Biomed Imaging Interv J 2006; 2(2):e12
© 2006 Biomedical Imaging and
Diffusion weighted MR imaging in acute vertebral
compression fractures: differentiation between malignant and benign causes
AA Bhugaloo1, MBBS, MRad,
BJJ Abdullah1, MBBS, FRCR,
YS Siow2, MBBS, MS(Ortho),
KH Ng1, PhD, MIPEM, DABMP
1 Department of Biomedical Imaging, Faculty of
Medicine, University of Malaya, Kuala Lumpur, Malaysia
2 Department of Orthopaedic Surgery, Faculty of Medicine, University
of Malaya, Kuala Lumpur, Malaysia
Aim: The primary objective of this study was to
evaluate the specificity and sensitivity of diffusion weighted MR imaging (DWI)
in the differentiation and characterisation between benign and malignant
vertebral compression fractures compared with conventional T1 WI, T2 WI and fat
suppressed contrast enhanced T1 WI in the Malaysian population.
Materials and Methods: Thirty five patients with 68
vertebral compression fractures were imaged using the conventional T1 WI, T2
WI, fat suppressed contrast enhanced T1-weighted, and steady state free
precession diffusion-weighted (SSFP DWI) sequences on a 1.5 T MR scanner.
Signal intensities were analysed qualitatively for all the sequences by
comparison to adjacent normal marrow. A quantitative assessment of the signal
intensity in the SSFP DWI was also performed.
Results: T1 WI and T2 WI images are of limited
diagnostic value because of the variability in signal intensities. Contrast
enhanced images had sensitivity and specificity of 93% and 71%, respectively
with a negative predictive value (NPV) of 93%. On diffusion-weighted MR
imaging, sensitivity was 87% with specificity of 92%. The positive predicative
value (PPV) and NPV were both 90%. The quantitative assessment of ratio
revealed a statistical significant difference between the benign (0.96) and the
malignant (1.73) group of lesion (Mann-Whitney U-test, p=0.0001).
Conclusions: We found that absence of contrast
enhancement has a high NPV (90%) while SSFP DWI has both a high PPV (90%) and
high NPV (90%) in detecting malignant vertebral compression fractures.
Furthermore, in our study the ratio of lesion intensity technique offers an
excellent criterion to differentiate between the benign and malignant lesions,
and the presence of iso- or hypointensity of the collapsed vertebral bodies is
suggestive of a benign lesion while hyperintensity is highly suggestive of
malignancy. We also found that using the NLMR showed a statistical significant
difference between the malignant and benign groups (p<0.0001) with
osteoporotic and malignant lesions have mean values of 0.96 (SD 0.25) and 1.73
(SD 0.4) respectively. © 2006 Biomedical Imaging and Intervention Journal. All
Keywords: Diffusion weighted imaging; MRI; metastases;
Vertebral fractures may be detected on radiographs, computed
tomography or radionuclide studies, but in today?s clinical environment, the
specific discrimination between benign and malignant vertebral compression
fractures relies heavily on MR imaging features. Since most bony metastases are
hematogeneous in origin, the axial skeleton is the most common site of skeletal
metastases initially due to abundant vascularisation and red bone marrow .
However, osteoporotic compression fractures are also a common occurrence in the
spine and can be confused with metastatic compression fracture in the acute
phase. Since the prognosis and management differs in these two entities,
accurate diagnosis is important.
The primary objective of this study was to evaluate the
specificity and sensitivity of diffusion weighted MR imaging (DWI) in the
differentiation and characterisation between benign and malignant vertebral
compression fractures compared with conventional T1 WI, T2 WI and fat
suppressed contrast enhanced T1 WI in the Malaysian population.
MATERIALS AND METHODS
The study was carried out prospectively from July 2002 to
June 2004. Thirty five consecutive patients with a history of vertebral
compression fracture detected by other imaging modalities were included.
