Fusion Image–Based Programming After Subthalamic Nucleus Deep Brain Stimulation

PEER-REVIEW REPORTS

Fusion Image–Based Programming After Subthalamic Nucleus Deep Brain Stimulation Sun Ha Paek1,3,4,6,7, Hee Jin Kim2, Ji Young Yoon2, Jae Heok Heo2, Cheolyoung Kim8, Mi Ryoung Kim1, Yong Hoon Lim1, Keyong Ran Kim1, Jin Wook Kim1, Jung Ho Han1, Dong Gyu Kim1, Beom S. Jeon2,3,4,5

Key words 䡲 Advanced Parkinson disease 䡲 Electrode positions 䡲 Fused image– based programming 䡲 Preoperative MRI 䡲 Postoperative CT Abbreviations and Acronyms CT: Computed tomography DBS: Deep brain stimulation LEDD: Levodopa equivalent daily dose MER: Microelectrode recording MMSE: Mini-mental status examination MRI: Magnetic resonance imaging PD: Parkinson disease SEADL: Schwab and England Activities of Daily Living SF-36: Short-form-36 health survey STN: Subthalamic nucleus UPDRS: Unified Parkinson Disease Rating Scale 1

From the Departments of Neurosurgery and 2 Neurology, 3Movement Disorder Center, and Clinical Research Institute, Seoul National University Hospital; 5Neuroscience Research Institute, 6Cancer Research Institute, and 7Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine; and 83D Lab, CyberMed Inc., Seoul, Korea 4

To whom correspondence should be addressed: Beom S. Jeon, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2011) 75, 3/4:517-524. DOI: 10.1016/j.wneu.2010.12.003

䡲 OBJECTIVE: To propose fusion image– based programming to adjust patients with advanced Parkinson disease (PD) effectively after subthalamic nucleus (STN) deep brain stimulation (DBS). 䡲 METHODS: Between January 2007 and July 2008, 38 patients with advanced PD were consecutively treated with STN DBS. The electrode positions and information regarding their contacts with STN were determined via fusion of the images of preoperative magnetic resonance imaging (MRI) and of postoperative computed tomography (CT) obtained 1 month after STN DBS. Postoperative programming was performed using the information of electrode positions based on the fused images. All patients were evaluated with a prospective protocol of the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr Staging, Schwab and England Activities of Daily Living (SEADL), levodopa equivalent daily dose (LEDD), short-form-36 health survey (SF-36), and neuropsychological tests before and at 3 months and 6 months after surgery. 䡲 RESULTS: There was a rapid and significant improvement of motor symptoms, especially tremor and rigidity, after STN stimulation, with low morbidity. Stimulation led to an improvement in the off-medication UPDSR III scores of the patients of approximately 55% at 3 months and 6 months after STN DBS. Dyskinesia was significantly improved (74% at 3 months and 95% at 6 months) after STN DBS. In addition, LEDD values decreased to 50% of the level observed before surgery within 1 month after STN DBS. 䡲 CONCLUSIONS: Programming based on fused images of preoperative MRI and postoperative CT after STN DBS was performed quickly, easily, and efficiently.

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INTRODUCTION Subthalamic nucleus (STN) deep brain stimulation (DBS) is a standard therapy for patients with advanced Parkinson’s disease (PD) and intolerance for long-term use of medication (2, 8, 13). DBS programming is a time-consuming task, however, that requires a long period of adjustment after surgery (5, 14, 19). Traditionally, DBS programming follows a standardized step-bystep approach (14, 19). The basic algorithm for DBS programming comprises three parts: (i) initial programming during the postoperative period, (ii) initiation of longterm stimulation, and (iii) stimulation adjustment during the stabilization period

(first 3– 6 months after surgery) (5, 19). This approach tests each electrode one by one to detect the best stimulation parameters. Generally, the starting point is set at a pulse width of 60 ␮s and a frequency of 130 Hz. Subsequently, the amplitude threshold is determined to induce a clinical response and side effects using monopolar stimulation for each electrode contact, with a stepwise increase in amplitude (0.2– 0.5 V). If clinical improvement is observed without side effects, the amplitude is increased further to determine the threshold of onset of adverse effects. If no beneficial or adverse effects are observed within the available amplitude range, the next contact is selected and tested. The electrode contact with the lowest threshold that induces a benefit and the largest therapeutic width (ie, highest threshold for side ef-

