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RESEARCH Open Access
Magnetic resonance imaging, computed
tomography, and 68Ga-DOTATOC positron
emission tomography for imaging skull base
meningiomas with infracranial extension treated
with stereotactic radiotherapy - a case series
Reinhold Graf1*†, Michail Plotkin2†, Ingo G Steffen2, Reinhard Wurm3, Peter Wust1, Winfried Brenner2,
Volker Budach1 and Harun Badakhshi1
Abstract
Introduction: Magnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron
emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial
extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.
Methods: Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and 68Ga-DOTATOC PET/CT prior to
fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma
extension, visible on MRI ± CT (MRI/CT) or PET, and were evaluated further. The respective findings were reviewed
independently, analyzed with respect to correlations, and compared with each other.
Results: Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients
(81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which
were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the
SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases
and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm3, which
was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm3).
Conclusions: 68Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma
invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to
conventional imaging modalities that are often inconclusive in the SB region.
Keywords: Meningioma, Skull Base, 68Ga-DOTATOC, PET, Stereotactic radiotherapy
Introduction
Meningiomas are common intracranial tumours with 25
to 30% located at the skull base (SB) [1]. When originat-
ing from the anterior clinoid process or medial sphenoid
wing, they have an increased propensity to invade bone
[2], which is a strong risk factor for recurrence [3].
Meningiomas in this location tend to progress transcra-
nially or invade the infracranial spaces via natural open-
ings [2,4] and recur in up to 45% of cases after surgery
[5]. There is a strong correlation between the extent of
resection and rate of recurrence [6]; therefore, accurate
determination of tumour extension is critical for plan-
ning the magnitude of surgery and/or radiotherapy.
Computed tomography (CT) and magnetic resonance
imaging (MRI) are widely used in the diagnosis of SB
meningiomas and complement each other in the ability
to determine tumour extent [7]. CT has proven to be
* Correspondence: reinhold.graf@charite.de
† Contributed equally
1Department of Radiation Oncology, Charité Universitätsmedizin Berlin,
Berlin, Germany
Full list of author information is available at the end of the article
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HEAD & FACE MEDICINE
© 2012 Graf et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
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more effective than MRI in diagnosing bone infiltrations
at the anterior region of the SB [8,9]; while, MRI ima-
ging of the cranial base has a high sensitivity due to
excellent spatial and contrast resolution. However, espe-
cially in the central SB, there are structures with high
signal intensity and high contrast-enhancement in MRI,
which make it difficult to exactly delineate meningioma
tissue from normal structures [10].
Receptor imaging offers an additional tool for imaging
meningiomas. Meningiomas show high expression of
several receptors, including somatostatin receptors (SR)
subtype 2 (SSTR 2) [11,12]. Recently the somatostatin
analogue, 1,4,7,10-tetraazacyclododecane-N,N’,N”,N"’-
tetraacetic-acid-D-Phe1-Tyr3-octreotide (68Ga-DOTA-
TOC) labeled with the positron emitter 68Ga (half-life,
68 min) was developed. 68Ga-DOTATOC is a positron
emission tomography (PET) tracer and shows up to
nine-fold higher affinity to SSTR 2, as compared to the
SPECT ligand 111In-DTPA-octreotide [13]. In studies
conducted by Henze et al., all meningiomas evaluated
showed a high 68Ga-DOTATOC uptake [14,15]. In a
pilot study, the same group recently performed CT,
MRI, and 68Ga-DOTATOC PET examinations on 26
patients with intracranial meningiomas before radiother-
apy. 68Ga-DOTATOC-PET provided additional informa-
tion concerning the spread of the tumour and led to a
significant modification of the gross tumour volume in
about two thirds of the patients examined [16]. The
acquisition of 68Ga-DOTATOC scans on PET/CT scan-
ners helps to estimate the relation of PET findings to
anatomical structures. In our own study using 68Ga-
DOTATOC-PET/CT, the gross tumour volume was
modified based on 68Ga-DOTATOC-PET data in 28/39
patients with positive PET scans [17].
In the present study, the results of MRI, CT, and
68Ga-DOTATOC PET were retrospectively compared in
a study group of 16 patients with SB meningiomas. The
influence of PET imaging on pretherapeutic detection of
transgression of the SB was evaluated and the influence
of PET on the definition of tumour extent was
quantified.
