A literature review of magnetic resonance imaging sequence advancements in visualizing functional neurosurgery targets

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  • 1 University Health Network, Toronto;
  • | 2 Joint Department of Medical Imaging, University of Toronto, Ontario, Canada;
  • | 3 Functional Neurosurgery Unit, Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, United Kingdom;
  • | 4 Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto;
  • | 5 Krembil Brain Institute, Toronto, Ontario;
  • | 6 Department of Psychology, Concordia University, Montreal, Quebec, Canada; and
  • | 7 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
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OBJECTIVE

Historically, preoperative planning for functional neurosurgery has depended on the indirect localization of target brain structures using visible anatomical landmarks. However, recent technological advances in neuroimaging have permitted marked improvements in MRI-based direct target visualization, allowing for refinement of “first-pass” targeting. The authors reviewed studies relating to direct MRI visualization of the most common functional neurosurgery targets (subthalamic nucleus, globus pallidus, and thalamus) and summarize sequence specifications for the various approaches described in this literature.

METHODS

The peer-reviewed literature on MRI visualization of the subthalamic nucleus, globus pallidus, and thalamus was obtained by searching MEDLINE. Publications examining direct MRI visualization of these deep brain stimulation targets were included for review.

RESULTS

A variety of specialized sequences and postprocessing methods for enhanced MRI visualization are in current use. These include susceptibility-based techniques such as quantitative susceptibility mapping, which exploit the amount of tissue iron in target structures, and white matter attenuated inversion recovery, which suppresses the signal from white matter to improve the distinction between gray matter nuclei. However, evidence confirming the superiority of these sequences over indirect targeting with respect to clinical outcome is sparse. Future targeting may utilize information about functional and structural networks, necessitating the use of resting-state functional MRI and diffusion-weighted imaging.

CONCLUSIONS

Specialized MRI sequences have enabled considerable improvement in the visualization of common deep brain stimulation targets. With further validation of their ability to improve clinical outcomes and advances in imaging techniques, direct visualization of targets may play an increasingly important role in preoperative planning.

ABBREVIATIONS

ANT = anterior nucleus of the thalamus; CNR = contrast-to-noise ratio; DBS = deep brain stimulation; DWI = diffusion-weighted imaging; ET = essential tremor; FGATIR = fast gray matter acquisition T1 inversion recovery; FLASH = fast low-angle shot; FLAWS = fluid and white matter sequence; GP = globus pallidus; GPe = GP externus; GPi = GP internus; GRE = gradient echo; IR = inversion recovery; MDEFT = modified equilibrium Fourier transform; MPRAGE = magnetization-prepared rapid acquisition with gradient echo; PD = Parkinson’s disease; PDW = proton density–weighted; PSIR = phase-sensitive inversion recovery; QSM = quantitative susceptibility mapping; rsfMRI = resting-state functional MRI; SN = substantia nigra; SNR = signal-to-noise ratio; SPACE = sampling perfection with application-optimized contrasts by using different flip angle evolution; STIR = short T1 inversion recovery; STN = subthalamic nucleus; SWI = susceptibility-weighted imaging; T1W = T1-weighted; T2W = T2-weighted; T2*W = T2-star-weighted; UHF = ultra–high-field; VC = ventrocaudal; VIM = ventral intermediate nucleus; WAIR = white matter attenuated inversion recovery.

OBJECTIVE

Historically, preoperative planning for functional neurosurgery has depended on the indirect localization of target brain structures using visible anatomical landmarks. However, recent technological advances in neuroimaging have permitted marked improvements in MRI-based direct target visualization, allowing for refinement of “first-pass” targeting. The authors reviewed studies relating to direct MRI visualization of the most common functional neurosurgery targets (subthalamic nucleus, globus pallidus, and thalamus) and summarize sequence specifications for the various approaches described in this literature.

METHODS

The peer-reviewed literature on MRI visualization of the subthalamic nucleus, globus pallidus, and thalamus was obtained by searching MEDLINE. Publications examining direct MRI visualization of these deep brain stimulation targets were included for review.

RESULTS

A variety of specialized sequences and postprocessing methods for enhanced MRI visualization are in current use. These include susceptibility-based techniques such as quantitative susceptibility mapping, which exploit the amount of tissue iron in target structures, and white matter attenuated inversion recovery, which suppresses the signal from white matter to improve the distinction between gray matter nuclei. However, evidence confirming the superiority of these sequences over indirect targeting with respect to clinical outcome is sparse. Future targeting may utilize information about functional and structural networks, necessitating the use of resting-state functional MRI and diffusion-weighted imaging.

CONCLUSIONS

Specialized MRI sequences have enabled considerable improvement in the visualization of common deep brain stimulation targets. With further validation of their ability to improve clinical outcomes and advances in imaging techniques, direct visualization of targets may play an increasingly important role in preoperative planning.

In Brief

The authors reviewed MRI sequences used for preoperative deep brain stimulation target visualization. A variety of MRI sequences have been designed for this purpose, each with their specific strengths and limitations. The authors provide a summary framework to optimize MRI visualization of deep brain stimulation targets.

Functional neurosurgery is dedicated to modulating aberrant circuits associated with a wide range of neurological conditions.1 Broadly speaking, this can be achieved by lesioning (e.g., radiosurgery, radiofrequency ablation, and MR-guided focused ultrasound) or electrical stimulation of key brain structures (deep brain stimulation [DBS]). While principally employed for the treatment of movement disorders such as Parkinson’s disease (PD), essential tremor (ET), and dystonia, the field, mainly driven by DBS, has seen its spectrum of potential indications expand to psychiatric (e.g., obsessive-compulsive disorder, Tourette syndrome, depression, and anorexia nervosa) and cognitive (e.g., Alzheimer’s disease) disorders.2 While direct MRI visualization of the targeted brain structures was used early on,3 generally it has been insufficient for preoperative planning.4

Indirect targeting methods, which estimate the location of targets in relation to fixed and identifiable anatomical landmarks on MRI, have traditionally been used because DBS targets could not be visualized on ventriculography and CT.4 However, indirect targeting fails to account for interindividual variability in the location of target structures.5 To improve DBS targeting accuracy, indirect targeting methods were coupled with a variety of other techniques, such as intraoperative microelectrode recordings and intraoperative stimulation testing in awake patients.6 However, these methods are associated with prolonged procedural times and require multiple penetrations of deep brain structures, increasing the risk of intra- and postoperative complications.7

Routine brain MRI sequences acquired with standard field strengths and acquisition parameters have shortcomings in visualizing DBS targets.8–10 However, with advances in stereotactic frames, MRI hardware, and pulse sequences, direct visualization of certain structures, such as the subthalamic nucleus (STN), is replacing indirect targeting methods for preoperative planning at some institutions.7,11 Nonetheless, other structures, including thalamic nuclei, still require indirect targeting, as their direct radiological visualization remains challenging.12,13 MRI techniques optimizing white/gray matter contrast14,15 or leveraging differences in tissue composition such as iron content16 have been developed to improve the delineation of DBS targets. The therapeutic effects achieved with DBS surgery hinge on the precise and selective modulation of the intended target structure, maximizing treatment efficacy while minimizing any off-target spillover into neighboring structures that might produce adverse effects. Therefore, it seems plausible that direct MRI targeting will be increasingly incorporated into preoperative planning at most institutions.

