Diffusion-weighted imaging (DWI): clinical applications in

oncologic disease

Poster No.: C-1488

Congress: ECR 2012
Type: Educational Exhibit
Authors: J. C. Mariano Rodriguez, M. M. Duh, A. Rodriguez Lacabra, J.
Bartrina Rosell, M. ABADAL PRADES, M. Fernandez Planas;
Mataró/ES
Keywords: Neoplasia, Imaging sequences, MR-Functional imaging, MR,
Oncology
DOI: 10.1594/ecr2012/C-1488

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Learning objectives

The purpose of this poster is to show our experience in the use of functional imaging -
extra cranial DMI technique in this case-, to make a brief description of the technique,
and to show the additional information that it can provide in the study of neoplasm.

Background

Diffusion-weighted Imaging (DWI) technique is based on the detection of motion of water

molecules in vivo that is restricted in several situations such as isquemia, tumors and
abscesses. In this poster we review the basic principles, the protocols used and the
applications of the technique, especially for tumor detection and characterization.

Key words:

Diffusion-weighted Imaging (DWI)

Signal-to-noise ratio (SNR)

Apparent diffusion coefficient (ADC)

Magnetic resonance (MR)

DWI has been used for at least ten years in the diagnosis of brain disease.

Currently, and for the past few years, its potential in the study of extra cranial pathology
has been shown. Among the applications that have attracted the most interest we can find
oncologic disease. DWI is useful in the diagnosis, staging and monitoring of malignancy.
It is becoming an "everyday tool" in the management of breast, neck, lung, abdomen,
pelvis and musculoskeletal RMN studies.

Imaging findings OR Procedure details

Material and Method:

In October 2010 we added the DWI sequence in breast, abdomen, pelvis and
musculoskeletal RMN studies as routine. We perform them in a Signa Horizon 1,5 Tesla
system. Body Coil. DWI-EPIsequence. TE: 96(minimum); TR: 6000; b value: 1000; Matrix

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size: 160 x 160. FOV: 40. Section Thickness: 9 mm. GAP: 1 mm. NEX: 1, Frec. Dir: D/
L. Nº Slices: 17. Duration: 24 seg. We calculate the apparent diffusion coefficient (ADC)
in a work station with Func Tool GE software.

What is Diffusion-weighted Imaging (DWI)?

Diffusion-weighted Imaging is a "molecular-functional" RMN sequence that provides

information about structural tissue changes. For the last few years its importance and
use has been increasing in the study of oncologic patients.

Based on the random movement of water molecules, it gives qualitative information about
tissues cellularity and the integrity of plasmatic membranes and, quantitative analyses of
this water movement by calculating the apparent diffusion coefficient (ADC).

The advantages of the technique are that it can be performed in mostly all the RM
equipments, the fast scan time and that there is no need to use endovenous contrast
agents.

More specifically, the use of DWI in oncology facilitates the detection and characterization
of lesions that are nondifferenciable in other routine sequences between benign or
malignant processes and it is also useful in monitoring of treatment and detection of
recurrence.

In terms of basic principles, DWI gives information about the free movement of water
molecules (Brownian movement) in the different tissues of the body. Therefore, in cysts,
bladder, blood vessels, ducts and big intercellular space tissues water moves more
freely without restriction and will show loss of signal after the application of diffusion
gradients. On the contrary, in solid tumors of high cellularity where there is a significant
reduction in extracellular space and in tissues that have lost the integrity of the plasmatic
membranes, free water movement is restricted. Therefore, there will be greater signal
after the application of diffusion gradients.

Stejskal y Tanner first described the sequence nowadays used to quantify ADW in vivo.
They adapted a T2-weighted sequence with the application of two bipolar gradients/
dephasing gradient prior to the 180º pulse, followed by a symmetric rephasing gradient
after the 180º pulse. They chose a T2-weighted sequence because it has an echo time
(TE) long enough to allow the insertion of two gradients, a dephasing and a rephasing
gradient (fig.1).

Contrary to the static water molecules, the mobile ones will not be fully rephased, resulting
in a reduction in overall T2 signal intensity proportional to the gradient amplitude. The
parameter used to vary the gradient amplitude and duration is the b value. The sensitivity

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of the diffusion sequence is modified by varying the b value in an inverse relationship.
The less b value used, the most sensitivity, but less specificity.