Materials and Methods
Between May 2006 and November 2010, a group of 50
consecutive patients with 56 SB meningiomas under-
went planning CT, MRI, and 68Ga-DOTATOC-PET/CT
(with contrast-enhanced CT) prior to the start of ther-
apy. Fifty meningiomas showed areas with high 68Ga-
DOTATOC uptake. Infracranial extension was visible in
MRI/CT or PET in 16/50 patients, who formed the
study group and were further analysed in a retrospective
manner. There was infracranial extension in all patients.
In addition, some patients showed extracranial extension
to other sites (not infracranial, four orbit and one
maxillary sinus). These extensions were not evaluated in
this study. The study group included 11 women and 5
men with a mean age of 54.4 (range 25-73) years. Eleven
patients had undergone surgery and/or radiotherapy and
5 patients had not received any therapy before. Patho-
histologically, there were 7 meningiomas with a WHO
grade 1 tumour (9 unknown). Nine meningiomas under-
went FSRT as primary treatment without histological
confirmation, when imaging morphology and clinical
course suggested the diagnosis of a WHO grade I or II
meningioma. The study was based on the Declaration of
Helsinki and the principles of ‘good clinical practice’.
The protocol was approved by the ethics committee of
our institution. Written informed consent was obtained
from all patients before enrolment into the study. Writ-
ten informed consent was obtained from the patient for
publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Details of imaging the tumour volume for fractionated
radiotherapy in the Charité medical school have been
described elsewhere [17]. Briefly, following the planning-
CT, MR imaging of the skull was performed with the
use of a head coil in most patients with a 1.0 T scanner
(Siemens Harmony™, Siemens Medical Solutions, Erlan-
gen, Germany). Regularly, magnetization-prepared rapid
gradient echo (MP-RAGE) T1-weighted sequences were
used for coregistration after intravenous application of
Gadolinium-DTPA ([Gd], Magnevist™, Schering AG,
Berlin, Germany) at a dosage of 0.1 mmol/kg of body
weight. These 3-D volume datasets at a 1- (to 1.5) mm
slice thickness offer high spatial resolution and allow for
coronal and sagittal reformations, enabling contouring
in orthogonal planes.
Details of functional imaging have been described pre-
viously [17]. 68Ga-DOTATOC was applied intravenously
followed by a tracer uptake phase of 60 min, as recom-
mended by Henze et al. [15]. The applied dose of 68Ga-
DOTATOC was between 70 and 120 MBq (1.9-3.2
mCi). The patient was placed in a dedicated positioning
device for the head using an additional cushion and
bandages for fixation. A contrast enhanced low-dose CT
scan (detector collimation, 16 × 1.5 mm; tube current,
100 mAs; tube voltage, 120 kV; gantry rotation time, 0.8
s) of the entire head was performed for attenuation cor-
rection. PET was acquired in a single bed position with
a 16 cm axial FOV from the base of the skull to the ver-
tex and an emission time of 20 minutes. PET emission
data were reconstructed as coronal, axial, and sagittal
using a 128 × 128 matrix.
Planning-CT, MRI, and PET data were coregistered
using the treatment planning software BrainSCAN™
v.5.1 (BrainLAB AG, Feldkirchen, Germany). CT, MRI,
and PET were fused automatically using image fusion
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software and a mutual information algorithm. The valid-
ity of image fusion has been successfully tested pre-
viously by Grosu et al. [18].
The windowing of 68Ga-DOTATOC-PET was defined
visually following the method published by Astner et al.
[19]. The threshold of PET was adapted to tumours visi-
ble by MRI in regions where the tumour bordered nor-
mal brain tissue and could be outlined with high
precision, e.g., where the meningioma bordered normal
brain matter. Under the assumption that the 68Ga-
DOTATOC-PET uptake in meningiomas is homoge-
neous [20], the tumour borders (defined on 68Ga-
DOTATOC-PET images in slices with well defined bor-
ders by MRI) were used to outline the tumour margins
on 68Ga DOTATOC-PET images in regions where the
margins were not visible by MRI.
All examinations in one patient were performed
within a time frame of 14 days. A checklist for local
tumour extension and infiltration of bone and sites was
used in this study. Conventional imaging findings were
regularly interpreted by two experienced radiologists.