Here, the goal was to review the many different MRI techniques that have been developed to date to enhance visualization of the most common gray matter nuclei targeted with DBS while also discussing the relevant anatomy and clinical indications of these structures. Finally, we discuss the potential implications of expected MRI advancements on DBS surgery.

Search Methods

A comprehensive search was conducted on June 1, 2020, using the MEDLINE database. The goal was to perform a scoping study, reviewing the literature to examine the extent of research activity, to summarize research findings, and to identify research gaps. The protocol for this scoping study was based on the framework proposed by Arksey and O’Malley,17 with the incorporation of modifications proposed by Levac et al.18 The search strategy employed terms related to “magnetic resonance imaging” and “deep brain stimulation” and the most common neurosurgical targets (see Appendix and Supplementary Fig. 1 for detailed search methods, syntaxes, and a protocol flow diagram). To maintain the clinical relevance of this review, only studies using clinically used field strengths (i.e., 1.5T or 3T MRI) were included.

Most Common DBS Targets

Figure 1 provides a visual comparison between nonoptimized routine (red outline) and optimized (green outline) MRI sequences from the literature to visualize DBS targets. Accompanying acquisition parameters are detailed in Table 1. These optimized MR images were selected based on general trends among studies comparing MRI sequences for visualizing common DBS targets (Table 2).

FIG. 1.
FIG. 1.

Examples of optimized sequences and postprocessing methods for enhanced MRI visualization of DBS targets. Zoomed-out and zoomed-in MR images of the STN (A–F), GPi (G–L), and thalamus (M–R) are shown in addition to the corresponding slice from the atlas of Mai et al.98 The green outline identifies MR images from the literature aiming at improving visualization of DBS targets, whereas the red outline identifies routinely acquired (nonoptimized) T1W (left), T2W (middle), and PDW (right) images for comparison. Details pertaining to their publication and acquisition parameters are included in Table 1. The STN is shown on coronal images, whereas the GPi and thalamus are shown on axial images. AMd = nucleus anteromedial; DL = nucleus dorsolateral; Inl = nucleus intermediolateral; Med = nucleus medial; PLR = prelemniscal radiations; Pu = putamen; SNC = substantia nigra compacta; Thal = thalamus; TSE = turbo spin echo; ZI = zona incerta. The atlas images were published in Atlas of the Human Brain (4th edition), Mai J, Majtanik M, Paxinos G, pp 239 and 406, Elsevier Academic Press, copyright Elsevier 2015. Panel C: reprinted with permission from Senova S, Hosomi K, Gurruchaga JM, et al. Three-dimensional SPACE fluid-attenuated inversion recovery at 3 T to improve subthalamic nucleus lead placement for deep brain stimulation in Parkinson’s disease: from preclinical to clinical studies. J Neurosurg. 2016;125(2):472–480. Panel D: reprinted from Neuroimage. 47(suppl 2), Sudhyadhom A, Haq IU, Foote KD, Okun MS, Bova FJ. A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR), pp T44–T52, copyright 2009, with permission from Elsevier. Panel E: reprinted by permission from Springer Nature. Int J Comput Assist Radiol Surg. 10(3):329–341, Multicontrast unbiased MRI atlas of a Parkinson’s disease population, Xiao Y, Fonov V, Beriault S, et al., copyright 2015, https://www.springer.com/journal/11548. Panel F: reprinted with permission from Rasouli J, Ramdhani R, Panov FE, et al. Utilization of quantitative susceptibility mapping for direct targeting of the subthalamic nucleus during deep brain stimulation surgery. Oper Neurosurg (Hagerstown). 2018;14(4):412–419, by permission of Oxford University Press on behalf of the Congress of Neurological Surgeons. Panel J: Slightly modified with permission from Hirabayashi H, Tengvar M, Hariz MI. Stereotactic imaging of the pallidal target. Mov Disord. 17(suppl 3):S130–S134, Wiley & Sons, © 2002 Movement Disorder Society. Panel K: Slightly modified from Nowacki A, Fiechter M, Fichtner J, et al. Using MDEFT MRI sequences to target the GPi in DBS surgery. PLoS One. 2015;10(9):e0137868, © 2015 Nowicki et al. CC BY 4.0 International license (https://creativecommons.org/licenses/by/4.0/). Panel L: Slightly modified with permission from Magn Reson Imaging. 63, Beaumont J, Saint-Jalmes H, Acosta O, et al. Multi T1-weighted contrast MRI with fluid and white matter suppression at 1.5T, pp 217–225, Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved. Reprinted with permission. Panel P: reprinted with permission from Buentjen L, Kopitzki K, Schmitt FC, et al. Direct targeting of the thalamic anteroventral nucleus for deep brain stimulation by T1-weighted magnetic resonance imaging at 3 T. Stereotact Funct Neurosurg. 2014;92(1):25–30, © 2013 S. Karger AG, Basel. Panel Q: reprinted by permission from Springer Nature. Clin Neuroradiol. 27(4):511–518, Optimized depiction of thalamic substructures with a combination of T1-MPRAGE and phase: MPRAGE, Bender B, Wagner S, Klose U, copyright 2017. https://www.springer.com/journal/62/. Panel R: reprinted from Brain Stimul. 5(4), Vassal F, Coste J, Derost P, et al. Direct stereotactic targeting of the ventrointermediate nucleus of the thalamus based on anatomical 1.5-T MRI mapping with a white matter attenuated inversion recovery (WAIR) sequence, pp 625–633, copyright 2012, with permission from Elsevier. Figure is available in color online only.

TABLE 1.

