influence the IVIM measurements is that some of the placental slices’ intensity curves deviated slightly from the expected bi-exponential appearance.
The deviation might have influenced the measurements more than first thought.
Intensity curves for each placental slice were generated to evaluate the quality of the IVIM measurements, in order to see if they had a bi-exponential appearance. Some placental slices showed disturbances on the intensity curves of the line charts, see Figure 12. Fitting the IVIM parameters is sensitive to motion artefacts, field inhomogeneity and magnetic susceptibility artefacts (22), which could have caused the disturbances.
However, when looking at the intensity curves generated for the placenta as a whole, rather than its slices, the curves follow the expected development, see Figure 13.
Additionally, image quality was checked prior to inclusion, and should be of adequate quality. Despite this, the deviant curves may have influenced the IVIM parameters that were collected, and affected the values of D, D*, f and (1-f). The collected data should nonetheless provide a reasonable estimate of them, since intensity curves of the placenta as a whole were deemed good.
5.2.1.2 IVIM and optional slice removal
Another study removed suboptimal slices prior to analysis of IVIM data (17), which was not done in this study. This was a study of the placenta volume as a whole, and not only a section of the placenta, so it was chosen to keep all slices in order to get an idea of the placenta as a whole despite some slices being suboptimal. This can of course have
influenced the IVIM results negatively. However, placing the ROI over the entire placenta volume and not only a selected area can also be seen as an advantage. In other studies, where the ROI was placed over the entire placental volume they found correlations between f and gestational age. There is some speculation as to whether placing a ROI only over part of the placenta has led to some studies not finding the same correlation
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(19). Despite some of the placental slices being slightly degraded, the data can
nonetheless provide interesting results, because it is unlikely that this would have caused large deviations in the data.
5.2.1.3 IVIM and choice of b-values
When obtaining IVIM-data at least half of the obtained b-values should be less than 250 s/mm2 (13), and more than four b-values are needed to calculate IVIM-parameters (20). This study had b-values of 0, 5, 10, 25, 50 and 200, which means that both
requirements are fulfilled. However, other studies done on IVIM imaging of the placenta, have had more b-values, such as 11 (b 1000) (20), 10 (b 1000) (19) and 16 (b 0-900) b-values (17). In order to distinguish different diffusion properties across tissue classes, the IVIM analysis is dependent on the range and number of the acquired b-values (24). Moreover, a different study stated that using 10 b-b-values was on the low side for high quality IVIM studies. Also, it was stated that additional low b-values might add to the accuracy of acquired IVIM values in organs with high arterial perfusion (64).
This may be an indication that this study could have benefited from more b-values, and in addition including higher b-values. Having a larger number of and higher b-values might have aided in finding the optimal cut-off threshold and fitting IVIM data. The choice of b-values may therefore have affected results in this study. However, having a larger number of b-values is not without complications. Problems relating to increased scan time due to many b-values can arise, such as many breath holds and fetal and maternal movement. Optionally, the scan time can be reduced, but this could affect image quality. Furthermore, if only part of the placenta has been evaluated to compensate for time, valuable information may be missing and make comparisons between studies more difficult. It is therefore seen as an advantage that the entirety of the placenta was measured with few breath holds, despite a lower number of b-values being used. Another aspect regarding choice of b-values is that the range can influence which vessel size the sequence is sensitive to (16), but IVIM will still be sensitive to all randomly flowing blood in each voxel (38).
5.2.1.4 IVIM and choice of cut-off threshold
A study has shown that the IVIM parameters are strongly dependent on the b-value threshold (64). They investigated what the optimal threshold was in various abdominal organs, and in this way minimizing IVIM model fitting errors. The optimal threshold varied between 20 and 300 s/mm2 for abdominal organs. The liver for instance had an optimal threshold between 20 and 40 s/mm2, while kidneys had 150-300 s/mm2, which shows great variation between organs. In this study a cut-off threshold of 50 s/mm2 was chosen after inspecting intensity curves of the included placentas. Perhaps if more b-values were available between 50 and 200, a different cut-off threshold may have become apparent. The same study also found that using a threshold that was too high resulted in D and D* values being lower, and f values being higher. Using a threshold that was too low had the opposite effect. In addition in was shown that D* was the most sensitive to varying thresholds, and showed most variation. Another aspect of using a higher than optimal threshold is that D and f values would continually change, likely due to increased noise effects at higher b-values. However, since both D and f of this study had relatively small standard deviations, it could indicate that this was not the case.
Furthermore, the study suggested that standard thresholds for organs should be used to increase the stability of the method, and facilitate standardization and comparability between studies. Another study also emphasized that there was no consensus on the best approach of handling IVIM data (38). Future research should try to find an optimal
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threshold for placental imaging, also taking into account possible variations due to
gestational age. Based on these findings, it seems likely that the chosen cut-off threshold could strongly affect results and comparison between studies.