Advances in Molecular Imaging, 2013, 3, 23-36
http://dx.doi.org/10.4236/ami.2013.33005 Published Online July 2013 (http://www.scirp.org/journal/ami)
Identification and Localization of Prostate Cancer with
Combined Use of T2-Weighted, Diffusion Weighted MRI
and Proton MR Spectroscopy, Correlation with
Histopathology
Baki Hekimoğlu1, Hasan Aydin1, Volkan Kızılgöz1, İdil Güneş Tatar1, Ali Rıza Ugan2, İrem Paker3
1Radiology Department, Dışkapı Yıldırım Beyazıt Education and Research Hospital, Ankara, Turkey
2Urology Department, Dışkapı Yıldırım Beyazıt Education and Research Hospital, Ankara, Turkey
3Pathology Department, Dışkapı Yıldırım Beyazıt Education and Research Hospital, Ankara, Turkey
Email: dr.hasanaydin@hotmail.com
Received May 1, 2013; revised June 3, 2013; accepted June 10, 2013
Copyright © 2013 Baki Hekimoğlu et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Purpose: To predict the diagnostic performance of combined use of T2-weighted imaging (T2W)-diffusion weighted
MRI (DWI) and apparent diffusion coefficient (ADC)-proton MR spectroscopy (H-MRS) for the detection of prostate
cancer, correlated to histopathology as the reference standard. Method: After institutional review board approval, 40
patients with prostate cancer were included in this retrospective research. Two readers evaluated the results of T2W,
DWI-ADC mapping and H-MRS independently for the depiction of prostate cancer. Reference standard was the TRUS-
guided biopsy and the surgical histopathological results. Statistical analysis was assessed by Fisher’s exact t-test, Wil-
coxon signed rank test, variance analysis test with Kappa (k) values and receiver operating characteristics (ROC) curve
for ADC values, Cho/Cit and Cho + Cre/Cit ratios for each observer. Results: Both readers declined 46% sensitivity
and 68% specificity for T2W sequence, 29% sensitivity and 82% specificity for DWI-ADC mapping and 49%
specificity for Cho/Cit and Cho + Cre/Cit ratios, 69% sensitivity for Cho/Cit 70% sensitivity for Cho + Cre/Cit ratios of
H-MRS. T2W + DWI-ADC mapping + H-MRS (Cho/Cit and Cho + Cre/Cit ratios) regarded 81% sensitivity and 66%
specificity, with significant statistical differences to the reference histopathology (p < 0.05). Conclusion: Combination
of T2W, DWI and H-MRS were more sensitive and more accurate than either sequences alone, for prostate cancer
localization and detection.
Keywords: MRI; Prostate Cancer; DWI; H-MRS; T2W
1. Introduction
For the elder men with high blood level of prostate-spe-
cific antigen (PSA), the definite diagnosis of prostate
cancer is based on biopsy, obtained invasively by en-
dorectal sonographic guidance (TRUS) [1-3]. However,
it has several limitations like, lower sensitivity and speci-
ficity for the detection and local staging of prostate can-
cer, limited potential to delineate the malignant foci,
lower diagnostic rate for extra-capsular extension of dis-
ease, have high false-negative rates up to 40% and at the
same time high false-positive rates due to benign pro-
static disease like prostatitis, hemorrhage, prostate hy-
perplasia and post-treatment sequela [1,3-5]. MR imag-
ing, a non-invasive diagnostic tool, has shown a great
confidence for the evaluation and management of pros-
tate cancer [1,2,4-9]. MRI of prostate with combined
pelvic and endorectal coil, has become an accepted
method for staging of this cancer [1,4,6,9-12], T2W-MR
imaging facilitate appropriate data for the treatment
planning of prostate cancer via aiding for the detection,
localization and staging of prostate cancer which also
include the extra-capsular extension and seminal vesicle
invasion [1,4,7,13,14]. However, T2W imaging has quite
good sensitivity but lower specificity for tumor detection
and discrimination of cancer from non-malignant tissues,
to further improve the sensitivity and mainly the speci-
ficity of it; Functional MR imaging techniques like 3D
H-MRS, dynamic contrast enhanced MRI and DWI-
ADC mapping have been proposed to be added to the
routine prostate MR protocole for the entire diagnosis of
C
opyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL.
24
cancer [1,2,4,7,10,12,14-16]. A significant reduction of
citrate(Cit) and elevation of choline(Cho), increased Cho/
Cit and Cho + Cre/Cit ratios have been documented for
the diagnosis of prostatic adenocarcinoma in 3D H-MRS,
compared to the normal prostate tissue and recently
3D-chemical shift imaging (CSI) has been shown to fa-
cilitate sensitivity and specificity for tumor detection up to
95% respectively [2,4-6,8-11]. DWI-ADC mapping also
has potentials for the detection of prostate cancer; ADC
values have clinical utility in the depiction of prostate
cancer, mean ADC values for malignant peripheral-tran-
sitional and central zone prostatic foci are lower than of
those benign prostatic tissues [2,4,7,12,14,16-19]. Addi-
tion of those high-MR imaging techniques to routine T2W
prostate imaging have been found to improve the detec-
tion and localization of prostatic cancer [2,4,7,12,14,
15,17]. The goal of our present study was to utilize ret-
rospectively the diagnostic performance of combined use
of T2W, DWI-ADC mapping and H-MRS for the detec-
tion of prostate cancer, correlated to histopathology as
the reference standard.
2. Material and Methods
The research was approved by institutional review board.
Between June 2010 and September 2012, 40 consecutive
male patients; age ranged between 54 - 82 years, 69 years
mean) with histologically proven prostate cancer without
any contraindications for an MR examination of the
prostate, were included in this retrospective research. For
the analysis of ADC values and H-MRS (Cho/Cit and
Cho + Cre/Cit ratios) of cancer patients, data of 5 normal
control group patients were taken as the reference. None
of the patients had previous surgical procedures, radia-
tion or hormonal therapy and none of the patients were
excluded from the research due to image distortion. Pa-
tients were admitted to MR unit from Urology Depart-
ment, all the patients underwent a clinical rectal exami-
nation, blood PSA levels (total-free) and biopsy yields
were also examined. The interval between MRI and
TRUS-guided biopsy was 2 - 6 weeks, 4 weeks mean and
the surgical approaches were about 1 - 3 weeks after MRI.
