Circuitous Goal of bSTN deep brain stimulator in parkinson disease: A study with fusion MRI guided by Computed Axial tomography and microneurosensor recording MER techniques

Hypothesis

Even though the technique of intra operative ventriculography incorporates in the elimination of cerebrospinal fluid from ventricles6 which gives dependable detection and discovery of the posterior commissure and anterior-commissure that are historic pointers and sign-posts for circuitous targeting methods. 4 On the contrary to ventriculography, MRI and CAT CT are least insidious—invasive, simplicity, alleviates and done with ease. Since, the hitch with targeting STN is that, it is a small biconvex lens and almond shaped diamond structure and markedly not perceptible on the MRI attributable to need of distinction or contrast and disparity amid STN and the neighboring structures.8, 9 The STN can be visualized on the MRI but other methods such as Lozano’s technique where a position 3 mm lateral to the superolateral border of the red nucleus is targeted have been studied and found to be effective areas for stimulation. 10

Owing to noise and distortion (poor temporal resolutions of MRI), the visibility of STN on MR imaging and also inadequate clarity of the anterior-commissure and posterior-Cummins and subthalamic-nuclei by CT, the amalgamation of stereotactic frame based CAT and magnetic resonance techniques are contemplated to fuse the progress and gaining of the two techniques, augment the spatio-temporal resolutions and precision of the confinement. Plus targeting of the STN and electrophysiological micro-recordings are employed through deep brain stimulus to guarantee the better implantation of microelectrodes along the subthalamic-homunculus4, 11 and to identify MER signatures (or patterns) that correlate with improved motor symptoms. 2

But, magnetic resonance neuroimaging on idiopathic Parkinson disease subjects (patients) may be intricate due to their cardinal motoric-feature manifestations that includes few problems to patients such as palpable-tremor, rigorous dystonia asymmetric tremors like stooped forward with gradient trunk and presumably having complexity and impenetrability in gait 4, 5, 6. Therefore, to overcome this limitation in reaching and targeting the STN, it can be hypothesized with fused techniques such as fusion MRI guided by computed axial tomography and electro-physiological micro recordings.

Surgery

3.1 All PD patients who were wheelchair or bed bound, had dementia or severe psychiatric disturbances were excluded. The perpendicular and perpendicular distances between the midpoint of the head frame and the brain midline at the septum pellu-cidum intensity and the greater perimeter of the two-sided lens on a skeletal and undernourished part brain scan by CAT were distincted as the perpendicular-deviation and perpendicular-variation. Following the anesthesia, a CRW-frame was applied such that the frame was centered on the midline to allow for the maximum symmetry between the right and left hemispheres of the brain such that it was as analogous as probable to the anterior-commissure(AC) to the posterior-Cummins(PC) and right-hemisphere of the brain to the left-hemisphere brain symmetrical-planes (see Figure 1).

Figure 1

(A). Ear strip-chart depicting the equilibrium and perfect arrangement   of of the    CRW-frame     CRW-frame and pinning helped for fixing the frame, and reduce the perpendicular and    horizontal-variations between RH-side and LH side. 4, (B). The head frame was fixed which was medial on the midline, hence setting for symmetry maximally between RH and LH of the brain such that    it was concurrent as possible to the AC and PC RH-plane - left HS-plane. 4

A stereotactic 1 millimeter thickness, section-angle analogous to CRW-frame, and CAT image was acquired with the geometrical frame-based stereotactic computed axial functional tomography (the CAT).

