Exploring in vivo placental microcirculation and microstructure in different pregnancies of normal pregnancy and pregnancy-induced hypertension through intravoxel incoherent motion MRI at the plateau area

Exploring in vivo placental microcirculation and microstructure in different pregnancies of normal pregnancy and pregnancy-induced hypertension through intravoxel incoherent motion MRI at the plateau area | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exploring in vivo placental microcirculation and microstructure in different pregnancies of normal pregnancy and pregnancy-induced hypertension through intravoxel incoherent motion MRI at the plateau area Fei Liu, Zhanyue Yan, Lianyun Kang, Zhenning Gan, Shenlan Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4752678/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background A preliminary study of placental microcirculation and microstructure in healthy pregnant women in different trimesters and pregnancy-induced hypertension (PIH) at plateau through intravoxel incorrelation movement (IVIM). Methods A retrospective analysis was conducted at Qinghai Red Cross Hospital from August 2019 to January 2022. All subjects(18,28 pregnant women in the second trimester/third trimester[PWST/PWTT], 26 PIH) underwent ultrasound,MRI-IVIM examinations.The true diffusion coefficient ( D ),false diffusion coefficient ( D *), perfusion fraction ( f ) values of the whole placenta and different placental sites, estimated fetal weight (EFW) and postnatal weight were measured and recorded. The statistic was analyzed by independent sample t test or single factor ANOVA,multiple comparisons of placental quantitative parameters between subjects were analyzed by the Bonferroni method. The correlations between placental IVIM parameters and fetal weight, GA and GW were analyzed by Pearson correlation analysis. Results No significant differences among the different placental parts of the PWST. The difference among the placenta in PWTT- f (maternal side>fetal side, P PWST- D (maternal side, P PIH- f (fetal side, whole placenta, P PIH- D (maternal side, whole placenta, P PIH( P <0.05).PWTT- f (maternal side)was negatively correlated with EFW ( r =-0.579, P = 0.005), PWTT- f (maternal side) was negatively correlated with GW ( r =-0.441, P = 0.005). Discussion IVIM could effectively analyze and evaluate the characteristic of placental microcirculation and microstructure in normal and PIH pregnant women at plateau. Placenta microcirculation intra-voxel incoherent motion(IVIM) Pregnancy-Induced Hypertension(PIH) plateau area Figures Figure 1 Figure 2 Figure 3 Background The placenta is responsible for crucial functions such as endocrine and immune regulation, nutrition, and respiration, which are primarily carried out through placental blood perfusion and diffusion [1] . Ultrasound imaging has been the most commonly used method to gain insight into the intricacies of the placenta, providing valuable information about its anatomy, location, and size. However, its limitations have become apparent when assessing placental microcirculation and microstructure [2] . To supplement ultrasound imaging, conventional MRI has been employed as an adjunctive tool. Functional magnetic resonance imaging (fMRI) that has shown promise in detecting placental blood microcirculation，microstructure and blood oxygen metabolism among other vital physiological parameters [3] . In this study, fMRI intravoxel incoherent motion (IVIM) was utilized to investigate the state of microcirculation perfusion and microstructure. By noninvasively separating the movement of microscopic water molecules inside and outside tissue cells and blood vessels, this magnetic resonance imaging technology offers a comprehensive evaluation of the physiological state of organs throughout the body [4] . Pregnancy-Induced Hypertension（PIH） poses a significant threat to the health of mother and child, including: gestational hypertension, preeclampsia, eclampsia, chronic hypertension during pregnancy, and chronic hypertension complicated with preeclampsia [5] . Globally, the incidence of PIH ranges from 6% to 8% [6] . Interestingly, in the plateau (≥2500m), the prevalence of PIH was nearly twice than in the plain, with a staggering 63% increase in the likelihood of stillbirth [7,8] . With the population in the plateau areas on the rise, it became increasingly pertinent to delve into the changes in the microcirculation and microstructure of PIH and normal placenta in these environments. At present, most studies using MRI-IVIM have mainly been used to distinguish fetal growth restriction, normal placenta from placenta accreta spectrum disorder, and diseases of other organs [9,10] , but there are few studies on placental microcirculation and microstructure in plateau areas during PIH and normal late pregnancy.Understanding these alterations will not only aid in the management and prevention of PIH，but also shed light on the unique challenges faced by pregnant women residing in plateau regions. Methods 2.1 Subjects Retrospective analysis was performed on 26 cases of PIH diagnosed in the obstetrics department of Qinghai Red Cross Hospital during the third trimester (6 cases of preeclampsia, 20 cases of pregnancy-induced hypertension), 28 cases of healthy pregnant women in the third trimester(PWTT) and 18 cases of healthy pregnant women in the second trimester(PWST) from August 2019 to January 2022 (Table 1). Inclusion criteria (1) Generations living in a plateau area (altitudes≥2500m) (2) single birth; (3) Pregnant women do not smoke, alcoholism, genetic metabolic diseases. Exclusion criteria :(1) fetal malformation, multiple births; (2) pregnancy with diabetes, thyroid disease; (3) pregnancy with pelvic tumor; (4) placental abruption; (5) placenta accreta spectrum disorder ;(6) Clinical data of pregnant women were incomplete or images could not be evaluated.（Figure 1） 2.2 Diagnostic criteria of Hypertensive disorders of pregnancy Adopt ISSHP classification, diagnosis & management recommendations of the hypertensive disorders during pregnancy [11] . 2.3 Research method Imaging: MRI acquisition We utilized the Siemens Skyra 3.0T MRI scanner with a 4-channel body phase controlled surface coil to capture images within a single breath-holding interval. The scan encompassed the region from the diaphragm to the symphysis pubis. The pregnant woman assumed a supine or lateral position,with the foot positioned forward. To optimize the efficiency and minimize time spent in the scanning process, we limited the scanning to IVIM scans: featuring a field of view (FOV) of 380mm×380mm, a layer thickness of 5.5mm, a matrix size of 192×120, and 8 b values (0,50,100,150,200,250,500,800 s/mm 2 ). The total scanning time was 6 minutes and 32 seconds.. Sonography All pregnant women underwent abdominal ultrasound examination using the LOGIQ E9 ultrasound scanner(GE Healthcare,WI) after receiving MRI examination. The senior attending physician specializing in abdominal ultrasound diagnosis measured the fetal double parietal diameter, head circumference, abdominal circumference, femur length and humerus length, respectively. The mean values of these parameters were then input into the software, and the estimating fetal weight(EFW) was assessed using the Had-lock formula. Imaging: Postprocessing We utilized the MITK-diffusion software(Copyright © German Cancer Research Center (DKFZ), Division of Medical Image Computing (MIC)) to identify the maximum layer of placenta on the IVIM image(b=0) as the measuring center for all pregnant women. We made sure to avoid the large blood vessels, infarcts and calcification areas. Three regions of interest (ROIs) were defined on the fetal side, maternal side and central area of the placenta.Fetal side was considered as the side where the placental edge faced the fetus, while the opposite side was considered the maternal side. The area between them was defined as the central area. In addition, we also measured the whole placenta. Two adjacent layers of the maximum layer were also assessed by two radiologists. The parameters of IVIM and the double exponential model were obtained, and the perfusion fraction ( f ), standard diffusion coefficient ( D ) and false diffusion coefficient ( D ∗ ) were calculated by means of average values. Used a double exponential model S b /S 0 = (1- f ) ·exp(-b D )+f·exp[-b ( D + D ∗ )] (S 0 and S b were signal intensity at b values of 0s/mm 2 and b values of 0, 50, 100, 150, 200, 250, 500 and 800s/mm 2 ,respectively). (Figure 2A-E) D represents simple diffusion of water molecules, D ∗ represents capillary microcirculation perfusion, and f represents the ratio of the capillary volume in voxels to the total tissue volume. 