All the MRI procedures and Multi-voxel spectroscopic
analysis were carried out with an 8-channel 1.5 T MR
scanner (Philips Achieva, Philips Medical systems, Nether-
lands) by using a 4-channel standard pelvic-phased array
coil. Whole prostate and seminal vesicles were visualized
in every patient.
Parameters of prostate imaging in this research were,
T2W sequence: Performed in axial and coronal planes
with turbo spin echo, for axial one; 400*400 FOV,
240*320 matrix, 5175/64: TR/TE, 4 mm slice thickness, 2
NEX, duration of scan about 2.27 min, for coronal plane;
200*200 FOV, 256*320 matrix, 3800/104: TR/TE, 4 mm
slice thickness, 2 NEX, continued about 2.33 min. DWI-
ADC mapping: Performed in transverse plane with
3D-echo planar imaging 300*400 FOV, 144*192 matrix,
2200/84: TR/TE, 2 mm slice thickness, acquisition time
about 2.37 min, b = 800 s/mm2 ADC values were manu-
ally constructed on a pixel-by-pixel basis from six parts of
prostate. H-MRS acquisitions: Organized in 3D (Axial-
sagittal-coronal) planes, Multivoxel approach with point-
resolved spectroscopic sequence (PRESS); 200*200 FOV,
1500/135 msec.: TR/TE, time of scan was about 5.45
min.
12 of the patients had several osteoblastic bone metas-
tasis (Dorsal-lumbosacral vertebrae, bilateral iliac wings
and sacroiliac joints, ribs and sternoclavicular joints),
pelvic-abdominal lymphadenopathies which had been
undergone to radiotherapy and chemotherapy, considered
as inoperable group, TRUS-guided biopsy was the refer-
ence standard in this group. Remaining 28 patients had
operation; 5 of them undergone to transurethral resection
and 23 had radical prostatectomy, gold standard was the
operation and histopathological results in this group. All
the surgical procedures were performed by a 15 years ex-
perienced urologic surgeon and his team-mates. Analysis
of data set: For tumour localization; Prostate was di-
vided into 2 halves: Right (R) and Left (L), then to 3
parts: Apex(A)-transitional(T) zone (middle)-periphe-
ral(P) zone(base), each part then was divided into three
compartments (Median-mid and lateral). Thus in each
case, we had 18 regions of interest (ROI) within the
whole prostate of each patient. In order to avoid discor-
dance of exact localizations for image evaluations and
the biopsy site through whole prostate, multiple ROI’s
were placed through each halves, parts and compart-
ments of each prostate. The readers graded the ROI posi-
tive if cancer was found out in any compartment of R and
L, A-T and P. Two radiologists (Reader 1 and 2) with 3
and 2 years of experience for the interpretation of T2W,
DWI-ADC mapping and H-MRS respectively, they in-
dependently reviewed all images of MRI, spectral analy-
sis and post-processing were carried out by using a soft-
ware of Philips Achieva Netherland work-shop. Both
readers were aware that all MR sequences included in
this research, were derived from patients with a bi-
opsy-proven prostate cancer but were unaware of the
major cancer localizations of through the prostate histo-
pathologically, also had no prior knowledge about PSA
levels and Gleason scores of patients. Both readers pre-
sented the H-MRS and ADC results with consensus, for
T2W sequence; In case of discordance between readers:
Reader 3 with 7 years of experience, reviewed the un-
consensed images and predicted the final decision. There
were no intra-interobserver variability between both
readers, no variability observed between reader 3 and the
other readers either (p > 0.05). Both readers evaluated all
the MR images in a random patient case order. At first,
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL. 25
T2W images were evaluated, the criteria for cancer
presence was a mass or nodule homogenously low-signal
intensity with ill-defined margins [1,4,8,10,12]. Second,
DWI-ADC mapping were interpreted, diagnostic criteria
was the focal or conglomerated areas or lesions, hyper-
intense in DWI and hypointense in ADC mapping, rela-
tive to surrounding prostate [1,4,7,12,16-19]. ADC val-
ues of each ROI for both prostate cancer and healthy
control group patients were measured manually on the
Philips Achieva work station, then compared to each
other statistically. ROC curve analysis according to ADC
values of both group patients for both readers, were also
investigated. Third, H-MRS was evaluated: Multivoxel
approach with PRESS voxel excitation by band-selective
inversion with gradient dephasing, water-lipid suppres-
sion and spatial encoding by chemical shift imaging with
high resolution at all three dimensions via 3D-TE: 135
acquisition [4-6,9,20-23]. With the application of Ham-
ming filter; Effective standard voxel size of 1 × 1 × 1.5
cm was obtained, magnetic field homogeneity was opti-
mized by using both automated and manual shimming,
phase encoding was applied to produce 3D-MR spectro-
scopic arrays of proton spectra throughout the prostate
[2,4,5, 7,21,24], after post-processing of the time-domain
by zero filling to 1024 points, multiplication by Hanning
filter, Fourier transformation and phase-baseline correc-
tion, spectral data was analyzed to provide standard de-
viation and peak estimates of choline(Cho), citrate(Cit)
and creatine(Cre) resonances, Cit resonance was found at
2.6 ppm, Cre at 3.0 and Cho resonance at 3.2 ppm, re-
spectively [4,6,9,21,23,25-28]. For further analysis, Cho/
Cit and Cho + Cre/Cit ratios were used for the tumour
depiction; Voxels with more than 30% tumour based on
biopsy, were taken as positive ROI for the presence of
cancer. Voxels were considered to be malignant if Cho/Cit
and Cho + Cre/Cit ratios were at least 2 standard devia-
tions higher than the average ratio of the normal control
group results [2,4,6,8,9,21,25]. Both ratios for each ROI
with prostate cancer and healthy control group patients
were measured automatically on the workstation, results
of both groups compared to each other statistically, ROC
curve analysis according to Cho/Cit and Cho + Cre/Cit
ratios of both group patients for both readers were also
determined.
