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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

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography... Introduction: Magnetic resonance imaging (MRI) and computed tomography (CT) with Ga-DOTATOC positron emission tomography ( Ga-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 Ga-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 cm , which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm ). Conclusions: Ga-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, Ga-DOTATOC, PET, Stereotactic radiotherapy Introduction Meningiomas in this location tend to progress transcra- Meningiomas are common intracranial tumours with 25 nially or invade the infracranial spaces via natural open- to 30% located at the skull base (SB) [1]. When originat- ings [2,4] and recur in up to 45% of cases after surgery ing from the anterior clinoid process or medial sphenoid [5]. There is a strong correlation between the extent of wing, they have an increased propensity to invade bone resection and rate of recurrence [6]; therefore, accurate [2], which is a strong risk factor for recurrence [3]. determination of tumour extension is critical for plan- ning the magnitude of surgery and/or radiotherapy. Computed tomography (CT) and magnetic resonance * Correspondence: reinhold.graf@charite.de † Contributed equally imaging (MRI) are widely used in the diagnosis of SB Department of Radiation Oncology, Charité Universitätsmedizin Berlin, meningiomas and complement each other in the ability Berlin, Germany to determine tumour extent [7]. CT has proven to be Full list of author information is available at the end of the article © 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. Graf et al. Head & Face Medicine 2012, 8:1 Page 2 of 6 http://www.head-face-med.com/content/8/1/1 more effective than MRI in diagnosing bone infiltrations maxillary sinus). These extensions were not evaluated in at the anterior region of the SB [8,9]; while, MRI ima- this study. The study group included 11 women and 5 ging of the cranial base has a high sensitivity due to men with a mean age of 54.4 (range 25-73) years. Eleven excellent spatial and contrast resolution. However, espe- patients had undergone surgery and/or radiotherapy and cially in the central SB, there are structures with high 5 patients had not received any therapy before. Patho- signal intensity and high contrast-enhancement in MRI, histologically, there were 7 meningiomas with a WHO which make it difficult to exactly delineate meningioma grade 1 tumour (9 unknown). Nine meningiomas under- tissue from normal structures [10]. went FSRT as primary treatment without histological Receptor imaging offers an additional tool for imaging confirmation, when imaging morphology and clinical meningiomas. Meningiomas show high expression of course suggested the diagnosis of a WHO grade I or II several receptors, including somatostatin receptors (SR) meningioma. The study was based on the Declaration of subtype 2 (SSTR 2) [11,12]. Recently the somatostatin Helsinki and the principles of ‘good clinical practice’. analogue, 1,4,7,10-tetraazacyclododecane-N,N’,N”,N"’- The protocol was approved by the ethics committee of tetraacetic-acid-D-Phe1-Tyr3-octreotide ( Ga-DOTA- our institution. Written informed consent was obtained TOC) labeled with the positron emitter Ga (half-life, from all patients before enrolment into the study. Writ- 68 min) was developed. Ga-DOTATOC is a positron ten informed consent was obtained from the patient for emission tomography (PET) tracer and shows up to publication of this case report and accompanying nine-fold higher affinity to SSTR 2, as compared to the images. A copy of the written consent is available for SPECT ligand 111In-DTPA-octreotide [13]. In studies review by the Editor-in-Chief of this journal. conducted by Henze et al., all meningiomas evaluated Details of imaging the tumour volume for fractionated showed a high Ga-DOTATOC uptake [14,15]. In a radiotherapy in the Charité medical school have been pilot study, the same group recently performed CT, described elsewhere [17]. Briefly, following the planning- MRI, and Ga-DOTATOC PET examinations on 26 CT, MR imaging of the skull was performed with the patients with intracranial meningiomas before radiother- use of a head coil in most patients with a 1.0 T scanner apy. Ga-DOTATOC-PET provided additional informa- (Siemens Harmony™, Siemens Medical Solutions, Erlan- tion concerning the spread of the tumour and led to a gen, Germany). Regularly, magnetization-prepared rapid significant modification of the gross tumour volume in gradient echo (MP-RAGE) T1-weighted sequences were about two thirds of the patients