Radiol med (2014) 119:758766

DOI 10.1007/s11547-014-0395-y

MUSCULOSKELETAL RADIOLOGY

Role of whole-body diffusion-weighted MRI in detecting bone

metastasis
Riccardo Del Vescovo Giulia Frauenfelder Francesco Giurazza
Claudia Lucia Piccolo Roberto Luigi Cazzato Rosario Francesco Grasso
Emiliano Schena Bruno Beomonte Zobel

Received: 26 June 2013 / Accepted: 22 November 2013 / Published online: 18 March 2014
Italian Society of Medical Radiology 2014

Abstract
Purpose The aim of this study was to compare the results
of whole-body diffusion-weighted magnetic resonance
(DW-MR) imaging with staging based on computed
tomography (CT) and nuclear scintigraphy using Tc99m
results as the standard of reference.
Methods and materials Seventeen patients with known
malignant tumours were included in the study. The thorax
and the abdomen were imaged using breath-hold diffusionweighted imaging and T1-weighted imaging sequences in
the coronal plane. Location and size of osseous metastases
were documented by two experienced radiologists. Wholebody DW-MR imaging findings were compared with
results obtained at skeletal scintigraphy and CT bone
survey.
Results The mean examination time for whole-body DWMR imaging was 25.5 min. All bone metastases regardless
of the size were identified with whole-body DW-MR
imaging; MR imaging depicted more bone metastases than
CT. Skeletal scintigraphy depicted osseous metastases in
13 patients (with greater sensitivity to the lower limb),
whereas whole-body DW-MR imaging revealed osseous
metastases in 13 patients (with greater sensitivity to the
spine). DW-MR did not show good results for detection of
rib cage metastases. The additional osseous metastases

R. Del Vescovo (&)
G. Frauenfelder
F. Giurazza

C. L. Piccolo
R. L. Cazzato
R. F. Grasso
B. B. Zobel
Department of Radiology, Campus Bio-Medico University
of Rome, Rome, Italy
e-mail: r.delvescovo@unicampus.it
E. Schena
Department of Biomedical Engineering, Campus Bio-Medico
University of Rome, Rome, Italy

123

seen with MR imaging were confirmed at follow-up

examinations and some had a change in therapy. MR
identified 22 % more metastatic lesions when compared to
bone scintigraphy and 119 % when compared to CT. Bone
scintigraphy identified 80 % more metastatic lesions when
compared to CT. On a per-patient basis, whole-body DWMR imaging revealed sensitivity and specificity values of
100 %.
Conclusion Whole-body DW-MR imaging was more
sensitive in the detection of osseous metastases than were
skeletal scintigraphy and CT bone survey.
Keywords MR
Whole-body MR
Metastasis
Bone
lesions
CT
Bone scintigraphy

Introduction
Diffusion-weighted imaging (DWI) is a quantitative magnetic resonance technique that measures the random
(Brownian) motion of water molecules in biological tissues. Free diffusion represents chaotic and high water
mobility. In human tissues, water motion is locally hindered by the presence of cell membranes, vascular structures and fibrotic tissues, so the degree of restriction to
water diffusion is inversely correlated to tissue cellularity
and the integrity of the cell membranes. By measuring
water mobility in tissues, it is therefore possible to obtain
information about local microstructural differences and the
presence of any pathological alterations. Widely used in
the study of intracranial diseases and cerebrovascular
accidents [1], DWI is of increasing interest for the detection of primary or metastatic cancers [2, 3], as tumoural
tissue consists of densely cellular and highly vascularised
structures.