The strength of the diffusion sensitizing gradient is determined by the b value (measured
in seg/mm2). The b value indicates the gradient amplitude, the duration of the applied
gradient, and the time interval between paired gradients. When a DWI is performed
different b values are used to obtain the images, in our practice, 0 and 1000 seg/mm2.

Signal interpretation and quantitative analysis of DWI.

The Apparent diffusion coefficient (ADC) is the parameter to quantify the DWI. It
represents the slope of the line that results from the logarithm of the signal intensity (y-
axis) versus the b values (x- axis), usually 0 and another one between 0 and 1000 seg/
mm2 (fig.2).

Therefore the ADC is calculated in seg/mm2 and it is usually represented in a parametric

map in gray or colour scale on which regions of low signal intensity (dark grey or blue)
with a low ADC value signify restricted diffusion, typically seen in tumors.

It is important to mention that the signal intensity seen in the DWI sequence is created
by the water molecule movement and the T2 relaxation time. This "T2 effect" that can be
mistaken with restricted diffusion is called "shine-through".

Hence, the ADC map allows quantifying DWI and is useful to avoid this pitfall because
a region with truly restricted diffusion will demonstrate low signal intensity on the ADC
map, but lesions with high fluid content will show high signal intensity on T2-weighted
images and on diffusion images.

This undesirable effect can also be reduced by decreasing the TE and increasing the b
value, but it can never be completely eliminated.

The computer calculates the ADC for each pixel and represents it in a parametric map,
as explained before. It is possible to select a region of interest (ROI) on that map and
obtain the exact ADC value for a certain tissue:

ADC=log[(S0/S1)/(b1-b0)]

S0: signal intensity in b0 sequences

S1: signal intensity in DWI images

b1: b value from 1 to 100-1500 seg/mm2

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b0: 0 seg/mm2

When analysing a diffusion-weighted image it is important to be aware of the strengths

and limitations of the technique. A combined interpretation of diffusion-weighted images
with conventional MR images has been shown to increase accuracy in the interpretation
of the pathologies.

Besides, images can be modified at the workstation merging the sequences with higher
spatial resolution with the diffusion images to simultaneously assess the anatomical and
functional information.

The ADC is independent from the magnetic field and is useful to define which tissues are
really restricted in the DWI sequences and which ones show the shine through effect.

In our practice, we have found that the ADC cut value to differentiate benign from
malignant lesions is 0.0012 seg/mm2, which coincides with the one mentioned in most
of the reference articles.

Drawbacks and pitfalls:

Diffusion-weighted imaging may be performed with a number of different techniques,

including spin-echo, fast spin-echo, gradient-echo, and echoplanar imaging, with the
latter being the one used in our hospital.

The major limitations of diffusion-weighted MR imaging are:

(a) the low signal-to-noise ratio (SNR) inherent in the technique and, (b) susceptibility to
artifact, which is associated with echoplanar imaging.

Strategies that may be used to increase SNR include:

-Using a higher field strength, not possible in our case because we perform studies with
a 1.5 T magnetic field.

-Minimizing echo time (<100 msec), we use 96 sec.

-Increasing the number of signals acquired (two or three), which must be balanced
against the resulting increase in imaging time, (NEX 1or 2).

-Using of a coarse matrix (128##128 at 1.5 T in our case, maximum 160 x 160, with
higher values SNR decreases).

-Increasing the section thickness (typically a minimum of 6-7

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mm), we use 9 mm.

-We always perform the DWI sequence in the axial plane because artifacts appear in
other planes.

-Field of view: we reduce it the most until artifacts appear on the obtained image.

-Gap value: 1 mm or less which allows to post process images appropriately.

Clinical applications:

Nowadays NMR techniques have become an indispensable tool in Oncology in the

diagnosis and staging of malignancy and in the evaluation of local and disseminated
neoplasm. A correct staging is decisive in the choice of treatment. Multiplanar capacity
and the ability to characterize different tissues using functional sequences are the
best advantages of NMR technique.

It is also useful in monitoring the effectiveness of treatment and in the detection of

recidiva.

DWI is a functional sequence and a part of the complete MNR study. It is very promising
because of the many advantages it presents compared with only morphologic techniques
such as great contrast image, high sensitivity and fast performing time.

