A Preliminary Experience with Use of Intraoperative Magnetic Resonance Imaging in Thalamic Glioma Surgery: A Case Series of 38 Patients

Accepted Manuscript A preliminary experience with use of intraoperative MRI in thalamic glioma surgery: A case series of 38 patients Xuan Zheng, MS, Xinghua Xu, MD, Hui Zhang, MD, Qun Wang, MS, Xiaodong Ma, MD, Xiaolei Chen, MD, Guochen Sun, MD, Jiashu Zhang, MD, Jinli Jiang, MD, Bainan Xu, MD, Jun Zhang, MD PII:

S1878-8750(16)00248-5

DOI:

10.1016/j.wneu.2016.01.092

Reference:

WNEU 3730

To appear in:

World Neurosurgery

Received Date: 3 November 2015 Revised Date:

19 January 2016

Accepted Date: 20 January 2016

Please cite this article as: Zheng X, Xu X, Zhang H, Wang Q, Ma X, Chen X, Sun G, Zhang J, Jiang J, Xu B, Zhang J, A preliminary experience with use of intraoperative MRI in thalamic glioma surgery: A case series of 38 patients, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.01.092. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT A preliminary experience with use of intraoperative MRI in thalamic glioma surgery: A case series of 38 patients Xuan Zheng†, MS, Xinghua Xu†, MD, Hui Zhang, MD, Qun Wang, MS, Xiaodong

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Ma, MD, Xiaolei Chen, MD, Guochen Sun, MD, Jiashu Zhang, MD, Jinli Jiang, MD, Bainan Xu, MD, Jun Zhang*, MD

China

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† Those authors contributed equally to this work

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Department of Neurosurgery, PLA General Hospital, 28 Fuxing Rd, Beijing, 100853,

*Corresponding authors: Jun Zhang Tel: +86-13911229472 Fax: +86-021-64085875

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E-mail: [email protected]

Running Title: Use of iMRI in thalamic glioma surgery Key words: thalamic glioma, microsurgery, intraoperative MRI, diffusion tensor

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image, functional MRI

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ACCEPTED MANUSCRIPT Introduction Thalamic tumors are relatively uncommon, accounting for 1–5% of all brain tumors1-3. They are mainly gliomas, most of which are astrocytomas4. Since thalamic gliomas

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are deep-located and are encompassed by important structures such as the internal capsule and subthalamus, surgical resection was not recommended in the past5. With the improvements of surgical techniques and neuroimaging, surgical related morbidity

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and mortality of thalamic glioma have been declining. Extent of resection,

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pathological grade, and onset age are the main impacting factors of prognosis6. So far, curative resection might be the most efficient way to relieve tumor-induced symptoms6, 7.

Diffusion tensor imaging (DTI) and white matter tractography, which have been

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widely used in neurosurgery today, are valuable tools for surgical planning and have positive influence on clinical outcomes of patients receiving supratentorial tumor resection8-10. DTI and white matter tractography are capable of identifying the motor

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fibers within the posterior limb of the internal capsule (PLIC) and preventing

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iatrogenic disruption during tumor resection11, optimizing the approach to these deep-located lesions. However, some unsolved problems such as brain shift affect the feasibility and reliability of this technique2, 7, 12. Intraoperative magnetic resonance imaging (iMRI) has been applied for brain tumor resection in recent years. iMRI has absolute advantages in evaluating the extent of resection, avoiding the injury of vital structures surrounding the lesion and correcting the brain shift caused by tumor debulking or CSF loss during the surgery13-15. Very 2

ACCEPTED MANUSCRIPT few studies concerning the resection of thalamic gliomas in the iMRI system have been reported. In this study, we retrospectively evaluated the clinical impact of neuronavigation and iMRI on preserving neurological function during the resection of

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thalamic gliomas. Material and methods Patients

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In this study, we reviewed patients who were pathologically diagnosed with thalamic

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glioma and underwent tumor resection in the high-field 1.5T iMRI suite (IMRIS, Canada) integrated with a standard neuronavigation system (BrainLab, Germany) between January 2009 and June 2015. Patients with incomplete clinical information and patients who had ever received chemotherapy or radiotherapy were excluded.

