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The value of intraoperative sonography in low grade glioma surgery
Clinical Neurology and Neurosurgery 131 (2015) 64–68
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
The value of intraoperative sonography in low grade glioma surgery Athanasios K. Petridis a,∗,1 , Maxim Anokhin a,1 , Jan Vavruska a , Mehran Mahvash b , Martin Scholz a a b
Wedau Kliniken Duisburg, Sana Konzern, Department of Neurosurgery, Duisburg, Germany Department of Neurosurgery, Clinic of Cologne University of Witten-Herdecke, Duisburg, Germany
a r t i c l e
i n f o
Article history: Received 10 December 2014 Received in revised form 2 February 2015 Accepted 3 February 2015 Available online 11 February 2015 Keywords: Intraoperative sonography Low grade glioma Neuronavigation
a b s t r a c t Objective: There is a number of different methods to localize a glioma intraoperatively. Neuronavigation, intraoperative MRI, 5-aminolevulinic acid, as well as intraoperative sonography. Every method has its advantages and disadvantages. Low grade gliomas do not show a specific signal with 5-aminolevulinic acid and are difficult to distinguish macroscopically from normal tissue. In the present study we stress out the importance of intraoperative diagnostic ultrasound for localization of low grade gliomas. Methods: We retrospectively evaluated the charts and MRIs of 34 patients with low grade gliomas operated in our department from 2011 until December 2014. The efficacy of ultrasound as an intraoperative navigational tool was assessed. In 15 patients ultrasound was used and in 19 not. Only histologically proven low grades gliomas (astrocytomas grade II) were evaluated. Results: In none of the patients where ultrasound (combined with neuronavigation) was used (N = 15) to find the tumors, the target was missed, whereas the exclusive use of neuronavigation missed the target in 5 of 19 cases of small subcortical low grade gliomas. Conclusions: Intraoperative ultrasound is an excellent tool in localizing low grade gliomas intraoperatively. It is an inexpensive, real time neuronavigational tool, which overcomes brain shift. Even when identifying the tumors with ultrasound is very reliable, the extend of resection and the decision to remove any residual tumor with the help of ultrasound is at the moment unreliable. © 2015 Elsevier B.V. All rights reserved.
1. Introduction It has been shown that surgical extension of a tumor, as well as the tumor grade is essential for the prolonged survival of glioma patients [1–3]. There are different methods, which are helpful to localize the glioma and allow extended tumor resection, such as 5-aminolevulinic acid, intraoperative MRI as well as intraoperative ultrasound [2,4–7]. Every different method has its advantages and disadvantages. In low grade gliomas the tumor does not enhance by contrast and is visualized well by T2-weighted and Flair MRI [5]. However after resection of the tumor and the resulting brainshift the intraoperative interpretation of the MRI data can be difficult. Apart from this, intraoperative MRI is expensive and not available in every neurosurgical center whereas ultrasonography is associated with lower costs. Intraoperative ultrasound identifies low
∗ Corresponding author at: Department of Neurosurgery, Wedau Kliniken Duisburg, Zu den Rehwiesen 9, 45077 Duisburg, Germany. Tel.: +49 203 7332425; fax: +49431 7332156. E-mail address: [email protected] (A.K. Petridis). 1 AKP and MA contributed equally. http://dx.doi.org/10.1016/j.clineuro.2015.02.004 0303-8467/© 2015 Elsevier B.V. All rights reserved.
grade gliomas as hyperechoic and homogenous tumors and helps to localize subcortical lesions under a normal appearing brain surface [8–10]. At the beginning of the use of ultrasound by Reid in 1978 [11] the image quality was low therefore the method was not used by neurosurgeons routinely. Today the technology of ultrasound has been improved significantly, providing the surgeon with a very valuable tool in identifying the tumor [12] and even make a preliminary diagnosis of the tumor as low or high grade glioma [3]. In the present study we investigate the value of intraoperative ultrasound to localize low grade gliomas in comparison to neuronavigation.
