Original Article
Reference Ranges of Fetal Cisterna Magna Length and Area Measurements by 3-Dimensional Ultrasonography Using the Multiplanar Mode
Journal of Child Neurology 2015, Vol. 30(2) 209-215 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814535496 jcn.sagepub.com
Ana Paula Passos, MD1, Edward Araujo Ju´nior, MD, PhD1, Rafael Frederico Bruns, MD, PhD2, Luciano Marcondes Machado Nardozza, MD, PhD1, and Antonio Fernandes Moron, MD, PhD1
Abstract This study aimed to establish reference values for the length and area of the fetal cisterna magna using the multiplanar mode of 3-dimensional ultrasonography. A cross-sectional study including 224 normal pregnant women between 17 weeks 0 days and 29 weeks 6 days of gestation was carried out. The area and length of the fetal cisterna magna were measured in the axial plane at the level of the cerebellar transverse diameter. Reliability was determined by intraclass correlation coefficient. The mean length and area of the fetal cisterna magna ranged from 0.50 + 0.10 to 0.79 + 0.18 cm and 0.95 + 0.18 to 3.09 + 0.62 cm2, respectively. Intraobserver reliability for the length and area (intraclass coefficients: 0.86 and 0.91, respectively) and interobserver reliability (intraclass coefficients: 0.64 and 0.82, respectively) were good. Three-dimensional ultrasonography using the multiplanar mode is a reliable method for the determination of reference values for the length and area of the fetal cisterna magna. Keywords area, cisterna magna, fetus, length, multiplanar mode, reference ranges, 3-dimensional ultrasound Received December 16, 2013. Received revised March 21, 2014. Accepted for publication March 30, 2014.
Cisternae are spaces larger than the subarachnoid, characterized by a greater accumulation of cerebrospinal fluid compared with other regions. The main cisternae are the cisterna magna, pontine, interpeduncular, and chiasmatic.1 The cisterna magna is located in the posterior fossa, between the anterior face of the cerebellum and the dorsal part of the bulb, and continues caudally into the spinal subarachnoid space, connecting to the fourth ventricle through the middle opening.2 Evaluation of the posterior fossa by 2-dimensional ultrasonography allows the identification of several anomalies such as Dandy-Walker malformation and megacisterna magna.3 A cutoff length of 10 mm is indicative of an enlargement of the cisterna magna.4,5 Changes in the anteroposterior length of the fetal cisterna magna during pregnancy have been evaluated by 2-dimensional ultrasonography in only a few studies, which found an increase in length with advancing gestation.6,7 Therefore, the use of a fixed cutoff anteroposterior length at all gestational ages can lead to diagnostic errors. Moreover, the measurement of the length of the fetal cisterna magna is subject to bias because of the difficulty in standardizing the exact reference points. This shortcoming could be addressed
by assessing the area because of the irregular shape of the cisterna magna. Methods for the evaluation of the vermis area of the cerebellum and fetal corpus callosum have been described8,9; however, no study has evaluated this parameter in the cisterna magna. Three-dimensional ultrasonography in multiplanar mode provides an exact plane for measuring fetal brain structures and allows its offline evaluation.10 Recently, measurements of the anteroposterior diameter of the fetal cisterna magna by 2- and 3-dimensional ultrasonography between 18 and 24 weeks of
1
Department of Obstetrics, Federal University of Sa˜o Paulo, Sa˜o Paulo-SP, Brazil 2 Department of Gynecology and Obstetrics, Federal University of Parana´, Curitiba-PR, Brazil Corresponding Author: Edward Araujo Ju´nior, MD, PhD, Department of Obstetrics, Federal University of Sa˜o Paulo, Rua Carlos Weber, 956 apt. 113 Visage, Vila Leopoldina, Sa˜o Paulo – SP, Brazil. Email: [email protected]
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Figure 1. (A) Acquisition of the volume of the fetal skull by 3-dimensional ultrasonography, with reference to the plane of measurement of the lateral ventricles. (B) Measurement of the anteroposterior length of the cisterna magna. (C) Measurement of the area of the cisterna magna.
gestation were compared using the extended imaging virtual organ computer-aided analysis method.11 There are no reports describing the use of 3-dimensional ultrasonography in the multiplanar mode to measure the length and area of the fetal cisterna magna during pregnancy. The objective of this study was to construct reference values for the length and area of the fetal cisterna magna using 3-dimensional ultrasonography in the multiplanar mode in pregnant women between 17 weeks 0 days and 29 weeks 6 days of gestation.