examined [16]. The used for coregistration after intravenous application of acquisition of Ga-DOTATOC scans on PET/CT scan- Gadolinium-DTPA ([Gd], Magnevist™, Schering AG, ners helps to estimate the relation of PET findings to Berlin, Germany) at a dosage of 0.1 mmol/kg of body weight.These 3-Dvolumedatasetsat a 1- (to 1.5) mm anatomical structures. In our own study using Ga- DOTATOC-PET/CT, the gross tumour volume was slice thickness offer high spatial resolution and allow for modified based on Ga-DOTATOC-PET data in 28/39 coronal and sagittal reformations, enabling contouring patients with positive PET scans [17]. in orthogonal planes. In the present study, the results of MRI, CT, and Details of functional imaging have been described pre- 68 68 Ga-DOTATOC PET were retrospectively compared in viously [17]. Ga-DOTATOC was applied intravenously a study group of 16 patients with SB meningiomas. The followed by a tracer uptake phase of 60 min, as recom- influence of PET imaging on pretherapeutic detection of mended by Henze et al. [15]. The applied dose of Ga- transgression of the SB was evaluated and the influence DOTATOC was between 70 and 120 MBq (1.9-3.2 of PET on the definition of tumour extent was mCi). The patient was placed in a dedicated positioning quantified. device for the head using an additional cushion and bandages for fixation. A contrast enhanced low-dose CT Materials and Methods scan (detector collimation, 16 × 1.5 mm; tube current, Between May 2006 and November 2010, a group of 50 100 mAs; tube voltage, 120 kV; gantry rotation time, 0.8 consecutive patients with 56 SB meningiomas under- s) of the entire head was performed for attenuation cor- went planning CT, MRI, and Ga-DOTATOC-PET/CT rection. PET was acquired in a single bed position with (with contrast-enhanced CT) prior to the start of ther- a 16 cm axial FOV from the base of the skull to the ver- apy. Fifty meningiomas showed areas with high Ga- tex and an emission time of 20 minutes. PET emission DOTATOC uptake. Infracranial extension was visible in data were reconstructed as coronal, axial, and sagittal MRI/CT or PET in 16/50 patients, who formed the using a 128 × 128 matrix. study group and were further analysed in a retrospective Planning-CT, MRI, and PET data were coregistered manner. There was infracranial extension in all patients. using the treatment planning software BrainSCAN™ In addition, some patients showed extracranial extension v.5.1 (BrainLAB AG, Feldkirchen, Germany). CT, MRI, to other sites (not infracranial, four orbit and one and PET were fused automatically using image fusion Graf et al. Head & Face Medicine 2012, 8:1 Page 3 of 6 http://www.head-face-med.com/content/8/1/1 software and a mutual information algorithm. The valid- bony lesions. Two meningiomas showed infracranial ity of image fusion has been successfully tested pre- invasion along the vessels without bony abnormalities in viously by Grosu et al. [18]. CT. Evaluation of meningioma infiltration in the bony The windowing of Ga-DOTATOC-PET was defined foramina by CT showed most tumorous changes were visually following the method published by Astner et al. evident in the foramen rotundum and the foramen ovale [19]. The threshold of PET was adapted to tumours visi- (Table 1). In lesions accompanied by structural changes blebyMRI in regionswhere thetumourborderednor- of these foramina, infiltrative growth into skeletal mus- mal brain tissue and could be outlined with high cle was present in 8 lesions (62%). precision, e.g., where the meningioma bordered normal The mean and median of the MRI/CT and PET brain matter. Under the assumption that the Ga- volumes were almost identical. We analysed involve- DOTATOC-PET uptake in meningiomas is homoge- ment of six designated infracranial spaces in each neous [20], the tumour borders (defined on Ga- patient, resulting in a total of 96 sites. All 16 meningio- DOTATOC-PET images in slices with well defined bor- mas grossly extended into at least one infracranial site. ders by MRI) were used to outline the tumour margins The infratemporal fossa and pterygopalatine fossa were on Ga DOTATOC-PET images in regions where the mostly involved. The visualization of tumour expansion margins were not visible by MRI. into designated infracranial spaces by MRI/CT and PET All examinations in one patient were performed and a comparison between both modalities are shown in within a time frame of 14 days. A checklist for local Table 2, with PET demonstrating a slightly better visibi- tumour extension and infiltration of bone and sites was lity of the involved areas compared with MRI/CT. With used in this study. Conventional imaging findings were respect to the infracranial sites evaluated, there were 7 