2. Materials and methods Thirty-four patients with histologically proven low grade gliomas (astrocytoma grade II only) have been operated in our department from 2011 until December 2014. The patients charts as well as the surgical reports and the pre- and postoperative MRIs, were retrospectively evaluated for the intraoperative use of diagnostic ultrasound (N = 15). The focus of the study was to evaluate if the use of ultrasound was helpful in finding the tumor. Other
A.K. Petridis et al. / Clinical Neurology and Neurosurgery 131 (2015) 64–68
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Fig. 1. Profile of low grade gliomas. (A) Age distribution of patients with low grade glioma. Peak age was in the 4th and 5th decade. (B) In most patients a subtotal resection of the tumor had been performed. The reason for subtotal resection was tumor grow in eloquent areas not permitting a total resection without risk of neurological deficits. (C) Tumor localization showed a distribution of the tumors in all brain areas with highest frequency in the frontal lobe. The distribution of tumors in different areas is similar to the size of the lobes.
parameters evaluated, were the completeness of tumor resection, patient age, tumor location, tumor progress. In all patients intraoperative neuronavigation was used to localize the tumor. The follow up period was from 1 month – 14 years (mean follow up 1.6 years, patients with longer follow up periods than 2011 had been operated in other hospitals and were treated in our department after 2011 and their data had been taken in our databank for the present retrospective study). Six patients lost from follow up since they moved to other areas or other countries. The follow up was conducted every 3 months for the first year and afterwards every 6 months. The ultrasound probe (small and large end fire) was covered in a sterile sheath and saline gel was used as an acoustic coupling agent. The probe was gently positioned on the dura mater or on the brain surface when the dura mater was opened. The cavity was rinsed with sterile saline to create a sonographic bath. The ultrasound device used was the HI VISION PreirusTM (Hitachi). The small probe had a 19 and 29 mm diameter (EUP V53W; 4.5 MHz) and the large probe had a diameter of 24 and 36 mm (EUP C532; 4.5 MHz). Statistical analysis was performed with 2 -test with significance at p < 0.05.
3. Results Twenty-one patients were males and 13 females. A subtotal resection was performed in 19 patients (55.8%), a biopsy in 9 (stereotactic in 3 patients) (26.4%) and a gross total resection in 6 (17.6%) (Fig. 1B). Most of the tumors (19/34, 55.8%) were located in the frontal lobe. Gross total resection was performed only in tumors
Fig. 2. Ultrasound guided glioma localization. In all patients where ultrasound was used to find the tumor (combined with neuronavigation) the tumor was found. Only use of neuronavigation missed the target in 5 of 19 patients.
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Fig. 3. Surgery of low grade glioma in a 45 y.o. male patient. (A) T2 weighted MRI showing a hyperintense signal in the left frontal lobe. In the left picture a T1 image with contrast shows no enhancement of the tumor. (B) Post-surgically the tumor is completely removed. (C) Intraoperative 5 aminolevulinic acid did not visualize the tumor since low grade gliomas are not illuminated by 5 aminolevulinic acid. Macroscopically the tumor could not be distinguished from normal tissue even if it was located cortically. (D) Sonography identified the tumor clearly and the glioma was resected. (E) Sonography after resection shows the cavity but in the rim of the resection there is a hyperechoic signal, which does not allow a clear differentiation of normal tissue from tumor.
