SYNOPSIS OF DISSERTATION

I, Dr. INGOLE SARANG MANOHARRAO have registered for

Primary DNB in Radio-diagnosis at SAIFEE HOSPITAL, Mumbai
from March 2014 to March 2017.
My

topic

MAGNETIC

for

thesis

is

RESONANCE

ROLE

OF

MULTIPARAMETRIC

IMAGING(MRI)

IN

PROSTATE

CANCER under the guidance of Dr. RAJEEV MEHTA; M.D,

D.M.R.E, PROF. & H.O.D. IMAGING, SAIFEE HOSPITAL, MUMBAI.

Herewith attaching the thesis protocol for approval.

TITLE

: ROLE OF MULTIPARAMETRIC MAGNETIC

RESONANCE IMAGING (MRI) IN PROSTATE
CANCER

NAME

: DR. INGOLE SARANG MANOHARRAO

SUBJECT

: DNB RADIODIAGNOSIS, PRIMARY

JOINING

: 31st MARCH 2014

INSTITUTE

: SAIFEE HOSPITAL, MUMBAI.

TRAINING
DURATION
DNB GUIDE

: MARCH 2014 TO MARCH 2017.

: DR.RAJEEV MEHTA M.D, D.M.R.E
PROF. & HEAD OF IMAGING,
SAIFEE HOSPITAL
MUMBAI

1.1 INTRODUCTION
2

Prostate cancer is the most commonly diagnosed malignancy in

men, with almost one-fourth of males diagnosed with
malignancy having cancer of the prostate. In India prostate
cancer has an incidence rate of 3.9 per 100,000 men and is
responsible for 9% of all cancer-related mortality. 1
Prostate cancer is evaluated by a combination of clinical and
biopsy data, including the clinical stage [based on the digital
rectal examination (DRE)], serum prostate-specific antigen
(PSA) level and the Gleason score at biopsy.
Today the detection of prostate cancer typically begins with
prostate-specific-antigen (PSA) levels and/or digital rectal
examination (DRE). If either of these are abnormal, a
transrectal ultrasound (TRUS) followed by guided biopsy is
often the next step.
However, there are some shortcomings with this modality, such
as:
1.

Dependence on the skill and experience of the operator.

2.

Limited field of view.

3.

Less accurate assessment of spread and hence staging.

The false negative rate of TRUS-guided biopsies is estimated to

be between 15% and 34%2. Also problems arise when, despite
a high degree of suspicion for cancer (based upon PSA/DRE), a
pathological diagnosis cannot be confirmed.
The superior soft tissue resolution, multiplanar imaging
capability, and technical refinements have established MRI as
3

the most accurate modality for the detection and staging of

prostate cancer. MRI is now been widely used as a staging tool
after a diagnosis is made through a transrectal biopsy. 3
Traditional prostate MR imaging has been based on
morphologic imaging with standard T1-weighted and T2weighted sequences, which has limited accuracy. Recent
advances include additional functional and physiologic MR
imaging techniques (diffusion weighted imaging, MR
spectroscopy, and dynamic contrast enhanced imaging), which
allow extension of the obtainable information beyond anatomic
assessment. In multi-parametric imaging, the anatomical and
functional information is integrated. Thus multi-parametric MR
imaging provides the highest accuracy in diagnosis and staging
of prostate cancer4.

