The purpose of this study is to assess the efficacy of second-look Trans- rectal Ultrasound guided biopsy by comparing the histopathological results obtained by Trans Rectal Ultra Sound guided extended sextant core biopsy of the prostate done before and after localization of lesions using MRI & MRS done prior to the procedure.

1. MRI Guided Trans Rectal Ultrasound Biopsy: A Molecular
Approach to Diagnosing Prostatic Cancer

2. Page 1 of 18
MRI guided trans rectal ultrasound biopsy: a molecular
approach to diagnosing prostatic cancer
Poster No.: C-1785
Congress: ECR 2013
Type: Scientific Exhibit
Authors: B. Raghavan, A. Wasim, P. Gopalakrishnan, R. BALAJI, J.
Govindaraj, M. Logudas; Chennai/IN
Keywords: Genital / Reproductive system male, Oncology, MR-Spectroscopy,
Ultrasound, Biopsy, Tissue characterisation
DOI: 10.1594/ecr2013/C-1785
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Purpose
Trans Rectal Ultra Sound gives an idea of the morphology of the prostate gland but it
is not a good predictor for malignancy. Though Trans Rectal Ultra Sound is used for
obtaining samples for histopathology, the sampling of the prostate gland is a systematic
one involving not just the ultrasound detected abnormalities but all areas of the gland
even if they appear normal by ultrasound.
MRI and MR Spectroscopy is morphological and functional imaging and is a better
indicator of malignancy (1). Second-look ultrasound (2) after MRI in breast is done
routinely to locate the lesion and biopsy under ultrasound guidance as MRI guided
biopsies in the MRI suite are expensive & time consuming as opposed to the more
efficient ultrasound guided biopsy.
The purpose of this study is to assess the efficacy of second-look Trans- rectal Ultrasound
guided biopsy by comparing the histopathological results obtained by Trans Rectal
Ultra Sound guided extended sextant core biopsy of the prostate done before and after
localization of lesions using MRI & MRS done prior to the procedure.
Methods and Materials
The study was conducted as a prospective controlled analytical study at Apollo Speciality
Hospital, 320 Padma Complex, Anna Salai, Chennai- 600035.
Out of a total of 60 patients who were referred by the urologist between September 2011
and February 2012 for prostate biopsy either due to elevated sPSA , abnormal DRE or
symptoms suggesting prostate cancer, only 52 patients fulfilled the inclusion criteria and
were included.
Inclusion criteria:
• Patientswith elevated sPSA levels (>4.0 ng/dl) or with sudden increase of
sPSA values in two health examinations.
• Abnormal digital rectal examination (DRE),
• Associated urinary symptoms include dysuria, increased frequency of
urination or difficulty initiating urine
• Patients with history of prostatic enlargement.
Exclusion criteria:

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• Patients who were previously diagnosed and treated for prostate cancer,
• Patients with known local or distant metastasis on presentation
• Patients who have recently undergone TRUS biopsy of the prostate.
The final study population consisted of 45 patients. Informed consent was obtained from
all the patients prior to the procedure. The patients underwent MRI with MR Spectroscopy
followed by extended sextant targeted core tissue prostate biopsies, performed under
TRUS guidance with reference to suspicious areas on MRI and MR Spectroscopy in
addition to the regular core tissue biopsies.
After adequate bowel preparation and informed consent, the patients underwent T2 high
resolution MR imaging of the prostate in axial, sagittal and coronal planes. Spectroscopy
was planned with reference to the MR images in all three planes and effort was taken to
include the entire prostate avoiding the bladder and adjacent structures to reduce signal
to noise ratio (SNR) and to confine the voxels within the prostate margins. All images were
analyzed for changes in signal intensity in the prostate, and spectroscopy was acquired
from the entire prostate including the suspicious areas.
Fourier transformation, phase adjustment, frequency adjustment, baseline correction and
calculation of the Cho+Cr/Cit (CCr) ratios were automatically performed. The total exam
took approximately 20 to 30 minutes.
MR image Analysis
The T2 weighted images were analyzed for low signal intensity in contrast to the normal
high signal intensity especially in the peripheral zone as majority (70%) of the tumors
arise from there. The other suspicious nodules with ill defined margins which showed
low signal intensity were also taken into account. Capsular breach and seminal vesicle
involvement were made note of.
3D MR spectroscopy imaging evaluation
T2-weighted images were taken as the reference images, and voxels with suspected
tumorous lesions were identified. The CCr ratios from the tumorous lesions and from the
rest of the prostate were tabulated . In case of contamination resulting in non-diagnostic
spectroscopy spectrum, manual adjustment of the baseline was attempted. Voxels were
considered to be sufficient for analysis if there was adequate visual match between the
baseline and the obtained spectrum.
The classification system described by Kurhanewicz et al was used (3) . In that system
voxels are considered suspicious for cancer if the ratio of choline and creatine to citrate
is at least 2 standard deviations (SDs) higher than the average ratio for the normal voxels
which are calculated from the control population. Voxels are considered very suspicious