located in the frontal lobe (6/19, 31%) whereas in the brainstem only biopsies (2/2, 100%) had been performed (Fig. 1C). The patients with gross total tumor removal showed no tumor progress in the time of follow up (16%, 0/6, in one patient with more than 95% resection there was a recurrence after 8 years of progression free survival) whereas the progress rate in biopsied patients was 33% (3/9) and in subtotally removed tumors 16% (3/19). However the differences did not reach statistical significance and the follow up time as well as the number of patients is not high enough to provide any meaningful conclusion. 3.1. Tumor location The surgeries were performed by experienced attending surgeons. However not all of them used ultrasound to locate the tumor. In few cases of the patient group where diagnostic ultrasound had not been used, the histology could not show a definitive diagnosis and the surgery was performed again. The target was missed in one stereotactic biopsy (1/3, 33%) and in 4 open microsurgical biopsies. In 4/19 (21%) patients with open microsurgery and no use of diagnostic ultrasound the target was missed whereas in all of the 15 patients with use of ultrasound the target was hit (0%). Statistical significance was not reached (Fig. 2). 3.2. Illustrative cases Figs. 3 and 4 show examples of gross total surgical removal of a low grade glioma with ultrasound use intraoperatively. In comparison to the brain tissue the tumor tissue shows high and homogenous echogenicity. Fig. 5 shows an example of a tumor (according to MRI spectroscopy). The microsurgical biopsy reached only the border of the tumor and histology showed only “reactive cells”. A second surgery had been performed to reveal the
histological diagnosis of low grade glioma cells (probable) in a highly reactive tissue. 3.3. Patients with tumor progress Apart from the evaluation of the value of ultrasound we also evaluated the natural history of the low grade gliomas in our patient population. The mean time follow up was 1.6 years with three patients have been followed up for 11 years, 9, years and 7 years but treated in another hospital first and came for treatment to our department after 2011. The first patient was treated in 2003 with a nearly total excision of a right frontal astrocytoma grade II and than a progress appeared in 2011 and again in 2014. The patient had a progression free survival for 8 years and is still alive now, 11 years after first surgery. The second long term follow up patient was operated 9 years ago. The first progress was diagnosed 8 years after the first surgery. The third patient was operated 7 years ago and had a progression free survival for 4 years. All three patients are still alive and followed up in a 6 month interval at our department. The fourth patient with a tumor progress was biopsied 3 years ago on a precentral tumor and progress could be seen 3 years ago. The fifth patient had a tumor in the foramen Monroi, which was removed subtotally 2 years ago and progressed after 2 years. The sixth patient was operated with a biopsy on a thalamic low grade glioma and showed a minimal progress after 1 year. A seventh patient had a subtotal resection on a precentral tumor and showed progress after a year. 4. Discussion Intraoperative ultrasound localized the tumor in all cases, whereas intraoperative navigation, which does not follow brain shift during surgery, had a significant failure rate especially in
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Fig. 4. Intraoperative ultrasound identification of the tumor. (A) The sonography visualizes the tumor, which is hyperechoic, as well as a cyst into the tumor. (B) After removal of the tumor the cavity is seen but similar to Fig. 4A the margin of the resection cavity is hyperechoic making the decision of further removal of tissue difficult if relied only on the sonogram.
Fig. 5. Failure of tumor removal in a case where the target was localized only by neuronavigation in a 36 y.o. female patient. (A) The MR spectroscopy of normal tissue of the patient in a region remote from the tumor. (B) MR-spectrogram in the tumor. The choline peak is seen suggesting with a high probability that the tissue is a tumor. (C) After open biopsy of the tumor, histology could not find any tumor tissue but only reactive astrocytes. The post-surgical MRI shows that the biopsy was taken from the tumor margin. (D) A second surgery was performed with the aim of tumor reduction (tumor is close to the motoric cortex). Ultrasound helped to identify the tumor and remove a significant part of the tumor tissue. Right image: the tumor before surgery, Left: MRI after second surgery (white arrow: tumor).
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subcortically localized low grade gliomas. Sonography proved its value as a real time imaging and is not affected by brain shift, which starts at opening the dura mater and increases during tumor removal. Even vessels close to the tumor can be visualized by switching into color Doppler sonography mode. In low grade gliomas there is less peritumoral edema than in high grade gliomas, therefore the margins between the tumor and the adjacent normal brain are not obscured by edema, rendering the value of ultrasound higher in low grade gliomas [12]. But even with peritumoral edema intraoperative ultrasound seems to be also of help in identification of high grade gliomas [13]. There are studies, which correlate the histopathological findings of gliomas in the tumor infiltration zone with the sonographic signal and indicated that intraoperative ultrasound could show sonographic signs of residual tumor in the borders of “gross total resected tumors” [13–15]. On the other hand the hyperechoic rim around the resection cavity is a non-specific finding [13]. Even edema could be distinguished from solid tumor and improve tumor extension as shown in a study by LeRoux [9,10]. In our experience however, intra-operative ultrasound was very useful in identifying the tumor and delineating its margins before starting tumor removal. After the tumor was removed the quality of the ultrasound in identifying tumor remnants in the margins of the cavity decreased significantly and became unreliable. Gerganov et al. [4] also remarked that during tumor removal of low grade gliomas identification of the gliomas sonographically was excellent but there were difficulties in interpretation of tumor remnants when a tumor cavity was created. Blood, cottonoids, proteinaceus fluid can decrease the quality of the ultrasound image. Apart from our experience there are other studies indicating the high value of ultrasound intraoperatively in judging the boundaries of low grade gliomas [15]. Even if there is a great possibility in differentiating residual glioma from normal brain in low grade gliomas, in high grade gliomas it would be more efficient to rely on other methods like 5-aminolevulinic acid [2]. Unfortunately 5-aminolevulinic acid does not illuminate low grade gliomas. There is a number of studies which focus on distinguishing normal brain tissue from residual tumor ultrasonographically since intraoperative sonography is an easy to handle, inexpensive modality and most important, real-time, which is not affected by brain shift [3,15]. On the other hand, neuronavigation allows an accurate localization of the tumor, but it cannot exclude intraoperative dynamic changes of brain shift, which can be initiated by the loss of cerebrospinal fluid, tumor debulking or even brain deformation caused by positioning of the head [3].
