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Differential MRI diagnosis between brain abscesses and necrotic or cystic

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diffusion-weighted images

Article  in  Magnetic Resonance Imaging · August 2003

DOI: 10.1016/S0730-725X(03)00084-5 · Source: PubMed

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 Magnetic Resonance Imaging 21 (2003) 645– 650

Differential MRI diagnosis between brain abscesses and necrotic or

cystic brain tumors using the apparent diffusion coefficient and
normalized diffusion-weighted images
Lydie Nadal Desbaratsa, Sandra Herlidoua, Giovanni de Marcoa, Catherine Gondry-Jouetb,
Daniel Le Garsc, Hervé Deramondb, Ilana Idy-Perettia,d,*
a
Biophysique et Traitement de l’Image Médicale, UMR 6600 CNRS, Université Picardie Jules Verne, CHU Amiens, France
b
Laboratoire de Radiologie, CHU Amiens, France
c
Laboratoire de Neurochirurgie, CHU Amiens, France
d
Laboratoire de Biophysique et Médecine Nucléaire, Hôpital Lariboisière, APHP, Paris, France

Received 18 July 2001; accepted 4 December 2002

Abstract
Magnetic Resonance Diffusion-Weighted Imaging (DWI) has been reported to be helpful for the differential diagnosis between abscesses
and cystic/necrotic brain tumors. However the number of patients is still limited, and the sensitivity and specificity of the method remain
to be confirmed. The primary purpose of this study was to investigate a larger sample of patients, all investigated under the same
experimental conditions, in order to obtain statistically significant data. Moreover, there is no consensus about the appropriate values of b
required to use to make an accurate diagnosis from DWI. The secondary purpose of this study was to determine the discriminating threshold
b values for raw diffusion-weighted images and for normalized diffusion-weighted images. On the basis of 14 abscesses, 10 high-grade
gliomas and 2 metastases, we show that the calculation of accurate Apparent Diffusion Coefficient (ADC) values gives a specificity rate of
100%. Without ADC calculation, we show that image normalization is required to make an accurate differential diagnosis, and we highlight
the ability of DWI to discriminate between brain abscesses and cystic/necrotic brain tumors using normalized signal intensity at lower b
values (503 s/mm2) than usual. © 2003 Elsevier Inc. All rights reserved.

Keywords: ADC; Signal intensity; Diffusion-weighted images; MRI; Brain abscess; Necrotic or cystic tumor

1. Introduction Diffusion-weighted MRI (DWI) provides unique infor-

Differential diagnosis between cerebral abscesses in cap-
sule stage and intracerebral cystic or necrotic tumors is
impossible using conventional Magnetic Resonance Imag-
ing (MRI). Typically, contrast-enhanced MRI reveals ring
enhancement of a brain abscess that is similar to the ring
enhancement of a cystic or necrotic high-grade glioma or
metastasis. Clinically, the neurologic symptoms, the ab-
sence of hyperthermia and/or infectious symptoms in ab-
scesses may often lead to an erroneous diagnosis. However
early identification of a brain abscess is important, because
this potentially fatal lesion can be treated successfully by
stereotaxic aspiration and antibiotic therapy.
* Corresponding author. Tel.: ⫹33-1-49-95-81-06; fax: ⫹33-1-49-95-
81-15.
E-mail address: ilana.peretti@lrb.ap-hop-paris.fr (I. Idy-Peretti).
mation about the molecular translational motion of water
[1]. This technique has been applied to various intracranial
lesions including acute cerebral stroke, demyelinating dis-
ease and tumors [2– 4]. DWI is also useful for differentiat-
ing between epidermoid and arachnoid cysts [3,5]. Recent
publications suggest that DWI and apparent diffusion coef-
ficient (ADC) calculations can be helpful in establishing a
differential diagnosis between abscess and cystic/necrotic
tumor [6 –9]. However previous reports described DWI data
and ADC calculations for only small numbers of patients
which made it impossible to assess the specificity and sen-
sitivity. Furthermore, although many investigators have
worked on raw diffusion-weighted images in clinical studies
[7], there is no consensus about the appropriate higher b
value.
The aim of this study was to propose a simple and
reliable way of improving the differential diagnosis between

0730-725X/03/$ – see front matter © 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0730-725X(03)00084-5
646 L. Nadal Desbarats et al. / Magnetic Resonance Imaging 21 (2003) 645– 650

Fig. 1. A 41-year-old woman with a surgically proven left parietal pyogenic brain abscess. a) T2-weighted image, b) precontrast T1-weighted image, c)
contrast-enhanced T1 image, d) diffusion-weighted image b ⫽ 80 s/mm2, e) diffusion-weighted image b ⫽ 724 s/mm2.