Methods A prospective cross-sectional study that included normal pregnant women who were between 17 weeks 0 days and 29 weeks 6 days of gestation was conducted between August 2010 and January 2012. This study was approved by the Ethics Committee of the Federal University of Sa˜o Paulo, and pregnant women provided written informed consent. The patients were randomly selected, and all ultrasound examinations were performed in the Fetalmed Clinic, Curitiba-PR, Brazil. All patients were evaluated only once, and postnatal results were not obtained. All examinations were performed by a single examiner (APP) using a Voluson 730 Expert device brand 3-dimensional ultrasound (General Electric Medical Systems, Zipf, Austria). The analysis was performed off line using the program 4D Views version 10.0 (General Electric Medical Systems). The inclusion criterion was a singleton pregnancy with gestational age confirmed until 13w0d by crown-rump length. Exclusion criteria were fetal malformations detected by ultrasonography, pregnant
women with chronic diseases (hypertension, diabetes mellitus, or collagenosis), fetuses with estimated weight below the 10th percentile or above the 90th percentile according to the method of Hadlock et al,12 reduced image quality due to increased body mass index >30 kg/m2, or presence of surgical scar.
Case Summary Initially, real-time 2-dimensional ultrasonography was performed to determine the biometric parameters, amniotic fluid index and the morphology. Then, a 3-dimensional neurosonogram was carried out as second step examination with the following ultrasound settings: insonation angle was standardized at 50 to 70 according to gestational age, normal speed mode, high quality, and harmonic mode. When the fetus was at rest, the patient was required to maintain apnea for a few seconds and the scanning box was activated to encompass the entire fetal head (volume of interest). Volume data sets were acquired using the lateral ventricle as the standard reference plane. The image was displayed in the 3 orthogonal planes using multiplanar mode as follows: axial (A, acquisition plane), sagittal (B), and coronal (C) (Figure 1A). Plane A was selected as a reference plane and displaced in the craniocaudal direction using the REF SLICE key until the acquisition of the default plane for measuring the transverse cerebellar diameter, as proposed by Goldstein et al.13 Then, a 1 1 arrangement was used and the image was magnified to occupy 75% of the screen. The MEASURE key was activated and the anteroposterior fetal cisterna magna length was measured. For this purpose, the 2 diametrically most distant points in the vermis and the internal face of the occipital bone were used as standard parameters
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Figure 2. Scatter-plot of the length (A) and area (B) of the fetal cisterna magna according to gestational age. and the length was measured at this level (Figure 1B). The internal region of the fetal cisterna magna was drawn manually (Figure 1C) to calculate the value of the area. Only a single volume of the fetal skull was collected. The data were stored in the memory of the device and then transferred to compact discs for off-line analysis by a single operator (APP). Data were transferred to the spreadsheet program Excel 2007 (Microsoft Corp, Redmond, WA) and analyzed by SPSS (version 18.0, SPSS Inc, Chicago, IL) and GraphPad (version 5.0, GraphPad Software, San Diego, CA). For descriptive analyses, the means, medians, standard deviations, and minimum and maximum values for the length and area of the cisterna magna at each gestational age were calculated. To construct reference ranges for the length and area of the fetal cisterna magna as a function of gestational age, polynomial regressions were calculated and adjustments were made by the determination coefficient (R2). The 5th, 50th, and 95th percentiles were determined for each gestational age according to the method proposed by Altman and Chitty.14 For calculations of reliability and agreement, the same investigator performed a second random measurement of 50 volumes with an interval of at least 30 days after the first (intraobserver), whereas a second examiner (RFB) performed a third measurement of the same 50 volumes. Both examiners were blinded to each other’s results. The intraclass correlation coefficient was used for the evaluation of intraand interobserver reliability, whereas the limits of agreement and Bland-Altman plots15 were used to assess intra- and interobserver agreement. Statistical level of P 30 weeks resulted in failure in 62% of cases because of occipital ossification. Furthermore, after 30 weeks of gestation, inclusion of the entire fetal head within the scanning window during 3-dimensional ultrasonography is difficult,9,10 and minor clinical diagnoses of anomalies of the posterior fossa are important after this gestational age. We did not perform a power analysis to calculate sample size. According to Royston, to construct reference intervals with 90%