5. Conclusion Intraoperative ultrasound guided localization of low grade gliomas combined with neuronavigation, especially in small subcortical lesions, is an excellent tool in the neurosurgeons armamentarium. With ultrasound guidance there was a 0% failure rate of localizing a low grade glioma. Conflict of interest The authors declare that there are no conflicts of interest. References [1] Hervey-Jumper SL, Berger MS. Role of surgical resection in low- and high-grade gliomas. Curr Treat Options Neurol 2014;16:284. [2] Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, et al. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 2008;62:564–76, discussion 564-576. [3] Wang J, Liu X, Ba YM, Yang YL, Gao GD, Wang L, et al. Effect of sonographically guided cerebral glioma surgery on survival time. J Ultrasound Med 2012;31:757–62. [4] Gerganov VM, Samii A, Giordano M, Samii M, Fahlbusch R. Two-dimensional high-end ultrasound imaging compared to intraoperative MRI during resection of low-grade gliomas. J Clin Neurosci 2011;18:669–73. [5] Mahvash M, Konig R, Urbach H, von Ortzen J, Meyer B, Schramm J, et al. FLAIR/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery. Neurosurgery 2006;58. ONS69-75; discussion ONS69-75. [6] Pamir MN, Ozduman K, Dincer A, Yildiz E, Peker S, Ozek MM. First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection. J Neurosurg 2010;112:57–69. [7] Tronnier VM, Bonsanto MM, Staubert A, Knauth M, Kunze S, Wirtz CR. Comparison of intraoperative MR imaging and 3D-navigated ultrasonography in the detection and resection control of lesions. Neurosurg Focus 2001;10:E3. [8] Hol PK, Dullerud R, Nordby HK. Intraoperative ultrasonography in brain surgery. Tidsskr Nor Laegeforen 1992;112:2346–8. [9] Le Roux PD, Berger MS, Wang K, Mack LA, Ojemann GA. Low grade gliomas: comparison of intraoperative ultrasound characteristics with preoperative imaging studies. J Neurooncol 1992;13:189–98. [10] Leroux PD, Winter TC, Berger MS, Mack LA, Wang K, Elliott JP. A comparison between preoperative magnetic resonance and intraoperative ultrasound tumor volumes and margins. J Clin Ultrasound 1994;22:29–36. [11] Reid MH. Ultrasonic visualization of a cervical cord cystic astrocytoma. Am J Roentgenol 1978;131:907–8. [12] Sosna J, Barth MM, Kruskal JB, Kane RA. Intraoperative sonography for neurosurgery. J Ultrasound Med 2005;24:1671–82. [13] Woydt M, Krone A, Becker G, Schmidt K, Roggendorf W, Roosen K. Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection. Acta Neurochir (Wien) 1996;138:1391–8. [14] Mair R, Heald J, Poeata I, Ivanov M. A practical grading system of ultrasonographic visibility for intracerebral lesions. Acta Neurochir (Wien) 2013;155:2293–8. [15] Tian YJ, Lin S, Liu HZ, Wang LS, He W, Zhang MZ, et al. Value of intra-operative ultrasound in detecting the boundaries of intra cranial gliomas. Zhonghua Yi Xue Za Zhi 2009;89:1305–8.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
The value of intraoperative sonography in low grade glioma surgery Athanasios K. Petridis a,∗,1 , Maxim Anokhin a,1 , Jan Vavruska a , Mehran Mahvash b , Martin Scholz a a b
Wedau Kliniken Duisburg, Sana Konzern, Department of Neurosurgery, Duisburg, Germany Department of Neurosurgery, Clinic of Cologne University of Witten-Herdecke, Duisburg, Germany
a r t i c l e
i n f o
Article history: Received 10 December 2014 Received in revised form 2 February 2015 Accepted 3 February 2015 Available online 11 February 2015 Keywords: Intraoperative sonography Low grade glioma Neuronavigation