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for cancer if the ratio of choline and creatine to citrate is higher than 3 SDs above the
average ratio.
TRUS biopsy
The imaging protocol for TRUS included detailed assessment of the prostate and seminal
vesicles in both the sagittal and axial planes and estimation of gland volume in grey scale
and color (FIG 1). The prostate was analyzed for morphology the presence of any hypo,
iso or hyperechoic lesions. Extended sextant core tissue biopsies were performed under
TRUS (FIG 2) guidance by two senior consultant radiologists with more than 20 years
experience.
Extended sextant biopsy is being followed in our institution where two samples from
the upper, three from the mid and two from lower gland are taken from either sides,
amounting to a total of 14 tissue samples for each case. Any visible nodule was biopsied
and separately sent for HPE.
Subsequently the T2W MR images were used as reference during TRUS biopsy and
suspicious areas which showed low signal on T2WI and/or had an elevated CCr ratio on
spectroscopy were also sampled in addition to the regular extended sextant biopsies by
visual approximation in reference to the anatomic division of the prostate into sextants ,
i.e. right and left base, mid-gland, and apex. (FIG 3)
The samples obtained were sent for histopathology examination in separately labelled
bottles. The histopathology results were taken as gold standard for analysis.
Images for this section:

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Fig. 1: TRUS of normal prostate

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Fig. 2: Endorectal probe fitted with an adapter that accepts the needle of a spring-loaded
biopsy gun

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Fig. 3: T2W axial and coronal sections of the normal prostate and a normal CCr ratio on
MR spectroscopy. Normal TRUS image of the prostate at the mid-gland level with biopsy
needle in the right and left lobe

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Results
Out of the 45 patients who underwent biopsy, 21 patients were diagnosed with prostate
cancer from one or more locations and 24 patients were tumor free.
The study comprises a total of 242 loci from the base, mid gland and apex of prostate of
the 45 patients. All these patients underwent MRI and proton MR spectroscopy followed
by TRUS examination and TRUS guided extended sextant biopsy of the prostate.
Results of TRUS
HPE
TUMOR NO TUMOR
TOTAL
POSITIVE 58 36 94
NEGATIVE 30 118 148
TRUS
TOTAL 88 154 242
Estimate 95% CI
Sensitivity 0.641 0.555 to 0.74
Specificity 0.742 0.693 to 0.801
PPV 0.617 0.516 to 0.709
NPV 0.781 0.725 to 0.844
P value <0.001
Results of MRI
Areas which showed low signal intensity on high resolution T2W images were identified.
Based on these, spectroscopy was planned and CCr ratios were obtained from the entire
prostate and from the areas which were suspicious for tumor.
Out of 242 loci which were studied, hypointense signal suggesting tumor was seen in
115 loci on T2W images. 88 of these loci contained tumor on HPE.
Results of Spectroscopy
Of the 242 voxels, 49 voxels which were proven on HPE as normal showed CCr ratios in
the range of 0.16 and 1.16. The mean CCr ratio from the normal prostate was 0.49 ±0.21
compared to CCr ratio of 0.75±0.16 obtained in the study by Keisuke Saito et al.(4)