Based on usual geometrical co – ordinates of the target structure of the geometry of the brain-atlas, a circuitous target was chosen for CAT. The projected co – ordinates for the goal position was 12 millimeters cross starting the peduncle, 3millimeter following the mid-commissural-point, and few-millimeters (4mm to 5mm) under the anterior-commissure and posterior-Cummins-line. The protected Trans frontal lobe trajectory to the object was positioned circa ~15º from the sagittal-plane and 60º to 70º in the frontal and lateral path while avoiding cortical and peri—ventricular—veins. Roughly, touching (more-or-less) the subthalamus, the microrecording signal dynamics and motion movement portrayed augmented amplitudes correlated to the subthalamic-nuclei. Once lead gone on to the STN, the settings of neighboring commotion amplified stridently, and giant-amplitudes (due to stimulus intensity) asymmetrical and uneven lop-sided and spikes through firing-rates by means of frequencies (30Hertz and 70Hertz) depicted. The exit of the tip and tilt of the microelectrode beyond the nucleus subthalamic was signified with a shrink in adjacent-noise and the occurrence of spontaneous impulsive—neuronal-activity (spur of the movement) contrasted along whilst the lead was in the subthalamic-nucleus.

As soon as the neuronal-activity runs into and which was distinctive of the SNpc that was differentiated by the expected dis—charges at 75Hertz to 110Hertz, and then the signal recording was stopped. The inferior circumference of zero (0) contact was embedded in to SNpr. Hence, this zero contact touches contacts 2 or 3 probably positioned behind the retral i.e., dorsal sensori-motor area of nuclei (subthalamic). The length of the unilateral nuclei (dogged by microrecording) was the space linking the microrecording ingress in to nuclei and egress out of nuclei. When it is ≤ 4mm, we impeded the signal-recording following 2-trajectories on both-sides. Since, electrode (3389 consists of 4iridium-platinum cylindrical surfaces with 1.27mm diameter were implanted and hence testing has to done. Therefore, by employing stimulator (externus) intra operative bi-polar test stimulus’s for checking the dykinesia`s were accomplished. The stimulus voltage was steadily augmented from 3volts to 3.5volts. For corroborating the lead contact, subjects undergone for T2-weighted imaging. Following a week of the first implantation, the electrodes were connected to a hypodermic (situated subcutaneously in the epidermis) programmable pulse generator (PPG). Every subject was clinically and technically administered mono polar stimulus and impulses by means of setting the factors—parameters disjointly in the range of 2.5 volts to 4.3volts, with 60mSeconds pulse-width, and 90Hertz to 190Herts frequency ranges.

To identify MER signatures (or patterns) that correlate with improved motor-symptoms, the electro-physiological confirmation and fine-tuning of the target region was confirmed by invoking the smart programme—software (Medtronic). The uses of electrophysiological microrecording technique as of the STN and intra-operative stimulus have helped in clearly demarcating the nuclei (subthalamic). 2, 4 The following 2Figure 2 and 2 depict the signal acquisition of STN recording.

Figure 2

Microrecording in a discrete-level in a discrete-channel

Figure 3

Microrecording in the central channel over 11mm and showing the typical firing pattern with irregular firing and broad baseline noted from -1.00 onwards…

Recording in the mid channel over 11mm and shows the typical firing pattern with asymmetrical and lopsided firing and broad baseline noted from -1.00 levels (Figure 3), 2

Evaluation

The subjects were evaluated by the Unified Parkinson Disease Rating Scale stage-III-scores. The difference in the post op UPDRS-stage-III scores of the subjects between the DBS “OFF” and “ON” in the “OFF- medication-state” was distinct as depicted in A. The pre op baseline score in med OFF state was distinct as depicted in B and the pace and the progression of UPDRS-stage-III score was distinct as given by AB (100). 12 For the perpendicular-deviation, the CAT picture of septum pellu-cidum which was very near to anterior-commissure and posterior-Cummins perpendicular line was selected.

Figure 4

Computed axial tomography (CAT) image. The perpendicular dashed-line (C to L) pointing towards septum-pellu-cidum. C is the mid-point of the horizontal line (i.e., on the axis-X).