1.2 REVIEW OF LITERATURE

Historically, prostate cancer screening is based on assessment
of the level of PSA elevation and results of digital rectal
examination (DRE). Both markers have suboptimal accuracy for
the diagnosis of prostate cancer.
DRE is affected by interexaminer variability, irrespective of
experience, and is limited to assessment of peripheral zone
tumors. However DRE still remains a fundamental part of
screening owing to its being part of the clinical examination
without additional cost, its ubiquitous availability, and its ability
to allow identification of the tumor in 14% of men with prostate
cancer according to Okotie OT et al(2007)5.
PSA screening was recognized as a screening tool in 1991. Its
introduction has led to a significant decrease in stage at
diagnosis and to detection of tumors of very small volume
(often <0.5 cm3) and of low Gleason score (6).
However for PSA levels under 10 ng/mL, elevation above the
threshold of 4 ng/mL (values above this threshold are
commonly regarded as abnormal) has low specificity for
prostate cancer. In 70%80% of patients with mild elevation of
PSA level, the increased PSA level is in fact caused by benign
conditions such as benign prostatic hyperplasia (BPH) or
5

prostatitis, resulting in a false-positive PSA test result.

Thompson et al(2004) concluded that at least 15% and up to
44% of biopsy-proved prostate cancers occur in patients with
PSA levels in the accepted normal range below 4 ng/mL 6.
Transrectal US alone is not recommended for initial screening
(eg, according to the current screening guidelines of the
American Cancer Society and the Centers for Disease Control
and Prevention) owing to
Lack of supportive data on sufficient specificity or ability
to significantly increase the detection rate of prostate
cancer and
Its significant cost when used as a screening tool.

Transrectal US is mainly used to provide visual guidance for

biopsy. According to Spajic B et al(2007), at transrectal US,
most prostate cancers (60%70%) are hypoechoic to the
normal peripheral zone, whereas up to 40% of lesions are not
distinguished from the background normal parenchyma owing
to its isoechogenicity7. Evaluation of the transition zone with
transrectal US is very limited. In a large study conducted by
Svetec D et al(1998), transrectal US was found to have only a
15.2% positive predictive value in detection of cancers versus
28% for DRE. Thus both techniques are unable to allow
differentiation of an abundance of benign processes mimicking
prostate cancer from true-positive cases 8. With prostate biopsy,
cancer can be missed in up to 10%38% of men eventually
found to have prostate cancer.
6

Of all non-invasive anatomic imaging modalities, MR imaging is

most suited for evaluation of the prostate, as it has unmatched
ability to depict detail of the prostate owing to its excellent softtissue contrast. Computed tomography (CT) does not provide
sufficient soft-tissue contrast beyond size assessment of the
prostate. Although CT is valuable in the evaluation of pelvic
lymphadenopathy and bone metastases, MR imaging and bone
scanning have been found superior in their assessment by
Dotan et al(2008)9.
MR imaging of the prostate most commonly employs T2 and T1
weighted imaging with most systems operating at 1.5 Tesla.
This has produced variable results for staging accuracy, in
particular for detecting ECE and SVI.
Rouvire et al(2006) , in a meta-analysis of 10 studies all
performed at 1.5 Tesla, reported staging accuracy rates ranging
from 60-80%, with a mean sensitivity and specificity of 53%
and 83% respectively10.
Diffusion-weighted imaging can add valuable information about
tissue at the cellular level to the information from conventional
T1-weighted and T2-weighted imaging. Because diffusion
weighted imaging measures the Brownian motion of water
molecules, it provides important information about the
functional environment of water in tissue and reflects the
cellular status of normal and pathologic tissue. According to
Hosseinzadeh et al(2004) reduced diffusion of water in
prostate cancer has been attributed to the increased cellularity
of malignant lesions, with reduction of the extracellular space
7

