The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy
Günzel et al. BMC Urology
The addition of a sagittal image fusion improves the prostate cancer detection in a sensor-based MRI /ultrasound fusion guided targeted biopsy
Karsten Günzel 0 1 3
Hannes Cash 0 1 3
John Buckendahl 0 1 3
Maximilian Königbauer 0 1 3
Patrick Asbach 1 2
Matthias Haas 1 2
Jörg Neymeyer 0 1 3
Stefan Hinz 0 1 3
Kurt Miller 0 1 3
Carsten Kempkensteffen 0 1 3
0 Department of Urology, Charité - University Medicine Berlin , Hindenburgdamm 30, 12203 Berlin , Germany
1 Karsten Günzel and Hannes Cash are co-first authors
2 Departement of Radiology, Charité - University Medicine Berlin , Hindenburgdamm 30, 12203 Berlin , Germany
3 Department of Urology, Charité - University Medicine Berlin , Hindenburgdamm 30, 12203 Berlin , Germany
Background: To explore the diagnostic benefit of an additional image fusion of the sagittal plane in addition to the standard axial image fusion, using a sensor-based MRI/US fusion platform. Methods: During July 2013 and September 2015, 251 patients with at least one suspicious lesion on mpMRI (rated by PI-RADS) were included into the analysis. All patients underwent MRI/US targeted biopsy (TB) in combination with a 10 core systematic prostate biopsy (SB). All biopsies were performed on a sensor-based fusion system. Group A included 162 men who received TB by an axial MRI/US image fusion. Group B comprised 89 men in whom the TB was performed with an additional sagittal image fusion. Results: The median age in group A was 67 years (IQR 61-72) and in group B 68 years (IQR 60-71). The median PSA level in group A was 8.10 ng/ml (IQR 6.05-14) and in group B 8.59 ng/ml (IQR 5.65-12.32). In group A the proportion of patients with a suspicious digital rectal examination (DRE) (14 vs. 29%, p = 0.007) and the proportion of primary biopsies (33 vs 46%, p = 0.046) were significantly lower. The rate of PI-RADS 3 lesions were overrepresented in group A compared to group B (19 vs. 9%; p = 0.044). Classified according to PI-RADS 3, 4 and 5, the detection rates of TB were 42, 48, 75% in group A and 25, 74, 90% in group B. The rate of PCa with a Gleason score ≥7 missed by TB was 33% (18 cases) in group A and 9% (5 cases) in group B; p-value 0.072. An explorative multivariate binary logistic regression analysis revealed that PI-RADS, a suspicious DRE and performing an additional sagittal image fusion were significant predictors for PCa detection in TB. 9 PCa were only detected by TB with sagittal fusion (sTB) and sTB identified 10 additional clinically significant PCa (Gleason ≥7). Conclusion: Performing an additional sagittal image fusion besides the standard axial fusion appears to improve the accuracy of the sensor-based MRI/US fusion platform.
Multiparametric magnetic resonance imaging; Targeted biopsy; Prostate cancer detection; MRI/US fusion biopsy
Prostate cancer (PCa) is the most common malignancy of
men and the only tumour, which is diagnosed according
to the guidelines by untargeted systematic biopsies of the
entire organ [1, 2]. Because prostate cancer is often not
visualized in conventional transrectal ultrasound, there is a
risk to miss clinically significant PCa (Gleason ≥7) with a
random systematic transrectal prostate biopsy (SB) [3, 4].
Due to a high soft-tissue contrast, a high resolution
(T2weighted anatomical sequences) and the registration of
functional parameters (diffusion-weighted and dynamic
contrast-enhanced sequences (DWI and DCE), MR
spectroscopy imaging) a multiparametric magnetic resonance
imaging (mpMRI) of the prostate provides a high
sensitivity, specificity and negative predictive value in the
detection and localization of clinically significant prostate
cancers [5, 6]. For standardization of evaluation of the
mpMRI the “European Society of Urogenital Radiology”
(ESUR) established the “Prostate Imaging Reporting and
Data System” (PI-RADS), which introduced a 5-point
Likert scale for each region (peripheral and central
glandular sections) with corresponding scores for each
sequence (T2, DWI, DCE, and MR-Spectroscopy) [7, 8].
