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© 2008 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 27:1-6 • 0278-4297

Intraobserver and Interobserver Reproducibility of 3-Dimensional Power Doppler Vascular Indices in Assessment of Solid and Cystic-Solid Adnexal Masses

Juan Luis Alcázar, MD, David Rodriguez, MD, Pedro Royo, MD, Rosendo Galván, MD, Silvia Ajossa, MD and Stefano Guerriero, MD

Department of Obstetrics and Gynecology, Clinica Universitaria de Navarra, University of Navarra, Pamplona, Spain (J.L.A., P.R., R.G.); Department of Obstetrics and Gynecology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain (D.R.); and Department of Obstetrics and Gynecology, Ospedale San Giovanni di Dio, University of Cagliari, Cagliari, Italy (S.A., S.G.).

Address correspondence to Juan Luis Alcázar, MD, Department of Obstetrics and Gynecology, Clinica Universitaria de Navarra, Avenida Pio XII 36, 31008 Pamplona, Spain. E-mail: jlalcazar{at}unav.es


   Abstract
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 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objective. The purpose of this study was to assess the intraobserver and interobserver reproducibility of 3-dimensional (3D) power Doppler angiography–derived vascular indices in evaluation of vascularized solid and cystic-solid adnexal masses. Methods. Stored 3D power Doppler angiographic volume data from 12 consecutive women with a diagnosis of a complex adnexal mass (6 cystic-solid and 6 solid) evaluated and treated at our institution were retrieved from our database for analysis. Two examiners performed the calculations blinded to each other. Calculations were performed offline in a computer using Virtual Organ Computer-Aided Analysis software (plane A, 9° rotation step) to assess volume and vascularization (vascularization index, flow index, and vascularization-flow index) from solid areas within the tumor. In all cases, a definitive histologic diagnosis was obtained. Intraobserver and interobserver reproducibility was assessed by calculating the intraclass and interclass correlation coefficients for each index. Results. All tumors proved to be malignant after surgical removal. Intraobserver reproducibility for both examiners and interobserver reproducibility were high for all indices (interclass correlation coefficient > 0.95). Conclusions. Three-dimensional power Doppler angiography is a reproducible technique for offline assessment of stored 3D volume data of vascularized adnexal masses.

Key Words: power Doppler sonography • reproducibility • 3-dimensional sonography

Abbreviations: FI, flow index • 3D, 3-dimensional • 3D-PDA, 3-dimensional power Doppler angiography • VFI, vascularization-flow index • VI, vascularization index • VOCAL, Virtual Organ Computer-Aided Analysis


   Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Three-dimensional power Doppler angiography (3D-PDA) is a new technique that allows objective assessment of tumor vascularization by means of analysis of the power Doppler signal.1 With Virtual Organ Computer-Aided Analysis (VOCAL) software, 3 vascular indices from a given tissue volume can be estimated: vascularization index (VI), flow index (FI), and vascularization-flow index (VFI).1

We proposed this technique as a method for predicting ovarian cancer in vascularized solid and cystic-solid adnexal masses because we found that all 3 of these vascular indices were significantly higher in the solid portions of malignant lesions compared with benign ones.2 Subsequent studies have reported results similar to ours.3–5 However, the question of reproducibility of this technique in this clinical setting still needs to be solved.

The aim of this study was to evaluate the intraobserver and interobserver reproducibility of 3D-PDA in assessment of vascularized solid and cystic-solid adnexal masses.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Stored 3D-PDA volume data from 12 consecutive unselected women with a diagnosis of a solid (n = 6) or cystic-solid (n = 6) adnexal mass with central vascularization as detected by power Doppler sonography were retrieved from our database for analysis. All patients had been evaluated and treated at our institution between January and June 2007. The patients’ mean age was 55 years, ranging from 41 to 71 years. All patients underwent surgery for tumor removal, and a definitive histologic diagnosis was obtained in every case. Our Institutional Review Board approved the study, and all women gave informed consent.

Volume Acquisition
All women were evaluated before surgery by 3-dimensional (3D) transvaginal sonography with a Voluson 730 Expert system (GE Healthcare, Milwaukee, WI) according to a predefined scanning protocol by 1 author (J.L.A.).2 Briefly, first B-mode sonography was performed to characterize the adnexal mass morphologically. Lesions were classified as unilocular solid, multilocular solid, and solid. After B-mode evaluation was done, the 2-dimensional power Doppler gate was activated to assess tumor vascularization. Power Doppler settings were set to achieve maximum sensitivity to detect low velocity flow without noise (frequency, 5 MHz; power Doppler gain, –7.4; dynamic range, 20–40 dB; edge, 1; persistence, 2; color map, 5; gate, 2; filter, L1; and pulse repetition frequency, 0.6 kHz). Central vessel vascularization was defined in the presence of color spots within the suspicious areas of the tumor (thick papillary projections, solid areas, or central parts of solid tumors). Then the 3D volume was activated to obtain a 3D box from those suspicious areas (eg, thick papillary projections, solid areas, or, in the case of mostly solid tumors, the whole tumors if possible). In some cases of large tumors, more than 1 volume was obtained. In small tumors, 1 volume was enough to capture the whole volume, whereas in large solid tumors, more than 1 volume was needed to assess the whole tumor. In each case, only 1 volume, the same for both observers, was used for analysis.