Optimized MRI acquisition parameters

RoutineRef 31Ref 34Ref 36Ref 29RoutineRef 15Ref 55Ref 56RoutineRef 63Ref 64Ref 13
Fig. 1 panelABCDEFGHIJKLMNOPQR
TargetSTNSTNSTNSTNSTNGPiGPiGPiGPiThalThalThalThal
SequenceT1WT2WFLAIRFGATIRT2*WQSMT1WT2WPDWPDW TSEMDEFTFLAWST1WT2WPDWMPRAGEMPRAGE*WAIR
DiseaseHealthyPDPD, ETPDPDHealthyPDPD, dystHealthyHealthyHealthyHealthyPD, ET
No. of pts1110PD 2, ET 12512211148PD 6, dyst 71111169PD 13, ET 7
MRI manufacturerSigna Excite, GEVerio, SiemensAllegra, SiemensTrim Trie, SiemensDiscovery MR750, GESigna Excite, GEMagnetom Impact Expert, SiemensMagnetom Trio Trim, SiemensMagnetom Aera, SiemensSigna Excite, GEVerio, SiemensTrio, SiemensSonata, Siemens
Field strength (T)1.533331.51.031.51.51.51.5331.5
Matrix256 × 224512 × 512320 × 256256 × 256256 × 256256 × 256320 × 256256 × 256210 × 256256 × 224 × 176180 × 192256 ×256320 ×256256 ×256320 × 240 × 224NANA
FOV (mm)NA250 × 250256 × 192NA25NANANA250NA225 × 240NANA256 × 256NA
Slice thickness (mm)211NA11.41121NA1.411NA1NA
TE (msec)2090.363724.3921.0NA5.392.4930152.482.325.392.49306.73.413
TR (msec)4503750600030003043.812.43600295040007.92350012.4360029502.9123004500
TI (msec)NA02100409NANA300NANANANA403/1030300NANA1100700160
Flip angle (°)901802315209090NA166/820909078NA 
Bandwidth (kHz)24419578113045062.55712297.7NANA2405712297.7160130NA
Head coilHead receive-transmit coil12-channel coilNA32-channel head coilNAHead receive-transmit coilHead coil12-channel20-channel head coilHead receive-transmit coil32-channel head coil32-channel head coilNA
Voxel size (mm)NANANA0.95 × 0.95 × 0.95NANANANA1.25 × 1.25 × 1.4NA0.8 × 0.8 × 0.8NA0.52 × 0.62 × 2.0
Acquisition time (mins)7:498:177:0011:147:05NA3:1311:507:506:0512:0010:273:1311:507:5020:0019:3919:06

Dyst = dystonia; FOV = field of view; NA = not applicable; pts = patients; Thal = thalamus; TSE = turbo spin echo.

Acquisition parameters used to optimize visualization of the STN, GPi, and thalamus as shown in Fig. 1. Sequences in boldface type are routine (nonoptimized) sequences for comparison.

TABLE 2.

Comparison of MRI sequences for visualizing common DBS targets

Authors & YearField Strength (T)“Optimal” Sequence(s)Other Sequences ComparedImage Quality Metric
STN
 van Laar et al., 2016493/1.5T2W TSE(3T)T2W TSE(1.5T)TC, SNR
 Senova et al., 2016313/1.53D SPACE FLAIRT2WCcontour
 Heo et al., 2015463FLAIRT2W TSE, T2*W FFERater, CR
 Sarkar et al., 2015471.5FSTIRT2W FSESNR
 Nagahama et al., 2015443T2W SWANT2W FSE, T2*W GRECNR
 Lefranc et al., 2014433HR 3D SWAN3D T1W + Gd, 3D T2W SERater
 Liu et al., 2013163QSMT2W, T2*W, R2*, phase, SWIRater, CNR
 Kerl et al., 2012263T2*W FLASH 2DSWI, T2W SPACE, T1W MPRAGE, T2W FLAIRRater, CNR
 Ben-Haim et al., 2011481.5T2W FSE/IR–SPGRT2W FSE/IRNA
 O’Gorman et al., 2011451.5SWIPDW FSE, PSIR, DESPOT1, IR-FSPGR, TE40 GRE, T2W FSECNR
 Sudhyadhom et al., 2009343FGATIRT2W 3D FLAIR, T2W 3D MPRAGECNR, CR
 Kitajima et al., 2008333FSTIRT2W FSERater, CNR
 Elolf et al., 2007953T2*W FLASHT2W TSENA
GPi
 Maruyama et al., 2019963T2WPDWCR
 Ide et al., 2017583PADRESWI-like, T2WRater
 Liu et al., 2013163QSMT2W, T2*W, R2*, phase, SWIRater, CNR
 Nölte et al., 201293T2*W FLASH 2D, SWI, SWI-MIPT2W SPACE, T2*W FLASH 2D HB, FLAIR, T1W MPRAGERater, CNR, SNR
 O’Gorman et al., 2011451.5SWIPDW FSE, PSIR, DESPOT1, IR-FSPGR, TE40 GRE, T2W FSECNR
 Sudhyadhom et al., 2009343FGATIRT2W 3D FLAIR, T2W 3D MPRAGECNR, CR
Thal
 Li et al., 20209733D GRE/QSM3D T1W, 2D T2WCNR
 Grewal et al., 2018623HR FGATIRHR MPRAGE, MPRAGENA
 Bender et al., 2017643MPRAGE*Phase, T1W MPRAGERater
 Jiltsova et al., 2016691.5STIRT1W MPRAGENA

Ccontour= contrast of the contour; CR = contrast ratio; DESPOT1 = driven equilibrium single-pulse observation of T1; FFE = fast field echo; FSE = fast spin echo; FSPGR = fast spoiled gradient echo; FSTIR = T1-weighted fast spin echo–based inversion recovery; HB = high bandwidth; HR = high resolution; MIP = minimum intensity projection; PADRE = phase difference enhanced imaging; R2* = R2* mapping; rater = qualitative scoring by raters; SE = spin echo;SPGR = spoiled gradient echo; SWAN = T2*-weighted angiography; TC = tissue contrast; TE40 = echo time 40.

Studies comparing MRI sequences to optimally visualize the STN, GPi, and thalamus are listed. Sequences in boldface type show the reference or “standard” sequence used in each study. The metric of image quality that the authors used for comparison is provided.

Subthalamic Nucleus

Relevant Anatomy

The STN is a small (approximately 8 mm in the maximal transverse histological dimension19), almond-shaped gray matter structure located inferior to the thalamus. It features complex neuroanatomical relationships, being bounded by the internal capsule anterolaterally, the substantia nigra (SN) ventrolaterally, cerebellothalamic fibers posteromedially, and fields of Forel and zona incerta superiorly (Fig. 2A).20,21 The STN has three main functional subdivisions: a superior, posterior, and lateral sensorimotor area; a central associative area; and an emotive medial, anterior, and inferior tip.21–23

FIG. 2.
FIG. 2.

Three-dimensional representations of DBS targets and relevant neighboring anatomy. A: The STN (orange) is shown medial to the internal capsule, lateral to the red nucleus, superior to the SN, and inferior to the thalamus. B: The GPi (green) is shown medial to the GPe, inferolateral to the thalamus, and superior to the optic tract. C: The thalamus (pink) is shown medial to the internal capsule and superior to the STN and hypothalamus. Structures are overlaid on coronal (A and C) and left oblique (B) T1W MR images of the brain (ICBM 2009b nonlinear asymmetrical Montreal Neurological Institute template). Anatomical structures are derived from the DISTAL atlas50 and visualized in 3D with Lead-DBS (www.lead-dbs.org). Figure is available in color online only.

