There have been advances in prenatal care which have improved fetal mortality and pregnancy outcomes, but identifying early sensitive biomarkers of placental health has been limited. It has been proposed that IVIM imaging could be used as an in vivo placental biomarker (24). Despite MRI being more expensive and less available than US (12), MRI can complement US. Certain pathologies of the placenta can only be diagnosed after birth, such as fetal vascular malperfusion. A study has shown f’s potential as an in vivo marker for placental dysfunction, in particular fetal vascular malperfusion (19). This indicates that MRI could be invaluable in these cases, and that the diagnosis could be made prior to birth. Also, imaging with US can be problematic in certain cases such as posterior located placentas (3), advanced gestational age or obese women (12). From this we can see that it could be beneficial to use MRI more frequently for diagnostics.
Additionally, it has been shown that US underestimates volume measurements compared to MRI (31). Perhaps MRI should become a standardized procedure, due to MRI’s ability
43
to give both anatomical and functional images without the use of Gd. Furthermore, the image quality of this study was deemed to be good. Even though some images were excluded due to artefacts, they would likely be good enough for a diagnostic setting, especially the bFFE images because fewer of them were the reason for exclusion due to artefacts. This further supports that MRI should be used more than it is. Moreover, MR images can be valuable in preoperative and intervention planning (5). It should however be reserved for challenging cases due to the availability limitations and expenses
involved. To improve short- and long-term pregnancy outcomes, the mechanism of placental function and growth needs to be better established. Once this is in place, future screening, surveillance and treatment can be customized for the mother and fetus (24).
Future research would also benefit from agreement on how to categorize placentas based on their location, as this would make it easier to compare results between studies.
Techniques for anatomical imaging are well developed and used, but IVIM imaging of the placenta could benefit from further research, such as standardized methods, b-values and cut-off thresholds. This study has attempted to find distribution of volume and IVIM measurements of the placenta, but they have been influenced by a small sample size, few b-values and some disturbances of the intensity curves which may have led to degradation of the measurements. To gain true distribution of volume and IVIM
parameters a greater number of participants must be sampled in the future from several places in the country and world. Moreover, these measurements only apply to gestational week 25-27, so research of other gestational ages must also be performed. It would be possible to use PLAVO’s second MRI scans performed at week 34-36 for further research, in regards to finding distribution and examining how the values change over time. These were however also performed in the supine position, which could affect IVIM results. It would therefore be of interest to see if IVIM parameter f is also influenced by lateral and supine patient positioning, like the ASL method was. Future research in this area could prove useful and beneficial. Furthermore, determining optimal correction methods, analysis models, sequences, b-values and cut-off thresholds for IVIM imaging would be beneficial for future research (24), to avoid these factors being a source of error.
44
Values and distribution of volume and IVIM parameters in placentas at 25-27 weeks of gestation were determined in this study. The volume measurement of
464.45 ± 92.25 cm3 was in good agreement with measurements made using other methods, confirming the accuracy of the method used in this study. Additionally, there was good agreement between the radiographer’s and radiologist’s volume
measurements. When considering volumes depending on placental location these were found to be 476.42 cm3 for anterior placement, 459.63 cm3 for posterior placement and 434.22 cm3 for both anterior and posterior placement. The mean values and standard deviation of IVIM parameters (D, D*, f and (1-f)) were 277.45 ±36.23×10-5 mm2/s, 739.54 ± 211.15×10-5 mm2/s, 14.2 ± 2.7% and 88.4 ± 2.8%, respectively. The level of agreement with other studies when considering the IVIM parameters was less than for volume. Compared to previous findings D and (1-f) were higher, while D* and f were lower. In regard to correlation analysis, volume did not correlate with any of the IVIM parameters. This was in line with expectations.
In carrying out analyses and assessment to answer the specific research questions, some other conclusions were reached that go beyond the research questions that formed the objective of the study. MRI used for volume measurements and diagnosing pathology appears to be a precise and valid method that should be considered for use more routinely as a complementary examination to US. Despite IVIM imaging being a
promising technique, it remains problematic in a placental setting and further research is needed to optimize and standardize methods to avoid various factors being a source of error. Such research should focus on optimal sequences, cut-off thresholds and choice of b-values, and make use of larger sample sizes from multiple locations and several
gestational ages. Research is also needed to determine whether or not supine and lateral positioning affects f.
