Advances in Technical Aspects of Deep Brain Stimulation Surgery

1. Dr. Shahnawaz Alam
Guided by: Dr. Vikas Chandra Jha
HOD, Dept. of Neurosurgery
Advances in Technical Aspects
of
Deep Brain Stimulation
Surgery

2. Objectives:
 Developments in preoperative imaging
 Array of novel stereotactic techniques
 Emergence of various atlases and their functionality
 Planning software
 Perioperative developments
 Implementation of microelectrode recordings (MERs)
 Types of electrodes and their function in stimulation
 Implantable pulse generators
 Emergence of robotics

3. Introduction
• DBS is an established technology that enables direct intervention on neural circuits
by implantation of electrodes in specific intracranial targets followed by local
neuromodulation.
• The ability to directly modulate regions though a minimally invasive procedure has
generated proven benefits for patients with a wide variety of neurological disorders like
intractable epilepsy, Parkinson’s disease, dystonia, and essential tremor, OCD,
depression, and more.
• The modern era of DBS has brought substantial growth and technical innovations
that have improved the technique and delivery of stimulation.

5. Preoperative Imaging
• From the pioneering work of Spiegel, Tasker and Talairach with targeting based on
pneumoencephalography with the implementation of anterior (AC) and posterior
commissure (PC) lines in stereotaxis to the modern use of CT and MRI in directly
visualizing brain structures have played a central role in guiding stereotactic surgeries.
• Optimization of commonly used MRI sequences can improve visualization of DBS
targets. Inversion time of T1w sequences may be optimized, allowing suppression of
gray matter and enabling identification of the main thalamic groups.
• Inversion recovery (IR) have also improved visualization of DBS targets. One such
sequence, fast grey matter T1 inversion recovery (FGATIR), nulls white matter
signal and generates improved visualization of the GPi with delineation of the internal
medullary lamina.
• 7T MRI has been shown to be superior to 1.5T and 3T MRI when visualizing DBS
targets.

6. Optimized 3T MRI images for visualizing DBS targets. a Zoomed out and zoomed
in MRI of the globus pallidus internus (axial 3T FGATIR image); (b) thalamus
(coronal 3T WAIR image sequence); and (c) subthalamic nucleus.

7. Stereotactic Frames
• Lars Leksell transformed stereotactic neurosurgery in 1949 with the development of a
frame relying on centripetal targeting instead of rectilinear adjustments in a Cartesian
coordinate system.
• This significant innovation dramatically improved the efficacy and flexibility of the
stereotactic frame.
• In the past several decades, newer technologies, such as 3D printing, have enabled
production of platforms with comparable accuracy and flexibility.

8. Leksell SAS Cosman Roberts Well SAS
 STarFix microTargeting Platform
(FHC, Bowdoin, USA)
 NexFrame stereotactic system
(Medtronic, Minneapolis, USA)
 SmartFrame system (ClearPoint Neuro,
Solana Beach, CA)
 Neuromate/ ROSA Robot
• Technologies associated
with DBS lead placement
including frame-based,
frameless, and robotic
methods.

9. The STarFix System
• The STarFix microTargeting Platform (FHC, Bowdoin, ME, USA) is a customized
miniframe that attaches rigidly to previously placed bone fiducial screws.
• This platform was enabled by early additive manufacture (3D printing) technology
that allows for precise customization and the possibility of multiple simultaneous
trajectories incorporated into the same frame.
• Konrad et al. measured a targeting error for this platform of 1.24 ± 0.4 mm in DBS
cases when brain shift was minimal.
• The multiple trajectories that can be achieved provide the opportunity of time savings
in bilateral DBS procedures.
• A variation of this platform technology is known as the Microtable which is cut from a
flat piece of polycarbonate and attached to four legs of varying lengths to give the
desired trajectory.

10. StarFix Apparatus. a Computer visualization of a dual-trajectory StarFix platform
for bilateral DBS. b Visualization of a multi-trajectory STarFix platform. c
Microtable with mounting hardware for STarFix, denoted by white arrow.

