Using MDEFT MRI Sequences to Target the GPi in DBS Surgery
Using MDEFT MRI Sequences to Target the GPi in DBS Surgery
Andreas Nowacki 0 1
Michael Fiechter 0 1
Jens Fichtner 0 1
Ines Debove 0 1
Lenard Lachenmayer 0 1
Michael Schüpbach 0 1
Markus Florian Oertel 0 1
Roland Wiest 0 1
Claudio Pollo 0 1
0 1 Department of Neurosurgery, Inselspital, University Hospital Bern, and University of Bern , Bern , Switzerland , 2 Department of Neurology, Inselspital, University Hospital Bern, and University of Bern , Bern , Switzerland , 3 Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital Bern, and University of Bern , Bern , Switzerland
1 Editor: Noam Harel, University of Minnesota, UNITED STATES
Recent advances in different MRI sequences have enabled direct visualization and
targeting of the Globus pallidus internus (GPi) for DBS surgery. Modified Driven Equilibrium
Fourier Transform (MDEFT) MRI sequences provide high spatial resolution and an excellent
contrast of the basal ganglia with low distortion. In this study, we investigate if MDEFT
sequences yield accurate and reliable targeting of the GPi and compare direct targeting
based on MDEFT sequences with atlas-based targeting.
13 consecutive patients considered for bilateral GPi-DBS for dystonia or PD were included
in this study. Preoperative targeting of the GPi was performed visually based on MDEFT
sequences as well as by using standard atlas coordinates. Postoperative CT imaging was
performed to calculate the location of the implanted leads as well as the active electrode(s).
The coordinates of both visual and atlas based targets were compared. The stereotactic
coordinates of the lead and active electrode(s) were calculated and projected on the
On MDEFT sequences the GPi was well demarcated in most patients. Compared to
atlasbased planning the mean target coordinates were located significantly more posterior.
Subgroup analysis showed a significant difference in the lateral coordinate between dystonia
(LAT = 19.33 ± 0.90) and PD patients (LAT = 20.67 ± 1.69). Projected on the segmented
preoperative GPi the active contacts of the DBS electrode in both dystonia and PD patients
were located in the inferior and posterior part of the structure corresponding to the motor
part of the GPi.
MDEFT MRI sequences provide high spatial resolution and an excellent contrast enabling
precise identification and direct visual targeting of the GPi. Compared to atlas-based
targeting, it resulted in a significantly different mean location of our target. Furthermore, we
observed a significant variability of the target among the PD and dystonia subpopulation
suggesting accurate targeting for each individual patient.
Deep brain stimulation (DBS)is a neurosurgical technique including the insertion of electrodes
that deliver electrical current to target nuclei. The globus pallidus internus (GPi) has
emerged as the target structure for DBS of dystonia and GPi-DBS is effective in the treatment
of motor symptoms in PD patients[2,3]. Apart from a thorough selection of appropriate
patients, the right timing of surgery and adequate stimulation parameters of the implanted
electrodes, optimal electrode targeting and placement is a crucial step determining
postoperative outcome in DBS surgery[4,5]. A few millimeters of targeting inaccuracy can lead to
suboptimal placement of the electrode contacts within the desired target. In this case, higher
stimulation intensity was needed to achieve the same therapeutic effect at the expanse of an
increased risk of side effects affecting postoperative outcome.
In principle, there are two ways of targeting of the selected structure. In case of indirect
targeting, the neurosurgeon selects the target based on a human brain atlas. The selected
target in the atlas is referred to an internal reference of the patient i.e. the AC-PC line that can
be located by ventriculography or magnetic resonance imaging (MRI). Distances are then
deduced from the human atlas to fit to each patient. However, there are individual variations
in coordinates of subcortical nuclei based on the AC-PC-line. Similarly, the anatomical and
functional target might have a different spatial position in each individual. To improve
targeting, microelectrode recording (MER) has been applied. MER allows visualization of
neural activity of different brain structures at a multi-unit level or even single neuron activity.
MER provides a qualitative information on the specific electrical firing of a given brain
target and provides spatial refinement of the actual position of the intended target. The
application of MER together with intraoperative macrostimulation allows assurance of the
accurate electrode placement and compensates for intraoperative brain shift or imaging
Modern MRI techniques with improved image quality enable direct targeting: the surgeon
selects the target by visualization of the intended target structure from the patient`s MRI of the
head[7,8]. In principle, direct targeting should improve the problem of inadequacy of indirect
targeting caused by inter-individual differences of human brain anatomy.