Using a dedicated workstation, two experienced nuclear
medicine physicians interpreted PET/CT fused images
and their CT and PET components. If there was dis-
agreement, the comparison results were reached by
consensus.
The planning CT scans obtained with bone window
settings (window width 2000 Hounsfield units, centre
level 500 Hounsfield units) were used to determine the
signs of erosion of adjacent bone or hyperostotic
changes [21]. Tumour-specific abnormalities were
defined as hyperintense or Gd enhancing structures in
MRI and tracer enhancing areas in PET, often a “side-
to-side” comparison with MRI was used to determine if
a structure was normal or abnormal [22]. Visualization
of bony structure changes, tumours spreading to the
bony canals or foramina, communication with the mid-
dle fossa, and infracranial tumour expansion were com-
pared in MRI, CT, and PET images. In an additional
step, the infracranial volume was delineated using MRI/
CT and 68Ga DOTATOC-PET separately. The statistical
software R, version 2.11.1 (R Foundation for Statistical
Computing, Vienna, Austria) was used for statistical
analysis. Non-parametric differences were analysed using
the Wilcoxon test (at a 0.05 level of significance).
Results
All meningiomas showed areas with high 68Ga DOTA-
TOC uptake, enabling delineation in MRI ± CT and
PET in each case. The majority (75%) of lesions involved
the sphenoid bone. Volumes measured by MRI were
enlarged in MRI/CT by a mean additional volume of 2.3
ml (7.2% of the MRI volumes) that was only identifiable
in CT. Osteolytic lesions represented the majority of
bony lesions. Two meningiomas showed infracranial
invasion along the vessels without bony abnormalities in
CT. Evaluation of meningioma infiltration in the bony
foramina by CT showed most tumorous changes were
evident in the foramen rotundum and the foramen ovale
(Table 1). In lesions accompanied by structural changes
of these foramina, infiltrative growth into skeletal mus-
cle was present in 8 lesions (62%).
The mean and median of the MRI/CT and PET
volumes were almost identical. We analysed involve-
ment of six designated infracranial spaces in each
patient, resulting in a total of 96 sites. All 16 meningio-
mas grossly extended into at least one infracranial site.
The infratemporal fossa and pterygopalatine fossa were
mostly involved. The visualization of tumour expansion
into designated infracranial spaces by MRI/CT and PET
and a comparison between both modalities are shown in
Table 2, with PET demonstrating a slightly better visibi-
lity of the involved areas compared with MRI/CT. With
respect to the infracranial sites evaluated, there were 7
cases with negative MRI/CT and positive PET, resulting
in discrepancies in 7 of the 96 sites evaluated (7%) and
7 of the 42 sites affected (17%). The infracranial volume
delineable by PET was larger than the volume delineable
by MRI, although it did not reach the level of signifi-
cance (p = 0.06). Example images are shown in Figure 1.
Discussion
Transcranial meningiomas spread through the foramina
of the skull, entering the pterygoid region through the
floor of the middle cranial fossa, suture lines, and the
foramina of the skull [23,24]. This group of meningio-
mas is characterized by a high rate of recurrence, up to
45% in some studies [2,25,26]. Recurrence correlates
with the extent of resection in neurosurgery [6] and
extent of coverage in stereotactic radiosurgery [27].
Tumorous invasion of SB bone without hyperostosis
was addressed in a study by Pieper et al. [28], where
each of the eight patients showed erosion of the middle
fossa floor and extension through the cranial base fora-
mina, specifically the rotundum and ovale, without evi-
dence of hyperostosis. The prevalence of lytic changes is
in accordance with our findings. Of the 16 patients with
infracranial extension, identified by MRI/CT or PET,
there was association with bony changes in 13 patients
(88%). These findings confirmed the observation of Leo-
netti et al. [2] that there was a strong correlation
between radiologically visible invasion of osseous struc-
tures of the middle cranial and infracranial growth of
meningiomas. Furthermore, in patients in whom struc-
tural bone changes were identified preoperatively, histo-
pathological findings showed the tumour grossly
invaded the skeletal muscle in all cases; while, this was
only visible with imaging in 62% of cases in our study.