cerebral abscesses and cystic or necrotic brain tumors. We 2.2. MRI

used the mean signal intensity on T1 and T2 weighted
conventional MR images, and calculated the ADC using 8 b
values. We also determined the discriminating threshold for
b values for diffusion-weighted raw images and for diffu-
sion-weighted normalized images.
2. Patients and Methods
2.1. Patients
From May 1997 to December 2000, we reviewed 26
ring-enhancing intracranial lesions in 24 consecutive pa-
tients (7 females, 17 males, aged 5–77 years (mean age 54.8
⫾ 16.2 years)). Twelve patients (14 lesions) presented with
surgically confirmed pyogenic brain abscesses. Their le-
sions measured 1.6-5 cm in diameter and were located in the
frontal (n ⫽ 4), parietal (n ⫽ 2), temporal (n ⫽ 2), and
occipital (n ⫽ 3) lobes, the thalamus (n ⫽ 2) and the
cerebellum (n ⫽ 1). Ten patients (10 lesions) had surgically
confirmed high-grade gliomas with a large necrotic or cystic
portion and two patients (2 lesions) had metastases. For the
rest of the study, the metastases were pooled with high-
grade lesions, because their ADC and DW image intensities
were the same. The tumors were 2-6 cm in diameter and
were located in the frontal (n ⫽ 4), fronto-parietal (n ⫽ 1),
parietal (n ⫽ 2), temporal (n ⫽ 2), and occipital (n ⫽ 1)
lobes, the thalamus (n ⫽ 1) and the cerebellum (n ⫽ 1). All
the intracranial lesions consisted of a central cavity with a
rim of contrast-enhancement on routine MR images after
gadolinium-chelate injection. The 14 abscesses were at the
capsule stage, and all cystic or necrotic parts of tumors were
identified on contrast-enhanced images from their more or
less regular ring enhancement (Figs. 1 and 2).
Magnetic resonance examinations were performed, using
a head coil, on a 1.5T clinical MRI system (Signa Horizon-
tal, Echospeed 5.8: General Electric Medical Systems, Buc,
France). After sagittal Fast Multi Planar Spoiled Grass
(FMPSPGR) T1-weighted scout images, at 90° angle,
(300/4 ms [TR/TE]), conventional MR images were ob-
tained in the axial-oblique bicomisural plane with the fol-
lowing parameters: 22 slices, slice thickness: 5 mm/1.5 mm
gap, 24 ⫻ 18 cm Field of View, 512 ⫻ 224 matrix and 1
NEX. The sequences were performed as follows: a) Fast
T2-weighted spin echo sequence, (4000/112 ms). b) Precon-
trast T1-weighted spin echo sequence, (320/9 ms). c) The
pulse sequence used for diffusion-weighted image was sin-
gle shot spin echo EPI sequence, (2000/100 ms), 7 slices
centered on the lesion, with a 128 ⫻ 64 matrix. The diffu-
sion gradient strength ranged from 0 to 1.75 G/cm with
increments of 0.25 G/cm. The 8 corresponding b values
were 0, 20.1, 80.5, 181, 322, 503, 724.5, 986.1 s/mm2. The
diffusion gradients were applied simultaneously along the
three orthogonal directions (x, y, z). d) Contrast-enhanced
T1-weighted spin echo images, (320/9 ms), were obtained
after i.v. administration of meglumine gadoteric acid (Gd-
DOTA) (Dotarem, Guerbet, Aulnay s/s Bois, France) at
dose of 0.1 mmol/kg.
2.3. Image analysis
2.3.1. Mean Signal Intensity on T1- and T2-weighted
images
For each subject, a slice was chosen on both T1- and
T2-weighted images where the lesion was the most clearly