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Conventional MRI and DTI scan were performed on each patient after hospitalization for tumor confirmation and surgical planning. The location of the tumor was determined according to the position of the center of tumor.

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Finally, a total of 38 patients (25 males and 13 females) were recruited in the study.

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Each patient’s gender, age of onset, tumor sides, disease course, clinical presentation, pre- and postoperative muscle strength of the involved side, postoperative complications, neuroimaging data and pathological data were collected. The initial surgical approach of each patient was determined according to patient’s neuroradiological features, anatomical knowledge and surgical guidelines published and widely acknowledged.16-18 Preoperative MRI and DTI tractography 3

ACCEPTED MANUSCRIPT Pre- and intra-operative MR images were obtained with the same protocol. The MRI sequences included a T1-weighted three-dimensional (3D) magnetization prepared rapid acquisition gradient echo sequence with the following specifications: repetition

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time (TR) 2020 milliseconds, echo time (TE) 4.38 milliseconds, field of view (FOV) 25 × 25 cm, matrix 256 × 256, and slice thickness 1 mm. T2 weighted image specifications included: TR 6490 milliseconds, TE 98 milliseconds, FOV 23 × 18.3

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cm, matrix 512 × 307, and slice thickness 3 mm. DTI sequence (single-shot spin-echo

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diffusion-weighted echo planar imaging sequence) specifications included: TR 9200 milliseconds, TE 86 milliseconds, FOV 24 × 24 cm, matrix 128 × 128, slice thickness 1.9 mm, and b value = 1000 s/mm2.

The image sets generated were processed on an iPlan 3.0 workstation (Brainlab,

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Germany). All the image sets were automatically coregistered with each other and fused to the anatomic images using an automatic rigid registration. A significance threshold of P < 0.001 was considered for the identification of activated clusters. A

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qualified neuroradiologist blinded to patients’ clinical outcomes documented the

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anatomic location of activation domain on each patient’s images. After data processing, the fiber tracts such as the fasciculus arcuatus and tractus pyramidalis as well as the tumor itself were visualized via a reconstructed 3D image (Fig. 1). A senior neurosurgeon then chose a surgical approach that would achieve maximum tumor resection with minimum injury to the normal brain tissue according to the 3D images. On the intraoperative microscopic image, the important structures and the tumor were outlined so that the surgeon could identify the relative relationship of 4

ACCEPTED MANUSCRIPT them and ensure safe resection. Intraoperative MRI When the neurosurgeon had the impression of a satisfying resection or further

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removal of the lesion might endanger eloquent important areas, an iMRI scan was performed to verify the extent of resection. The scanning sequences were the same as the preoperative MR imaging. The operation came to an end when there was no

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macroscopic hemorrhage and the entire tumor had been resected or the residual tumor

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was impossible to resect. Otherwise, we updated the navigation system with newly acquired intraoperative images to correct the inaccuracy caused by brain shift and continued the surgery. The course was repeated until a satisfactory result was achieved or closure was deemed necessary to prevent a catastrophic outcome such as

Outcome assessment

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permanent damage to the thalamus.

The pre- and post-operative volume of each tumor was calculated by a free and open

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source software 3D slicer (www.slicer.org), which is supposed to be a more precise

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method compared with traditional formula. We defined gross total resection (GTR) as the absence of macroscopic residual or no enhancement on the MR images, subtotal resection as residual of <10% of the whole tumor, and partial resection as residual of >10%.

The histological type and pathologic grades were based on the World Health Organization (WHO) 2007 classification criteria. For the benefit of data analysis, gliomas of WHO I and II were classified into the low-grade group and cases of WHO 5

ACCEPTED MANUSCRIPT III and IV were classified into the high-grade group. Patients with high-grade gliomas were recommended with chemotherapy and radiotherapy besides surgical resection according to treatment guidelines. We instructed all patients to attend outpatient

enhanced MRI scanning at 6 months post discharge. Statistic analysis

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follow-up, undergo formal neurological examination and take conventional and

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All statistical analyses were performed with SPSS Statistics 21 (IBM Corp. USA).