Modified driven equilibrium Fourier transform (MDEFT) imaging is a T1-based MRI
technique characterized by a high spatial resolution and an excellent contrast among grey and
white matter with less gray matter density variability and a good signal to noise ratio. Based
on these properties, MDEFT MR imaging allows a good anatomical representation of the basal
ganglia i.e. the caudate-putamen and the external (GPe) as well as internal (GPi) part of the
globus pallidus (Fig 1). This qualifies MDEFT as a good candidate among MRI sequences
appropriate for direct targeting in the field of DBS. The purpose of this study is to use MDEFT
sequences to directly target the GPi in patients selected for DBS surgery and to evaluate the
accuracy and reliability of this targeting technique.
Fig 1. Representative axial T2-weighted (a) and MDEFT (b) sequence of a patient undergoing DBS implantation of the GPi. Note the good
demarcation of the subnuclei of the basal ganglia on the MDEFT image.
Patients and Methods Patients
In our study we prospectively analyzed a consecutive series of 13 patients with dystonia or PD
undergoing bilateral electrode implantation for DBS of the GPi. Overall 26 electrodes were
implanted. The population consists of 7 men and 6 women (12 adults, 1 child) with a mean age
of 57,6 ± 20,1 years with PD (n = 6), inherited generalized dystonia (DYT 6, n = 1), segmental
dystonia (n = 5) and inherited combined dystonia (n = 1) following the 2013 consensus
classification. Population characteristics are shown in Table 1. In our study, children were defined
as subjects younger than 16 years of age. Extensive preoperative evaluations taking into account
clinical, neuroradiological and biochemical investigations were performed by specialized
movement disorder neurologists. All patients or their legal guardian provided written consent
for the procedure. The study was approved by the Swiss Ethics Committee on research
involving humans. All patients were clinically assessed and DBS parameters adapted and documented
after three months follow-up in our outpatient clinic for movement disorders.
Each patient received a preoperative MRI. Imaging was performed with a 12-channel head coil
for signal reception on a 3 T MRI system (MAGNETOM Trio™ Tim, Siemens, Germany). A
standard gadolinium-enhanced T1-weighted magnetization prepared rapid gradient-echo
(MPRAGE) protocol (160 slices, 1mm thickness) was followed by 3D MDEFT sequence.
According to Deichmann et al. MDEFTsequence is characterized by
preparation–acquisition cycles with the structure: 90°–τ1–180°–τ2–acquisition. During the preparation part, the
longitudinal magnetization is saturated by the 90° pulse, relaxes partially during τ1, is inverted
Stimulation parameters [voltage (V)/ pulse
width (μs)/ frequency (Hz)]
aage at operation in years
bsymptom duration in years; m, male; f, female; D, dystonia; PD, Parinson’s disease;GPi, globus pallidus internus; GPe, globus pallidus externus; IC,
internal capsule, c pulse generator as anode
by the 180° pulse, and relaxes again during τ2, resulting in a T1-weighted longitudinal
magnetization. τ1 and τ2 are given by Eq 1:
where TI is the total duration of the magnetization preparation experiment. In this case, the
optimized acquisition parameters included 256 x 224 x 176 matrix points yielding a nominal
isotropic resolution of 1mm (repetition time 7.92 ms; echo time 2.48 ms; flip angle 16 degrees;
inversion with symmetric timing 910 ms; fat saturation) and 12 minutes total acquisition time
as described previously.
Target planning and lead implantation
MRI was performed prior to DBS implantation. Targets and trajectories were planned based
on the MRI using BrainLab software iPlan NET (Brainlab AG, Germany). The MPRAGE and
MDEFT sequences were fused by applying a rigid fusion-algorithm. The neurosurgeon marked
the anterior and posterior commissure (AC-PC). In a first step, the target was chosen on
MPRAGE images based on the atlas of Schaltenbrand and Wahren as described previously
. The standard coordinates were the following: lateral distance LATSch = 20–22 mm
depending on each patient`s width of the third ventricle; anterior-posterior distance APSch = 2–3 mm
depending on each patient`s AC-PC-length (2 mm if AC-PC was < 25 mm) and vertical
coordinate VERTSch = 1–2 mm inferior. These atlas-based coordinates were documented in each
patient. All coordinates are relative to the midcommissural point (MCP).
In a second step, planning was made independently and exclusively based on MDEFT
sequences. The target was selected by visual recognition of the GPI boundaries on MDEFT
sequence principally on axial as well as coronal sections. The GPI was segmented according to
its demarcated boundaries (BrainLab, Germany) and the target was chosen in the posterior
third of the ventral portion of the GPi maintaining a distance to the internal capsule of
approximately 3 mm and to the optic tract of approximately 2–3 mm. The AP, LAT and VERT
coordinates with reference to the MCP were calculated and compared to the atlas-based target
Differences between coordinates were calculated in the AP, LAT and VERT axis as well as
the Euclidian difference to compare both targets. AP, LAT and VERT distances as well as the
Euclidian distance of each target related to the closest actual electrode were also calculated.