In order to prevent influences of T2W imaging upon
later sequences and creating a bias through all three MRI
sequences, both readers independently evaluated T2W
datas of all patients in a different case order, then analysed
the forthcoming sequences also in a random patient case
order, quite different than the order of T2W images so
we believe that both readers can accurately interpret the
real potentials of DWI-ADC mapping and H-MRS to
detect exact localization of prostate cancers.
All the statistical analyses were performed by using a
software program (SPSS for Windows, SPSS, Chicago-
Illinois). Statistical correlation of T2W sequence to bi-
opsy and histopathology, was assessed by Fisher’s exact
t-test, Wilcoxon signed rank test was used to compare
malignant tissue with control group for the following
variables: ADC values, Cho/Cit and Cho + Cre/Cit ratios,
cancerous nodules were paired to normal prostatic tissue
of control group patients. Intra and interobserver vari-
ability between readers were calculated by Variance
analysis test with Kappa (k) values. k values between
0.80 - 1.00 indicated perfect agreement, k from 0.6 to 0.8
presented high agreement, k values between 0.4 to 0.6 in-
dicated moderate agreement, k value 0.2 to 0.4 presented
fair agreement, k value between 0 - 0.20 indicated slight
agreement [29,30]. p < 0.05 was considered to indicate a
statistically significant difference for both tests. Receiver
operating characteristics (ROC) curve was also fitted to
obtain cut-off values for ADC, Cho/Cit and Cho +
Cre/Cit ratios for each observer to determine malignant
prostate nodules by using area under this curve (AUC).
3. Results
Tables 1(a) and (b) summarizes the data of patients in-
cluding, age-PSA levels-Gleason scores, readers results
and common lists for T2W and for DWI-ADC values,
MRS acquisition of Cho/Cit and Cho + Cre/Cit ratios for
cancer and normal control group patients. Gleason scores
of the patients ranged between 5 - 10, mean 3 + 4 = 7,
PSA levels of them had the range between 1.6 - 139.53
ng/ml, 70.6 ng/ml: median.
For T2W sequences: Reader 1 declared 100 malig-
nancy and reader 2 predicted 96 cancerous foci through
all cancer patients. Both readers presented perfect agree-
ment without any significant statistical differences to each
other (p > 0.05, k: 0.893). Regarding to biopsy yields;
Common results of readers declined 46% sensitivity and
68% specificity for the depiction of prostatic cancer with
significant statistical differences (p < 0.05) (Table 2,
Graphic 1(a), Figure 1).
For DWI and ADC mapping: Reader 1 predicted 50
cancerous areas and reader 2 regarded 43 malignancy
through all prostates included in this research. Both
readers presented significant statistical differences to
each other with perfect agreement (p < 0.05, k: 0.900).
With regard to biopsy; Common DWI results of readers
declined 29% sensitivity and 82% specificity for detect-
ing prostate cancer without any statistical differences (p
> 0.05) (Table 2, Figure 2). Mean ADC values in the
cancer group was about 5.03 ± 7.22 × 103 s/mm2, didn’t
present any significant statistical differences to biopsy
results (p > 0.05), 3.89 ± 3.69 × 103 s/mm2 in the control
group, didn’t present any significant statistical differen-
ces to biopsy results either ( > 0.05), but both groups p
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL.
Copyright © 2013 SciRes. AMI
26
Table 1. (a) List of patients with results; (b) Control group.
(a)
REGIONAL CLASSIFICATION FOR PROSTATE
RIGHT PERIPHERAL (RP)
RIGHT TRANSITIONAL (RT)
RIGHT CENTRAL (RC)
LEFT PERIPHERAL (LP)
LEFT TRANSITIONAL (LT)
LEFT CENTRAL (LC)
MR SEQUENCES
T2 WEIGHTED (T2W)
DIFFUSION AND ADC (DWI-ADC)
MR SPECTROSCOPY (MRS)
PSA: Prostate Spesific Antigen (ng/mL)
fPSA: Free PSA level, tPSA: Total PSA level
INTEROBSERVER STATEMENT FOR MRS RESULTS
DIFFERENCE BETWEEN OBSERVERS:
DBO: Observer 1 (+) , Observer 2 ()
DBO: Observer 1 () , Observer 2 (+)
CON: CONSENSUS (“POSITIVE” ACCORDING TO TWO
OBSERVERS AT LEAST)
NN: CONSENSUS (“NEGATIVE” ACCORDING TO TWO
OBSERVERS AT LEAST)