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After confirmation of normal distribution, data are expressed as mean ± SD. Continuous variables were analyzed with independent samples t test and categorical variables with the chi-square test. Values of P < 0.05 were considered statistically significant.

Clinical features

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Results

A total of 38 patients (25 males and 13 females) were included in this study. Their

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clinical characteristics are summarized in Table 1. All patients were primarily

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diagnosed with unilateral thalamic glioma, which was confirmed by specialized neuropathologist. The mean age was 37.0 ± 18.2 years (9–73). The average course of disease was 2.4 ± 2.5 months (0.13-10). Headache (22/38) and motor deficit (18/38) were the leading causes of admission. Other common symptoms included nausea and vomiting (10/38), unilateral sensory deficit (9/38), blurred vision and/or visual field defect (6/38), facioplegia (4/38) and seizures (3/38), Table 2. Hemiplegic paralysis (18/38) and intracranial hypertension (16/38) were the most common neurological 6

ACCEPTED MANUSCRIPT findings on physical examination. Of all the tumors, 39.5% (15/38) were in the left side while 60.5% (23/38) were in the right side, and all the 38 patients were right-haned.

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Surgical approaches The neurosurgeon chose the optimal surgical approach according to the pre-operative MRI. The most important principle is to keep away from eloquent white matter tracts

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such as corticospinal tracts and optic radiation. Finally, we performed a transcortical

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occipital approach in 16 (42.1%) patients, transoccipital lateral ventricle approach in 11 (28.9%) patients, transtemporal lateral ventricle approach in seven (18.4%) patients, transcortical frontal approach in three (7.9%) patients and transcallosal approach in one (2.6%) patient.

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Surgical and pathological results

As for the extent of resection, we achieved GTR in 26 (68.4%) patients, subtotal resection in nine (23.7%) patients, and partial resection in three (7.9%) patients. Four

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patients experienced tumor recurrence and three of them underwent a reoperation by

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the original approach.

The specific pathological results were as follows. Five (13.2%) patients had pilocytic astrocytoma (WHO I): four received GTR and the other received subtotal resection However, the patient received subtotal resection (93% resected) got a recurrence 3 months after discharge and the pathology result remained WHO . Seven (18.4%) patients had WHO grade II gliomas, including one pilomyxiod astrocytoma, one gemistocytic astrocytoma, one pleomorphic xanthoastrocytoma, two diffuse 7

ACCEPTED MANUSCRIPT astrocytoma and two oligoastrocytoma. All these patients received GTR or subtotal resection. Fifteen patients had WHO grade III gliomas, including six anaplastic oligodendroglioma, eight anaplastic astrocytoma,and one anaplastic ependymoma. Of

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these 15 patients, GTR was achieved in 11 (73.3%), subtotal resection in one (6.7%) and partial resection in three (20%). The resection rate of these three partial resected patients was 79%, 86% and 82% respectively. One patient with anaplastic

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astrocytoma received GTR but had a recurrence 15 months after the first

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hospitalization. The pathological results turned into glioblastoma (WHO IV) and the patient refused to get a reoperation. 11 patients had glioblastoma (WHO IV): GTR was achieved in eight patients and subtotal resection was achieved in three patients. Two of the 11 GTR patients experienced tumor recurrence and received a second

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surgical resection 6 and 21 months later. According to the group standard mentioned above, the low-grade group contained 12 patients while the high-grade group contained 26.

