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Eur Radiol (2008) 18: 707–715
DOI 10.1007/s00330-007-0779-7
UROGENITAL
Leo Pallwein
Michael Mitterberger
Alexandre Pelzer
Georg Bartsch
Hannes Strasser
Germar M. Pinggera
Friedrich Aigner
Johann Gradl
Dieter zur Nedden
Ferdinand Frauscher
Received: 8 May 2007
Revised: 20 July 2007
Accepted: 27 August 2007
Published online: 16 October 2007
# European Society of Radiology 2007
Ultrasound of prostate cancer: recent
advances
Abstract Prostate cancer is the most
common cancer in men. In the future,
a significant further increase in the
incidence of prostate cancer is ex-
pected. Therefore, improvement of
prostate cancer diagnosis is a main
topic of diagnostic imaging. The sys-
tematic prostate biopsy (“ten-core
biopsy”) is now the “gold standard” of
prostate cancer diagnosis but may
miss prostate cancer. Contrast-
enhanced colour Doppler ultrasound
(US) and elastography are evolving
methods that may dramatically change
the role of US for prostate cancer
diagnosis. Contrast-enhanced colour
Doppler US allows for investigations
of the prostate blood flow and con-
sequently for prostate cancer visual-
ization and therefore for targeted
biopsies. Comparisons between
systematic and contrast-enhanced tar-
geted biopsies have shown that the
targeted approach detects more can-
cers and cancers with higher Gleason
scores with a reduced number of
biopsy cores. Furthermore, elastogra-
phy, a new US technique for the
assessment of tissue elasticity has
been demonstrated to be useful for the
detection of prostate cancer, and may
further improve prostate cancer stag-
ing. Therefore, contrast-enhanced
colour Doppler US and elastography
may have the potential to improve
prostate cancer detection, grading and
staging. However, further clinical
trials will be needed to determine the
promise of these new US advances.
Keywords Ultrasound
.
Colour/
power Doppler
.
Contrast agent
.
Elastography
.
Prostate cancer
Introduction
Prostate cancer is the most common cancer in men. In the
future, a significant further increase in the incidence of
prostate cancer is expected. Therefore improvement of
prostate cancer detection is a main topic of diagnostic
imaging.
In 2006, it was estimated that there were 230,000 new
cases and 30,500 deaths due to prostate cancer in the
United States [1]. More than 70% of cases are diagnosed in
men over age 65. The death rate from prostate cancer has
been declining since the early 1990s but, as stated, a further
increase in the incidence of prostate cancer is expected in
future years. The American Cancer Society guidelines for
the early detection of prostate cancer include annual
screening by digital rectal examination (DRE) and serum
prostate-specific antigen (PSA) levels for men age 50 years
or older who have a ten-year life expectancy [2].
PSA is used for early diagnosis of prostate cancer and for
monitoring for disease recurrence. Men with a PSA level
greater than 2.5 ng/ml have a 20% chance of finding
prostate cancer at biopsy, and this increases to 50% if the
PSA is greater than 10 ng/ml. As PSA is not a specific test
for prostate cancer; other tests have been and are being
developed [3].
It is known that the frequency of finding prostate cancer
relies on the zonal anatomy of the prostate gland. Cancer is
found in the peripheral zone in approximately 80%, in the
transition zone in 15% and in the central zone in 5% [4].
Ninety-five percent of prostate cancers are adenocarcino-
L. Pallwein (*)
.
F. Aigner
.
J. Gradl
.
D. zur Nedden
.
F. Frauscher
Department of Radiology II, Medical
University of Innsbruck,
Anichstrasse 35,
6020 Innsbruck, Austria
e-mail: Leo.Pallwein@uibk.ac.at
Tel.: +43-512-5044811
Fax: +43-512-5044873
M. Mitterberger
.
A. Pelzer
.
G. Bartsch
.
H. Strasser
.
G. M. Pinggera
Department of Urology, Medical
University of Innsbruck,
Innsbruck, Austria
mas that develop in the acini of the prostatic ducts. Other
histologies are rare and do not have specific imaging
features. The Gleason grade is used to quantify the
histologic characteristics of prostate tumours.
Because tumours may not be visualized by conventional
ultrasound (US), systematic biopsy has been advocated.