The target defined on MDEFT MRI images was used for the DBS lead implantation
exclusively. The entry point was selected 2.5 to 3 cm lateral to the midline at the level of the coronal
suture. Each planning was performed by the senior neurosurgeon (C.P.). The trajectory was
planned so as to avoid sulci, vessels and ventricles based on MPRAGE images. On the day of
surgery a Leksell G frame (Elekta instruments, Sweden) was placed and a high-resolution,
stereotactic CT scan was performed and co-registrated with the preoperative MRI (Brainlab AG,
Intraoperative MER using two to three microelectrode channels was performed from 10
mm above the target in 1 mm- and further 0.5 mm-steps to confirm the boundaries of the
target structure. Intraoperative clinical assessment was performed by the senior neurologist (M.
S.). The intraoperative trajectories (i.e. the central one) and consequently the final position of
the permanent lead were exclusively based on direct targeting on MDEFT sequences.
According to the best MER and macroelectrode stimulation results, the site of implantation of the
definitive electrode was chosen. The DBS electrode model Activa 3389 (Medtronic, USA)
bearing 4 stimulating contacts made of a platinum/iridium alloy (1.27 mm in diameter, contact 1.5
mm in length, two adjacent contacts are separated by 0.5 mm) was implanted in each patient.
The lead was fixed on the cranium using Stimloc microplates (Medtronic, USA). A
postoperative high-resolution CT scan of the patients head together with the Leksell frame was done
immediately after the surgical procedure to rule out hemorrhage and document correct
electrode positions. One day after the initial operation a pulse generator (Activa PC, Medtronic,
USA) was implanted in the infraclavicular space and connected to the DBS brain lead with a
subcutaneous tunneled cable.
Lead location and GPi segmentation
Lead locations were determined using a postoperative high resolution CT scan. Postoperative
CT images were fused with the preoperatively acquired MRI MPRAGE and MDEFT sequences
by applying a rigid fusion algorithm. This method was demonstrated to be accurate for
identifying the postoperative lead location. The AC-PC based Cartesian coordinate system was
used to represent two visibly determined points along the lead: the tip of the electrode artifact
(most distal point of the lead visible on the postoperative CT) was measured as well as a second
point in the course of the lead typically 20–30 mm above the tip of the lead. The vector between
these two points constitutes the direction vector of the lead:
with !uconstituting the direction vector between T (tip of the lead) and S (second point)
The exact location of each active contact with its corresponding AP, LAT and VERT
coordinates relative to AC-PC was calculated by the vector equation of the lead based on its known
and fixed geometry of the DBS lead:
with !Pconstituting the position vector of any point P along the lead and !Tis the position vector
of the tip of the lead.
The location of the active contact was identified on the postoperative CT and projected onto
the fused preoperative MRI MDEFT sequence to visualize the precise position of the active
contact relative to the patient`s pallidal anatomy. Where two adjacent contacts were
stimulated, the geometric mean of the two stimulated contacts was used. To determine the spatial
relationship between the active contact and the GPi, we determined the segmented GPi and its
anterior, posterior, medial, lateral, ventral and dorsal boundaries. The segmentation of the GPi
was performed by visual depiction with the help of 3 T MDEFT sequences. Deichmann et al.
 demonstrated excellent signal-to-noise-ratios of 37.6 ± 2.5 of 3 T MDEFT sequences
allowing for reliable differentiation between grey and white matter. The posterior (P), anterior (A),
lateral (L) and medial (M) points were identified visually on MDEFT sequences at the level of
the active contact. P and A were determined at the posterior and anterior intersection of the
internal capsule and the medial intermedullary lamina respectively. L and M were determined
at the border of the GPi and the medial intermedullary lamina and the internal capsule
respectively on a horizontal line perpendicular to the AP-line and crossing the active contact (Fig 2A
and 2B). The ventral (V) and dorsal (D) points were set respectively at the ventral border of the
GPi (transition with white matter) and the internal capsule, on a vertical line perpendicular to
ML-line also crossing the active contact (Fig 2C).
The distance between each of these three axes (antero-posterior, medio-lateral and
ventrodorsal) was calculated and considered the anteroposterior (AP), mediolateral (ML) and
ventrodorsal (VD) extent of the GPi. The intersection (S) of a line corresponding to each of these axes
and the perpendicular of this line crossing the active contact was calculated by simple vector
equation. The distance between the most anterior, medial and ventral point of the GPi and the
intersection S was calculated and considered the antero-intersection- (AS-),
medio-intersection- (MS-) and ventro-intersection- (VS-) distance respectively. The ratios of the AP-,
MLand VD-distances to the AS-, MS- and VS-distances were calculated (AP-Index = AS/AP;
ML-Index = MS/ML; VD-Index = VS/VL) and denoted the relative distance from the active
contact from the most anterior, medial and ventral border of the GPi respectively (Fig 2).