Fig. 2. A 61-year-old man with a pathologically proven right frontal malignant glioma a) T2-weighted image, b) precontrast T1-weighted image, c)
contrast-enhanced T1 image, d) diffusion-weighted image b ⫽ 80 s/mm2, e) diffusion-weighted image b ⫽ 724 s/mm2.
 L. Nadal Desbarats et al. / Magnetic Resonance Imaging 21 (2003) 645– 650
visible. An ROI was then selected visually and drawn as
large as possible (approximately 100 pixels, depending on
the lesion). A total of 42 ROIs was selected for T1 and T2:
20 for abscesses and 22 for cystic or necrotic tumors. No
T1-weighted images were available for 4 patients (4 ab-
scesses and 1 high-grade glioma), and so the imaging data
from these patients were discarded. The mean signal inten-
sity was then calculated for each ROI.
The diffusion-weighted images (DWI) were analyzed
off-line using an Advantage Windows 2.0 workstation run-
ning Functool version 1.9b (General Electric Medical Sys-
tem Software, Buc, France). The images were assessed on
the basis of ADC calculations on one hand, and on the
signal intensity itself on the other hand.
Pixel by pixel ADC maps were calculated from the 8 b
value images using a nonlinear regression model. Regions
of interest (ROIs) containing 15 to 150 pixels passing
through the lesion were chosen on each slice: 1 or 2 ROIs
inside the cavity marked off by Gd-DOTA (depending on
the cavity size), one or two ROIs in the surrounding
edema, one or two ROIs in the contralateral white matter
and one ROI in the cerebrospinal fluid (CSF). No ROI
was taken in the enhanced rim of the mass to avoid a
partial volume effect. The aim was to characterize the lesions
and differentiate between abscesses and necrotic/cystic tumor
cavities.
Signal intensities from the ROIs previously chosen for
abscesses and necrotic/cystic tumor cavities were collected
for the 8 b value images. The signal intensities for each b
value and each disease were pooled and plotted as Raw
Signal Intensity versus b. The signal intensity (SI) of DW
images is expressed as SI ⫽ SI0 ⫻ exp(-b ADC). We also
plotted the Normalized Signal Intensity (SI/SI0) versus b.
2.4. Statistical analysis
For each group, the ADC values from each slice and each
patient were pooled. The different groups of samples from
patients with abscesses were: ADC inside abscess cavity
(ADCa), edema surrounding abscess (ADCo-a), white mat-
ter (ADCwm-a) and cerebrospinal fluid (ADCcsf-a), and
those from patients with cystic or necrotic tumor lesions
were: (ADCtk), edema surrounding cystic or necrotic le-
sions (ADCo-tk), white matter (ADCwm-tk) and cerebro-
spinal fluid (ADCcsf-tk). A Mann-Whitney rank sum test
was performed to compare ADC values between the groups.
Significant p values were defined as p ⬍ 0.01. The results
are expressed as the median [range].
For raw or normalized DWI signal intensities, the results
obtained using the 8 b values were compared for the two
diseases using the Mann-Whitney rank sum test. Significant
p values were defined as p ⬍ 0.01. The results are expressed
as the median [range].
647
Fig. 3. Scatter plot representing signal intensity means of T1 weighted
images versus signal intensity means of T2 weighted images.
3. Results
3.1. Signal Intensity mean from T1- and T2-images
Signal intensity means from T1- versus T2-weighted con-
ventional images are shown in Fig. 3. Abscess clusters
(white) cannot be distinguished from tumor clusters (black).
Abscess cavities and cystic/necrotic tumors cannot be dis-
tinguished by visual inspection of T1 and T2 weighted
conventional images (Figs. 1 and 2).
3.2. ADC
An accurate ADC based on 8 b values was calculated for
all selected regions (Table 1). The high-grade gliomas and
the two metastases all had high ADC values [2.02-2.30 ⫻
10⫺3 mm2/s and 2.68-2.79 ⫻ 10⫺3 mm2/s) and so their data
were pooled. The Mann-Whitney rank sum test was statis-
tically different for abscesses and cystic/necrotic tumors.
Moreover median ADC values were 0.57 ⫻ 10⫺3 mm2/s
[0.25 ⫻ 10⫺3 mm2/s ⫺ 1.09 ⫻ 10⫺3 mm2/s] for abscesses
versus 2.54 ⫻ 10⫺3 mm2/s [1.15 ⫻ 10⫺3 mm2/s ⫺3.59 ⫻
10⫺3 mm2/s] for cystic/necrotic tumors. The two ranges of
values did not overlap. This made it possible to reach an
unambiguous differential diagnosis between these two con-
ditions. An ADC of 1.10 ⫻ 10⫺3 mm2/s could be set as the
discrimination threshold between abscesses and necrotic/
cystic tumors. Using this threshold value, the specificity rate
in this study is 100%.
In contrast, there was no statistical difference between
ADCo-a and ADCo-tk, or between ADCcsf-a and ADCcsf-
tk. However, the Mann-Whitney rank sum test did reveal a
statistical difference between the two white matter groups
ADCwm-a and ADCwm-tk, although there was a consider-
able degree of overlap between the two sets of values.
648 L. Nadal Desbarats et al. / Magnetic Resonance Imaging 21 (2003) 645– 650

Fig. 4a. Raw signal intensities on DWI from ROIs chosen in the central cavities of lesions versus b values. White vertical boxes and E for Abscesses, Gray
vertical boxes and F for Cystic/Necrotic tumors. The vertical box represents values between the 25th and 75th percentiles, the 5th and 95th percentiles are
displayed as symbols. n is the number of patients and N the number of measurements.

