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Disappearance of tumor contrast on contrast-enhanced FLAIR imaging of cerebral gliomas
Magnetic Resonance Imaging 18 (2000) 513–518
Disappearance of tumor contrast on contrast-enhanced FLAIR imaging of cerebral gliomas Marco Essig*, S.O. Schoenberg, J. Debus, G. van Kaick Department of Radiology, German Cancer Research Center, 69120 Heidelberg, Germany Received 23 August 1999; 13 February 2000
Abstract Contrast-enhanced fluid-attentuated inversion recovery (FLAIR) magnetic resonance (MR) imaging has shown to be a valuable diagnostic modality in the assessment of cerebral gliomas. In this study we report of a potential pitfall regarding the delineation of enhancing tumor parts on contrast enhanced FLAIR imaging. In a limited number of patients, the administration of gadolinium obscures the area of contrast enhancement on contrast enhanced FLAIR images. Therefore the delineation of the macroscopic tumor parts, which are of great importance for the treatment planning is substantially worsened. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Fluid attenuated inversion recovery; Cerebral gliomas; T1-time; Contrast media
1. Introduction Magnetic resonance imaging (MRI) is the most sensitive imaging modality in the detection and delineation of primary intraaxial brain tumors (gliomas) [1]. For detecting cerebral gliomas, T2-weighted sequences were widely accepted to be the most sensitive imaging modality [1] because as in many other pathologic conditions the prolongation of the T2 relaxation time by tumor tissue results in a high contrast between the lesion and brain tissue [2,3]. Enhancing regions in anaplastic or malignant gliomas are generally equated with the more solid part of the tumors and histopathologic correlation has proved that enhancing areas on contrast enhanced scans largely correspond to the densely cellular, hypervascular tissue of viable tumor [4]. On non-enhanced T1-weighted images, these areas are hypointense to the surrounding normal tissue indicating a substantially prolonged T1 time. In recent studies, a fluidattenuated inversion-recovery (FLAIR) MR sequence has shown to be a valuable imaging sequence in the assessment of cerebral gliomas [5,6]. FLAIR produces heavily T2weighted and cerebrospinal fluid (CSF)-nulled MR images [7,8] which allows a better delineation of tumors close to * Corresponding author. Tel.: ⫹49-6221-42-2525; fax: ⫹49-6221-422531. E-mail address: [email protected] (M. Essig).
CSF filled structures. Therefore, FLAIR MR imaging is currently used as a routine sequence in most MR centers and has replaced proton-density sequences. Due to a mild T1 weighting of the FLAIR sequence, which is induced by the long inversion time used for the CSF suppression, FLAIR images obtained after administration of i.v. gadolinium can be used to detect pathologic enhancement [9]. This effect has shown to further enhance the delineation of intraaxial tumors and other contrast enhancing CNS diseases [9,10]. In some circumstances, e.g., radiotherapy planning or neurosurgical navigation, where only a limited number of images can be applied, contrast enhanced FLAIR may be used as a solitary sequence to save time and to avoid potential errors from e.g., image fusion. In this report, we present a potential pitfall regarding the use of contrast enhanced FLAIR imaging alone in patients with enhancing anaplastic or malignant cerebral gliomas.
2. Materials and methods 2.1. Patient studies Eighty patients (49 female and 31 male, age range 21– 68 years, mean age 42 years), with enhancing cerebral tumors histologically confirmed as anaplastic (WHO Grade III) or malignant (WHO Grade IV) cerebral gliomas were exam-
0730-725X/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S 0 7 3 0 - 7 2 5 X ( 0 0 ) 0 0 1 3 9 - 9
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M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
Table 1 Lession delineation of contrast-enhanced FLAIR vs. conventional MRI Score
p Value
Reader I
Reader II
FLAIR
FLAIR
Superior
Equal
47 24 CE FLAIR significantly better p ⬍ 0.01
Kappa
FLAIR
FLAIR
FLAIR
FLAIR
Inferior
Superior
Equal
Inferior
9
51 19 CE FLAIR significantly better p ⬍ 0.01
10
0.85
Displayed are the number of patients. the score was: 1 ⫽ FLAIR superior; 2 ⫽ FLAIR equal; 3 ⫽ FLAIR inferior.