2.4 Statistical methods SPSS 22.0 software was used for processing, continuous variable data are expressed as (± S ), independent sample t tests or one-way analysis of variance were used, and multiple comparisons among the three groups of placental quantitative parameters were analyzed by the Bonferroni method. The correlations between placental IVIM parameters and the EFW, postnatal weight, gestational age and gestational weeks were analyzed by Pearson correlation analysis. The consistency analysis of data measured by two radiologists was analyed by the Bland-Altman method,and P < 0.05 was considered statistically significant. Results Bland-Altman showed that the IVIM parameters of the three groups were within the range of 1.96 times standard deviation, with good consistency. 3.1 Placental characteristics of normal PWST The maternal and fetal sides of 18 normal PWST placentas were indistinguishable from those of the IVIM parameter maps. The D value on the maternal side of the placenta was lower than that on the fetal side ( P > 0.05), and the f and D * values on the maternal side of the placenta were greater than those on the fetal side ( P > 0.05).(Table.2) 3.2 Placental characteristics of normal PWTT 28 normal placentas from PWTT pregnant women were distinguishable on the maternal and fetal sides by an IVIM parametric map, and 4 cases were not. Between the fetal and maternal sides of the placenta are interlaced in strips in the D , D * , f value diagram. The value of D and D * on the maternal side of placenta were greater than the fetal side ( P > 0.05), and the value of f on the maternal side of the placenta was greater than that on the fetal side ( P < 0.05).(Table.3) 3.3 Placental characteristics of PIH 26 PIH placentas on the maternal and fetal sides could not distinguish on the IVIM parametric map. The values of f , D and D * on maternal side of placenta were higher than the fetal side, but no statistical significance ( P > 0.05).(Table.4) 3.4 Comparison of placental IVIM parameters among PWTT and PWST The D value on the maternal side of PWTT placenta was higher than PWST ( P 0.05).(Table.5) 3.5 Comparison of placental IVIM parameters,EFW and postnatal weight among three groups The fetal side and whole placental f values in normal PWTT were higher than PIH ( P < 0.05), the maternal side and whole placental D values in normal PWTT were higher than PIH ( P < 0.05), the EFW and postnatal weight in normal PWTT were higher than PIH ( P < 0.05).(Table.6) 3.6 Relationship of placental IVIM parameters with gestational age, gestational weeks,EFW and postnatal weight in normal PWTT The f value of PWTT on maternal side was negatively correlated with EFW ( r MS f =-0.579, P =0.005), and f value of PWTT on maternal side was negatively correlated with gestational weeks ( r MS f =-0.441, P =0.005).（figure 3） D * , D value of PWTT were not correlated with EFW,postnatal weight,gestational age and gestational weeks ( P > 0.05). f , D and D * value of PIH and PWST had no correlation with gestational age,gestational weeks,EFW and postnatal weight. Discussion Background & Principle of IVIM imaging and Placental Interpretations PIH posed a significant risk to the health of pregnant women and the growth and development of the fetus, with adverse potential effects throughout the entire pregnancy and beyond, warranting clinical attention. Research had indicated [12] that PIH was associated with abnormal placental morphology and a higher incidence of early placental poor perfusion in cases of combined PIH and fetal growth restriction compared to isolated fetal growth restriction. Moreover, the prevalence of PIH was nearly double in pregnant women residing at high altitudes (≥2500m) compared to those at lower altitudes [7] . With the growing population at high altitudes, understanding the changes in placental microcirculation and microstructure in both normal and PIH-affected pregnancies in these areas was crucial. IVIM-DWI had the capability to differentiate between actual water molecule diffusion movement and capillary blood flow movement, providing a comprehensive assessment of tissue diffusion and perfusion through quantitative parameters ( D , D * , f value). The D value related to the actual diffusion of water molecules, cell density and cytoplasmic ratio, while the value of D * was associated with diffusion movement, mean capillary length and blood flow velocity related to capillary perfusion. The f value pertained to the proportion of blood flow movement in capillaries and the richness of capillaries within a unit voxel [13,14] . Given the rich vascularization on the maternal side of the placenta, alongside the fetal side and the interstitium comprising the placental circulatory system [15] , understanding the hemodynamics of this system and the interstitial function is crucial in evaluating placental structural and functional changes [16] . Research aimed at uncovering and understanding the placental circulatory system and interstitial diffusion perfusion function at high altitudes holded promise for clinical assessment of placental health. Principal Findings The results of this study indicated that there were no significant differences in IVIM parameters between the maternal side, fetal side and central region of the placenta in PWST at high altitude areas. However, the IVIM parameters differed from those in PWTT. For example, the D value of the maternal side of the PWTT placenta was higher than PWST ( P < 0.05), suggesting that the organizational structure on the maternal side of PWST placenta was not fully mature,and the corresponding functions of microcirculation and microstructure were yet to mature. In PWTT, the f value of the maternal side of placenta was higher than the fetal side ( P < 0.05), which was in line with the research results of Antonelli [17] et al in the plain areas, indicating that the water molecules in this area were mainly related to blood flow movement, which was associated with the rich uterine spiral arteries and capillaries on the maternal side of the placenta and the fast speed of blood flow. The f value of the maternal side of PIH placenta was slightly higher than the fetal side ( P > 0.05). Compared with PWTT, the f value of maternal side and whole placenta of PIH were lower than PWTT ( P 0.05), which was different from the results of the plain areas [17] , suggesting that the diffusion activities related to water molecules and capillary blood flow movement on the fetal side were altered in plateau areas. The differences may be related to the pathological changes of placenta caused by hypoxia in plateau areas, such as increased blood vessels and villi, thinning of chorion, vascular syncytia, and deposition of cellulose-like material [18] . Worth noting was that the difference of D value between the maternal and fetal side was not significant, indicating that under hypoxia, compensatory reaction such as the increase of placental blood vessels and the formation of vascular syncytial membrane could not promote the diffusion movement. Additionally, the D values of the maternal side and the whole placenta in PWTT were higher than those of PIH ( P < 0.05), suggesting