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Clinical outcomes

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In the low-grade group (12 patients), two (16.7%) patients experienced functional improvement immediately after surgery, six (50%) had little change, and four (33.3%) experienced deterioration. The corresponding numbers were four (15.4%), 10 (38.5%), and 12 (46.2%) in the high-grade group (26 patients). Three patients experienced postoperative cortical sensory loss, of whom were all in high-grade group, and two were partly recovered one week after surgery and the left one remained the same till discharge. One (8.3%) patient in the low-grade group suffered from homonymous 8

ACCEPTED MANUSCRIPT hemianopsia compared with three (11.5%) in the high-grade group. No patient died during hospitalization. All five patients with pilocytic astrocytoma were in stable condition at 6 months after

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the operation. Of the seven patients with WHO grade II glioma, three were stable at the last follow-up, three lost to follow-up at 15 months, 15months and 18months after surgery respectively. One died 2.5 years after surgery. Of the 15 patients with WHO

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grade III glioma, seven were clinically stable at last follow-up (2–18 months) after

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adjuvant chemoradiotherapy, six lost to follow-up 6-15 months after surgery, and two died 13 and 17 months after surgery. For the 11 patients diagnosed with glioblastoma, after adjuvant chemoradiotherapy, four were clinically stable with a longest follow-up period of 22 months (range, 3–22 months), five lost to follow-up 3–12 months after

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surgery, and two patients experienced a recurrence 9 and 24 months after surgery. Both of them received a reoperation.

The mean length of hospital stay was 18.7±5.6 days. The mean length of post-op

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stay was 15.3±6.2days, which was a little longer than the patients underwent other

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brain tumors surgeries with a mean length of 8.6±5.8 days. This prolonged post operation course might attribute to the invisible damage to the thalumus. We did KPS evaluation before and 3 months after surgery for each patient except for one with tumor recurrence and one who underwent tumor resection 2 months before our study. KPS score was improved from 92.5±8.3 to 95.2±5 in low-grade group while the score was to 91.1±8.7 from 86.9±8.2 in high-grade group. Effect of iMRI use 9

ACCEPTED MANUSCRIPT After the first intraoperative scan, surgery was terminated in 24 patients. GTR was achieved in 16 (42.1%) patients and subtotal resection was achieved in five (13.2%) (Fig.1). Eight patients with subtotal resection or partial resection underwent no further

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resection owing to tumor infiltration of eloquent cortex or fiber bundles. In 14 patients who underwent further resection after the first iMRI scan, 10 patients received GTR and four received subtotal resection (Fig.2). Finally, 26 (68.4%) patients received

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GTR and nine (23.7%) received subtotal resection. The rate of GTR was increased

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from 42.1% to 68.4% with the help of iMRI. Hemorrhages were discovered in three patients on the intraoperative scan. All these three patients underwent hematomas cleaning operation and no postoperative hemorrhage was observed. Discussion

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The thalamus is a large mass of gray matter that is ventrally separated by the hypothalamic sulcus and divided into different nuclear groups. It is located in the forebrain superior to the midbrain near the center of the brain, and nerve fibers project

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from it to the cerebral cortex in all directions. The medial surface of the thalamus

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constitutes the upper part of the lateral wall of the third ventricle, and is connected to the corresponding surface of the opposite thalamus by a flattened gray band, the interthalamic adhesion. The position of the PLIC in relation to thalamic tumor is the most important factor determining the surgical approach5,16,19,20. Clinical presentation of thalamic gliomas The most common clinical presentations of our patients were headache and motor deficit, which was in keeping with data from the literature9, 21, 22. Headache was the 10

ACCEPTED MANUSCRIPT main manifestation of increased Intracranial Cerebral Pressure (ICP) caused by tumor mass effect or by obstructive hydrocephalus due to the intraventricular tumor growth and compression of midline structures. Tumor compression effect is the initial reason

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for motor deficit, though tumor invasion definitely plays a role. Tumor grow patterns vary among different pathological types10, so the pathological results may also correlate with clinical presentation. Of the 21 patients with pre-operative motor deficit,

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13 patients (61.9%) got improvement after surgery. Homonymous hemianopia

damaged during the approach. Evolution of treatment

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occurred in four (10.5%) patients, probably because of the optic radiation was

Thalamic gliomas are relatively more common in children and juveniles. In a study

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from Albright1 more than half of tumors were high-grade gliomas. In our study, 64.2% (26/38) patients had high-grade glioma. Only 28.9% (11/38) patients were <18 years old, less than those reported by most other studies1, 2, 4, 9, 16, 17, 23. The reason for this