11. The NexFrame System
• The Medtronic NexFrame stereotactic system (NexFrame, Medtronic, Minneapolis,
MN, USA) is a skull mounted device for DBS lead placement. Consists of 3
components: an image guided probe, a passive reference frame, and a stereotactic tower.
• It is used in conjunction with bone-anchored fiducials to offer an alternative to frame-
based stereotaxy. The bone fiducials provide a rigid base for paired-point registration.
• Compared to other registration methods used for frameless targeting (i.e; adhesive
fiducials or surface registration), registration with bone fiducials produces the
registration accuracy required for DBS. A minimum of 5 bone fiducials are required to
register the NexFrame for surgical navigation.

12. Paired-point using the bone-anchored
fiducials. The tip of the image-guided
probe (white) is placed in the divot of one
of the five bone-anchored fiducials. The
optical camera of the navigation system
(not pictured) triangulates the relative
position of the image-guided probe to the
passive reference frame (blue).
The NexFrame tower. On the right, the ring assembly
is mounted to the skull and the reference frame
bracket assembly connects the passive reference
frame to the ring assembly; there is no socket
assembly. On the left, the socket assembly has been
placed on the ring assembly, and the image-guided
probe is secured to the socket assembly. The socket
assembly is able to rotate on the ring assembly. The
socket sweep is illustrated with the red arrow.

13. • The tower is comprised of a ring assembly, which is mounted to the skull at the site of the
burr hole; a socket assembly, which rotates on the ring and contains a sweep mechanism;
and a reference frame bracket assembly, which secures the passive reference frame to
the ring assembly.
• Alignment with the target is performed by rotating and sweeping the socket until the
trajectory intersects with the target.
• Once the trajectory is locked in, the navigation software provides the distance to target
and the DBS lead is placed.

14. The SmartFrame System
• Many patients who are good candidates for DBS, such as children or adults with
significant anxiety or severe involuntary movements, may not be able to tolerate
awake surgery.
• An interventional MRI (iMRI)-guided procedure that allows for real-time anatomical
imaging, with the goal of achieving very accurate lead placement in patients who are
under GA, is one possible solution for these patients.
• The procedure is performed within the isocenter of a high-field diagnostic magnet,
often in a radiology suite rather than in an operating room.
• A disposable skull mounted aiming device is used instead of a stereotactic frame.
Initially, this was done using an aiming device with two degrees of freedom, not
specifically designed for iMRI applications.

15. • Based on this experience, a second generation device was developed to improve ease of
use and accuracy of targeting; this device included improved mechanical controls and
an integrated software package (SmartFrame, ClearPoint Neuro, Solana Beach, CA).
• The SmartFrame has four degrees of freedom: “pitch” and “roll” controls for
performing an initial rapid approximate alignment in conjunction with oblique axial
imaging orthogonal to the alignment stem of the device, and finer X and Y controls used
in conjunction with oblique coronal and sagittal imaging through the long axis of the
device for fine adjustment of the final aim.
• The radial error of lead placement (deviation of the lead trajectory from the intended
trajectory in the axial plane) averaged 0.6 mm.

16. SmartFrame mounting device apparatus and use. a The SmartFrame skull
mounted aiming device, b Oblique coronal and sagittal images aligned with
the long axis of the alignment stem to adjust or confirm the final aim.

17. Stereotactic Atlases
• Human stereotactic atlases allow surgeons to determine Cartesian coordinates for
targeting structures in the thalamus or the basal ganglia by referring to anatomic
landmarks shown on myelin-stained thin slice brain sections.
• Since their introduction in clinical practice in the early 1950s, these atlases have had a
major impact on the practice of “indirect targeting” mostly by referring to structures in
the third ventricle, especially the inter-commissural line that “connects” the AC and PC.
• Schaltenbrand and Bailey atlas in 1959, and its second edition, the Schaltenbrand and
Wahren atlas in 1977. The latter contained an “electroanatomical atlas” alongside
pure morphology.
• New formats include printed atlases accompanied by digital media, purely electronic
atlases, software installed on commercially available workstations, and internet-
based tools available as free shareware or on a pay-per-use basis.

18. • In contrast to the classical print formats, these new platforms also provide pseudo or
even true 3D space, and allow for segmenting, scaling, and morphing of overlay
atlases according to the individual’s anatomy.
• The contemporary stereotactic atlases provide many features beyond morphology, with
data on fiber tracts or on vessels and enhanced information on function and
connectivity.
• More recently, age-dependent and ethnicity-specific characteristics have been taken
into consideration. All of this information may be relevant when positioning segmented
DBS electrodes.
• Despite these advances in atlases, direct targeting has become the preferred method in
most centers worldwide due to developments in neuroimaging. Direct targeting is
based on patient-specific MRI.