variation between the 5th and 95th percentiles of distribution, the analysis of 20 patients per week is recommended.19 In this study, we proposed the assessment of 18 patients per week in 13 gestational ages. The objective would be to assess 234 patients, which is in agreement as suggested by Royston.19 A 10-mm cutoff length of the cisterna magna is used as the standard parameter to indicate fetal abnormalities of the posterior fossa.4,5 However, some evidence suggests that the length of the fetal cisterna magna increases with gestational age.17,20 Two studies assessed changes in the length of the fetal cisterna magna during pregnancy by 2-dimensional ultrasonography. In a study by Serhatlioglu et al,6 130 pregnant women between 16 and 38 weeks of gestation were evaluated, and statistically significant differences in the length of the fetal cisterna magna were observed in the second and third trimesters; however, no reference values for each gestational age or reliability and agreement values were provided. In a study by Koktner et al,7 the authors evaluated the length of the fetal cisterna magna in 194 pregnant women between 16 and 24 weeks of gestation. The authors observed a linear correlation with gestational age, with the mean length of fetal cisterna magna ranging from 3.26 to 5.90 mm during this gestational period. In the present study, we observed a slightly greater mean length (5.0-7.1 mm) during the same gestational period. However, their study evaluated only the second trimester, and the changes in the length of the fetal cisterna magna in the third trimester cannot be estimated; furthermore, reliability and agreement were not evaluated. The reference range for length and area of the cisterna magna in the fetus calculated at different gestational age have been constructed by the first time using 3-dimensional ultrasound in multiplanar mode with the respective reliability and agreement values. Three-dimensional ultrasonography allowed the identification of the exact axial plane of measurement of the cisterna magna through the use of the REF SLICE key. Although it is not essential for 2-dimensional measurement, the multiplanar mode allows faster and more practical analysis of fetal central nervous system analysis because of automatic capture which allows the examiner to perform offline evaluation on his personal computer.9 We have observed a low correlation between the length of the cisterna magna and gestational age, which indicates that this parameter is not adequate for advanced gestational ages. We have attempted to develop a simple and easy method for the measurement of the fetal cisterna magna length and area by 3-dimensional ultrasonography in the multiplanar mode. We chose to use only the REF SLICE key in the craniocaudal direction to determine the transverse cerebellar diameter in a simple and reproducible manner, and thus to test an ultrasound technique and its application in clinical setting. The technique described by Pilu et al21 is needed to collect the volume in the standardized plane, including the cavum septum pellucidum and transverse cerebellar diameter, which are difficult to assess in advanced gestational ages. Accurate measurement of the cisterna magna can be a challenge in the third trimester. In addition to the required use of the standard pattern of the transverse diameter of the cerebellum,13
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Figure 3. Bland-Altman plot showing the mean relative difference between 2 measurements performed by a single examiner (intraobserver) plotted against the difference in their means for the length (A) and area (B) of the fetal cisterna magna.
Figure 4. Bland-Altman plot showing the mean relative difference between 2 measurements performed by 2 observers (interobserver) plotted against the difference in their means for the length (A) and area (B) of the fetal cisterna magna.
which must include the cavum of the septum pellucidum, midbrain, and cerebral hemispheres, the angle of the transducer remains an issue that needs to be considered. According to Laing et al,22 if the transducer is angled in a semicoronal plane, the cisterna magna could falsely appear enlarged in approximately 40% of cases. This limitation may explain the low interobserver reliability in the measurement of the length of the fetal cisterna magna in this study, in which the intraclass correlation coefficient was 0.64. According to Shrout and Fleiss, an intraclass correlation coefficient between 0.40 and 0.75 is considered satisfactory.23 However, as the outcome is related to gestational age and the heterogeneity in the sample population was large (17 weeks 0 days and 29 weeks 6 days), higher
intraclass correlation coefficients, usually >0.80, are expected for application in clinical practice.24 Only 1 study has evaluated the length of the fetal cisterna magna by 3-dimensional ultrasonography. De Barros et al11 compared the measurements of the fetal cisterna magna in 69 normal pregnant women of 16w0d and 24w6d of gestation using the three-dimensional extended imaging method (multislice view). They observed that the 3-dimensional ultrasonography measurements were significantly higher than those obtained by 2-dimensional ultrasonography, and concluded that 3-dimensional ultrasonography allows the identification of the exact plane for the measurement of the length of the cisterna magna, resulting in more accurate measurements.