and restriction of the motion of a larger portion of water

molecules to the intracellular space. Therefore, diffusionweighted imaging provides an important quantitative
biophysical parameter that can be used to differentiate benign
from malignant prostate tissue11.
MR Spectroscopy provides spatial information about the relative
concentration of different intracellular metabolites in
contiguous small voxels of prostatic tissue. The healthy
prostate gland produces an ample amount of a citratecontaining secretion, resulting in a high citrate content and a
low choline level. In the case of prostate cancer, the choline
level is significantly elevated and the citrate content is reduced
due to the metaplastic processes of the cell membranes. An
increase in the choline-to-citrate ratio or the (choline +
creatine)/citrate ratio is often used as a marker of malignancy
in prostate cancer and increases the specificity of diagnosis;
however, it is most reliable in the peripheral zone. When
combined with anatomic imaging, Coakley et al(2002) have
found MR spectroscopy to increase the accuracy of tumor
volume estimation in prostate cancer12. More recent data by
Crehange et al(2010), have shown significantly increased
choline to-citrate ratios and larger tumor volumes in stage T2b
or higher tumors than in stage T2a or lower tumors, further
suggesting a potential of MR spectroscopy for tumor volume
estimation and staging.
DCE(Dynamic Contrast Enhanced) MR imaging is an advanced
prostate imaging modality that allows derivation of parameters
that are closely related to microvascular properties and
8

angiogenesis in tissues. In prostate cancer, increased tumor

vascularity leads to early hyperenhancement (higher and
earlier peak enhancement than in normal tissue) and rapid
washout of contrast material from the tumor, in comparison
with normal prostate tissue. Microvascular alterations and
neovascularity are in general most severe in prostate cancer, in
comparison with other processes in the prostate such as BPH or
prostatic intraepithelial neoplasia.
Sciarra A et al(2008) suggested that DCE MR imaging in
combination with MR spectroscopy allows detection of prostate
cancer in 46% of patients with prior negative transrectal US
guided biopsy results and a persistently elevated PSA level (4
10 ng/mL), versus a prostate cancer detection rate of 24% with
repeat transrectal USguided biopsy in these patients 13.
In the latest meta-analysis to determine accuracy of
multiparametric MRI for prostate cancer detection conducted
by Maarten de Rooij et al(2014) have shown specificity of
0.88 (95% CI, 0.820.92) and sensitivity of 0.74 (95% CI, 0.66
0.81) for prostate cancer detection, with negative predictive
values (NPVs) ranging from 0.65 to 0.94. Thus high specificity
with variable but high NPVs and sensitivities implies a potential
role for multiparametric MRI in detecting prostate cancer 14.
1.3 AIMS AND OBJECTIVES
1 To determine the diagnostic accuracy of MRI for evaluation
and detection of prostate cancer.
2 To determine diagnostic accuracy of conventional MR
imaging (T1,T2) and newer functional techniques:
9

diffusion-weighted imaging (DWI) and dynamic contrastenhanced MRI (DCE-MRI) and MR Spectroscopy.
3 To determine role of MRI in staging of prostate cancer.
4 To evaluate residual or recurrence of cancer in selected
post treatment follow up cases.

1.4 MATERIALS AND METHODS

Study design: Cross sectional study

Study area: This study will be conducted at Saifee Hospital,
Mumbai
10

Study Duration: 24 months (April 2014 to April 2016)

Study population:
Patients referred to the radiology department MRI division for
suspected cases of prostate cancer will be studied.
Inclusion Criteria:
All male patients from Saifee Hospital, Mumbai referred for MRI
evaluation of prostate with clinical suspicion of prostate cancer
(PSA level >4 ngm/ml, hard prostate in digital rectal
examination, and suspicious area at transrectal US) or TRUS
biopsy proven cases of prostate cancer.
Exclusion Criteria:
All patients having cardiac pacemakers, prosthetic heart
valves, cochlear implants or any metallic implants.
Claustrophobic patients
Patients who are not willing for the study.
In

addition,

patients

having

high

S.Creatinine

levels

(>1.5mg/dl) and low eGFR (<30ml/min), and /or with contrast

allergy, contrast study is avoided.

Sample size:
As per the previous years record of hospital, on an average
number of MRI done on monthly basis for evaluation of prostate
cancer were found x1=1 to x2 =2 cases.
11

As data collection duration is 24 months, the expected sample

size will be
24(x1) + 24 (x2) = 24x1+24x2 =36 (approximately)
2

The final analysis will be done on the total number of study

individuals who were diagnosed with the help of MRI.