ined on a standard 1.5 Tesla clinical MR scanner by FLAIR and conventional MR imaging before and after contrast media application. The first 18 of these patients were previously published [10]. The imaging protocol included T1-weighted SE, PD- and T2-weighted FSE and FLAIR prior to administration of gadolinium. After the application of a standard dose of 0.1 mmol/kg BW of Gd-DTPA (Magnevist™, Schering, Berlin, Germany) T1 and FLAIR imaging was repeated using identical imaging parameters.For all sequences, 23 slices with a matrix-size of 168 ⫻ 256, a rectangular field of view 180 ⫻ 240 mm, slice thickness 5 mm with an interslice gap of 1 mm were acquired. For PD- and T2-weighted images a FSE technique was used with TR/TE1/TE2 ⫽ 3000/22/90 ms, echo-train length ⫽ 5. The acquisition time was 1:57 min for both echoes. The FLAIR sequence was used with TR/ TE ⫽ 9000/123 ms, an echo-train length of 7 and an inversion time (TI) of 2340 ms leading to a high lesion-to-whitematter contrast and allowing the acquisition of 23 sections in 3:36 min. For T1-weighted imaging a SE sequence with TR/TE ⫽ 600/15 ms and an acquisition time of 2:23 min was used. The acquired images before and after contrast media application were compared using quantitative and qualitative criteria. For quantitative assessment signal intensities were measured by a region of interest (ROI) analysis of the tumor, background, CSF and image noise. Mean tumor signal was measured within a homogenous region in the central area of the tumor. ROIs were placed in the non-enhancing tumor parts. In cases of enhancing tumors, an additional ROI was
placed within a homogeneously enhancing area. Background signal was measured in normal appearing white matter tissue adjacent to the tumor. The standard deviation of the noise was measured in the phase-encoding direction in regions outside the head. From the ROI data tumor-to-background contrast and tumor-to-background contrast-to-noise (C/N) ratios were calculated. The qualitative criteria was the delineation of enhancing tumor areas from surrounding non-enhancing tumor parts. Therefore the conventional imaging sequences were compared as a group with the FLAIR images using a three point scale with 1 ⫽ CE (contrast-enhanced) FLAIR superior; 2 ⫽ CE FLAIR equal; 3 ⫽ CE FLAIR inferior. All evaluations were analyzed independently by two MR-experienced readers. For statistical analysis a McNemar test was used. The interobserver variability was assessed with the statistics.
3. Results and discussion FLAIR imaging was found to be superior to conventional MR imaging in the delineation of the gross tumor volume and the delineation of the enhancing from the non enhancing tumor parts (Table 1, Fig. 1). In the qualitative analysis, the tumor contrast was best on the contrast enhanced FLAIR images (Table 2). However, in ten patients (3 female and 7 male, age range 31– 63 years, mean age 44 years) out of the series of 80, the gadolinium enhanced FLAIR images were rated inferior to the conventional sequences in the delinea-
Table 2. Tumor contrast and contrast-to-noise ratio Tumor-to-background contrast Before CM T2 T1 FLAIR
1.1 ⫾ 0.3 ⫺0.1 ⫾ 0.2a 0.8 ⫾ 0.4b c
Tumor-to-background contrast-to noise After CM
Before CM
After CM
— 0.5 ⫾ 0.3a 1.6 ⴞ 0.9a
41.3 ⫾ 15.5 ⫺5.0 ⫾ 1.2b 20.4 ⫾ 12.4b b
Displayed are the mean values and standard deviation; highest values marked in bold. a Fast FLAIR statistically higher than all other imaging modalities at the 0.01 level using a one tailed paired t-test. b T2-weighted FSE significantly higher than T1-weighted SE and fast FLAIR at the 0.01 level using a one tailed paired t-test. c No statistical difference using a one tailed paired t-test.