a b s t r a c t Objective: There is a number of different methods to localize a glioma intraoperatively. Neuronavigation, intraoperative MRI, 5-aminolevulinic acid, as well as intraoperative sonography. Every method has its advantages and disadvantages. Low grade gliomas do not show a specific signal with 5-aminolevulinic acid and are difficult to distinguish macroscopically from normal tissue. In the present study we stress out the importance of intraoperative diagnostic ultrasound for localization of low grade gliomas. Methods: We retrospectively evaluated the charts and MRIs of 34 patients with low grade gliomas operated in our department from 2011 until December 2014. The efficacy of ultrasound as an intraoperative navigational tool was assessed. In 15 patients ultrasound was used and in 19 not. Only histologically proven low grades gliomas (astrocytomas grade II) were evaluated. Results: In none of the patients where ultrasound (combined with neuronavigation) was used (N = 15) to find the tumors, the target was missed, whereas the exclusive use of neuronavigation missed the target in 5 of 19 cases of small subcortical low grade gliomas. Conclusions: Intraoperative ultrasound is an excellent tool in localizing low grade gliomas intraoperatively. It is an inexpensive, real time neuronavigational tool, which overcomes brain shift. Even when identifying the tumors with ultrasound is very reliable, the extend of resection and the decision to remove any residual tumor with the help of ultrasound is at the moment unreliable. © 2015 Elsevier B.V. All rights reserved.
1. Introduction It has been shown that surgical extension of a tumor, as well as the tumor grade is essential for the prolonged survival of glioma patients [1–3]. There are different methods, which are helpful to localize the glioma and allow extended tumor resection, such as 5-aminolevulinic acid, intraoperative MRI as well as intraoperative ultrasound [2,4–7]. Every different method has its advantages and disadvantages. In low grade gliomas the tumor does not enhance by contrast and is visualized well by T2-weighted and Flair MRI [5]. However after resection of the tumor and the resulting brainshift the intraoperative interpretation of the MRI data can be difficult. Apart from this, intraoperative MRI is expensive and not available in every neurosurgical center whereas ultrasonography is associated with lower costs. Intraoperative ultrasound identifies low
∗ Corresponding author at: Department of Neurosurgery, Wedau Kliniken Duisburg, Zu den Rehwiesen 9, 45077 Duisburg, Germany. Tel.: +49 203 7332425; fax: +49431 7332156. E-mail address: [email protected] (A.K. Petridis). 1 AKP and MA contributed equally. http://dx.doi.org/10.1016/j.clineuro.2015.02.004 0303-8467/© 2015 Elsevier B.V. All rights reserved.
grade gliomas as hyperechoic and homogenous tumors and helps to localize subcortical lesions under a normal appearing brain surface [8–10]. At the beginning of the use of ultrasound by Reid in 1978 [11] the image quality was low therefore the method was not used by neurosurgeons routinely. Today the technology of ultrasound has been improved significantly, providing the surgeon with a very valuable tool in identifying the tumor [12] and even make a preliminary diagnosis of the tumor as low or high grade glioma [3]. In the present study we investigate the value of intraoperative ultrasound to localize low grade gliomas in comparison to neuronavigation.