regularly interpreted by two experienced radiologists. cases with negative MRI/CT and positive PET, resulting Using a dedicated workstation, two experienced nuclear in discrepancies in 7 of the 96 sites evaluated (7%) and medicine physicians interpreted PET/CT fused images 7 of the 42 sites affected (17%). The infracranial volume and their CT and PET components. If there was dis- delineable by PET was larger than the volume delineable agreement, the comparison results were reached by by MRI, although it did not reach the level of signifi- consensus. cance (p = 0.06). Example images are shown in Figure 1. The planning CT scans obtained with bone window settings (window width 2000 Hounsfield units, centre Discussion level 500 Hounsfield units) were used to determine the Transcranial meningiomas spread through the foramina signs of erosion of adjacent bone or hyperostotic of the skull, entering the pterygoid region through the changes [21]. Tumour-specific abnormalities were floor of the middle cranial fossa, suture lines, and the defined as hyperintense or Gd enhancing structures in foramina of the skull [23,24]. This group of meningio- MRI and tracer enhancing areas in PET, often a “side- mas is characterized by a high rate of recurrence, up to to-side” comparison with MRI was used to determine if 45% in some studies [2,25,26]. Recurrence correlates a structure was normal or abnormal [22]. Visualization with the extent of resection in neurosurgery [6] and of bony structure changes, tumours spreading to the extent of coverage in stereotactic radiosurgery [27]. bony canals or foramina, communication with the mid- Tumorous invasion of SB bone without hyperostosis dle fossa, and infracranial tumour expansion were com- was addressed in a study by Pieper et al. [28], where paredinMRI,CT, andPET images.Inanadditional each of the eight patients showed erosion of the middle step, the infracranial volume was delineated using MRI/ fossa floor and extension through the cranial base fora- CT and Ga DOTATOC-PET separately. The statistical mina, specifically the rotundum and ovale, without evi- software R, version 2.11.1 (R Foundation for Statistical dence of hyperostosis. The prevalence of lytic changes is Computing, Vienna, Austria) was used for statistical in accordance with our findings. Of the 16 patients with analysis. Non-parametric differences were analysed using infracranial extension, identified by MRI/CT or PET, the Wilcoxon test (at a 0.05 level of significance). there was association with bony changes in 13 patients (88%). These findings confirmed the observation of Leo- Results netti et al. [2] that there was a strong correlation All meningiomas showed areas with high Ga DOTA- between radiologically visible invasion of osseous struc- TOC uptake, enabling delineation in MRI ± CT and tures of the middle cranial and infracranial growth of PET in each case. The majority (75%) of lesions involved meningiomas. Furthermore, in patients in whom struc- the sphenoid bone. Volumes measured by MRI were tural bone changes were identified preoperatively, histo- enlarged in MRI/CT by a mean additional volume of 2.3 pathological findings showed the tumour grossly ml (7.2% of the MRI volumes) that was only identifiable invaded the skeletal muscle in all cases; while, this was only visible with imaging in 62% of cases in our study. in CT. Osteolytic lesions represented the majority of Graf et al. Head & Face Medicine 2012, 8:1 Page 4 of 6 http://www.head-face-med.com/content/8/1/1 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. CT and MRI scanning have being estimated adequate extent of infracranial expansion could be missed by for surgery for a long time [29,30]; although, anatomical MRI/CT alone as 7/16 cases were positive by PET and imaging methods have their limitations for target deli- negative by MRI/CT. neationininfiltrativelesions and postoperatively [16]. Other studies found Ga DOTATOC-PET improved We found the infracranial volume delineable by PET the delineation of SB meningiomas compared with MRI/ was larger than the volume by MRI/CT and the true CT in the context of FSRT. Henze et al. [14] examined Table 2 Comparison of MRI/CT and PET findings for detection of infracranial invasion in meningiomas with SB transgression on a lesional basis. Pat. Volume Volume Infracranial Infracranial Infracranial Infracranial Infracranial Infracranial Infracranial Infracranial No. MRI/CT PET invasion invasion invasion invasion invasion invasion volume volume 3 3 (cm ) (cm ) ITF PPF Masticator Carotideal Para- Retro- MRI/CT PET (cm ) space space pharyngeal pharyngeal (cm ) space space 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. Graf et al. Head & Face Medicine 2012, 8:1 Page 5 of 6 