The sextant approach has been suggested by Hodge and
coworkers. It involves three cores from each lobe in a
parasagittal plane at the base, midgland, and apex of the
prostate and yields approximately a 25% cancer detection
rate when the serum PSA levels are between 4 and 20 ng/ml.
[5] In men with a persistently elevated serum PSA level
and a negative initial biopsy, repeat biopsy demonstrates
cancer in 20–23% of cases. More than 20% of men
require more than two sets of biopsies for diagnosis. [6]
To decrease the rate of repeat biopsies, an increased
number of cores have been advocated by some investi-
gators. [7] Further improvements with higher number of
cores (up to 45) have been performed; however, a recent
study has shown that 24-core saturation prostate biopsy
did not appear to offer benefit over a ten-core biopsy as an
initial biopsy technique. [8]
Based on the above-mentioned, new imaging techniques
are desirable to improve prostate cancer diagnosis. In this
article we discuss the value of contrast-enhanced US and
elastography.
Contrast-enhanced US
Colour/power Doppler US
Prostate cancer tissue is associated with an increased
microvessel density (MVD) due to the proliferation of
neovessels. In malignant tissue, the microvessels are small
and uniform [9, 10]. Increased MVD is also associated with
the progression of prostate cance [11–13]. Conventional
colour/power Doppler US imaging can not visualize
microvessels, but contrast-enhanced US can. US contrast
agents enable improved detection of low-volume blood
flow by increasing the signal-to-noise ratio [14–16] and
therefore allow a more complete delineation of the
neovascular anatomy, by enhancing the signal strength
from small vessels. Further US contrast agents are confined
to the vascular lumen until they dissolve and they are many
times more reflective than blood, thus improving flow
detection. The US contrast agent vibrations generate higher
harmonics to a much greater degree than surrounding
tissues.
Bree [17] demonstrated the potential use of contrast-
enhanced colour Doppler to enhance the diagnostic yield in
a group of 17 patients with normal grey-scale transrectal
US and elevated PSA values. Correlation of biopsy sites
with colour Doppler US abnormalities revealed a sensitiv-
ity of 54%, a specificity of 78%, a positive predictive value
(PPV) of 61%, and a negative predictive value (NPV) of
72% for the detection of prostate cancer. Three of the cases
with a positive contrast-enhanced biopsy site had negative
transrectal US random biopsy within the previous year.
Frauscher et al. [18] compared contrast-enhanced colour
Doppler US targeted biopsy of the prostate with grey-
scale US guided systematic biopsy. Two hundred and
thirty male screening volunteers were included and the
US contrast agent, Levovist (Schering, Berlin, Germany),
was used. Cancer was detected in 69 of the 230 patients
(30%), including 56 (24.4%) by contrast-enhanced
targeted biopsy and in 52 (22.6%) by systematic biopsy.
Cancer was detected by targeted biopsy alone in 17
patients (7.4%) and by systematic biopsy alone in 13
(5.6%). The detection rate for targeted biopsy cores
(10.4% or 118 of 1,139 cores) was significantly better
than for systematic biopsy cores (5.3% or 123 of 2,300
cores, P<0.001), and contrast enhanced targeted biopsy
in a patient with cancer was 2.6-fold more likely to
detect prostate cancer than systematic US-guided biopsy.
Pelzer et al. [19] thereafter investigated the impact of a
combined approach of contrast-enhanced colour Doppler
targeted biopsy and systematic biopsy for the prostate
cancer detection in 380 men with PSA 4.0 –10 ng/ml.
Cancer was detected in 143 of 380 patients (37.6%, mean
total PSA 6.2 ng/ml). The cancer detection rate for
targeted biopsy and for systematic biopsy was 27.4% and
27.6%, respectively. The overall cancer detection rate
with the two methods combined was 37.6%. Similarly to
the previous study, contrast-enhanced targeted biopsy in a
patient with cancer was 3.1-fold more likely to detect
cancer than systematic biopsy. They concluded that
colour Doppler targeted biopsy allows for the detection
of cancers that can not be found on systematic biopsy,
with a significantly reduced number of biopsy cores.
However, the combined use of colour Doppler targeted
and systematic biopsy allows for maximal cancer
detection with a detection rate of 37.6% in patients
with PSA 4–10 ng/ml.