Radiol med (2014) 119:758766

Diagnostic work-up in the evaluation of oncological

patients includes some staging procedures that play key
therapeutic and prognostic roles. Since metastases may
affect any organ, imaging techniques most commonly
involve computed tomography (CT), magnetic resonance
(MR), ultrasonography (US) and bone scintigraphy (BS).
Bone scintigraphy is one of the most frequently ordered
investigations for suspected bone metastases, particularly
during oncological follow-up, and it remains a reference
modality for oncologists [4], although there are wellknown limitations affecting its specificity and sensitivity
[5]. Despite the increasing use of DWI as an adjunct in
evaluating tumour patients due to its relatively easy and
time-effective application, systematic reports evaluating its
technical feasibility, especially in terms of image quality
and robustness of apparent diffusion coefficient (ADC)
measurements are rare and only focus on limited parts of
the body, with few experiences addressing whole-body
DWI. Moreover, experience with DWI within the concept
of whole-body MRI including conventional T1w and shorttau inversion recovery (STIR) sequences in the diagnostic
practice is still limited [6].
The aim of our study was to assess the diagnostic value
of whole-body MRI, including DWI sequences, in the
detection of skeletal metastases in comparison with wholebody CT and BS to determine the utility of whole-body
DWI as a component of the whole-body MR examination
for the diagnosis and follow-up in patients affected by bone
metastases. Moreover, we wanted to verify the application
and diagnostic value of each technique depending on the
different anatomical distributions of skeletal metastases.

Materials and methods

Patients
From January 2011 to March 2012, a total of 17 patients
(11 women and six men; mean, age 57 years; age range
4076 years) with malignant tumours were included in this
retrospective study to detect bone metastasis. Histological
proof of malignancy at the site of primary tumour was
obtained in all cases.
Malignant tumour locations were: breast (n = 7), prostate (n = 2), lung (n = 2), pancreas (n = 1), stomach
(n = 1), bladder (n = 1), colon (n = 1), thyroid (n = 1),
and lymph node (n = 1). All patients gave their informed
consent prior to each examination.
Patients were recruited either during staging procedures
or follow-up. They were examined using whole-body DWMR imaging as well as whole-body CT and BS, with an
average interval of 14 days (range 030 days). The inclusion criteria were as follows: adults with histologically

759
Table 1 Patient characteristics
Patient

Age (years)

Gender

Primary tumour

41

Breast

53

Breast

45

Breast

40

Breast

62

Breast

61

Prostate

69

Prostate

57

Pancreas

69

Lung

10

46

Lymph node

11
12

57
62

M
M

Thyroid
Colon

13

53

Breast

14

76

Lung

proven primary tumour, curative treatment at least 1 year

before the examination and no history of another
malignancy.
The patients characteristics are summarised in Table 1.
Whole-body DW-MR imaging
Due to convention derived from various reports in the literature [68], the examination was designed as a wholebody examination, although only regions from the head to
the middle of the tibia were considered.
All MRI examinations were performed using a 1.5-T
Siemens Magnetom Avanto System (Siemens Healthcare,
Erlangen, Germany) with the patient in supine and feetfirst position with arms in adduction. A moving tabletop
and tabletop extender were used, generating a longitudinal field of view (FOV) of 2,000 mm and a transverse
FOV of 530 mm. The larger FOV enables head-to-toe
scanning of all adult patients without repositioning [9].
Two sequences were used for the whole-body MRI: T1
gradient echo sequences; single-shot STIR spin-echo (SE)
echo-planar imaging sequences for DWI, conducted with
two b values of 50 and 500 s/mm2. Diffusion weighting
was archived by applying pairs of motion-probing gradients before and after the 180 radiofrequency pulse of
the spin-echo T2-weighted sequence in three orthogonal
directions (X, Y and Z). Conventional T1 turbo spin-echo
(TSE) and T2 STIR were acquired both in the axial plane
from the base of the skull to the middle of the tibia and
for the whole spine in the sagittal plane, divided into five
stacks. Every stack consisted of 54-slice TSE images that
were acquired using the integrated body coil only.
Intravenous paramagnetic contrast agent was not
administered.

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Other technical parameters were: slice thickness 6 mm,