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fects) is finally selected for long-term stimulation. We deemed that the determination of the best electrode contacts closest to the STN can be performed more easily and quickly via the fused image of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT). Previously, we reported a method to estimate the electrode positions after STN DBS using a mutual information technique (12). The image fusions of preoperative MRI and postoperative CT taken 1 month after STN DBS using the mutual information technique enabled the identification of the three-dimensional location of the leads and of each contact in relation to the STN. We hypothesize that we can select the electrode contacts closest to the STN for postoperative DBS programming with ease and confidence

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within a short-term period after STN DBS based on the information provided by such fused images (4, 7, 11). We report the shortterm clinical outcome of patients with advanced PD, focusing on the efficacy and practicability of fusion image– based programming after STN DBS.

FUSION IMAGE–BASED PROGRAMMING AFTER STN DBS

Table 1. Characteristics of 38 Patients Treated with Subthalamic Nucleus Deep Brain Stimulation Variable Male-to-female ratio Age (years)

15:23 58.2 (30–73)

METHODS

Body weight (kg)

58.5 ⫾ 10.5 (41.2–80.8)

Using a prospective protocol, this study included 38 patients with advanced PD who were consecutively treated with STN DBS between January 2007 and July 2008. The evaluation protocol before and after STN DBS was previously described elsewhere (9, 15). Neurologic evaluations were performed using the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr staging, and Schwab and England Activities of Daily Living (SEADL) before and at 3 months and 6 months after STN DBS. The preoperative and postoperative evaluation protocols of PD at the Movement Disorder Center of Seoul National University Hospital generally followed the Core Assessment Program for Intracerebral Transplantations protocol. The levodopa equivalent daily dose (LEDD) was computed for each antiparkinsonian medication by multiplying the total daily dosage of each drug by its potency relative to a standard levodopa preparation that was assigned the value of 1, as described previously (6, 9, 15). The ShortForm-36 Health Survey (SF-36) and neuropsychological tests were also evaluated before and 6 months after STN DBS.

Symptom duration (years)

12.2 ⫾ 5.3 (5–33)

Medication duration (years)

10.6 ⫾ 3.3 (5–16)

Selection and Characteristics of Patients The indication for STN DBS was advanced idiopathic PD with at least two cardinal features of parkinsonism (tremor, rigidity, and bradykinesia); a good response to levodopa; and drug-induced side effects (eg, dyskinesia and unsatisfactory management of fluctuations with medication). Patients with severe cognitive impairment or dementia, ongoing psychiatric problems, unsatisfactory general condition, or inability to comply with the study protocol were excluded. The clinical characteristics of these 38 patients are summarized in Table 1. Surgical Technique Surgical procedures were previously described elsewhere (6, 9, 15). In all cases, a

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LEDD (mg/day)

793.4 ⫾ 527.0

Total score of UPDRS On medication

30.8 ⫾ 14.4 (11–73)

Off medication

65.7 ⫾ 18.1 (29.5–109.0)

Subscore of UPDRS part III On medication

20.3 ⫾ 11.7 (2.5–56.0)

Off medication

40.9 ⫾ 13.4 (14.5–69.0)

Hoehn and Yahr score On medication

2.4 ⫾ 0.5 (1.0–4.0)

Off medication

3.1 ⫾ 0.9 (2.0–5.0)

SEADL On medication

83.3 ⫾ 10.1 (60–100)

Off medication

64.2 ⫾ 13.6 (30–90)

Good awake time (%) Dyskinesia disability

13.3 ⫾ 5.6

erators were implanted subcutaneously under general anesthesia in a single session. Bilateral STN DBS was performed in 33 patients, and unilateral STN DBS was performed in 5 patients. Patients underwent three-dimensional spiral stereotactic CT using 1-mm slice thickness immediately and 1 month after DBS.