Roy et al. [20] evaluated the accuracy of contrast-
enhanced colour Doppler US to guide biopsy for the
detection of prostate cancer. They investigated 85 patients
with grey-scale and colour Doppler before and during
intravenous injection of US contrast agent made of
galactose-based air microbubbles (Levovist, Schering,
Berlin, Germany). The diagnostic efficiency with and
without contrast medium injection for detecting prostate
cancer were compared based on biopsy results. They
found cancer in a total of 58 biopsy sites in 54 patients.
Contrast-enhanced colour Doppler had higher sensitivity
(93%) than unenhanced colour Doppler (54%), while
specificity increased only 79% to 87% for enhanced
imaging. Roy et al. concluded that contrast enhanced
colour Doppler endorectal US increases the detection of
prostate cancer, by improving sensitivity, while the
difference in specificity was not as pertinent. Obtaining
708
additional biopsy cores of suspicious enhancing foci sig-
nificantly improves the detection rate of cancer.
Recently, Mitterberger et al. [21] evaluated systematic
prostate biopsy versus contrast-enhanced colour Doppler
targeted biopsy for the impact on Gleason score findings.
The study included 690 men and the US contrast agent
Sonovue (Bracco, Milano, Italy) was applied. Prostate
cancer was identified in 221 of 690 subjects (32%) with a
mean PSA of 4.6 ng/ml (range: 1.4-35.0 ng/ml). Cancer
was detected in 180 of 690 subjects (26%) with contrast-
enhanced targeted biopsy, and in 166 of 690 patients (24%)
with systematic biopsy. The Gleason score of all 180
cancers detected by contrast-enhanced targeted biopsy was
6 or higher, mean 6.8. The Gleason score of all 166 cancers
detected by systematic biopsy ranged from 4 to 8 and the
mean Gleason score was 5.4. Since contrast-enhanced
biopsy detected significantly higher Gleason scores
compared with systematic biopsy, this techniques may
allow identification of more aggressive cancers, which is
important for defining prognosis and deciding treatment.
Since flow abnormalities, resulting from prostatitis, may
result in false positive findings on contrast-enhanced
Doppler US, Mitterberger et al. [22] studied the effect of
pre-medication of dutasteride, a dual 5-alpha-reductase
inhibitor, on prostatic blood flow prior prostate biopsy and
the impact on prostate cancer detection. Thirty-six patients
(age range, 52–74 years) with elevated PSA were treated
with dutasteride 14 days prior prostate biopsy. Contrast-
enhanced colour Doppler US was performed before, 7 and
14 days after dutasteride treatment. A reduction of blood
flow was observed already after 7 days, whereas maximum
flow reduction was observed after 14 days. Twelve patients
(33%) of our cohort were found to have suspicious blood
flow and prostate cancer, and six cancers (17%) were
detected solely by contrast-enhanced targeted biopsy.
Therefore, pre-medication of dutasteride seems to reduce
prostatic blood flow in benign prostatic tissue and therefore
improves prostate cancer detection by using contrast-
enhanced Doppler US.
Contrast-enhanced colour Doppler has also been as-
sessed in three-dimensional (3D) US imaging. Bogers et al.
[23] evaluated contrast-enhanced 3D transrectal Doppler
US before and after intravenous administration of 2.5 g
Levovist (Schering, Berlin, Germany). Subsequently, ran-
dom and/or directed transrectal US-guided biopsies were
performed. Prostate cancer was detected in 13 of 18
patients. Vascular anatomy was judged abnormal in
unenhanced images in six cases, of which five proved
malignant. Enhanced images were considered suspicious
for malignancy in 12 cases, including one benign and 11
malignant biopsy results. Sensitivity of enhanced images
was 85% (specificity 80%), compared with 38% for
unenhanced images (specificity 80%) and 77% for
conventional grey-scale transrectal US (specificity 60%).
Among six patients who showed no grey-scale abnormal-
ities, vascular patterns were judged abnormal in four cases,
of which three were malignant. Based on these findings,
they concluded that contrast-enhanced 3D power Doppler
angiography is feasible in patients with suspicion of
prostate cancer who are scheduled for prostate biopsies.