http://www.head-face-med.com/content/8/1/1 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. Ga-DOTATOC-PET/CT allowed markedly better delineation of the extent of infiltrative, infracranial extension compared with both CT and MRI. 8 meningiomas with Ga DOTATOC-PET and found Conclusions valuable additional information regarding the extent of In this study, the extent of local meningioma invasion meningiomas located beneath osseous structures, espe- detected by MRI/CT and Ga-DOTATOC-PET were cially at the SB. Later, the same group reported their not consistent. Ga-DOTATOC-PET is a sensitive experiences in 26 patients with meningiomas. They functional method for demonstrating the dimensions found 73% of the planned target volume for definitive of infracranial meningioma infiltration and may contri- radiotherapy treatment was significantly modified by the bute to FSRT planning in cases where CT and MRI use of Ga-DOTATOC-PET [16]. In our previous are not conclusive in regions that are difficult to study, which included 42 patients with meningiomas (27 image. SB), we used Ga-DOTATOC-PET/CT to detect modi- fication of the gross tumour volume in 72% of patients List of abbreviations used [17]. The tumour extent visible by MRI/CT compared MRI: Magnetic resonance imaging; CT: Computed tomography; SB: Skull to Ga-DOTATOC-PET/CT was larger in 23% and base; MRI/CT: MRI ± CT; PET: Positron emission tomography; Ga-DOTATOC- PET: Ga-DOTATOC positron emission tomography; F: Female; M: Male; L: smaller in 49% of cases. Dammers et al. described a case Left; R: Right; SP: Sphenoid bone; TE: Temporal bone; OC: Occipital bone; NC: in which radioguided resection of a meningioma, using No changes; OV: Foramen ovale, RO: Foramen rotundum; ITF: Infratemporal 111indium-labelled somatostatin receptors, enhanced fossa; PPF: Pterygopalatine fossa. the extent of the resection and discussed how this could Author details be of potential use in maximizing the resection of Department of Radiation Oncology, Charité Universitätsmedizin Berlin, meningiomas involving the cranial base region [31]. Berlin, Germany. Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. Department of Radiation To our knowledge, descriptions of infracranial exten- Oncology, Klinikum Frankfurt (Oder), Germany. sion of SB meningiomas in the context of FRST are sparse. We reviewed the published studies concerning Authors’ contributions RG analyzed the CT, MRI, and PET data, performed the analysis, and drafted delineation of SB meningiomas with Ga-DOTATOC the first version of the manuscript. MP supervised the analysis of the PET PET [14-17,32-34] and other tracers [19,35,36] and data and revised the manuscript. RW made substantial contributions to the found transcranial extension of SB meningiomas was conception and design of the study. PW contributed to the analysis and interpretation of data. VB participated in designing the study and approved not mentioned, probably due to the comparably lower the treatment concepts. WB approved the final version of the manuscript. numbers of SB meningiomas examined. HB coordinated the recruitment of patients and data acquisition. All authors When MRI/CT showed meningioma infiltration in the participated in critical discussion of the data and the conclusions. All authors improved the manuscript and approved the final version. bony foramina, visualisation of the involvement by PET lacked small details, which may have been due to the Competing interests higher slice thickness and lower spatial resolution of The authors declare that they have no competing interests. PET (in comparison to MRI/CT). Several other draw- Received: 29 October 2011 Accepted: 4 January 2012 backs in this study have been discussed previously [17]. Published: 4 January 2012 As found in most studies on the target volume defini- tion of meningiomas, this study is limited by the lack of References 1. Preston-Martin S: Descriptive epidemiology of primary tumors of the histological verification. To address the problem of the brain, cranial nerves and cranial meninges in Los Angeles County. choice of threshold levels [15,16], a fixed threshold Neuroepidemiology 1989, 8:283-295. could be useful for tumour segmentation to reduce 2. 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Pieper DR, Al-Mefty O, Hanada Y, Buechner D: Hyperostosis associated • No space constraints or color figure charges with meningioma of the cranial base: Secondary changes or tumour • Immediate publication on acceptance invasion. Neurosurg 1999, 44:742-746. 22. Schmalfuss IM, Camp M: Skull base: pseudolesion or true lesion? Eur • Inclusion in PubMed, CAS, Scopus and Google Scholar Radiol 2008, 18:1232-1243. • Research which is freely available for redistribution 23. Farr HW, Gray GF, Vrana M, Panio M: Extracranial meningioma. J Surg Oncol 1973, 5:411-420. Submit your manuscript at www.biomedcentral.com/submit http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Head & Face Medicine Springer Journals