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Regarding the measurement of the area of the fetal cisterna magna, there are no studies in the medical records describing its application. We observed a good correlation between the area of the fetal cisterna magna and gestational age, which is best explained by a linear equation. This model has shown that area is a better parameter than length for evaluating the fetal cisterna magna, particularly in the third trimester, because it is less subject to bias such as that introduced by the head and the flexed fetal position, as observed in our data. In a study evaluating the length and area of the fetal corpus callosum in transfrontal view in 293 healthy pregnant women between 20 and 33 weeks of gestation, Araujo Ju´nior et al9 have showed that area is a reliable and consistent parameter. We believe that area should be the first parameter to be used in order to assess the fetal cisterna magna, despite the fact that it is more time consuming. Despite the use of both parameters in the conventional plane, the area has showed a better correlation with gestational age and better reproducibility. The multiplanar mode was used only to facilitate these measurements, mainly at an advanced gestational age. Our results indicate that 3-dimensional ultrasonography is not superior to 2-dimensional ultrasonography for the measurement of the fetal cisterna magna. Recently, our group published a study in which the fetal cisterna magna volume was assessed by 3-dimensional ultrasonography using the virtual organ computer-aided analysis method. In that study, we have used the same number of cases as in the present study, and we have determined the reference range of the fetal cisterna magna volume between 17 weeks 0 days and 29 weeks 6 days of gestation. In addition, we have showed good and low intra- and interobserver reproducibility, respectively.25 The main limitation of this study was the use of only the axial plane as the reference to measure the length and area of the fetal cisterna magna. However, this was a pioneer study in which we have attempted to develop a simple and reproducible method to assess the length and area of the fetal cisterna magna using 3-dimensional ultrasonography in the multiplanar mode. We believe that the technique is kept simple and reproducible by using only the axial plane for these measurements, which was confirmed by our results. The use of other orthogonal planes would be more difficult and time consuming, which would limit its clinical application. During the advanced gestational ages, measuring the length of the fetal cisterna magna in the standard plane is difficult using the cavum septum pellucidum and transverse cerebellar diameter as landmarks. In these cases, the multiplanar mode using the axial plane at the level of the lateral ventricles as the reference would be of particular importance, because it is easy and quick to obtain. Despite the limitations of the standardized acquisition plane in the multiplanar mode, we believe that our data will serve as a reference for future studies on the standardization of fetal cisterna magna measurements by 3-dimensional ultrasonography. In summary, we have calculated reference values for the length and area of the fetal cisterna magna by 3-dimensional ultrasonography using the multiplanar mode. As these curves proved reliable and consistent, we believe that they can be
applied in fetuses with suspected posterior fossa malformations, especially after the 24th week of gestation. Acknowledgments The authors would like to thank Dr. Wellington de Paula Martins at the Department of Gynecology and Obstetrics, Faculty of Medicine of Riberira˜o Preto, Sa˜o Paulo University for the statistical analysis.
Author Contributions APP and RFB collected the data for the study. APP wrote the manuscript. EAJ conceived and designed the study. LMMN and AFF reviewed the study. AFF supervised the study.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval This study was approved by the Ethics Committee of the Federal University of Sa˜o Paulo (0676/11), and pregnant women who agreed to participate voluntarily signed consent forms.
References 1. Moore KL, Persaud TV, Torchia MG. O sistema nervoso. Desenvolvimento da medula espinhal. Formac¸a˜o das meninges, da medula espinhal. In: Moore KL, Persaud TV, Torchia MG, eds. Embriologia clı´nica. 8th ed. Rio de Janeiro: Elsevier; 2008:391-393. 2. Machado AB. Meninges—Lı´quor. In: Machado AB, ed. Neuroanatomia funcional. 2nd ed. Sa˜o Paulo: Atheneu; 2002:49-53. 3. Parisi MA, Dobyns WB. Human malformations of the midbrain and hind-brain: review and proposed classification scheme. Mol Genet Metab. 2003;80:36-53. 4. Haimovici AJ, Doubilet PM, Benson CB, Frates MC. Clinical significance of isolated enlargement of the cistern magna (>10 mm) on antenatal sonography. J Ultrasound Med. 1997;16:731-736. 5. Long A, Moran P, Robson S. Outcome of fetal cerebral posterior fossa anomalies. Prenat Diagn. 2006;26:707-710. 6. Serhatlioglu S, Kocakoc E, Kiris A, et al. Sonographic measurement of the fetal cerebellum, cisterna magna, and cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy. J Clin Ultrasound. 2003;31:194-200. 7. Koktener A, Dilmen G, Kurt A. The cisterna magna size in normal second-trimester fetuses. J Perinat Med. 2007;35:217-219. 8. Vin˜als F, Mun˜oz M, Naveas R, et al. The fetal cerebellar vermis: anatomy and biometric assessment using volume contrast imaging in the C-plane (VCI-C). Ultrasound Obstet Gynecol. 2005; 26:622-627. 9. Araujo Ju´nior E, Visentainer M, Simioni C, et al. Reference values for the length and area of the fetal corpus callosum on 3-dimensional sonography using the transfrontal view. J Ultrasound Med. 2012;31:205-212. 10. Alves CM, Araujo Ju´nior E, Nardozza LM, et al. Reference ranges for fetal brain fissure development on 3-dimensional
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sonography in the multiplanar mode. J Ultrasound Med. 2013;32: 269-277. de Barros FS, Bussamra LC, Araujo Ju´nior E, et al. Comparison of fetal cerebellum and cisterna magna length by 2D and 3D ultrasonography between 18 and 24 weeks of pregnancy. ISRN Obstet Gynecol. 2012;2012:286141. Hadlock FB, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology. 1991; 181:129-133. Goldstein I, Reece EA, Pilu G, et al. Cerebellar measurements with ultrasonography in the evaluation of growth and development. Am J Obstet Gynecol. 1987;156:1065-1069. Altman DG, Chitty LS. Charts of fetal size, I: methodology. Br J Obstet Gynaecol. 1994;101:29-34. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307-310. Bertucci E, Gindes L, Mazza V, et al. Vermian biometric parameters in the normal and abnormal fetal posterior fossa: three-dimensional sonographic study. J Ultrasound Med. 2011;30:1403-1410. Steiger RM, Porto M, Lagrew DC, Randall R. Biometry of the fetal cisterna magna: estimates of the ability to detect trisomy 18. Ultrasound Obstet Gynecol. 1995;5:384-390.
