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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE
KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1.
Name of the Candidate
and Address
(in block letters)
Dr. NIJALINGAPPA
S/o CHIDANANDAPPA
# 5-5-272,
SWAMI VIVEKANANDA NAGAR,
YADGIR.
KARNATAKA - 585202.
2.
Name of the Institution
J.J.M. MEDICAL COLLEGE,
DAVANGERE – 577 004.
3.
Course of study and subject
POSTGRADUATE
M.D. IN RADIO-DIAGNOSIS
4.
Date of Admission to course
29/04/2010
5.
Title of the Topic
6.
BRIEF RESUME OF THE INTENDED WORK :
6.1 Need for the study :
“ROLE OF DIFFUSION WEIGHTED
MAGNETIC RESONANCE IMAGING IN
FOCAL LIVER LESIONS”.
The liver is an organ in which various benign or malignant primary or secondary
masses can be detected. Today, focal masses are diagnosed using ultrasonography
(USG) and/or computed tomography (CT). Additionally, magnetic resonance imaging
(MRI) is preferred when further characterization of these masses is needed. MRI has
many advantages (e.g., high contrast resolution, the ability to obtain images in any
plane, lack of ionizing radiation, and the safety of using particulate contrast media
rather than those containing iodine) that make it a favored modality. Lesion
morphology, signal intensity, and contrast enhancement pattern are taken into
consideration when characterizing masses with MRI; however, even if the data are
evaluated together, there can still be difficulties in the differentiation of benign and
malignant lesions.
1
Although dynamic contrast enhanced examinations have become a routine
component of abdominal imaging, the high cost/benefit ratio and risk of contrast media
side effects remain an issue. Moreover, sometimes it is not possible to distinguish
between highly vascular metastases and hemangiomas, even using dynamic
examinations.1
Diffusion is a physical property, which describes the microscopic random
movement of (water) molecules driven by their internal thermal energy. This
movement is known as Brownian motion. In biological tissues, water diffusion is
movement of water molecules in intracellular, extracellular and intravascular spaces.
Diffusion is affected by the biophysical properties of tissue cell organization (cell
membranes, fibers and macromolecules), density, microstructure and microcirculation.
Intracellular water diffusion is more hindered than that in the extracellular spaces
which are lacking natural barriers. Pathological processes which change the volume
ratio or physical nature of intra- and extracellular spaces affect the diffusion of water
molecules. Restricted or impeded diffusion is seen in tissues with high cellularity, e.g.
tumors, abscesses, fibrosis and cytotoxic edema. Relative free or unimpeded diffusion
is encountered in tissues with low cellularity or tissues with disrupted cell membranes,
for example in cysts and necrotic tissues.
DWI relies on measuring diffusion of water molecules in the tissue by MRI. It
uses a pulse sequence (T2-weighted spin echo sequence) and 2 strong motion probing
gradients on either side of the 180º refocusing pulse, known as the Stejskal-Tanner
sequence. The first gradient, prior to the 180º RF pulse is the dephasing (diffusion
sensitizing) gradient. The second gradient, after the RF pulse, is the rephasing gradient.