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

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Medicine & Public Health; Otorhinolaryngology; Oral and Maxillofacial Surgery; Dentistry
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1746-160X
DOI
10.1186/1746-160X-8-1
pmid
22217329
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Abstract

Introduction: Magnetic resonance imaging (MRI) and computed tomography (CT) with Ga-DOTATOC positron emission tomography ( Ga-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 Ga-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 cm , which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm ). Conclusions: Ga-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, Ga-DOTATOC, PET, Stereotactic radiotherapy Introduction Meningiomas in this location tend to progress transcra- Meningiomas are common intracranial tumours with 25 nially or invade the infracranial spaces via natural open- to 30% located at the skull base (SB) [1]. When originat- ings [2,4] and recur in up to 45% of cases after surgery ing from the anterior clinoid process or medial sphenoid [5]. There is a strong correlation between the extent of wing, they have an increased propensity to invade bone resection and rate of recurrence [6]; therefore, accurate [2], which is a strong risk factor for recurrence [3]. determination of tumour extension is critical for plan- ning the magnitude of surgery and/or radiotherapy. Computed tomography (CT) and magnetic resonance * Correspondence: reinhold.graf@charite.de † Contributed equally imaging (MRI) are widely used in the diagnosis of SB Department of Radiation Oncology, Charité Universitätsmedizin Berlin, meningiomas and complement each other in the ability Berlin, Germany to determine tumour extent [7]. CT has proven to be Full list of author information is available at the end of the article © 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. Graf et al. Head & Face Medicine 2012, 8:1 Page 2 of 6 http://www.head-face-med.com/content/8/1/1 more effective than MRI in diagnosing bone infiltrations maxillary sinus). These extensions were not evaluated in at the anterior region of the SB [8,9]; while, MRI ima- this study. The study group included 11 women and 5 ging of the cranial base has a high sensitivity due to men with a mean age of 54.4 (range 25-73) years. Eleven excellent spatial and contrast resolution. However, espe- patients had undergone surgery and/or radiotherapy and cially in the central SB, there are structures with high 5 patients had not received any therapy before. Patho- signal intensity and high contrast-enhancement in MRI, histologically, there were 7 meningiomas with a WHO which make it difficult to exactly delineate meningioma grade 1 tumour (9 unknown). Nine meningiomas under- tissue from normal structures [10]. went FSRT as primary treatment without histological Receptor imaging offers an additional tool for imaging confirmation, when imaging morphology and clinical meningiomas. Meningiomas show high expression of course suggested the diagnosis of a WHO grade I or II several receptors, including somatostatin receptors (SR) meningioma. The study was based on the Declaration of subtype 2 (SSTR 2) [11,12]. Recently the somatostatin Helsinki and the principles of ‘good clinical practice’. analogue, 1,4,7,10-tetraazacyclododecane-N,N’,N”,N"’- The protocol was approved by the ethics committee of tetraacetic-acid-D-Phe1-Tyr3-octreotide ( Ga-DOTA- our institution. Written informed consent was obtained TOC) labeled with the positron emitter Ga (half-life, from all patients before enrolment into the study. Writ- 68 min) was developed. Ga-DOTATOC is a positron ten informed consent was obtained from the patient for emission tomography (PET) tracer and shows up to publication of this case report and accompanying nine-fold higher affinity to SSTR 2, as compared to the images. A copy of the written consent is available for SPECT ligand 111In-DTPA-octreotide [13]. In studies review by the Editor-in-Chief of this journal. conducted by Henze et al., all meningiomas evaluated Details of imaging the tumour volume for fractionated showed a high Ga-DOTATOC uptake [14,15]. In a radiotherapy in the Charité medical school have been pilot study, the same group recently performed CT, described elsewhere [17]. Briefly, following the planning- MRI, and Ga-DOTATOC PET examinations on 26 CT, MR imaging of the skull was performed with the patients with intracranial