3.3. DWI
Raw signal intensities versus b values for abscesses and
cystic/necrotic tumors are shown in Fig. 4a. The overlap
between the signal intensities of the two groups, persists up
to b values of 986 s/mm2. Consequently, diagnoses based on
raw DWI images may lead to the wrong conclusion.
Normalized signal intensities versus b values, for ab-
scesses and cystic/necrotic tumors, are shown in Fig. 4b. For
normalized signal intensities, low b values such as 322
s/mm2 could provide an accurate diagnosis, and there was
no overlap between the normalized signal intensities of the
two groups at the higher b values. Using normalized DWI,
it is possible to increase the accuracy of the diagnosis even
at lower b values than usual.
4. Discussion
It can be difficult to reach a differential diagnosis of
ring-enhancing intracranial mass lesions on the basis of
clinical symptoms and conventional MRI. We found that
neither visual inspection nor measuring signal intensity
means from T1- and T2-weighted images can differentiate
between abscesses and cystic/necrotic tumors. However, if
an early and accurate diagnosis can be made, antibiotics can
be used successfully to treat brain abscesses.
The literature includes reports of 1H MR spectroscopy
studies used to characterize [10 –13] and classify brain tu-
mors [14 –16] and of their ability to provide differing spec-
tral patterns for abscesses and for cystic or necrotic lesions.
Some in vivo localized studies [17–22] describe the pres-
ence of end-products of bacterial break-down, such as ami-
no-acid residues, along with lactate and acetate in abscesses,
whereas only lactate is present in high grade gliomas. More
recently, Grand et al. [23], have compared in vivo localized
spectroscopy and in vitro spectroscopy, and have shown
differential spectroscopic patterns in both types of lesion
based on the quantification of the amino-acids. This tech-
nique is certainly attractive, but not available at every im-
aging center.
Diffusion-weighted MRI provides images in which the
contrast is dependent on the molecular motion of water [1]

