Three-dimensional MRI evaluation of the effect of bladder volume on prostate translocation and distortion

Fifteen healthy male volunteers were included in this prospective, institutional review board-approved study, with written informed consent obtained in all cases.

MRI examinations were carried out on a 3T MR750 magnet (General Electric Healthcare, Waukesha, WI, USA) using a 32-channel phased-array body coil. The protocol comprised: high-resolution axial T2-weighted (T2w) fast recovery fast spin echo (FRFSE) sequence, TR/TE of 3663/102 ms field-of-view (FOV) 22×22 cm², slice thickness/gap 3.0/0.0 mm, in-plane resolution 0.85×0.57 mm, and 3 signal averages; sagittal T2w cube sequence, FOV 22×22 cm², slice thickness/gap 2.0/0.0 mm, in-plane resolution 0.43×0.43 mm. MRI was performed on 4 consecutive days, with participants completing the following different preparations prior to imaging, with MR images acquired pre and post-void:

Preparation 1. Pass urine, no drinking 2 hours prior to scanning

Preparation 2. Pass urine, no drinking 1 hour prior to scanning

Preparation 3. Pass urine and drink 250 mL water 1 hour prior to scanning

Preparation 4. Pass urine and drink 500 mL water 1 hour prior to scanning

The overall workflow diagram designed for MR image processing is depicted in Figure 1. Figure 1A represents the first phase of our procedure for the quantitative evaluation of the prostate translocation and distortion. For each study, the co-registration of the two MRI sequences was manually performed using ITK-SNAP in consensus with a board-certified uro-radiologist with 8-years’ experience in reporting prostate MRI studies – ITK-SNAP is a well-known medical image analysis framework based on the C++ Insight Toolkit (ITK) library. The registration was carried out in the sagittal plane according to bony landmarks (i.e., pelvic bones and lumbar spine) aiming to preserve the effects of soft-tissue deformation and movement.21, 22 The obtained affine transformation matrix (i.e., rigid-body transformations along with the scaling to take into account different FOVs) was then applied by means of advanced normalisation tools (ANTs).23, 24 For each pre-/post-void MRI scan pair for each of the four preparations, the pre-void scan (i.e., ‘moving’ volume) was co-registered in this way against the corresponding post-void scan (i.e., ‘fixed’ volume). Each co-registered image was then reformatted in the axial plane to allow for a more accurate and clinically relevant prostate delineation. The prostate was then manually delineated, by means of an in-house software tool, from the most inferior to the most superior location where the prostatic tissue could be clearly identified, excluding the seminal vesicles, according to the independently acquired high-resolution T2w FRFSE axial images.

Figure 1

For more detailed analyses, the prostate was subdivided into apex, mid-gland, and base sectors by dividing the whole prostate gland into thirds and into the anterior and posterior gland for assessing distortion directions in the axial plane. More details about the computational and physical concepts underlying our analysis are provided in Supplementary Material. Briefly, by exploiting the computational framework for prostate deformation assessment proposed by Gill et al., the two prostate outlines under investigation are aligned to their centres, the slice delineations of the ‘moving’ volume are then translated onto the ‘fixed’ reference system (Figure 1B).25 The ‘resultant translocation’ t_res is then computed to characterise the global translocation of the prostate (Figure 1C). The Root Mean Square (RMS) value of the magnitude of the resultant translocation vector is calculated by averaging over all the slices. Finally, Figure 1d shows the ‘resultant distortion’ d_res for evaluating the combined effects of both translational and local distortions; three examples of distortion maps, along with the corresponding fixed and moving volumes, are displayed in Figure 2.

Figure 2

Bladder volumes were calculated by using whole volume segmentation on sagittal T2w cube sequence using an in-house tool developed in Matlab (Math Works, Natick, MA, USA).26 Relative bladder volume difference was defined as absolute volume difference divided by post-void bladder volume. Rectal distention was derived using maximum sagittal and axial dimensions (anal canal to peritoneal reflection), and subjectively scored following a previously reported 5-point Likert scale: 1 = no stool/gas, 2 = minimal, 3 = small amount, 4 = moderate, 5 = large amount of stool/gas.27

Bladder and rectal volumes are potential confounders that may alter prostate position, thus a division into two groups was performed according to any change or otherwise in rectal and/or bladder volume. Important change in rectal distention was based on the work of Villiers et al., where no effect on prostate translocation was demonstrated when rectal volume was <56 mL, equivalent to our baseline score of 2/5.10, 27 Thus, significant rectal distension was defined when an increase or decrease in scoring by ≥ 1 point was observed, however changes in rectal volume for a baseline score of < 2 were disregarded.10, 27 Significant bladder distension change was defined if there was ≥ 2 fold change of bladder volume. The inclusion into the bladder-change group required no significant change in rectal distension and, likewise, inclusion criterion into the rectal-change group mandated no significant bladder volume change. Studies with concomitant change in both bladder and rectal volume were excluded. The translocation cut off values of 3 mm and 5 mm were defined according to the values in the literature, as a tight planning of target volume (PTV) margin is needed for hypo-fractionation regimens in order to increase target dose whilst minimizing dose to the surrounding tissues.28, 29 Typically, a 3 mm to 5 mm PTV margin is recommended clinically to limit the dosimetric consequences of both intrafraction and interfraction motion.28, 29

All prostate contouring was conducted by a single observer. After the primary prostate contouring, in order to assess intra-observer repeatability, a subset of 10 studies were randomly selected, and the prostate was re-contoured in a blinded fashion by the same observer at a separate sitting. We applied the same computerized image analysis methods devised for quantitatively evaluating the bladder volume effect on prostate translocation and distortion. In particular, the two prostate gland delineations, performed on the same MRI study by the same radiologist, were employed in place of the prostate volumes delineated on the pre-/post-void MRI scan pairs (concerning the four preparations investigated).