that the actual diffusion of water molecules in the placenta of PIH was impaired, which may be related to the reduction of placental villus volume and surface area in PIH [8] and hypoxia and ischemia at plateau area [19] . Under the combined action of these two factors, placental ischemia and maternal-fetal material exchange capacity declined, ultimately leading to lower EFW and postnatal weight than PWTT ( P < 0.05). Additionally, it was observed that the central region between the maternal and fetal sides of the placenta in PWTT was the transition zone, with no significant difference in the parameters of IVIM ( P > 0.05). However, there was a certain correlation between maternal and fetal sides in the parameters of IVIM. This region was inferred to be the placental lobular, indicating that IVIM technology could effectively evaluate the placental microstructure [20] . Furthermore, the f value on the maternal side of the placenta was negatively correlated with EFW in PWTT ( r maternal side f =-0.579, P=0.005), which differed from that in the plain area, indicating that the compensatory changes of the placenta caused by hypoxia-ischemia in the plateau area, such as increased placental blood vessels and villi, could result in a reduction of the blood filling space on the maternal side. Consequently, the blood flow volume per unit villus surface area decreased [21] , leading to a decrease in the f value on the maternal side of the placenta and ultimately inadequate fetal supply. Additionally, the f value on the maternal side of PWTT was also negatively correlated with gestational weeks ( r maternal f =-0.441, P =0.04). This may be attributed to an increase in placental villi proliferation and maturation, leading to a denser arrangement, narrowing of the intervillous space, and a further reduction in the maternal blood filling space as gestational weeks progress [22] . This eventually lead to a further decrease in the f value on the maternal side. Limitations and Future research This study still had some limitations that need to be addressed. Firstly, the sample size of the three groups was small and lacked corresponding pathological control studies, highlighting the need for further expansion of the sample size. Additionally, different types of PIH should be classified,and exploring the characteristic of placental microcirculation and microstructure. Secondly, the IVIM parameter diagram could not completely distinguish the fetal and maternal circulatory system, suggesting the need for further optimization of IVIM parameters and post-processing algorithms in the future. Lastly, in the future research, it would be beneficial to explore the integration of artificial intelligence technology to extract more high-quality information and develop a practical artificial intelligence model to identify and address related issues. Conclusions The IVIM technology offered a dependable means for non-invasively separating placental tissue cells and observing the movement of microscopic water molecules within and outside placental blood vessels. It provided valuable insights into the state of microcirculation perfusion, allowing for the evaluation of placental function under both pathological and physiological conditions at both the micro and macro levels. In doing so, it brought a fresh perspective to the observation of characteristic in placental microstructure and microcirculation. Abbreviations PIH: pregnancy-induced hypertension IVIM: intravoxel incorrelation movement MRI: magnetic resonance imaging PWST: pregnant women in the second trimester PWTT: pregnant women in the third trimester D: diffusion coefficient D*: pseudo-diffusion coefficient f: perfusion fraction EFW:estimated fetal weight GA:gestational age GW:gestational weeks PW:Postnatal weight MS:Maternal side FS:Fetal side WP:whole placenta Declarations Ethical Approval and Consent to Participate This study was approved by the Medical Ethics Committee of Qinghai Red Cross Hospital（No. KY-2019-40）,and all participants signed informed consent. Consent to Publish Not applicable. Author contributions FL and GL designed the research; ZYY LYK and SLW recruited patients and collected clinical information; ZYY and ZNG collected and managed database; SLW and LYK were involved in review of data within the obstetrics registry and adjudication of hypertensive disorders of pregnancy; ZYY and LYK adjudicated adverse outcomes; FL and ZYY performed datas analysis. Funding This research was funded with support from the Qinghai Provincial Basic Research Program - Applied Basic Research Project (No. 2020-0301-ZJC-0089). Competing Interests The authors declare no competing interests. Data Availability statement Not applicable. Acknowledgement The authors are very grateful to all patients who consented and performed an MRI-IVIM scan. We thank Dr. Gang Liu for constructive critiques on the research and manuscript. We also thank Dr. Shenlan Wang for the recruitment of patients. References Burton GJ, Charnock-Jones DS, Jauniaux E. Regulation of vascular growth and function in the human placenta. Reproduction. 2009;138(6):895-902. doi:10.1530/REP-09-0092 Gowland P. Placental MRI. Semin Fetal Neonatal Med. 2005;10(5):485-490. doi:10.1016/j.siny.2005.05.001 Siauve N, Chalouhi GE, Deloison B, et al. Functional imaging of the human placenta with magnetic resonance. Am J Obstet Gynecol. 2015;213(4 Suppl):S103-S114. doi:10.1016/j.ajog.2015.06.045 Feng YZ, Chen XQ, Yu J, et al. Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients. Abdom Radiol (NY). 2018;43(10):2764-2773. doi:10.1007/s00261-018-1555-7. Brown MA, Magee LA, Kenny LC, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. doi:10.1016/j.preghy.2018.05.004 Lenfant C; National Education Program Working Group on High Blood Pressure in Pregnancy. Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich). 2001;3(2):75-88. doi:10.1111/j.1524-6175.2001.00458.x Imogen D,Grant,Dino A,Giussani,Catherine E,Aiken.Blood pressure and hypertensive disorders of pregnancy at high altitude: a systematic review and meta-analysis.[J].American journal of obstetrics&gynecology MFM,2021,3(5):100400.doi:10.1016/j.ajogmf.2021.100400. Di Martino DD, Avagliano L, Ferrazzi E, et al. Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets. Nutrients. 2022;14(16):3276. doi:10.3390/nu14163276. Alessandra,Maiuro,Giada, et al.Two-Compartment Perfusion MR IVIM Model to Investigate Normal and Pathological Placental Tissue.[J].Journal of magnetic resonance imaging : JMRI,2024,59(3):879-891. Wang Q, Yu G, Qiu J, Lu W. Application of Intravoxel Incoherent Motion in Clinical Liver Imaging: A Literature Review. J Magn Reson Imaging. Published online November 1, 2023. doi:10.1002/jmri.29086. Brown MA, Magee LA, Kenny LC, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. doi:10.1016/j.preghy.2018.05.004 Egbor M, Ansari T, Morris N, Green CJ, Sibbons PD. Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG. 2006;113(5):580-589. doi:10.1111/j.1471-0528.2006.00882.x Hu YC, Yan LF, Wu L, et al. Intravoxel incoherent motion diffusion-weighted MR imaging of gliomas: efficacy in preoperative grading. Sci Rep. 2014;4:7208. Published 2014 Dec 1. doi:10.1038/srep07208 Iima M. Perfusion-driven Intravoxel Incoherent Motion (IVIM) MRI in Oncology: Applications, Challenges, and Future Trends. Magn Reson Med Sci. 2021;20(2):125-138. doi:10.2463/mrms.rev.2019-0124 Solomon E, Avni R, Hadas R, et al. Major mouse placental compartments revealed by diffusion-weighted MRI, contrast-enhanced MRI, and fluorescence imaging. Proc Natl Acad Sci U S A. 2014;111(28):10353-10358. doi:10.1073/pnas.1401695111 Alison M, Chalouhi GE, Autret G, et al. Use of intravoxel incoherent motion MR imaging to assess placental perfusion in a murine model of placental insufficiency. Invest Radiol. 