In tissues with restricted diffusion, the effect of the dephasing gradient is cancelled out
by the rephasing gradient. This causes little impact on the overall T2 decay, reflected
as a maintained T2 signal in the tissue. When diffusion is not impeded, water
molecules can move a considerable distance between the dephasing and rephasing
gradients. The mobile water molecules will not be fully rephased and a reduction in
overall T2 signal intensity follows.2
The term b value refers to the strength of the diffusion sensitizing gradient. The b
value is proportional to the gradient amplitude, the duration of the applied gradient,
and the time interval between paired gradients and is measured in seconds per square
millimeter .Diffusion-weighted imaging is performed with at least two b values,
including a b value of 0 sec/mm2 and a higher b value of 500–1000 sec/mm2
depending on the body region or organ being imaged.3
2
Diffusion coefficients in DWI are reflected in the apparent diffusion
coefficient (ADC, expressed in mm2/s).2
The ADC represents the slope (gradient) of a line that is produced when the
logarithm of relative signal intensity of tissue is plotted along the y-axis versus b
values along the x-axis Quantitative analysis of diffusion-weighted imaging findings
can be performed only if at least two b values are used for imaging. In liver b values of
0 and 500–600 sec/mm2 are typically used. Although at least two b values are required
for diffusion weighted imaging analysis, the application of a greater number of b
values will improve the accuracy of the calculated ADC. The disadvantage of using
multiple high b values is an associated increase in scanning time.3
The use of DWI in other parts of the body is relatively new, but very promising
for the detection and differentiation of benign and malignant lesions, imaging for
dissemination in oncological patients before treatment and for follow-up after
treatment of liver tumors. Besides this, DWI is thought to be capable of predicting the
response to therapy of malignant tumors. 2
Diffusion images should be interpreted in conjunction with conventional
sequences. In patients who cannot receive gadolinium-based contrast agents, DW MR
imaging has the potential to be a reasonable alternative technique to contrast-enhanced
imaging.4
Thus a study design to evaluate the contribution of imaging science towards the
evaluation and diagnosis of focal liver lesions
6.2 Review of literature :
A total of 77 patients and 65 healthy controls were enrolled in the study. DWMRI was performed with b-factors of 0, 500 and 1000 s/mm(2), and the apparent
diffusion coefficients (ADC) values of the normal liver and the lesions were
calculated. The mean ADC value of the focal liver lesions were as follows: simple
cysts (3.16 +/- 0.18 x 10(-3) mm(2)/s), hydatid cysts (2.58 +/- 0.53 x 10(-3) mm2/s),
hemangiomas (1.97 +/- 0.49 x 10(-3) mm(2)/s), metastases (1.14 +/- 0.41 x 10(-3)
mm(2)/s) and hepatocellular carcinomas (HCC) (1.15 +/- 0.36 x 10(-3) mm(2)/s). The
mean ADC values of all the disease groups were statistically significant when
compared with the mean ADC value of the normal liver (1.56 +/- 0.14 x 10-3mm2/s),
(P < 0.01). There were also statistically significant differences among the ADC values
of hemangiomas and HCC metastases (P < 0.01), and simple and hydatid cysts
3
(P < 0.008). However, there was no statistically significant difference between HCC
and metastases. The present study showed that ADC measurement has the potential to
differentiate benign and malignant focal hepatic lesions5
A total of 542 lesions in 382 patients were evaluated. ADC values were measured
in 166 hemangiomas, 112 hepatomas, 107 metastases, 95 cysts, 10 abscesses, 43 FNH,
and nine adenomas. ADCs of 1.5 and 1.6 (×10−3 mm2/second) were selected as
threshold values to separate benign and malignant lesions. There was high
interobserver agreement in ADC measurements for all lesion types. The mean ADCs
for cysts was 3.40 (×10 −3mm2/second), hemangiomas 2.26, FNH 1.79, adenomas 1.49,
abscesses 1.97, HCC 1.53, and metastases 1.50. The mean ADC for benign lesions was
2.50 and for malignant lesions was 1.52. Cysts were easily distinguished from other
lesions. There was, however, overlap between solid benign and malignant lesions.6
In study 104 patients with focal liver masses .DWI was performed with b values
of 0, 50, and 400s/mm2. Of these, 76 patients had lesions larger than 2 cm diameter,
radiologic or pathologic characterization of the lesion, and diagnostic quality DWI.
The apparent diffusion coefficient (ADC) of the largest liver lesion was measured. The
analyzed lesions were hemangioma (n = 17), cysts (n = 5), hepatocellular cancer
(HCC) (n = 41), adenoma (n = 3), focal nodular hyperplasia (FNH) (n = 6), and
metastases (n = 4). The mean (standard deviation) ADC values (10−5 mm2/second) of
hemangiomas, cysts, FNH, and HCC were 156.8 (54.1), 190.2 (43.0), 130.1 (81.9), and
107.6 (32.7). The ADC of cysts and hemangiomas were significantly higher than that
of other lesions.7
51 solid focal lesions (26 patients) with MRI, using conventional sequences and
diffusion-weighted imaging obtained with EPI mode with different values of "b".