IN THE LAST COLUMN, “BIOPSY” MEANS BIOPSY RESULTS. THIS
COLUMN INDICATES THE REGIONS WHICH ARE MALIGNANT AC-
CORDING TO PATOLOGY RESULT AND “GLEAS ON ” MEANS THE
GLEASON SCORE OF THE MALIGNANT REGIONS
IN T1W, T2W, DWI-ADC, C+ COLUMNS RESULTS ARE
WRITTEN BY BOLD BLACK LETTERS IF THERE IS NO
INTEROBSERVER DIFFERENCE. IN THESE COLUMNS,
BLUE LETTERS ARE THE RESULTS REFER ONLY TO
OBSERVER 1 AND RED ONES ONLY TO OBSERVER 2
THE GREEN LINES INDICATE THE PATIENTS IN CONTROL
GROUP
MRS
N Name Age tPSA
fPSA T2W DWI-ADC RATIO
RP RT RC LP LT LC
Biopsy and
Gleaso n
Cho/Ci CONCONCONCON CON CON
1 A.B. 69 24.67 RT, RP, LC RP, LP Cho + Cr/CİCON CON CON CON CON CON
LC, RC, LP
3 + 3 = 6
Cho/Ci CONCONCONCON DBO CON
2 B.A. 67 45.97 LP, LT, RP,
RC, LC RC Cho + Cr/CİCONCONCONCON DBO CON
RP, RT, RC,
LP, LT, LC
3 + 3 = 6
Cho/Ci CONNNNNNN CON CON
3 C.A. 71 24.13 RP, LP RP
Cho + Cr/CİCON NNNNNN CON CON
LP, LT
3 + 3 = 6
Cho/Ci NNCONCONCON CON CON
4 O.B. 77 22.86
20.26 LP, LC LP Cho + Cr/CİNNCON CON CON CON CON
LP, LT, LC
4+3 = 7
Cho/Ci DBO DBO CON CON CON CON
5 E.B. 74 19.88 RP, LP
Cho + Cr/CİDBO DBO CON CON CON CON
RP, RT, RC
4 + 5 = 9
Cho/Ci CONNNNNNN NN NN
6 E.E. 68
139.53
20.9 RP, LP RP, LP Cho + Cr/CİCON NN NN NN NN NN
RP, RT, RC,
LP
5 + 5 = 10
Cho/Ci CONCONCONCON CON CON
7 G.A. 74 7.87 LP NN Cho + Cr/CİCON CON CON CON CON CON
RP, LP
4 + 4 = 8
Cho/Ci NNCONNNCON CON CON
8 H.A. 69 100
16.4 LP, LT, RT, RC LP, LT Cho + Cr/CİNNCONNNCON CON CON
LC, LP
4 + 4 = 8
Cho/Ci CONCONCONCON CON NN
9 H.Ü. 64 10.97 RT, RP, LP
Cho + Cr/CİCON CON CON CON CON NN
LP, LT, LC
3 + 3 = 6
MRS
N Name Age tPSA
fPSA T2W DWI-ADC RATIO
RP RT RC LP LT LC
Biopsy and
Gleaso n
Cho/Ci CONNNCONCON CON NN
10 H.Y. 78 8.01
10.2 LP, RP, LC RP, LP Cho + Cr/CİCONNNCON CON CON NN
RP, RT, RC,
LP
3 + 3 = 6
B. HEKİMOĞLU ET AL. 27
Continued
Cho/Ci CONCONNNCON CON NN
11 H.K. 80 59.26 LP, RP, LT LP, LT Cho + Cr/CİCON CONNNCON CON NN
RP, RT, RC,
LP, LT, LC
4 + 4 = 8
Cho/Ci CONCONCONCON NN CON
12 R.Ç. 68 10.6
RP, RT, LP, LT LP, RP Cho + Cr/CİCONCONCONCON NN CON
RP, RT, RC
4 + 4 = 8
Cho/Ci CON NNNNNN CON NN
13 H.S. 74 5.28 NN RP Cho + Cr/CİCON NNNNNN CON NN
LT
3 + 3 = 6
Cho/Ci CONCONNNNN NN CON
14 İ.A. 77
31.02
3.89 RP, RT, LP LP Cho + Cr/CİCONCONNN NN NN CON
RT, RC, LT,
LC
4 + 3 = 7
Cho/Ci NNNNCONCON CON CON
15 İ.U. 81 70.14 RT NN Cho + Cr/CİNNCON CON CON CON CON
RP, RT, RC,
LP, LT, LC
3 + 3 = 6
Cho/Ci DBO NN NN NN NN CON
16 İ.Y. 65 12.02 RP, RT RP, LP Cho + Cr/CİDBO NN NN NN NN CON
RC
2 + 3 = 5
Cho/Ci NNNNCONNN NN CON
17 A.S. 71 45.73
LC, RC, LP, RT LP Cho + Cr/CİNN NNCONNN NN CON
RP, RT, RC,
LP, LT, LC
3 + 4 = 7
Cho/Ci CONCONCONCON CON CON
18 M.Ş. 62 26.40 RP, LP RP Cho + Cr/CİCON CON CON CON CON CON
RP, RT, RC
3 + 3 = 6
MRS
N Name Age tPSA
fPSA T2W DWI-ADC RATIO
RP RT RC LP LT LC
Biopsy and
Gleaso n
Cho/Ci CONNNNNCON NN NN
19 H.K. 68 6.35
RP, RT, LP, LC RP, RT Cho + Cr/CİCON NNNN CON NN NN
LP
3 + 3 = 6
Cho/Ci CONCONCONCON CON CON
20 M.Y. 68 18.42
LP, LT, LC, RP LP, LT, LC, RPCho + Cr/CİCON CON CON CON CON CON
LP, LT, LC
3 + 4 = 7
Cho/Ci DBO NN CON NN CON CON
21 M.G. 72 11.19
1.33 RP, LP RP, LP Cho + Cr/CİDBO NN CON NN CON CON
LP, LT, LC,
RP, RT, RC
4 + 4 = 8
Cho/Ci CONCONCONCON NN NN
22 M.K. 60 37.39 RP RP Cho + Cr/CİCONCONCONCON NN NN
RP, RT
3 + 3 = 6
Cho/Ci CON NNNNCON NN NN
23 H.G. 73 85.62
RP, LP, LC, RT Cho + Cr/CİCON NNNN CON NN NN
RP, RT, RC,
LP, LT, LC
3 + 4 = 7
Cho/Ci CONNNCONCON NN CON
24 Ö.K. 62 7.47 LP, RT, LC, RC LC, RC Cho + Cr/CİCON NN CONCON NN CON
RP, RT
3 + 3 = 6
Cho/Ci CONCON NNNN CON NN
25 Ö.K 78 72.29 RP, RT, LT RP, RT Cho + Cr/CİCONCON NNNN CON NN
RP, RT, RC,
LP, LT, LC
4 + 4 = 8
Cho/Ci CON NNNNNN CON NN
26 R.P. 71 18.51
6.93 LP LP, LT Cho + Cr/CİCON NNNNNN CON NN
RP, LT
3 + 3 = 6
Cho/Ci CONCONCONCON CON CON
27 Ş.A. 75 37.10
RP, LP, RT, LT LT, RC, LC Cho + Cr/CİCON CON CON CON CON CON
RP, RT, RC,
LP, LT, LC
5 + 4 = 9
MRS
N Name Age tPSA
fPSA T2W DWI-ADC RATIO
RP RT RC LP LT LC
Biopsy and
Gleaso n
Cho/Ci CONCONCONCON CON CON
28 S.H. 61 20,49
3.62 RP, RT
Cho + Cr/CİCON CON CON CON CON CON
RP, RT, RC,
LP, LT, LC
4 + 4 = 8
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL.