COLORECTAL CANCER

Endorrectal sonography is the technique of choice in the earliest staging of colorectal

cancer (categories T1 and T2, when the tumor has not grown beyond the inner layer
(mucosa) of the colon or rectum). High resolution MNR becomes essential to determine
tumoral spread in T3 category (the tumor has spread through the muscularis propria and
into the outermost layers of the colon or rectum but not through them) and the invasion
of nearby organs or tissues (T4 category). The MNR protocol of study in the staging
of colorectal cancer stage includes multiplanar (axial, sagital, coronal) T2-weighted
images sequences and can be completed with the evaluation of retroperitoneum to detect
lymphatic spread and the study of the liver. We have incorporated the DWI sequence to
this protocol (Fig. 3).

It is also useful in the assessment of cancer response to therapy and detection of tumor
recurrence. Postsurgical fibrotic changes in the pelvis can make it more difficult to detect
tumor recurrence in exclusively anatomic studies. DWI images provide further information

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about surgery complications (abscesses) that may arise or existence of residual tumor
(Fig.4, 5).

Regarding to the lymph nodes, it has been demonstrated that the diameter of invaded
and non invaded mesorectum nodes is similar (5 mm or less in 50% of the positive
nodes). DWI increases sensitivity and specificity in ganglionar involvement. It is important
to mention tha tlymphadenopathy at diffusion-weighted imaging may be confounded
by the restricted diffusion that is frequently displayed by both hyperplastic and normal
lymph nodes as a result of their dense cellularity, which may increase the false positive
diagnosis.

PANCREATIC LESIONS

Conventional MNR combined with DWI may provide additional information to radiologists
evaluating patients who have cystic or solid neoplasms of the pancreas.

Simple cysts have higher signal intensity on diffusion-weighted images with a b value of 0
sec/mm2 and lower signal intensity on high b-value images (high ADC). In contrast, solid
neoplasms of the pancreas show increased signal intensity relative to the pancreas on
diffusion-weighted images with a b value of 0 sec/mm2 and relatively high signal intensity
on high b-value images (low ADC) (Fig.6).

However, diffusion-weighted imaging may not always be capable of helping to

characterize solid lesions as inflammatory or neoplastic because of an overlap in the low
ADC values between the two types, or to characterize liquid lesions as simple cysts or
cystic malignancies (high ADC values in both cases may be shown) but it is helpful in
differentiating abscess from seudocysts in pancreatitis (Fig.7.)

LIVER LESIONS

The characterization of solid liver lesions in MRI is mainly based on their morphology,
their signal in T2 sequence and their behaviour with paramagnetic contrast. Specific
contrast agents can be used. However, some solid lesions present atypical behaviour in
conventional MNR studies and it still remains difficult to accurately differentiate benign
from malignant lesions. DWI sequence can be easily incorporated to the routine protocol
before or after doing the dynamic sequence because it is not affected by the use of
contrast agents. (Fig. 8, 9, 10).

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Many publications have demonstrated that ADC analysis improves the diagnosis of
malignancies, abscesses and benign lesions. Lower restriction and higher ADC values
are found in benign lesions.

Our findings mostly coincide with publications. However, in atypical hepatocarcinomas

we have not found restricted diffusion. The DWI shows an "inverted" image with low signal
in b0 and b500 to 1000. We believe that this effect can be caused by the extremely fast
movement of the molecules within the arterial flow.

MUSCULOESKELETAL LESIONS

DWI sequence increases sensitivity in the detection and characterization of malignant

osseous lesions combined with conventional sequences (T1, STIR, TSE T2 fat sat). For
this reason, in our practice we add this sequence when primary malignancy or metastasis
is suspected. Metastasis and abscess restrict the free movement of water molecules but
benign edema and necrosis do not restrict the free movement of water molecules.

Moreover, we found incidental metastasis when performing other organ studies when
DWI sequence was added. ( Fig. 11, 12, 13 ).

We have also used ADW sequence in the study of soft tissue lesions (Fig. 14) which
increase the differentiation of abscesses and hypercellular masses.

BREAST CANCER

Conventional breast NMR studies morphology and dymamic behaviour of tumors that
provide information about the vascularization and capillary permeability to differentiate
malignant from benign tumors. Its sensitivity is 98% with less specificity (75, 5%) due
to the overlapping of malignant and benign characteristics of the tumors. In the article
Breast, diffusion-weighted imaging (DWI), dynamic contrast-enhanced MRI (DCE-MRI),
MRI.10.2214/AJR.10.4258) the specificity in the diagnosis of breast cancer increases up
to 89,2% when the DWI sequence is added to the conventional protocol.