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discrepancy might be that we only included patients who were treated surgically,

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while biopsy was more acceptable to young patients. Studies commonly consider maximum extent of resection as a positive predictive value for longer survival in glioma patients24. Maximal tumor resection with crucial neurological function preserved is the supreme goal of modern neurosurgery. In the past, owing to high morbidity and mortality associated with radical resection of these deep-seated tumors, stereotactic biopsy followed by radiotherapy or chemotherapy was favored in the treatment of thalamic gliomas. There are few data in 11

ACCEPTED MANUSCRIPT the literature on the clinical outcome of patients undergoing resective surgery for thalamic tumors because these tumors are uncommon and are rarely operated on. The first declaration of “thalamic gliomas can be surgically removed with an acceptable

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risk” was made by Steiger et al.20 in 2000. With the advances in neuroimaging and microsurgical techniques, risk of surgery for thalamic glioma has been declining25-27. Functional neuronavigation and iMRI

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Functional neuronavigation is a technique that guides surgical procedures by

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integrating DTI and fMRI with a neuronavigation system. DTI-based fiber tractography has become a feasible method for visualizing white matter tracts in the brain. Using DTI, neurosurgeons can objectively reconstruct and mark primary fiber tracts like the corticospinal tract and optic radiation, which are then integrated into the

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navigation system to avoid intraoperative injury.

However, during the surgery, the brain parenchyma becomes distorted because of cerebrospinal fluid loss, edema, and tumor resection, which then leads to brain shift.

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Most patients in our study had large tumors, many had increased ICP with an enlarged

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ventricular system. All these factors would make the brain shift more remarkable, resulting in reduced neuronavigation reliability. Intraoperative MRI, one of the most advanced currently available techniques6, 8, 28, has been proved helpful for operations of many brain lesions, especially for small deep-seated tumors. This technique provides nearly real-time images, which allow detection of residual tumors and intraoperative complications. Furthermore, it enables intraoperative update of registration compensating for brain shift caused by outflow of 12

ACCEPTED MANUSCRIPT cerebrospinal fluid, deformation from retraction and effects of gravity29. The advantages of iMRI for cerebral glioma resection have been investigated many times6, 8, 15, 29

.

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A combination of iMRI and functional neuronavigation unites the advantages of intraoperative resection control, brain shift compensation, and neurological function preservation by displaying white matter tracts intraoperatively15. In this study, the

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GTR rate was enhanced from 42.1% to 68.4% using iMRI, Moshel et al.30 reported

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the highest GTR of 99% with a sample size of 72. However, those 72 patients were all diagnosed with pilocytic astrocytoma, which was relatively easy to resect. Another advantage of iMRI is its sensitive discernment of surgically induced hemorrhage13, 28. In our series, hemorrhage was identified in three patients during the iMRI scan and

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was evacuated immediately. Postoperative hemorrhage, a common complication of glioma surgery28, occurred in none of our patients. The use of iMRI combined with functional neuronavigation could maximize surgical

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resection of thalamic glioma without increasing morbidity and mortality rates.

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However, this was a retrospective study with a small sample size, further randomized controlled trials are needed to confirm our findings. Conclussion

For thalamic gliomas, resective surgery is possible and desirable despite the relatively high risk of surgical-related morbidity and mortality. iMRI is a safe and appropriate method to improve the extent of resection of thalamic gliomas. More prospective studies as well as similar research need to be conducted to confirm our conclussion. 13

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Limitation This is a retrospective study, some information such as the visual exam about

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the patients couldn’t be so complete. Since this is our first step in studying the advantages of iMRI in thalamic glioma surgeries, more attention will be paid for such issues in the future and a more comprehensive study will be designed for our further

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study.

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Conflicts of interest

The authors declare that they have no conflicts of interest.

Funding

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81271365)

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This study was support by National Natural Science Foundation of China (No.

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ACCEPTED MANUSCRIPT References 1. Albright AL. Feasibility and advisability of resections of thalamic tumors in pediatric patients. J Neurosurg. 2004; 100:468-472.

study of 27 cases. Acta Neurochir (Wien). 1987; 85:125-127.