2013;48(1):17-23. doi:10.1097/RLI.0b013e318271a5f8. Antonelli A, Capuani S, Ercolani G, et al. Human placental microperfusion and microstructural assessment by intra-voxel incoherent motion MRI for discriminating intrauterine growth restriction: a pilot study. J Matern Fetal Neonatal Med. 2022;35(25):9667-9674. doi:10.1080/14767058.2022.2050365. Wilsterman K, Cheviron ZA. Fetal growth, high altitude, and evolutionary adaptation: a new perspective. Am J Physiol Regul Integr Comp Physiol. 2021;321(3):R279-R294. doi:10.1152/ajpregu.00067.2021. Zamudio S. The placenta at high altitude. High Alt Med Biol. 2003;4(2):171-191. doi:10.1089/152702903322022785. Bonel HM, Stolz B, Diedrichsen L, et al. Diffusion-weighted MR imaging of the placenta in fetuses with placental insufficiency. Radiology. 2010;257(3):810-819. doi:10.1148/radiol.10092283 Jung EJ, Cho HJ, Byun JM, et al. Placental pathologic changes and perinatal outcomes in placenta previa [published correction appears in Placenta. 2019 Mar;78:54]. Placenta. 2018;63:15-20. doi:10.1016/j.placenta.2017.12.016 Gude NM, Roberts CT, Kalionis B, et al. Growth and function of the normal human placenta. Thromb Res. 2004;114(5-6):397-407. doi:10.1016/j.thromres.2004.06.038. Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files table.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4752678","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":330348374,"identity":"75090046-f590-441d-8fff-4401e76af785","order_by":0,"name":"Fei Liu","email":"","orcid":"","institution":"Qinghai Red Cross Hospital , Xining city, Qinghai Province, China","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Liu","suffix":""},{"id":330348375,"identity":"7a9e9d39-220f-477d-ad2b-dd06083cd9d7","order_by":1,"name":"Zhanyue Yan","email":"","orcid":"","institution":"Qinghai Red Cross Hospital , Xining city, Qinghai Province, China","correspondingAuthor":false,"prefix":"","firstName":"Zhanyue","middleName":"","lastName":"Yan","suffix":""},{"id":330348376,"identity":"f774d6b1-c6a3-429c-bfb0-586b2c0e6d2c","order_by":2,"name":"Lianyun Kang","email":"","orcid":"","institution":"Qinghai Red Cross Hospital , Xining city, Qinghai Province, China","correspondingAuthor":false,"prefix":"","firstName":"Lianyun","middleName":"","lastName":"Kang","suffix":""},{"id":330348377,"identity":"042f5ac3-e123-485c-b438-000bb4e9adf8","order_by":3,"name":"Zhenning Gan","email":"","orcid":"","institution":"Qinghai Red Cross Hospital , Xining city, Qinghai Province, China","correspondingAuthor":false,"prefix":"","firstName":"Zhenning","middleName":"","lastName":"Gan","suffix":""},{"id":330348378,"identity":"bcf58b61-3047-4b84-9fcf-e9e19184baac","order_by":4,"name":"Shenlan Wang","email":"","orcid":"","institution":"Qinghai Red Cross Hospital , Xining city, Qinghai Province, China","correspondingAuthor":false,"prefix":"","firstName":"Shenlan","middleName":"","lastName":"Wang","suffix":""},{"id":330348379,"identity":"463f5e79-0179-48b2-ba13-ba11ffc116be","order_by":5,"name":"Gang Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIie3PMUsDMRTA8RcCOYfXZr2jRb9CoFARyt1XSTm4ycHxhg6BQlyKrr1v4eScEtAl6AeoQ0FwzoFoQRA7WDp5cRTMf3qE94MXgFjsD9an3wNLrt+9rCfIueombE/6aMbgXTXMliZA9sNxKsek0XYilAyQBAV5nT3lOpXVM7pHFGCIb8+7DkNBh3cvpcbN/QjrNZ5SRbPmNkBSZkuWTNUA3RrPlGG0FySfOwIlDHr6AYWRYUJabXN2VLGs0eY3hF1QcmUlQ0eFdyVmy9W88y+c2xuyfbPFyeWCbGSdF5zPV77tILuSDwSYqsMDUT+tHla2AEVwKxaLxf5vXyGsTHEUldUCAAAAAElFTkSuQmCC","orcid":"","institution":"Qinghai Red Cross Hospital , Xining city, Qinghai Province, China","correspondingAuthor":true,"prefix":"","firstName":"Gang","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-07-17 00:54:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4752678/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4752678/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63156410,"identity":"4f3ab492-9e67-4a6e-b998-8b842106d26c","added_by":"auto","created_at":"2024-08-23 21:12:33","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53887,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient inclusion and grouping\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4752678/v1/66588f8020b2e76798787dfd.jpg"},{"id":63156755,"identity":"220c25d9-c22f-4adc-b7e9-585971d8c5e4","added_by":"auto","created_at":"2024-08-23 21:20:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5428582,"visible":true,"origin":"","legend":"\u003cp\u003eA. The whole placenta is delineated with the largest area of placenta as the measuring center.\u003c/p\u003e\n\u003cp\u003eB. IVIM-\u003cem\u003ef\u003c/em\u003ediagram of a normal placenta.\u003c/p\u003e\n\u003cp\u003eC. IVIM-\u003cem\u003eD \u003c/em\u003ediagramof a normal placenta.\u003c/p\u003e\n\u003cp\u003eD. IVIM-\u003cem\u003eD*\u003c/em\u003ediagram of a normal placenta.\u003c/p\u003e\n\u003cp\u003eE. Fit the double exponential model graph.\u003c/p\u003e","description":"","filename":"2copy.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4752678/v1/5d92ff86b7297903ea6f8cf4.jpg"},{"id":63156412,"identity":"28a48640-d35b-4178-834b-dc8ef808c7f6","added_by":"auto","created_at":"2024-08-23 21:12:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":19678,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between maternal side of PWTT and EFW(left), Relationship between maternal side of PWTT and GW(right)\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4752678/v1/e7c81ae65ad1a762ab775711.jpg"},{"id":66694452,"identity":"57caaa52-23cc-43d2-b126-e8f9f798fb98","added_by":"auto","created_at":"2024-10-15 14:32:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6037207,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4752678/v1/10e8c4fa-bc6e-48c4-b57d-be347f22e8f2.pdf"},{"id":63156413,"identity":"628611f0-9fff-463c-8e5b-5939336f58d4","added_by":"auto","created_at":"2024-08-23 21:12:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":56691,"visible":true,"origin":"","legend":"","description":"","filename":"table.docx","url":"https://assets-eu.researchsquare.com/files/rs-4752678/v1/5ee8ca41f6e5865ce47a88ca.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exploring in vivo placental microcirculation and microstructure in different pregnancies of normal pregnancy and pregnancy-induced hypertension through intravoxel incoherent motion MRI at the plateau area","fulltext":[{"header":"Background","content":"\u003cp\u003eThe placenta is responsible for crucial functions such as endocrine and immune regulation, nutrition, and respiration, which are primarily carried out through placental blood perfusion and diffusion \u003csup\u003e[1]\u003c/sup\u003e. Ultrasound imaging has been the most commonly used method to gain insight into the intricacies of the placenta, providing valuable information about its anatomy, location, and size. However, its limitations have become apparent when assessing placental microcirculation and microstructure \u003csup\u003e[2]\u003c/sup\u003e. To supplement ultrasound imaging, conventional MRI has been employed as an adjunctive tool. Functional magnetic resonance imaging (fMRI) that has shown promise in detecting placental blood microcirculation，microstructure and blood oxygen metabolism among other vital physiological parameters\u003csup\u003e[3]\u003c/sup\u003e. In this study, fMRI intravoxel incoherent motion (IVIM) was utilized to investigate the state of microcirculation perfusion and microstructure. By noninvasively separating the movement of microscopic water molecules inside and outside tissue cells and blood vessels, this magnetic resonance imaging technology offers a comprehensive evaluation of the physiological state of organs throughout the body\u003csup\u003e[4]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003ePregnancy-Induced Hypertension（PIH） poses a significant threat to the health of mother and child, including: gestational hypertension, preeclampsia, eclampsia, chronic hypertension during pregnancy, and chronic hypertension complicated with preeclampsia \u003csup\u003e[5]\u003c/sup\u003e. Globally, the incidence of PIH ranges from 6% to 8%\u003csup\u003e[6]\u003c/sup\u003e. Interestingly, in the plateau (\u0026ge;2500m), the prevalence of PIH was nearly twice than in the plain, with a staggering 63% increase in the likelihood of stillbirth \u003csup\u003e[7,8]\u003c/sup\u003e. With the population in the plateau areas on the rise, it became increasingly pertinent to delve into the changes in the microcirculation and microstructure of PIH and normal placenta in these environments. At present, most studies using MRI-IVIM have mainly been used to distinguish fetal growth restriction, normal placenta from placenta accreta spectrum disorder, and diseases of other organs\u003csup\u003e\u0026nbsp;[9,10]\u003c/sup\u003e, but there are few studies on placental microcirculation and microstructure in plateau areas during PIH and normal late pregnancy.Understanding these alterations will not only aid in the management and prevention of PIH，but also shed light on the unique challenges faced by pregnant women residing in plateau regions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1 Subjects\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRetrospective analysis was performed on 26 cases of PIH diagnosed in the obstetrics department of Qinghai Red Cross Hospital during the third trimester (6 cases of preeclampsia, 20 cases of pregnancy-induced hypertension), 28 cases of healthy pregnant women in the third trimester(PWTT) and 18 cases of healthy pregnant women in the second trimester(PWST) from August 2019 to January 2022 (Table 1). Inclusion criteria (1) Generations living\u0026nbsp;in a\u0026nbsp;plateau area\u0026nbsp;(altitudes\u0026ge;2500m)\u0026nbsp;(2) single birth; (3) Pregnant women do not smoke, alcoholism, genetic metabolic diseases. Exclusion criteria :(1) fetal malformation, multiple births; (2) pregnancy with diabetes, thyroid disease; (3) pregnancy with pelvic tumor; (4) placental abruption; (5) placenta accreta spectrum disorder ;(6) Clinical data of pregnant women were incomplete or images could not be evaluated.（Figure 1）\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003e2.2 Diagnostic criteria of Hypertensive disorders of pregnancy\u003c/strong\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdopt ISSHP classification, diagnosis \u0026amp; management recommendations of the hypertensive disorders during pregnancy\u003csup\u003e[11]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2.3\u003c/strong\u003e \u003cstrong\u003eResearch method\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImaging: MRI acquisition\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe utilized the Siemens Skyra 3.0T MRI scanner with a 4-channel body phase controlled surface coil to capture images within a single breath-holding interval. The scan encompassed the region from the diaphragm to the symphysis pubis. The pregnant woman assumed a supine or lateral position,with the foot positioned forward. To optimize the efficiency and minimize time spent in the scanning process, we limited the scanning to IVIM scans: featuring a field of view (FOV) of 380mm\u0026times;380mm, a layer thickness of 5.5mm, a matrix size of 192\u0026times;120, and 8 b values (0,50,100,150,200,250,500,800 s/mm\u003csup\u003e2\u003c/sup\u003e). The total scanning time was 6 minutes and 32 seconds..\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eSonography\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll pregnant women underwent abdominal ultrasound examination using the LOGIQ E9 ultrasound scanner(GE Healthcare,WI) after receiving MRI examination. The senior attending physician specializing in abdominal ultrasound diagnosis measured the fetal double parietal diameter, head circumference, abdominal circumference, femur length and humerus length, respectively. The mean values of these parameters were then input into the software, and the estimating fetal weight(EFW) was assessed using the Had-lock formula.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eImaging: Postprocessing \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe utilized the MITK-diffusion software(Copyright\u003csup\u003e\u0026copy;\u003c/sup\u003eGerman Cancer Research Center (DKFZ), Division of Medical Image Computing (MIC)) to identify the maximum layer of placenta on the IVIM image(b=0) as the measuring center for all pregnant women. We made sure to avoid the large blood vessels, infarcts and calcification areas. Three regions of interest (ROIs) were defined on the fetal side, maternal side and central area of the placenta.Fetal side was considered as the side where the placental edge faced the fetus, while the opposite side was considered the maternal side. The area between them was defined as the central area. In addition, we also measured the whole placenta. Two adjacent layers of the maximum layer were also assessed by two radiologists. The parameters of IVIM and the double exponential model were obtained, and the perfusion fraction (\u003cem\u003ef\u003c/em\u003e), standard diffusion coefficient (\u003cem\u003eD\u003c/em\u003e) and false diffusion coefficient (\u003cem\u003eD\u003c/em\u003e\u003csup\u003e\u0026lowast;\u003c/sup\u003e) were calculated by means of average values. Used a double exponential model S\u003csub\u003eb\u003c/sub\u003e/S\u003csub\u003e0\u003c/sub\u003e = (1-\u003cem\u003ef\u003c/em\u003e) \u0026middot;exp(-b\u003cem\u003eD\u003c/em\u003e)+f\u0026middot;exp[-b (\u003cem\u003eD\u003c/em\u003e+\u003cem\u003eD\u003c/em\u003e\u003csup\u003e\u0026lowast;\u003c/sup\u003e)] (S\u003csub\u003e0\u003c/sub\u003e and S\u003csub\u003eb\u003c/sub\u003e were signal intensity at b values of 0s/mm\u003csup\u003e2\u003c/sup\u003e and b values of 0, 50, 100, 150, 200, 250, 500 and 800s/mm\u003csup\u003e2\u003c/sup\u003e,respectively). (Figure 2A-E) \u003cem\u003eD\u003c/em\u003e represents simple diffusion of water molecules, \u003cem\u003eD\u003c/em\u003e\u003csup\u003e\u0026lowast;\u003c/sup\u003e represents capillary microcirculation perfusion, and \u003cem\u003ef\u003c/em\u003e represents the ratio of the capillary volume in voxels to the total tissue volume.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4\u003c/strong\u003e \u003cstrong\u003eStatistical methods\u003c/strong\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSPSS 22.0 software was used for processing, continuous variable data are expressed as (\u0026plusmn;\u003cem\u003eS\u003c/em\u003e), independent sample \u003cem\u003et\u003c/em\u003e tests or one-way analysis of variance were used, and multiple comparisons among the three groups of placental quantitative parameters were analyzed by the Bonferroni method. The correlations between placental IVIM parameters and the EFW, postnatal weight, gestational age and gestational weeks were analyzed by Pearson correlation analysis. The consistency analysis of data measured by two radiologists was analyed by the Bland-Altman method,and \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e\n"},{"header":"Results","content":"\u003cp\u003eBland-Altman showed that the IVIM parameters of the three groups were within the range of 1.96 times standard deviation, with good consistency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1 Placental characteristics of normal PWST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe maternal and fetal sides of 18 normal PWST placentas were indistinguishable from those of the IVIM parameter maps. The \u003cem\u003eD\u003c/em\u003e value on the maternal side of the placenta was lower than that on the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05), and the\u003cem\u003e\u0026nbsp;f\u003c/em\u003e and D\u003csup\u003e*\u003c/sup\u003e values on the maternal side of the placenta were greater than those on the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).