— 21.4 ⫾ 13.7a 43.6 ⴞ 21.2a
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
515
Fig. 1. T2-weighted FSE (a), FLAIR (b), contrast-enhanced T1-weighted SE (c), and contrast-enhanced FLAIR (d) in a 45-year-old patient with right insular high grade glioma (grade IV). T2-weighted FSE and non enhanced FLAIR depict an area of increased signal involving right insular region. After contrast media application a region of pathologic enhancement appear in the anterior and central portion of the tumor. On T1-weighted SE images these areas are clearly depicted, however the gross tumor volume as seen on the T2-weighted images could not be delineated. On contrast enhanced FLAIR imaging a substantial enhancement could be observed with a significant increase of the signal in the enhancing tumor parts leading to a parallel depiction of the enhancing and non enhancing tumor parts on one imaging sequence.
516
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
Fig. 2. Non-enhanced FLAIR (a), contrast-enhanced FLAIR (b), and contrast-enhanced T1-weighted SE (c) in a 46-year-old patient with histologically confirmed left frontal anaplastic astrocytoma (WHO Grade III). The area of hypointensity on non enhanced FLAIR (a, arrows) is congruent with the later enhancing macroscopic tumor on T1 weighted SE and could be clearly delineated from the surrounding non enhancing tumor tissue. After contrast media, a substantial contrast enhancement occurred on FLAIR (b) with equal signal of enhancing and non enhancing tumor tissue. Thereafter the delineation of the different tumor components was inferior than on the non-enhanced images (a).
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
tion of the enhancing tumor parts. In these patients, a disappearance of an initially present intratumoral contrast on the non enhanced FLAIR images was observed after the administration of contrast media (Fig. 2). In all of theses cases, the later enhancing tumor parts initially presented as hypointense compared to the non-enhancing tumor parts and the edema on non-enhanced FLAIR, which may indicate a pronounced prolongation of the apparent T1 relaxation times in theses tissues (Fig. 2a). Therefore the different tumor parts could be clearly delineated on the nonenhanced FLAIR and conventional MR imaging. After gadolinium was administered, the enhancing portions of the tumor were similar in signal intensity to areas with prolonged T2 signal, resulting in inferior delineation of the enhancing tumor tissue (Fig. 2b). Enhancing regions in malignant gliomas are generally equated with the more solid part of the tumors and histopathological correlation have proved that enhancing areas on contrast enhanced scans largely correspond to the densely cellular, hypervascular tissue of viable tumor [4]. The knowledge of the exact macroscopic tumor margins is essential for the treatment decision and planning in these patients. As to the treatment of gliomas, the main goal of surgery is the gross total resection of the tumor along its macroscopic boundaries, which obtains histologic confirmation, and increases the survival time [11,12]. The macroscopic tumor boundaries have to be defined prior to surgery. After surgical intervention, the suppression of the CSF makes residual or recurrent tumors more conspicuous, which might be very useful in the further management of these patients, e.g., further treatment planning. In radiotherapy the main target volume is congruent with the whole tumor volume including the enhancing tumor tissue, which is the center of the highest radiation applied [13]. Previous studies using contrast enhanced FLAIR imaging [9,10] have shown that the method enables the concurrent depiction of the enhancing and non-enhancing tumor parts in one single imaging sequence. Additionally, contrast enhanced FLAIR achieved the best tumor contrast and contrast-to-noise ratios (Table 2 and Ref. 10). This was found to be very helpful in the exact delineation of the tumor boundaries and therefore in the target volume definition in neurosurgery and radiotherapy. FLAIR was also found to be a valuable imaging sequence if only a limited number of images can be used such as in radiotherapy planning or neurosurgical navigation. The use of a sequence displaying both T1 and T2 changes is time saving and potential errors by the use of image fusion algorithms can be avoided. However T1-weighted MR imaging is still the gold standard for displaying pathologic contrast enhancements and could not be replaced by FLAIR. In this study, we report on a fraction of patients in which the use of contrast media decreased the tumor contrast on FLAIR imaging. In all these patients, the later enhancing tumors were initially hypointense indicating a substantial prolongation of the T1 relaxation time. Because the FLAIR