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2. Beks JW, Bouma GJ, Journee HL. Tumours of the thalamic region. A retrospective

3. Bergsneider M, Sehati N, Villablanca P, McArthur DL, Becker DP, Liau LM.

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Mahaley Clinical Research Award: extent of glioma resection using low-field (0.2 T)

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versus high-field (1.5 T) intraoperative MRI and image-guided frameless neuronavigation. Clin Neurosurg. 2005; 52:389-399.

4. Berman JI, Berger MS, Mukherjee P, Henry RG. Diffusion-tensor imaging-guided tracking of fibers of the pyramidal tract combined with intraoperative cortical

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stimulation mapping in patients with gliomas. J Neurosurg. 2004; 101:66-72. 5. Broadway SJ, Ogg RJ, Scoggins MA, Sanford R, Patay Z, Boop FA. Surgical management of tumors producing the thalamopeduncular syndrome of childhood. J

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Neurosurg Pediatr. 2011; 7:589-595.

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6. Buchfelder M, Schlaffer SM. Intraoperative magnetic resonance imaging during surgery for pituitary adenomas: pros and cons. Endocrine. 2012; 42:483-495. 7. Cheek WR, Taveras JM. Thalamic tumors. J Neurosurg. 1966; 24:505-513. 8. Chen X, Xu BN, Meng X, Zhang J, Yu X, Zhou D. Dual-room 1.5-T intraoperative magnetic resonance imaging suite with a movable magnet: implementation and preliminary experience. Neurosurg Rev. 2012; 35:95-109. 9. Cuccia V, Monges J. Thalamic tumors in children. Childs Nerv Syst. 1997; 15

ACCEPTED MANUSCRIPT 13:514-520; discussion 521. 10. Dimitri R, Giovanni C, Chantal C, Stephane B, Anne L, Eric T, Anne W, Guillaume T. Thalamic Lesions: A Radiological Review: Hindawi Publishing

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Corporation Behavioural Neurology; 2014. 11. Fernandez C, Maues de Paula A, Colin C, Quilichini B, Bouvier-Labit C, Girard N, Scavarda D, Lena G, Figarella-Branger D. Thalamic gliomas in children: an

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extensive clinical, neuroradiological and pathological study of 14 cases. Childs Nerv

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Syst. 2006; 22:1603-1610.

12. Foroglou N, Zamani A, Black P. Intra-operative MRI (iop-MR) for brain tumour surgery. Br J Neurosurg. 2009; 23:14-22.

13. Hall WA, Truwit CL. Intraoperative MR-guided neurosurgery. J Magn Reson

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Imaging. 2008; 27:368-375.

14. Hall WA, Truwit CL. Intraoperative MR imaging. Magn Reson Imaging Clin N Am. 2005; 13:533-543.

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15. Nimsky C, Ganslandt O, Hastreiter P, Fahlbusch R. Intraoperative compensation

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for brain shift. Surg Neurol. 2001; 56:357-364; discussion 364-355. 16. Ozek MM, Ture U. Surgical approach to thalamic tumors. Childs Nerv Syst. 2002; 18:450-456.

17. Sai Kiran NA, Thakar S, Dadlani R, Mohan D, Furtado SV, Ghosal N, Aryan S, Hegde AS. Surgical management of thalamic gliomas: case selection, technical considerations, and review of literature. Neurosurg Rev. 2013; 36:383-393. 18. Marc B, Matthieu V, Patrick D. Surgical resection of thalamic tumors in children: 16

ACCEPTED MANUSCRIPT approaches and clinical results. Childs Nerv Syst. 2007; 23:753–760. 19. Moshel YA, Elliott RE, Monoky DJ, Wisoff JH. Role of diffusion tensor imaging in resection of thalamic juvenile pilocytic astrocytoma. J Neurosurg Pediatr. 2009;

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4:495-505. 20. Steiger HJ, Gotz C, Schmid-Elsaesser R, Stummer W. Thalamic astrocytomas: surgical anatomy and results of a pilot series using maximum microsurgical removal.