We also determined the targeting error of each lead as the AP- and LAT-distance between
the intended target on pre-operative MRI scans and the actual position of the lead at the level
of the intended target (same VERT value). The vector of error representing the Euclidean
distance can between the intended target (APi, LATi) and the actual tip of the electrode (APt,
Fig 2. Determination of the AP-, ML- and VD-Index of the active contact C. A: A line between the most anterior (A) and posterior (P) points of the GPi
constitutes the AP-line. Another line through the active contact C and perpendicular to AP intersects the AP-line in S. The AP-Index can be calculated as
AP-Index = AS/AP. B: The medial (M) and lateral (L) point of the GPi are located on a line perpendicular to the AP-line crossing the active contact C. The
ML-Index can be calculated as ML-Index = MC/ML. C: The ventral (V) and dorsal (D) point of the GPi are located on a line perpendicular to the ML-line
crossing the active contact C. The VD-Index can be calculated as VD-Index = VC/VD. D: An overlay of the postoperative CT-scan at the level of the active
contact and the MDEFT MRI sequence shows the border of the GPi after segmentation reveals the position of the active contact in relation to the anatomical
borders of the GPi.
LATt) was calculated by Eq 2:
ðAPi APtÞ þ ðLATi LATtÞ
Data were analyzed with descriptive/parametric statistics using SPSS software (version 20,
IBM, USA). The Kolmogorov-Smirnov test was used to test for normal distribution of data
sets. Two-sided student`s t-test was applied to test for statistical significance. A p-value < 0.05
was considered statistically significant.
The caudate-putamen and the pallidum with the subdivision of the GPe and GPi were well
demarcated in most patients as the grey scale and contrast were adapted with BrainLab
software for the best visualization of the target region (Fig 3).
A total of 26 atlas-based and MDEFT-based targets were obtained. We found a mean
atlasbased target of LAT = 20.92 ± 0.95 mm, AP = 2,83 ± 0.34 mm, VERT = -1.91± 0.72 mm and a
mean MDEFT-based target of LAT = 19.95± 1.46 mm, AP = 2,47± 0.72 mm and VERT =
-2.58 ± 1.29 mm. In all three directions we obtained a statistical significance between these
coordinates (Table 2). We obtained an average of differences (Δ) between target coordinates
defined by MDEFT-based and atlas-based targeting of ΔLAT = 1.13 ± 0.75 mm,
ΔANT = 0.61 ± 0.53 mm and ΔVERT = 1.31 ± 1.13 mm yielding a ΔEuclidian difference of
2.1 ± 1.05 mm (Table 2)
The mean distance between the atlas-based target and closest electrode was
ΔLAT = 1.04 ± 0.75 mm, ΔAP = 1.05 ± 0.62 mm and ΔVERT = 0.14 ± 0.2. Similarly, the mean
distance between MDEFT-based target and closest electrode was ΔLAT = 0.8 ± 0.67 mm,
ΔANT = 0.63 ± 0.4 mm and ΔVERT = 0.09 ±0.12 mm. In the LAT and AP directions, these
distances were statistically significant. (Table 3).
Comparing the target coordinates of PD and dystonia patients based on direct visual
targeting, a significant difference with more lateral values in the lateral coordinate in PD patients
compared to dystonia patients was observed (Table 4).
Across the whole cohort the mean coordinates of the tip of the lead were 19.85± 1.62mmin
the lateral direction, 2.81± 1.13mmin the anterior direction and -3.77± 1.27mmin the vertical
direction (all relative to MCP). The central trajectory was selected as the site of implantation of
the definitive lead in 88% of all cases due to the best electrophysiological results of MER and
clinical improvement after intraoperative testing. The vector of error determined at the level of
the intended target was 1.07 ± 0.64 mm. There was no systematic deviation between the
intended target and actual lead position. Fig 4A shows an example of the reconstruction of the
implanted DBS lead crossing the GPi in the posterior part.
Fig 3. Representative MDEFT sequences of different patients undergoing DBS implantation of the GPi. (GPi, globus pallidus internus; GPe, globus
pallidus externus; Put, Putamen)
Further analysis of the lead location in PD and dystonia patients showed a significant
difference in the lateral coordinate between these subgroups with a more lateral position of the tip of
the lead in PD patients (Table 5).