517
technique was developed to reduce the CSF (very long T1 relaxation time), tissues with an increased load of tumor cells will also be reduced in signal intensity. On non-enhanced FLAIR imaging this enables to clearly delineate tissues with different amount of tumor cell density, which correlates with the later enhancing macroscopic tumor tissue. In a small number of cases, areas of tumor enhancement on the FLAIR sequences had signal intensity similar to adjacent areas with prolonged T2 signal intensity. This made it difficult to differentiate enhancing an non enhancing regions of the tumor on the contrast-enhanced FLAIR images. The assimilation of the signal leads to a decreased delineation of the macroscopic tumor parts which has to be taken into consideration for the image interpretation, especially if FLAIR imaging is used only after contrast media application or as the sole treatment planning imaging modality. We would therefore recommend to use contrast enhanced FLAIR imaging in combination with non-enhanced FLAIR sequences and contrast enhanced T1-weighted imaging. In conclusion, administration of contrast media could obscure areas of enhancing tumor in patients with cerebral gliomas on FLAIR MR imaging. The assimilation of the signal in different tumor parts is most likely induced by a prolonged T1 relaxation time in the macroscopic tumor tissue which is equaled by the noticeable contrast enhancement of these tumor parts on enhanced FLAIR images. Therefore, we recommend not to rely entirely on the contrast-enhanced FLAIR images in patients with enhancing cerebral gliomas.
References [1] Brant-Zawadski M, Norman D, Newton TH. Magnetic resonance imaging of the brain: the optimal screening technique. Radiology 1984;152:71–7. [2] Byrne TN. Imaging of gliomas. Semin Oncol 1994;21:162–71. [3] Yuh WTC, Halloran JI, Mayr NA, Fisher DJ, Nguyen HD, Simonson TM. Dose of contrast material in the MR imaging evaluation of central nervous system tumors. J Magn Reson Imaging 1994;4:242–9. [4] Earnest F IV, Kelly PJ, Scheithauer BW, et al. Cerebral astrocytomas: histopathologic correlation of MR and CT contrast enhancement with stereotactic biopsy. Radiology 1988;166:823–7. [5] Tsuchiya K, Mizutani Y, Hachiya J. Preliminary evaluation of fluidattenuated inversion-recovery MR in the diagnosis of intracranial tumors. Am J Neuroradiol 1996;17:1081– 6. [6] Essig M, Hawighorst H, Schoenberg SO, et al. Fast fluid-attenuated inversion-recovery (FLAIR) MR imaging in the assessment of intraaxial brain tumors. J Magn Reson Imaging 1998;8:789 –98. [7] De Coene B, Hajnal JV, Gatehouse P, et al. MR of the brain using fluid-attenuated inversion recovery (FLAIR) pulse sequences. Am J Neuroradiol 1992;13:1555– 64. [8] Rydberg JN, Hammond CA, Grimm RC, et al. Initial clinical experience in MR imaging of the brain with a fast fluid-attenuated inversion-recovery pulse sequence. Radiology 1994;193:173– 80. [9] Mathews VP, Caldemeyer KS, Lowe MJ, Greenspan SL, Ulmer JL. Brain: gadolinium-enhanced fast fluid-attenuated inversion recovery MR imaging. Radiology 1999;211:257– 63.
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M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
[10] Essig, M., Schoenberg SO, Hawighorst H, et al. Cerebral gliomas and metastases: assessment with contrast enhanced fast fluid-attenuated inversion-recovery MR imaging. Radiology 1999;210:551–7. [11] Ciric I, Vick NA, Mikhael MA, Cozzens J, Eller T, Wash A. Aggressive surgery for malignant supratentorial gliomas. Clin Neurosurg 1990;36:375– 83.
[12] Albert FK, Forsting M, Sartor K, Adams HP, Kunze S. Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery 1994;34:45– 61. [13] Shrieve DC, Loeffler JS. Advances in radiation therapy for brain tumors. Neurol Clin 1995;13:773–93.