DWI gives additional molecular information on the tissues (cellularity, necrosis, edema)
increasing specificity. It is also useful in monitoring neoadyuvant treatments. ( Fig. 15,
16).

KIDNEYS AND BLADDER

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DWI can be used in patients that are allergic to iodinated contrast and in patients with
renal failure. It is useful in differentiating malignancies infected from complex cysts and
pyonephrosis. (Fig. 17,18,19)
In our experience it has also contributed in the diagnosis of urinary tract neoplasm. (Fig.
20,21)

THORAX

We have found that DWI is very helpful in detecting pleural malignancies. However, the
results in lung studies lesions are not so promising. Breath artifacts, heart movement
artifacts and air artifacts decrease SNR. We have found no difference between studies
performed with free or hold breath. (Fig. 11)

OVARIAN MASSES

Adnexal masses present a special diagnosis challenge. Determination of the degree

of suspicion for malignancy is critical and it is based largely on imaging appearance.
Endovaginal ultrasonography (US) is the most practical modality for assessment of
ovarian tumors because it is readily available and has a high negative predictive value.
Morphologic analysis of adnexal masses is accurate for identifying masses as either
low risk or high risk. The most important morphologic features are non-fatty solid
(vascularized) tissue, thick septations, and papillary projections. Color Doppler US helps
identify solid, vascularized components in a mass.

Magnetic resonance (MNR) imaging is better reserved for problem solving when US
findings are nondiagnostic or equivocal because, although it is more accurate for
diagnosis, it is also more expensive. The signal intensity characteristics of ovarian
masses make a systematic approach to diagnosis possible. Mature cystic teratomas,
cysts, endometriomas, leiomyomas, fibromas, and other lesions can be accurately
diagnosed .Fat-saturated sequences help distinguish between hemorrhage and fat. The
multiplanar capacity of NMR facilitates to detect adjacent organ invasion and peritoneal
implants in case of ovarian cancer.

Several publications about DWI applications in the diagnosis of ovarian masses and cyst
demonstrate that the ADC value is helpful in differentiating tumoral from normal tissue but
it is important to mention that certain normal tissues such as the endometrium are highly
cellular and, as such, demonstrate restricted diffusion, which should not be misinterpreted
as disease. Some overlapping can be found in abscess and some hemorrhagic cysts.
(Fig. 22, 23)

We believe that diffusion-weighted imaging is a fast sequence that analysed in correlation

with anatomic sequences is helpful in defining the volume and location of malignant

Page 9 of 37
disease sites at initial staging, identifying recurrence, and differentiating tumors from
treatment-induced changes.

CERVICAL CANCER.

As we have already discussed in the other section of this poster, Diffusion-weighted

MR imaging provides important new information non invasively. This unique modality
is helpful in initial staging of known malignancies, differentiating benign from malignant
lesions, assessing treatment response, and determining the presence of disease
recurrence and can be applied in the study of cervical neoplasm. (Fig.24)

Images for this section:

Fig. 1: Schematic illustrates the SE EPI-DWI sequence ( Stejskal y Tanner ) It is a T2-

weighted sequence with the application of bipolar gradients prior and after the 180 RF
pulse. The effect on water molecules (black circles) within tissue with low cellularity, their

Page 10 of 37
signal does not completely rephase with the second gradient, resulting in a loss in signal
intensity.

Fig. 2: Graph illustrates the logarithm of signal intensity versus b values at diffusion-
weighted imaging of normal tissue (black circles) versus tissue restricted diffusion (red
circles).

Page 11 of 37
Fig. 3: Rectal adenocarcinoma T3d-N1. Diffusion-restricted tumor (arrow head d, e) and
regional node (arrows). DWI / FSE T2 fusion (f, i).

Page 12 of 37
Fig. 4: Recurrence of rectal cancer. TC with metal artifacts due to hip replacement (Fig.
a) that degrade the image. Nonspecific changes in FSE T2 sequence (Fig. b). In the DWI-
EPI sequence there is a site that restricts the diffusion (arrows in c, d).

Page 13 of 37
Fig. 5: Sacral osteomyelitis. Patient with operated on rectal cancer, perineal pain. CT
shows nonspecific changes (fig. a, f). DWI-EPI shows edema and a diffusion-restricted
area (arrows in c, d, e).

Page 14 of 37
Fig. 6: Adenocarcinoma in the head of pancreas. Note restricted-diffusion and low ADC
value.