6 Conclusion
45
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Appendix A: Table 7: Number of voxels collected from each IVIM map (D, D*, f and (1-f)). Zero value voxels were excluded in NordicICE and therefore the number of voxels varies between maps, even though the same ROI was used.
Appendix B: Table 8: Shows placental volumes for the radiographer and radiologist at placental level, and the difference between them (radiologist -
radiographer). It also shows placental location.
Appendix C: Descriptive statistics tables for all IVIM parameters (D, D*, f and (1-f)) Table 9: Descriptive statistics for IVIM parameter D showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis are ×10-5 mm2/s.
Table 10: Descriptive statistics for IVIM parameter D* showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis are ×10-5 mm2/s.
Table 11: Descriptive statistics for IVIM parameter f showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis, represent the fraction the voxel occupied by perfusion.
Table 12: Descriptive statistics for IVIM parameter (1-f) showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis represent the fraction of the voxel not occupied by perfusion.
Appendices: detailed data tables
Appendix A
Table 7: Number of voxels collected from each IVIM map (D, D*, f and (1-f)).
Zero value voxels were excluded in NordicICE and therefore the number of voxels varies between maps, even though the same ROI was used.
Placenta
Numbers of voxels in each IVIM map
D D* f (1-f)
1 48540 48615 42778 48622
2 55259 55323 44142 55326
3 56282 56902 46963 56916
4 49952 50187 42850 50215
5 54374 54998 48029 55002
6 34556 34623 28294 34628
7 67497 67593 49636 62635
8 94320 94322 82944 94330
9 36976 37060 33345 37065
10 40974 41203 31804 41234
11 31889 31913 23231 31920
12 36553 36731 28042 36750
13 41004 41003 30398 41013
14 52184 52452 39846 52481
15 32890 33620 26202 33629
16 56251 56371 49124 56375
17 57754 58737 50529 58744
18 48584 48810 40974 49443
19 39500 39549 30621 39562
Appendix B
Table 8: Shows placental volumes for the radiographer and radiologist at placental level, and the difference between them (radiologist - radiographer). It also shows placental location.
Placenta
Radiographer’s volume (cm3)
Radiologist’s volume (cm3)
Difference in volume (cm3)
Placental location
1 406.49 424.09 17.60 Anterior
2 424.42 432.04 7.62 Anterior + posterior
3 489.77 546.50 56.73 Posterior
4 397.38 426.87 29.49 Anterior
5 468.48 544.13 75.65 Anterior
6 408.41 459.98 51.57 Anterior + posterior
7 515.65 545.20 29.55 Posterior
8 728.17 790.31 62.14 Anterior
9 422.39 408.75 -13.64 Posterior
10 445.36 429.63 -15.73 Posterior
11 333.06 366.66 33.60 Anterior
12 451.28 537.82 86.54 Anterior
13 394.51 429.13 34.63 Anterior
14 630.86 698.59 67.72 Anterior
15 416.17 429.95 13.78 Posterior
16 557.36 579.52 22.16 Anterior
17 468.42 456.14 -12.27 Posterior
18 469.84 485.05 15.21 Anterior + posterior
19 396.63 398.66 2.03 Anterior
Appendix C
Table 9: Descriptive statistics for IVIM parameter D showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis are ×10-5 mm2/s.
Descriptive statistics for D (diffusion coefficient) Placenta
Table 10: Descriptive statistics for IVIM parameter D* showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis are ×10-5 mm2/s.
Descriptive statistics for D* (pseudodiffusion coefficient) Placenta
Mean ± Std.