Another analysis by the same group suggested that 3D
contrast-enhanced power Doppler US is a better diagnostic
tool than the DRE, PSA level, grey-scale US or power
Doppler US alone. The most suitable diagnostic predictor
for prostate cancer was a combination of 3D contrast-
enhanced power Doppler US and PSA level [24].
Sedelaar et al. [25] demonstrated the correlation between
MVD and 3D contrast-enhanced power Doppler imaging.
In all patients, the enhanced side of the prostate was
correlated with a higher MVD count. Concerning the MVD
and the colour pixel density, Strohmeyer et al. [26] found
similar results using contrast-enhanced colour Doppler US
using the US contrast agent Levovist (Schering, Berlin,
Germany).
Grey-scale harmonic US
Modern contrast-specific imaging techniques, such as
grey-scale harmonic US, use the nonlinear behaviour of
the microbubbles to increase sensitivity and specificity to
detect signals reflected by microbubbles and allow for US
perfusion imaging. Grey-scale harmonic US (i.e. phase
inversion, pulse inversion techniques) offers compared
with colour/power Doppler US a greater temporal and
spatial resolution, and allows for excellent microbubble
detection. Therefore with the use of this technique the
visualisation of prostate cancer may be further improved.
Halpern et al. [27] used grey-scale and wide-band
harmonic US to compare areas of contrast material
enhancement in the prostate at US with whole-mount
radical prostatectomy specimens to determine if the use of
contrast material improves the detection rate of prostate
cancer. US was performed in 12 subjects with prostate
cancer prior to radical prostatectomy. Each gland was
evaluated with grey-scale harmonic US at baseline and
again during intravenous infusion of a microbubble
contrast agent. Areas of contrast enhancement were
identified prospectively in the transverse plane at the
base, midgland, and apex of the prostate. The US findings
were compared with whole-mount prostatectomy speci-
mens. 31 foci of cancer were present at pathologic
evaluation, with multiple foci of cancer in 11 of the 12
glands. Contrast-enhanced imaging demonstrated an addi-
tional five cancer foci in the outer gland (P=0.025). Seven
additional sites of focal contrast enhancement were
identified. Five of these sites corresponded to foci of
hyperplasia. Two sites were false-positive with no patho-
logic abnormality. Therefore contrast-enhanced US of the
prostate can improve sensitivity for the detection of cancers
in the outer gland, but it can also demonstrate focal
enhancement in areas of benign hyperplasia. (Fig. 1)
709
Halpern et al. evaluated grey-scale harmonic US for
directed biopsy for prostate cancer detection. [28] The
study group consisted of 40 patients, which were evaluated
with harmonic grey-scale US. Sextant biopsy sites were
scored prospectively on a six-point scale for suggestion of
malignancy at baseline during contrast infusion and after
bolus administration. Cancer was identified in 30 biopsy
sites in 16 of the patients (40%). A suspicious site
identified during contrast-enhanced US was 3.5-times
more likely to have positive biopsy findings at than an
adjacent site that was not suggestive of malignancy (P<
0.025). When a suspicious site was evaluated with an
additional biopsy core, the site was five times more likely
to have a biopsy with positive findings than a standard
sextant site (P<0.01). They noted no difference in
diagnostic accuracy between continuous infusion of and
bolus administration of the contrast agent. Though con-
trast-enhanced grey-scale harmonic US improves the
sonographic detection of malignant foci in the prostate,
and allows for targeted biopsy.
To further improve the survival of microbubbles in the
blood flow, harmonic grey -scale US can be performed
with an intermittent imaging mode. [29, 30] Intermittent
imaging uses a reduced frame rate to lower the energy
deposition into tissue, improve the survival time of
microbubbles, and increase the parenchymal enhancement
provided by US contrast agents. Intermittent harmonic
imaging (IHI) was used to assess prostate cancer detection
with contrast-enhanced US. A total of 301 subjects referred
for prostate biopsy were evaluated with contrast-enhanced
US using continuous harmonic imaging (CHI) and inter-
mittent harmonic imaging (IHI) with interscan delay times
of 0.2, 0.5, 1.0, 2.0 s, as well as continuous colour and
power Doppler. Targeted biopsy were obtained from sites
of greatest enhancement, followed by sextant biopsy. In
104 of 301 subjects (35%) cancer was found. Cancer was
found in 15.5% (175 of 1133) of targeted cores and 10.4%
(188 of 1806) of sextant cores (P<0.01). Among subjects
with cancer, targeted cores were twice as likely to be
positive [odds ratio (OR)=2.0, P<0.001]. IHI demonstra-
ted a statistically significant benefit over baseline imaging
(P<0.05). Therefore contrast-enhanced US with IHI
provided a significant improvement in discrimination
between benign and malignant biopsy sites, and may
therefore improve prostate cancer detection.