intersection gap 1.8 mm, echo train length 184, echospacing 0.87 ms, receiver bandwidth 1,628 Hz/pixel,
number of excitations 3, GRAPPA 2, matrix 106 9 192.
The overall scan time for every whole-body MR examination was less than 35 min, including positioning and
acquisition of all data sets. The average interpretation time
for the whole-body MR images was approximately 9 min.
Computed tomography
All CT exams were performed using a 64-slice CT scanner
(Siemens, Somatom Sensation). CT was performed from
the skull to the pelvic floor according to a standardised
protocol. CT parameters were as follows: 240 mAs,
120 kV, 0.5 s/rotation, 5 mm slice thickness. An intravenous iodine-based contrast medium was administrated and
bone lesions were studied during the portal venous phase.
The mean acquisition time, including needle insertion for
the administration of contrast medium, was 7 min.
Metastases were classified as osteolitic, mixed and osteoblastic, with regard to their density measured in Hounsfield
Units (HU), depending on the primary tumour
characteristics.
Bone scintigraphy
Whole-body planar imaging in the anterior and posterior
positions was performed 3 h after intravenous injection of
740 MBq of Tc99m-HMDP (Schering Pharma, Brussels,
Belgium). Images were acquired using a dual-headed
whole-body scanner with a low-energy, high-spatial-resolution collimator. The preset scan speed was 12 cm/min
and the matrix size 256 9 1,024 pixels.
Image analysis
On whole-body MR, a lesion was considered positive for
metastatic bone disease when there was a focal, or a diffuse, hypointense bone marrow signal compared with
adjacent muscle on T1-weighted images and intermediate
or high signal intensity relative to the surrounding marrow
on STIR imaging, which could not be explained by a
degenerative, inflammatory or traumatic cause [10]. Areas
of low signal intensity on both T1-weighted and STIR
sequences were interpreted as sclerosis. Furthermore, criteria for malignancy were periosteal tumour infiltration or,
for evaluation of the spine, signal changes extending into
the pedicles and bulging of the anterior or posterior margin
of the vertebral body [11]. Lesions were considered benign
if there was a high signal intensity on T1-weighted images
or if they were located close to degenerative changes of the
vertebral endplates or near joint surfaces.

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Radiol med (2014) 119:758766

On DWI, a lesion was considered malignant when there

was a focal or diffuse signal intensity increase in conjunction with the b value increment. Lesions located
directly adjacent to degenerative changes of the vertebral
endplates or near joint surfaces or without high signal
intensity on DWI were considered not to be malignant [12]
(Figs. 1, 2).
For each patient, a whole-body reconstruction in coronal
scan planes was performed both for T1-weighted sequences
and DW images with ADC map; the images were obtained
by the union of three separate acquisition stacks, divided
into the neck-thorax, abdomen-pelvis and femur-tibia.
Starting from T1-weighted sequences, low signal
intensity lesions were detected and then were confirmed on
the DW sequence, calculating the total number of metastases per patient and the average size of the metastases in
relation to the anatomical district examined. Furthermore,
depending on the measurement, the skeletal lesions were
grouped into three size ranges (110 mm; 1120 mm;
[20 mm). BS was not considered for this classification
due to the difficulty in obtaining an accurate value of lesion
size.
On CT, images obtained with the bone window permitted measurement of the HU in healthy and pathological
bone tissue. Malignant lesions were suggested by the presence of lytic, sclerotic, or mixed lytic-sclerotic intramedullary changes or bone lesions with accompanying
adjacent soft tissue abnormality. In the spine, lesions
located at the posterior part of the body, or at the pedicles,
were considered malignant, whereas lesions located at the
facet joins, endplates or posterior aspect of the spinous
process were considered benign [13].
On BS, a focal lesion was regarded to be malignant
when the distribution and pattern of focal tracer accumulation could not be explained by degenerative or posttraumatic changes.
A classification system was created for each technique,
based on the anatomical distribution of bone metastases.
Considering the low sensitivity of DW-MR imaging in the
evaluation of skeletal metastases in regions such as the
skull and ribs and, on the other hand, the high sensitivity of
BS in detecting metastases in regions such as skull and
thorax bones [14, 15], the division into locations considers
three regions for each examination: axial skeleton (AS:
cervico-thoracic and lumbo-sacral spine, clavicle, pelvis)
lower limbs (LL: lower extremities up to the tibial diaphysis) and chest (CH: sternum, ribs, scapula, including the
proximal humerus and the mandible). The division by
anatomical distribution is intended to ensure maximum
uniformity of the data and the best comparison among the
radiological techniques considered.
The analysis was carried out on each of the 17 patients,
for a total of 48 examined areas.