Clinical Indications for DBS Targeting

The sensorimotor STN is the main target for PD, whereas DBS of the associative and emotive STN has been investigated as a treatment for obsessive-compulsive disorder.1,2

Direct MRI Visualization

T2-weighted (T2W) and inversion recovery (IR) imaging have classically been the most common approaches used to directly visualize the STN.24,25 More recently, susceptibility-weighted imaging (SWI) and T2-star-weighted (T2*W) imaging have been employed. Finally, novel image processing techniques, such as quantitative susceptibility mapping (QSM) applied to SWI-based acquisitions, have shown promise in enhancing MRI visualization of the STN.8 The STN is most reliably demarcated from the adjacent zona incerta and SN on coronal slices.26

Most commonly, T2W sequences have been used for direct targeting of the STN.25 In these sequences, the nucleus can be identified as a hypointense lentiform structure—presumably due to iron deposition27—measuring approximately 7 mm in the maximal radiological dimension.19 The interface between the STN and SN is not always visible on T2W images, especially at 1.5T28 (and also at 3T29). Moreover, visualizing the STN on T2W sequences will only lead to improved targeting if stereotactic images are optimized for contrast and if they are processed to minimize geometric distortion.30

IR sequences aim to enhance the visualization of a given structure by selectively suppressing certain tissues with a specific composition. When using a FLAIR sequence, which nulls the signal from fluid, the STN remains hypointense with reduced geometric distortion compared with routine T2W imaging. Although there is limited evidence comparing FLAIR sequences to other visualization techniques, Senova et al.31 showed that preoperative targeting in PD patients with a 3T FLAIR sequence (3D SPACE [sampling perfection with application-optimized contrasts by using different flip angle evolution] FLAIR) was associated with both minimal geometric distortion and significantly higher contrast with surrounding structures, as well as better clinical outcomes at 12 months over routine T2W imaging (Table 1, Fig. 1C, and Supplementary Fig. 2C). However, similar to T2W sequences, the STN borders adjacent to the SN remain difficult to delineate, even at 3T.26

Other less commonly used IR sequences have also been used to visualize STN for DBS surgical planning; these include short T1 inversion recovery (STIR), which nulls signal from fat; phase-sensitive inversion recovery (PSIR); and more recently, fast gray matter acquisition T1 inversion recovery (FGATIR), intended to null the white matter signal.25 Notably, PSIR is the only sequence in which the geometric distortion with a stereotactic head frame has been shown to be less than 1% at 1.5T,32 while the STIR sequence has demonstrated increased contrast between the STN and SN at 3T, offering improved delineation of the inferior STN border.33 Finally, FGATIR has shown promise in visualizing all STN borders in PD and ET patients, owing to increased contrast-to-noise ratio (CNR) (Table 1, Fig. 1D, and Supplementary Fig. 2D).34 Despite encouraging results, the use of these IR sequences in clinical settings remains relatively low to date, perhaps due to the specialized knowledge base required, single-vendor implementation, and the need for replication of relevant findings in larger studies.

SWI uses gradient echo (GRE) sequences, which enhance the effect created by magnetic susceptibility differences between tissues. In particular, these are valuable for imaging the increased iron content of the STN in the context of neurodegenerative diseases and aging.35 The paramagnetic property of the STN can be leveraged to enhance its differentiation from neighboring structures. SWI images, as well as accompanying T2*W26,36 and SWPI (susceptibility-weighted phase imaging),37 have been successfully used to visualize all STN boundaries (Table 1, Fig. 1E, and Supplementary Fig. 2E). However, these techniques are limited by geometric distortion, which has been shown to be as much as 0.8, 0.5, and 0.7 mm in the x, y, and z planes, respectively, in a fast low-angle shot (FLASH) sequence.38 These distortions arise from the nonlocal susceptibility effect, which causes geometric distortion and, consequently, blurring and enlargement of STN borders, commonly observed in GRE sequences.25 This occurs because the high iron content of the STN creates a local magnetic field in MRI, which induces the relaxation of protons in surrounding tissues, thereby producing a susceptibility effect outside the STN even in the absence of a susceptibility source. Moreover, the nonuniform distribution of iron in the STN disproportionately exaggerates the distortion of certain borders.25

QSM is a postprocessing technique that allows for quantification and correction of geometric distortions when visualizing the STN with GRE sequences (Table 1, Fig. 1F, and Supplementary Fig. 2F).8,29 This technique reduces the nonlocal susceptibility effect by providing a clearer picture of tissue susceptibility and magnetic properties, irrespective of patient position (and thus STN orientation).25,39 In addition, it provides a more accurate measurement of brain iron concentration, allowing for improved discrimination of surrounding iron-rich gray matter structures, including the SN, in PD patients. As with other SWI-based sequences, the geometric accuracy of QSM postprocessing has had limited validation in larger clinical studies, although Rasouli et al. showed a strong correlation of QSM with intraoperative microelectrode recording delineation of the STN in 25 PD patients.29 Furthermore, the technique remains difficult to implement at most clinical centers, as image generation is technically demanding and often requires a significant amount of processing time.40 However, online reconstruction techniques have shown promise in addressing these practical limitations, reducing the image construction time to less than 30 seconds on standard computers.41 Nonetheless, QSM reconstruction algorithms remain a work in progress.42

Table 2 lists studies that have compared sequences for direct STN visualization. In general, susceptibility-based sequences16,26,4345 and optimized IR sequences such as FGATIR and STIR31,33,34,4648 demonstrated superior signal-to-noise ratio (SNR) and CNR compared with the more traditionally used T2W and IR (e.g., FLAIR) sequences. Indeed, routine T2W and IR sequences have repeatedly offered suboptimal visualization of all STN borders at 1.5T. Unsurprisingly, higher-field-strength MRI (i.e., 3T) can improve STN border visualization with these sequences.31,49

Globus Pallidus

Relevant Anatomy

Named after its pallid appearance on anatomical specimens, the globus pallidus (GP) is a lens-shaped gray matter structure situated between the putamen and internal capsule (Fig. 2B). The putamen and GP, which together form the lentiform nucleus, are demarcated by the external medullary lamina. The GP itself is divided into two constituent parts by the medial medullary lamina: the GP internus (GPi) and GP externus (GPe).34 The GPi borders the optic tract ventrally and the internal capsule medially. The motor component is functionally segregated in the posterior GPi.50

Clinical Indications for DBS Targeting

After the STN, the GPi is the most common target for DBS in the management of PD.2 Although both sites arguably provide similar motor benefits, the STN contributes to medication intake reduction, whereas the GPi may be better suited for PD patients with cognitive impairment and medication-associated dyskinesias.51,52 The GPi is also the main target for dystonia and has shown promise in the treatment of Tourette syndrome.2 While uncommonly used, stimulation of the GPe has also been shown to improve PD symptoms.53

