Three-dimensional power Doppler derived vascular indices: what are we measuring and how are we doing it?

The role of Doppler in the assessment of fetal and placental blood flow is well-established1. However, as exemplified by the large variability of results published in the literature, its role in the evaluation of uterine and ovarian hemodynamics is not so clearly defined. Velocimetric indices such as pulsatility index and resistance index have been shown to provide useful information on uterine perfusion and angiogenesis in the ovarian follicle and certain cancers, but have not been adopted to any significant degree into clinical practice. Because of the advantages of power Doppler compared with conventional two-dimensional color Doppler2, some investigators have advocated its use for blood flow mapping3,4. However, this technique only provides information on the ‘vascular map’ of a given region of interest and assessment relies largely on the subjective impression of the examiner. The advent of three-dimensional (3D) power Doppler ultrasound has begun a new era in tissue and organ vascularization research. Using this technique, we can now assess a virtually reconstructed vascular tree within a volume of interest5 and can ‘objectively’ determine its vascularization by calculating indices using the specially designed VOCAL TM software (GE Medical Systems, Zipf, Austria)6. Objective and non-invasive quantification of vascularization of a given tissue volume holds much promise, particularly because this method has proved to be highly reproducible between observers (thereby overcoming one of the main limitations of conventional Doppler ultrasound)7–9. Since the pioneering study of Pairleitner et al.6 in 1999, more than 100 papers have been published analyzing the role of 3D power Doppler ultrasound in almost all areas of obstetrics and gynecology, including placental and fetal vascularization10,11, reproductive medicine12,13, gynecological endocrinology14, gynecological oncology15–17, breast pathology18 and the pelvic floor19. Despite this abundance of literature on the application of 3D power Doppler ultrasound, it seems that so far few have stopped to ask what we are measuring. Calculation of the three 3D power Doppler ultrasound vascular indices, the vascularization index (VI), flow index (FI) and vascularization flow index (VFI), is based on and related to the total and relative amounts of power Doppler information within the volume of interest. VI denotes the ratio of color-coded voxels to all voxels within the volume and is expressed as a percentage, FI represents the mean power Doppler signal intensity from all color-coded voxels and VFI is the simple mathematical relationship derived from multiplying VI by FI and dividing the result by 1006. Both FI and VFI are unitless and are expressed as a numerical value ranging from 0 to 100. The indices are thought to reflect the number of vessels within the volume of interest (VI), the intensity of flow at the time of the 3D sweep (FI), and both blood flow and vascularization (VFI)6. Although our knowledge about what these indices are actually measuring is limited, most examiners involved with the use of power Doppler are aware that several factors affect the power Doppler signal20,21. Yet, studies evaluating how machine settings affect measurements are scanty22. In this issue of the Journal, three papers make a significant contribution to the understanding of what these indices are measuring and how machine settings affect the measurements23–25. All three studies were performed in an in-vitro setting using a flow phantom experiment. In the first study by Raine-Fenning et al.23, the authors evaluated the relationship of VI, FI and VFI values with vessel number, flow rate, attenuation and ‘erythrocyte’ density. They found a positive linear relationship between VI and VFI and all these factors except attenuation, which showed a negative relationship. In other words, with increasing number of vessels, volume flow or erythrocyte density, VI and VFI values increase. In the case of VI, these findings are particularly interesting. VI actually quantifies the number of color-coded voxels, which does not necessarily mean the number of vessels. However, in this phantom study, the authors found a correlation between the number of color-coded voxels and ‘number of vessels’. This finding is in agreement with preliminary data from in-vivo studies that showed that VI correlates positively with microvessel density count as assessed by immunohistochemical techniques26. In contrast, the further the object under investigation is from the transducer, the lower the values obtained. This is of clinical relevance, because the route – transvaginal or transabdominal – should be taken into account when performing the calculations, as should the distance between the probe and the object under investigation. However, Raine-Fenning et al. found that FI showed a ‘more complex cubic relationship that is not always logical’. This could indicate that FI is less predictable than VI and VFI. For example, they discovered that VI and VFI increase steadily with an increasing number of vessels, while FI reached a peak with three vessels and decreased