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CT and MRI scanning have being estimated adequate
for surgery for a long time [29,30]; although, anatomical
imaging methods have their limitations for target deli-
neation in infiltrative lesions and postoperatively [16].
We found the infracranial volume delineable by PET
was larger than the volume by MRI/CT and the true
extent of infracranial expansion could be missed by
MRI/CT alone as 7/16 cases were positive by PET and
negative by MRI/CT.
Other studies found 68Ga DOTATOC-PET improved
the delineation of SB meningiomas compared with MRI/
CT in the context of FSRT. Henze et al. [14] examined
Table 1 Patient characteristics and CT findings
Pat. No. Gender Age Location Bony changes (Location) Bony changes (Type) Bony changes (foramen ovale/rotundum)
1 F 47 L sphenopetral SP/—/OC Lytic OV/RO
2 M 56 R petroclival —/TE/— Lytic –/–
3 F 56 R sphenopetroclival —/TE/— Lytic OV/RO
4 F 53 L spenoid ridge SP/TE/— Mixed OV/RO
5 M 47 L sphenopetroorbital SP/TE/— Mixed OV/RO
6 F 51 L sphenoidal SP/TE/— Lytic OV/–
7 F 63 R sphenoidal SP/TE/— Hyperostotic OV/RO
8 F 66 R sphenoidal SP/TE/— Mixed OV/RO
9 M 63 L spheniodal SP/—/— Lytic OV/–
10 F 57 L petroclival SP/—/OC Mixed OV/—
11 M 25 L spheniodal SP/TE/— Lytic OV/—
12 F 37 L temporobasal —/—/— NC —/—
13 F 50 L sphenoorbtal SP/—/— Lytic OV/RO
14 F 73 R sphenoorbital SP/—/— Hyperostotic OV/RO
15 M 53 L petroclival –/—/— NC —/—
16 F 74 R sphenopetroclival –/—/— Lytic OV/—
F = Female; M = Male; L = Left; R = Right; SP = Sphenoid bone; TE = Temporal bone; OC = Occipital bone; NC = No changes; OV = Foramen ovale, RO =
Foramen rotundum.
Table 2 Comparison of MRI/CT and PET findings for detection of infracranial invasion in meningiomas with SB
transgression on a lesional basis.
Pat.
No.
Volume
MRI/CT
(cm3)
Volume
PET
(cm3)
Infracranial
invasion
Infracranial
invasion
Infracranial
invasion
Infracranial
invasion
Infracranial
invasion
Infracranial
invasion
Infracranial
volume
Infracranial
volume
ITF PPF Masticator
space
Carotideal
space
Para-
pharyngeal
space
Retro-
pharyngeal
space
MRI/CT
(cm3)
PET (cm3)
1 52.2 69.3 MRI/CT+PET MRI/CT+PET MRI/CT+PET 15.9 26.9
2 12.4 7.3 MRI/CT+PET MRI/CT+PET 3.4 2.4
3 13.9 23.1 PET PET PET 0 0.3
4 21.7 10.6 PET PET PET 0.15 1.6
5 68.2 100.6 MRI/CT+PET MRI/CT+PET MRI/CT+PET - 15.4 21.7
6 30.5 43.1 MRI/CT+PET MRI/CT+PET MRI/CT+PET 12.2 17.7
7 62.8 106.0 MRI/CT+PET MRI/CT+PET MRI/CT+PET 24.4 30.6
8 39.7 41.5 MRI/CT+PET MRI/CT+PET MRI/CT+PET 2.2 2.5
9 17.6 19.0 MRI/CT+PET MRI/CT+PET 8.8 9.0
10 35.2 28.5 MRI/CT+PET MRI/CT+PET 8.0 9.7
11 52.5 41.0 MRI/CT+PET MRI/CT+PET MRI/CT+PET 21.7 24.4
12 9.6 15.0 PET 0 0.3
13 4.6 3.5 MRI/CT+PET MRI/CT+PET MRI/CT+PET 10.0 6.0
14 76.0 67.8 MRI/CT+PET MRI/CT+PET MRI/CT+PET 9.3 6.1
15 27.1 8.0 MRI/CT+PET MRI/CT+PET 0.3 0
16 19.6 39.4 MRI/CT+PET MRI/CT+PET PET 1.2 1.6
ITF = Infratemporal fossa; PPF = Pterygopalatine fossa.