The correlation of the level of PI-RADS with the overall
detection rate of PCa and the detection of significant PCa
has been demonstrated in various studies [9–13]. The
increasing utilization of mpMRI of the prostate and the
consecutive MRI/ultrasound fusion guided targeted biopsy
(TB) resulted in an improved detection of PCa compared
to SB, the current standard of care [14–17]. A difficulty is
the exact fusion of mpMRI with transrectal ultrasound for
TB. Various possibilities of MRI/ultrasound (MRI/US)
image fusion, such as cognitive fusion, sensor-based fusion
or organ-based fusion are available to perform TB. Despite
the technological progress of different fusion platforms,
several studies have shown that clinically significant PCa
can still be overlooked by TB [17–20]. For the
sensorbases TB we previously analyzed the possible pitfalls of
TB, such as reader variability for mpMRI, an imprecise
targeting of the suspicious lesion . Traditionally
sensor-based fusion of the MRI image and the real-time
ultrasound image is performed by the operator in the axial
plane according to anatomical landmarks (i.e. prostatic
apex, periprostatic vessels, BPH nodes etc.). In order to
further improve the targeting accuracy and reduce a
possible image fusion error, this study evaluated the use of an
additional image fusion in the sagittal plane according to a
3-point technique. In a cohort of 791 men, who
underwent a MRI/US fusion biopsy with an organ-based fusion
system, Hong et al. demonstrated that the combination of
axial and sagittal approaches detected more clinically
significant PCa . For sensor-based fusion platforms
there is currently no data on the effect of an added sagittal
In the period of July 2013 to September 2015, 251
patients, who showed at least one suspicious lesion on
mpMRI (PI-RADS ≥3) and underwent a consecutive TB in
combination with a 10-core systematic prostate biopsy
(SB), were consecutively included into the retrospective
analysis. The indication for a mpMRI has largely been
provided by attending outpatient urologists. Parts of the
cohort were analysed in a previous study . All patients
were recorded regardless to the number of prior prostate
biopsies. The data collection was based on the patients
medical history, clinical findings and the physical patient
files. Patient data was prospectively collected in a START
conform database . The analysis in regard to the axial
and sagittal image fusion was performed retrospectively.
All patients signed an informed consent for the
intervention, data acquisition and data evaluation. The study was
performed according to the declaration of Helsinki and
the analysis was approved by the Institutional Review
Board of the Charité University Medicine Berlin.
Multiparametric magnetic resonance imaging
A 3-Tesla mpMRI (Magnetom Skyra, Siemens Medical
Systems, Erlangen, Germany) without an endorectal coil was
performed for all patients before prostate biopsy. The MRI
protocol contained high spatial resolution T2-weighted
turbo spin-echo sequences in axial, sagittal and coronal
orientation, axial turbo spin-echo T1 weighted images, axial
diffusion weighted images (b-values 0.400 and 800 s/mm )
and dynamic contrast-enhanced sequences. The evaluation
of the mpMRI was performed by experienced radiologists
according to the guidelines of the European Society of
Urogenital Radiology (ESUR) . From a PI-RADS score of
3, the indication for MRI/US fusion biopsy was made.
MRI-ultrasound fusion prostate biopsy and systematic
The prostate biopsies were performed under antibiotic
prophylaxis with a fluoroquinolone according to the EAU
guidelines , with a high-end ultrasound device HiVision
Preirus (Hitachi Medical Systems, Tokyo, Japan) and an
endocavity endfire probe (EUP V53W, Hitachi Medical
Systems, Tokyo, Japan). All biopsies were taken in
lithotomy position. At first TB were performed. T2 and DWI
sequences of the axial planes in mpMRI were imported to
the ultrasonic device. After that, the suspicious lesions
were marked in axial orientation of the mpMRI sequences
by the urologist experienced with mpMRI. The MRI/US
image fusion was performed using sensor-based
registration. The movement of the probe with an attached tracker
was detected in a low magnetic field (0.1 Tesla), which
was generated by a mini bird receiver. Until December
2014 only axial MRI/US image fusion was performed. For
this purpose, the same plane in ultrasound and MRI was
identified according to anatomical landmarks (prostatic
apex, periprostatic vessels, BPH nodes, intraprostatic
cysts) Depending on the anatomical conditions, the angle
of axial plane in the MRI image was corrected to match
the angulation of the ultrasound probe and image. The
previously marked suspect lesions were transferred to the
real-time ultrasound image by the platform’s software,
followed by a 2–5 targeted biopies in an axial orientation.