Radiol med (2014) 119:758766

761

Fig. 1 A 46-year-old female patient with breast cancer: whole-body magnetic resonance imaging in the coronal plane shows a vertebral bone
lesion in T1-weighted (a) and diffusion-weighted (b) sequences (arrows). Bone window imaging of the coronal CT (c) shows no vertebral lesions

Fig. 2 A 58-year-old male patient with lung cancer: whole-body

magnetic resonance imaging in the coronal plane demonstrates a right
iliac bone lesion in T1-weighted (a) and diffusion-weighted

(b) sequences (white arrows), while coronal CT (c) with the bone
window shows no lesions in the same district

Each whole-body DW-MRI and CT examination was

evaluated by two radiologists (D.V.R. and G.R.) with,
respectively, 5 and 10 years of experience in the field of
oncological imaging. They independently read the images,
and any discrepancies were resolved by a discussion to
reach a final consensus. To assess interobserver agreement,
Cohens kappa coefficient was evaluated. Bone scintigrams
were evaluated by two experienced nuclear medicine
physicians. Bone metastases were assumed in the event of
clear evidence of a skeletal lesion on each procedure
(Fig. 3).

subjected to BS. No metastases were found in the upper

and lower extremities.
The final study considers 14 patients. CT was positive in
11/14 cases (79 %); Whole-body MRI and BS were positive in 13/14 (93 %). We compared the results of wholebody DW-MRI with those of CT and BS.
The total number of lesions identified with the three
different procedures was n = 74 for CT, n = 162 for
whole-body DW-MRI and n = 133 for BS. The DW-MRI
analysis showed an elevated interobserver agreement in the
assessment of lesion number, as demonstrated by Cohens
kappa coefficient (k = 0.83).
For 11/14 patients, whole-body MRI and CT concordantly demonstrated metastatic spread, but were disconcordant for lesion number in 1/11 (9.1 %) cases. In the
remaining 10/11 (90.9 %) cases, discordant results demonstrated 94 % of the additional lesions detectable by
whole-body MRI (138 vs. 71). In the other 3/14 cases, two
(cases #5 and #13) had positive whole-body MRI and
negative CT. In these two cases, MRI detected multiple
metastases in the axial region and lower limbs; the other
one (case #4) had negative results on both examinations.

Results
All whole-body MRI, BS and CT were completed successfully by patients without any adverse effects.
We detected bone metastases in 14 of 17 patients, with
an overall incidence of 82 %. Fourteen of 17 patients
completed all three of the examinations; the other three
patients, after a diagnosis of bone metastases on CT,
showed negative results on MRI so these patients were not

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Radiol med (2014) 119:758766

Fig. 3 A 69-year-old male

patient with prostate cancer:
whole-body magnetic resonance
imaging in the coronal plane
demonstrates a left acetabular
lesion in T1-weighted (a),
diffusion-weighted (b) and
ADC maps (b) sequences (white
arrows), while bone
scintigraphy (d) was considered
negative for bone metastases in
the same district

For 12/14 patients, whole-body MRI and BS concordantly demonstrated metastatic lesions, but were disconcordant for lesion number and involvement site in only
1/12 (8.3 %) patients (case #7). In the remaining 11/12
(91.7 %) cases, discordant results demonstrated 23 % of
the additional lesions detectable by whole-body MRI (159
vs. 129).
For the other 2/14 cases, one (case #3) had positive
whole-body MRI and negative BS results; in this patient,
whole-body MRI detected three metastatic lesions in the
axial region. One patient, conversely, had positive BS and
negative whole-body MRI (case #4) results; in this patient,
BS detected a total of three metastases, two of them in the
axial skeleton (pelvis) and the other in the chest (rib).
Hence, MR identified 22 % more metastatic lesions when
compared to BS and 119 % more than CT. Bone scintigraphy identified 80 % more metastatic lesions when compared to CT.

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The lesions observed using the different diagnostic

procedures are shown in Table 2 and are categorised by
anatomical site. In each of the 14 patients and for each
technique, lesions were counted in every anatomical site
(AS, LL and CH). The results show that more lesions are
observable with MR compared to CT in the axial skeleton
(121 vs. 45) and in the lower limbs (34 vs. 11), while MR
presents limited sensitivity in identifying lesions in the
chest (7 vs. 18).
It can be inferred, by comparing the results obtained
with whole-body MRI and BS, that more lesions are
observable using whole-body MRI in both the axial skeleton (121 vs. 48) and lower limbs (34 vs. 26). However, BS
found more lesions in the chest (59 vs. 7). Whole-body
DW-MRI is characterised by an advanced sensitivity in
identifying lesions in the lower limbs and axial skeleton,
while presenting a limited receptivity in the chest. The
results of lesion distribution are shown in Graph 1. In