Electrode Localization After Subthalamic Nucleus Deep Brain Stimulation The image fusion between preoperative MRI and postoperative CT was performed using the mutual information technique (Lucion; Cybermed, Inc., Seoul, Korea), as previously described elsewhere (Figure 1) (4, 6, 7, 9, 11, 15, 16). This method enabled the identification of the three-dimensional location of the leads and of each contact in relation to the STN. Figure 1A shows the fusion images of preoperative MRI images and postoperative CT images acquired 1 month after surgery. The locations of the eight contacts of the leads in all 38 patients were plotted bilaterally onto the human brain atlas of Schaltenbrand and Wahren, based on the information obtained from the fused images of preoperative MRI and postoperative CT, as depicted in Figure 1B (18).

2.1 ⫾ 1.5

LEDD, levodopa equivalent daily dose; SEADL, Schwab and England Activities of Daily Living; UPDRS, Unified Parkinson Disease Rating Scale.

stereotactic Leksell-G frame (Elekta Instruments AB, Stockholm, Sweden) was mounted on the head of the patient under local anesthesia. A 1.5T MRI scanner (Genesis Signa; GE Medical Systems, Milwaukee, Wisconsin, USA) was used for the preoperative planning. The STN was localized using a combination of MRI, microelectrode recording (MER), and stimulation technique, as previously described elsewhere (6, 9, 15). A multichannel parallel probe (five channels, the so-called Ben Gun) was used for MER, and stimulation was applied. Generally, the left STN target was approached first and was followed by the right STN target in bilateral cases. The quadripolar electrodes (DBS 3389; Medtronic Sofamor Danek, Minneapolis, Minnesota, USA) were inserted under local anesthesia and the implantable pulse gen-

Fusion Image–Based Programming After Subthalamic Nucleus Deep Brain Stimulation Previous antiparkinsonian medications were stopped, and the STN DBS was turned on 1 day after surgery, with unipolar stimulation of contact no. 1 at 0.5–1.0 V, 60 Hz, and 130 ␮s. The medication was restarted and adjusted to fit the patient’s status of motor functions with continuation of the initial stimulation of the DBS parameters during the admission. At 1 month after surgery, when the brain shift caused by cerebrospinal fluid leakage was stabilized, a three-dimensional estimation of electrode position was performed based on the information obtained from the fused images of preoperative MRI and postoperative CT acquired 1 month after STN DBS surgery, as previously mentioned (7). Using an N’vision programmer (Medtronic, Minneapolis, Minnesota, USA), the contacts of the electrodes closest to the STN and stimulation parameters were selected by the neurologist for long-term stimulation,

WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2010.12.003

PEER-REVIEW REPORTS SUN HA PAEK ET AL.

FUSION IMAGE–BASED PROGRAMMING AFTER STN DBS

Figure 1. Image analysis system. (A) Fusion images of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) acquired 1 month after surgery. In the fused images, the MRI images are in black and white and the CT images are pseudocolored. The pseudocoloring of the CT images was adjusted so that the leads would appear in red. Fused axial and sagittal images show that the leads were located within the subthalamic nucleus (STN). The MRI image shows the tissue loss from the previous two thalamotomies performed in 1993 and 1994 at another hospital. The atlas of Schaltenbrand and Wahren was overlaid on the fused coronal and sagittal images. (B) Location of the leads and of the eight contacts was plotted onto the human brain atlas of Schaltenbrand and Wahren based on the CT/MRI fusion images. The location of each contact was measured from the distal end of the lead. In this patient, the right lead lies in the center of the STN, contact 2 is within the STN, and contacts 1 and 3 straddle the border of the STN. Contact 0 is below the STN. The left lead is in the lateral part of the STN, contacts 2 and 3 are within the STN, and contacts 0 and 1 are below the STN.