Lesions corresponded to 20 hemangiomas, 12 focal nodular hyperplasia (FNH), 5
hepatocellular carcinoma (HCC), and 14 metastases. The statistical analysis allowed us
to determine optimal cutoff level (ADC 1.28 x 10-3mm2/s) to differentiate benign from
malignant lesions. ADC values of benign lesions were significantly higher than those
of the malignant ones; the hemangioma was the solid lesion with higher ADC values,
followed by FNH, HCC and metastases, with lower values. Registered mean values
were 1.68, 1.30, 1.08 and 1.03 (x10-3mm2/s), respectively. In our view, the diffusionweighted technique should be used to supplement conventional MRI for proper
characterization of solid liver lesions.8
30 patients that underwent upper abdominal MRI examinations because of
hepatic masses that were found to be ≥1 cm in size with conventional sequences, and
were additionally evaluated with diffusion-weighted MRI. Diffusion-weighted images
and ADC maps in the axial plane were obtained .Mean ADC measurements were
4
calculated among the 30 cases involving 41 hepatic masses. Of the 41 hepatic masses,
24 were benign and 17 were malignant. Benign lesions included 6 cysts, 14
hemangiomas, 2 abscesses, and 2 hydatid cysts. Malignant masses included 8
metastases, 4 hepatocellular carcinomas, 4 cholangiocellular carcinomas, and 1 gall
bladder adenocarcinoma. The highest ADC values were for cysts and hemangiomas.
The mean ADC value of benign lesions was 2.57 +/- 0.26 x 10-3mm2/s, whereas
malignant lesions had a mean ADC value of 0.86 +/- 0.11 × 10-3 mm2/s. The mean
ADC value of benign lesions was significantly higher than that of malignant lesions (P
< 0.01). Diffusion-weighted MRI with quantitative ADC measurements can be useful
in the differentiation of benign and malignant liver lesions.9
Diffusion-weighted imaging performed in 46 patients with 74 known focal
hepatic lesions (11 hemangiomas, 15 metastases, and 48 hepatocellular carcinomas
[HCCs]). Mean values for ADCs and CNRs of all lesions were calculated. The mean
values for ADCs were different for each type of tumor (5.39 x 10-3 mm2/sec +/- 1.23
in hemangiomas, 2.85 x 10-3 mm2/sec +/- 0.59 in metastases, and 3.84 x 10-3 mm2/sec
+/- 0.92 in HCCs), and each of them was significantly greater than the mean values for
ADCs of the normal liver (2.28 x 10(-3) mm2/sec +/- 1.23 in normal liver [p < .05]
except metastasis versus normal liver [p < .1]).Also, the mean values for ADCs were
based on differences of ADC values. Only four (6%) of 63 malignant tumors (three
HCCs and one metastasis) could not be differentiated from hemangiomas. Mean values
for ADCs differed for the three types of the hepatic lesions and were higher than
ADCs of the normal liver. Diffusion-weighted imaging may be useful for increased
detection of HCCs and metastases and in distinguishing these entities from
hemangiomas.10
Zech et al reported a higher sensitivity for DWI compared to conventional MRI
in the detection of HCC in the cirrhotic liver (98% for DWI vs 83%-85% for MRI.11
Fifty-two patients with extrahepatic primary malignant tumors underwent 1.5-T
MRI that included DW EPI and the following variants of T2-weighted TSE
techniques: breath-hold fat-suppressed HASTE, breath-hold fat-supressed TSE,
respiration-triggered fat-suppressed TSE, breath-hold STIR, and respiration-triggered
STIR. A total of 118 hepatic metastatic lesions (mean diameter, 12.8 mm; range, 3–84
mm) were evaluated. Accuracy values were higher (p < 0.001) with DW EPI (0.91–
0.92) than with the T2-weighted TSE techniques (0.47–0.67). Imaging with the
HASTE sequence (0.47–0.52) was less accurate (p < 0.05) than imaging with the
breath-hold TSE, breath-hold STIR, respiration-triggered TSE, and respirationtriggered STIR sequences (0.59–0.67). Sensitivity was higher (p< 0.001) with DW EPI
(0.88–0.91) than with T2-weighted TSE techniques (0.45–0.62). For small (≤ 10 mm)
metastatic lesions only, the differences in sensitivity between DW EPI (0.85) and T25
weighted TSE techniques (0.26–0.44) were even more pronounced. DW EPI was more
sensitive and more accurate than imaging with T2-weighted TSE techniques. Because
of the black-blood effect on vessels and low susceptibility to motion artifacts, DW EPI
was particularly useful for the detection of small (≤ 10 mm) metastatic lesions.12
Diffusion-weighted echo-planar imaging was performed in 51 patients with 59
hepatic masses (41 malignant tumors, nine hemangiomas, and nine cysts). Apparent
diffusion coefficient (ADC) values were obtained with two motion-probing gradients
(b = 30 and 1,200 sec/mm2) during each of the breath-hold periods, and an ADC map
was constructed. The ADC value of malignant masses (1.04 x 10-3 mm2/sec) was
significantly lower (P < .01) than that of benign masses (hemangiomas [1.95 x 10-3
mm2/sec] and cysts [3.05 x 10-3 mm2/sec]), although the T2s showed considerable
overlap. A small amount of overlap in ADC values occurred among malignant tumors,
hemangiomas, and cysts. ADC values of two cystic masses from ovarian carcinomas
were within the range of those of hemangiomas. These preliminary results indicate that
diffusion-weighted MR imaging can be useful in characterizing focal liver masses.