28
Continued
Cho/Ci CONCONNNNN NN NN
29 S.Ö. 78 10.93
1.62 RP, LP, RT RP
Cho + Cr/CİCONCONNN NN NN NN
RP, RT, RC
3 + 3 = 6
Cho/Ci CONCONNNCON CON CON
30 Ş.M.E 82 15,08
1.58 RP, RT, LP RP, RT Cho + Cr/CİCON CONNNCON CON CON
RP, RT, RC,
LP, LT, LC
3 + 5 = 8
Cho/Ci CONCONCONCON CON DBO
31 S.Ö. 69 67.4
19.9 LP, RP, LT LP, RP Cho + Cr/CİCON CON CON CON CON DBO
LT, RP, RT
RC
3 + 3 = 6
3 + 4 = 7
Cho/Ci CONCONCONCON CON CON
32 Z.K. 59 16.57 LP, LT LP Cho + Cr/CİCON CON CON CON CON CON
LP, RP, RC,
LT
4 + 3 = 7
Cho/Ci CONCONCONCON CON NN
33 A.K. 70 100
21.17 RP, RT, LP, LT LP, RP Cho + Cr/CİCON CON CON CON CON NN
LP, LT, LC,
RP, RT, RC
3 + 4 = 7
Cho/Ci CONNNNNCON CON CON
34 M.B. 61 4.81
1.05 RP, LP, RC LP, LT Cho + Cr/CİCONNNNNCON CON CON
LP, LT, LC
3 + 3 = 6
Cho/Ci
35 V.Ö 64 56.53
3.73 RP, LP, RT LT Cho + Cr/Cİ
RP, RT, RC,
LP, LT, LC
3 + 4 = 7
Cho/Ci
36 O.E. 64 1.60
0.68 LP, LT Cho + Cr/Cİ
RP, RT, RC,
LP, LT, LC
3 + 4 = 7
MRS
N Name Age tPSA
fPSA T2W DWI-ADC RATIO
RP RT RC LP LT LC
Biopsy and
Gleaso n
Cho/Ci
37 H.Ç 59 12.63 RP, LP Cho + Cr/Cİ
LP, RP, RC,
LT
3 + 4 = 7
Cho/Ci
38 N.A 62 5.90
RP, LP, RT, LT Cho + Cr/Cİ
LP, LT, LC
3 + 4 = 7
Cho/Ci NNCONNNNN NN CON
39 M.A 66 10.6
Cho + Cr/CİNNCONNN NN NN CON
RP, RC
3 + 3 = 6
Cho/Ci NNNNNNCON CON NN
40 M.A 54 32.8 LP, LT
Cho + Cr/CİNNNNNNCON CON NN
RP, RT, RC
LP, LT, LC
4 + 3 = 7
(b)
MRS
N Name Age tPSA
fPSA T2W DWI-ADC RATIO
RP RT RC LP LT LC
Biopsy and
Gleaso n
Cho/Ci NNCONNNCON CON CON
01 H.K. 59 4.58 LP, LT LP, LT, LC
Cho + Cr/CİNNCONNNCON CON CON
BENIGN
Cho/Ci NNNNCONNN NN NN
02 N.A. 63 12.35 LP NN Cho + Cr/CİNN NNCONNN NN NN
BENIGN
Cho/Ci NNCONNNCON NN NN
03 N.T. 61 5.79 RP, LP, LT RP, LP Cho + Cr/CİNN CON NN CON NN NN BENIGN
Cho/Ci NNCONNNNN NN NN
04 M.G. 75 8.03 LP, RC, LC LP, RC, LC Cho + Cr/CİNNCONNN NN NN NN
BENIGN
Cho/Ci NNNNNNNN NN NN
05 K.A. 72 4.90 Cho + Cr/CİNN NN NN NN NN NN BENIGN
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL.
AMI
29
Table 2. The results of T2W MRI and DWI-ADC MRI with
respect to biopsy results.
Biopsy
Positive Negative
Total
n 67 34 101
Positive
% 66.3% 33.7% 100.0%
n 80 71 151
T2W
Negative
% 53.0% 47.0% 100.0%
n 147 147 252
Total
% 58.3% 58.3% 100.0%
p = 0.038; Sensitivity = 0.46; Specificity = 0.68
Biopsy
Positive Negative
Total
n 34 17 51
Positive
% 66.7% 33.3% 100.0%
n 82 77 159
DWI-
ADC
Negative
% 51.6% 48.4% 100.0%
n 126 116 210
Total
% 60.0% 55.2% 100.0%
p = 0.075; Sensitivity = 0.29; Spesivity = 0.82
(a)
(b)
Graphic 1. (a) ROC curve analysis of cancer patients for
ADC values; (b) ROC curve analysis of control group for
ADC values.
Figure 1. Axial (A) and coronal (B) T2W of a patient. Focal
hypointensity in both peripheral regions, especially on the
left side.