(Table.2)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Placental characteristics of normal PWTT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e28 normal placentas from PWTT pregnant women were distinguishable on the maternal and fetal sides by an IVIM parametric map, and 4 cases were not. Between the fetal and maternal sides of the placenta are interlaced in strips in the \u003cem\u003eD\u003c/em\u003e, \u003cem\u003eD\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e, \u003cem\u003ef\u003c/em\u003e value diagram. The value of \u003cem\u003eD\u003c/em\u003e and\u003cem\u003e\u0026nbsp;D\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e on the maternal side of placenta were greater than the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05), and the value of \u003cem\u003ef\u003c/em\u003e on the maternal side of the placenta was greater than that on the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05).(Table.3)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Placental characteristics of PIH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e26 PIH placentas on the maternal and fetal sides could not distinguish on the IVIM parametric map. \u0026nbsp;The values of\u003cem\u003e\u0026nbsp;f\u003c/em\u003e, D and \u003cem\u003eD\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e on maternal side of placenta were higher than the fetal side, but no statistical significance (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).(Table.4)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4\u003c/strong\u003e \u003cstrong\u003eComparison of placental IVIM parameters among PWTT and PWST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003eD\u003c/em\u003e value on the maternal side of PWTT placenta was higher than PWST (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), and the values of\u003cem\u003e\u0026nbsp;f\u0026nbsp;\u003c/em\u003eand \u003cem\u003eD\u003c/em\u003e\u003csup\u003e*\u003c/sup\u003e of MS, FS and WP in PWTT placenta were higher than PWST (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).(Table.5)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5\u003c/strong\u003e \u003cstrong\u003eComparison of placental IVIM parameters,EFW and postnatal weight among three groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe fetal side and whole placental \u003cem\u003ef\u003c/em\u003e values in normal PWTT were higher than PIH (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), the maternal side and whole placental \u003cem\u003eD\u003c/em\u003e values in normal PWTT were higher than PIH (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), the EFW and postnatal weight in normal PWTT were higher than PIH (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05).(Table.6)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.6\u003c/strong\u003e \u003cstrong\u003eRelationship of placental IVIM parameters with gestational age, gestational weeks,EFW and postnatal weight in normal PWTT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003ef\u003c/em\u003e value of PWTT on maternal side was negatively correlated with EFW (\u003cem\u003er\u003c/em\u003eMS\u003cem\u003e\u003csub\u003ef\u003c/sub\u003e\u003c/em\u003e=-0.579, \u003cem\u003eP\u003c/em\u003e=0.005), and \u003cem\u003ef\u003c/em\u003e value of PWTT on maternal side was negatively correlated with gestational weeks (\u003cem\u003er\u003c/em\u003eMS\u003csub\u003ef\u003c/sub\u003e=-0.441, \u003cem\u003eP\u003c/em\u003e=0.005).（figure 3）\u003cem\u003eD\u003csup\u003e*\u003c/sup\u003e\u003c/em\u003e,\u003cem\u003eD\u003c/em\u003e value of PWTT were not correlated with EFW,postnatal weight,gestational age and gestational weeks (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). \u003cem\u003ef\u003c/em\u003e, \u003cem\u003eD\u003c/em\u003e and \u003cem\u003eD\u003csup\u003e*\u003c/sup\u003e\u003c/em\u003e value of PIH and PWST had no correlation with gestational age,gestational weeks,EFW and postnatal weight.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBackground \u0026amp; Principle of IVIM imaging and Placental Interpretations\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;PIH posed a significant risk to the health of pregnant women and the growth and development of the fetus, with adverse potential effects throughout the entire pregnancy and beyond, warranting clinical attention. Research had indicated \u003csup\u003e[12]\u003c/sup\u003e that PIH was associated with abnormal placental morphology and a higher incidence of early placental poor perfusion in cases of combined PIH and fetal growth restriction compared to isolated fetal growth restriction. Moreover, the prevalence of PIH was nearly double in pregnant women residing at high altitudes (\u0026ge;2500m) compared to those at lower altitudes \u003csup\u003e[7]\u003c/sup\u003e. With the growing population at high altitudes, understanding the changes in placental microcirculation and microstructure in both normal and PIH-affected pregnancies in these areas was crucial.\u003c/p\u003e\n\u003cp\u003eIVIM-DWI had the capability to differentiate between actual water molecule diffusion movement and capillary blood flow movement, providing a comprehensive assessment of tissue diffusion and perfusion through quantitative parameters (\u003cem\u003eD\u003c/em\u003e, \u003cem\u003eD\u003csup\u003e*\u003c/sup\u003e\u003c/em\u003e, \u003cem\u003ef\u0026nbsp;\u003c/em\u003evalue). The\u003cem\u003e\u0026nbsp;D\u003c/em\u003e value related to the actual diffusion of water molecules, cell density and cytoplasmic ratio, while the value of \u003cem\u003eD\u003csup\u003e*\u003c/sup\u003e\u003c/em\u003e was associated with diffusion movement, mean capillary length and blood flow velocity related to capillary perfusion. The \u003cem\u003ef\u0026nbsp;\u003c/em\u003evalue pertained to the proportion of blood flow movement in capillaries and the richness of capillaries within a unit voxel \u003csup\u003e[13,14]\u003c/sup\u003e. Given the rich vascularization on the maternal side of the placenta, alongside the fetal side and the interstitium comprising the placental circulatory system \u003csup\u003e[15]\u003c/sup\u003e, understanding the hemodynamics of this system and the interstitial function is crucial in evaluating placental structural and functional changes\u003csup\u003e\u0026nbsp;[16]\u003c/sup\u003e. Research aimed at uncovering and understanding the placental circulatory system and interstitial diffusion perfusion function at high altitudes holded promise for clinical assessment of placental health.\u003c/p\u003e\n\u003cp\u003ePrincipal Findings\u003c/p\u003e\n\u003cp\u003eThe results of this study indicated that there were no significant differences in IVIM parameters between the maternal side, fetal side and central region of the placenta in PWST at high altitude areas. However, the IVIM parameters differed from those in PWTT. For example, the \u003cem\u003eD\u003c/em\u003e value of the maternal side of the PWTT placenta was higher than PWST (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), suggesting that the organizational structure on the maternal side of PWST placenta was not fully mature,and the corresponding functions of microcirculation and microstructure were yet to mature.