Fig. 4b. Normalized signal intensities on DWI from ROIs chosen in the centers of lesions versus b values. White vertical boxes and E for Abscesses, Gray
vertical boxes and F for Cystic/Necrotic tumors. Vertical box represents values between the 25th and 75th percentiles, the 5th and 95th percentiles are
displayed as symbols: n is the number of patients and N the number of measurements.
 L. Nadal Desbarats et al. / Magnetic Resonance Imaging 21 (2003) 645– 650
and may be altered as a result of disease. The clinical
potential of diffusion-weighted imaging is likely to be great-
est in the study of acute stroke, both for the early detection
of cerebral infarcts and for monitoring subsequent ischemic
damage. The clinical use of the technique is now becoming
routine for the diagnosis of stroke [24]. Another potential
application is mapping the development and maturation of
white matter [25]. More recently, DWI has also been ap-
plied to brain tumor processes [4].
Functional MRI, like diffusion-weighted imaging, has
occasionally been used to diagnose cerebral abscesses.
However, so far only a small number of abscesses have been
reported, 5 papers report a total of 17 abscesses. In one case
report, Ebisu et al. [6] showed that diffusion weighted
image had high signal intensity in a brain abscess. Kim et al.
[7] reported a markedly hyperintense signal in abscesses,
whereas necrotic or cystic brain tumors gave a hypointense
signal. These studies were based on signal intensity images,
rather than on the calculated apparent diffusion coefficient.
More recently, Desprechins et al. [9] showed that it is
possible to reach a differential diagnosis based on the high
signal intensity in diffusion imaging and a strongly reduced
apparent diffusion coefficient. Noguchi et al. [8], investi-
gating 2 pyogenic brain abscesses and 6 high-grade gliomas,
reported a significant difference between the ADC values,
but underline a potential methodological problem, since an
inaccurate ADC value could result if only two b values are
used.
So far, depending on the authors, publications report the
use of 2 or more b values to calculate ADC, and in addition
there is no agreement about the appropriate b value to use to
obtain the most accurate diagnosis. Because of the low
incidence of abscesses, the preliminary studies involved
only small numbers of patients [6,8,9], however, we were
able to use a larger sample, which allowed us to detect a
statistically significant difference between the groups.
We used 8 b values to calculate accurate ADC values and
found that those for white matter were statistically different
in the abscess and high-grade glioma groups. This discrep-
ancy may be attributable to the differing locations of the
slices containing lesions. The ROIs in the white matter were
not always at same spot, because we centered the 7 slices for
diffusion-weighted imaging on the lesion. The anisotropy
and non-homogeneous composition of the white matter can
account for some of the statistical difference between the
two groups, although there is a huge degree of overlap
between the two ranges of values. For the central cavity of
both lesion groups, the statistical difference was accompa-
nied by an absence of any overlap between the two ranges
of ADC values. This made it possible to determine a thresh-
old CDA value below which a lesion can be classified as an
abscess, with a specificity rate of 100%. In this study, this
threshold value is 1.10 ⫻ 10⫺3 mm2/s. Recently, Burdette et
al. [26] have shown that brain ADC values may be slightly
overestimated if a two-point technique is used instead of a
six-point technique. Nowadays, commercially available
649
clinical software uses 2 b values to calculate the ADC and
we must be very cautious about interpreting these data if we
are to obtain a reliable diagnosis. Our findings show low
ADC values in abscesses, and these low ADC values are
attributable to the presence of pus [6]. Pus is a highly
viscous, thick, mucoid fluid consisting of inflammatory
cells, bacteria, proteoneous exudate and fibrinogen [9]. Be-
cause of this high viscosity, diffusion water motion is se-
verely curtailed. The high ADC values we find in cystic or
necrotic lesions are attributable to an intra-cavity fluid that
is less viscous than that found in abscesses. It consists of
necrotic tissue debris and contains fewer inflammatory cells
than abscess fluid. However, Holtas et al. [27] have recently
reported a low ADC in a ring-enhancing metastasis. Parks et
al. [28] reported 7 metastases, 2 of which had a low ADC.
Holtas et al. suggest that early stage tumor necrosis with
intracellular edema, but as yet no liquefaction, may give
DWI findings similar to those for abscesses at the capsule
stage. In our case, the metastases were probably in the
liquefaction stage and similar to high-grade gliomas. In our
study, the metastases and the high-grade gliomas behaved
similarly. They both had a high ADC, and so we included
both these processes in a single group.
High DWI signal intensity for brain abscesses is usually
associated with a reduced ADC value and, conversely, low
DWI signal intensity is associated with a high ADC value
for cystic or necrotic tumors, including metastases [8,28].
Our results closely match these observations. Another goal
of this study was to find out what b value can be used as the
cutoff threshold between abscesses and necrotic or cystic
tumors for raw DWI signal intensity and for normalized
DWI signal intensity.
Up to b ⫽ 986 s/mm2, we found that the raw DWI signal
intensities for abscess and cystic or necrotic tumors overlap.
We have to take into consideration that DWI signal intensity
is influenced not only by water diffusion, but also by the
intrinsic T2 property of the tissue being examined (the T2
shine through effect) [29]. At high b values, the T2 effect is
presumably negligible, but in clinical practice, considering
only DWI obtained with high b values, often 1000 s/mm2,
can lead to a mistaken diagnosis. This is similar to the
situation for stroke. Interpreting DW images without ADC
calculations may lead to the wrong interpretation of stroke
data with respect to stroke evolution [30,31]. On the other
hand, working with normalized signal intensities makes it
possible to eliminate the T2 shine through effect. In our
study of normalized images, starting from b ⫽ 503 s/mm2,
the overlap between the two ranges of signal intensities
disappears. This could make it possible to carry out diffu-
sion weighted MRI at lower b values and/or lower gradient
strength. According to these results, image normalization is
required to interpret the diffusion-weighted images properly
and to avoid false negative interpretations. Commercially
available clinical software is based on 2 b values: b ⫽ 0
s/mm2 and 1000 s/mm2. This means that it is necessary to
analyze normalized images before making a diagnosis, but
650 L. Nadal Desbarats et al. / Magnetic Resonance Imaging 21 (2003) 645– 650
post-processing software does not offer the option of rapidly
normalizing the signal intensity of the images.
5. Conclusion
It is often impossible to reach a differential diagnosis
between brain abscesses and cystic or necrotic brain tumors
using conventional MRI. DWI is a useful tool to explore
water diffusion and to make this differential diagnosis pos-
sible. Working on the raw DWI signal intensity, even at
high b values, could lead to an erroneous clinical interpre-
tation. Image normalization seems to be a better way, mak-
ing it possible to avoid this T2 shine-through phenomenon
and to reach an accurate diagnosis even at low b values.
Unfortunately, no commercially available software allows
to normalize images automatically. This means that to avoid
the T2 shine through phenomenon, we need to calculate
ADC values. Our study included the largest number of
abscesses so far reported, and we calculated an accurate
ADC using 8 b values. This allowed us to propose a thresh-
old ADC value.
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