Disappearance of tumor contrast on contrast-enhanced FLAIR imaging of cerebral gliomas Marco Essig*, S.O. Schoenberg, J. Debus, G. van Kaick Department of Radiology, German Cancer Research Center, 69120 Heidelberg, Germany Received 23 August 1999; 13 February 2000
Abstract Contrast-enhanced fluid-attentuated inversion recovery (FLAIR) magnetic resonance (MR) imaging has shown to be a valuable diagnostic modality in the assessment of cerebral gliomas. In this study we report of a potential pitfall regarding the delineation of enhancing tumor parts on contrast enhanced FLAIR imaging. In a limited number of patients, the administration of gadolinium obscures the area of contrast enhancement on contrast enhanced FLAIR images. Therefore the delineation of the macroscopic tumor parts, which are of great importance for the treatment planning is substantially worsened. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Fluid attenuated inversion recovery; Cerebral gliomas; T1-time; Contrast media
1. Introduction Magnetic resonance imaging (MRI) is the most sensitive imaging modality in the detection and delineation of primary intraaxial brain tumors (gliomas) [1]. For detecting cerebral gliomas, T2-weighted sequences were widely accepted to be the most sensitive imaging modality [1] because as in many other pathologic conditions the prolongation of the T2 relaxation time by tumor tissue results in a high contrast between the lesion and brain tissue [2,3]. Enhancing regions in anaplastic or malignant gliomas are generally equated with the more solid part of the tumors and histopathologic correlation has proved that enhancing areas on contrast enhanced scans largely correspond to the densely cellular, hypervascular tissue of viable tumor [4]. On non-enhanced T1-weighted images, these areas are hypointense to the surrounding normal tissue indicating a substantially prolonged T1 time. In recent studies, a fluidattenuated inversion-recovery (FLAIR) MR sequence has shown to be a valuable imaging sequence in the assessment of cerebral gliomas [5,6]. FLAIR produces heavily T2weighted and cerebrospinal fluid (CSF)-nulled MR images [7,8] which allows a better delineation of tumors close to * Corresponding author. Tel.: ⫹49-6221-42-2525; fax: ⫹49-6221-422531. E-mail address: [email protected] (M. Essig).
CSF filled structures. Therefore, FLAIR MR imaging is currently used as a routine sequence in most MR centers and has replaced proton-density sequences. Due to a mild T1 weighting of the FLAIR sequence, which is induced by the long inversion time used for the CSF suppression, FLAIR images obtained after administration of i.v. gadolinium can be used to detect pathologic enhancement [9]. This effect has shown to further enhance the delineation of intraaxial tumors and other contrast enhancing CNS diseases [9,10]. In some circumstances, e.g., radiotherapy planning or neurosurgical navigation, where only a limited number of images can be applied, contrast enhanced FLAIR may be used as a solitary sequence to save time and to avoid potential errors from e.g., image fusion. In this report, we present a potential pitfall regarding the use of contrast enhanced FLAIR imaging alone in patients with enhancing anaplastic or malignant cerebral gliomas.
2. Materials and methods 2.1. Patient studies Eighty patients (49 female and 31 male, age range 21– 68 years, mean age 42 years), with enhancing cerebral tumors histologically confirmed as anaplastic (WHO Grade III) or malignant (WHO Grade IV) cerebral gliomas were exam-
0730-725X/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S 0 7 3 0 - 7 2 5 X ( 0 0 ) 0 0 1 3 9 - 9
514
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
Table 1 Lession delineation of contrast-enhanced FLAIR vs. conventional MRI Score
p Value
Reader I
Reader II
FLAIR
FLAIR
Superior
Equal
47 24 CE FLAIR significantly better p ⬍ 0.01
Kappa
FLAIR
FLAIR
FLAIR
FLAIR
Inferior
Superior
Equal
Inferior
9
51 19 CE FLAIR significantly better p ⬍ 0.01
10
0.85
Displayed are the number of patients. the score was: 1 ⫽ FLAIR superior; 2 ⫽ FLAIR equal; 3 ⫽ FLAIR inferior.