Direct MRI Visualization

In our center’s experience, T2W and proton density–weighted (PDW)15 (Table 1, Fig. 1J, and Supplementary Fig. 2J) sequences are most commonly used for direct visualization of the GP. In contrast to the STN, the GPi is better appreciated on axial slices.9 On T2W images, the GP can be seen as a hypointense structure,54 whereas it is mildly hyperintense on PDW images.15 At lower field strengths (i.e., 1.5T), these sequences generally visualize the optic tract, external medullary lamina and adjacent putamen, and the internal capsule bordering the posteromedial side of the GP. Delineation of additional boundaries, such as the medial medullary lamina, may not always be reliably obtained.15 Among other sequences, Nowacki et al.55 investigated the use of a T1-weighted (T1W) sequence in dystonia patients, specifically the modified equilibrium Fourier transform (MDEFT) technique, which is employed at high field strengths due to its advantageous contrast characteristics. Using this MDEFT approach at 3T field strength, the caudate putamen and pallidal subdivisions, the GPe and GPi, were well demarcated in most patients (Table 1 and Fig. 1K). Because the central trajectory was used in 88% of all cases, MDEFT-based planning was deemed accurate and reliable.

IR sequences, on which the pallidum appears as a hypointense structure, have also been used. IR spin echo sequences (e.g., IR-FSE [fast spin echo]) at 1.5T have been shown to visualize the optic tract and external medullary lamina.54 FGATIR additionally allowed delineation of the internal medullary lamina.34 FGATIR has further been modified to enhance the distinction between the GPi and GPe by using parameters suppressing the fluid and white matter sequence (FLAWS) (Table 1, Fig. 1L, and Supplementary Fig. 2L).56 In this study, FLAWS was generated through the registration of two contrasts, the standard T1W anatomical contrast of the brain (i.e., magnetization-prepared rapid acquisition with gradient echo [MPRAGE]) and suppression of the white matter signal (i.e., FGATIR), demonstrating enhanced visualization of subcortical structures in healthy participants.

As with the STN, susceptibility-based sequences permit direct visualization of the pallidum. T2*W and QSM sequences have been shown to discern the GPi and GPe in PD patients.57 However, with an SWI-like sequence at 3T, Ide et al.58 showed that the medial medullary lamina was less readily identifiable with increasing age, which may be related to increased mineralization in the GP and/or a loss of myelin.

Few studies have compared sequences for direct visualization of the GP and its subdivisions in a head-to-head manner (Table 2). A handful of reports found that the GPi was best visualized using susceptibility-based sequences when compared with T1W, T2W, or IR sequences at 1.5T and 3T.9,16,45,58 Another report found that, at 3T, the internal medullary lamina in PD and ET patients was better visualized on an FGATIR sequence compared with the more commonly employed FLAIR and T1W imaging (i.e., MPRAGE).34 While these findings are not necessarily conflicting, additional studies comparing sequences would be helpful in establishing a consensus for optimal visualization of the pallidum and its internal architecture.

Thalamus

Relevant Anatomy

A large gray matter structure, the thalamus is located immediately above the hypothalamus and medial to the posterior limb of the internal capsule, forming the lateral wall of the third ventricle and floor of the lateral ventricles (Fig. 2C). Within the thalamus, the internal medullary lamina divides the structure into anterior, mediodorsal, ventral, and lateral groups, with each group comprising several distinct nuclei.59 Functionally, the thalamus has a distinct topographical organization. In simple terms, the posterior part contributes to sensory processing, whereas the motor thalamic relay is located in the ventrolateral part. Finally, the anterior and mediodorsal nuclear groups are considered to be involved in limbic and associative functions, respectively.59

Clinical Indications for DBS Targeting

Stimulation of the thalamic ventral intermediate nucleus (VIM) is well established for the management of ET and, to a lesser extent, tremor secondary to other pathological conditions, such as multiple sclerosis or stroke.2 Modulation of the ventrocaudal (VC) nucleus has been performed to treat chronic pain disorders, particularly central poststroke pain.60 Additionally, the centromedian nucleus (part of the intralaminar nuclei) has been targeted for multiple neurological and psychiatric indications, including Tourette syndrome, PD, and epilepsy, while stimulation of the anterior nucleus of the thalamus (ANT) has shown potential in suppressing global seizure activity in epilepsy patients.1,2

Direct MRI Visualization

Thalamic nuclei, including the VIM, are notoriously difficult to visualize on routine MRI sequences and often necessitate the use of atlas-derived coordinates for preoperative planning.61 On routinely acquired T1W and T2W sequences, the thalamus is mildly hyperintense and hypointense, respectively.62 Despite its many nuclei, it appears fairly homogeneous with little distinction between subdivisions. However, studies in healthy participants have shown that the inversion time of T1W sequences may be optimized, allowing suppression of gray matter.14,63 The resulting gray and white matter differentiation enables identification of the main thalamic groups: anterior, dorsomedial, lateral, and ventral.14 Optimizing the repetition time of T1W imaging (i.e., MPRAGE) has also been shown to enable specific delineation of the ANT, improving targeting prior to DBS epilepsy surgery (Table 1, Fig. 1P, and Supplementary Fig. 2P).63 To further optimize visualization of the thalamic nuclei, MPRAGE has been combined with phase data from 3D GRE sequences, which enabled the distinction of additional thalamic substructures such as the VIM (Table 1 and Fig. 1Q).64 These techniques have yet to be demonstrated in diseased populations.

In one study using a 3T PDW sequence, it was possible to visualize the VIM in healthy subjects as a mildly hypointense band crossing the anterior third of the thalamus, from lateral to medial.65 However, it was inconsistently seen at 1.5T. Furthermore, the sensory thalamic nuclei (i.e., VC nucleus) was seen as another hypointense band located posteriorly.65 Using a PDW sequence at 3T, direct targeting of the VIM has been successfully performed in a tremor patient.66

IR sequences have also enabled visualization of the VIM. Specifically, studies have shown the VIM to be slightly hyperintense relative to the posterior nuclei on STIR sequences.67,68 IR sequences, including STIR and FGATIR, have also been used for targeting of the ANT based on delineation of the mammillothalamic tract, which terminates in the ANT.62,69,70 An IR sequence suppressing signal from white matter (i.e., white matter attenuated inversion recovery [WAIR]) has demonstrated significant enhancement of contrast between different gray matter territories in PD and ET patients, with promise in visualizing the internal subdivisions of the thalamus (Table 1, Fig. 1R, and Supplementary Fig. 2R).13 On WAIR, the VIM appears as a hypointense band crossing the ventrolateral region of the thalamus relative to the surrounding nuclei.