Location of active contacts
Across the entire cohort the mean coordinates of the stimulated contact relative to the MCP
were LAT = 20.53± 1.75mm, AP = 3.89 ± 1.00mm and VERT = -0.38 ± 1.41mm. Further
analysis of the active contact location between the two subgroups of PD and dystonia patients
revealed a significant difference in the lateral coordinate: active contacts were located more
lateral in PD patients (21.45 ± 2.00 mm) compared to dystonia (19.74± 1.01 mm) patients
(p < 0.02).
When the location of the stimulating contacts relative to the internal anatomy of the
pallidum was considered, we found that the active contact was located purely within the GPi in
73% of all cases. In 19% the active contact was at the border of the GPi to the GPe, in 8% of the
cases it was at the border of the internal capsule and the GPi (Table 1). Further analysis of the
stimulating contact relative to the borders of the GPi indicated a position in the posterior and
ventral part of the GPi with a mean AP-index of 0.62, VD-index of 0.35 and a mean ML-index
of 0.63 (Fig 4B). No significant differences in the AP-, MV- and VD-Indices between PD and
dystonia patients were observed.
Values are means ± SD in mm
1 p-value calculated with unpaired t-test of same variance; n reflects the number of investigated cases.
Table 3. Comparison of the average of the differences (Δ) of LAT-, AP- and VERT-coordinates between the selected target defined by direct
MDEFT-based and indirect atlas-based planning.
Values are means ± SD in mm
1 p-value calculated with unpaired t-test of same variance; n reflects the number of investigated cases.
We justify our clinical investigation of the impact of 3 T MDEFT sequences on direct targeting
of the GPi on the basis of results found in previous studies using MDEFT at ultrahigh field
strength 7 T MRI. These studies demonstrated the possibility of acquiring narrow brain
radiological windows near to histological resolution enabling accurate localization of brainstem
therapeutic targets[14,15]. Recent results showed that MDEFT sequences yield anatomical
images with high contrast and low noise levels at 3 T field strengths but to date, no studies
investigated the use of MDEFT for target planning in the field of DBS surgery.
Our results suggest that direct visual targeting of the GPi based on MDEFT MRI sequences
is both accurate and reliable. The percentage of electrodes implanted via the central trajectory
was determined as a marker of reliability. The central trajectory points to the intended target.
In case of conflicting results of MER and macrostimulation combined with intraoperative
clinical testing, other trajectories are tested and the permanent DBS lead is implanted according to
the best MER and clinical testing results. In our series of patients the central trajectory was
used in 88% of all cases, which indicates, that our intended target defined by MDEFT-based
planning was set at the correct anatomical site. The mean vector of error at the level of the
intended target was small with 1.07 mm indicating a close correspondence of the intended
target and the actual position of the lead. Apart from targeting inaccuracy, other factors may affect
the final position of the permanent lead such as (1) intraoperative brain shift induced by the
guiding tube and electrode penetration into the brain, intraoperative cerebrospinal fluid loss
and pneumencephalus[16,17] and/or (2) inaccuracy of the stereotactic device. Although we did
not systematically analyze the different factors inducing potential brain shift, the high
percentage of permanent lead implantation in the central trajectory in this series suggests a minor role
of brain shift in the interpretation of our results, as we regularly and systematically check the
accuracy of the stereotactic device before each surgical procedure.
Additionally, MDEFT MRI sequences enabled to perform a 3D segmentation of the GPi of
each patient and to analyze the DBS lead location as well as the location of the stimulating
Values are means ± SD in mm; PD Parkinson`s disease
1p-value calculated with unpaired t-test of same variance; n reflects the number of investigated cases.
Fig 4. Reconstruction of the implanted DBS leads and 3D-scatterplot of the actice contact position. A: Reconstruction of DBS leads of a patient with
bilateral DBS demonstrates lead location in the posterior part of the GPi. B: 3D-scatterplot of the actice contact position (red dots) relative to the border of the
GPi. Position of the vast majority of the active contacts is in the posterior (AP-Index > 0.5) and ventral (VD-Index < 0.5) part of the GPi.