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Table 2. Surgical Outcome of 38 Patients with Parkinson Disease After Bilateral Subthalamic Nucleus Deep Brain Stimulation P Value

Total UPDRS

Medication

DBS

On

Off

On

On

Off

Off On

On

33.4 ⫾ 14.8 38.0 ⫾ 13.6

On

On

Off

Dyskinesia Disability

0.038 ⬍ 0.001* ⬍ 0.001* 0.203

14.4 ⫾ 8.3

14.5 ⫾ 6.1

0.004*

0.005*

18.6 ⫾ 8.4

18.1 ⫾ 8.0

0.001*

0.001*

2.4 ⫾ 0.5

2.5 ⫾ 0.5

0.729

2.6 ⫾ 0.4

2.6 ⫾ 0.5

0.001*

0.337 ⬍ 0.001*

83.3 ⫾ 10.1

On

Off

LEDD (mg/day)

0.015 ⬍ 0.001*

64.2 ⫾ 13.6

Off On

6 Months vs Baseline

2.4 ⫾ 0.5

Off SEADL

3 Months vs Baseline

3.1 ⫾ 0.9

Off On

25.3 ⫾ 10.4 33.4 ⫾ 14.2

20.3 ⫾ 11.7

On

Off

24.5 ⫾ 12.8 33.7 ⫾ 16.4 40.9 ⫾ 13.4

Off Hoehn and Yahr score

6 Months

30.8 ⫾ 14.4

Off UPDRS III

3 Months

65.7 ⫾ 18.1

Off On

Baseline

86.1 ⫾ 9.9

86.6 ⫾ 9.7

80.6 ⫾ 13.7

80.5 ⫾ 14.3

0.185 ⬍ 0.001*

0.085 ⬍ 0.001*

2.1 ⫾ 1.5

0.5 ⫾ 1.1

0.3 ⫾ 0.8

⬍ 0.001*

⬍ 0.001*

793.4 ⫾ 527.0

285.3 ⫾ 387.2

246.5 ⫾ 322.1

⬍ 0.001*

⬍ 0.001*

DBS, deep brain stimulation; LEDD, levodopa equivalent daily dose; SEADL, Schwab and England Activities of Daily Living; UPDRS, Unified Parkinson Disease Rating Scale. *P ⬍ 0.01 and statistical significance with use of the Bonferroni correction method to avoid a type I error when conducting multiple analyses over time.

based on the information collected from the fused images of preoperative MRI and postoperative CT acquired 1 month after surgery. The patients were not allowed to modify the settings of the DBS by themselves. The stimulation parameters for long-term stimulation were adjusted by the neurologist during the outpatient clinic follow-up, based on the information obtained from the fused images of preoperative MRI and postoperative CT acquired 1 month after surgery. Whenever DBS parameter adjustment was necessary thereafter, the patient visited the Movement Disorder Center of Seoul National University Hospital during the follow-up period. Monopolar and multipolar stimulations were chosen on a case-by-case basis to achieve better responses of motor function from the patients.

Statistical Analysis The data are presented as the means ⫾ standard deviation. We used the paired Student t test or the paired Wilcoxon signed-rank test

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Figure 2. Levodopa equivalent daily dose (LEDD) changes associated with subthalamic nucleus (STN) deep brain stimulation (DBS) in 38 patients with Parkinson disease (PD). Preoperative LEDD was 793.4 mg/day ⫾ 527.0. LEDD decreased postoperatively to 285.5 mg/day ⫾ 271.6 at 2 weeks (P ⬍ 0.001), 326.8 mg/day ⫾ 344.3 at 1 month (P ⬍ 0.001), 256.8 mg/day ⫾ 283.6 at 2 months (P ⬍ 0.001), 277.8 mg/day ⫾ 402.3 at 3 months (P ⬍ 0.001), and 245.3 mg/day ⫾ 342.9 at 6 months (P ⬍ 0.001) after STN stimulation.

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Table 3. Unified Parkinson Disease Rating Scale III Subscores of 38 Patients with Parkinson Disease After Bilateral Subthalamic Nucleus Deep Brain Stimulation P Value