10. Page 9 of 18
On the basis of this data the threshold value for the diagnosis of prostate cancer by H-
MRS was determined to be #0.91, which is equivalent to the mean +2 SD of the CCr ratio
for a normal prostate in our study. The corresponding threshold value for cancer in the
study by Keisuke Saito et al was # 1.07 (4).
In 21 patients with prostate cancer, tumor was found in 96 loci on HPE. Of these, 8 loci
could not be evaluated due to non-diagnostic spectrum on MR spectroscopy. The mean
CCr ratio (+3SD) for a very high suspicion for prostate cancer was calculated to be 1.41
±0.75 compared to 1.40±0.20 seen in the study by Keisuke Saito et al (4).
Sensitivity, specificity, positive predictive value, negative predictive value and ROC
curves were calculated from 242 voxels of 45 patients based on the threshold value of
#0.91.
MRI and MRS combined
HPE
TUMOR NO TUMOR
TOTAL
POSITIVE 86 27 113
NEGATIVE 2 127 129
Combined MRI
and MRS
TOTAL 88 154 242
Estimate 95% CI
Sensitivity 0.977 [0.921 to 0.994]
Specificity 0.825 [0.757 to 0.877]
PPV 0.761 [0.675 to 0.83]
NPV 0.984 [0.945 to 0.996]
P value <0.001
Combining MRI and MRS, the sensitivity, specificity, positive predictive and negative
predictive values in our study were 97.7%, 82.5%, 76.1% and 98.4% which is comparable
to Axel Wetter et al, who obtained a combined MRI and MRS statistical data of
75%,93%,75% and 93% respectively.(5)
Similarly, the study by E. Squillaci et al combining MRI and MRS too showed a greater
specificity of 90 %. The sensitivity, positive and negative predictive values were 71, 89
and 74 % respectively (6).
MRI & MRS COMBINED

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Sensitivity Specificity Positive
predictive
value
Negative
predictive
value
Our study 97% 83% 76% 98%
Axel wetter et
al
75% 93% 75% 93%
E. Squillaci et
al
71% 90% 89% 74%
Senstivity & Specificity of TRUS ,MRI, MRS
Furthermore, overall TRUS features of the prostate were evaluated and compared with
the HPE results obtained after biopsy and statistical analysis was done (Fig 4). We
obtained a statistically significant sensitivity of 64%, specificity of 74%, positive predictive
value of 61 % and negative predictive value of 78% which is higher compared to other
studies which have shown sensitivity and specificity of TRUS guided biopsy to be around
40 - 50 % (7). This increase in sensitivity and specificity compared to earlier studies is
mainly due to the role of MRI and MRS in localizing the areas suspicious for malignancy
on TRUS. Since MRI and MRS combined had a higher statistical significance, this
reflected in better sample yield on TRUS guided prostate biopsy thereby improving the
overall detection of prostate cancer.
Evaluation of TRUS detected nodules :
19 hypo and hyperechoic suspicious nodules were identified on TRUS during the
extended sextant biopsy procedure. These nodules were evaluated for echogenicity and
vascularity. They were subsequently biopsied separately and sent for HPE (Fig 5).
On HPE, 6 nodules showed the presence of tumor (FIG 6), 9 nodules showed hyperplasia
(FIG 7), 2 were normal prostatic tissue , 1 was indeterminate and 1 showed acute
inflammation.
Retrospectively, on spectroscopy analysis of the nodules which were identified on TRUS,
5 out of the 6 nodules which showed the presence of tumor had a CCr > 0.91 (i.e +3 SDs
from normal) . 11 nodules showed a CCr within +1 standard deviation from the normal
threshold value of 0.49 and 3 nodules had a CCr +2 standard deviations from 0.49 (Fig 8).
Images for this section:

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Fig. 4
Fig. 5: HPE of 19 nodules identified in TRUS.

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Fig. 6: TRUE POSITIVE MRI shows hypointense peripheral zones with capsular breach
on the left. MRS shows elevated CCr ratios from in all voxels including nodules in the
peripheral zones, suspicious for carcinoma. TRUS shows ill defined hypoechoic nodules
in both lobes. Adenocarcinoma was seen on HPE in all samples.