2. Materials and methods Thirty-four patients with histologically proven low grade gliomas (astrocytoma grade II only) have been operated in our department from 2011 until December 2014. The patients charts as well as the surgical reports and the pre- and postoperative MRIs, were retrospectively evaluated for the intraoperative use of diagnostic ultrasound (N = 15). The focus of the study was to evaluate if the use of ultrasound was helpful in finding the tumor. Other
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65
Fig. 1. Profile of low grade gliomas. (A) Age distribution of patients with low grade glioma. Peak age was in the 4th and 5th decade. (B) In most patients a subtotal resection of the tumor had been performed. The reason for subtotal resection was tumor grow in eloquent areas not permitting a total resection without risk of neurological deficits. (C) Tumor localization showed a distribution of the tumors in all brain areas with highest frequency in the frontal lobe. The distribution of tumors in different areas is similar to the size of the lobes.
parameters evaluated, were the completeness of tumor resection, patient age, tumor location, tumor progress. In all patients intraoperative neuronavigation was used to localize the tumor. The follow up period was from 1 month – 14 years (mean follow up 1.6 years, patients with longer follow up periods than 2011 had been operated in other hospitals and were treated in our department after 2011 and their data had been taken in our databank for the present retrospective study). Six patients lost from follow up since they moved to other areas or other countries. The follow up was conducted every 3 months for the first year and afterwards every 6 months. The ultrasound probe (small and large end fire) was covered in a sterile sheath and saline gel was used as an acoustic coupling agent. The probe was gently positioned on the dura mater or on the brain surface when the dura mater was opened. The cavity was rinsed with sterile saline to create a sonographic bath. The ultrasound device used was the HI VISION PreirusTM (Hitachi). The small probe had a 19 and 29 mm diameter (EUP V53W; 4.5 MHz) and the large probe had a diameter of 24 and 36 mm (EUP C532; 4.5 MHz). Statistical analysis was performed with 2 -test with significance at p < 0.05.
3. Results Twenty-one patients were males and 13 females. A subtotal resection was performed in 19 patients (55.8%), a biopsy in 9 (stereotactic in 3 patients) (26.4%) and a gross total resection in 6 (17.6%) (Fig. 1B). Most of the tumors (19/34, 55.8%) were located in the frontal lobe. Gross total resection was performed only in tumors
Fig. 2. Ultrasound guided glioma localization. In all patients where ultrasound was used to find the tumor (combined with neuronavigation) the tumor was found. Only use of neuronavigation missed the target in 5 of 19 patients.
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Fig. 3. Surgery of low grade glioma in a 45 y.o. male patient. (A) T2 weighted MRI showing a hyperintense signal in the left frontal lobe. In the left picture a T1 image with contrast shows no enhancement of the tumor. (B) Post-surgically the tumor is completely removed. (C) Intraoperative 5 aminolevulinic acid did not visualize the tumor since low grade gliomas are not illuminated by 5 aminolevulinic acid. Macroscopically the tumor could not be distinguished from normal tissue even if it was located cortically. (D) Sonography identified the tumor clearly and the glioma was resected. (E) Sonography after resection shows the cavity but in the rim of the resection there is a hyperechoic signal, which does not allow a clear differentiation of normal tissue from tumor.
located in the frontal lobe (6/19, 31%) whereas in the brainstem only biopsies (2/2, 100%) had been performed (Fig. 1C). The patients with gross total tumor removal showed no tumor progress in the time of follow up (16%, 0/6, in one patient with more than 95% resection there was a recurrence after 8 years of progression free survival) whereas the progress rate in biopsied patients was 33% (3/9) and in subtotally removed tumors 16% (3/19). However the differences did not reach statistical significance and the follow up time as well as the number of patients is not high enough to provide any meaningful conclusion. 3.1. Tumor location The surgeries were performed by experienced attending surgeons. However not all of them used ultrasound to locate the tumor. In few cases of the patient group where diagnostic ultrasound had not been used, the histology could not show a definitive diagnosis and the surgery was performed again. The target was missed in one stereotactic biopsy (1/3, 33%) and in 4 open microsurgical biopsies. In 4/19 (21%) patients with open microsurgery and no use of diagnostic ultrasound the target was missed whereas in all of the 15 patients with use of ultrasound the target was hit (0%). Statistical significance was not reached (Fig. 2). 3.2. Illustrative cases Figs. 3 and 4 show examples of gross total surgical removal of a low grade glioma with ultrasound use intraoperatively. In comparison to the brain tissue the tumor tissue shows high and homogenous echogenicity. Fig. 5 shows an example of a tumor (according to MRI spectroscopy). The microsurgical biopsy reached only the border of the tumor and histology showed only “reactive cells”. A second surgery had been performed to reveal the