19. Planning Software
• DBS planning software integrates preoperative imaging, stereotactic atlases, and a
fiducial system in a user friendly and intuitive format that optimizes direct and indirect
targeting of electrodes.
• After selecting an MRI field strength (including 7T, if possible; minimum 1.5T) and the
ideal sequence for the target (e.g., T1, T2, FGATIR), image fusion is performed.
• While T1w thin-cut “stereotactic” axial imaging fused to other sequences allows for
targeting of the STN or GPi, it is common to use CT as a reference image to confirm
spatial accuracy.

20. • Ideally, the planning software of the future should be intuitive to use and largely
automated, auto-populating relevant imaging studies through secure, cloud-based
services.
• Images should be overlaid with 3D anatomic and functional atlases. Optimization
algorithms will be incorporated to target, based on intended lead, and safe trajectories
will be automatically generated.
• MER recordings will automatically and wirelessly be communicated to the planning
station and will be mapped along the anatomic trajectory. Automated algorithms will
give real-time feedback to the surgeon in terms of changes to optimal target or
trajectory safety.
• None of these novel advances will obviate the need for neurosurgeons to be intimately
familiar with neuroanatomy and to be able to proceed with the surgery in the
inevitable event of complex system failure.

21. Comparison of preoperative planning platforms

22. Registration of atlases to imaging. a FGATIR MRI scan depicted in native patient space. An
equidistant grid is overlaid. b The scan is nonlinearly co-registered to Montreal Neurological (2009)
space using default parameters in Lead-DBS. Note the nonlinear distortion introduced to the image as
indicated by the skewed grid lines. c After registration, the human motor thalamus is overlaid with the
normalized image, now showing spatial agreement. Such registrations work in both directions (and
are hence termed “diffeomorphic”). Once a solution is found, it can be applied to the image (porting it
to template space) or to the atlas (porting it to native subject space).

23. Intraoperative imaging to determine proper lead placement. a Use of intraoperative CT to image lead
position intraoperatively prior to closure. Imaging is being obtained prior to removal of the stylet from the
DBS lead. b Intraoperative CT merged with preoperative MRI indicates the location of contact of electrode
within the globus pallidus interna, the latter visualized using a fast gray matter acquisition T1 inversion
recovery (FGATIR) sequence.

24. Perioperative
“Asleep” versus “Awake” DBS Surgery
• The premise behind “asleep” DBS is that accurate anatomical placement of leads can
produce equivalent functional outcomes as lead placement guided by the traditional
method of awake testing.
• The anatomical target is visualized on MRI and the accuracy of lead placement is
assessed using intraoperative imaging.
• The consideration of asleep DBS resulted in part from advances in MRI, increased
availability of intraoperative 3D imaging and decades of clinical data on the efficacy
of DBS surgery.
• Awake surgery is guided by a discerning neurological exam to assess clinical benefit
and side effects during test stimulation and interpretation of electrophysiological data.
• With asleep DBS, there is greater reliance upon the navigation software, the quality of
the MR images, and target selection by the surgeon.

25. • Sources of error that may require repositioning of the lead must be factored into both
approaches.
• Include intrinsic and human errors with the stereotactic frame, hidden errors in the
navigation software, image distortion from the magnetic field, and brain shift
resulting from pneumocephalus or changes in head position.
• Ultimately, effective DBS surgery should include some means of confirming that the
lead is appropriately placed at the time of surgery. This can be done with test
stimulation, electrophysiological recordings, or intraoperative imaging.

26. MERs (Microelectrode Recordings) &
LFP(Local Field Potentials)
• Offer neurophysiological validation of brain target location. MER allows the recording
of action potentials and the identification of specific neurons through the detection of
neural signatures including spike firing rate, amplitude, morphology, and response to
electrical stimulation.
• For example, SNpr cells exhibit high frequency, low amplitude spikes that are inhibited
with electrical stimulation, while STN cells have high amplitude, low-frequency spikes
that do not exhibit inhibition to stimulation.
• The summation of multiple frequency bands (alpha, beta, theta, etc.) leads to a
synthesis of the composite LFP time series. Power changes in individual frequency
bands are reflected in the time-series as small voltage fluctuations.
• Such information can help distinguish functional subdomains of targets to a millimetric
scale. An example is increased beta band power in motor STN compared to its nonmotor
ventral territory.
• LFPs can be acquired from both the high impedance microelectrodes and the low
impedance DBS leads.