contact with reference to the anatomical borders of the GPi. Our analysis showed that the
position of the active contacts in both PD and dystonia patients was in the posterior and ventral
part of the GPi. This is of particular interest as several groups have correlated the best
therapeutic effect of DBS of the GPi for dystonia and PD with stimulating contact position in the
posterior and ventral portion of the GPi which has been denoted the motor part of the GPi
The present findings demonstrate that MDEFT MRI sequences have an impact on targeting
Compared to atlas-based planning, the preoperative target coordinates using MDEFT
sequences were located significantly more medial, inferior and more posterior. Apart from
determining the differences of the average target coordinates, we also calculated the average of
the differences of target coordinates, which allows us to estimate the average effect of
MDEFTbased targeting technique. Determining the average of the differences of target coordinates
defined by MDEFT- and atlas-based planning led to a mean targeting difference of 2.1 mm in
each patient. Furthermore, we compared of the closest distance between the intended target
Values are means ± SD in mm; PD Parkinson`s disease
1 p-value calculated with unpaired t-test of same variance
defined by (1) MDEFT-based targeting and (2) indirect atlas-based targeting and the actual
DBS lead location. Our analysis revealed significantly smaller differences of the LAT- and
APcoordinates between the intended target and actual lead location in case direct targeting, which
further supports the hypothesis of MDEFT sequences leading to more accurate planning.
Interestingly, we found a difference of the lateral coordinate between PD and dystonia
patients. Subgroup analysis of the preoperative target coordinates as well as the postoperative
DBS lead location and the location of the active contact between dystonia and PD patients
showed a significantly higher value of the lateral coordinate in the PD subgroup indicating a
more lateral position of the planned target and DBS lead. The most probable explanation for
this finding might be a difference in demographic characteristics between the PD and dystonia
cohort as PD patients were significantly older than dystonia patients. Age-related atrophy
might explain this difference. In our series, the width of the third ventricle in PD patients
was larger compared to dystonia patients. Apart from age there might be differences in brain
anatomy due to the different underlying pathophysiological mechanisms of Parkinson disease
and dystonia. Parkinson’s disease is a progressive neurodegenerative disorder whereas dystonia
Furthermore, despite the difference of the mean lateral coordinate of the stimulating
contact, there was no difference of the position of the active contact relative to the borders of the
segmented GPi between PD and dystonia patients. This finding supports the interindividual
variability of the location of the GPi, especially in these two subgroups.
Other sequences have been described for direct visualization of target structures in DBS
surgery that shall be discussed below to embed our results in the context of already published
work. Menuel et al. found that T2-weighted imaging resulted in greater distortions compared
to T1-weighted sequences to demonstrate the subthalamic nucleus. Sudhyadhom et al.
described a Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) sequence with
higher contrast and contrast to noise ratio compared to MPRAGE or T2-weighted Fluid
Attenuated Inverse Recovery (FLAIR) images allowing for sharper delineation of subcortical DBS
target structures. Although the authors gave a precise description of the qualitative
(subjective visual analysis) and quantitative (contrast to noise ratio- and contrast ratio-analysis)
advantages of FGATIR over other sequences, there are currently no data evaluating a potential
impact of this sequence on targeting accuracy in functional neurosurgery.
Vayssiere et al. compared target coordinates of the GPi obtained by direct visual targeting
based on T1-weighted MRI sequences with those determined using an atlas. In accordance to
our results, the authors found a significant difference between the target coordinates obtained by
MRI-based and atlas-based targeting. However, no specific information about the MRI sequence
properties as well as the postoperative DBS lead location is provided by the authors. Reich et al.
described a 1.5 T fast spin-echo inversion-recovery (FSE-IR) sequence to target the GPi. The
authors found, that FSE-IR sequences lead to good signal to noise ratio but the slice thickness
was relatively thick (2–3 mm).The impact of FSE-IR on targeting accuracy and postoperative
outcome in DBS of the GPi was analyzed by Pinsker et al. who found that the atlas-based
standard coordinates were modified in 43% of the patients based on direct visualization of the GPi
. The number of implanted permanent electrodes along the central trajectory was 67% and
64% respectively based on IR-FSE sequences compared to 88% in our patient population. A
possible explanation to this difference might be the minor slice thickness (1 mm) and higher
field strength of 3 T MDEFT sequences leading to more accurate depiction of the GPi. A
summary of the parameters of the different above mentioned sequences is given in Table 6.Currently,
no conclusions can be drawn about which of the above discussed MRI sequences yields most
accurate and reliable targeting of the GPi. Future studies comparing different MRI sequences
and including clinical outcome data are needed to specifically answer this question.
T1-w 3D FGATIR19
T1-w 2D FSE-IR21
There are some limitations of our study. First, we performed a high resolution CT for
postoperative DBS lead location and active contact position analysis. The postoperative CT-scan
was co-registered with the preoperative MRI by using a rigid fusion algorithm. There is an
ongoing debate about the reliability and accuracy of postoperative DBS lead location analysis
based on postoperative CT and MRI. CT/MR image fusion has been demonstrated to provide
an accuracy of up to 1 mm. Hemm et al. analyzed the DBS lead artifact on CT and could
demonstrate a precise localization of the four contact-zone of the lead. Comparison of the
DBS lead artifact on postoperative MRI and CT scan has been shown to be comparable and
equally eligible for postoperative localization analysis.