Deviation
Median Minimum Maximum Skewness Kurtosis 5th
%
25th
%
50th
%
75th
%
95th
% 1 681.33 ± 506.96 573.28 1.318 6589 2.419 10.870 127.84 363.74 573.28 850.04 1618.38 2 779.57 ± 600.36 644.38 0.745 8562 2.564 14.246 127.39 389.30 644.38 1005.01 1867.78 3 826.87 ± 638.00 691.16 1.630 8150 2.005 7.154 112.48 397.74 691.16 1075.86 2039.25 4 504.99 ± 451.37 409.27 1.912 9562 3.821 30.533 66.94 239.06 409.27 627.29 1253.81 5 895.52 ± 717.81 726.66 1.379 6894 2.087 5.956 143.40 431.58 726.67 1116.88 2431.00 6 634.50 ± 423.91 558.31 0.867 4334 1.635 4.900 110.97 345.91 558.31 823.59 1414.84 7 711.59 ± 555.90 600.60 1.859 9297 2.049 10.289 74.38 319.82 600.60 959.47 1727.41 8 731.07 ± 487.61 632.93 0.883 4413 1.469 3.296 138.72 394.59 632.93 942.77 1683.40 9 950.86 ± 637.71 838.67 1.773 8865 1.976 9.297 175.54 515.97 838.67 1242.93 2076.19 10 618.21 ± 526.83 500.76 1.555 7775 2.506 12.301 63.76 267.49 500.76 811.79 1583.14 11 503.97 ± 454.62 399.85 1.101 5507 2.956 15.249 55.08 218.10 399.85 646.58 1289.09 12 564.33 ± 492.82 459.38 1.830 9150 3.586 30.637 62.23 252.57 459.38 737.56 1423.88 13 612.98 ± 414.13 547.36 0.864 4323 1.623 5.507 89.93 324.26 547.36 815.42 1348.07 14 704.39 ± 631.04 556.80 1.375 6874 2.397 9.887 60.49 279.09 556.80 926.62 1898.61 15 760.14 ± 642.71 599.27 1.101 5507 1.757 4.597 67.20 302.94 599.27 1027.79 2030.25 16 732.70 ± 530.79 621.31 1.216 6079 1.888 5.725 125.24 381.78 621.31 927.71 1773.96 17 944.30 ± 696.20 815.86 1.717 8587 2.280 10.315 142.56 491.23 815.86 1213.48 2179.63 18 1398.31±1261.65 1097.76 2.6970 13485 2.503 9.371 142.95 593.38 1097.76 1785.54 3670.88 19 495.69 ± 395.09 421.24 1.193 5966 2.654 15.365 60.86 238.66 421.24 640.81 1182.57
Table 11: Descriptive statistics for IVIM parameter f showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis, represent the fraction the voxel occupied by perfusion.
Descriptive statistics for f (perfusion fraction) Placenta
Mean ± Std.
Deviation
Median Minimum Maximum Skewness Kurtosis 5th
%
25th
%
50th
%
75th
%
95th
% 1 0.1337 ±0.1043 0.1096 0.00016 0.7940 1.604 3.458 0.0157 0.0610 0.1096 0.1756 0.3444 2 0.1434 ±0.1110 0.1180 0.00011 0.8769 1.333 2.293 0.0140 0.0607 0.1180 0.1966 0.3644 3 0.1560±0.1129 0.1347 0.00016 0.7795 1.225 1.963 0.0172 0.0720 0.1347 0.2127 0.3753 4 0.1262 ±0.1067 0.0961 0.00017 0.8675 1.533 2.857 0.0118 0.0496 0.0962 0.1704 0.3475 5 0.1596 ±0.1121 0.1384 0.00014 0.6908 0.973 0.828 0.0177 0.0725 0.1384 0.2226 0.3801 6 0.1212 ±0.0915 0.1026 0.00013 0.6640 1.413 2.791 0.0128 0.0544 0.1026 0.1631 0.3035 7 0.1426 ±0.1054 0.1223 0.00017 0.8401 1.143 1.787 0.0133 0.0613 0.1223 0.2014 0.3421 8 0.1531 ±0.1036 0.1342 0.00013 0.6532 0.878 0.559 0.0191 0.0729 0.1342 0.2149 0.3511 9 0.1888 ±0.1174 0.1746 0.00010 0.8664 0.737 0.466 0.0257 0.0986 0.1746 0.2604 0.4070 10 0.1279 ±0.1016 0.1045 0.00017 0.8356 1.486 3.119 0.0119 0.0537 0.1045 0.1752 0.3308 11 0.1018 ±0.0933 0.0757 0.00013 0.6535 1.802 4.174 0.0077 0.0357 0.0757 0.1369 0.2907 12 0.1164 ±0.1002 0.0897 0.00018 0.8764 1.664 3.882 0.0095 0.0442 0.0897 0.1580 0.3183 13 0.1145 ±0.0848 0.0977 0.00013 0.6460 1.293 2.669 0.0110 0.0505 0.0977 0.1603 0.2686 14 0.1497 ±0.1232 0.1206 0.00017 0.8589 1.590 3.270 0.0136 0.0612 0.1206 0.2003 0.3989 15 0.1484 ±0.1094 0.1260 0.00017 0.8447 1.215 1.977 0.0152 0.0661 0.1260 0.2067 0.3563 16 0.1398 ±0.0986 0.1200 0.00014 0.6927 1.066 1.173 0.0162 0.0581 0.1200 0.1923 0.3342 17 0.1969 ±0.1292 0.1784 0.00016 0.8243 0.911 0.985 0.0236 0.0988 0.1784 0.2712 0.4371 18 0.1760 ±0.1376 0.1462 0.00010 0.8620 1.474 2.707 0.0176 0.0769 0.1462 0.2376 0.4556 19 0.0977 ±0.0812 0.0784 0.00015 0.7645 1.893 6.072 0.0095 0.0405 0.0784 0.1319 0.2481
Table 12: Descriptive statistics for IVIM parameter (1-f) showing the mean, standard deviation, median, minimum, maximum, skewness, kurtosis and percentiles (5, 25, 50, 75 and 95). All values except skewness and kurtosis represent the fraction of the voxel not occupied by perfusion.