Selected patients were imaged within six weeks from the time of presentation. Patients
with history of vertebral compression fracture of more than six weeks, patients
who were not MR compatible as well as patients who had vertebral collapse
secondary to disciitis or osteomyelitis (as they had other features to suggest
their diagnosis e.g. paravertebral enhancing collection and/or loss of disc
spaces with erosion of the endplates) and those with sclerotic lesions were
excluded from the study. Patients with vertebral fractures secondary to severe
trauma were also excluded.
The study group consisted of 13 men and 22 women, ranging
from 25 to 88 years, with a mean age of 62.7 (SD 14.2) and a median age of
64.5. The 68 vertebral compression fractures were noted. The patients were
imaged using the conventional T1 WI, T2 WI, fat suppressed contrast enhanced
T1-weighted, and steady state free precession diffusion-weighted (SSFP DWI)
sequences  (Table 1) using a spinal phased array coil on a 1.5 Tesla super
conducting MR System (Magnetom Vision, Siemens, Erlangen, Germany). The SSFP
DWI sequence used 18 NEX with a diffusion pulse length of 2 ms. The diffusion
gradient was 24mT/m with a relatively low b value (165s/mm2). The diffusion
gradient was applied only in the readout direction based on the previous
observation that no diffusion anisotropy was found in either the phase or slice
direction . Additional axial views were obtained only in those cases where
the marrow changes were focal.
Table 1 Scan parameters for the MR sequences
The SSFP sequence was chosen as the other types of DWI (Spin
Echo and EPI) were not available on our system. In addition, SSFP MR Diffusion
technique has relatively good image quality, SNR and Contrast to Noise Ratios
and can be acquired with a relatively short acquisition time (approx. 1 min and
49 seconds in our study) with moderate gradient strengths. Also, there have
been numerous studies using this sequence and would therefore be more
comparable with the work of others.
The 68 lesions were distributed from the sixth cervical to
the fifth lumbar vertebral bodies with most occurring in the T10 to L2
vertebral bodies (50/68). The medical records of these patients were reviewed
(BJJA, AAB, YSS) to document the final diagnosis based on either or both
clinical and histopathological grounds.
Of the 68 lesions in 35 patients, 38 lesions were
established as being benign, while the remaining 30 were categorised as
malignant. With regards to the metastases: seven of the lesions were from a
sarcoma, four from lung carcinoma, and two each from nasopharyngeal carcinoma,
breast carcinoma, hepatocellular carcinoma, renal cell carcinoma and
Non-Hodgkin lymphoma. In addition, four of collapsed vertebral bodies were due
to multiple myeloma.
The images obtained were analysed both qualitatively and
quantitatively. For qualitative evaluation, the images were analysed and
categorised by two experienced radiologists (BJJA, AAB) independently and then
in a consensus review. The lesions were characterised as focal or multiple,
with or without involvement of the vertebral elements. The signal intensities
of the fractured vertebra were visually compared with that of the presumed
normal vertebra on all (T1 WI, T2 WI, fat suppressed contrast [CE] enhanced
T1-weighted and DWI) and categorised as hypointense, isointense or hyperintense
relative to the areas of presumed normal marrow. Statistical evaluation of the
qualitative analysis between the two groups was performed using the
Mann-Whitney U test.
For the quantitative assessment, the SSFP DWI MR images were
analysed with the aid of the OSIRIS software versions 4.19 (Geneva, Switzerland).
Signal intensity in the fractured vertebra was quantified by placing a ROI over
the lesion. The size of the ROI used occupied at least three quarters of the
area of abnormal or normal signal intensity but excluding the end-plates,
cortical margins, disc spaces or adjacent normal or abnormal marrow. The
abnormal marrow was that seen completely in the selected sagittal DWI images
(to reduce partial voluming) while for normal adjacent marrow all the sequences
were evaluated (T1, T2, CE MRI and DWI) to ensure that there were no signal
abnormalities within the vertebral body selected. The ROI was placed at
approximately the same distance from the posterior part of the vertebral body.