\u003c/p\u003e\n\u003cp\u003eIn PWTT, the \u003cem\u003ef\u003c/em\u003e value of the maternal side of placenta was higher than the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), which was in line with the research results of Antonelli \u003csup\u003e[17]\u003c/sup\u003e et al in the plain areas, indicating that the water molecules in this area were mainly related to blood flow movement, which was associated with the rich uterine spiral arteries and capillaries on the maternal side of the placenta and the fast speed of blood flow. The \u003cem\u003ef\u003c/em\u003e value of the maternal side of PIH placenta was slightly higher than the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). Compared with PWTT, the \u003cem\u003ef\u0026nbsp;\u003c/em\u003evalue of maternal side and whole placenta of PIH were lower than PWTT (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003eIn the PWTT, \u003cem\u003eD\u003c/em\u003e and \u003cem\u003eD\u003csup\u003e*\u003c/sup\u003e\u003c/em\u003e values on the maternal side of the placenta were higher than the fetal side (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05), which was different from the results of the plain areas\u003csup\u003e[17]\u003c/sup\u003e, suggesting that the diffusion activities related to water molecules and capillary blood flow movement on the fetal side were altered in plateau areas. The differences may be related to the pathological changes of placenta caused by hypoxia in plateau areas, such as increased blood vessels and villi, thinning of chorion, vascular syncytia, and deposition of cellulose-like material\u003csup\u003e[18]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWorth noting was that the difference of \u003cem\u003eD\u003c/em\u003e value between the maternal and fetal side was not significant, indicating that under hypoxia, compensatory reaction such as the increase of placental blood vessels and the formation of vascular syncytial membrane could not promote the diffusion movement. Additionally, the \u003cem\u003eD\u003c/em\u003e values of the maternal side and the whole placenta in PWTT were higher than those of PIH (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), suggesting that the actual diffusion of water molecules in the placenta of PIH was impaired, which may be related to the reduction of placental villus volume and surface area in PIH\u003csup\u003e[8]\u003c/sup\u003e and hypoxia and ischemia at plateau area\u003csup\u003e[19]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eUnder the combined action of these two factors, placental ischemia and maternal-fetal material exchange capacity declined, ultimately leading to lower EFW and postnatal weight than PWTT (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). Additionally, it was observed that the central region between the maternal and fetal sides of the placenta in PWTT was the transition zone, with no significant difference in the parameters of IVIM (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). However, there was a certain correlation between maternal and fetal sides in the parameters of IVIM. This region was inferred to be the placental lobular, indicating that IVIM technology could effectively evaluate the placental microstructure\u003csup\u003e[20]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFurthermore, the\u003cem\u003e\u0026nbsp;f\u0026nbsp;\u003c/em\u003evalue on the maternal side of the placenta was negatively correlated with EFW in PWTT (\u003cem\u003er\u003c/em\u003e maternal side\u003cem\u003e\u0026nbsp;f\u003c/em\u003e=-0.579, P=0.005), which differed \u0026nbsp;from that in the plain area, indicating that the compensatory changes of the placenta caused by hypoxia-ischemia in the plateau area, such as increased placental blood vessels and villi, could result in a reduction of the blood filling space on the maternal side. Consequently, the blood flow volume per unit villus surface area decreased\u003csup\u003e[21]\u003c/sup\u003e, leading to a decrease in the \u003cem\u003ef\u003c/em\u003e value on the maternal side of the placenta and ultimately inadequate fetal supply. Additionally, the\u003cem\u003e\u0026nbsp;f\u003c/em\u003e value on the maternal side of PWTT was also negatively correlated with gestational weeks (\u003cem\u003er\u0026nbsp;\u003c/em\u003ematernal \u003cem\u003ef\u003c/em\u003e=-0.441, \u003cem\u003eP\u003c/em\u003e=0.04). This may be attributed to an increase in placental villi proliferation and maturation, leading to a denser arrangement, narrowing of the intervillous space, and a further reduction in the maternal blood filling space as gestational weeks progress\u003csup\u003e\u0026nbsp;[22]\u003c/sup\u003e. This eventually lead to a further decrease in the f value on the maternal side.\u003c/p\u003e\n\u003cp\u003eLimitations and Future research\u003c/p\u003e\n\u003cp\u003eThis study still had some limitations that need to be addressed. Firstly, the sample size of the three groups was small and lacked corresponding pathological control studies, highlighting the need for further expansion of the sample size. Additionally, different types of PIH should be classified,and exploring the characteristic of placental microcirculation and microstructure.\u003c/p\u003e\n\u003cp\u003eSecondly, the IVIM parameter diagram could not completely distinguish the fetal and maternal circulatory system, suggesting the need for further optimization of IVIM parameters and post-processing algorithms in the future.\u003c/p\u003e\n\u003cp\u003eLastly, in the future research, it would be beneficial to explore the integration of artificial intelligence technology to extract more high-quality information and develop a practical artificial intelligence model to identify and address related issues.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe IVIM technology offered a dependable means for non-invasively separating placental tissue cells and observing the movement of microscopic water molecules within and outside placental blood vessels. It provided valuable insights into the state of microcirculation perfusion, allowing for the evaluation of placental function under both pathological and physiological conditions at both the micro and macro levels. In doing so, it brought a fresh perspective to the observation of characteristic in placental microstructure and microcirculation.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003ePIH: pregnancy-induced hypertension\u003c/p\u003e\n\u003cp\u003eIVIM: intravoxel incorrelation movement\u003c/p\u003e\n\u003cp\u003eMRI: magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003ePWST: pregnant women in the second trimester\u003c/p\u003e\n\u003cp\u003ePWTT: pregnant women in the third trimester\u003c/p\u003e\n\u003cp\u003eD: diffusion coefficient\u003c/p\u003e\n\u003cp\u003eD*: pseudo-diffusion coefficient\u003c/p\u003e\n\u003cp\u003ef: perfusion fraction\u003c/p\u003e\n\u003cp\u003eEFW:estimated fetal weight\u003c/p\u003e\n\u003cp\u003eGA:gestational age\u003c/p\u003e\n\u003cp\u003eGW:gestational weeks\u003c/p\u003e\n\u003cp\u003ePW:Postnatal weight\u003c/p\u003e\n\u003cp\u003eMS:Maternal side \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFS:Fetal side \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWP:whole placenta\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Medical Ethics Committee of Qinghai Red Cross Hospital（No. KY-2019-40）,and all participants signed informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFL and GL designed the research; ZYY LYK and SLW recruited patients and collected clinical information; ZYY and ZNG collected and managed database; SLW and LYK were involved in review of data within the obstetrics registry and adjudication of hypertensive disorders of pregnancy; ZYY and LYK adjudicated adverse outcomes; FL and ZYY performed datas analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded with support from the Qinghai Provincial Basic Research Program - Applied Basic Research Project (No. 2020-0301-ZJC-0089).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are very grateful to all patients who consented and performed an MRI-IVIM scan. \u0026nbsp;We thank Dr. Gang Liu for constructive critiques on the research and manuscript. We also thank Dr. Shenlan Wang for the recruitment of patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBurton GJ, Charnock-Jones DS, Jauniaux E. Regulation of vascular growth and function in the human placenta. Reproduction. 2009;138(6):895-902. doi:10.1530/REP-09-0092\u003c/li\u003e\n\u003cli\u003eGowland P. Placental MRI. Semin Fetal Neonatal Med. 2005;10(5):485-490. doi:10.1016/j.siny.2005.05.001\u003c/li\u003e\n\u003cli\u003eSiauve N, Chalouhi GE, Deloison B, et al. Functional imaging of the human placenta with magnetic resonance. Am J Obstet Gynecol. 2015;213(4 Suppl):S103-S114. doi:10.1016/j.ajog.2015.06.045\u003c/li\u003e\n\u003cli\u003eFeng YZ, Chen XQ, Yu J, et al. Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients. Abdom Radiol (NY). 2018;43(10):2764-2773. doi:10.1007/s00261-018-1555-7.\u003c/li\u003e\n\u003cli\u003eBrown MA, Magee LA, Kenny LC, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis \u0026amp; management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. doi:10.1016/j.preghy.2018.05.004\u003c/li\u003e\n\u003cli\u003eLenfant C; National Education Program Working Group on High Blood Pressure in Pregnancy. Working group report on high blood pressure in pregnancy. J Clin Hypertens (Greenwich). 2001;3(2):75-88. doi:10.1111/j.1524-6175.2001.00458.x \u003c/li\u003e\n\u003cli\u003eImogen D,Grant,Dino A,Giussani,Catherine E,Aiken.Blood pressure and hypertensive disorders of pregnancy at high altitude: a systematic review and meta-analysis.[J].American journal of obstetrics\u0026amp;gynecology MFM,2021,3(5):100400.doi:10.1016/j.ajogmf.2021.100400.\u003c/li\u003e\n\u003cli\u003eDi Martino DD, Avagliano L, Ferrazzi E, et al. Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets. Nutrients. 2022;14(16):3276. doi:10.3390/nu14163276.\u003c/li\u003e\n\u003cli\u003eAlessandra,Maiuro,Giada, et al.Two-Compartment Perfusion MR IVIM Model to Investigate Normal and Pathological Placental Tissue.[J].Journal of magnetic resonance imaging : JMRI,2024,59(3):879-891.\u003c/li\u003e\n\u003cli\u003eWang Q, Yu G, Qiu J, Lu W. Application of Intravoxel Incoherent Motion in Clinical Liver Imaging: A Literature Review. J Magn Reson Imaging. Published online November 1, 2023. doi:10.1002/jmri.29086.\u003c/li\u003e\n\u003cli\u003eBrown MA, Magee LA, Kenny LC, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis \u0026amp; management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. doi:10.1016/j.preghy.2018.05.004\u003c/li\u003e\n\u003cli\u003eEgbor M, Ansari T, Morris N, Green CJ, Sibbons PD. Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG. 2006;113(5):580-589. doi:10.1111/j.1471-0528.2006.00882.x \u003c/li\u003e\n\u003cli\u003eHu YC, Yan LF, Wu L, et al. Intravoxel incoherent motion diffusion-weighted MR imaging of gliomas: efficacy in preoperative grading. Sci Rep. 2014;4:7208. Published 2014 Dec 1. doi:10.1038/srep07208\u003c/li\u003e\n\u003cli\u003eIima M. Perfusion-driven Intravoxel Incoherent Motion (IVIM) MRI in Oncology: Applications, Challenges, and Future Trends. Magn Reson Med Sci. 2021;20(2):125-138. doi:10.2463/mrms.rev.2019-0124\u003c/li\u003e\n\u003cli\u003eSolomon E, Avni R, Hadas R, et al. Major mouse placental compartments revealed by diffusion-weighted MRI, contrast-enhanced MRI, and fluorescence imaging. Proc Natl Acad Sci U S A. 2014;111(28):10353-10358. doi:10.1073/pnas.1401695111\u003c/li\u003e\n\u003cli\u003eAlison M, Chalouhi GE, Autret G, et al. Use of intravoxel incoherent motion MR imaging to assess placental perfusion in a murine model of placental insufficiency. Invest Radiol. 2013;48(1):17-23. doi:10.1097/RLI.0b013e318271a5f8.\u003c/li\u003e\n\u003cli\u003eAntonelli A, Capuani S, Ercolani G, et al. Human placental microperfusion and microstructural assessment by intra-voxel incoherent motion MRI for discriminating intrauterine growth restriction: a pilot study. J Matern Fetal Neonatal Med. 2022;35(25):9667-9674. doi:10.1080/14767058.2022.2050365.\u003c/li\u003e\n\u003cli\u003eWilsterman K, Cheviron ZA. Fetal growth, high altitude, and evolutionary adaptation: a new perspective. Am J Physiol Regul Integr Comp Physiol. 2021;321(3):R279-R294. doi:10.1152/ajpregu.00067.2021. \u003c/li\u003e\n\u003cli\u003eZamudio S. The placenta at high altitude. High Alt Med Biol. 2003;4(2):171-191. doi:10.1089/152702903322022785.\u003c/li\u003e\n\u003cli\u003eBonel HM, Stolz B, Diedrichsen L, et al. Diffusion-weighted MR imaging of the placenta in fetuses with placental insufficiency. Radiology. 2010;257(3):810-819. doi:10.1148/radiol.10092283\u003c/li\u003e\n\u003cli\u003eJung EJ, Cho HJ, Byun JM, et al. Placental pathologic changes and perinatal outcomes in placenta previa [published correction appears in Placenta. 2019 Mar;78:54]. Placenta. 2018;63:15-20. doi:10.1016/j.placenta.2017.12.016\u003c/li\u003e\n\u003cli\u003eGude NM, Roberts CT, Kalionis B, et al. Growth and function of the normal human placenta. Thromb Res. 2004;114(5-6):397-407. doi:10.1016/j.thromres.2004.06.038.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Placenta, microcirculation, intra-voxel incoherent motion(IVIM), Pregnancy-Induced Hypertension(PIH), plateau area","lastPublishedDoi":"10.21203/rs.3.rs-4752678/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4752678/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eA preliminary study of placental microcirculation and microstructure in healthy pregnant women in different trimesters and pregnancy-induced hypertension (PIH) at plateau through intravoxel incorrelation movement (IVIM).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective analysis was conducted at Qinghai Red Cross Hospital from August 2019 to January 2022. All subjects(18,28 pregnant women in the second trimester/third trimester[PWST/PWTT], 26 PIH) underwent ultrasound,MRI-IVIM examinations.The true diffusion coefficient (\u003cem\u003eD\u003c/em\u003e),false diffusion coefficient (\u003cem\u003eD\u003c/em\u003e*), perfusion fraction (\u003cem\u003ef\u003c/em\u003e) values of the whole placenta and different placental sites, estimated fetal weight (EFW) and postnatal weight were measured and recorded. The statistic was analyzed by independent sample t test or single factor ANOVA,multiple comparisons of placental quantitative parameters between subjects were analyzed by the Bonferroni method. The correlations between placental IVIM parameters and fetal weight, GA and GW were analyzed by Pearson correlation analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNo significant differences among the different placental parts of the PWST. The difference among the placenta in PWTT-\u003cem\u003ef\u003c/em\u003e(maternal side\u0026gt;fetal side, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). Compare with PWST, PWTT\u0026gt;PWST- \u003cem\u003eD\u003c/em\u003e(maternal side,\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). In contrast to PIH,PWTT\u0026gt;PIH-\u003cem\u003ef\u003c/em\u003e(fetal side, whole placenta,\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), PWTT\u0026gt;PIH-\u003cem\u003eD\u003c/em\u003e(maternal side, whole placenta,\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).EFW and postnatal weight of PWTT \u0026gt; PIH(\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).PWTT-\u003cem\u003ef\u003c/em\u003e(maternal side)was negatively correlated with EFW (\u003cem\u003er\u003c/em\u003e=-0.579, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), PWTT-\u003cem\u003ef\u003c/em\u003e(maternal side) was negatively correlated with GW (\u003cem\u003er\u003c/em\u003e=-0.441, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005).\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eIVIM could effectively analyze and evaluate the characteristic of placental microcirculation and microstructure in normal and PIH pregnant women at plateau.\u003c/p\u003e","manuscriptTitle":"Exploring in vivo placental microcirculation and microstructure in different pregnancies of normal pregnancy and pregnancy-induced hypertension through intravoxel incoherent motion MRI at the plateau area","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-23 21:12:29","doi":"10.21203/rs.3.rs-4752678/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"54a814b5-5083-46f7-a2e6-0824bc684ea7","owner":[],"postedDate":"August 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-15T14:23:59+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-23 21:12:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4752678","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4752678","identity":"rs-4752678","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}