Abnormal Cardiovascular 24Segment 24Segment 24Segment Sphericity Index of the Right and Left Ventricles in Fetuses with Growth Restriction

Introduction. Fetuses with growth restriction have been reported to have an abnormal sphericity index (SI) of the right and left ventricles of the heart when dividing the end-diastolic basal-apical length by the basal transverse width for each chamber. This study was conducted to evaluate the SI for 24 transverse segments distributed from the base (segment 1) to the apex (segment 24) of the right and left ventricles to determine if an abnormal SI occurs at locations other than the basal segment. This article is protected by copyright. All rights reserved. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/uog.18820 A cc ep te d A rti cl e Methods. Thirty fetuses with growth restriction were evaluated between 25 and 37 weeks of gestation. The SI was computed for the right (RV) and left (LV) ventricles by dividing the enddiastolic basal-apical length by each of the 24 end-diastolic transverse segmental widths from the base (segment 1) to the apex (segment 24). The Z-score and centile for the SI from each of the 24 segments from each ventricle were computed using the mean and standard deviation from published equations. The 24-segment method at which the SI was <10 centile or >90 centile was compared to the basal segment (1) using Chi-Square analysis to determine the number of fetuses with an abnormal SI. Findings. In fetuses with growth restriction, an abnormal SI for any of the 24 transverse segments occurred in 73% (22/30) and was distributed as follows: 17% involved both ventricles, 23% involved only the right ventricle, and 33% involved only the left ventricle. Compared to the 24-segment model, using only the 1 basal segment from the right ventricle identified significantly fewer (58%, 7/12) fetuses with an abnormal SI (P<0.01). Similarly, using only the 12 segment in the mid-portion of the RV identified significantly fewer fetuses (50%, 6/12) with an abnormal SI (P <0.005). Combining measurements of both the 1 and 12 segments from the RV identified 83% of fetuses with an abnormal SI and was not significantly different from the 24segment model. When compared to the 24-segment model, using only the 1 basal segment from the LV identified significantly fewer (63%, 10/16) fetuses with an abnormal SI (P<0.006). Similarly, using only the 12 segment in the mid-portion of the chamber identified (75%, 12/16), a significantly lower number of fetuses with an abnormal SI (P <0.03) when compared to the 24segment model. Combining measurements of both the 1 and 12 segments identified 81% (13/16) of fetuses with an abnormal SI and was not significantly different from the 24-segment model. This article is protected by copyright. All rights reserved. A cc ep te d A rti cl e Conclusions. The SI of 24-segments of the right and left ventricles provides a comprehensive method to examine the shape of the ventricular chambers and identifies more fetuses that are growth restricted with an abnormal SI than only using the basal segment. This article is protected by copyright. All rights reserved. A cc ep te d A rti cl e Introduction Deterioration of cardiac function is associated with the following independent changes: (1) change in ventricular shape from an elliptical to a globular shape, (2) increase in end-diastolic volume, and (3) decreased ventricular function. Chronic pressure overload has been associated with ventricular hypertrophy while ventricular dilatation is a response to volume overload. Both responses are an attempt to maintain stroke volume when disease states are present which alter myocardial dynamics. These changes have been termed remodeling. One method for assessing the shape of the ventricle is to measure the sphericity index (SI), which is derived by computing the ratio between the end-diastolic basal-apical length and the enddiastolic transverse width (Figure 1). The SI has been examined in adults, children, neonates, and fetuses and found to be a useful tool to detect abnormal cardiac function resulting from remodeling of the ventricular chamber. In the fetus the SI has been measured using three methods; two of which use either the basal or mid-transverse segment of the ventricle (Figure 1), while the third measures 24 transverse segments located from the base (1) to the apex (24) of each ventricle (Figure 2). 14,19-24 Previous studies evaluating fetuses with growth restriction have evaluated the SI using the basal transverse segment in the computation (Figure 1). 20-23 Because of the parallel circulation in the fetus and the differential effect disease states may have on the shape of the right and left ventricles, this study was conducted to evaluate the SI for 24 transverse segments using an offline analytic technique that has been previously described. The reason for evaluating 24 transverse segments is because the SI may be increased or decreased in value at locations within the ventricular chamber other than the base of the ventricle (Figure 2). This article is protected by copyright. All rights reserved. A cc ep te d A rti cl e MATERIALS AND METHODS Control Population Normal mean and standard deviation equations for the 24 segment SI were used from a previous publication in which the authors found that the SI for each segment did not change with gestational age or fetal biometry. Fetuses with Growth Restriction Thirty fetuses with growth restriction, defined as an estimated fetal weight below the 10 centile, as per recommendations from the American College of Obstetricians and Gynecologists, were selected from an ongoing study evaluating fetal growth at the University of Colorado. Measurements of the biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight were obtained and the corresponding centiles computed using equations from Hadlock et al. 27, 28 The Doppler Pulsatility index (PI) of the umbilical and middle cerebral arteries were measured and the cerebroplacental ratio computed. These values were classified per recent recommendations. All patients signed a consent form to participate in the study that was approved by Colorado Multiple Institutional Review Board. Ultrasound Image Acquisition and Orientation Two-dimensional images of the four-chamber view were obtained using a Voluson E10 system (GE Healthcare, Milwaukee, WI). Images were optimized to enhance the borders between the blood pool and endocardium. Three to ten second cine clips of the four-chamber view were stored as Digital Imaging and Communications in Medicine (DICOM) files and exported to an This article is protected by copyright. All rights reserved. A cc ep te d A rti cl e offline cloud database (Tricefy, Inc. San Diego, CA). The DICOM image frame rate was equivalent to the frame rate acquisition at the time of the examination. Evaluation of the Four-Chamber View Using Offline Speckle Tracking Software Once the 2-dimensional images of the 4-chamber view were obtained and stored in the DICOM format, they were imported into an offline cardiac software program for analysis (2D Cardiac Performance) developed by TomTec Imaging Systems, Gmbh (Munich, Germany). As previously described, end-diastole and end-systole were identified from an M-Mode derived from the 2dimensional image of the four-chamber view from which a single cardiac cycle was identified. From the single cardiac cycle the tracing was adjusted in the end-systolic and end-diastolic reference image frames so that it encompassed the endocardium from the insertion of the atrioventricular valves on the lateral wall, the apex, and ending at the insertion of the atrioventricular valves on the interventricular septum. 24, 25 Following the adjustments, the automated analysis detected the endocardial border during diastole and systole. Once the analysis for each ventricle was completed, the raw data was exported to an ASCII text file. The text file was imported into an Excel® spreadsheet that had been programed to compute the end-diastolic SI for 24 transverse segments as has been previously described. For descriptive purposes, segments 1-8 were defined as the basal section, segments 9-16 as the mid-section, and segments 17-24 as the apical section of each ventricle. The Z-score and centile for each of the 24 segments in the growth-restricted fetuses were computed using the following equations: Equation (1) Z-Score = (SI Growth Restricted Fetus Mean SI Reference 24)/Standard Deviation Reference 24 This article is protected by copyright. All rights reserved. A cc ep te d A rti cl e Equation (2) Centile = Normsdist * (Z-score), which is an Excel spreadsheet function. The segments in which the centile was <10 or >90 were identified for each of the 24 segments from each fetus with growth restriction and grouped by their basal, mid, and apical locations within the ventricular chamber. Chi-Square analysis was used to compare the number of fetuses identified with an abnormal SI using the 24-segment technique vs. using only the basal (segment 1) or mid (segment 12) segments. 19-23