After an analysis of possible reasons for targeted biopsy
failure, as of December 2014 the targeted biopsies were
performed after MRI/US image fusion in both the axial
and sagittal plane . The total number of targeted
biopsies remained unchanged. For the sagittal image fusion, a
T2-weighted sequence in sagittal orientation was used to
mark the bladder neck, the apex of the prostate and the
seminal vesicle angle. Based on these marks the MRI and
the ultrasound image were fused by the software.
Thereafter, TB was carried out in a sagittal orientation of the
MRI and ultrasound image. For sampling, we used a long
biopsy needle (18 g × 25 cm, Bard Magnum biopsy
instrument, Tempe, United States). After performing TB, local
anaesthesia with a bupivacaine was injected at the dorsal
prostatic capsule and a 10-core SB was conducted without
changing the examiner. The SB scheme included cores
from: left/right apex, left/right lateral mid gland, left/right
base, left/right ventral and left/right para-urethral. All
tissue-samples were documented by their extraction
location and shipped separately for histopathological
evaluation by our experienced pathologists.
Group A included all patients who have received an MRI/
US image fusion only in the axial plane. Group B, are
included all patients who have received MRI/US image
fusion in the axial and sagittal plane. Figure 1 shows a flow
chart for the patient inclusion and the group distribution.
PASW Version 22 (SPSS Inc. 1998–2010, Chicago, Illinois
60606, USA) was used for statistical analyses. Categorical
data were presented by absolute and relative frequencies.
Continuous variables were measured by means and
standard deviation when normal distributed or by medians and
quartiles. Continuous variables were evaluated with the
Kolmogorov-Smirnov-test for normal distribution. We
used chi-square test, Student’s t-test and Mann-Whitney U
test to calculate statistical differences between numerical
and categorical variables. Univariate and multivariate
binary regression analysis were performed to evaluate
significant parameters in the descriptive analysis as predictors
for PCa detection. A p-value of p <0.05 was considered
Demographic data, clinical characteristics and MRI
findings are presented in Table 1 divided in group A
(patients without additional sagittal image fusion) and
group B (patients with additional sagittal image fusion).
The median age in group A was 67 years (IQR 61–72)
and in group B 68 years (IQR 60–71). Both groups
showed statistically similar prostate volumes (48 vs.
50 ml). The median PSA level in group A was 8.10 ng/
ml (IQR 6.05–14.00) and in group B 8.59 ng/ml (IQR
5.65–12.32). The proportion of patients with a
suspicious digital rectal examination (DRE) (14 vs. 29%, p =
0.007) and the proportion of patients with primary
biopsies (33 vs 46%, p = 0.041) were significantly lower
in group A. The rate of PI-RADS 3 lesions were
overrepresented in group A (19 vs. 9%; p = 0.044). With 43%
compared to 30% in group A PI-RADS 5 lesions were
more frequently represented in group B (p = 0.051). No
significant differences were observed for lesion
positions, number of suspicious lesions in mpMRI and
lesion sizes. The mean number of cores taken per patient
and the mean number of TB per patient were
significant higher in Group A (13.7 vs. 13.2 and 3.8 vs. 3.4;
p = 0.009 and 0.031). The analysis showed a significant
higher overall cancer detection rate (CDR) (85 vs. 72%;
p = 0.019) and a significant higher detection rate in TB
(76 vs. 55%; p = 0.001) in group B, please see Table 2.
Furthermore there was a significant lower number of
patients diagnosed with a clinically significant PCa in
group A (61 vs. 78%; p = 0.025). Classified according to
Fig. 1 Patient inclusion and group distribution. Group A included patients between July 2013 and December 2014 where an axial targeted biopsy was
the standard Group B included patients between December 2014 and September 2015 where and axial and sagittal targeted biopsy was performed
without increasing the total number of targeted biopsy cores
Table 1 Patient demographics and magnetic resonance
imaging findings (n = 251)
Median (IQR) age, years
Median (IQR) PSA. ng/ml
8.10 (6.05–14.00) 8.59 (5.65–12.32) 0.997
Median IQR) f/t PSA-ratio,% 12 (9–17)
Suspicous DRE, n (%)
No. of prior biopsies, n (%)
Maximum diameter of
Mean (SD) TBs per patient 3.8 (±1.5)
PSA prostate-specific antigen, IQR interquartile range, SD standard deviation,
DRE digital rectal examination, mpMRI multiparametric magnetic resonance
imaging, PI-RADS Prostate Imaging Reporting and Data System, TB
aFor patients with multiple lesions the highest PI-RADS score is stated
PI-RADS 3, 4 and 5, the detection rates of TB were 42,
48, 75% in group A and 25, 74, 90% in group B. The rate
of PCa with a Gleason score ≥7 missed by TB was 33%
(18 cases) in group A and 9% (5 cases) in group B (p =
0.072). The overall cancer detection rates and the
PIRADS based analyses for SB and TB for men without
suspicious DRE and prior negative biopsy are shown in
Additional file 1 Table S1 and Additional file 2 Table S2.
