To obtain the volume and IVIM data, two programs were used: IKT-SNAP (58, 59) and NordicICE (60). Prior to data collection I received training in both programs from a physicist and radiologist from the PLAVO group. The training was done with the physicist and radiologist separately, and took 1-2 hours with each of them. The instructions and training provided by PLAVO associates was based on images from both the first and second MRI scans. Additionally, images of placentas with pathology were shown, so that they could be recognised and avoided during data collection. The self-training was done on 10 random exams from the MRI scans performed in week 34-36, and performing the various measurements. Data collection was done on MRI scans performed during 25-27 weeks of gestation.
In both programs it was necessary to place regions of interest (ROI). To simplify ROI placements in both IKT-SNAP and NordicICE, a Wacom Cintiq 13HD Creative Pen Display (model: DTK-1301) pen tablet connected to a laptop was used. This made it possible to draw ROI with a pen rather than a mouse – simplifying the task in terms of convenience, speed and precision. The pen tablet was calibrated before each use. The number of slices with a ROI placed on them can be seen in Table 4.
3.3.1 Volume measurements
The sagittal bFFE images were used to obtain volume data using the Waqom Cintiq 13HD pen tablet. The bFFE images were loaded in IKT-SNAP, and then a ROI was placed on each individual slice of the placenta until the entire placenta was traced (see Figure 9 for an example of ROI placement in IKT-SNAP).
During ROI placement the decidua, maternal side of the placenta, was avoided. The DW-images (b=5) were used to help differentiate the decidua from the rest of the placenta (see Figure 10). The DWI and bFFE images were kept side by side during ROI placement, to aid in decidua differentiation. In cases where it proved difficult to distinguish the transition from placenta to uterus on the sagittal images, reconstructed transverse and coronal images were made for guidance. When the entire placenta was marked, IKT-SNAP was used to compute the volume of the marked area.
Table 4: The left side of the table shows how many slices were used to cover the entire area during imaging, while the right side shows how many slices contained placenta and had a ROI placed. The numbers depict range (mean).
Number of slices per sequence Number of slices containing placenta
bFFE DWI bFFE DWI
42-54 (47.0) 19-25 (21.8) 24-38 (31.0) 11-17 (13.7)
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Figure 9: Image from IKT-snap (59) showing a placed ROI (coloured area) in both an anterior (image A) and anterior + posterior (image B) placed placenta. The transition between fetal and maternal side of placenta can also be seen (grey vs coloured area).
Figure 10: DW-image of placenta from the same slice where b=0 (A) and b=5 (B, C). In image B the green arrow indicates where the decidua begins (the darker area), which is easily seen and makes it easier to avoid while placing the ROI (Image C; red arrow pointing towards red ROI line).
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3.3.2 IVIM measurements
The sagittal DW-images were loaded into the NordicICE software. A similar approach was used for placing ROI on the entire placenta on the DW-images with the Waqom Cintiq 13HD pen tablet. Again, the decidua was avoided, and the ROI were drawn on b=5 to easily distinguish it (see Figure 10 for an example of avoiding decidua during ROI
placement in NordicICE). While placing ROI on the DWI, the bFFE was also here kept side by side to help differentiate the decidua in tough cases.
After the ROI were placed, NordicICE was used to generate maps of D, D*, f and (1-f), see Figure 11 for an example of maps. From the maps of D, D*, f and (1-f) the
corresponding value of each voxel was extracted. The number of voxels extracted from each placenta for each map can be seen in Table 7 (in appendix). The number of extracted voxels collected per placenta for D ranged from 31889 to 94320, D* ranged from 31913 to 94322, f ranged from 23231 to 82944, and (1-f) ranged from 31920 to 94330. Zero value voxels were excluded in NordicICE and therefore the number of voxels varies slightly between maps, even though the same ROI was used.
Figure 11: Maps from the same slice of the same placenta of D*, D, f and (1-f) from NordicICE (60). Colouring has been added to more easily visualize differences in them. The voxel value is reflected in the assigned colour: higher values have colours from the top end of the colour scale to the right, while lower values have darker colours at the bottom end of the scale.
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When extracting the various IVIM distributions, a bi-exponential approach with a cut-off threshold of 50 s/mm2 was used for creating the maps. To help evaluate the quality of the IVIM-data collected from the maps, logarithmic intensity curves of the b-values signal decay for every placental slice was generated in NordicICE. The data from the intensity curves was processed in SPSS, and line charts for all included participants were generated: examples of these can be seen in Figure 12. Each chart line was based on the mean voxel values of that slice for a specific b-value. The charts could be used to express whether the intensity curves followed the expected development for a bi-exponential function, or were characterized by disturbances. The line charts were also used to decide the optimal cut-off threshold, which was determined to be 50. Each logarithmic intensity curve in the line charts was based on the mean voxel values collected for each b-value for each slice. These values from each slice were in turn used to create a mean for the entire placenta, which can be seen in Figure 13. This was done for all placentas, and the data is summarized in Table 5.
After evaluating the intensity curves of each slice, the placentas were deemed to be good, or have minor or major disturbances on some of their slices. This was done by checking the line charts visually and scoring them. Three (≈16%) placentas had no disturbances, nine (≈47%) had minor disturbances and seven had “major” disturbances (≈37%). This does not mean that all slices of the placenta were classified as having, for example major disturbances, but that certain slices did. In Figure 12, the top line chart shows an example of a slice (bottom blue line) with a “major” disturbance, while the bottom line chart shows a line chart without disturbances. Despite there being some disturbances of some slices, we can see in Figure 13 that the mean sum of slices has the expected appearance. After evaluating the intensity curves of each slice and placenta as a whole were deemed to be of adequate quality with few disturbances in total.
Table 5: Shows how the voxel intensity values vary across all 19 placentas depending on the b-value. The mean (± standard deviation), minimum and maximum values are shown. The values are based on the intensity curves created in NordicICE.
b-value 0 5 10 25 50 200
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Figure 12: Line charts from SPSS showing the b-value curve of all slices of a placenta, based on the voxel value intensity. Each line represents a single slice and shows how the voxel value intensity changes depending on the b-value. Each line is based on the mean voxel values of that slice for a specific b-value. The top line chart shows an example where all slices do not follow the expected bi-exponential curve, while in the bottom line chart it is possible to see that they follow an
approximate bi-exponential development. Additionally, they show if the slices were affected by disturbances: the top chart shows an example of a slice (bottom blue line) with a “major”
disturbance, while the bottom line chart shows one without disturbances.
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