For H-MRS: Reader 1 found out Cho/Cit and Cho +
Cre/Cit ratios of cancer patients as 5.36 ± 5.70, 7.63 ±
8.45. These ratios were 5.30 ± 5.71 and 7.59 ± 8.47 for
reader 2. In the control group; Cho/Cit and Cho + Cre/Cit
ratios were 0.69 ± 1.11, 1.06 ± 1.42 for both readers
(Table 3, Figure 3).These values were taken as the
threshold ratio through all zones of prostate (RA, RT,
RP, LA, LT, LP) for being benign. According to Cho/
Cit and Cho + Cre/Cit ratios, cancer patients had signifi-
cant statistical differences against normal control group
(p < 0.05). With regard to biopsy yields Cho/Cit and Cho
+ Cre/Cit ratios of both reader’s results had significant
statistical differences, with 49% specificity for both ratios,
regarded significant statistical differences to each other
according to mean ADC values (p < 0.05) (Table 3,
Graphic 1(a)). With correspondence to ADC values in
the cancer group; Threshold cut-off value for the ROC
curve was 0.55 s/mm2, AUC; 0.462 ± 0.052. Cut-off
values 0.55 s/mm2 had 100% sensitivity and specificity
to diagnose prostate cancer with ADC values of cancer
patients (Graphic 1b). For the control group; ROC curve
regarded cut-off value 0.06 s/mm2, AUC; 0.389 ± 0.183.
Cut-off values equal or greater than 0.06 s/mm2, pre-
sented 100% sensitivity and specificity (Graphic 1(c)).
Copyright © 2013 SciRes.
B. HEKİMOĞLU ET AL.
30
Table 3. The results of H-MRS according to each observers (O1: observer 1 and O2: observer 2), cho/ci ratio and Cho +
Cr/Ci ratio for both observers with respect to biopsy results.
Group Ratio-Observer Biopsy n Mean Std. Deviationt Sd p
Positive 6 0.69 1.11
Cho/Ci-O1
Negative 24 2.59 3.79
1.200 28 0.240
Positive 6 0.69 1.11
Cho/Ci-O2
Negative 24 2.59 3.79
1.200 28 0.240
Positive 6 1.06 1.42
Cho + Cr/Ci-O1
Negative 24 3.38 5.26
1.060 28 0.298
Positive 6 1.06 1.42
Control
Cho + Cr/Ci-O2
Negative 24 3.38 5.26
1.060 28 0.298
Positive 136 5.36 5.70
Cho/Ci-O1
Negative 80 3.92 5.52
1.810 214 0.072
Positive 136 5.30 5.71
Cho/Ci-O2
Negative 80 4.19 5.63
1.388 214 0.167
Positive 136 7.63 8.45
Cho + Cr/Ci-O1
Negative 80 6.54 10.15
0.853 214 0.394
Positive 136 7.59 8.47
Patients
Cho + Cr/Ci-O2
Negative 80 6.91 10.22
0.526 214 0.599
Biopsy
Positive Negative
Total
n 98 53 151
Positive
% 64.9% 35.1% 100.0%
n 44 51 95
MRS(Cho/Ci)
Negative
% 46.3% 53.7% 100.0%
n 142 104 246
Total
% 57.7% 42.3% 100.0%
p = 0.005; Sensitivity = 0.69; Specificity = 0.49
Biopsy
Positive Negative
Total
n 100 53 153
Positive
% 65.4% 34.6% 100.0%
n 42 51 93
MRS (Cho + Cr/Ci)
Negative
% 45.2% 54.8% 100.0%
n 142 104 246
Total
% 57.7% 42.3% 100.0%
p = 0.002; Sensitivity = 0.70; Spesivity = 0.49
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL. 31
Figure 2. Two consecutive T2W images of a patient (A,B)
show irregular hypointens area on the right peripheral zone,
DWI (C) and ADC mapping (D) depicts restricted diffusion
in the left peripheral, transitional and central zones.
Figure 3. T2W image (A) shows irregular hypoinensity on
the right side (in peripheral, transitional and central zones)
and H-MRS (B) depicts high Cho/Cit ratio in right periph-
eral zone.
69% sensitivity for Cho/Cit and 70% sensitivity for Cho +
Cre/Cit ratio (p < 0.05) (Table 3, Graphic 1(a), Figure
4). With ROC curve analysis; Both readers had 0.99
cut-off value for Cho/Cit and 0.98 for Cho + Cre /Cit
ratios, AUC of Cho/Cit: 0.613 ± 0.04 for reader 1—
0.593 ± 0.022 for reader 2, AUC of Cho + Cre/Cit: 0.606
± 0.01 for reader 1—0.587 ± 0.033 for reader 2. For both
readers; Cut-off value equal or greater than 0.99 for
Cho/Cit, 0.98 for Cho + Cre/Cit ratios; regarded 100%
sensitivity and specificity (Graphics 2(a)-(d)). For con-
trol group ROC curve analysis; Both readers had the
same evaluation: Cut-off value for Cho/Cit ratio was
equal or more than 0.990 under the AUC: 0.420 ± 0.111,
regarded 100% sensitivity and specificity. Cut-off value
for Cho + Cre/Cit ratio was equal or more than 0.940,
under the AUC; 0.465 ± 0.105, indicated100% sensitiv-
ity and specificity. (Graphics 3(a) and (b)).
When we compare each sequences statistically; T2W
Figure 4. T2W image (A), shows hypointens area both pe-
ripheral zones (especially right side). H-MRS (B) depicts
high Cho/Cit ratio in right peripheral zone. DWI (C) and
ADC map (D) reveal prominent restricted diffusion in these
zones.
sequence had significant statistical superiority to DWI-
ADC mapping with 50% sensitivity and 92% specificity
(p < 0.05) (Table 4). H-MRS for both Cho/Cit and
Cho+Cre/Cit ratios had significant statistical superiority
over DWI, had 78% sensitivity for both ratios—43%
specificity for Cho/Cit and 42% specificity for Cho +
Cre/Cit ratios (p > 0.05) (Table 4). H-MRS for Cho +
Cre/Cit ratio, regarded statistical superiority over T2W
sequence with 73% sensitivity and 42% specificity (p <
0.05) and also superior to T2W sequence in case of Cho/
Cit ratio without any statistical proof by 70% sensitivity
and 42% specificity (p > 0.05). By the combined use of
these three sequences; T2W + DWI-ADC map + H-MRS
(Cho/Cit and Cho + Cre/Cit ratios) regarded 81% sensi-
tivity and 66% specificity, with significant statistical
differences to the reference standard, histopathology (p <
0.05).