Across the very small number of studies comparing thalamic visualization sequences, IR sequences have been found to be superior to routine T1W imaging (Table 2).62,69

Limitations

As recently as 15 years ago, indirect targeting based on anatomical landmarks was the mainstay of preoperative surgical planning for most functional neurosurgery services. However, advances in MRI hardware and techniques have allowed direct targeting to become more accessible and clinically feasible.25 Despite these improvements, there is limited consensus on the optimal MRI sequences for direct visualization of common DBS targets. While addressing this issue, this review contains significant limitations, highlighting gaps in the literature that future studies may seek to confront. First, a large proportion of the studies were performed in healthy volunteers, which may not accurately reflect the radiological findings in DBS patients (Supplementary Table 1). For example, patients with PD, the most common DBS indication, demonstrate more pronounced brain atrophy and decreased white matter volume than healthy subjects.71,72 This phenomenon, compounded by normal age-related atrophy, has been hypothesized to underlie the decreased STN visibility in older PD patients.10 Second, demonstrable improvements in image quality and the use of novel sequences are limited by the persistent requirement of using specific head coils (usually lower SNR and potentially geometric distortion) that may not physically accommodate stereotactic head frames. Alternatively, frameless techniques or MRI/CT coregistration may be used. However, this may add errors of coregistration that reduce first-pass accuracy.73 Third, an important practical consideration of these novel sequences is that while the delineation of DBS targets is improved, it may be difficult to visualize frame or frameless fiducials, as well as other anatomical landmarks, such as the anterior and posterior commissures, which are commonly used to provide the overall anatomical picture necessary for preoperative planning. Consequently, an MRI/MRI registration—between a sequence visualizing DBS targets and an anatomical sequence—may be required. The accuracy of coregistering these optimized sequences to anatomical MRI sequences has not been thoroughly assessed in the literature. For example, Rasouli et al.29 described a registration method between QSM and T1W without providing accuracy measurement. Novel composite sequences simultaneously acquire a sequence providing both anatomical details and DBS target visualization, which may mitigate the problem.36 Additionally, to leverage the advantages provided by these optimized sequences, generally 3T and coils incompatible with stereotactic head frames have to be used, which creates an additional step of coregistration with a CT scan, potentially introducing geometric error. While such coregistrations inherently introduce error, a systematic review of MRI/CT fusion for localization of electrode placement concluded that fusion was an accurate, reliable, and safe modality for assessing electrode location.74 Fourth, studies that quantitatively compare sequences with regard to visualization and clinical outcomes remain few and far between, with little evidence establishing the superiority of one sequence over another. Most importantly, geometric distortions associated with most of these optimized sequences remain to be tested. Finally, studies also investigating whether direct target visualization definitively improves clinical outcomes when compared with indirect targeting should be done.

Summary Framework to Optimize MRI Visualization of DBS Targets

As highlighted in Fig. 1, marked improvements in direct visualization of targets when using optimized, rather than routine (nonoptimized), sequences have been made. Importantly, as discussed in this review, there is little quantitative evidence favoring specific sequences for visualization of each DBS target. In general, Table 2 seems to suggest that IR sequences, for example, FGATIR, provide improved visualization for the STN, GPi, and thalamus. This is a potential option for centers that do not have the requisite expertise needed to design their own optimized MRI protocols, or implement postprocessing techniques such as QSM, for each DBS target. Finally, when implementing new sequences in their surgical planning, neurosurgeons should audit their own targeting accuracy and assess for systematic errors that may have originated from geometric distortions and other sources of error.75,76

Future Directions

Direct visualization of the most common DBS targets, namely the STN, GPi, and thalamus, has markedly improved in recent years. Further improvement may be expected as ultra–high-field (UHF) MRI becomes more widely available (Fig. 3A and B). Higher magnetic field strengths offer increased SNR, which in turn allows increased spatial resolution, permitting the delineation of smaller neuroanatomical structures.7779 UHF MRI also confers a superior CNR, improving the ability to differentiate between two small abutting structures.78,79 Given these advantages, it is unsurprising that UHF MRI has been shown to better visualize DBS targets than 1.5T and 3T with comparable acquisition times.80 However, while higher magnetic field strengths may improve visualization per se, they are also more prone to susceptibility effects and image distortions,25,81 theoretically leading to a greater risk of mistargeting. Furthermore, UHF MRI has not been utilized in conjunction with commercially available stereotactic frames to date. This necessitates that UHF MR images be coregistered with stereotactic images acquired using another modality (e.g., CT) for preoperative targeting, a step that can introduce registration errors.73 Finally, the risks of DBS systems in UHF MRI have not been thoroughly evaluated, potentially limiting the widespread clinical applicability of this technology.82 Taking these aforementioned caveats into consideration, it is clear that further studies are needed to compare UHF MRI with conventional MRI (1.5T and 3T) for surgical targeting, with clinical outcomes being used as the primary endpoint. With the advent of image distortion correction methods,83 continued testing is required to elucidate potential benefits, obstacles, and tradeoffs presented by UHF MRI.

FIG. 3.
FIG. 3.

Potential implications of expected MRI advancements on DBS surgery. A: Coronal 7T white matter–nulled T1W MPRAGE image at the level of the thalamus from a healthy individual. Reprinted from Neuroimage 84, Tourdias T, Saranathan M, Levesque IR, Su J, Rutt BK, Visualization of intra-thalamic nuclei with optimized white matter–nulled MPRAGE at 7T, Neuroimage, pp 534–545, copyright 2014, with permission from Elsevier. B: Coronal 7T balanced steady-state free precession (bSSFP), which is a modified fast imaging employing steady-state acquisition (FIESTA) sequence, obtained at the level of the thalamus from a healthy individual. Reprinted from Lenglet C, Abosch A, Yacoub E, et al. Comprehensive in vivo mapping of the human basal ganglia and thalamic connectome in individuals using 7T MRI. PLoS One. 2012;7(1):e29153, copyright 2012 Lenglet et al. CC BY 3.0 license (https://creativecommons.org/licenses/by/3.0/). C–E: White matter tracts derived from DWI of approximately 1000 healthy subjects overlaid on a sagittal 7T FLASH MR image. The dentato-rubro-thalamic tract, a target for tremor, is shown (green) alongside a 3D representation of the thalamus (blue) derived from the DISTAL atlas (C).50 The medial forebrain bundle, which has been targeted for treatment of depression and obsessive-compulsive disorder, is shown (purple; D). The cingulum bundle (red), minor forceps (yellow), and uncinate fasciculus (blue), which have been used to guide targeting of the subcallosal region for depression, are shown (E). Panels C–E were constructed using data described in Edlow et al.99 Figure is available in color online only.