With the exception of cystic metastatic tumors, the technique may be especially useful
in tumors that appear markedly hyperintense on T2-weighted images due to a long
T2.13
Thirty-eight patients with focal liver lesions that were detected by US or CT
scan underwent diffusion weighted MRI (DWI) in addition to routine MRI. Two b
values (b=0 s/mm2, 1000 s/mm2) were used and the quantitative analysis of the
diffusion (ADC) was calculated. The liver masses were diagnosed on histology or had
characteristic MRI findings and follow up of more than 6 months. The analyzed
lesions were hemangioma (n = 9), cysts (n = 2), hepatocellular cancer (HCC) (n = 20),
and metastases (n = 7). The diffusion-weighted MRI sequence is a useful diagnostic
tool and it can contribute to accurate diagnosis and discrimination between benign and
malignant hepatic masses. DWI can significantly reduce the need for intravenous
administration of contrast medium in evaluation of malignancies.14
6.3 Objectives of the study :
 Detection and characterization of focal liver lesions.
 Differentiation of benign from malignant liver lesions.
 Differentiation of liver metastasis from primary liver lesions
6
7.
MATERIAL AND METHODS :
7.1 Source of data :
The main sources of data for the study are patients from the following teaching
Hospital attached to Bapuji Education Association, J.J.M. Medical College,
Davangere.
1. Bapuji Hospital.
2. Chigateri General Hospital.
3. S.S. Institute of Medical Sciences & Research Centre
7.2. Method of collection of data (including sampling procedure if any):

All patients referred to the department of Radio diagnosis Patients of all age
groups referred to MRI clinically suspected of focal liver lesions. Patients with
indeterminate lesions detected on USG or CT in a period of 1 year 2 months
from October 2011 to November 2012 will be subjected for the study.
 Initially a minimum of 30 cases are intended to be taken up, however the scope
of increasing the number of cases exists depending upon the availability within
the Study period.
 Abdomen will be assessed in axial, sagittal and coronal planes.
 Recommended sequences: spin-echoT1WI, fast SE T2WI in axial and coronal
plane, gradient echo(GE) and DWI, Post contrast dynamic study(whenever
indicated)
Inclusion criteria :
The study include:
 All patients referred for MRI with clinically suspected focal
liver lesions and patients with indeterminate liver lesions detected on
USG or CT
Exclusion criteria:
The study will exclude:
 All patients having cardiac pacemakers, prosthetic heart valves, cochlear
implants or any metallic implants.
 Patient having history of claustrophobia.
 All patients who do not consent to be a part of the study.
7
Duration of study: 1 year 2 month.
Data Analysis:
By Proportion.
7.3 Does the study require any investigations or interventions to be conducted on
patients or other humans or animals? If so, please describe briefly.
Yes
 The study is mainly based on investigations as Radiology itself is a tool of
investigation. Interventions would be done as and when it is indicated alone.
 The study involves only humans.
 Informed consent would be taken after explaining about and before any
procedure.
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
Yes.
Ethical clearance has been obtained from the Research and Dissertation
Committee/ Ethical Committee of the institution for this study.