4. Discussion
Screening fundamentals of prostate cancer were based on
those patients diagnosed at imaging, tend to present a
more favorable stage compared to the diagnosed cases,
with a possible decreased rate of specific mortality due to
prostate cancer [1,2,5]. Magnetic resonance imaging was
commonly utilized for tumor staging, clearly demon-
strating prostate anatomy and representing focal or dif-
fuse lesions through the prostate [1,4-8]. MR imaging
was also widely used for an extensive evaluation of pa-
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL.
32
(a) (b)
(c) (d)
Graphic 2. (a) ROC curve analysis of MRS (Cho/Ci) ratio in cancer patients for observer 1; (b) ROC curve analysis of MRS
(Cho/Ci) ratio in cancer patients for observer 2; (c) ROC curve analysis of MRS (Cho + Cr/Ci) ratio in cancer patients for
observer 1; (d) ROC curve analysis of MRS (Cho + Cr/Ci) ratio in cancer patients for observer 2.
tients with prostate cancer, for its capacity of observation
of the primary disease and locoregional lymph nodes
involvement [1,5-9]. On T1-weighted images, prostate
appereance was homogenous with isointense signal,
zonal anatomy and intraprostatic diseases were not dem-
onstrated respectively but could be used to detect areas of
post-biopsy hemorrhages [1,4,5,15]. T2-weighted imag-
ing might regard the cancer with hypointense signal at
different prostatic zones but those T2-signal lost areas
might also be due to a number of causes; including in-
flammation, glandular fibrosis and dysplasia, hemorrhage,
calcification etc., predicting better sensitivity (78% - 89%)
with lower specificity (40% - 55%) in the detection and
localization of prostate cancer [1,4,5,7,10,12,14]. Addi-
tional procedures, such as DWI-ADC mapping and MR-
Spectroscopy should be applied to achieve a more spe-
cific diagnosis and more accurate localization of cancer
[1,2,4,7,12,16-21]. Combined T1 and T2-W MR imaging
plus H-MRS or H-MRS plus DWI or routine MR imag-
ing plus DWI indicated higher sensitivity (81% - 95%)
and specificity (76% - 91%) as seen in the reported arti-
cles [2,7,10,12,14,16,17,20].
H-MRS provides information about the metabolite
concentrations within a voxel to show the aggressiveness
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL. 33
(a)
(b)
Graphic 3. (a) ROC curve analysis of MRS (Cho/Ci) ratio in
control group; (b) ROC curve analysis of MRS (Cho +
Cr/Ci) ratio in control group.
of the cancer, to improve the tumor localization and
volume estimation with MRI [1,4,9,15,21,23,24]. DWI-
ADC mapping assesses the Brownian motion of free
water in tissues, normal prostate tissue is rich in glandu-
lar tissue which has higher water diffusion rates, mostly
depicted on ADC mapping, prostate cancer show re-
stricted diffusion with high signal on DWI and low signal
on ADC maps [1,2,4,7,12,16,17]. DWI is an intrinsically
low signal to noise ratio sequence, with noisy images and
susceptibility artefacts therefore technique benefits from
higher field strengths and surface coils, higher b-values
can improve lesion detection [1,7,14,18,31-33].
Concerned with T2W-MR imaging, DWI plus ADC
Table 4. The comparison of MRS (Cho/Ci and Cho + Cr/Ci)
results with T2W MRI results and comparison between
combination of three sequences to the biopsy results.
T2W
Positive Negative Total
n 64 80 144
Positive
%44.4% 55.6% 100.0%
n 27 57 84
MRS
(Cho/Ci)
Negative
%32.1% 67.9% 100.0%
n 91 137 228
Total
%39.9% 60.1% 100.0%
p = 0.070; Sensitivity = 0.70; Specificity = 0.42
T2W
Positive Negative
Total
n66 80 146
Positive
%45.2% 54.8% 100.0%
n25 57 82
MRS
(Cho + Cr/Ci)
Negative
%30.5% 69.5% 100.0%
n91 137 228
Total
%39.9% 60.1% 100.0%
p = 0.035; Sensitivity = 0.73; Specificity = 0.42
Biopsy
Positive Negative
Total
n89 58 147
Positive
%60.5% 39.5% 100.0%
n21 30 51
T2 +
DWI-ADC
+ MRS Negative
%41.2% 58.8% 100.0%
n110 88 198
Total
%55.6% 44.4% 100.0%
p = 0.022; Sensitivity = 0.81; Specificity = 0.34
mapping and H-MRS, there were few reports in the lit-
erature. Shimofusa et al. [16] demonstrated a study of 37
patients with prostate cancer, 3 readers evaluated the
results of T2W imaging alone and combined T2W and
DWI. Sensitivity ranged between 73% - 86% for T2W
alone and 84% - 86% for combined use of T2W and
DWI images, specificity ranged between 74% - 83% for
T2W alone and 78% - 91% for combined T2W and DWI
use which were significantly higher than our results.
Haider et al. [12] also compared T2-weighted imaging
alone and combined use of T2W and DWI for the local-
ization of prostate cancer in 49 patients, presented 54%
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL.
34
sensitivity and 91% specificity for T2W images alone
and 81% sensitivity and 84% specificity for combined
T2W and DWI sequences use, their sensitivities for T2W
alone T2W + DWI use and specificity for T2W images
were higher than our results, specificity for combined use
of T2W and DWI images, was almost the same with us.