Technique and Tools: The MRI study will be performed on all

the male patients coming for MRI Prostate study. The target
region for scanning is the pelvis.
Informed consent to participate in the study will be obtained
from each volunteer.
Patient Preparation: The males should ideally fast for a
period of 4 hrs before the examination to prevent contrast
related complication and to reduce bowel peristalsis artifacts. S.
Creatinine level of all the patients are obtained and eGFR
calculated using Cockcroft-Gault Formula.

Machine:
MAGNETOM Avanto, Version syngoMR2004V, 1.5 T MR
12

Scanner from Siemens (Erlangen, Germany) with gradient field

strength of 40mT/m2.

Coil : SENSE XL TORSO coil.

Position of the patient : Supine
Scan Protocol:
MR imaging

will

be

performed

by

taking

following

sequences.
-T1W, T2W and STIR sequences in both axial and coronal
planes. In addition T2W sequence in sagittal plane is
obtained.
-Diffusion

Weighted

Imaging

corresponding ADC maps.

-Dynamic post gadolinium

in

(dose

axial
0.1-

plane

with

0.2mmol/kg)

enhanced MRI was performed in axial, coronal and sagittal

planes in all cases without contraindications.
-MR Spectroscopy was performed in cases with suspicious
areas identified on previous sequences.
Images are acquired with high spatial resolution and small
field of view with slice thickness of 3 mm.

Data collection:

The indication, clinical findings, prior

imaging findings and MRI findings of all the patients will be

recorded and DICOM images will be saved in CD format for
future reference. Follow up will be obtained whenever available.

13

Data Analysis:
After data collection, Data entry will be done in excel, Data
analysis will be done with the help of appropriate statistical
software.
Quantitative data will be presented with the help of mean,
Standard deviation, Median and inter quartile range (IQR).
Qualitative data will be presented with the help of frequency
and

percentage

table.

Association

among

various

study

parameter will be assessed with the help of chi-square test. pvalue < 0.05 will be taken as level of significance.
Wherever possible co-relation with histopathological findings
will be done and analysed.

1.5 REFERENCES
1.

Jemal, A., Center, M. M., DeSantis, C. & Ward, E. M. Global

patterns of cancer incidence and mortality rates and
trends. Cancer Epidemiol. Biomarkers Prev. 19, 18931907
(2010).
14

2.

Tempany, C., Franco, F. & Brazil, P. Prostate MRI: Update

and current roles. 41, 1722 (2012).

3.

Thompson, I. et al. Guideline for the management of

clinically localized prostate cancer: 2007 update. J. Urol.
177, 21062131 (2007).

4.

Bonekamp D, Jacobs MA, El-Khouli R, Stoianovici D, M. K.

Advancements in MR Imaging of the Prostate: From
Diagnosis to Interventions. Radiographics 677703 (2011).

5.

Okotie, O. T. et al. Characteristics of Prostate Cancer

Detected by Digital Rectal Examination Only. Urology 70,
11171120 (2007).

6.

Lucia, M. S. et al. Prevalence of prostate cancer among

men with a prostate-specific antigen level < or =4.0 ng per
milliliter. 22392246 (2004).

7.

Spajic, B. et al. The Incidence of Hyperechoic Prostate

Cancer in Transrectal Ultrasound-Guided Biopsy
Specimens. Urology 70, 734737 (2007).

8.

Svetec, D. et al. Prostate rebiopsy is a poor surrogate of

treatment efficacy in localized prostate cancer. J. Urol. 159,
16061608 (1998).

9.

Dotan, Z. A. Bone imaging in prostate cancer. Nat Clin Pr.

Urol 5, 434444 (2008).