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Fig. 7: Benign prostatic hypertrophy on MRI and TRUS with normal CCr ratios on MRS.
HPE confirmed BPH

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Fig. 8

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Conclusion
MRI and MR Spectroscopy is a non-invasive procedure which does not require special
hardware and there is no radiation involved. The total time taken for MR imaging of the
prostate including MR spectroscopy analysis is around 25 minutes. The addition of MR
spectroscopy to the protocol contributes to only 6 minutes of the total scanning time. MR
Spectroscopy as a technique has to be standardized for each individual MR unit and the
patient population.
This study is one of the early studies where an attempt has been made to establish the
normal CCr ratios in our population. A CCr ratio threshold value of 0.91 can objectively
differentiate between benign and malignant lesions as inferred from this study.We have
found the results of MR spectroscopy to correlate well with histopathology with a high
degree of specificity (83%) and few false positives (3%) (FIG 6) and false negatives (5%)
(FIG 7) which are comparable to other studies byAxel Wetter et al andE. Squillaci et al.
However MR Spectroscopy cannot be done in isolation as a stand-alone procedure as
anatomical and morphological analysis in identifying the abnormal areas is required.
The zonal anatomy, capsular breach, invasion of the seminal vesicles and bladder base
form an important part in local staging. These are analyzed by T2W high resolution MR
imaging.
TRUS guidance for prostate biopsy is primarily used as a convenient real time method to
perform a meticulous and methodical biopsy avoiding the urethra, seminal vesicles and
bladder base. There has been a progressive trend to increase the number of cores taken
from the prostate in an attempt to increase the sensitivity of cancer detection.
Therefore MR imaging of the prostate combined with MR spectroscopy can be effectively
used as a modality for detection of prostate cancer and create a more accurate localizing
method for targeted TRUS guided biopsies. Multi-modality fusion techniques using MRI
and MR spectroscopy can increase the accuracy and efficiency of targeted TRUS guided
biopsies in diagnoses of prostate cancer.
Images for this section:

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Fig. 9: MRI showes diffuse hypointensity in both peripheral zones. Cystic areas
appearing hyperintense on T2W sequences are seen in the right lobe. MRS shows
elevated CCr ratios from both peripheral zones, suspicious of carcinoma. TRUS shows
heteroechoic areas in both lobes of prostate with no definite cystic areas. HPE showed
inflammation with abscess.

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Fig. 10: Normal MRS from entire gland including hypointense foci in left peripheral zone
and right central zone of mid-gland seen on MRI. TRUS showing ill defined nodular
hypoechoic areas in both lobes with subsequent biopsy from the nodule in the right lobe.
HPE showed adenocarcinoma.

19. Page 18 of 18
References
1. Filip G. Claus, Hedvig Hricak, Robert R. Hattery :Pretreatment Evaluation
of Prostate Cancer: Role of MR Imaging and 1H MR Spectroscopy ;
RadioGraphics 2004;24:S170
2. MR-Directed ("Second-Look") Ultrasound Examination for Breast Lesions
Detected Initially on MRI: MR and Sonographic Findings Hiroyuki Abe, Robert
A. Schmidt, Rajshri N. Shah, et al; AJR February 2010 vol. 194 no. 2 370-377
3. Kurhanewicz J, Vigneron DB, Hricak H, Narayan P, Carroll P, Nelson SJ.
Three-dimensional 1H spectroscopic imaging of the in situ human prostate
with high spatial (0.24 to 0.7 cm3) spatial resolution. Radiology 1996; 198:795-
805.
4. Keisuke saito et al :Clinical efficacy of proton magnetic resonance
spectroscopy (1H-MRS) in the diagnosis of localized prostate cancer ;
ANTICANCER RESEARCH 28: 1900 (2008)
5. Axel Wetter, Tobias A. Eng Darius, Nadjmabadi Klaus Fliessbach, Thomas
Lehnert, Jessen Gurung, Wolf-Dietrich Beecken, Thomas J. Vog:Combined
MRI and MR Spectroscopy of the Prostate Before Radical ProstatectomyAJR
2006; 187:726
6. E. Squillaci, G. Manenti, S. Mancino, M. Carlani, M. Di Roma, V. Colangelo, G.
Simonetti.MR Spectroscopy of Prostate Cancer. Initial Clinical Experience.J.
Exp. Clin. Cancer Res., 2005; 527
7. Beerlage HP, Aarnink RG, Ruijter ET, et al. Correlation of transrectal
ultrasound, computer analysis of transrectal ultrasound and histopathology of
radical prostatectomy specimen. Prostate Cancer Prostatic Dis 2001; 4:56-62
Personal Information
Dr.Bagyam Raghavan
Consultant Radiologist
Apollo Speciality Hospitals
Chennai.INDIA
e-mail: drbagyam@gmail.com.

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