18. Filly RA, Cardoza JD, Goldstein RB, Barkovich AJ. Detection of fetal central nervous system anomalies: a practical level of effort for a routine sonogram. Radiology. 1989;172:403-408. 19. Royston P. Constructing time-specific reference ranges. Stat Med. 1991;10:675-690. 20. Araujo Ju´nior E, Martins WP, Rolo LC, et al. Normative data for fetal cisterna magna length measurement between 18 and 24 weeks of pregnancy. Childs Nerv Syst. 2014;30:9-12. 21. Pilu G, Ghi T, Carletti A, et al. Three-dimensional ultrasound examination of the fetal central nervous system. Ultrasound Obstet Gynecol. 2007;30:233-245. 22. Laing FC, Frates MC, Brown DL, et al. Sonography of the fetal posterior fossa: false appearance of mega-cisterna magna and Dandy-Walker variant. Radiology. 1994;192:247-251. 23. Shrout PE, Fleiss JL. Intraclass correlation: uses in assessing rater reliability. Psychol Bull. 1979;86:420-428. 24. Bartlett JW, Frost C. Reliability, repeatability and reproducibility: analysis of measurements errors in continuous variables. Ultrasound Obstet Gynecol. 2008;31:466-475. 25. Araujo Ju´nior E, Passos AP, Bruns RF, et al. Reference range of fetal cisterna magna volume by three-dimensional ultrasonography using the VOCAL method. J Matern Fetal Neonatal Med. 2013 [Epub ahead of print].
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Reference Ranges of Fetal Cisterna Magna Length and Area Measurements by 3-Dimensional Ultrasonography Using the Multiplanar Mode
Journal of Child Neurology 2015, Vol. 30(2) 209-215 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814535496 jcn.sagepub.com
Ana Paula Passos, MD1, Edward Araujo Ju´nior, MD, PhD1, Rafael Frederico Bruns, MD, PhD2, Luciano Marcondes Machado Nardozza, MD, PhD1, and Antonio Fernandes Moron, MD, PhD1
Abstract This study aimed to establish reference values for the length and area of the fetal cisterna magna using the multiplanar mode of 3-dimensional ultrasonography. A cross-sectional study including 224 normal pregnant women between 17 weeks 0 days and 29 weeks 6 days of gestation was carried out. The area and length of the fetal cisterna magna were measured in the axial plane at the level of the cerebellar transverse diameter. Reliability was determined by intraclass correlation coefficient. The mean length and area of the fetal cisterna magna ranged from 0.50 + 0.10 to 0.79 + 0.18 cm and 0.95 + 0.18 to 3.09 + 0.62 cm2, respectively. Intraobserver reliability for the length and area (intraclass coefficients: 0.86 and 0.91, respectively) and interobserver reliability (intraclass coefficients: 0.64 and 0.82, respectively) were good. Three-dimensional ultrasonography using the multiplanar mode is a reliable method for the determination of reference values for the length and area of the fetal cisterna magna. Keywords area, cisterna magna, fetus, length, multiplanar mode, reference ranges, 3-dimensional ultrasound Received December 16, 2013. Received revised March 21, 2014. Accepted for publication March 30, 2014.