Reinsberg et al. [2] reported increased specificity without
a reduction in sensitivity, for combined DWI and 2D-
HMRS use with comparison to the use of MR-spectros-
copy or DWI alone in the voxels containing 70% or more
tumour tissues, with 80% - 90% sensitivity and specific-
ity. Our results for Cho/Cit ratio and ADC values were
almost the same with lower accuracy.
Mazaheri et al. [7] carried out a research with com-
bined DWI and H-MRS use for detecting prostate can-
cers, regarded significantly higher Cho/Cit ratios and
lower ADC values in tumor containing voxels with 85% -
81% sensitivity and specificity, better than use of DWI or
H-MRS alone. Our results for Cho/Cit ratio and ADC
values were almost the same with lower accuracy. Kumar
et al. [31] reported a positive correlation between ADC
values and Cho/Cit Cho + Cre/Cit ratios in men with
elevated PSA levels, reflecting a direct relationship be-
tween the reduction of citrate levels and structural changes
of prostate tissue associated with malignancy.
Yagcı et al. [17] declared that DWI+T2W didn’t pro-
vide significant statistical increase in the diagnostic per-
formance of MRI, with comparison to DWI alone for
peripheral zone cancer detection and localization with
1.5 T scanner.
To our belief, this was the first research in the literature
analyzing the combined use of T2-weighted imaging,
H-MRS and DWI-ADC mapping to detect prostate cancer
accurately. We hypothesize that combined information of
non-invasive morphologic and functional MR techniques,
Multiparametric MR imaging approach rather than use of
either sequences alone, could easily improve the detection,
localization and staging of prostate cancers. In this re-
search; None of the included sequences alone had ade-
quate sensitivity and specificity for the identification of
cancer as T2W imaging had 46% sensitivity and 68%
specificity, DWI and ADC mapping had 29% sensitivity
and 82% specificity, H-MRS acquisition with Cho/Cit
and Cho + Cre/Cit ratios had 49% specificity for both
ratios, 69% sensitivity for Cho/Cit and 70% sensitivity
for Cho + Cre/Cit ratio. Even for the use of H-MRS (Most
sensitive sequence) and DWI (Most specific one); Was
not high enough to diagnose the cancer accurately as three
of 10 prostate cancers were missing. In order to improve
and validate these results for each sequences; Combina-
tion of these MR sequences via multiprametric approach
should aid for the depiction and exact localization of
prostate cancer. When we add DWI to T2-weighted im-
aging, the sensitivity raised to 52% with statistical corre-
lation to biopsy without significant improvement in the
specificity (%65, p < 0.05), combination of T2W imaging
with H-MRS; A reliable increase for sensitivity was in-
dicated with lower specificity (80% sensitivity and 32%
specificity) without any statistical proof over histopa-
thology (p > 0.05). By combined use of H-MRS and DWI,
an increase in sensitivity with lower specificity under
statistical approvement to reference standard, was pre-
dicted (77%/43%, sensitivity/specificity) (p < 0.05). By
Multiparametric MR imaging approach via combined use
of all three sequences ; Sensitivity was improved to 81%,
a reliable increase for specificity, especially higher than
H-MRS use alone were also observed (66%), multipa-
rametric approach did not acquire more specific results
rather than the acquisition of other two sequences alone,
with significant statistical correlation to the gold standard
(p < 0.05).
We thought that Multiparametric MR imaging ap-
proach of these sequences might supply beneficial datas
and increase the specificity more than the H-MRS usage
alone. By adding T2W and DWI sequences with the ap-
plication of pelvic-phase array coil; Disadvantages due to
lack of endorectal coil and lower spatial resolution should
be overcome. An additional MR imaging technique like
dynamic contrast enhanced scan might be added to routine
prostate MR imaging protocol in order to get higher sen-
sitivity and increase the specificity.
There were several limitations of this research; First,
as we didn’t have a proper endorectal coil for routine
practice, all MRI procedures were acquired by pel-
vic-phase array coil, this might further cause lower sensi-
tivity and specificity, especially for the DWI-ADC map-
ping and H-MRS acquisitions. This was the major limita-
tion of this research. Second, relatively a small sampled
size and retrospective study design could influence sta-
tistical analysis, needed to be confirmed prospectively
with large number of cases. Third, small sized tumours
within central gland and transitional zone especially <5
mm, were easily misdiagnosed by routine T2W se-
quences and ADC values, Cho + Cre/Cit-Cho/Cit ratios
might not accurately reflect the real tumour situation
either and an elevated false-positive rate for benign con-
ditions, such as prostatitis-hemorrhage-glandular hyper-
plasia-fibrosis etc. might further influence lower speci-
ficity of this research especially on T2W sequence [4,
14,32,33]. Forth; MRI was performed approximately 4
weeks after prostate biopsy, this factor might cause spec-
tral degradation for H-MRS [15,23] and degrade metabo-
lite signal to noise ratio for MR Spectroscopy, could vary
between voxels of the same patient or between them
(distance of voxels from coil, magnetic field homogeneity
and relaxation times) that might have introduced vari-
ability for the outcome. Fifth, DWI had some disadvan-
tages like lower signal to noise ratio, distorted spatial
Copyright © 2013 SciRes. AMI
B. HEKİMOĞLU ET AL. 35
resolution, magnetic susceptibility and signal loss which
might affect the image quality and the outcome for de-
tection of exact cancer localization [4,14,19,31,33].
5. Conclusion
Our study indicated that Multiparametric MR imaging
approach by combined use of T2-weighted imaging, dif-
fusion-weighted MR imaging and proton MR-spectros-
copy, were more sensitive and more accurate than use of
either sequences alone. For exact localization and detec-
tion of prostate cancer; if these advanced and newer MR
sequences were included in the routine prostate MR pro-
tocole; Characterization of prostatic malignancy, dis-
crimination of benign and malignant prostatic tissues,
would be significantly improved.
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