Descriptive statistics for (1-f) (diffusion extravascular space fraction) Placenta
Mean ± Std.
Deviation
Median Minimum Maximum Skewness Kurtosis 5th
%
25th
%
50th
%
75th
%
95th
%
1 0.8823 ±0.1071 0.9038 0.2060 1 -1.525 3.191 0.669 0.837 0.903 0.961 1
2 0.8856 ±0.1147 0.9118 0.1232 1 -1.345 2.177 0.657 0.828 0.912 0.983 1
3 0.8713 ±0.1183 0.8926 0.2204 1 -1.179 1.671 0.643 0.807 0.893 0.970 1
4 0.8923 ±0.1082 0.9210 0.1326 1 -1.540 2.874 0.669 0.847 0.921 0.974 1
5 0.8607 ±0.1175 0.8808 0.3092 1 -0.943 0.678 0.631 0.792 0.881 0.955 1
6 0.9196 ±0.0950 0.9196 0.3360 1 -1.363 2.488 0.715 0.853 0.920 0.980 1
7 0.8954 ±0.1101 0.9226 0.1600 1 -1.232 1.669 0.684 0.831 0.922 1 1
8 0.8654 ±0.1092 0.8834 0.3468 1 -0.839 0.397 0.658 0.799 0.883 0.953 1
9 0.8302 ±0.1250 0.8424 0.1336 1 -0.662 0.215 0.601 0.751 0.842 0.928 1
10 0.9013 ±0.1042 0.9264 0.1642 1 -1.505 3.005 0.694 0.850 0.994 0.993 1
11 0.9259 ±0.0916 0.9548 0.3464 1 -1.950 4.842 0.738 0.891 0.954 1 1
12 0.9111 ±0.1006 0.9392 0.1236 1 -1.732 4.046 0.708 0.867 0.939 0.996 1
13 0.9152 ±0.0885 0.9352 0.3540 1 -1.323 2.340 0.750 0.864 0.935 1 1
14 0.8863 ±0.1250 0.9176 0.1410 1 -1.632 3.368 0.635 0.829 0.917 0.996 1
15 0.8843 ±0.1145 0.9082 0.1552 1 -1.226 1.758 0.664 0.821 0.908 0.988 1
16 0.8782 ±0.1033 0.8960 0.3072 1 -1.017 0.981 0.676 0.821 0.896 0.960 1
17 0.8307 ±0.1379 0.8470 0.1756 1 -0.844 0.654 0.578 0.747 0.847 0.944 1
18 0.8541 ±0.1417 0.8842 0.1380 1 -1.437 2.557 0.575 0.786 0.884 0.968 1
19 0.9244 ±0.0823 0.9442 0.2356 1 -1.853 5.652 0.770 0.887 0.944 0.994 1
NTNU Norwegian University of Science and Technology Faculty of Medicine and Health Sciences Department of Circulation and Medical Imaging
Master ’s thesis
Heidi Hamill Gorman
MRI of the placenta
Measurements of volume and intravoxel incoherent motion at weeks 25-27 of gestation
Master’s thesis in Medical Magnetic Resonance Imaging May 2020