Radiol med (2014) 119:758766

763

Table 2 Anatomical distribution of bone metastases in different

patients
Patient

CT

WB-DW-MRI

BS
AS

AS

LL

CH

AS

LL

CH

LL

CH

31

10

3
4

10

10

14

11

10

10

34

19

10

22

12

13

10

14

10

21

10

CT computed tomography, WB-DW-MRI whole-body diffusionweighted magnetic resonance imaging, BS bone scintigraphy, AS
axial skeleton, LL lower limbs, CH chest

particular, regarding the axial district, whole-body DWMRI showed a higher number of lesions, followed by BS
and then by CT. For the lower limbs, whole-body DW-MRI
still showed a higher number of lesions, followed by BS
and then by CT. For the chest region, there was a marked
higher sensitivity of BS in detecting bone metastases;
otherwise, whole-body DW-MRI had a lower sensitivity in
detecting bone lesions in the chest.

Comparing the results obtained using whole-body MRI

and CT and classifying them based on lesion dimension, it
might be inferred that more lesions are observable with MR
regardless of the lesion size: 158 % increase in observed
lesions with a diameter (d) measuring less than 10 mm (98
vs. 50), 79 % with a diameter measuring between 10 and
20 mm (50 vs. 28) and 62 % with a diameter C20 mm (13
vs. 8). Results for lesion size are shown in Graph 2. In both
whole-body DW-MRI and CT, a subdivision based on
lesion size was made, underlining how whole-body DWMRI had a higher sensitivity in detecting bone metastases
independently from size in comparison with CT, and it also
showed that in both procedures, the majority of lesions
were included in the dimension group beneath 10 mm.
Patient-by-patient analysis revealed multiple lesions on
BS in 11/13 (84 %) of the patients with positive MRI
findings and multiple lesions on MRI in 12/13 (92 %) of
the patients with positive BS. Analysis of the 42 examined
areas revealed metastatic bone metastases in 30 (72 %)
regions. CT demonstrated tumour spread in 17/30 areas
(57 %), while whole-body MRI demonstrated spread in
23/30 (77 %) and BS in 24/30 (80 %). None of the enrolled
patients was classified as an equivocal case.

Discussion
One of the most common sites of distant metastases is the
cellular bone marrow (5070 %), especially in patients
with breast and prostate cancer. Bone metastases cause
much of the morbidity and disability in patients suffering
from tumours [16]. Traditionally, BS has been the standard

Graph 1 Anatomical
distribution of bone metastases.
Whole-body DW-MRI results
are in light grey, BS results are
in dark grey and CT results are
in black

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Radiol med (2014) 119:758766

Graph 2 Detection of bone

metastasis considering lesions
size. Whole-body DW-MRI
versus CT

imaging investigation used for the detection or exclusion of

skeletal metastases, and it is widely used to assess metastatic spread in patients with breast, prostate or lung cancer
[17, 18], as BS is more sensitive when sufficient osteoblastic reaction has occurred. However, supplemental
imaging studies are needed to define unclear findings, as
BS has limited specificity [19].
Whole-body MRI within a single session has become
feasible for the evaluation of the presence of metastases
and/or for the evaluation of primary cancers, due to recent
advances [15, 20, 21] such as short data-acquisition times,
no ionising radiation and no injection of isotopes or contrast medium. In several studies, whole-body MRI has
shown better results than skeletal scintigraphy [12, 16, 22
24] in the detection of bone metastases. In addition, with
the development of the body diffusion-weighted technology with background body signal suppression by Takahara
et al. [7], high spatial resolution whole-body DWI has
become available.
The diagnostic added value of whole-body DWI
sequences has been established [12]. In comparison with
conventional whole-body MRI, its sensitivity, specificity
and positive predictive value (PPV) in detecting bone
metastases are superior to those of both conventional MRI
and BS.
Particularly, whole-body DWI excels at bone marrow
assessment for diagnosis and for therapy evaluation, where
it can potentially address unmet clinical and pharmaceutical needs for reliable measurement of tumour response
[25]. With this modality, no ionising radiation is administered and no injection of any contrast medium is necessary,
allowing whole-body DWI to be used in routine clinical
practice.
Moreover, multislice CT has been proposed as an
alternative to BS for whole-body screening of the skeletal
system due to an equivalence found by Groves et al. [26]