27. • Advanced signal processing techniques and artificial intelligence algorithms are
emerging to automate the interpretation of MER and LFP by detecting spectral
signatures of the raw spiking data and automatically calculating nuclear subdomains and
boundaries.
• The created “stimulation maps” are valuable tools for evaluation and orientation of the
region.
• Can analyze upto 5 electrodes simultaneously and suggest the best final implantation
location based on real-time data.

28. LFPs and Power spectra assist in target localization. Top panel shows a 3D rendering of
the surgical trajectory of a microelectrode superimposed on a coronal MRI. a denotes the
area of zona incerta. b, c denote dorsal and ventral STN border, respectively. d denotes
substantia nigra. The lower panel shows an example of in vivo intraoperative MER of the
surgical trajectory shown above. The overlay (bottom right) displays the power spectrum
of LFPs obtained from dorsal and ventral STN (b, c). The asterisk on the spectra denotes
an increased beta band power in dorsal STN (black) compared to ventral STN (red).

29.  Limitations, especially in relation to alleviation of symptoms:
 GPi, immediate clinical positive effects of intraoperative stimulation are rarely seen.
 Intraoperative evaluation of gait and balance is not feasible.
 Similar tremor arrest may be achieved from neighboring structures, such as the Vim of
the thalamus and caudal zona incerta.
 There is unpredictability of possible late emergence of side effects on chronic DBS that
are not evident during the intraoperative stimulation, such as alteration of speech
following STN DBS.

30. Confirmatory Imaging
• All sophistications used for targeting, trajectory, and pin-pointing, the only way to
ascertain the targeting precision is to verify it visually. So should stereotactic
neurosurgeons reason and act.
• With the advent of CT and especially MRI, one could immediately verify on a
stereotactic imaging the existence of possible pneumocephalus or early hematoma, and
one could verify the location of the lesion or the DBS lead, not only in stereotactic space
in relation to the frame coordinates, but also in relation to the desired anatomical brain
structure as visualized on MRI.
• In fact, a DBS surgery should not be considered complete and the frame should not be
detached from the head before confirmation by stereotactic imaging of accurate lead
placement. This is the essence of the concept of image-guided and image verified
functional stereotactic neurosurgery.

31. • Image-fusion software with inherent and variable fusion errors is used to evaluate
the approximate position of the leads.
• The benefit of proper stereotactic imaging during surgery or immediately after
carries many advantages: to validate the accuracy of the procedure in stereotactic
space; allow repositioning of the lead in the same surgical session if its location is not
optimal; and allow an exact confirmation of the position of each of the electrode contacts
in the target area.

32. Structural MRI implemented for GPi DBS. Top panel, a postoperative stereotactic 1.5T
proton density MRI, with 2 mm-thick contiguous axial scans from level of AC-PC to 6 mm
below. Bottom panel, contacts 0, 1, 2, and 3 of a Medtronic DBS electrode with depiction
of their placement in the postero-ventro-lateral GPi.

33. Robotics
• Robotic arms have been used in the functional neurosurgical operating room since the
1980s, with the first description of the PUMA (Programmable Universal Machine for
Assembly), an apparatus aimed to hold a needle for brain biopsy.
• In 1987, Benabid et al. described the first surgical version of the Neuromate, with an
ultrasound-based registration mode, designed to perform robotic-guided brain biopsy, but
also to implant DBS leads or to perform stereoelectroencephalography (sEEG).
• The typical robotic arm used in the field of stereotactic surgery is a supervisory controlled
system that allows the surgeon to:
(1) Plan offline, using dedicated software, a trajectory on a set of CT or MRI;
(2) Download the surgical plan to the surgical robot; and
(3) Supervise the robot that executes the plan.