The desire to expand the indications for DBS and improve on traditional targets has contributed to a paradigm shift in preoperative targeting. Rather than discrete structures, such as deep gray matter nuclei, optimal targets may include white matter pathways84,85 or focal hubs of functional networks,86 which are entities that are not necessarily appreciated on structural sequences at any field strength. Moreover, there is a growing appreciation that optimal targets may differ between patients, reflecting both heterogeneity within specific disorders and underlying interindividual differences in brain “wiring.” To be appreciated, white matter tracts and functional networks require both highly specialized MRI sequences—diffusion-weighted imaging (DWI) tractography and resting-state functional MRI (rsfMRI), respectively—and fairly complex postprocessing. While rsfMRI networks have been shown to predict improvement in STN stimulation for PD, this technique remains experimental.86 Conversely, structural connectivity profiles have been shown to retrospectively correlate with clinical outcome,61 and tractography-based targeting of the dentato-rubro-thalamic tract (DRTT) and medial forebrain bundle has already been employed as a clinical treatment for ET and psychiatric disorders, respectively (Fig. 3C–E).87,88 DRTT has been seldom used to prospectively guide DBS targeting.89 However, the protocol for a randomized controlled trial comparing the efficacy of VIM DBS (the traditional DBS target for tremor) and DRTT DBS has been published.90 Outside of DBS, prospective DRTT targeting with MRI-guided focused ultrasound was shown to provide excellent symptom relief in patients with tremor.91 Since many of the proposed targets trialed for psychiatric disorders, such as the medial forebrain bundle for treatment-resistant depression and obsessive-compulsive disorder, are white matter structures, tractography-based targeting is required. Tractography has also been used to functionally segment gray matter targets, such as the STN or thalamus, based on their white matter projections to the cortex, thereby potentially offering an alternative method to demarcate zones of clinical interest within these structures.92,93 This method has not been thoroughly investigated in a prospective fashion. Overall, rsfMRI and DWI tractography provide an opportunity to both refine current targets using network-centered approaches and better visualize new or emerging targets that are not amenable to visualization with structural MRI sequences. The limitations of these emerging techniques need to be considered, particularly their validation in prospective studies, which is generally lacking.

Conclusions

Due to technological advances in neuroimaging, most DBS targets can currently be visualized on MRI to some degree, providing an adjunct to indirect targeting. Progress in this field largely stems from the development of optimized sequences and acquisition parameters and has also been furthered by the increasing use of 3T MRI in clinical settings. It is expected that direct visualization will continue to improve, eventually enabling sufficient visualization of additional targets such as the pedunculopontine nucleus,94 which are thus far difficult to appreciate.

While direct visualization of DBS targets has the benefit of taking into account interpatient anatomical variability and encouraging more individualized preoperative planning, studies are needed to definitely establish the superiority of direct targeting over indirect targeting, and to establish which visualization techniques have the highest spatial fidelity for each target. Upcoming developments in this field are likely to relate to UHF MRI, which is expected to provide markedly higher SNR and CNR, along with the emergence of techniques such as rsfMRI and DWI tractography. These advancements in MRI techniques offer the possibility of refining existing targets and discovering new targets by tapping into distributed functional or structural networks.

Acknowledgments

We would like to acknowledge Asma Naheed and Nicole Bennett for providing their technical expertise to acquire the nonoptimized sequences included in Table 1 and Fig. 1.

This work is supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG NE 2276/1-1) (C.N.), the RR Tasker Chair in Functional Neurosurgery at University Health Network, and a Tier 1 Canada Research Chair in Neuroscience. L.Z. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The corresponding author (A.M.L.) confirms that he had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Appendix

A comprehensive search was conducted on June 1, 2020, using the MEDLINE database. The goal was to perform a scoping study,17,18 reviewing the literature to examine the extent of research activity, to summarize research findings, and to identify research gaps. Compared with systematic reviews, scoping studies are a type of literature review that tend to address broader topics that may include many different study designs. Consequently, they are less likely to address very specific research questions and assess the quality of included studies. Thus, a scoping study is one method for reviewing the literature and mapping key concepts. The limitations of this method include the lack of evidence, the lack of quality appraisal, and the disregard of the relative weight of evidence in favor of a particular conclusion. Nevertheless, we provide a rigorous and transparent method to summarize the field of MRI sequence advancements in visualizing functional neurosurgery targets. Consultation of key stakeholders, including neurosurgeons (M.P., L.Z., and S.K.K.), a neurologist (A.F.), neuroradiologists (W.K. and D.M.), and a physicist (C.J.S.), provided an opportunity for insights beyond those found in the literature.

Search terms consisted of a combination of exploded MeSH and free-text terms that comprised (exp Magnetic Resonance Imaging OR (MRI OR magnetic resonance imag*).kw,tw.) AND (exp Electric Stimulation Therapy OR (stimulat* OR DBS).kw,tw.) AND (exp limbic system, OR exp subthalamus, OR exp thalamus) OR (STN OR subthal* OR thalam* OR GPi OR GPe OR globus pallidus).kw,tw.)). In addition, 22 records identified through a preliminary search were added to the 3002 publications retrieved by the final search strategy. Using an online literature review management software (www.covidence.org), two reviewers (C.T.C. and A.T.) initially screened the titles and abstracts and subsequently screened full-text articles. Disagreements were settled by a consensus decision after discussion with a third reviewer (A.B.). After two rounds of screening, 62 eligible articles were compiled and extracted (Supplementary Fig. 1). Study inclusion criteria were human studies that pertained to direct visualization or segmentation of the STN, GP, and thalamus using clinically used field strengths (i.e., 1.5T or 3T MRI). The exclusion criteria were lack of full text, review articles, and articles in languages other than English, German, or French. Data extraction was performed independently by two authors (C.T.C. and A.T.) using a preconstructed spreadsheet with the following headings: publication year, patient demographics, surgical target, and acquisition parameters. The findings were summarized in a narrative fashion.

Disclosures

Dr. Zrinzo: consultant for Medtronic, Boston Scientific, and Elekta. Dr. Kalia: consultant for and honoraria from Medtronic. Dr. Fasano: grants, personal fees, and nonfinancial support from Abbvie, Medtronic, and Boston Scientific; personal fees from Sunovion, Chiesi Farmaceutici, and UCB; and grants and personal fees from Ipsen. Dr. Lozano: consultant for Medtronic, Boston Scientific, Abbott, and Insightec; and scientific director of Functional Neuromodulation.

Author Contributions

Conception and design: Lozano, Boutet, Loh. Acquisition of data: Boutet, Loh, Chow, Taha. Analysis and interpretation of data: Lozano, Boutet, Loh, Chow, Taha, Elias, Neudorfer, Germann, Paff. Drafting the article: Boutet, Loh, Chow, Elias, Neudorfer, Germann, Paff. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Administrative/technical/material support: Lozano. Study supervision: Lozano.