Recently, more sensitive contrast-enhanced US tech-
niques came available, such as cadence contrast-pulse
sequence (CPS) US technique (Siemens Medical Solutions,
Mountain View, Calif.). This novel US technique processes
the reflections of a series of US pulses, which results in an
optimized contrast-to-tissue ratio and a microbubble con-
trast-only image can be constructed. The detailled technical
specifications of the technique are described by Phillips
et al. [31]
CPS technique has been shown to be useful for
intraoperative detection of liver tumours and follow-up
after radiofrequency ablation therapy of hepatocellular
carcinomas. [32, 33]
We have used CPS imaging for detection of prostate
cancer in a small series of 20 patients referred for prostate
biopsy for CPS targeted biopsies. CPS technique was used
to assess the intraprostatic vasculature during microbubble
administration. Transrectal US was performed using a 8C4
probe with a transmitting frequency varying between 4 and
5.0 MHz. To reduce micobubble destruction a low
mechanical index (0.14) was used. The US contrast agent
SonoVue, was administered by bolus injection, to a
maximum dose of 4.8 ml. The blood flow of the peripheral
zone was evaluated, and areas of faster and higher contrast
enhancement were defined as suspicious for malignancy.
Up to five targeted biopsies were performed from
suspicious areas, and subsequently another investigator
performed ten systematic biopsies in a standard spatial
distribution. CPS imaging found suspicious areas on
contrast enhancement in 11 of 20 cases (55%) and targeted
biopsy revealed cancer in eight of the 11 cases (73%).
Systematic biopsy found cancer in five of 20 subjects
(25%). In the nine subjects without any abnormal findings
on CPS, systematic biopsy was negative for cancer. Based
on these preliminary CPS imaging seems to improve
prostate cancer detection. Furthermore this technique may
have the potential to reduce the number of men scheduled
to biopsy. (Fig. 2)
Even these preliminary results are promising, technical
improvements of microbubble imaging techniques are
necessary. We found in 3 of 11 cases an abnormal contrast
enhancement, however no cancer on biopsy. This might
rely on the fact that the contrast enhancement was assessed
subjectively. Quantification of contrast enhanced US
information is generally based upon a classification or
subjective estimation by the examiner. [34] Both these
approaches are highly user dependent. A system for
objective evaluation was presented by Cosgrove et al.
[35], who introduced a method of colour pixel and vessel
Fig. 1 Transverse contrast-enhanced grey-scale US image of the
prostate. The hyperechoic cancer on the right side and mid gland is
visible by enhancement and ascertained by biopsy
710
counting. However, this method is cumbersome and does
not distinguish pixels with different flow velocity.
Although the detection of prostate cancer with contrast-
enhanced Doppler US may be improved relative to baseline
US, uncertainty remains in the interpretation of contrast-
enhanced Doppler US images. In a study, 16% (59/360) of
contrast-enhanced transrectal US images were rated as
indeterminate with respect to vascular enhancement. [29]
Therefore objective assessment of contrast agent kinetics
may markedly improve the value of these contrast-specific
imaging techniques.
Recently, we have used a prototype software from
Bracco Research, Switzerland, which allows for objective
assessment of contrast enhancement (echo power), in a few
cases with prostate cancer. Contrast enhancement as a
function of time was measured in two regions-of-interest
drawn in the prostate. The mean transit time obtained from
the time-intensity curve measured in normal prostate tissue
(yellow curve) was 1 min 41 s, while the corresponding
value measured in the suspect area was 14 s. In the latter
case, a very fast wash-in was followed by a rapid wash-out
of the microbubble contrast agent, which is typical for
malignant lesions. Huber et al. [36] used a computer-
assisted assessment of microbubble transit time in breast
lesions. They reported that after microbubble injection,
breast carcinomas and benign lesions behave differently in
degree, onset, and duration of US enhancement. Thus, time
intensity curves may also be useful as another objective
measure to differentiate benign from malignant prostatic
tissue (Fig. 3).