ined on a standard 1.5 Tesla clinical MR scanner by FLAIR and conventional MR imaging before and after contrast media application. The first 18 of these patients were previously published [10]. The imaging protocol included T1-weighted SE, PD- and T2-weighted FSE and FLAIR prior to administration of gadolinium. After the application of a standard dose of 0.1 mmol/kg BW of Gd-DTPA (Magnevist™, Schering, Berlin, Germany) T1 and FLAIR imaging was repeated using identical imaging parameters.For all sequences, 23 slices with a matrix-size of 168 ⫻ 256, a rectangular field of view 180 ⫻ 240 mm, slice thickness 5 mm with an interslice gap of 1 mm were acquired. For PD- and T2-weighted images a FSE technique was used with TR/TE1/TE2 ⫽ 3000/22/90 ms, echo-train length ⫽ 5. The acquisition time was 1:57 min for both echoes. The FLAIR sequence was used with TR/ TE ⫽ 9000/123 ms, an echo-train length of 7 and an inversion time (TI) of 2340 ms leading to a high lesion-to-whitematter contrast and allowing the acquisition of 23 sections in 3:36 min. For T1-weighted imaging a SE sequence with TR/TE ⫽ 600/15 ms and an acquisition time of 2:23 min was used. The acquired images before and after contrast media application were compared using quantitative and qualitative criteria. For quantitative assessment signal intensities were measured by a region of interest (ROI) analysis of the tumor, background, CSF and image noise. Mean tumor signal was measured within a homogenous region in the central area of the tumor. ROIs were placed in the non-enhancing tumor parts. In cases of enhancing tumors, an additional ROI was
placed within a homogeneously enhancing area. Background signal was measured in normal appearing white matter tissue adjacent to the tumor. The standard deviation of the noise was measured in the phase-encoding direction in regions outside the head. From the ROI data tumor-to-background contrast and tumor-to-background contrast-to-noise (C/N) ratios were calculated. The qualitative criteria was the delineation of enhancing tumor areas from surrounding non-enhancing tumor parts. Therefore the conventional imaging sequences were compared as a group with the FLAIR images using a three point scale with 1 ⫽ CE (contrast-enhanced) FLAIR superior; 2 ⫽ CE FLAIR equal; 3 ⫽ CE FLAIR inferior. All evaluations were analyzed independently by two MR-experienced readers. For statistical analysis a McNemar test was used. The interobserver variability was assessed with the statistics.
3. Results and discussion FLAIR imaging was found to be superior to conventional MR imaging in the delineation of the gross tumor volume and the delineation of the enhancing from the non enhancing tumor parts (Table 1, Fig. 1). In the qualitative analysis, the tumor contrast was best on the contrast enhanced FLAIR images (Table 2). However, in ten patients (3 female and 7 male, age range 31– 63 years, mean age 44 years) out of the series of 80, the gadolinium enhanced FLAIR images were rated inferior to the conventional sequences in the delinea-
Table 2. Tumor contrast and contrast-to-noise ratio Tumor-to-background contrast Before CM T2 T1 FLAIR
1.1 ⫾ 0.3 ⫺0.1 ⫾ 0.2a 0.8 ⫾ 0.4b c
Tumor-to-background contrast-to noise After CM
Before CM
After CM
— 0.5 ⫾ 0.3a 1.6 ⴞ 0.9a
41.3 ⫾ 15.5 ⫺5.0 ⫾ 1.2b 20.4 ⫾ 12.4b b
Displayed are the mean values and standard deviation; highest values marked in bold. a Fast FLAIR statistically higher than all other imaging modalities at the 0.01 level using a one tailed paired t-test. b T2-weighted FSE significantly higher than T1-weighted SE and fast FLAIR at the 0.01 level using a one tailed paired t-test. c No statistical difference using a one tailed paired t-test.