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Acta Neurochir (Wien). 2000; 142:1327-1336; discussion 1336-1327.

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21. Hirose G, Lombroso CT, Eisenberg H. Thalamic tumors in childhood. Clinical, laboratory, and therapeutic considerations. Arch Neurol. 1975; 32:740-744. 22. Wald SL, Fogelson H, McLaurin RL. Cystic thalamic gliomas. Childs Brain. 1982; 9:381-393.

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23. Woo SY, Donaldson SS, Cox RS. Astrocytoma in children: 14 years' experience at Stanford University Medical Center. J Clin Oncol. 1988; 6:1001-1007. 24. Sanai N, Berger MS. Glioma extent of resection and its impact on patient

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outcome. Neurosurgery. 2008; 62:753-764; discussion 264-756.

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25. Johansen-Berg H, Behrens TE, Sillery E, Ciccarelli O, Thompson AJ, Smith SM, Matthews PM. Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus. Cereb Cortex. 2005; 15:31-39.

26. Lyons MK, Kelly PJ. Computer-assisted stereotactic biopsy and volumetric resection of thalamic pilocytic astrocytomas. Report of 23 cases. Stereotact Funct Neurosurg. 1992; 59:100-104. 17

ACCEPTED MANUSCRIPT 27. Traynor C, Heckemann RA, Hammers A, O'Muircheartaigh J, Crum WR, Barker GJ, Richardson MP. Reproducibility of thalamic segmentation based on probabilistic tractography. Neuroimage. 2010; 52:69-85.

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28. Kubben PL, ter Meulen KJ, Schijns OE, ter Laak-Poort MP, van Overbeeke JJ, van Santbrink H. Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. Lancet Oncol. 2011; 12:1062-1070.

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29. Chen X, Weigel D, Ganslandt O, Buchfelder M, Nimsky C. Prediction of visual

NeuroImage. 2009;45:286–97.

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field deficits by diffusion tensor imaging in temporal lobe epilepsy surgery.

30. Moshel YA, Link MJ, Kelly PJ. Stereotactic volumetric resection of thalamic

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pilocytic astrocytomas. Neurosurgery. 2007; 61:66-75.

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ACCEPTED MANUSCRIPT Figure legends Fig. 1. 27-year-old female presenting with left hemiparalysis for 6 months, revealing a right thalamic tumor. A: Preoperative reconstruction image with the patient in a prone

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position. Pyramidal tracts (purple) and sensory tracts (red) were inferoanterior to the tumor (green), while the arcuate fasciculus (yellow) was anterolateral to the tumor. B, C: Conventional magnetic resonance scan in the axial view. D, E: Contrast-enhanced

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image showing relatively clear margins

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T1-weighted image showing a heterogeneously enhanced solid tumor. F: T2-flair

Fig. 2. Intraoperative MRI scans. A, B: The first interaoperative MRI shows that the majority of the tumor was resected. C: The enhanced dot on the lateral side is residual tumor targeted after updating of the navigation system. D-F: The second iMRI shows

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that the enhanced dot was removed and gross total resection was achieved.

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ACCEPTED MANUSCRIPT Table 1 Comparison of clinial features and surgical outcome between low-grade gliomas and high-grade gliomas High-grade group [WHO grade III & IV] (n=28, 68.4%)

0.503 0.632 0.418 0.911 0.407 0.849 0.499

18 (69.2%) 5 (19.2%) 3 (11.5%)

26 (68.4%) 9 (23.7%) 3 (7.9%)

0.822 0.394 0.498

86.9±8.2 91.1±8.7

86.8±8.8 92.4±8.4

0.038* 0.124

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16 (61.5%) 13 (50%) 8 (30.8%) 7 (26.9%) 3 (11.5%) 3 (11.5%) 3 (11.5%)

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* clinically significant, P < 0.05

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6 (50%) 5 (41.7%) 2 (16.7%) 3 (25%) 3 (25%) 1 (8.3%) 0 (0%)

92.5±8.3 95.2±5.0

P value 0.034* 0.381

40.8±18.8* 18:8

8 (66.7%) 4 (33.3%) 0 (0%)

Totally 37.0±18.2 25:13

28.6±14.2* 7:5

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Mean age (years) Male: female Clinical presentation (n,%) Headache motor deficit nausea and vomiting sensory deficit visual impairment facioplegia seizures Postoperative outcome gross total resection subtotal resection partial resection KPS scores preoperative 3 months after operation

Low-grade group [WHO grade I & II] (n=12, 31.6%)

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Clinical features and surgical outcome

ACCEPTED MANUSCRIPT No.