10. Rouvire, O., Hartman, R. P. & Lyonnet, D. Prostate MR

imaging at high-field strength: Evolution or revolution? Eur.
Radiol. 16, 276284 (2006).
11. Hosseinzadeh, K. & Schwarz, S. D. Endorectal diffusionweighted imaging in prostate cancer to differentiate
malignant and benign peripheral zone tissue. J. Magn.
Reson. Imaging 20, 654661 (2004).

15

12. Coakley, F. V. et al. Prostate Cancer Tumor Volume:

Measurement with Endorectal MR and MR Spectroscopic
Imaging. Radiology 223, 9197 (2002).
13. Sciarra, A. et al. Role of Dynamic Contrast-Enhanced
Magnetic Resonance (MR) Imaging and Proton MR
Spectroscopic Imaging in the Detection of Local Recurrence
after Radical Prostatectomy for Prostate Cancer. Eur. Urol.
54, 589600 (2008).
14. De Rooij, M., Hamoen, E. H. J., Ftterer, J. J., Barentsz, J. O.
& Rovers, M. M. Accuracy of multiparametric MRI for
prostate cancer detection: a meta-analysis. AJR. Am. J.
Roentgenol. 202, 34351 (2014).

16

1.6 STUDY PROFORMA

DATE :

REGISTER No(SH No.):

CASE No:

NAME OF THE PATIENT:

AGE:

SEX:

CLINICAL HISTORY:

a
b
d

EXAMINATION:
RS:
CVS:
PER ABDOMEN:
CNS EXAMINATIONS:

Previous Imaging Findings:

MRI Prostate Findings:

PATIENT INFORMATION SHEET

Topic: MULTIPARAMETRIC MAGNETIC RESONANCE
IMAGING IN PROSATE CANCER

17

This is research study to evaluate the usefulness of MRI in

Prostate Cancer. This helps in detection and management of
the disease.
There will not be any active participation of patient in this
study.
MRI of the patient will be done as a routine work up to diagnose
and determine treatment plan.
Data collected in this study will be patients data of routine
work up.
MRI of the patient will be decision making in management of
the patient.
Claustrophobic patients and patients with metallic implants will
be excluded from this study.
As referring doctor advises MRI and it is part of work up of the
patient for further management, patient will have to fulfill the
cost of MRI on his own.
Patients name or identity in any manner will not be disclosed.
Patient is going to participate in this study on his will and has
freedom to withdraw from the research at any time without
penalty.
Patient should not have objection to publish this data in journal.
In all cases identity of patient and confidentiality of data will be
ensured.
Name of investigator-Dr. Sarang Manoharrao Ingole.
Primary DNB in Radiodiagnosis,
Saifee hospital , Mumbai
Mobile no-9967033730.

18

INFORMED CONSENT FORM

Name of the patient:
Registration No:

Date:
Case No:

Title of the Project: MULTIPARAMETRIC MAGNETIC

RESONANCE IMAGING IN PROSTATE CANCER
I have received the information sheet on the above study and
have read and / or understood the written information. I have
been given the chance to discuss the study and ask questions.
I consent to take part in the study and I am aware that my
participation is voluntary. I understand that I may withdraw at
any time without this affecting my future care.
I understand that the information collected about me from my
participation in this study and sections of any of my medical
notes may be looked at by responsible persons (ethics
committee members / regulatory authorities). I give access to
these individuals to have access to my records. I understand I
will receive a copy of the patient information sheet and the
signed informed consent form.

Printed name of subject in

Date of signature
Capitals

Signature / Thumb
Impression of subject

Printed name of Legally

Date of signature
Acceptable Representative ( LAR)

Signature / Thumb
Impression of LAR

Printed name of Person

Date of signature
Taking Consent

Signature of

Printed name of
Date of signature

Signature of

person taking consent

19

Impartial Witness

Impartial witness

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1.7 Approval of Ethical Committee & its Composition:

1.8 Approval of Scientific Committee & its composition:

(Signature of the Candidate)

(Signature of the Guide)

(Signature of Head of the Department)

Institution)
25

(Signature of Head of the

26