meningiomas before radiother- use of a head coil in most patients with a 1.0 T scanner apy. Ga-DOTATOC-PET provided additional informa- (Siemens Harmony™, Siemens Medical Solutions, Erlan- tion concerning the spread of the tumour and led to a gen, Germany). Regularly, magnetization-prepared rapid significant modification of the gross tumour volume in gradient echo (MP-RAGE) T1-weighted sequences were about two thirds of the patients examined [16]. The used for coregistration after intravenous application of acquisition of Ga-DOTATOC scans on PET/CT scan- Gadolinium-DTPA ([Gd], Magnevist™, Schering AG, ners helps to estimate the relation of PET findings to Berlin, Germany) at a dosage of 0.1 mmol/kg of body weight.These 3-Dvolumedatasetsat a 1- (to 1.5) mm anatomical structures. In our own study using Ga- DOTATOC-PET/CT, the gross tumour volume was slice thickness offer high spatial resolution and allow for modified based on Ga-DOTATOC-PET data in 28/39 coronal and sagittal reformations, enabling contouring patients with positive PET scans [17]. in orthogonal planes. In the present study, the results of MRI, CT, and Details of functional imaging have been described pre- 68 68 Ga-DOTATOC PET were retrospectively compared in viously [17]. Ga-DOTATOC was applied intravenously a study group of 16 patients with SB meningiomas. The followed by a tracer uptake phase of 60 min, as recom- influence of PET imaging on pretherapeutic detection of mended by Henze et al. [15]. The applied dose of Ga- transgression of the SB was evaluated and the influence DOTATOC was between 70 and 120 MBq (1.9-3.2 of PET on the definition of tumour extent was mCi). The patient was placed in a dedicated positioning quantified. device for the head using an additional cushion and bandages for fixation. A contrast enhanced low-dose CT Materials and Methods scan (detector collimation, 16 × 1.5 mm; tube current, Between May 2006 and November 2010, a group of 50 100 mAs; tube voltage, 120 kV; gantry rotation time, 0.8 consecutive patients with 56 SB meningiomas under- s) of the entire head was performed for attenuation cor- went planning CT, MRI, and Ga-DOTATOC-PET/CT rection. PET was acquired in a single bed position with (with contrast-enhanced CT) prior to the start of ther- a 16 cm axial FOV from the base of the skull to the ver- apy. Fifty meningiomas showed areas with high Ga- tex and an emission time of 20 minutes. PET emission DOTATOC uptake. Infracranial extension was visible in data were reconstructed as coronal, axial, and sagittal MRI/CT or PET in 16/50 patients, who formed the using a 128 × 128 matrix. study group and were further analysed in a retrospective Planning-CT, MRI, and PET data were coregistered manner. There was infracranial extension in all patients. using the treatment planning software BrainSCAN™ In addition, some patients showed extracranial extension v.5.1 (BrainLAB AG, Feldkirchen, Germany). CT, MRI, to other sites (not infracranial, four orbit and one and PET were fused automatically using image fusion Graf et al. Head & Face Medicine 2012, 8:1 Page 3 of 6 http://www.head-face-med.com/content/8/1/1 software and a mutual information algorithm. The valid- bony lesions. Two meningiomas showed infracranial ity of image fusion has been successfully tested pre- invasion along the vessels without bony abnormalities in viously by Grosu et al. [18]. CT. Evaluation of meningioma infiltration in the bony The windowing of Ga-DOTATOC-PET was defined foramina by CT showed most tumorous changes were visually following the method published by Astner et al. evident in the foramen rotundum and the foramen ovale [19]. The threshold of PET was adapted to tumours visi- (Table 1). In lesions accompanied by structural changes blebyMRI in regionswhere thetumourborderednor- of these foramina, infiltrative growth into skeletal mus- mal brain tissue and could be outlined with high cle was present in 8 lesions (62%). precision, e.g., where the meningioma bordered normal The mean and median of the MRI/CT and PET brain matter. Under the assumption that the Ga- volumes were almost identical. We analysed involve- DOTATOC-PET uptake in meningiomas is homoge- ment of six designated infracranial spaces in each neous [20], the tumour borders (defined on Ga- patient, resulting in a total of 96 sites. All 16 meningio- DOTATOC-PET images in slices with well defined bor- mas grossly extended into at least one infracranial site. ders by MRI) were used to outline the tumour margins The infratemporal fossa and pterygopalatine fossa were on Ga DOTATOC-PET images in regions where the mostly involved. The visualization of tumour expansion margins were not visible by MRI. into designated infracranial spaces by MRI/CT and PET