Patients’ gender

Course of disease

patients’ age

pre-op

Post-op

scanning

resection

(F/M)*

(month)

(year)

muscle strength

muscle strength

times

rate**

M

3

18

4

4

1

Sub

2

M

0

31

5

4

1

Sub

3

M

2

17

1

4+

1

GTR

4

M

2

25

5

4

1

GTR

5

F

10

18

3

5

2

Sub

6

M

2

17

4

4

2

Sub

7

F

4

46

3+

2+

1

GTR

8

M

6

39

5

5-

1

GTR

9

F

0

18

5

5

1

GTR

10

M

3

14

5

5

2

GTR

11

F

1

45

5-

4

2

GTR

12

F

0

55

5

5

2

GTR

13

F

0

24

5

3

1

partial

14 15

M M

2

58

5

5

1

GTR

16

M

5

17

M

2

18

M

6

19

M

2

20

M

3

21

M

1

22

M

23

M

24

F

25

F

26

M

27

F

28

M

29

M

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5

2

GTR

58

1

1

1

GTR

54

3

1

1

GTR

38

5

2

1

GTR

54

4

3

1

Sub

73

3

4

1

Sub

62

4

4

1

GTR

0

51

5

5

1

partial

0

26

4

4+

1

GTR

6

39

5

5

1

partial

6

27

4

4-

2

GTR

0

11

4

1

2

GTR

1

47

3

0

3

GTR

2

66

3+

0

1

Sub

0.5

18

3+

2

5

GTR

F

1

9

5

5

1

GTR

F

9

61

5

3

1

GTR

M

1

56

5

5

1

GTR

M

1

20

5-

3

1

GTR

M

0

46

4+

4+

1

GTR

35

M

0.5

13

5

5

2

Sub

36

F

0.5

44

4

4

2

Sub

37

M

3

17

5

5

2

GTR

38

F

1

42

5

4

3

GTR

32 33 34

EP

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31

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48

30

3

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* F stands for female and M stands for male ** GTR gross total resection; sub subtotal or near total resection; partial partial resection

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ACCEPTED MANUSCRIPT

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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Abbreviations list iMRI, intra-operative magnetic resonance imaging; DTI, difussion tensor imaging;

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PLIC, posterior limb of the internal capsule; 3D, three-diemensional; ICP, intracranial pressure;

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GTR, gross total resection;

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WHO, World Health Organization

ACCEPTED MANUSCRIPT Title: A preliminary experience with use of intraoperative MRI in thalamic glioma surgery: A case series of 38 patients Authors: Xian Zheng, Xinghua Xu, Hui Zhang, Qun Wang, Xiaodong Ma, Xiaolei

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Chen, Guochen Sun, Jiasu Zhang, Jinli Jiang, Bainan Xu, Jun Zhang We wish to confirm that there are no known conflicts of interest associated with this

publication and there has been no significant financial support for this work that could have influenced its outcome.

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We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not

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listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.

We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing

intellectual property.

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we confirm that we have followed the regulations of our institutions concerning

We further confirm that any aspect of the work covered in this manuscript that has

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involved either experimental animals or human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged

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within the manuscript.

We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from [email protected]

ACCEPTED MANUSCRIPT Highlights 1 GTR remains a mainstay treatment of thalamic gliomas 2 Intra-operative MRI may play an active role in resecting deep-seated brain tumors

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3 GTR rate was 68.4% under the assistant of iMRI conbined with neuronavigation system

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4 IMRI can reduced operational complications such as epidural hematoma