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Original Article
Acta Medica Anatolia
Volume 4 Issue 4 2016
High Resolution T2-Weighted Dixon Based Whole Body Magnetic
Resonance Imaging in Detecting Bone Metastasis; Initial Results
Ali Özgen1, Nalan Alan Selçuk2, Orhan Önder Eren3, Özlem Uysal Sönmez3, Hasan Atilla Özkan4, Başak Oyan Uluç3
Department of Radiology, Yeditepe University, İstanbul, Turkey
Department of Nuclear Medicine, Yeditepe University, İstanbul, Turkey
3
Department of Oncology, Yeditepe University, İstanbul, Turkey
4
Department of Hematology, Yeditepe University, İstanbul, Turkey
1
2
Abstract
Introduction: Whole body magnetic resonance imaging (WB-MRI) has been used in detecting bone metastasis. Conventional
MR sequences used in whole body imaging are mostly T1W and STIR. Our aim is to determine the value of high resolution T2weighted mDixon (T2WmD) WB-MRI in detecting bone metastasis in comparison to bone scintigraphy and positron emission
tomography-computed tomography (PET-CT).
Methods: Sixteen patients were enrolled in the study. Twelve patients with malignant disease (4 patients with breast cancer,
4 patients with thyroid medullary carcinoma, 2 patients with multiple myeloma, 1 patient with monoclonal gammopathy,
and 1 patient with neuroendocrine tumor) were imaged with high resolution T2WmD based WB-MRI and PET-CT while 4
patients with prostate cancer were imaged with WB-MRI and bone scintigraphy. Images were reviewed by a nuclear medicine
specialist and by a radiologist blinded to each other’s findings.
Results: Twelve patients were diagnosed as having bone metastasis both by nuclear medicine imaging and by WB-MRI. PET-CT
and bone scintigraphy revealed 4 lesions that could not be detected by WB-MRI in 2 patients whereas WB-MRI detected 16
additional small lesions that could not be shown by PET-CT or bone scintigraphy in 3 patients.
Conclusion: We conclude that high resolution T2WmD based WB-MRI is a very promising method in detecting bone metastasis
and further studies with larger patient populations are suggested.
Keywords: Magnetic resonance imaging, bone scintigraphy, PET-CT, bone metastasis.
Received: 27.07.2016
Accepted: 25.09.2016
Introduction
Metastatic disease of bone may accompany up to
70% of cancer patients (1,2). After the lungs and
liver, bone is the most common organ affected by
metastases (2,3). Detection of skeletal involvement
in cancer patients is very important for staging of the
disease and therefore choosing the optimal therapy.
Prevention or treatment of possible complications
such as pain, instability, and fractures due to
metastatic involvement of bones are also mandatory
in evaluating cancer patients.
Many nuclear medicine and radiological imaging
methods have been used in detecting bone involvement
of malignant disease (4). In the last decade, studies on
whole body magnetic resonance imaging (WB-MRI)
in detecting bone metastasis without using ionizing
radiation has gained some popularity. Although bone
scintigraphy and positron emission tomographycomputed tomography (PET-CT) have
been traditionally used, many MR imaging protocols
with or without gadolinium based contrast medium
have been implemented in search for early and
accurate detection of bone metastasis in WB-MRI
(5-10). Besides some conventional sequences,
short tau inversion recovery (STIR) sequence for
obtaining better contrast-to-noise ratio (CNR) and
T1-weighted imaging with or without gadolinium
based contrast medium have been used extensively
in WB-MRI (6-10). Dixon imaging method could also
provide relatively high resolution images and good
CNR. Although this technique has been widely used
in imaging of the abdomen and the extremities, to
the best of our knowledge, has not been used in as a
single sequence in WB-MRI. The aim of this study is
to evaluate the value of high resolution T2-weighted
mDixon (T2WmD) imaging as a single sequence
in detection of bone metastasis in comparison to
skeletal scintigraphy and PET-CT.