An explorative multivariate binary logistic regression
analysis revealed that PI-RADS, a suspicious DRE and
performing an additional sagittal image fusion were
significant predictors for PCa detection in TB, please see
Table 2 Cancer Detection Rate and Gleason pattern
PI-RADS 3 (n = 39)
PI-RADS 4 (n = 126)
PI-RADS 5 (n = 86)
Detected GS ≥7 in TB
Missed PCa (GS ≥7) in TB
CDR = Cancer Dection Rate; GS = Gleason Score; SB = Random Biopsy; TB = Target
biopsy; * % of GS ≥7 detected by TB
Since the introduction of MRI/US fusion biopsy of the
prostate, several studies have demonstrated an
improvement in prostate cancer detection rates as well as the
identification of clinically relevant tumours [14, 15, 24–26]. Due
to this increasing value of MRI/US fusion biopsy for
Sagittal image fusion
Maximum diameter of lesion
3 (n = 8)
4 (n = 43)
5 (n = 38)
1–10 (n = 27)
11–20 (n = 50)
>20 (n = 12)
Localization of lesion
Apex (n = 35)
Midgland (n = 32)
Base (n = 22)
Anterior (n = 28)
Table 4 Cancer Detection Rate of the Targeted Biopsy in relation to an axial and sagittal image fusion
Group B n = 89
Overall CDR in TB (sTB + aTB)
Additional PCa detected
only by sTB*
aTB = axial fusion TB; sTB = sagittal fusion TB; * compared to overall CDR or TB (aTB + sTB);
#Either detection of GS ≥7 only by sTB or Gleason upgrade in the sTB biopsy core compared to the aTB core; percentage of GS ≥7 detected by TB (aTB + sTB) n = 53
primary diagnosis and monitoring of prostate cancer
various fusion systems have been established. A variety fusion
systems (UroNav, BiopSee, Urostation, Artemis,
HiVisonPreirus, etc.) have been reported in the current literature
[13, 14, 22, 24, 26, 27]. Uniform treatment regimens for the
implementation of MRI/US fusion biopsies do not exist. In
a large patient cohort Hong et al. demonstrated for organ
based MRI/US fusion biopsies that the combination of
sagittal and axial biopsy approaches identified additional
clinically significant prostate cancers . It can be assumed
that the correctness of the image fusion of MRI and
transrectal ultrasound has an important influence on the
accuracy of targeted sampling. Our study showed a significant
increase in prostate cancer detection rate of TB by 55% in
the group without sagittal fusion to 76% in the group with
additional sagittal fusion and the improvement remained
even when men with a positive DRE and a primary biopsy
were excluded. In addition, the proportion of detected
clinically significant PCa (Gleason-score ≥7) increased from
61% in group A to 78% in group B. The sole analysis of the
detection rates of axial TB results in an increase of 56 to
66% in group B. The observed increase in detection rates
might be related to various factors. In the sensor-based
MRI/US image fusion, the same layers in the T2-weighted
MRI sequence and the transrectal ultrasound image in axial
or sagittal orientation are fused. Identifying the same layers
in MRI and US are the basis of fusion accuracy. Angular
deviations of the display plane in transrectal ultrasound and
MRI lead to inaccuracies of image fusion. In our study, the
angle correction for axial image fusion was carried out
manually by the urologist. In the sagittal image fusion, the
angular offset is software-based by three identical points,
which are simultaneously marked in MRI and ultrasound
in two different layers. Gaziev et al. showed an increase in
the detection rate of prostate cancer by performing perineal
MRI/US fusion biopsies of the prostate with increasing
experience of the examiner . It is tempting to speculate,
that in our study the learning curve of the examiner has
likewise lead to an increase in the detection rate in the TB
after implementation of additional sagittal image fusion.