Supplemental Information

Online-Only Content

Supplemental material is available with the online version of the article.

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Illustration from Fan et al. (pp 1298–1309). Copyright Jun Fan. Published with permission.

  • View in gallery

    Examples of optimized sequences and postprocessing methods for enhanced MRI visualization of DBS targets. Zoomed-out and zoomed-in MR images of the STN (A–F), GPi (G–L), and thalamus (M–R) are shown in addition to the corresponding slice from the atlas of Mai et al.98 The green outline identifies MR images from the literature aiming at improving visualization of DBS targets, whereas the red outline identifies routinely acquired (nonoptimized) T1W (left), T2W (middle), and PDW (right) images for comparison. Details pertaining to their publication and acquisition parameters are included in Table 1. The STN is shown on coronal images, whereas the GPi and thalamus are shown on axial images. AMd = nucleus anteromedial; DL = nucleus dorsolateral; Inl = nucleus intermediolateral; Med = nucleus medial; PLR = prelemniscal radiations; Pu = putamen; SNC = substantia nigra compacta; Thal = thalamus; TSE = turbo spin echo; ZI = zona incerta. The atlas images were published in Atlas of the Human Brain (4th edition), Mai J, Majtanik M, Paxinos G, pp 239 and 406, Elsevier Academic Press, copyright Elsevier 2015. Panel C: reprinted with permission from Senova S, Hosomi K, Gurruchaga JM, et al. Three-dimensional SPACE fluid-attenuated inversion recovery at 3 T to improve subthalamic nucleus lead placement for deep brain stimulation in Parkinson’s disease: from preclinical to clinical studies. J Neurosurg. 2016;125(2):472–480. Panel D: reprinted from Neuroimage. 47(suppl 2), Sudhyadhom A, Haq IU, Foote KD, Okun MS, Bova FJ. A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR), pp T44–T52, copyright 2009, with permission from Elsevier. Panel E: reprinted by permission from Springer Nature. Int J Comput Assist Radiol Surg. 10(3):329–341, Multicontrast unbiased MRI atlas of a Parkinson’s disease population, Xiao Y, Fonov V, Beriault S, et al., copyright 2015, https://www.springer.com/journal/11548. Panel F: reprinted with permission from Rasouli J, Ramdhani R, Panov FE, et al. Utilization of quantitative susceptibility mapping for direct targeting of the subthalamic nucleus during deep brain stimulation surgery. Oper Neurosurg (Hagerstown). 2018;14(4):412–419, by permission of Oxford University Press on behalf of the Congress of Neurological Surgeons. Panel J: Slightly modified with permission from Hirabayashi H, Tengvar M, Hariz MI. Stereotactic imaging of the pallidal target. Mov Disord. 17(suppl 3):S130–S134, Wiley & Sons, © 2002 Movement Disorder Society. Panel K: Slightly modified from Nowacki A, Fiechter M, Fichtner J, et al. Using MDEFT MRI sequences to target the GPi in DBS surgery. PLoS One. 2015;10(9):e0137868, © 2015 Nowicki et al. CC BY 4.0 International license (https://creativecommons.org/licenses/by/4.0/). Panel L: Slightly modified with permission from Magn Reson Imaging. 63, Beaumont J, Saint-Jalmes H, Acosta O, et al. Multi T1-weighted contrast MRI with fluid and white matter suppression at 1.5T, pp 217–225, Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved. Reprinted with permission. Panel P: reprinted with permission from Buentjen L, Kopitzki K, Schmitt FC, et al. Direct targeting of the thalamic anteroventral nucleus for deep brain stimulation by T1-weighted magnetic resonance imaging at 3 T. Stereotact Funct Neurosurg. 2014;92(1):25–30, © 2013 S. Karger AG, Basel. Panel Q: reprinted by permission from Springer Nature. Clin Neuroradiol. 27(4):511–518, Optimized depiction of thalamic substructures with a combination of T1-MPRAGE and phase: MPRAGE, Bender B, Wagner S, Klose U, copyright 2017. https://www.springer.com/journal/62/. Panel R: reprinted from Brain Stimul. 5(4), Vassal F, Coste J, Derost P, et al. Direct stereotactic targeting of the ventrointermediate nucleus of the thalamus based on anatomical 1.5-T MRI mapping with a white matter attenuated inversion recovery (WAIR) sequence, pp 625–633, copyright 2012, with permission from Elsevier. Figure is available in color online only.

  • View in gallery

    Three-dimensional representations of DBS targets and relevant neighboring anatomy. A: The STN (orange) is shown medial to the internal capsule, lateral to the red nucleus, superior to the SN, and inferior to the thalamus. B: The GPi (green) is shown medial to the GPe, inferolateral to the thalamus, and superior to the optic tract. C: The thalamus (pink) is shown medial to the internal capsule and superior to the STN and hypothalamus. Structures are overlaid on coronal (A and C) and left oblique (B) T1W MR images of the brain (ICBM 2009b nonlinear asymmetrical Montreal Neurological Institute template). Anatomical structures are derived from the DISTAL atlas50 and visualized in 3D with Lead-DBS (www.lead-dbs.org). Figure is available in color online only.

  • View in gallery

    Potential implications of expected MRI advancements on DBS surgery. A: Coronal 7T white matter–nulled T1W MPRAGE image at the level of the thalamus from a healthy individual. Reprinted from Neuroimage 84, Tourdias T, Saranathan M, Levesque IR, Su J, Rutt BK, Visualization of intra-thalamic nuclei with optimized white matter–nulled MPRAGE at 7T, Neuroimage, pp 534–545, copyright 2014, with permission from Elsevier. B: Coronal 7T balanced steady-state free precession (bSSFP), which is a modified fast imaging employing steady-state acquisition (FIESTA) sequence, obtained at the level of the thalamus from a healthy individual. Reprinted from Lenglet C, Abosch A, Yacoub E, et al. Comprehensive in vivo mapping of the human basal ganglia and thalamic connectome in individuals using 7T MRI. PLoS One. 2012;7(1):e29153, copyright 2012 Lenglet et al. CC BY 3.0 license (https://creativecommons.org/licenses/by/3.0/). C–E: White matter tracts derived from DWI of approximately 1000 healthy subjects overlaid on a sagittal 7T FLASH MR image. The dentato-rubro-thalamic tract, a target for tremor, is shown (green) alongside a 3D representation of the thalamus (blue) derived from the DISTAL atlas (C).50 The medial forebrain bundle, which has been targeted for treatment of depression and obsessive-compulsive disorder, is shown (purple; D). The cingulum bundle (red), minor forceps (yellow), and uncinate fasciculus (blue), which have been used to guide targeting of the subcallosal region for depression, are shown (E). Panels C–E were constructed using data described in Edlow et al.99 Figure is available in color online only.

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