Correspondence: Ali Özgen, Department of Radiology, Yeditepe University, Istanbul, Turkey
Conflict of Interest: None
E-mail: [email protected]
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Özgen et al.
Materials and Method
MRI protocol
Patients
All MR examinations were performed on a 3.0T
machine (Ingenia; Philips Medical Systems, Best,
The Netherlands) with automatic moving tabletop.
Combination of one posterior and two anterior coils
covering whole torso and extremities, and one headneck coil covering the head and neck area with a total
of 106 channels. The acquired sequence was coronal
turbo spin echo T2WmD (TR 3351-3527/TE 70) with
4 images; water-only, in-phase, opp-phase, and fatonly. Acceleration factor was 4. Field of view was
300x550 mm for each station. Voxel size was 1x1x4
mm3, intersection gap was 0.4 mm. Fifty-five to sixty
coronal water-only and in-phase images obtained
from 6 stations were fused using manufacturer’s
standard software (Figure 1). Image time for each
station were between 2 minutes 10 seconds and
2 minutes 17 seconds. Each MRI examination was
performed in 25-30 minutes. All MRI examinations
were reviewed by the same radiologist with 16
years of experience blinded to nuclear medicine
examinations.
This prospective study was approved by the
institutional ethics committee. Informed consent
was obtained from all individual participants
included in the study. All procedures performed
in studies involving human participants were
in accordance with the ethical standards of the
institutional and/or national research committee
and with the 1964 Helsinki declaration and its later
amendments or comparable ethical standards.
Between July 2015 and March 2016, 16 adult
patients, 9 female and 7 male, with malignant
disease were involved in the study. Pathologically
proven diagnosis were breast cancer in 4 patients,
prostatic carcinoma in 4 patients, thyroid medullary
carcinoma in 4 patients, multiple myeloma in 2
patients, monoclonal gammopathy in 1 patient, and
neuroendocrine tumor in 1 patient. Mean age of the
patients was 54 years (range, 34-69 years). All patients
were referred to nuclear medicine and radiology
either from oncology or hematology departments
for detection of possible bone metastasis. Indication
of nuclear medicine imaging was made by patient’s
clinician. Patients with prostatic carcinoma were
imaged with bone scintigraphy whereas other
patients were imaged routinely with PET-CT. All
patients were also imaged by WB-MRI within one
week of nuclear medicine imaging independent of
nuclear medicine findings.
Bone scintigraphy
After 2-3 hours patients were given 20 mCi 99mTc
monodiphosphonate from antecubital vein, anterior
and posterior images were obtained using a 256x1024
matrix resolution low energy high resolution gamma
camera (Forte, Philips, The Netherlands). SPECT
images were also taken whenever necessary. All
bone scintigraphy examinations were reviewed by
the same nuclear medicine specialist with 12 years
of experience blinded to MRI examination findings.
PET-CT imaging
After 1 hour injection of 18F-FDG, images were
obtained using a PET-CT (Discovery IQ, General
Electric, USA) and reconstructed using ordered
subset expectation maximization (OSEM) method.
All PET-CT images were reviewed by the same nuclear
medicine specialist with 12 years of experience
blinded to MRI examination findings.
Acta Med Anatol 2016;4(4): 159-163
Figure 1. 35-year-old female patient with thyroid medullary carcinoma. A. Coronal fused water-only T2WmD image. B. Coronal fused
in-phase T2WmD image. Metastatic lesions are located in sacrum,
iliac bone and humerus (arrows). Note lesions are more prominant
in in-phase images.
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Özgen et al.
Image analysis
to very low resolution of nuclear medicine imaging
modalities. On the other side, WB-MRI detected
16 more lesions, equal or smaller than 12 mm, in 3
patients who already had other lesions all located
in vertebrae, pelvic bones and femur (Figures 2 and
3). Only 2 of them were retrospectively regarded as
suspicious on PET-CT while 9 of them could not be
imaged by neither scintigraphy nor PET-CT. We also
noted that CNR of lesions seen in in-phase imaging
were higher than in water-only images and in-phase
images documented 7 more lesions than water-only
images all equal or smaller than 6 mm.