Cisternae are spaces larger than the subarachnoid, characterized by a greater accumulation of cerebrospinal fluid compared with other regions. The main cisternae are the cisterna magna, pontine, interpeduncular, and chiasmatic.1 The cisterna magna is located in the posterior fossa, between the anterior face of the cerebellum and the dorsal part of the bulb, and continues caudally into the spinal subarachnoid space, connecting to the fourth ventricle through the middle opening.2 Evaluation of the posterior fossa by 2-dimensional ultrasonography allows the identification of several anomalies such as Dandy-Walker malformation and megacisterna magna.3 A cutoff length of 10 mm is indicative of an enlargement of the cisterna magna.4,5 Changes in the anteroposterior length of the fetal cisterna magna during pregnancy have been evaluated by 2-dimensional ultrasonography in only a few studies, which found an increase in length with advancing gestation.6,7 Therefore, the use of a fixed cutoff anteroposterior length at all gestational ages can lead to diagnostic errors. Moreover, the measurement of the length of the fetal cisterna magna is subject to bias because of the difficulty in standardizing the exact reference points. This shortcoming could be addressed
by assessing the area because of the irregular shape of the cisterna magna. Methods for the evaluation of the vermis area of the cerebellum and fetal corpus callosum have been described8,9; however, no study has evaluated this parameter in the cisterna magna. Three-dimensional ultrasonography in multiplanar mode provides an exact plane for measuring fetal brain structures and allows its offline evaluation.10 Recently, measurements of the anteroposterior diameter of the fetal cisterna magna by 2- and 3-dimensional ultrasonography between 18 and 24 weeks of
1
Department of Obstetrics, Federal University of Sa˜o Paulo, Sa˜o Paulo-SP, Brazil 2 Department of Gynecology and Obstetrics, Federal University of Parana´, Curitiba-PR, Brazil Corresponding Author: Edward Araujo Ju´nior, MD, PhD, Department of Obstetrics, Federal University of Sa˜o Paulo, Rua Carlos Weber, 956 apt. 113 Visage, Vila Leopoldina, Sa˜o Paulo – SP, Brazil. Email: [email protected]
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Figure 1. (A) Acquisition of the volume of the fetal skull by 3-dimensional ultrasonography, with reference to the plane of measurement of the lateral ventricles. (B) Measurement of the anteroposterior length of the cisterna magna. (C) Measurement of the area of the cisterna magna.
gestation were compared using the extended imaging virtual organ computer-aided analysis method.11 There are no reports describing the use of 3-dimensional ultrasonography in the multiplanar mode to measure the length and area of the fetal cisterna magna during pregnancy. The objective of this study was to construct reference values for the length and area of the fetal cisterna magna using 3-dimensional ultrasonography in the multiplanar mode in pregnant women between 17 weeks 0 days and 29 weeks 6 days of gestation.
Methods A prospective cross-sectional study that included normal pregnant women who were between 17 weeks 0 days and 29 weeks 6 days of gestation was conducted between August 2010 and January 2012. This study was approved by the Ethics Committee of the Federal University of Sa˜o Paulo, and pregnant women provided written informed consent. The patients were randomly selected, and all ultrasound examinations were performed in the Fetalmed Clinic, Curitiba-PR, Brazil. All patients were evaluated only once, and postnatal results were not obtained. All examinations were performed by a single examiner (APP) using a Voluson 730 Expert device brand 3-dimensional ultrasound (General Electric Medical Systems, Zipf, Austria). The analysis was performed off line using the program 4D Views version 10.0 (General Electric Medical Systems). The inclusion criterion was a singleton pregnancy with gestational age confirmed until 13w0d by crown-rump length. Exclusion criteria were fetal malformations detected by ultrasonography, pregnant
women with chronic diseases (hypertension, diabetes mellitus, or collagenosis), fetuses with estimated weight below the 10th percentile or above the 90th percentile according to the method of Hadlock et al,12 reduced image quality due to increased body mass index >30 kg/m2, or presence of surgical scar.
Case Summary Initially, real-time 2-dimensional ultrasonography was performed to determine the biometric parameters, amniotic fluid index and the morphology. Then, a 3-dimensional neurosonogram was carried out as second step examination with the following ultrasound settings: insonation angle was standardized at 50 to 70 according to gestational age, normal speed mode, high quality, and harmonic mode. When the fetus was at rest, the patient was required to maintain apnea for a few seconds and the scanning box was activated to encompass the entire fetal head (volume of interest). Volume data sets were acquired using the lateral ventricle as the standard reference plane. The image was displayed in the 3 orthogonal planes using multiplanar mode as follows: axial (A, acquisition plane), sagittal (B), and coronal (C) (Figure 1A). Plane A was selected as a reference plane and displaced in the craniocaudal direction using the REF SLICE key until the acquisition of the default plane for measuring the transverse cerebellar diameter, as proposed by Goldstein et al.13 Then, a 1 1 arrangement was used and the image was magnified to occupy 75% of the screen. The MEASURE key was activated and the anteroposterior fetal cisterna magna length was measured. For this purpose, the 2 diametrically most distant points in the vermis and the internal face of the occipital bone were used as standard parameters
Downloaded from jcn.sagepub.com at The University of Iowa Libraries on June 7, 2015