This was to compensate for any differences in signal intensity as a result of
image normalisation. A ratio of the quantified signal intensity of the
collapsed vertebra to the presumed normal vertebral bone marrow [termed
Normalised Lesion to Normal Marrow (NLNM) ratio] was then calculated and
normalised to the normal marrow as follows: [SI (abnormal marrow) ? SI (normal
marrow)]/ SI (normal marrow)].
The mean value of the NLNM ratio was calculated for each
category of compression fracture. A composite histogram was produced for all
the patients in the benign and the malignant group of fracture. A box plot of
NLNM ratio was also obtained for the benign and the malignant group of
compression fractures which shows a maximum and minimum value, together with a
mean value. Statistical analysis was performed by using Student?s t-test.
A p value of less than 0.05 was considered a statistically significant
Significance of focal or multiple lesions
Eighteen patients had a single lesion, while 17 patients had
two or more lesions (there were seven patients who had more than two lesions).
Of those with a single lesion, only 44% (8/18) had malignant compression
fractures with the remaining 56% (10/19) having osteoporotic fractures. For
those with more than one lesion, 59% (10/17) were diagnosed as having malignant
compression fracture while 41% (7/17) had osteoporotic compression fractures.
Role of conventional T1 and T2 weighted imaging
All the affected vertebrae in the benign group and 29 of the
30 lesions in malignant group of compression fractures were either isointense
or hypointense with respect to the presumed normal marrow on the T1 W images
(Table 2). On T2 WI, 50% (15/30) of the malignant lesions were either iso- or
hypointense, while the remainder (15/30) were hyperintense. Only 13% (5/38) of
osteoporotic compression fractures showed high signal intensity on the T2
Table 2 Signal Intensity of the fractures
on T1, T2, Contrast Enhancement and DWI.
With regards to changes of the end plates and disc spaces,
these changes were seen in 11% (4/38) and 10% (3/30) of the osteoporotic and
malignant groups respectively. Posterior element involvement was seen in 23%
(7/30) of lesions in the malignant group but in none of the osteoporotic
lesions (0/38). Paraspinal masses were seen in 5% (2/38) and 23% (7/30) of the
osteoporotic and malignant groups respectively. Cord compression was noted in
27% (8/30) of the malignant and 11% (4/38) of the osteoporotic groups.
Contrast enhanced images
On contrast enhanced imaging, 93% (28/30) of the malignant
and 29% (11/38) of the osteoporotic compression fractures showed enhancement
(Table 2). The sensitivity and specificity of contrast enhancement for
malignant vertebral compression fractures was 93% and 71% respectively. The
positive predictive value of contrast enhancement was 71% (28/39) while the
negative predictive value was 93% (27/29) i.e. the absence of enhancement makes
the likelihood of benign fractures high.
Qualitative analysis of DWI MR imaging
The signal intensities of the osteoporotic vertebral
fractures on the DWI was low in 68% (26/38) of lesions (Figure 1), isointense
in 24% (9/38) of lesions and hyperintense in only 8% (3/38) of lesions (Table
2). In the malignant group, the fractured vertebral bodies were hyperintense in
87% (26/30) of lesions (Figure 2) and hypointense in 13% (4/30) of cases, while
there were no lesions which were isointense. Using the presence of high signal
intensity on DWI as indicator of malignant disease, the sensitivity and specificity
of DWI was 87% and 92% respectively. Of the 26 malignant lesions which were
high signal on DWI, only 6 were high signal on T2 WI with 10 each being
iso-intense and low signal. The positive predictive value of high signal on DWI
for malignant fractures was 90% (26/29) while the negative predictive value was
also 90% (35/39). There were 2 lesions in one patient which showed contrast
enhancement even though the DWI signal was low.