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8 meningiomas with 68Ga DOTATOC-PET and found
valuable additional information regarding the extent of
meningiomas located beneath osseous structures, espe-
cially at the SB. Later, the same group reported their
experiences in 26 patients with meningiomas. They
found 73% of the planned target volume for definitive
radiotherapy treatment was significantly modified by the
use of 68Ga-DOTATOC-PET [16]. In our previous
study, which included 42 patients with meningiomas (27
SB), we used 68Ga-DOTATOC-PET/CT to detect modi-
fication of the gross tumour volume in 72% of patients
[17]. The tumour extent visible by MRI/CT compared
to 68Ga-DOTATOC-PET/CT was larger in 23% and
smaller in 49% of cases. Dammers et al. described a case
in which radioguided resection of a meningioma, using
111indium-labelled somatostatin receptors, enhanced
the extent of the resection and discussed how this could
be of potential use in maximizing the resection of
meningiomas involving the cranial base region [31].
To our knowledge, descriptions of infracranial exten-
sion of SB meningiomas in the context of FRST are
sparse. We reviewed the published studies concerning
delineation of SB meningiomas with 68Ga-DOTATOC
PET [14-17,32-34] and other tracers [19,35,36] and
found transcranial extension of SB meningiomas was
not mentioned, probably due to the comparably lower
numbers of SB meningiomas examined.
When MRI/CT showed meningioma infiltration in the
bony foramina, visualisation of the involvement by PET
lacked small details, which may have been due to the
higher slice thickness and lower spatial resolution of
PET (in comparison to MRI/CT). Several other draw-
backs in this study have been discussed previously [17].
As found in most studies on the target volume defini-
tion of meningiomas, this study is limited by the lack of
histological verification. To address the problem of the
choice of threshold levels [15,16], a fixed threshold
could be useful for tumour segmentation to reduce
interobserver variability. At our institution, re-evaluation
of our data using an algorithm that creates defined SUV
values is in progress.
Conclusions
In this study, the extent of local meningioma invasion
detected by MRI/CT and 68Ga-DOTATOC-PET were
not consistent. 68Ga-DOTATOC-PET is a sensitive
functional method for demonstrating the dimensions
of infracranial meningioma infiltration and may contri-
bute to FSRT planning in cases where CT and MRI
are not conclusive in regions that are difficult to
image.
List of abbreviations used
MRI: Magnetic resonance imaging; CT: Computed tomography; SB: Skull
base; MRI/CT: MRI ± CT; PET: Positron emission tomography; 68Ga-DOTATOC-
PET: 68Ga-DOTATOC positron emission tomography; F: Female; M: Male; L:
Left; R: Right; SP: Sphenoid bone; TE: Temporal bone; OC: Occipital bone; NC:
No changes; OV: Foramen ovale, RO: Foramen rotundum; ITF: Infratemporal
fossa; PPF: Pterygopalatine fossa.
Author details
1Department of Radiation Oncology, Charité Universitätsmedizin Berlin,
Berlin, Germany. 2Department of Nuclear Medicine, Charité
Universitätsmedizin Berlin, Berlin, Germany. 3Department of Radiation
Oncology, Klinikum Frankfurt (Oder), Germany.
Authors’ contributions
RG analyzed the CT, MRI, and PET data, performed the analysis, and drafted
the first version of the manuscript. MP supervised the analysis of the PET
data and revised the manuscript. RW made substantial contributions to the
conception and design of the study. PW contributed to the analysis and
interpretation of data. VB participated in designing the study and approved
the treatment concepts. WB approved the final version of the manuscript.
HB coordinated the recruitment of patients and data acquisition. All authors
participated in critical discussion of the data and the conclusions. All authors
improved the manuscript and approved the final version.
Competing interests
The authors declare that they have no competing interests.
Received: 29 October 2011 Accepted: 4 January 2012
Published: 4 January 2012
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Figure 1 A 49 year old male patient (No. 5) with a recurrent left petroclival meningioma with extension into the orbit, maxillary sinus,
and intracerebral areas. 68Ga-DOTATOC-PET/CT allowed markedly better delineation of the extent of infiltrative, infracranial extension compared
with both CT and MRI.
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