For bone scintigraphy, visual analysis was used
instead of a semiquantitative analysis. For PET-CT
interpretation, focally increased 18F-FDG uptake
was considered as malignant unless a benign lesion
was noted on the corresponding CT images. For
MRI interpretation, high intensity areas on wateronly and/or low intensity areas on in-phase images
noted in medullary bone with or without cortical
involvement were considered malignant unless a
benign etiology was suspected. Lesions with low
level of suspicion on each imaging modality were
followed-up and not considered as malignant. Bone
biopsy, contrast enhanced MRI, or high resolution
CT examinations were planned if a lesion was
considered suspicious and had the ability altering
the diagnosis or staging. Final diagnosis was made
on consensus and confirmed by imaging, histological
examination, and/or follow-up.
A)
B)
Results
All patients well tolerated WB-MRI examinations.
WB-MRI images were also considered diagnostic
in all patients. Minor artifacts at the edge of
some images of upper extremity scans were not
considered important and did not prevent optimum
interpretation of bones. Both signal-to-noise and
contrast-to-noise ratios were considered satisfactory
by the radiologist in a qualitative fashion.
Of 16 patients, 12 patients were diagnosed as having
bone metastasis based on consensus; 4 patients
with prostate cancer, 3 patients with breast cancer,
3 patients with thyroid medullary carcinoma, and 2
patients with multiple myeloma. Two bone biopsies
under CT guidance were performed by the same
radiologist to confirm metastasis and to obtain
definite histopathological diagnosis. No additional
imaging was necessitated in any of the patients.
Follow-up of the patients did not alter the initial
diagnosis in any of the patients.
Overall, 81 separate lesions in 12 patients were
noted both by bone scintigraphy/PET-CT and WBMRI. In all patients, diagnosis were successfully
made by bone scintigraphy or PET-CT examinations
and also by WB-MRI, resulting in 100% agreement.
Each bone scintigraphy and PET-CT detected 2
more lesions in 2 patients, who already had other
metastatic lesions, located on ribs (3 lesions) and
skull (1 lesion). Two of the lesions, 1 in skull and 1
in ribs, were retrospectively detected by WB-MRI
whereas other 2 lesions could not be detected. Size
of these lesions could not be exactly determined due
Acta Med Anatol 2016;4(4): 159-163
C)
Figure 2. 59-year-old male patient with prostatic carcinoma. A.
Bone scintigraphy showing multiple metastatic lesions. B. Wateronly and C. In-phase T2WmD images showing smaller metastatic
lesions that could not be differentiated on bone scintigraphy (arrows). Note in-phase images also documented 2 more small lesions
(thin arrows).
Discussion
Although scintigraphy and PET-CT are the traditional
methods of imaging in detecting bone metastasis,
WB-MRI with the advantage of not having ionizing
radiation have been studied in this area of diagnosis.
Various MR sequences with or without gadolinium
based contrast medium have been studied.
Conventional MR sequences used in whole body
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A)
Özgen et al.
B)
C)
Figure 3. 44-year-old female
patient with breast carcinoma.
A. Coronal PET-CT image showing metastatic lesions (arrows).
B. Water-only and C. In-phase
T2WmD images showing
smaller metastatic lesions in
pelvic bones that could not be
differentiated on PET-CT image (arrows). Note metastatic
lesions are more prominant in
in-phase images than in wateronly images.
imaging are mostly T1W and STIR sequences (6-10).
T1W images provides relatively higher resolution and
anatomic detail in a reasonable scan time while STIR
images provides higher CNR in a longer scan time
and lower resolution. Diffusion weighted imaging
(DWI) has been recently introduced in WB-MRI and
also used in detection of bone metastasis especially
with T1W imaging (8,10). Main disadvantage of DWI
is very low resolution, relatively longer scan times,
and low specifity.