Figure 1 Mid sagittal
MR images of the spine with an osteoporotic fracture of L1
vertebral body. Mid sagittal SSFP DWI MRI at a TE of 5ms (A)
and 3ms (B) show low signal intensity (arrow) in the collapsed
L1 vertebral body compared to the normal bone marrow in adjacent
vertebral bodies. There is no contrast enhancement of the
L1 vertebra (C) after gadolinium administration.T1 W MR image
(D) shows low signal in the L1 vertebra.
Figure 2 MR images of
a patient who presented with compression fracture of L2 vertebral
body. There are low signals on both T1 (A) and T2 (B)-weighted
MR images, with marked contrast enhancement (D) of L2 and
S1 vertebral bodies. SSFP DW MR image shows high signal in
the compressed L2 (arrow) as well as in S1 vertebral bodies
suggestive of malignancy. Further investigation revealed a
Quantitative analysis of DWI MR imaging
A frequency distribution was produced for both the benign
and the malignant group of vertebral compression fracture (Figure 3). The
Normalised Lesion to Normal Marrow (NLNM) ratio for the benign group of
compression fractures revealed a mean of -0.04 with a SD of +0.25 while that
for the malignant group was 0.74 with a SD of +0.47. A box plot of NLNM ratio
(Figure 4) was also obtained for each group of lesion. The quantitative
assessment revealed a statistical significant difference between the two groups
of lesions, (Mann-Whitney U-test, p=0.0001).
Figure 3 Frequency distribution
of the normalised ratio of lesion to normal marrow signal
intensity of malignant and benign vertebral compression fracture
Figure 4 Box and whisker
plot of the normalised ratio of lesion to normal marrow signal
intensity of benign and malignant compression fracture. The
boxes show minimum and maximum values for each category and
the whiskers indicate the =/- 2SD. Those values beyond these
(the outliers) are plotted but excluded from the calculation
of SD. The mean ratio, as indicated by a horizontal line in
the box, is 0.9 for the benign group of lesion and 1.65 for
the malignant group. The mean value is significantly different
for the two categories and there is no significant overlap
of values between the two boxes.
Benign vertebral lesions occur in approximately one third of
cancer patients  while metastatic vertebral lesions account for 39% of bony
metastases in patients with primary neoplasm . Differentiation between
malignant and benign vertebral compression fracture is a common problem in
medicine. This is especially so in the elderly patients who are predisposed to
benign compression fracture caused by osteoporosis, where establishing the
correct diagnosis is of great importance in determining treatment, surgical
approach, and prognosis [6,7]. In this group a benign fracture can result from
minor trauma and make the interpretation of the lesion difficult if there is a
known primary elsewhere.
Although MR imaging using conventional T1 WI and T2 WI has
proved helpful in differentiating between benign and malignant causes of
vertebral collapse, confident diagnosis is not always possible. Morphologic
signs such as the degree and pattern of bone marrow replacement, multiplicity
of lesions, paravertebral soft-tissue masses, infiltration of posterior
elements of the vertebrae [7-10] and presence of a fracture line in
osteoporotic fractures (as a linear hypointensity in the middle of the
compressed vertebral body or adjacent to a compressed endplate) usually seen on
T2- or post-contrast T1-weighted images [10,11] are common signs used for
assessing the cause of the fracture. Despite the use of these features, there
is still considerable overlap in the signal changes between acute to sub-acute
fractures from malignant fractures as was also found in this study [12,13]. The
presence of multiple collapsed vertebrae also does not suggest a benign or
malignant aetiology. In our study it was found that 59% of patients with
malignant involvement had multiple level involvements while this was seen in
41% of those with osteoporotic fractures.
CE is used to identify intramedullary spinal cord
abnormalities and extradural lesions (particularly in the epidural space) that
may result in compression of the spinal cord and alter proposed treatment,
however this has not been assessed to determine the underlying aetiology.