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Figure 2. Scatter-plot of the length (A) and area (B) of the fetal cisterna magna according to gestational age. and the length was measured at this level (Figure 1B). The internal region of the fetal cisterna magna was drawn manually (Figure 1C) to calculate the value of the area. Only a single volume of the fetal skull was collected. The data were stored in the memory of the device and then transferred to compact discs for off-line analysis by a single operator (APP). Data were transferred to the spreadsheet program Excel 2007 (Microsoft Corp, Redmond, WA) and analyzed by SPSS (version 18.0, SPSS Inc, Chicago, IL) and GraphPad (version 5.0, GraphPad Software, San Diego, CA). For descriptive analyses, the means, medians, standard deviations, and minimum and maximum values for the length and area of the cisterna magna at each gestational age were calculated. To construct reference ranges for the length and area of the fetal cisterna magna as a function of gestational age, polynomial regressions were calculated and adjustments were made by the determination coefficient (R2). The 5th, 50th, and 95th percentiles were determined for each gestational age according to the method proposed by Altman and Chitty.14 For calculations of reliability and agreement, the same investigator performed a second random measurement of 50 volumes with an interval of at least 30 days after the first (intraobserver), whereas a second examiner (RFB) performed a third measurement of the same 50 volumes. Both examiners were blinded to each other’s results. The intraclass correlation coefficient was used for the evaluation of intraand interobserver reliability, whereas the limits of agreement and Bland-Altman plots15 were used to assess intra- and interobserver agreement. Statistical level of P 30 weeks resulted in failure in 62% of cases because of occipital ossification. Furthermore, after 30 weeks of gestation, inclusion of the entire fetal head within the scanning window during 3-dimensional ultrasonography is difficult,9,10 and minor clinical diagnoses of anomalies of the posterior fossa are important after this gestational age. We did not perform a power analysis to calculate sample size. According to Royston, to construct reference intervals with 90%
variation between the 5th and 95th percentiles of distribution, the analysis of 20 patients per week is recommended.19 In this study, we proposed the assessment of 18 patients per week in 13 gestational ages. The objective would be to assess 234 patients, which is in agreement as suggested by Royston.19 A 10-mm cutoff length of the cisterna magna is used as the standard parameter to indicate fetal abnormalities of the posterior fossa.4,5 However, some evidence suggests that the length of the fetal cisterna magna increases with gestational age.17,20 Two studies assessed changes in the length of the fetal cisterna magna during pregnancy by 2-dimensional ultrasonography. In a study by Serhatlioglu et al,6 130 pregnant women between 16 and 38 weeks of gestation were evaluated, and statistically significant differences in the length of the fetal cisterna magna were observed in the second and third trimesters; however, no reference values for each gestational age or reliability and agreement values were provided. In a study by Koktner et al,7 the authors evaluated the length of the fetal cisterna magna in 194 pregnant women between 16 and 24 weeks of gestation. The authors observed a linear correlation with gestational age, with the mean length of fetal cisterna magna ranging from 3.26 to 5.90 mm during this gestational period. In the present study, we observed a slightly greater mean length (5.0-7.1 mm) during the same gestational period. However, their study evaluated only the second trimester, and the changes in the length of the fetal cisterna magna in the third trimester cannot be estimated; furthermore, reliability and agreement were not evaluated. The reference range for length and area of the cisterna magna in the fetus calculated at different gestational age have been constructed by the first time using 3-dimensional ultrasound in multiplanar mode with the respective reliability and agreement values. Three-dimensional ultrasonography allowed the identification of the exact axial plane of measurement of the cisterna magna through the use of the REF SLICE key. Although it is not essential for 2-dimensional measurement, the multiplanar mode allows faster and more practical analysis of fetal central nervous system analysis because of automatic capture which allows the examiner to perform offline evaluation on his personal computer.9 We have observed a low correlation between the length of the cisterna magna and gestational age, which indicates that this parameter is not adequate for advanced gestational ages. We have attempted to develop a simple and easy method for the measurement of the fetal cisterna magna length and area by 3-dimensional ultrasonography in the multiplanar mode. We chose to use only the REF SLICE key in the craniocaudal direction to determine the transverse cerebellar diameter in a simple and reproducible manner, and thus to test an ultrasound technique and its application in clinical setting. The technique described by Pilu et al21 is needed to collect the volume in the standardized plane, including the cavum septum pellucidum and transverse cerebellar diameter, which are difficult to assess in advanced gestational ages. Accurate measurement of the cisterna magna can be a challenge in the third trimester. In addition to the required use of the standard pattern of the transverse diameter of the cerebellum,13
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Figure 3. Bland-Altman plot showing the mean relative difference between 2 measurements performed by a single examiner (intraobserver) plotted against the difference in their means for the length (A) and area (B) of the fetal cisterna magna.