Fat suppressed T2-weighted (T2W) imaging might
theoretically supply higher resolution and good CNR
in a reasonable scan time. However, fat saturated
T2W images used in whole body imaging result in
some artifacts caused by large field of view due
to magnetic inhomogenity. Dixon method could
provide a homogenous fat suppression even in areas
of high magnetic susceptibility. T2WmD sequence
can provide 4 sets of image types using chemical
shift effect in a single session; water-only, in-phase,
Acta Med Anatol 2016;4(4): 159-163
opp-phase, and fat only while scan times remain
almost the same (11). Therefore, this technique has
been used in the last decade mostly in imaging of
the abdomen and the extremities. To the best of
our knowledge, there has been only a single study
in the literature including T2WmD imaging together
with other MR sequences and no study evaluating
the value of T2WmD imaging as a single sequence
in whole body MR imaging in detecting bone
metastasis (12).
In the literature, there were many studies about
value of WB-MRI in detecting bone metastasis in
comparison to bone scintigraphy and PET-CT (514). Bone scintigraphy is more sensitive in bone
forming osteoblastic tumors like prostate and breast
carcinomas than in osteolytic tumors. Although,
WB-MRI is shown to be equal or superior to bone
scintigraphy, clear superiority of MRI or PET-CT over
each other was not accepted in consensus (4,14).
However, 18F NaF PET-CT was shown to have the
highest sensitivity and specifity in detecting bone
metastasis in comparison to MRI, SPECT, 18F PET-CT,
CT, and bone scintigraphy (4).
In previous studies on WB-MRI, slice thickness were
generally between 6-8 mm (6-10). Spatial resolution
were also relatively low and pixel sizes were
between 1.7-4.8 mm2 (6-10). Therefore, to the best
of our knowledge, we present the highest spatial
resolution as 1x1 mm, and minimum voxel size as
4 mm3 in WB-MRI in the literature. High resolution
images with small voxel size theoretically might
result in ability to detect smaller lesions. Besides, we
presented a very short imaging time in comparison
to other studies in the literature. We believe that
using a 3.0T scanner with dedicated coils while using
a relatively new MR sequence adapted for whole
body imaging resulted in this consequence.
Although we present better results in detecting bone
metastasis in comparison to scintigraphy and PET-CT
in general, there were some lesions mostly located
in rib cage that could not be detected with WB-MRI.
This situation is consistent with the literature and
believed to be caused by respiratory movements
that would result in motion artifacts in MR images
(10,14). This shortcoming of some MR sequences
including T2WmD technique could probably be at
least partially overcomed using respiratory triggered
or breath hold imaging techniques in the future.
Our study has some limitations. First, we had very
limited number of patients included in this study
for an eligible statistical analysis. Second, although
observers were highly experienced in their fields, we
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lack interobserver variation data for both nuclear
medicine and radiology examinations. Third, we
lack comparison of T2WmD imaging with 18F NaF
PET-CT imaging, which has the highest sensitivity
and specifity in detecting bone metastasis. Finally,
although lesions accepted as metastasis were
confirmed by multiple imaging modalities and
follow-up, we lack histological reference standard
for every lesion due to ethical and logical reasons.
In conclusion, T2WmD imaging as a single sequence
may show equal or better results in detecting bone
Özgen et al.
metastasis from prostatic carcinoma in comparison
to bone scintigraphy and bone metastasis from
breast carcinoma, medullary thyroid carcinoma, and
multiple myeloma in comparison to PET-CT. Lack of
ionizing radiation, short imaging time, relatively high
resolution, and no need of contrast medium usage
are the main advantages of this imaging method.
This high-resolution imaging may further allow very
early detection of bone metastasis. Further studies
with larger patient populations are needed to reveal
exact value of this WB-MRI technique.
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