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between BS and CT in detecting bone metastases. However, a recent study comparing multidetector CT with MRI
in the detection of osseous metastases of the spine found a
greater sensitivity of MRI, with equivalent specificities
[27].
All of these data are in agreement with our study that
demonstrates that whole-body DW-MRI can be used for
assessment of bone metastases in patients with cancer.
Comparative studies of imaging methods have the major
bias that none of them can guarantee 100 % diagnostic
accuracy as each may be affected by false-positive and
false-negative results. Validation of a new imaging
method, such as whole-body DW-MRI, requires a comparison with the most consolidated standard in the clinical
management of patients [28].
Our results also demonstrate that whole-body MRI has a
higher diagnostic accuracy than CT and a comparable level
of agreement to BS in detecting bone metastases, independently from the primary tumour site. In terms of distribution of bone metastases, our study confirmed that
whole-body DW-MRI is better than BS in detecting lesions
in the axial skeleton. More importantly, there were two
cases in our sample in which BS was completely negative
for axial bone metastases, with positive results shown by
whole-body DW-MRI. Whole-body DW-MRI failed to
depict a considerable number of lesions in the ribs but
depicted more lesions in the spine, pelvis and lower limbs.
Thus, in an uncertain diagnosis concerning an axial skeletal
metastasis, the availability of DW sequences can help to
confirm/deny the suspect lesion. Whole-body DW-MRI
failed in the detection of lesions in the chest, as already
demonstrated in other studies [15, 29]. It has been suggested that this limitation is due to artefacts related to
pulsation and breathing movements in the thorax, which
make examination of the ribs, sternum and scapula more
difficult. Furthermore these flat bones are not well-

Radiol med (2014) 119:758766

visualised on coronal images [15]. Motion-related signal

intensity decreases may explain why metastatic lesions in
the bone marrow of the anterior chest wall are sometimes
relatively less conspicuous than lesions found in the spine
and paraspinal regions [25]. In terms of the dimensions of
bone metastases, the larger the size of the lesion, the
greater the ability of whole-body DW-MRI to find it in
comparison to CT.
In our series, a majority of cases were concerned
primary breast and prostate cancers, in which there were
too many lesions to count, in some cases hundreds [26].
Many of these lesions are often very small and not
identified on scintigraphy, but can be seen on MRI or
CT. Thus, we could diagnose diffuse bone involvement
(more than ten metastases) with a higher sensitivity than
with BS [16]. The detection of other extra-small lesions
probably makes a difference in patient management,
even if it is minimum. Comparing the results obtained
using whole-body MRI and CT and classifying them
based on lesion dimension, it might be inferred that more
lesions are observable using MR regardless of lesion
dimension.
Further, whole-body DW-MRI has a more extensive
anatomical coverage, which results in an ability to identify
also extraskeletal lesions with therapeutic and prognostic
significance.
This study has certain limitations. For ethical reasons,
patients could not be followed up with skeletal scintigraphy
after 6 months. Also due to ethical reasons, CT examinations, intended as total-body scans, were done not covering
the portion between the femoral diaphysis and tibial
proximal epiphysis. Thus, the very high difference in
detecting metastases (in particular in the lower limbs)
between whole-body DW-MRI and CT could be a result of
this limitation. Moreover, we were unable to obtain histological verification of all skeletal metastases. Another
limitation is related to the heterogeneity of the patients
primary tumours, in that BS, in which metastases are
usually depicted when sufficient osteoblastic reaction has
occurred, may demonstrate a lower sensitivity in tumours
eliciting a particularly poor osteoblastic response [30].
DWI seems to be a sensitive but rather unspecific
modality for the detection of bone metastatic disease.
High-quality prospective studies regarding whole-body
MRI in detecting bone metastases still need to be conducted [21].
In conclusion, to the best of the knowledge, no previous
studies have compared concurrently CT, whole-body DWMRI and BS. From the comparison of these modalities in
our present study, whole-body DW-MRI is confirmed as an
important complementary examination for the characterisation of bone metastases in patients with equivocal results
on CT or whole-body BS.

765
Conflict of interest Riccardo Del Vescovo, Giulia Frauenfelder,
Francesco Giurazza, Claudia Lucia Piccolo, Roberto Luigi Cazzato,
Rosario Francesco Grasso, Emiliano Schena, Bruno Beomonte Zobel
declare no conflict of interest.

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