— 21.4 ⫾ 13.7a 43.6 ⴞ 21.2a
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
515
Fig. 1. T2-weighted FSE (a), FLAIR (b), contrast-enhanced T1-weighted SE (c), and contrast-enhanced FLAIR (d) in a 45-year-old patient with right insular high grade glioma (grade IV). T2-weighted FSE and non enhanced FLAIR depict an area of increased signal involving right insular region. After contrast media application a region of pathologic enhancement appear in the anterior and central portion of the tumor. On T1-weighted SE images these areas are clearly depicted, however the gross tumor volume as seen on the T2-weighted images could not be delineated. On contrast enhanced FLAIR imaging a substantial enhancement could be observed with a significant increase of the signal in the enhancing tumor parts leading to a parallel depiction of the enhancing and non enhancing tumor parts on one imaging sequence.
516
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
Fig. 2. Non-enhanced FLAIR (a), contrast-enhanced FLAIR (b), and contrast-enhanced T1-weighted SE (c) in a 46-year-old patient with histologically confirmed left frontal anaplastic astrocytoma (WHO Grade III). The area of hypointensity on non enhanced FLAIR (a, arrows) is congruent with the later enhancing macroscopic tumor on T1 weighted SE and could be clearly delineated from the surrounding non enhancing tumor tissue. After contrast media, a substantial contrast enhancement occurred on FLAIR (b) with equal signal of enhancing and non enhancing tumor tissue. Thereafter the delineation of the different tumor components was inferior than on the non-enhanced images (a).
M. Essig et al. / Magnetic Resonance Imaging 18 (2000) 513–518
tion of the enhancing tumor parts. In these patients, a disappearance of an initially present intratumoral contrast on the non enhanced FLAIR images was observed after the administration of contrast media (Fig. 2). In all of theses cases, the later enhancing tumor parts initially presented as hypointense compared to the non-enhancing tumor parts and the edema on non-enhanced FLAIR, which may indicate a pronounced prolongation of the apparent T1 relaxation times in theses tissues (Fig. 2a). Therefore the different tumor parts could be clearly delineated on the nonenhanced FLAIR and conventional MR imaging. After gadolinium was administered, the enhancing portions of the tumor were similar in signal intensity to areas with prolonged T2 signal, resulting in inferior delineation of the enhancing tumor tissue (Fig. 2b). Enhancing regions in malignant gliomas are generally equated with the more solid part of the tumors and histopathological correlation have proved that enhancing areas on contrast enhanced scans largely correspond to the densely cellular, hypervascular tissue of viable tumor [4]. The knowledge of the exact macroscopic tumor margins is essential for the treatment decision and planning in these patients. As to the treatment of gliomas, the main goal of surgery is the gross total resection of the tumor along its macroscopic boundaries, which obtains histologic confirmation, and increases the survival time [11,12]. The macroscopic tumor boundaries have to be defined prior to surgery. After surgical intervention, the suppression of the CSF makes residual or recurrent tumors more conspicuous, which might be very useful in the further management of these patients, e.g., further treatment planning. In radiotherapy the main target volume is congruent with the whole tumor volume including the enhancing tumor tissue, which is the center of the highest radiation applied [13]. Previous studies using contrast enhanced FLAIR imaging [9,10] have shown that the method enables the concurrent depiction of the enhancing and non-enhancing tumor parts in one single imaging sequence. Additionally, contrast enhanced FLAIR achieved the best tumor contrast and contrast-to-noise ratios (Table 2 and Ref. 10). This was found to be very helpful in the exact delineation of the tumor boundaries and therefore in the target volume definition in neurosurgery and radiotherapy. FLAIR was also found to be a valuable imaging sequence if only a limited number of images can be used such as in radiotherapy planning or neurosurgical navigation. The use of a sequence displaying both T1 and T2 changes is time saving and potential errors by the use of image fusion algorithms can be avoided. However T1-weighted MR imaging is still the gold standard for displaying pathologic contrast enhancements and could not be replaced by FLAIR. In this study, we report on a fraction of patients in which the use of contrast media decreased the tumor contrast on FLAIR imaging. In all these patients, the later enhancing tumors were initially hypointense indicating a substantial prolongation of the T1 relaxation time. Because the FLAIR