8
8.
REFERENCES :
1)
Demir Öİ, Obuz F, Sağol Ö , Dicle O. Contribution of diffusion-weighted
MRI to the differential diagnosis of hepatic masses. Diagn Interv
Radiol.2007; 13:81-8.
2)
Kele p ,Van der Jagt, E. World J Gastroenterol. 2010 April 7; 16(13):
1567–1576.
3)
Qayyum A. Diffusion-weighted Imaging in the Abdomen and Pelvis:
Concepts and Applications. RadioGraphics 2009; 29:1797–1810.
4)
Taouli B, Koh DM. Diffusion-weighted MR imaging of the liver.
Radiology 2010 Jan;254(1):47-66.
5)
Kilickesmez O, Bayramoglu S, Inci E, Cimilli T. Value of apparent
diffusion coefficient measurement for discrimination of focal benign and
malignant
hepatic
masses.
J
Med
Imaging
Radiat
Oncol. 2009
Feb;53(1):50-5.
6)
Miller, F. H., Hammond, N., Siddiqi, A. J., Shroff, S., Khatri, G., Wang,
Y., Merrick, L. B. and Nikolaidis, P. (2010), Utility of diffusion-weighted
MRI in distinguishing benign and malignant hepatic lesions. Journal of
Magnetic Resonance Imaging, 32: 138–147.
7)
Sandrasegaran K, Akisik FM, Lin C, Tahir B, Rajan J, Aisen AM. The
Value of Diffusion-Weighted Imaging in Characterizing Focal Liver
Masses. Academic Radiology 2009 Oct ; 16(10) :1208-1214,
8)
Vergara ML et al. Diffusion­weighted MRI characterization of solid
liver lesions. Rev Chil Radiol 2010: 16 (1): 5­10.
9)
Demir OI, Obuz F, Sagol O and Dicle O. Contribution of diffusionweighted MRI to the differential diagnosis of hepatic masses Diagn Interv
Radiol 2007; 13:81-86
10)
Chikawa T, Haradome H, Hachiya J, Nitatori T, Araki T. Diffusionweighted MR imaging with a single-shot echoplanar sequence: detection
and characterization of focal hepatic lesions AJR Am J Roentgenol. 1998
Feb; 170(2):397-402.
9
11)
Zech CJ, Reiser MF, Herrmann KA. Imaging of hepatocellular carcinoma
by computed tomography and magnetic resonance imaging: state of the art.
Dig Dis. 2009; 27(2):114-24
12)
Bruegel M, Gaa J, Waldt S, Woertler K, Holzapfel K, Kiefer B, Rummeny
EJ. Diagnosis of hepatic metastasis: comparison of respiration-triggered
diffusion-weighted echo-planar MRI and five t2-weighted turbo spin-echo
sequences.AJR Am J Roentgenol. 2008 Nov;191(5):1421-9.
13)
Namimoto T, Yamashita Y, Sumi S, Tang Y, Takahashi M.Focal liver
masses:
characterization with
diffusion-weighted echo-planar
MR
imaging. Radiology. 1997 Sep; 204(3):739-44.
14)
Abbas I, Elghawabi.H. Diffusion mri of focal liver lesions.PJR, 2010JanMar; 1(20):01-07.
10
9.
Signature of candidate
10
Remarks of the guide
Diffusion-weighted
(DW)
MR
imaging
is
an
emerging, promising application for detection and
characterization of liver lesions.
11
Name & Designation of
(in block letters)
11.1 Guide
Dr. SHIVMURTHY.K.N M.D.,D.M.R.D.,
PROFESSOR,
DEPARTMENT OF RADIO-DIAGNOSIS,
J.J.M. MEDICAL COLLEGE,
DAVANGERE – 577 004.
11.2 Signature
11.3 Co-Guide (if any)
--
11.4 Signature
11.5 Head of the
Department
Dr. J . PRAMOD SETTY M.D.,
PROFESSOR AND HEAD,
DEPARTMENT OF RADIO-DIAGNOSIS,
J.J.M. MEDICAL COLLEGE,
DAVANGERE – 577 004.
11.6 Signature
12
Remarks of the
Chairman & Principal
12.2. Signature.
11
12