34. • Robotic arms allow unlimited trajectories, sub-millimetric applicative precision and
accuracy of lead insertion, and unlimited 3D navigation around the head.
• Different modes of co-registration are possible, including surface registration,
framebased registration, and frameless (bone fiducial) registration.
• There is no need to enter or check any x, y, and z coordinates, as the robot software
automatically computes the coordinates of the entry point and target into 3D space,
thereby negating human error.
• The surgeon only needs to click on an entry point and target on a defined set of
images. It is also possible to correct, if needed, the axis of any trajectory with very small
increments (0.5 mm or less). It remains critical for the surgeon to verify the safety of the
planned trajectory.

35.  A robotic arm must be used with caution and appropriate skills; Principles for the use
of stereotactic robotic arms:
 The head must be firmly fixed, to avoid inaccuracy, and to prevent any head
movement when a surgical tool is inserted into the brain.
 Intraoperative imaging at the beginning of the first trajectory to check for any
possible deviation and the depth of probe insertion; the 3D images obtained during
surgery can be easily and rapidly co-registered into surgical planning.
 The movement of the robot must be systematically supervised by the surgeon to
avoid any collision.
 Preventative maintenance of the robot must be regularly performed by the
manufacturer.

36. Advancements in robotic surgery and surgical visualization. a The Neuromate Robot used to
implant DBS leads, brain biopsy, and sEEG. A frame-based or ultrasound-based registration
was primarily used. b The ROSA Robot is used for the same aims but is now coupled with an
intraoperative CT scan, and uses a frameless registration based on bone fiducials.

37. Electrode Implantation Technique
The quadripolar deep brain stimulation electrode
and the internal pulse generator. (Courtesy of
Medtronic, Inc.)

38. Comparison of DBS leads and functionality

39. Postoperative
Imaging and Anatomical Modeling
• After the surgical procedure, a crucial
step that completes the technological
framework of DBS is to reconstruct
electrode placement. This is essential
to confirm successful localization in the
target structure and to guide stimulation
settings.
• Electrode localization can be confirmed
using X-ray images, registrations
between postoperative CT and
preoperative data, or acquiring
postoperative MRI (with the
advantage of showing both electrodes
and target structures in the same
image).
A combination of advanced approaches and
precise datasets may lead to useful and
meaningful DBS models. The figure shows a list of
approaches that were developed during the last 5
years to refine image registration, electrode
localization, and biophysical modelling.

41. .
The “Ideal” Candidate for DBS for parkinsonism
1) Age: 40-70 yrs
2) Symptomatic for 5-10 years or more
3) Initial good response to L-dopa
4) Severe dyskinesia
5) Marked “on/off” phenomena (Minimal “on-time” without dyskinesia)
6) Cognitively intact
7) Realistic expectations
8) Adequate social support
9) Access to programming of stimulators
 Final decision lies with Neurologist and Neurosurgeon.
International Journal of Contemporary Medicine Surgery and Radiology Volume
3 | Issue 3 | July-September 2018
DBS in India
12-25 lakhs 50-60 lakhs

42. Conclusions
• Our understanding and implementation of DBS as a therapeutic procedure are
rapidly expanding, with its great potential to modulate neurocircuitry at the tissue
level in a minimally invasive, but highly effective, manner.
• The techniques of DBS system implantation have been greatly improved by
developments and innovation in stereotactic technology, surgical techniques, and
imaging.
• Innovations in DBS technology and surgery promise to make DBS surgery more
accurate and effective, with potentially better outcomes for a wider spectrum of
patients.
• Additional multidisciplinary work is needed to translate these technological advances
into patient benefit.
• The parallel rise of novel brain imaging, new targeting techniques, improved
electrode and stereotactic frame hardware, the rise of robotics, and enhanced atlas
guides have enhanced technique, but may also come at a cost.

43. • The development of asleep DBS may be considered as an advance. Unfortunately, it
also means that the opportunity for a younger generation of neurosurgeons to learn
from stimulating the awake brain will be lost and that a technique which has, often
through fortuitous serendipity, been the driving force behind the introduction and
refinement of many brain targets, will pass into obscurity.
• Moreover, and oddly, this trend goes against a current interest in doing as many
neurosurgical operations as possible under local anesthesia, and it ignores the
potential risks of intubation and general anesthesia in patients who are often old and
debilitated.

44. References:
• Youmans and Winn neurological surgery 8th edition
• Functional Neurosurgery by Philip A. Starr, 2nd edition
• Internet
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