Once a 3D volume was obtained, it was stored on a hard disk (Sonoview; GE Healthcare, Kretztechnik, Zipf, Austria). The volume acquisition time lasted 2 to 6 seconds depending on the size of the volume box.

Volume and Power Doppler Index Calculations
The stored volumes were further analyzed using the VOCAL software by 2 different observers: observer A (J.L.A.), with 6 years of experience in 3D sonography; and observer B (D.R.), with 1 month of experience. Observer B had completed a 2-week specific training course on the use of the VOCAL software.

Calculations were performed offline on a personal computer. Measurements were undertaken in the manual mode. This was done by manually outlining the solid area assessed. We chose plane A and a 9° rotation step, which meant a total of 20 outlinings per solid area assessed (Figure 1Go). It should be stressed that we did not assess the whole tumor, except in some small, purely solid lesions, but just the solid area included in the 3D volume. This process took a mean of 4 minutes per volume. Three-dimensional vascular indices of those solid areas were calculated by the histogram function (Figure 2Go). The 3D volume is composed of voxels (smallest unit of volume). Voxels contain all the information about gray scale and color according to an intensity scale ranging from 0 to 100. According to these values, this measurement system obtains the mean grayness and power Doppler indices to evaluate vessels and blood flow.3 The VI, expressed as a percentage, measures the number of color voxels in the studied volume, representing the blood vessels within the tissue. The FI is the average color value of all color voxels, representing the average color intensity. The VFI is the average color value of all gray and color voxels.


Figure 1
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  		Figure 1. Sample volume from a solid area of an adnexal mass in the VOCAL software. The outline is shown by orange dots in plane A (top left) and yellow lines in planes B (top right) and C (bottom left).

 

Figure 2
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  		Figure 2. Vascular index calculation using the histogram function on the solid area, manually outlined by the operator.

 
Statistical Analysis
Each examiner performed calculations twice on the same volume data 1 week apart to assess intraobserver reproducibility. The second measurement of each observer was used to assess interobserver reproducibility. The observers were blinded to each other when performing calculations.

The Kolmogorov-Smirnov test was used to check the normal distribution of row data. The Student t test was used to compare continuous variables. P < .05 was considered statistically significant.

Intraobserver reproducibility was expressed as the difference between 2 measurement results obtained from the same observer. Interobserver reproducibility was expressed as the difference between 2 measurement results obtained by the 2 different observers. Intraobserver reproducibility and interobserver reproducibility were estimated according to the method of Bland and Altman,6 calculating the intraclass and interclass correlation coefficients.

The differences between the measured values were plotted against the mean of the 2 measurements to assess the relationship between the difference and the magnitude of the measurement.7 Limits of agreement (mean difference ± 1.96 SDs) were also calculated.

Statistical analysis was performed with the SPSS 13.0 statistical package (SPSS Inc, Chicago, IL). Graphics were plotted with MedCalc 8.0 software (MedCalc, Mariakerke, Belgium).


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
All tumors were malignant. Measurements for each observer are shown in Tables 1Go and 2Go. There were no statistical differences in mean values between both observers. Descriptive statistics of measurements are shown in Table 3Go.


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  		Table 1. Individual 3D-PDA Measurements for Observer A*
 

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  		Table 2. Individual Measurements of 3D-PDA for Observer B*
 

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  		Table 3. Descriptive Statistics of Measurements for the 2 Observers
 
Intraobserver reproducibility was high for both observers (Tables 4Go and 5Go). Interobserver reproducibility was also high (Table 6Go).


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  		Table 4. Intraobserver Reproducibility for Observer A
 

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  		Table 5. Intraobserver Reproducibility for Observer B
 

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  		Table 6. Interobserver Reproducibility Between Observers
 
Graphics showing relationships between the differences and the magnitudes of the measurements are depicted in Figures 3Go–6GoGoGo. These figures show the limits of agreement.


Figure 3
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  		Figure 3. Scatterplot showing differences between volume measurements, expressed as cubic centimeters, against the mean between both observers. Limits of agreement are shown. The mean decimal value is rounded.

 

Figure 4
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  		Figure 4. Scatterplot showing differences between VI measurements, expressed as percentages, against the mean between both observers. Limits of agreement are shown. The mean decimal value is rounded.

 

Figure 5
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  		Figure 5. Scatterplot showing differences between FI measurements against the mean between both observers. Limits of agreement are shown. The mean decimal value is rounded.