Elastography
It is known that cancer tissue shows an increase in both
vessel and cell density. While the increased vascularization
can be visualized with contrast-enhanced US, as stated
above, the increase of cell density in tumours leads to a
change of tissue elasticity. Krouskop et al. [37] described
that there is a significant difference in stiffness between
normal and neoplastic prostate and breast tissue. For
detection of changes in tissue elasticity, Ophir et al. [38]
developed in 1991 an imaging technique based on static
deformation and called it “strain imaging”. This imaging
modality is capable of visualising displacements between
US image pairs of tissue under “compression” . Elasto-
graphy is based on the fact that the backscattered US signal
changes its local characteristic pattern only to a comparably
small extent if the insonified tissue is slightly compressed
and decompressed (i.e. approximately up to 2%) during the
examination. A high internal correlation is maintained
within local regions of interest. However, time or space
differences between local regions of interest under different
compression ratios change with differences in compress-
ibility of the insonified tissue. Time differences between
two local regions of interest within two subsequent images
recorded under different compression ratios can be
calculated for each pixel of the images. Time differences
are not absolute but relative values since the compressibil-
ity of local tissue regions always depends on the
surrounding tissue and the applied compression force.
In order to reduce the time-consuming calculations,
Pesavento et al. [39] developed a fast cross-correlation
technique, which enables a real-time elastographical
imaging. With on-going technical advances, SE was
integrated in modern high-end US units. Real-time SE
has already shown its promising value in the detection and
differentiation of masses in the breast and thyroid gland
[40, 41]. Cochlin et al. [42] introduced real-time elasto-
graphy for the detection of prostate cancer in biopsy
specimens. In their study, elastography had a sensitivity of
51% and a specificity of 83% for the detection of prostate
cancer in individual patients and a sensitivity of 31% and a
specificity of 82% for the detection of individually
Fig. 2 Dual transverse view of
prostate imaged by cadence
contrast-pulse sequence (CPS)
US technique (Siemens Medical
Solutions, Mountain View,
Calif.). Rapid enhancement of
the left side was suspicious for
malignancy. Prostate cancer was
approved by biopsy
711
biopsied areas of the prostate. Sperandeo et al. [43] in 2003
reported the usefulness of elasticity imaging to differentiate
malignant from benign lesions. In their study, they used
tissue elasticity to detect cancer based on tissue deforma-
tion of grey-scale images under manual compression of the
prostate with a transrectal probe.
In a recent pilot study, patients with clinically localised
prostate cancer, who underwent radical prostatectomy,
were examined prospectively [44]. Prior to surgery these
patients were examined with conventional grey-scale US as
well as with real-time elastography. Areas suspicious for
prostate cancer were depicted. After surgery, the histolog-
ical specimens were compared with the transverse US
images and with elastography findings. Thirty-two foci of
prostate cancer were present at pathological evaluation,
with multiple foci of cancer in 13 of the 15 glands. Real-
time elastography detected 28 of 32 cancer foci (sensitivity:
88%). Four sites were false positive with no pathological
abnormality. The by-patient analysis demonstrated that
real-time elastography detected at least one cancer focus in
each of the 15 patients. Therefore, we concluded that real-
time elastography of the prostate is a sensitive new imaging
modality for the detection of prostate cancer. In 78.3% of
cases, elastography findings correlated with histological
findings.
Konig et al. [45] evaluated elastography for biopsy
guidance for prostate cancer detection. After imaging with
conventional grey-scale US in conjunction with real-time
elastography, 404 men underwent systematic sextant
biopsy. Prostate cancer was found in 151 of 404 cases
(37.4%). In 127 of 151 cases (84.1%), prostate cancer was
detected using real-time elastography as an additional
diagnostic feature. They concluded that it is possible to
detect prostate cancer with a high degree of sensitivity
using real-time elastography in conjunction with conven-
tional diagnostic methods for guided prostate biopsies.