histological diagnosis of low grade glioma cells (probable) in a highly reactive tissue. 3.3. Patients with tumor progress Apart from the evaluation of the value of ultrasound we also evaluated the natural history of the low grade gliomas in our patient population. The mean time follow up was 1.6 years with three patients have been followed up for 11 years, 9, years and 7 years but treated in another hospital first and came for treatment to our department after 2011. The first patient was treated in 2003 with a nearly total excision of a right frontal astrocytoma grade II and than a progress appeared in 2011 and again in 2014. The patient had a progression free survival for 8 years and is still alive now, 11 years after first surgery. The second long term follow up patient was operated 9 years ago. The first progress was diagnosed 8 years after the first surgery. The third patient was operated 7 years ago and had a progression free survival for 4 years. All three patients are still alive and followed up in a 6 month interval at our department. The fourth patient with a tumor progress was biopsied 3 years ago on a precentral tumor and progress could be seen 3 years ago. The fifth patient had a tumor in the foramen Monroi, which was removed subtotally 2 years ago and progressed after 2 years. The sixth patient was operated with a biopsy on a thalamic low grade glioma and showed a minimal progress after 1 year. A seventh patient had a subtotal resection on a precentral tumor and showed progress after a year. 4. Discussion Intraoperative ultrasound localized the tumor in all cases, whereas intraoperative navigation, which does not follow brain shift during surgery, had a significant failure rate especially in
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Fig. 4. Intraoperative ultrasound identification of the tumor. (A) The sonography visualizes the tumor, which is hyperechoic, as well as a cyst into the tumor. (B) After removal of the tumor the cavity is seen but similar to Fig. 4A the margin of the resection cavity is hyperechoic making the decision of further removal of tissue difficult if relied only on the sonogram.
Fig. 5. Failure of tumor removal in a case where the target was localized only by neuronavigation in a 36 y.o. female patient. (A) The MR spectroscopy of normal tissue of the patient in a region remote from the tumor. (B) MR-spectrogram in the tumor. The choline peak is seen suggesting with a high probability that the tissue is a tumor. (C) After open biopsy of the tumor, histology could not find any tumor tissue but only reactive astrocytes. The post-surgical MRI shows that the biopsy was taken from the tumor margin. (D) A second surgery was performed with the aim of tumor reduction (tumor is close to the motoric cortex). Ultrasound helped to identify the tumor and remove a significant part of the tumor tissue. Right image: the tumor before surgery, Left: MRI after second surgery (white arrow: tumor).
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subcortically localized low grade gliomas. Sonography proved its value as a real time imaging and is not affected by brain shift, which starts at opening the dura mater and increases during tumor removal. Even vessels close to the tumor can be visualized by switching into color Doppler sonography mode. In low grade gliomas there is less peritumoral edema than in high grade gliomas, therefore the margins between the tumor and the adjacent normal brain are not obscured by edema, rendering the value of ultrasound higher in low grade gliomas [12]. But even with peritumoral edema intraoperative ultrasound seems to be also of help in identification of high grade gliomas [13]. There are studies, which correlate the histopathological findings of gliomas in the tumor infiltration zone with the sonographic signal and indicated that intraoperative ultrasound could show sonographic signs of residual tumor in the borders of “gross total resected tumors” [13–15]. On the other hand the hyperechoic rim around the resection cavity is a non-specific finding [13]. Even edema could be distinguished from solid tumor and improve tumor extension as shown in a study by LeRoux [9,10]. In our experience however, intra-operative ultrasound was very useful in identifying the tumor and delineating its margins before starting tumor removal. After the tumor was removed the quality of the ultrasound in identifying tumor remnants in the margins of the cavity decreased significantly and became unreliable. Gerganov et al. [4] also remarked that during tumor removal of low grade gliomas identification of the gliomas sonographically was excellent but there were difficulties in interpretation of tumor remnants when a tumor cavity was created. Blood, cottonoids, proteinaceus fluid can decrease the quality of the ultrasound image. Apart from our experience there are other studies indicating the high value of ultrasound intraoperatively in judging the boundaries of low grade gliomas [15]. Even if there is a great possibility in differentiating residual glioma from normal brain in low grade gliomas, in high grade gliomas it would be more efficient to rely on other methods like 5-aminolevulinic acid [2]. Unfortunately 5-aminolevulinic acid does not illuminate low grade gliomas. There is a number of studies which focus on distinguishing normal brain tissue from residual tumor ultrasonographically since intraoperative sonography is an easy to handle, inexpensive modality and most important, real-time, which is not affected by brain shift [3,15]. On the other hand, neuronavigation allows an accurate localization of the tumor, but it cannot exclude intraoperative dynamic changes of brain shift, which can be initiated by the loss of cerebrospinal fluid, tumor debulking or even brain deformation caused by positioning of the head [3].