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Fig. 7: Serous "microcystic" cystadenoma of pancreas. The tumor does not show
restricted-diffusion ( fig. d).

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Fig. 8: Hepatic hemangioma (Fig. a, b, c.). Focal nodular hyperplasia ( Fig. d, e, f.)

Page 17 of 37
Fig. 9: Liver metastases of adenocarcinoma of ascendent colon (fig.a,b,c).
Hepatocellular carcinoma (fig.d,e,f ).

Page 18 of 37
Fig. 10: Liver abscess. Contrast images not performed due to IRC . Note the large
contrast on the DWI-EPI sequence( fig. e).

Page 19 of 37
Fig. 11: Pleural effusion. Cytopathology: adenocarcinoma of unknown origin. The DWI-
EPI sequence shows multiple pleural (arrows) and bone metastases( arrowsheads).
Bony lesions not visualized with CT. Definitive diagnosis: metastasis of prostate
adenocarcinoma.

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Fig. 12: Incidentally, bony metastases are found ( D12 and L2 ) during the performance
of DWI-EPI sequence in the study of liver metastasis from colorectal adenocarcinoma.

Page 21 of 37
Fig. 13: Jaw pain and fever. Normal CT scan. Pleomorphic sarcoma metastasis.

Page 22 of 37
Fig. 14: Liposarcoma of the thight.

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Fig. 15: Breast cancer. Note the excellent contrast y the diffusion-restricted tumor images
compared to normal tissue images (fig.c,d).

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Fig. 16: Same patient with good response after chemotherapy treatment. Note the
decreased signal on DWI-EPI sequence ( fig. a, b) and increased ADC values. (fig. c, d).

Page 25 of 37
Fig. 17: Renal neoplasm. Cytopathology: lymphoma.

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Fig. 18: Sero-Hematic pleural effusion and metastasis (arrows in a, b y c) of the left renal
neoplasia (arrows in d, e y f). Regional node diffusion-restricted (arrowheads in g, h, i).

Page 27 of 37
Fig. 19: Pyonefrosis in pacient who underwent cystectomy. Chronic left hydronefrosis
and fever. Restricted-diffusion in purulent content in the urinary left tract (imágenes c y d).

Page 28 of 37
Fig. 20: Bladder cancer in the left lateral wall.

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Fig. 21: Recurrence of transitional cell neoplasm in the right distal ureter (arrows) and
nodal homolateral (arrowheads).

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Fig. 22: Ovarian Cystadenocarcinoma.

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Fig. 23: Recurrence of ovarian neoplasm.

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Fig. 24: Cervical neoplasm. Iliac chains lymph nodes.

Page 33 of 37
Conclusion

DWI is an emergent technique and more prospective studies with a greater number of
patients have to be performed with long term monitoring to establish its real potential.

DWI is a promising sequence that is helpful to differentiate between bening and malignant
tumors, in the assessment of treatment response and in the diagnosis of abscesses.

The advantages of diffusion-weighted MR imaging are that it is completely noninvasive,

does not require exposure to ionizing radiation or injection of contrast agent, and requires
only a few additional minutes of scanning time. Thus, diffusion-weighted MR imaging can
easily be incorporated into a conventional rectal MR imaging protocol.

There are some drawbacks in DWI images currently used. Images are usually
characterized by low spatial resolution and the presence of artifacts. Furthermore, there
are considerable differences in b values chosen in the different institutions where DWI
is performed, and consequently differences in the mean value of ADC to differentiate
malignancies.

Finally, it is important to be aware of the potential pitfalls of diffusion-weighted MR imaging

and to review findings in conjunction with findings obtained with anatomic sequences.
Increasing familiarity with ADC calculation and manipulation software, including the ability
to fuse anatomic and diffusion data, will allow radiologists to gain confidence. In our
practice, the incorporation of ADW sequence to the routine protocols increases the
diagnostic accuracy and offers new additional molecular and functional information in the
study of malignancies.

Personal Information

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25-R. García Figueiras, C. Villalba Martín y S. Baleato González.

Masas renales benignas. SEDIA: Volumen 5: N.º 3- 2008: 23-24.

26-Reiko Woodhams, Saadallah Ramadan, Peter Stanwell, Satoko Sakamoto,

Hirofumi Hata, Masanori Ozaki,ShinichiKan, and Yusuke Inoue. Diffusion-weighted

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