517
technique was developed to reduce the CSF (very long T1 relaxation time), tissues with an increased load of tumor cells will also be reduced in signal intensity. On non-enhanced FLAIR imaging this enables to clearly delineate tissues with different amount of tumor cell density, which correlates with the later enhancing macroscopic tumor tissue. In a small number of cases, areas of tumor enhancement on the FLAIR sequences had signal intensity similar to adjacent areas with prolonged T2 signal intensity. This made it difficult to differentiate enhancing an non enhancing regions of the tumor on the contrast-enhanced FLAIR images. The assimilation of the signal leads to a decreased delineation of the macroscopic tumor parts which has to be taken into consideration for the image interpretation, especially if FLAIR imaging is used only after contrast media application or as the sole treatment planning imaging modality. We would therefore recommend to use contrast enhanced FLAIR imaging in combination with non-enhanced FLAIR sequences and contrast enhanced T1-weighted imaging. In conclusion, administration of contrast media could obscure areas of enhancing tumor in patients with cerebral gliomas on FLAIR MR imaging. The assimilation of the signal in different tumor parts is most likely induced by a prolonged T1 relaxation time in the macroscopic tumor tissue which is equaled by the noticeable contrast enhancement of these tumor parts on enhanced FLAIR images. Therefore, we recommend not to rely entirely on the contrast-enhanced FLAIR images in patients with enhancing cerebral gliomas.
References [1] Brant-Zawadski M, Norman D, Newton TH. Magnetic resonance imaging of the brain: the optimal screening technique. Radiology 1984;152:71–7. [2] Byrne TN. Imaging of gliomas. Semin Oncol 1994;21:162–71. [3] Yuh WTC, Halloran JI, Mayr NA, Fisher DJ, Nguyen HD, Simonson TM. Dose of contrast material in the MR imaging evaluation of central nervous system tumors. J Magn Reson Imaging 1994;4:242–9. [4] Earnest F IV, Kelly PJ, Scheithauer BW, et al. Cerebral astrocytomas: histopathologic correlation of MR and CT contrast enhancement with stereotactic biopsy. Radiology 1988;166:823–7. [5] Tsuchiya K, Mizutani Y, Hachiya J. Preliminary evaluation of fluidattenuated inversion-recovery MR in the diagnosis of intracranial tumors. Am J Neuroradiol 1996;17:1081– 6. [6] Essig M, Hawighorst H, Schoenberg SO, et al. Fast fluid-attenuated inversion-recovery (FLAIR) MR imaging in the assessment of intraaxial brain tumors. J Magn Reson Imaging 1998;8:789 –98. [7] De Coene B, Hajnal JV, Gatehouse P, et al. MR of the brain using fluid-attenuated inversion recovery (FLAIR) pulse sequences. Am J Neuroradiol 1992;13:1555– 64. [8] Rydberg JN, Hammond CA, Grimm RC, et al. Initial clinical experience in MR imaging of the brain with a fast fluid-attenuated inversion-recovery pulse sequence. Radiology 1994;193:173– 80. [9] Mathews VP, Caldemeyer KS, Lowe MJ, Greenspan SL, Ulmer JL. Brain: gadolinium-enhanced fast fluid-attenuated inversion recovery MR imaging. Radiology 1999;211:257– 63.
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[10] Essig, M., Schoenberg SO, Hawighorst H, et al. Cerebral gliomas and metastases: assessment with contrast enhanced fast fluid-attenuated inversion-recovery MR imaging. Radiology 1999;210:551–7. [11] Ciric I, Vick NA, Mikhael MA, Cozzens J, Eller T, Wash A. Aggressive surgery for malignant supratentorial gliomas. Clin Neurosurg 1990;36:375– 83.
[12] Albert FK, Forsting M, Sartor K, Adams HP, Kunze S. Early postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis. Neurosurgery 1994;34:45– 61. [13] Shrieve DC, Loeffler JS. Advances in radiation therapy for brain tumors. Neurol Clin 1995;13:773–93.