Unpaired Student’s t-test was used to compare continuous variables between two groups. Analysis of variance (ANOVA) was used to compare translocation and distortion in between prostatic sectors. Post hoc comparisons were adjusted for multiplicity using Bonferroni correction. Pearson’s correlation coefficient (r) was calculated to evaluate correlation. Significance was set at p < 0.05. Statistical analysis was performed with SPSS v.17.0 (SPSS Inc., Chicago, IL, USA).

The mean pre-void bladder volume was 237.3 ± 150.2 mL (range: 40.9–598.1), and mean average post-void volume 74.1 ± 46.4 mL (range: 32.9–203.4). The absolute difference in bladder volume change was 163.1 ± 126.1 mL (range: 8.0–515.9). The median value for rectal distension was 3 (range: 1–5). The mean average absolute change in rectal volume was 5.6 ± 6.2 mL (range: 0.0–30.2).

Whole prostate translocation of ≥ 5 mm was observed in 4/40 (10.0%) patients and ≥ 3 mm in 9/40 (22.5%) patients. Prostatic sector subdivision showed statistically significant differences in translocation between the base and apex (Table 1). Base translocation of ≥ 5 mm was observed in 5/40 (12.5%) patients and of ≥ 3 mm in 15/40 (37.5%) patients. Mid-base translocation of ≥ 5 mm was observed in 4/40 (10.0%) patients and ≥ 3 mm in 9/40 (22.5%) patients. Apex translocation of ≥ 5 mm was observed in 3/40 (7.5%) patients and of ≥ 3 mm in 4/40 (10.0%) patients. Figure 3A depicts prostate translocation plotted against bladder volume (pre-void, post-void, absolute difference). There was a significant difference when subdivision was made according to relative bladder volume difference. The group with ≥ 2-fold increase in bladder volume (N = 17) showed higher translocation values than the group with < 2-fold increase (N = 23) in bladder volume at 3.47 ± 2.21 mm versus 1.72 ± 0.65 mm, respectively (p < 0.01). The directions of prostatic translocation are shown in Figure 4. When plotting the prostate translocation against relative bladder volume difference, there was a moderate positive correlation (r = 0.64, p < 0.01) (Figure 3B), driven by prostate translocation in the antero-posterior (AP) direction, which was the only direction showing a significant difference.

Figure 3

Figure 4

Within the rectal group, the mean pre-void bladder volume was 84.4 ± 11.9 mL (range: 67.7– 99.0), and post-void bladder volume was 55.3 ± 9.9 mL (range: 38.8–70.9). The absolute difference in bladder volume change was 29.1 ± 14.7 mL (range: 8.2–48.0). On the pre-void study, the median value for rectal distension was 3 (range: 1–5) and on the post-void study the median value was 4 (range: 3–5). The average absolute difference in rectal change was 36.3 ± 19.7 mL (range: 14.5–77.5). Whole prostate translocation of ≥ 5 mm was observed in 2/8 (25.0%) patients and ≥ 3 mm in 7/8 (87.5%) of patients. There was no significant difference in translocation between the prostatic sectors (Table 1, Figure 4). Base translocation of ≥ 5 mm was observed in 4/8 (50.0%) patients and of ≥ 3 mm in 6/8 (75.0%) patients. Mid-gland translocation of ≥ 5 mm was observed in 3/8 (37.5%) patients and of ≥ 3 mm in 6/8 (75.0%) patients. Apex translocation of ≥ 5 mm was observed in 3/8 (37.5%) patients and of ≥ 3 mm in 6/8 (75.0%) patients. No correlation was found when plotting rectal volume against prostate translocation. Studies within the rectal group demonstrated significantly higher degrees of whole gland prostate distortion compared to the bladder group (Table 1).

Important differences were observed between the groups, with the rectal group showing higher levels of prostate distortion (Table 2). Similarly, important differences were observed between the groups in the degree of posterior whole gland distortion (Table 2). In the bladder group the maximum prostate distortions for whole gland, base, mid-gland and apex were 9.0 mm, 9.0 mm, 9.0 mm and 8.3 mm, respectively. In the rectal group the maximum prostate distortions for whole gland, base, mid-gland and apex were 10.1 mm, 9.5 mm, 10.1 mm and 6.6 mm, respectively. When plotting the whole gland distortion, there was a moderate positive correlation for relative bladder volume difference (r = 0.61, p < 0.01), but not for the rectum volume difference.

High reproducibility was observed with only minimal discrepancies. The reliability measurements for the translocation direction were 0.08 ± 0.07 mm (range: 0.00–0.27) in the latero-lateral (LL) direction; 0.11 ± 0.07 mm (range: 0.00–0.27) in the AP direction and 0.4 ± 0.03 mm (range: 0.00–0.10) in the supero-inferior (SI) direction. Whole gland RMS translocation reproducibility and distortion reproducibility are noted in Supplementary Table.