Second, the sample size of our prospective study population is small and heterogeneous as
it consists of PD patients and patients with various forms of dystonia. For this reason, we did
not include clinical outcome data. Third, the actual DBS lead implantation was performed
according to the anatomic target defined by MDEFT images exclusively. For this reason, we
cannot compare leads implanted using indirect planning with leads implanted using direct
planning. It would have certainly been interesting to compare leads implanted based on
MDEFT sequences with leads implanted based on atlas-based targeting. However, the patients
implanted according to atlas-based targeting in former times were not targeted and operated
by the same surgeon and therefore we believe that it would have introduced a systematic bias
when comparing these two groups. Furthermore, there is no clear reason to implant a patient
using indirect atlas-based targeting with MDEFT sequences available as the sequence provides
direct identification of the structure. Thus, we cannot conclude that direct targeting is superior
to atlas-based targeting in terms of technical and clinical outcome. However, we could
demonstrate that planning according to MDEFT leads to different mean target coordinates in the
study population and a mean correction of the putative optimised target of about 2.1 mm in
each individual patient.Our findings strongly suggest that direct visualization of the GPi using
MDEFT MRI sequences results in accurate targeting in (1) each individual patient and (2) our
two subgroups of patients. Further studies with higher patient numbers and correlation with
clinical outcome have to be conducted to draw conclusions about the clinical effect of MDEFT
based direct targeting of the GPi for DBS surgery.
3 T MDEFT MRI sequences provide high spatial resolution and an excellent contrast among grey
and white matter which enables precise identification of the GPi boundaries and direct visual
targeting of the GPi for DBS surgery. Compared to atlas-based targeting, it resulted in a significantly
different mean location of our target and, furthermore, a significant variability of the target among
the PD and dystonia subpopulation suggesting accurate targeting for each individual patient.
Conceived and designed the experiments: AN MO RW CP. Performed the experiments: AN
MF JF ID LL MS MO RW CP. Analyzed the data: AN MF RW CP. Contributed
reagents/materials/analysis tools: AN MF MS RW CP. Wrote the paper: AN MF JF ID LL MS MO RW CP.
1. Karas PJ , Mikell CB , Christian E , Liker MA , Sheth SA ( 2013 ) Deep brain stimulation: a mechanistic and clinical update . Neurosurg Focus 35 : E1 .
2. Kupsch A , Benecke R , Muller J , Trottenberg T , Schneider GH , et al. ( 2006 ) Pallidal deep-brain stimulation in primary generalized or segmental dystonia . N Engl J Med 355 : 1978 - 1990 . PMID: 17093249
3. Sako W , Miyazaki Y , Izumi Y , Kaji R ( 2014 ) Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation . J Neurol Neurosurg Psychiatry.
4. Tisch S , Zrinzo L , Limousin P , Bhatia KP , Quinn N , et al. ( 2007 ) Effect of electrode contact location on clinical efficacy of pallidal deep brain stimulation in primary generalised dystonia . J Neurol Neurosurg Psychiatry 78 : 1314 - 1319 . PMID: 17442760
5. Welter ML , Schupbach M , Czernecki V , Karachi C , Fernandez-Vidal S , et al. ( 2014 ) Optimal target localization for subthalamic stimulation in patients with Parkinson disease . Neurology 82 : 1352 - 1361 . doi: 10.1212/WNL.0000000000000315 PMID: 24647024
6. Kern DS , Kumar R ( 2007 ) Deep brain stimulation . Neurologist 13 : 237 - 252 . PMID: 17848864
7. Pinsker MO , Volkmann J , Falk D , Herzog J , Alfke K , et al. ( 2008 ) Electrode implantation for deep brain stimulation in dystonia: a fast spin-echo inversion-recovery sequence technique for direct stereotactic targeting of the GPI . Zentralbl Neurochir 69 : 71 - 75 . doi: 10.1055/s- 2007 -1004583 PMID: 18444217
8. Vayssiere N , Hemm S , Cif L , Picot MC , Diakonova N , et al. ( 2002 ) Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting of the globus pallidus internus in the performance of deep brain stimulation for treatment of dystonia . J Neurosurg 96 : 673 - 679 . PMID: 11990806
9. Deichmann R , Schwarzbauer C , Turner R ( 2004 ) Optimisation of the 3D MDEFT sequence for anatomical brain imaging : technical implications at 1 .5 and 3 T. Neuroimage 21: 757 - 767 . PMID: 14980579
10. Albanese A , Bhatia K , Bressman SB , Delong MR , Fahn S , et al. ( 2013 ) Phenomenology and classification of dystonia: a consensus update . Mov Disord 28 : 863 - 873 . doi: 10.1002/mds.25475 PMID: 23649720
11. Mordasini L , Weisstanner C , Rummel C , Thalmann GN , Verma RK , et al. ( 2012 ) Chronic pelvic pain syndrome in men is associated with reduction of relative gray matter volume in the anterior cingulate cortex compared to healthy controls . J Urol 188 : 2233 - 2237 . doi: 10.1016/j.juro. 2012 . 08.043 PMID: 23083652