 

Figure 6
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  		Figure 6. Scatterplot showing differences between VFI measurements against the mean between both observers. Limits of agreement are shown. The mean decimal value is rounded.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this study we assessed the reproducibility of 3D-PDA vascular index calculations in solid and cystic-solid adnexal masses. Our results show that this technique is highly reproducible. These results are similar to those reported by the single study addressing this question published to date.5 Jokubkiene et al5 also found this technique highly reproducible in a series of 25 adnexal masses. However, there were some methodological differences between that study and ours. First, we analyzed volumes exclusively from solid portions of the tumors, whereas Jokubkiene et al5 used the whole tumor volume or a 5-cm3 spherical sample from "the most vascularized area" subjectively assessed by the examiner. Therefore, it seems that 3D-PDA assessment is reproducible independently of how the sample is assessed.

It should be stressed that we tested the reproducibility of collected volumes. We did not test the reproducibility of the whole procedure, that is, volume acquisition. This might be a potential source of bias. Another potential source of bias in our study is that all tumors were malignant; thus, this series did not reflect the general tumor population. Notwithstanding, we think that 3D-PDA should only be used in selected populations because conventional B-mode and 2-dimensional power Doppler sonography can correctly classify most adnexal masses,8 and only those questionable solid or cystic-solid masses should be submitted to 3D sonography.9,10

Our results and those from Jokubkiene et al5 may be of clinical relevance when proposing this technique as a potential tool for discriminating benign from malignant adnexal masses. As a matter of fact, Geomini et al11 recently showed that 3D sonography adds relevant information in assessment of ovarian tumors when used in logistic models.

Furthermore, our data indicate that the learning curve for volume- and 3D-PDA-derived vascular indices is relatively short, and less experienced observers could achieve results similar to those of experienced observers when performing calculations in stored 3D volumes.

In conclusion, 3D-PDA assessment of stored volumes from solid and cystic-solid adnexal masses is reproducible.


   Footnotes
 
Received September 4, 2007, from the Department of Obstetrics and Gynecology, Clinica Universitaria de Navarra, University of Navarra, Pamplona, Spain (J.L.A., P.R., R.G.); Department of Obstetrics and Gynecology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain (D.R.); and Department of Obstetrics and Gynecology, Ospedale San Giovanni di Dio, University of Cagliari, Cagliari, Italy (S.A., S.G.). Revision requested September 26, 2007. Revised manuscript accepted for publication October 2, 2007.


   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Pairleitner H, Steiner H, Hasenoehrl G, Staudach A. Three-dimensional power Doppler sonography: imaging and quantifying blood flow and vascularization. Ultrasound Obstet Gynecol 1999; 14:139–143.[Medline]
  2. Alcázar JL, Mercé LT, García Manero M. Three-dimensional power Doppler vascular sampling: a new method for predicting ovarian cancer in vascularized complex adnexal masses. J Ultrasound Med 2005; 24:689–696.[Abstract/Free Full Text]
  3. Testa AC, Ajossa S, Ferrandina G, et al. Does quantitative analysis of three-dimensional power Doppler angiography have a role in the diagnosis of malignant pelvic solid tumors? A preliminary study. Ultrasound Obstet Gynecol 2005; 26:67–72.[Medline]
  4. Geomini PM, Kluivers KB, Moret E, Bremer GL, Kruitwagen RF, Mol BW. Evaluation of adnexal masses with three-dimensional ultrasonography. Obstet Gynecol 2006; 108: 1167–1175.[Abstract/Free Full Text]
  5. Jokubkiene L, Sladkevicius P, Valentin L. Does three-dimensional power Doppler ultrasound help in discrimination between benign and malignant ovarian masses? Ultrasound Obstet Gynecol 2007; 29:215–225.[Medline]
  6. Bland JM, Altman DG. Measurement error and correlation coefficients. BMJ 1996; 313:41–42.[Free Full Text]
  7. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1:307–310.[Medline]
  8. Alcázar JL, Mercé LT, Laparte C, Jurado M, López-García G. A new scoring system to differentiate benign from malignant adnexal masses. Am J Obstet Gynecol 2003; 188: 685–692.[Medline]
  9. Alcázar JL, Guerriero S. Three-dimensional power Doppler in ovarian tumors. Ultrasound Obstet Gynecol 2007; 29: 717–719.[Medline]
  10. Guerriero S, Ajossa S, Piras S. Three-dimensional quantification of tumor vascularity as a tertiary test after B-mode and power Doppler evaluation for detection of ovarian cancer. J Ultrasound Med 2007; 26:1271–1278.[Abstract/Free Full Text]
  11. Geomini PM, Coppus SF, Kluivers KB, Bremer GL, Kruitwagen RF, Mol BW. Is three-dimensional ultrasonography of additional value in the assessment of adnexal masses? Gynecol Oncol 2007; 106:153–159.[Medline]




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