Another important factor influencing the detection rate of
TB is the PI-RADS score [12, 13]. Our study cohort showed
a significant decrease of percentage of PI-RADS 3 lesions
and a non-significant increase in the proportion of
PIRADS 5 lesions in the patient group with additional sagittal
fusion. Also in the univariate and multivariate regression
analysis the level of PI-RADS was identified as a significant
predictor for PCa detection. This may have occurred to an
increased PCa detection in group B, but the sagittal image
fusion remained an independent predictor for cancer
detection by TB. A suspicious digital rectal examination as
described by Radtke et al. and Potter et al. presents a further
risk factor for the detection of PCa in TB and SB [18, 29].
Similar to the previously published studies, our univariate
and multivariate regression analyses of the whole cohort
revealed a significant correlation of a suspicious DRE with
PCa detection rate. The higher TB detection rate in group
B, that included more men with a suspicious DRE, may
therefore have been influenced, but the higher detection
rate in group B compared to group A persisted when the
analysis excluded men with a suspicious DRE. In our
regression analysis, the proportion of biopsy naive men was
not a significant predictor for PCa detection, although two
large studies showed an influence on cancer detection
[12, 22]. Therefore, the significantly higher proportion of
primary biopsies in group B may have affected the
detection rate of the TB. Again, the improved detection rate in
group B remained when men with a positive DRE and a
primary biopsy were excluded from the analysis.
The additional implementation of the sagittal image
fusion resulted in an increase in the detection rate of 10%
for TB. By sagittal fusion, nine (13%) additional prostate
cancers were detected and ten (19%) additional clinically
significant tumors were identified. The improvement of the
axial TB, when adding a sagittal TB was independent of the
lesion size or localization of the lesions. Moreover,
performing a sagittal image fusion was a significant predictor in
univariate and multivariate regression analysis for the
detection of prostate cancer in the TB. In the group of
patients with sagittal fusion, the proportion of overlooked
clinically significant tumors by TB dropped to 9%
compared to 33% in the group of patients without sagittal
fusion. The reduced rate of missed PCa after the
introduction of the sagittal image fusion was not accompanied with
an increase of the number of targeted biopsies.
Adding the sagittal image fusion when performing TB on
a sensor-based platform may reduce the targeting error that
may be inevitable in some cases . In our institution we
have therefore established the additional sagittal image
fusion firmly in our MRI/US fusion biopsy protocol.
Because of the retrospective study design the
investigation has several limitations. Unconsidered confounders
may have also influenced the study results, e.g. a selection
bias of patients by referring outpatient urologist. The
inhomogeneity of the two study groups in terms of baseline
characteristics may have affected the study results. To
ensure the data consistency, we performed logistic regression
analyses for the evaluation of predictors of PCa detection
by targeted biopsy. In order to clearly demonstrate the
impact of an additional sagittal image fusion on the detection
rate of TB would require prospective randomized studies.
Performing a sagittal image fusion in addition to the
standard the axial fusion improves the accuracy to detect
PCa by targeted biopsies performed with a sensor-based
MRI/US fusion platform.
Additional file 1: Table S1. Cancer Detection Rates in Group A and B
excluding men with abnormal DRE. (DOCX 19 kb)
Additional file 2: Table S2. Cancer Detection Rate and Gleason pattern
in Group A and B excluding men with abnormal DRE and including only
men with prior negative biopsy. (DOCX 19 kb)
DCE: Dynamic contrast-enhanced sequences; DWI: Diffusion-weighted;
ESUR: European society of urogenital radiology; mpMRI: Multiparametric
magnetic resonance imaging; MRI/US: MRI/ultrasound; PCa: Prostate cancer;
SB: Systematic transrectal prostate biopsy; TB: MRI/ultrasound fusion guided
Availability of data and materials
The datasets during and/or analysed during the current study available from
the corresponding author on reasonable request.
KG, HC, CK: Protocol/project development. KG, HC, JB, MK, PA, MH: Data
collection or management. KG, HC, CK: Data analysis. KG, HC, CK: Manuscript
writing/editing. PA, JN, SH, KM: Critical manuscript revision. JN, SH, KM, CK:
H. Cash reports receiving honoraria as a speaker on national conferences for
Hitachi Medical Systems. All other authors have no competing interests.
Consent for publication
Ethics approval and consent to participate
All patients signed an informed consent for the intervention, data acquisition
and data evaluation. The study was performed according to the declaration
of Helsinki. The analysis was approved by the Institutional Review Board of
the Charité University Medicine Berlin.
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