The perpendicular distance between the mid-point of the head-frame and the mid-line of brain on a fine tomography scan-part, thickness-of-slice is 1mm; at the septum-pellu-cidum level was evaluated preoperatively and distinct at the perpendicular deviation showed in (Figure 5) and the distance of the superior border of the bilateral lens on a skeletal CAT image part is 1mm, i.e., the thickness of slices (ToS) was pre operatively assessed which is distinctive as depicted in Figure 5 as perpendicular deviation.

Figure 5

A—B. CAT images for DBS operation with an interval distance of each 1mm (serially). Image A shows the better boarder of the right-lens indicated with down-arrow; left-lens was unavailable in this picture. C—D. Superior border of the left-lens (showed with down arrow. The perpendicular-deviation was calculated from image (serial) as 2mm.

By applying the microrecording system, the duration (distance end to end –length) of the nuclei (subthalamic) was distincted as an average o the space between the star-point (SP) and the end-points(EP) of the bSTN. The dimension—magnitude)-of-STN was 5.9mm (by the antero-posterior AP), 3.7mm (by means of medio-lateral ML), and 5mm (via d dorso-ventral DL). 13 Hence, the entry paths of the micro-recordings in to sub-thalamic-nuclei in the AL direction were verified that the proper measuring distance of the STN was between 4 and 6 mm.

Clinico—statistical analysis

Constant—capricious (variables) are demonstrated in Table 1 .

As the mean-standard-error(MSE) or mean standard-error-of-mean(SEM), whilst categorical-variables are demonstrated via frequencies/percentages(%). The dissimilarities of positive-effects versus adverse-effects were computed by sample t-tests for constant capricious(variables) and/or χ² test for categorical variables. The chi-square χ² @ 4.2866 for 1 degree of freedom, which is significant at 5%, with p ≤ 0.05, with χ² @ 9.2857, with 2 degree of freedom which is highly significant at 5% with p ≤ 0.0089. A series of uni-variate linear-regression was done for making out factors which were potentially connected by the progressions in the UPDRS-scores. The p-values ≤ 0.03 considered in this study for the variables.

Findings

The clinical details of all the subjects recapitulated in the Table 1. Following the therapeutic DBS surgical-operation, subject UPDRS-stage-III-scores progressed by 48±2.8% in the range of 20 to 81 measured up to subject’s baseline OFF-levedopa (medication OFF) scores. Mean recorded length difference of the STN among the first and last single recording trajectories was 5.37±0.16millmeters in the range of 3.99 to 7.50. The UPDRS-stage-III score progress was 48 and 2.8%. As per the micro signal recording (MER), the MSE length of the nuclei (subthalamic) was 5.37mm and 0.16mm in the range of 3.99 to 7.50. The mean of standard error mean or mean standard error (MSE) of bSTN stimulus factors of pulse-width, current-voltage, and frequency was 60±0, 3.3±0.06, and 135.48±4.93. The magnitude of the MSE, i.e., volume of the pneumo-cephali in the post op MRI was 5.29±2.02Cubic-centimeters (CC) in the range of 0 to 59. The MSE horizontal-deviation was 1.7mm±1.2mm in the range of 0mm to 5mm, and the perpendicular MSE deviation was 1.2mm±0.7mm in the range of 0mm to 2mm.

Multiple linear-regression-analysis (LRA) disclosed the augmented lengths of perpendicular-regression-coefficients (PRC) B:-0.0626; with high degree 95% of confidence interval (CI):-0.113 to -0.013, and perpendicular deviations B:-0.0497, 95%CI:-0.083 to -0.017 were coupled with less progression in the subjects on the UPD rating scale. Even though, the lead insertions can be executed by means of higher frequencies eventually, the lead insertion errors can takes place in all the modalities, such as imaging modalities, planning, frame, in opening of the burr hole, frame application fiducially, imaging and planning, burr hole opening, electrode insertion, and lead-fixation. As the targeting precision is distressed in various operational-steps, each pace desires to be meticulously and methodically observed to reduce potential errors if any.