Introduction: The cingulum bundle is thought to be related with high-order cognitive function and emotional regulation. Tumors involving the cingulate gyrus are uncommon and surgically challenging. They may infiltrate the cingulum as their site of origin, or they may displace it when they arise from paracingulate areas, in which case the cingulum may be preserved. The objective of this report is to apply dMRI to evaluate the integrity of the cingulum to differentiate cingulate from para-cingulate tumors.

Methods: Retrospective evaluation of our dMRI fiber tracking database was conducted to identify patients with tumors involving the cingulum. Lesions infiltrating and/or disrupting the cingulum bundle were subclassified as primary cingulate tumors and those lesions purely displacing the cingulum were subclassified as para-cingulate tumors. Surgical technique and results were retrospectively evaluated for each subgroup.

Results: Eleven patients with cingulate / para-cingulate tumors were identified. Pre-operative dMRI fiber tracking showed 4 (36.4%) tumors purely displacing the cingulum and 7 (63.6%) infiltrating and/or disrupting it. Ten patients underwent surgical resection and 1 underwent biopsy only. Surgical approaches included anterior and posterior interhemispheric, and transcortical. For primary cingulate tumors, we performed complete resection of the involved segment of the cingulum in five out of 6 cases (83.33%) while 1 had a subtotal resection. All four patients classified as paracingulate tumors underwent preservation of the cingulum, but achieving gross total resection in 3 and sub-total resection in 1, due to motor positive stimulation during resection. One (10%) patient had postoperative transient aphasia and right-sided hemiparesis, and nine (90%) had an uneventful postoperative period with improvement of their preoperative symptoms.

Conclusions: Advanced dMRI fiber tracking for surgical planning of cingulate tumors may allow cingulum bundle preservation in selected cases with maximal tumor resection and minimal rate of new post-operative deficits.

Patient Care: Preoperative planning of tumor affecting the cingulum using an advanced diffusion MRI fiber tracking technique may decrease postoperative complications, improve functional outcome after resection. This may translate in a shorter hospital stay, faster postoperative recovery, and decrease in health cost.

Learning Objectives: 1. Describe the different types of tumor involvement in the cingulate gyrus. 2. Describe the applications of an advanced dMRI fiber tracking method in the pre-operative evaluation of tumor affecting the cingulum. 3. Define possible benefits in patient outcome when using dMRI fiber tracking in preoperative planning comparing results from the previous series using regular imaging methods. 4. Describe further directions on the surgery of tumor involving the cingulate gyrus.