12. Schaltenbrand G , Wahren W ( 1977 ) Atlas for Stereotaxy of the Human Brain , ed 2. Stuttgart, Georg Thieme .
13. O'Gorman RL , Jarosz JM , Samuel M , Clough C , Selway RP , et al. ( 2009 ) CT/MR image fusion in the postoperative assessment of electrodes implanted for deep brain stimulation . Stereotact Funct Neurosurg 87 : 205 - 210 . doi: 10.1159/000225973 PMID: 19556830
14. Norris DG , Kangarlu A , Schwarzbauer C , Abduljalil AM , Christoforidis G , et al. ( 1999 ) MDEFT imaging of the human brain at 8 T . MAGMA 9 : 92 - 96 . PMID: 10555179
15. Soria G , De Notaris M , Tudela R , Blasco G , Puig J , et al. ( 2011 ) Improved assessment of ex vivo brainstem neuroanatomy with high-resolution MRI and DTI at 7 Tesla . Anat Rec (Hoboken) 294 : 1035 - 1044 .
16. Elias WJ , Fu KM , Frysinger RC ( 2007 ) Cortical and subcortical brain shift during stereotactic procedures . J Neurosurg 107 : 983 - 988 . PMID: 17977271
17. Petersen EA , Holl EM , Martinez-Torres I , Foltynie T , Limousin P , et al. ( 2010 ) Minimizing brain shift in stereotactic functional neurosurgery . Neurosurgery 67 : ons213 - 221 ; discussion ons221. doi: 10.1227/ 01. NEU.0000380991.23444.08 PMID: 20679927
18. Hamani C , Moro E , Zadikoff C , Poon YY , Lozano AM ( 2008 ) Location of active contacts in patients with primary dystonia treated with globus pallidus deep brain stimulation . Neurosurgery 62 : 217 - 223 ; discussion 223 - 215 . doi: 10.1227/01.neu. 0000317396 .16089. bc PMID : 18424989
19. Vayssiere N , van der Gaag N , Cif L , Hemm S , Verdier R , et al. ( 2004 ) Deep brain stimulation for dystonia confirming a somatotopic organization in the globus pallidus internus . J Neurosurg 101 : 181 - 188 . PMID: 15309906
20. Coffey CE , Wilkinson WE , Parashos IA , Soady SA , Sullivan RJ , et al. ( 1992 ) Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging . Neurology 42 : 527 - 536 . PMID: 1549213
21. Menuel C , Garnero L , Bardinet E , Poupon F , Phalippou D , et al. ( 2005 ) Characterization and correction of distortions in stereotactic magnetic resonance imaging for bilateral subthalamic stimulation in Parkinson disease . J Neurosurg 103 : 256 - 266 . PMID: 16175855
22. Sudhyadhom A , Haq IU , Foote KD , Okun MS , Bova FJ ( 2009 ) A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) . Neuroimage 47 Suppl 2: T44 - 52 . doi: 10.1016/j.neuroimage. 2009 . 04.018 PMID: 19362595
23. Reich CA , Hudgins PA , Sheppard SK , Starr PA , Bakay RA ( 2000 ) A high-resolution fast spin-echo inversion-recovery sequence for preoperative localization of the internal globus pallidus . AJNR Am J Neuroradiol 21 : 928 - 931 . PMID: 10815670
24. Pinsker MO , Volkmann J , Falk D , Herzog J , Steigerwald F , et al. ( 2009 ) Deep brain stimulation of the internal globus pallidus in dystonia: target localisation under general anaesthesia . Acta Neurochir (Wien) 151 : 751 - 758 .
25. Hemm S , Coste J , Gabrillargues J , Ouchchane L , Sarry L , et al. ( 2009 ) Contact position analysis of deep brain stimulation electrodes on post-operative CT images . Acta Neurochir (Wien) 151 : 823 - 829 ; discussion 829.
26. Pinsker MO , Herzog J , Falk D , Volkmann J , Deuschl G , et al. ( 2008 ) Accuracy and distortion of deep brain stimulation electrodes on postoperative MRI and CT . Zentralbl Neurochir 69 : 144 - 147 . doi: 10. 1055/s- 2008 -1077075 PMID: 18666049