Pallwein et al. [46] performed a prospective study to
determine whether a limited biopsy approach with
elastography-targeted biopsy of the prostate would detect
cancer as well as grey scale US-guided systematic biopsy
Fig. 3 Time-intensity curves were obtained with a Siemens Sequoia
US machine in CPS mode, after a single bolus injection of SonoVue
(4.8 ml) contrast agent. Contrast enhancement (Echo Power) as a
function of time was measured in two regions-of-interest (ROIs)
drawn in the prostate. The first ROI (red) was drawn in a suspicious
area; a second one (yellow) was drawn in an area representing
normal prostate tissue. The mean transit time (mTT) obtained from
the time-intensity curve measured in normal prostate tissue (yellow
curve) was 1 min 41 s, while the corresponding value measured in
the suspect area was 14 s. In the latter case, a very fast wash-in was
followed by a rapid wash-out of the contrast agent, which is typical
for a malignant lesion. On the right-hand side of the figure, a
parametric image of mTT shows in hot colours (red and yellow) the
suspicious area, i.e. the area corresponding to the tumour, where
mTT is substantially shorter compared with the rest of the prostate.
(Courtesy of Bracco Research, Switzerland)
712
with a larger number of biopsy cores. Two hundred and
thirty male screening volunteers, with a total prostate
specific antigen of 1.25 ng/ml or greater and free-to-total
prostate specific antigen less than 18%, were examined. In
each subject, five SE-targeted biopsies into suspicious
regions in the peripheral zone during elastographic exam-
ination versus ten systematic prostate biopsies were carried
out. The final cancer detection rate of the two techniques
was compared. Cancer was detected in 81 of the 230
patients (35%), including 68 (30%) by elastography
targeted biopsy and in 58 (25%) by systematic biopsy.
Cancer was detected by targeted biopsy alone in 23 patients
(10%) and by systematic biopsy alone in 13 patients (6%).
The overall cancer detection rate by patient was not
significantly different for elastography-targeted and sys-
tematic biopsy (P=0.134). The detection rate for elasto-
graphy-targeted biopsy cores (12.7% or 135 of 1,109 cores)
was significantly better than for systematic biopsy cores
(5.6% or 130 of 2,300 cores, P<0.001). SE-targeted biopsy
in a patient with cancer was 2.9-fold more likely to detect
prostate cancer than systematic US guided biopsy. In
comparison with the study of Konig et al. [45], an increase
in sensitivity and specificity including the outer prostate
gland only was found. They concluded that although an
increase in cancer detection was achieved by combining
targeted and systematic techniques in this screening
population, elastography-targeted biopsy alone is a reason-
able approach for decreasing the number of biopsy cores.
In a further study, the value of elastography for prostate
cancer detection was compared with systematic biopsy
findings in 492 patients, who were scheduled for system-
atic prostate biopsy [47]. Elastography of the prostate
(Hitachi EUB 8500, Hitachi Medical, Tokyo, Japan) was
performed prior biopsy, to assess tissue elasticity, and areas
with increased stiffness were considered as suspicious for
cancer. Cancer was detected in 321/2,952 (11%) outer
gland areas (74 in the basis, 106 in the mid-gland, 141 in
the apex). On elastography 533/2,952 (18.1%) suspicious
areas were detected and 258 of these areas (48.4%) showed
cancer. Elastography findings showed a good correlation
with the systematic biopsy results. The best sensitivity and
specificity was found in the apex region. Most false-
positive cancer findings (275/533 areas; 51.6%) were
associated with chronic inflammation and atrophy espe-
cially at the basal prostate areas. In conclusion, these new
computer-assisted techniques allow exact assessment of the
tissue elasticity and therefore for a good differentiation
between benignity and malignity (Fig. 4).
Conclusion
The recent advances in US for the detection, grading and
staging of prostate cancer are promising. New technical
developments allow for improved detection of smaller, low
flow vessels and better detection of areas of flow asymme-
try. Mandatory quantification of enhancement will make an
objective grading system available. In summary, contrast-
enhanced US and elastography seem to offer novel and
great potential in prostate cancer diagnosis.
Fig. 4 Dual image. Elasto-
grapic image of prostate (on the
left); the elastogram shows a
clearly visible stiffer area (blue
colour) with suspicion of a
prostate cancer on the left side
of the prostate. Corresponding
transverse grey-scale US image
of prostate with no clear evi-
dence for prostate cancer (on the
right)
713
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