References: Jones DK, Christiansen KF, Chapman RJ, Aggleton JP. Distinct subdivisions of the cingulum bundle revealed by diffusion MRI fibre tracking: implications for neuropsychological investigations. Neuropsychologia. 2013;51(1):67-78. 2. Wu Y, Sun D, Wang Y, Wang Y, Ou S. Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study. Front Neuroanat. 2016;10:84. 3. Vogt BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci. 2005;6(7):533-44. 4. Jang SH, Kwon HG. Focal Cingulum Injury by Minor and Direct Head Trauma: A Diffusion Tensor Tractography Study. Am J Phys Med Rehabil. 2016;95(2):e26-7. 5. Baek SO, Kim OL, Kim SH, Kim MS, Son SM, Cho YW, et al. Relation between cingulum injury and cognition in chronic patients with traumatic brain injury; diffusion tensor tractography study. NeuroRehabilitation. 2013;33(3):465-71. 6. Ezzati A, Katz MJ, Lipton ML, Zimmerman ME, Lipton RB. Hippocampal volume and cingulum bundle fractional anisotropy are independently associated with verbal memory in older adults. Brain Imaging Behav. 2016;10(3):652-9. 7. Kurki T, Himanen L, Vuorinen E, Myllyniemi A, Saarenketo AR, Kauko T, et al. Diffusion tensor tractography-based analysis of the cingulum: clinical utility and findings in traumatic brain injury with chronic sequels. Neuroradiology. 2014;56(10):833-41. 8. Whitford TJ, Lee SW, Oh JS, de Luis-Garcia R, Savadjiev P, Alvarado JL, et al. Localized abnormalities in the cingulum bundle in patients with schizophrenia: a Diffusion Tensor tractography study. Neuroimage Clin. 2014;5:93-9. 9. Yamamoto M, Kushima I, Kimura H, Hayashi A, Kawano N, Aleksic B, et al. White matter microstructure between the pre-SMA and the cingulum bundle is related to response conflict in healthy subjects. Brain Behav. 2015;5(10):e00375. 10. Chiang HL, Chen YJ, Shang CY, Tseng WY, Gau SS. Different neural substrates for executive functions in youths with ADHD: a diffusion spectrum imaging tractography study. Psychol Med. 2016;46(6):1225-38. 11. von Lehe M, Schramm J. Gliomas of the cingulate gyrus: surgical management and functional outcome. Neurosurg Focus. 2009;27(2):E9. 12. Oszvald A, Quick J, Franz K, Guresir E, Szelenyi A, Vatter H, et al. Resection of gliomas in the cingulate gyrus: functional outcome and survival. J Neurooncol. 2012;109(2):341-8. 13. Fernandes-Cabral DT, Zenonos GA, Hamilton RL, Panesar SS, Fernandez-Miranda JC. High-Definition Fiber Tractography in the Evaluation and Surgical Planning of Lhermitte-Duclos Disease: A Case Report. World Neurosurg. 2016;92:587 e9- e13. 14. Fernandez-Miranda JC, Pathak S, Engh J, Jarbo K, Verstynen T, Yeh FC, et al. High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications. Neurosurgery. 2012;71(2):430-53. 15. Yeh FC, Wedeen VJ, Tseng WY. Generalized q-sampling imaging. IEEE Trans Med Imaging. 2010;29(9):1626-35. 16. Yeh FC, Verstynen TD, Wang Y, Fernandez-Miranda JC, Tseng WY. Deterministic diffusion fiber tracking improved by quantitative anisotropy. PLoS One. 2013;8(11):e80713. 17. Fernandez-Miranda JC, Rhoton AL, Jr., Alvarez-Linera J, Kakizawa Y, Choi C, de Oliveira EP. Three-dimensional microsurgical and tractographic anatomy of the white matter of the human brain. Neurosurgery. 2008;62(6 Suppl 3):989-1026; discussion -8. 18. Abhinav K, Pathak S, Richardson RM, Engh J, Gardner P, Yeh FC, et al. Application of high-definition fiber tractography in the management of supratentorial cavernous malformations: a combined qualitative and quantitative approach. Neurosurgery. 2014;74(6):668-80; discussion 80-1. 19. Lazar M, Alexander AL, Thottakara PJ, Badie B, Field AS. White matter reorganization after surgical resection of brain tumors and vascular malformations. AJNR Am J Neuroradiol. 2006;27(6):1258-71. 20. Celtikci E, Celtikci P, Fernandes-Cabral DT, Ucar M, Fernandez-Miranda JC, Borcek AO. High-definition fiber tractography in evaluation and surgical planning of thalamopeduncular pilocytic astrocytomas in pediatric population: case series and review of literature. World Neurosurg. 2016. 21. Celtikci P, Fernandes-Cabral DT, Yeh FC, Panesar SS, Fernandez-Miranda JC. Generalized q-sampling imaging fiber tractography reveals displacement and infiltration of fiber tracts in low-grade gliomas. Neuroradiology. 2018;60(3):267-80. 22. Fernandes Cabral DT, Zenonos GA, Nunez M, Celtikci P, Snyderman C, Wang E, et al. Endoscopic Endonasal Transclival Approach for Resection of a Pontine Glioma: Surgical Planning, Surgical Anatomy, and Technique. Oper Neurosurg (Hagerstown). 2018. 23. Maier-Hein K, Neher P, Houde J-C, Cote M-A, Garyfallidis E, Zhong J, et al. Tractography-based connectomes are dominated by false-positive connections. bioRxiv. 2016:084137. 24. Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci. 2000;4(6):215-22. 25. Dedovic K, Slavich GM, Muscatell KA, Irwin MR, Eisenberger NI. Dorsal Anterior Cingulate Cortex Responses to Repeated Social Evaluative Feedback in Young Women with and without a History of Depression. Frontiers in behavioral neuroscience. 2016;10. 26. Lane RD, Reiman EM, Axelrod B, Yun L-S, Holmes A, Schwartz GE. Neural correlates of levels of emotional awareness: Evidence of an interaction between emotion and attention in the anterior cingulate cortex. Journal of Cognitive Neuroscience. 1998;10(4):525-35. 27. Hamani C, Mayberg H, Stone S, Laxton A, Haber S, Lozano AM. The subcallosal cingulate gyrus in the context of major depression. Biological psychiatry. 2011;69(4):301-8. 28. Lieberman MD, Eisenberger NI. Neuroscience. Pains and pleasures of social life. Science. 2009;323(5916):890-1. 29. Pittenger C, Bloch M, Wegner R, Teitelbaum C, Krystal JH, Coric V. Glutamatergic dysfunction in obsessive-compulsive disorder and the potential clinical utility of glutamate-modulating agents. Primary psychiatry. 2006;13(10):65. 30. Yasargil M. Limbic and paralimbic tumors. Microneurosurgery IV B New York, Thieme Medical Publishers. 1996:252-90. 31. Yasargil MG, Ture U, Yasargil DC. Surgical anatomy of supratentorial midline lesions. Neurosurg Focus. 2005;18(6B):E1. 32. Yasargil MG, von Ammon K, Cavazos E, Doczi T, Reeves JD, Roth P. Tumours of the limbic and paralimbic systems. Acta Neurochir (Wien). 1992;118(1-2):40-52. 33. 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(3):564-76; discussion -76. 34. Tate MC, Kim CY, Chang EF, Polley MY, Berger MS. Assessment of morbidity following resection of cingulate gyrus gliomas. Clinical article. J Neurosurg. 2011;114(3):640-7. 35. Talacchi A, Corsini F, Gerosa M. Surgical approaches to tumors of the anterior gyrus cinguli. Neurosurgery. 2010;66(6 Suppl Operative):245-51. 36. Talacchi A, Hasanbelliu A, Fasano T, Gerosa M. Interhemispheric approach to tumors of the posterior gyrus cinguli. Clin Neurol Neurosurg. 2013;115(5):597-602.