All examinations in one patient were performed and a comparison between both modalities are shown in within a time frame of 14 days. A checklist for local Table 2, with PET demonstrating a slightly better visibi- tumour extension and infiltration of bone and sites was lity of the involved areas compared with MRI/CT. With used in this study. Conventional imaging findings were respect to the infracranial sites evaluated, there were 7 regularly interpreted by two experienced radiologists. cases with negative MRI/CT and positive PET, resulting Using a dedicated workstation, two experienced nuclear in discrepancies in 7 of the 96 sites evaluated (7%) and medicine physicians interpreted PET/CT fused images 7 of the 42 sites affected (17%). The infracranial volume and their CT and PET components. If there was dis- delineable by PET was larger than the volume delineable agreement, the comparison results were reached by by MRI, although it did not reach the level of signifi- consensus. cance (p = 0.06). Example images are shown in Figure 1. The planning CT scans obtained with bone window settings (window width 2000 Hounsfield units, centre Discussion level 500 Hounsfield units) were used to determine the Transcranial meningiomas spread through the foramina signs of erosion of adjacent bone or hyperostotic of the skull, entering the pterygoid region through the changes [21]. Tumour-specific abnormalities were floor of the middle cranial fossa, suture lines, and the defined as hyperintense or Gd enhancing structures in foramina of the skull [23,24]. This group of meningio- MRI and tracer enhancing areas in PET, often a “side- mas is characterized by a high rate of recurrence, up to to-side” comparison with MRI was used to determine if 45% in some studies [2,25,26]. Recurrence correlates a structure was normal or abnormal [22]. Visualization with the extent of resection in neurosurgery [6] and of bony structure changes, tumours spreading to the extent of coverage in stereotactic radiosurgery [27]. bony canals or foramina, communication with the mid- Tumorous invasion of SB bone without hyperostosis dle fossa, and infracranial tumour expansion were com- was addressed in a study by Pieper et al. [28], where paredinMRI,CT, andPET images.Inanadditional each of the eight patients showed erosion of the middle step, the infracranial volume was delineated using MRI/ fossa floor and extension through the cranial base fora- CT and Ga DOTATOC-PET separately. The statistical mina, specifically the rotundum and ovale, without evi- software R, version 2.11.1 (R Foundation for Statistical dence of hyperostosis. The prevalence of lytic changes is Computing, Vienna, Austria) was used for statistical in accordance with our findings. Of the 16 patients with analysis. Non-parametric differences were analysed using infracranial extension, identified by MRI/CT or PET, the Wilcoxon test (at a 0.05 level of significance). there was association with bony changes in 13 patients (88%). These findings confirmed the observation of Leo- Results netti et al. [2] that there was a strong correlation All meningiomas showed areas with high Ga DOTA- between radiologically visible invasion of osseous struc- TOC uptake, enabling delineation in MRI ± CT and tures of the middle cranial and infracranial growth of PET in each case. The majority (75%) of lesions involved meningiomas. Furthermore, in patients in whom struc- the sphenoid bone. Volumes measured by MRI were tural bone changes were identified preoperatively, histo- enlarged in MRI/CT by a mean additional volume of 2.3 pathological findings showed the tumour grossly ml (7.2% of the MRI volumes) that was only identifiable invaded the skeletal muscle in all cases; while, this was only visible with imaging in 62% of cases in our study. in CT. Osteolytic lesions represented the majority of Graf et al. Head & Face Medicine 2012, 8:1 Page 4 of 6 http://www.head-face-med.com/content/8/1/1 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. CT and MRI scanning have being estimated adequate extent of infracranial expansion could be missed by for surgery for a long time [29,30]; although, anatomical MRI/CT alone as 7/16 cases were positive by PET and imaging methods have their limitations for target deli- negative by MRI/CT. neationininfiltrativelesions and postoperatively [16]. Other studies found Ga DOTATOC-PET improved We found the infracranial volume delineable by PET the delineation of SB meningiomas compared with MRI/ was larger than the volume by MRI/CT and the true CT in the context of FSRT. Henze et al. [14] examined Table 2 Comparison of MRI/CT and PET findings for detection of infracranial invasion in meningiomas with SB transgression on a lesional basis. Pat. Volume