5. Conclusion Intraoperative ultrasound guided localization of low grade gliomas combined with neuronavigation, especially in small subcortical lesions, is an excellent tool in the neurosurgeons armamentarium. With ultrasound guidance there was a 0% failure rate of localizing a low grade glioma. Conflict of interest The authors declare that there are no conflicts of interest. References [1] Hervey-Jumper SL, Berger MS. Role of surgical resection in low- and high-grade gliomas. Curr Treat Options Neurol 2014;16:284. [2] Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, et al. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 2008;62:564–76, discussion 564-576. [3] Wang J, Liu X, Ba YM, Yang YL, Gao GD, Wang L, et al. Effect of sonographically guided cerebral glioma surgery on survival time. J Ultrasound Med 2012;31:757–62. [4] Gerganov VM, Samii A, Giordano M, Samii M, Fahlbusch R. Two-dimensional high-end ultrasound imaging compared to intraoperative MRI during resection of low-grade gliomas. J Clin Neurosci 2011;18:669–73. [5] Mahvash M, Konig R, Urbach H, von Ortzen J, Meyer B, Schramm J, et al. FLAIR/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery. Neurosurgery 2006;58. ONS69-75; discussion ONS69-75. [6] Pamir MN, Ozduman K, Dincer A, Yildiz E, Peker S, Ozek MM. First intraoperative, shared-resource, ultrahigh-field 3-Tesla magnetic resonance imaging system and its application in low-grade glioma resection. J Neurosurg 2010;112:57–69. [7] Tronnier VM, Bonsanto MM, Staubert A, Knauth M, Kunze S, Wirtz CR. Comparison of intraoperative MR imaging and 3D-navigated ultrasonography in the detection and resection control of lesions. Neurosurg Focus 2001;10:E3. [8] Hol PK, Dullerud R, Nordby HK. Intraoperative ultrasonography in brain surgery. Tidsskr Nor Laegeforen 1992;112:2346–8. [9] Le Roux PD, Berger MS, Wang K, Mack LA, Ojemann GA. Low grade gliomas: comparison of intraoperative ultrasound characteristics with preoperative imaging studies. J Neurooncol 1992;13:189–98. [10] Leroux PD, Winter TC, Berger MS, Mack LA, Wang K, Elliott JP. A comparison between preoperative magnetic resonance and intraoperative ultrasound tumor volumes and margins. J Clin Ultrasound 1994;22:29–36. [11] Reid MH. Ultrasonic visualization of a cervical cord cystic astrocytoma. Am J Roentgenol 1978;131:907–8. [12] Sosna J, Barth MM, Kruskal JB, Kane RA. Intraoperative sonography for neurosurgery. J Ultrasound Med 2005;24:1671–82. [13] Woydt M, Krone A, Becker G, Schmidt K, Roggendorf W, Roosen K. Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection. Acta Neurochir (Wien) 1996;138:1391–8. [14] Mair R, Heald J, Poeata I, Ivanov M. A practical grading system of ultrasonographic visibility for intracerebral lesions. Acta Neurochir (Wien) 2013;155:2293–8. [15] Tian YJ, Lin S, Liu HZ, Wang LS, He W, Zhang MZ, et al. Value of intra-operative ultrasound in detecting the boundaries of intra cranial gliomas. Zhonghua Yi Xue Za Zhi 2009;89:1305–8.