Figure 4. Bland-Altman plot showing the mean relative difference between 2 measurements performed by 2 observers (interobserver) plotted against the difference in their means for the length (A) and area (B) of the fetal cisterna magna.
which must include the cavum of the septum pellucidum, midbrain, and cerebral hemispheres, the angle of the transducer remains an issue that needs to be considered. According to Laing et al,22 if the transducer is angled in a semicoronal plane, the cisterna magna could falsely appear enlarged in approximately 40% of cases. This limitation may explain the low interobserver reliability in the measurement of the length of the fetal cisterna magna in this study, in which the intraclass correlation coefficient was 0.64. According to Shrout and Fleiss, an intraclass correlation coefficient between 0.40 and 0.75 is considered satisfactory.23 However, as the outcome is related to gestational age and the heterogeneity in the sample population was large (17 weeks 0 days and 29 weeks 6 days), higher
intraclass correlation coefficients, usually >0.80, are expected for application in clinical practice.24 Only 1 study has evaluated the length of the fetal cisterna magna by 3-dimensional ultrasonography. De Barros et al11 compared the measurements of the fetal cisterna magna in 69 normal pregnant women of 16w0d and 24w6d of gestation using the three-dimensional extended imaging method (multislice view). They observed that the 3-dimensional ultrasonography measurements were significantly higher than those obtained by 2-dimensional ultrasonography, and concluded that 3-dimensional ultrasonography allows the identification of the exact plane for the measurement of the length of the cisterna magna, resulting in more accurate measurements.
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Journal of Child Neurology 30(2)
Regarding the measurement of the area of the fetal cisterna magna, there are no studies in the medical records describing its application. We observed a good correlation between the area of the fetal cisterna magna and gestational age, which is best explained by a linear equation. This model has shown that area is a better parameter than length for evaluating the fetal cisterna magna, particularly in the third trimester, because it is less subject to bias such as that introduced by the head and the flexed fetal position, as observed in our data. In a study evaluating the length and area of the fetal corpus callosum in transfrontal view in 293 healthy pregnant women between 20 and 33 weeks of gestation, Araujo Ju´nior et al9 have showed that area is a reliable and consistent parameter. We believe that area should be the first parameter to be used in order to assess the fetal cisterna magna, despite the fact that it is more time consuming. Despite the use of both parameters in the conventional plane, the area has showed a better correlation with gestational age and better reproducibility. The multiplanar mode was used only to facilitate these measurements, mainly at an advanced gestational age. Our results indicate that 3-dimensional ultrasonography is not superior to 2-dimensional ultrasonography for the measurement of the fetal cisterna magna. Recently, our group published a study in which the fetal cisterna magna volume was assessed by 3-dimensional ultrasonography using the virtual organ computer-aided analysis method. In that study, we have used the same number of cases as in the present study, and we have determined the reference range of the fetal cisterna magna volume between 17 weeks 0 days and 29 weeks 6 days of gestation. In addition, we have showed good and low intra- and interobserver reproducibility, respectively.25 The main limitation of this study was the use of only the axial plane as the reference to measure the length and area of the fetal cisterna magna. However, this was a pioneer study in which we have attempted to develop a simple and reproducible method to assess the length and area of the fetal cisterna magna using 3-dimensional ultrasonography in the multiplanar mode. We believe that the technique is kept simple and reproducible by using only the axial plane for these measurements, which was confirmed by our results. The use of other orthogonal planes would be more difficult and time consuming, which would limit its clinical application. During the advanced gestational ages, measuring the length of the fetal cisterna magna in the standard plane is difficult using the cavum septum pellucidum and transverse cerebellar diameter as landmarks. In these cases, the multiplanar mode using the axial plane at the level of the lateral ventricles as the reference would be of particular importance, because it is easy and quick to obtain. Despite the limitations of the standardized acquisition plane in the multiplanar mode, we believe that our data will serve as a reference for future studies on the standardization of fetal cisterna magna measurements by 3-dimensional ultrasonography. In summary, we have calculated reference values for the length and area of the fetal cisterna magna by 3-dimensional ultrasonography using the multiplanar mode. As these curves proved reliable and consistent, we believe that they can be
applied in fetuses with suspected posterior fossa malformations, especially after the 24th week of gestation. Acknowledgments The authors would like to thank Dr. Wellington de Paula Martins at the Department of Gynecology and Obstetrics, Faculty of Medicine of Riberira˜o Preto, Sa˜o Paulo University for the statistical analysis.
Author Contributions APP and RFB collected the data for the study. APP wrote the manuscript. EAJ conceived and designed the study. LMMN and AFF reviewed the study. AFF supervised the study.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval This study was approved by the Ethics Committee of the Federal University of Sa˜o Paulo (0676/11), and pregnant women who agreed to participate voluntarily signed consent forms.
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