Microsurgical anatomy of the subthalamic nucleus: correlating fiber dissection results with 3-T magnetic resonance imaging using neuronavigation

Abstract

OBJECTIVE Despite the extensive use of the subthalamic nucleus (STN) as a deep brain stimulation (DBS) target, unveiling the extensive functional connectivity of the nucleus, relating its structural connectivity to the stimulation-induced adverse effects, and thus optimizing the STN targeting still remain challenging. Mastering the 3D anatomy of the STN region should be the fundamental goal to achieve ideal surgical results, due to the deep-seated and obscure position of the nucleus, variable shape and relatively small size, oblique orientation, and extensive structural connectivity. In the present study, the authors aimed to delineate the 3D anatomy of the STN and unveil the complex relationship between the anatomical structures within the STN region using fiber dissection technique, 3D reconstructions of high-resolution MRI, and fiber tracking using diffusion tractography utilizing a generalized q-sampling imaging (GQI) model. METHODS Fiber dissection was performed in 20 hemispheres and 3 cadaveric heads using the Klingler method. Fiber dissections of the brain were performed from all orientations in a stepwise manner to reveal the 3D anatomy of the STN. In addition, 3 brains were cut into 5-mm coronal, axial, and sagittal slices to show the sectional anatomy. GQI data were also used to elucidate the connections among hubs within the STN region. RESULTS The study correlated the results of STN fiber dissection with those of 3D MRI reconstruction and tractography using neuronavigation. A 3D terrain model of the subthalamic area encircling the STN was built to clarify its anatomical relations with the putamen, globus pallidus internus, globus pallidus externus, internal capsule, caudate nucleus laterally, substantia nigra inferiorly, zona incerta superiorly, and red nucleus medially. The authors also describe the relationship of the medial lemniscus, oculomotor nerve fibers, and the medial forebrain bundle with the STN using tractography with a 3D STN model. CONCLUSIONS This study examines the complex 3D anatomy of the STN and peri-subthalamic area. In comparison with previous clinical data on STN targeting, the results of this study promise further understanding of the structural connections of the STN, the exact location of the fiber compositions within the region, and clinical applications such as stimulation-induced adverse effects during DBS targeting.

White matter dissection with the Klingler technique: a literature review

“…Details of the technique, including fixation, freezing and thawing, are described in detail in Table 2, which summarizes our results (Baran et al 2019;Bozkurt et al 2017;Burks et al 2017;Capilla-Guasch et al 2019;Costa et al 2018;De Benedictis et al 2014;de Castro et al 2005;Di Carlo et al 2019;Dini et al 2013;Fernandez-Miranda et al 2008;Flores-Justa et al 2019;Goryainov et al 2017;Gungor et al 2018;Ludwig and Klingler 1956;Kadri et al 2017;Koutsarnakis et al 2015;Latini 2015;Latini et al 2015;Mandonnet et al 2017;Martino et al 2010;Panesar et al 2019;Pescatori et al 2017;Peuskens et al 2004;Rigoard et al 2011;Sarubbo et al 2016;Serra et al 2017;Shah et al 2012;Silva and Andrade 2016;Silva et al 2017;Sincoff Ture et al 2000;Vergani et al 2014;Verhaeghe et al 2018;Wang et al 2013;Wu et al 2016a, b;Yakar et al 2018).…”

“…The aim of this step is to remove the formalin solution, which is irritating to the observer during the next step, which includes removing the arachnoid and vessels (Baran et al 2019;Capilla-Guasch et al 2019;Costa et al 2018;Di Carlo et al 2019;Goryainov et al 2017;Kadri et al 2017;Koutsarnakis et al 2015;Latini 2015;Latini et al 2015;Martino et al 2010;Panesar et al 2019;Pescatori et al 2017;Serra et al 2017;Silva and Andrade 2016;Silva et al 2017;Vergani et al 2014;Wu et al 2016a, b). Most authors removed the arachnoid before freezing except for a few who did it after this process is done or between episodes (Burks et al 2017;De Benedictis et al 2014;Gungor et al 2018;Peuskens et al 2004;Rigoard et al 2011;Sarubbo et al 2016;Shah et al 2012;Sincoff et al 2004). Adequately washing out formalin can be satisfactorily achieved with the brain placed in a container of still water (de Castro et al 2005).…”

“…In 3 laboratories, the freezing-thawing technique is used, which is believed to provide better penetration of formalin solution between myelinated fibers (de Castro et al 2005;Rigoard et al 2011;Sincoff et al 2004). After that time, the brain is thawed under running water (Bozkurt et al 2017;de Castro et al 2005;Gungor et al 2018;Ludwig and Klingler 1956;Martino et al 2010;Peuskens et al 2004;Silva and Andrade 2016;Silva et al 2017) or still water (Dini et al 2013;Klingler and Gloor 1960;Serra et al 2017;Shah et al 2012;Ture et al 2000) or is placed within formalin solution. This ends the preparation and makes the brain ready for dissection.…”

“…According to the initial description, the brain can be kept in 5% formalin solution, but for overnight or longer periods, the specimen should be kept in 2% solution. To minimize the unpleasant formalin odor, the brain in most of the manuscripts is kept in solution with lower formalin concentrations than those used for fixation (Capilla-Guasch et al 2019;Costa et al 2018) or in alcohol (Baran et al 2019;Goryainov et al 2017;Gungor et al 2018;Peuskens et al 2004). Some authors recommend re-freezing for a short period, such as 12 h, when there has to be a longer period without dissection (Goryainov et al 2017;Ture et al 2000).…”

“…When following the methods section of manuscripts that include white matter dissection, most authors state that their technique is following Klingler's original technique (Capilla-Guasch et al 2019;De Benedictis et al 2014;Di Carlo et al 2019;Dini et al 2013;Fernandez-Miranda et al 2008;Flores-Justa et al 2019;Gungor et al 2018;Martino et al 2010;Peltier et al 2006;Peuskens et al 2004;Serra et al 2017;Shah et al 2012;Vergani et al 2014;Verhaeghe et al 2018;Wang et al 2013;Wu et al 2016a), or that their own modification (Burks et al 2017;de Castro et al 2005;Goryainov et al 2017;Latini et al 2015;Rigoard et al 2011;Silva and Andrade 2016;Sincoff et al 2004) of the Klingler's technique is applied. This may be confusing for those who want to start their own dissections.…”