Benign vertebral fractures may also enhance after intravenous administration of
contrast media due to a breach in blood tissue. We found that using contrast
enhancement with fat suppression as an indicator of malignancy; the sensitivity
was 93%, the specificity was lower at only 71% while the negative predictive
value was found to be 93%. Even though dynamic contrast enhancement has been
evaluated in the characterisation of lesions in the brain, liver breast,
pelvis, etc,  this has not been evaluated in the spine.
Over the last decade, DWI MR imaging [15-17] of the
vertebral body  has received considerable attention and has been
successfully implemented for the differentiation of benign and malignant
fracture oedema (due to tumour infiltration) [19,20] although the usefulness is
still controversial [5,21]. DWI MRI provides unique tissue characterisation
that is complementary to that provided by conventional MR Imaging and is
sensitive to micro-structural changes. The reduced mobility of water in
pathologic fracture is the result of tumour cell accumulation and subsequent
reduction in the interstitial spaces that results in high signal intensity
compared with normal bone marrow. On the other hand, the increased mobility of
water attributed to an increase in the interstitial space in relation to oedema
or haemorrhage  in benign fractures [20,22-24] results in low signal
intensity in benign osteoporotic and traumatic fractures. On this basis DWI MRI
has been suggested to be useful particularly in the evaluation of vertebral
Bauer et al.  found 100% accuracy in the diagnosis
of malignant compression fractures using SSFP DWI. They also showed that even
though T1 Weighted spin echo and T2 Weighted STIR scans detected all fractures,
there was no discriminating power based on signal intensity or bone marrow
contrast ratio. In our study, we found that the SSFP DWI sequences showed a
high diagnostic accuracy in differentiating acute benign osteoporotic fracture
from pathological fractures with a sensitivity of 87%, a specificity of 92%
with a PPV of 90%. Even though the sensitivity of contrast enhanced MRI was
higher at 93%, the PPV was only 71%. We found that the NPV for low or
iso-intense on DWI was 90% for acute benign fractures.
Even though some studies  have demonstrated no advantage
of diffusion weighted scanning in the detection or characterisation of
vertebral metastases with only 34% being hyperintense on DWI, it has been
pointed out  that the patients enrolled were not the primary target group
for DWI in spine (i.e., patients with sclerotic metastases and previously
treated metastases). It has been suggested that the following inclusion
criteria be used for DWI: 1) unknown reason for the vertebral collapse, 2) lack
of sclerotic metastases, and 3) no prior therapy. None of our patients had any
prior therapy and those with sclerotic lesions were also excluded.
It has been suggested  that T2 ?shine through? may be
playing a prominent role in the appearance of the metastatic lesions on DWI and
that all the metastatic lesions that were hyperintense on DWI MRI are also
hyperintense on T2 WI. However, in our study we found that of the 26 malignant
lesions which were high signal on DWI, only 23% (6/26) were high signal on T2
WI suggesting that T2 shine through may not be the cause of increased signal on
FFSP DWI. We are unable to explain this difference, hence a study with a larger
sample size is suggested.
DWI appears to be reproducible with diverse diffusion
weighted MR techniques e.g. Spin Echo DWI, the Echo Planar DWI, and the Steady
State Free Precession DWI (SSFP) for the differentiation of benign from
malignant acute vertebral fractures . Both the spin echo (SE) and the
stimulated echo (STE) sequences have played a pioneering role in DWI with
relatively high signal-to-noise ratio (SNR) and lower sensitivity with respect
to homogeneities in the susceptibility of the measured object. However, these
sequences require long acquisition times and with significant ?ghosting?