Volume Infracranial Infracranial Infracranial Infracranial Infracranial Infracranial Infracranial Infracranial No. MRI/CT PET invasion invasion invasion invasion invasion invasion volume volume 3 3 (cm ) (cm ) ITF PPF Masticator Carotideal Para- Retro- MRI/CT PET (cm ) space space pharyngeal pharyngeal (cm ) space space 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. Graf et al. Head & Face Medicine 2012, 8:1 Page 5 of 6 http://www.head-face-med.com/content/8/1/1 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. Ga-DOTATOC-PET/CT allowed markedly better delineation of the extent of infiltrative, infracranial extension compared with both CT and MRI. 8 meningiomas with Ga DOTATOC-PET and found Conclusions valuable additional information regarding the extent of In this study, the extent of local meningioma invasion meningiomas located beneath osseous structures, espe- detected by MRI/CT and Ga-DOTATOC-PET were cially at the SB. Later, the same group reported their not consistent. Ga-DOTATOC-PET is a sensitive experiences in 26 patients with meningiomas. They functional method for demonstrating the dimensions found 73% of the planned target volume for definitive of infracranial meningioma infiltration and may contri- radiotherapy treatment was significantly modified by the bute to FSRT planning in cases where CT and MRI use of Ga-DOTATOC-PET [16]. In our previous are not conclusive in regions that are difficult to study, which included 42 patients with meningiomas (27 image. SB), we used Ga-DOTATOC-PET/CT to detect modi- fication of the gross tumour volume in 72% of patients List of abbreviations used [17]. The tumour extent visible by MRI/CT compared MRI: Magnetic resonance imaging; CT: Computed tomography; SB: Skull to Ga-DOTATOC-PET/CT was larger in 23% and base; MRI/CT: MRI ± CT; PET: Positron emission tomography; Ga-DOTATOC- PET: Ga-DOTATOC positron emission tomography; F: Female; M: Male; L: smaller in 49% of cases. Dammers et al. described a case Left; R: Right; SP: Sphenoid bone; TE: Temporal bone; OC: Occipital bone; NC: in which radioguided resection of a meningioma, using No changes; OV: Foramen ovale, RO: Foramen rotundum; ITF: Infratemporal 111indium-labelled somatostatin receptors, enhanced fossa; PPF: Pterygopalatine fossa. the extent of the resection and discussed how this could Author details be of potential use in maximizing the resection of Department of Radiation Oncology, Charité Universitätsmedizin Berlin, meningiomas involving the cranial base region [31]. Berlin, Germany. Department of Nuclear Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. Department of Radiation To our knowledge, descriptions of infracranial exten- Oncology, Klinikum Frankfurt (Oder), Germany. sion of SB meningiomas in the context of FRST are sparse. We reviewed the published studies concerning Authors’ contributions RG analyzed the CT, MRI, and PET data, performed the analysis, and drafted delineation of SB meningiomas with Ga-DOTATOC the first version of the manuscript. MP supervised the analysis of the PET PET [14-17,32-34] and other tracers [19,35,36] and data and revised the manuscript. RW made substantial contributions to the found transcranial extension of SB meningiomas was conception and design of the study. PW contributed to the analysis and interpretation of data. VB participated in designing the study and approved not mentioned, probably due to the comparably lower the treatment concepts. WB approved the final version of the manuscript. numbers of SB meningiomas examined. HB coordinated the recruitment of patients and data acquisition. All authors When MRI/CT showed meningioma infiltration in the participated in critical discussion of the data and the conclusions. All authors improved the manuscript and approved the final version. bony foramina, visualisation of the involvement by PET lacked small details, which may have been due to the Competing interests higher slice thickness and lower spatial resolution of The authors declare that they have no competing interests. PET (in comparison to MRI/CT). Several other draw- Received: 29 October 2011 Accepted: 4 January 2012 backs in this study have been discussed previously [17]. Published: 4 January 2012 As found in most studies on the target volume defini- tion of meningiomas, this study is limited by the lack of References 1. Preston-Martin S: Descriptive epidemiology of primary tumors of the histological verification. To address the problem of the brain, cranial nerves and cranial meninges in Los Angeles County. choice of threshold levels [15,16], a fixed threshold Neuroepidemiology 1989, 8:283-295. could be useful for tumour segmentation to reduce 2. 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