artifacts. Echo planar Imaging DWI can be performed within a few seconds,
reduces motion artifacts and allows calculation of the ADC value though with a
lower signal to noise ratio and is prone to susceptibility artifacts. It is
therefore limited in musculoskeletal imaging. SSFP  diffusion techniques
show relatively good image quality, signal to noise (SNR) and Contrast to Noise
Ratios and can be acquired with a relatively short acquisition time (approx. 1
min and 49 seconds in our study) with moderate gradient strengths. However, due
to its complicated signal generation and its T1 and T2 dependence, precise ADC
and b values cannot be calculated. The b value for different diffusion pulse
length can only be approximated from phantom measurements with known T1 and T2
The Apparent Diffusion coefficient (ADC) expresses the
diffusion of water protons in a region of interest and is calculated by a regression
analysis of the signal and overcomes the confounding relaxation phenomena,
so-called T2 shine-through effects, and perfusion effects that may mask
diffusion related SI patterns . The ADC of normal vertebrae is
significantly higher than that of vertebral metastases and it is proposed that
ADC is a dependable and quantifiable parameter with which to distinguish
metastases  and it might be used to monitor treatment by revealing
treatment-related changes in tissue characteristics . We were unable to
determine the ADC values due to the SSFP DWI sequence chosen.
DWI MRI also has a role in other types of tissues in the
musculoskeletal system; DWI may allow differentiation of viable and necrotic tumour
tissue , to study the diffusion in cartilages  and joint effusions from
degenerative osteoarthritis, inflammation or trauma , monitor the response
to medical therapy of metastatic spine disease , allow delineation of? acute
spinal cord ischemia, determine structural integrity of the spinal cord,
improved detection of ischemic lesions, clarification of the relationship
between clinical disability and structural damage to the cord (including
degenerative disorders), and monitoring of anti-inflammatory or neuroprotective
We were not able to confirm the histological diagnosis in
all our patients as it was not possible to obtain consent for biopsies
especially in those with a diagnosis of osteoporotic fractures. But with
follow-up of those without biopsies we were able to overcome this limitation.
We were unable to quantify the isotropic diffusion coefficient since we used a
SSFP DWI sequence and therefore were not able to quantify the ADC. In addition,
DWI SSFP may exhibit hyperintensity in infectious disease similar to tumourous
fracture in vertebral bodies [31,32] while false Negativity may be accounted
for by previous radiotherapy (due to necrosis as compared with viable tumour)
or due to excessive fibrosis and bleeding. Moreover, the signal intensity on
DWI MR Images depends on the b factor, which is strongly influenced by hardware
components, imaging parameters and the pulse sequence itself . This limits
comparison between subsequent investigations, for example, follow up studies
When the findings on routine MR sequences are not completely
conclusive for the diagnosis of acute benign or malignant vertebral body
compression fracture, then the use of both contrast enhancement and diffusion
weighted MR sequence may be helpful. We found that absence of contrast
enhancement has a high NPV (90%) while SSFP DWI has both a high PPV (90%) and
high NPV (90%) in detecting malignant vertebral compression fractures. Furthermore,
in our study the ratio of lesion intensity technique offers an excellent
criterion to differentiate between the benign and malignant lesions. At a TE of
5 ms, the presence of iso- or hypointensity of the collapsed vertebral bodies
is suggestive of a benign lesion while hyperintensity is highly suggestive of
With regards to the use of semi-quantitative diffusion
measurement, even though recent studies suggest that DWI intensity values alone
are highly unspecific [20,23], we found that using the NLMR showed a
statistical significant difference between the malignant and benign groups (p<0.0001)
with osteoporotic and malignant lesions having mean values of 0.96 (SD 0.25)
and 1.73 (SD 0.4) respectively.
We would like to acknowledge the assistance of Ms. Jeannie
Wong Hsiu Ding and Mr. Tan Jin Wooi for their assistance in preparing the
statistics and graphs.
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Received 12 August 2005; received in revised form 30 September 2005; accepted 19 December 2005
Correspondence: Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Tel: +603-79502069; Fax: +603-79581973; E-mail: email@example.com (Basri J.J. Abdullah).
Please cite as: Bhugaloo AA, Abdullah BJJ, Siow YS, Ng KH, Diffusion weighted MR imaging in acute vertebral compression fractures: differentiation between malignant and benign causes,
Biomed Imaging Interv J 2006;2(2):e12
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