Tremor

Medication

DBS

Baseline

On

Off

2.4 ⫾ 4.3

1.3 ⫾ 2.5

Off Rigidity

On

Off

On

4.5 ⫾ 3.2

3.7 ⫾ 2.7

Off Bradykinesia

On

Off

On

7.2 ⫾ 4.9

6.9 ⫾ 3.8

Off Gait

On

Off

On

1.1 ⫾ 0.8

1.0 ⫾ 0.7

Off Posterior stability

On

Off

On

0.9 ⫾ 0.9

1.1 ⫾ 0.7

Off Speech

On

Off

On

0.9 ⫾ 0.9 1.3 ⫾ 0.8

Off On

Off

0.008*

2.5 ⫾ 2.5

0.006*

3.5 ⫾ 2.8

⬍ 0.001*

0.005* ⬍ 0.001* ⬍ 0.001*

5.4 ⫾ 2.8 7.0 ⫾ 3.6

0.876 0.059 ⬍ 0.001*

0.037 ⬍ 0.001* 0.019

0.9 ⫾ 0.7 1.0 ⫾ 0.7

0.358 0.036 ⬍ 0.001*

0.104 ⬍ 0.001* 0.017

1.5 ⫾ 0.9 0.9 ⫾ 0.8

On

0.004*

1.3 ⫾ 0.9

1.6 ⫾ 0.9

Off

⬍ 0.001*

1.7 ⫾ 0.8 0.8 ⫾ 0.7

On

⬍ 0.001*

0.023

1.5 ⫾ 0.8

1.8 ⫾ 0.9

Off

1.1 ⫾ 1.9

0.553 0.014

14.6 ⫾ 6.0 5.5 ⫾ 4.1

On

1.0 ⫾ 2.2

12.9 ⫾ 6.3

14.5 ⫾ 5.4

Off

0.001*

8.1 ⫾ 3.9 2.6 ⫾ 2.6

On

6 Months vs Baseline

7.2 ⫾ 4.4

9.4 ⫾ 4.3

Off

3 Months vs Baseline

4.9 ⫾ 5.6 0.9 ⫾ 2.1

On

6 Months 4.1 ⫾ 5.6

4.8 ⫾ 4.8

Off On

3 Months

0.9 ⫾ 0.9 1.1 ⫾ 0.8

0.217 0.922 ⬍ 0.001*

0.364 0.001*

1.3 ⫾ 0.7

0.020

1.4 ⫾ 0.7

0.510

1.1 ⫾ 0.8

1.1 ⫾ 0.8

0.275

1.1 ⫾ 0.7

1.2 ⫾ 0.7

0.683

DBS, deep brain stimulation. *P ⬍ 0.01 and statistical significance with use of the Bonferroni correction method to avoid a type I error when conducting multiple analyses over time.

to compare the baseline data with the follow-up data. The significance level was set at P ⬍ 0.01 for all analyses, and the Bonferroni correction method was used to avoid type I errors during multiple analyses over time.

RESULTS Clinical Outcome There were 38 patients with advanced PD who were treated with STN DBS. Three of the patients received repeat surgery to reposition the electrodes. All patients were fol-

lowed up and evaluated 3 months and 6 months after the operation. The average hospital stay after surgery was 5.3 days ⫾ 1.6 (range 4 –12 days). The time of programming based on the fused image of preoperative MRI and postoperative CT acquired 1 month after STN DBS was 3.9 minutes ⫾ 0.8 (range 2.7–5.7 minutes). The number of office visits was 9.5 ⫾ 4.0 (range 4 –22), and the total programming time until 6 months after STN DBS was 36.2 minutes ⫾ 14.1 (range 12.7–79.5 minutes). With STN stimulation, the motor symptoms of the patients improved markedly compared with the preoperative status (Ta-

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ble 2). The off-medication total UPDRS scores of the patients improved with stimulation by 48% at 3 months and 6 months after STN DBS. The off-medication UPDSR III scores of the patients improved with stimulation by 55% at 3 months and 6 months after STN DBS. The dyskinesia disability scores of the patients improved with stimulation by 76% at 3 months and by 96% at 6 months after STN DBS. LEDD decreased postoperatively from 793.4 mg/day ⫾ 527.0 to 285.5 mg/day ⫾ 271.6 at 2 weeks (P ⬍ 0.001), 326.8 mg/day ⫾ 344.3 at 1 month (P ⬍ 0.001), 256.8 mg/day ⫾ 283.6 at 2 months (P ⬍ 0.001), 285.3 mg/day ⫾

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Table 4. Short-Form-36 Health Survey Outcomes in 38 Patients Scores SF-36 Scales

P value

Baseline

3 Months

6 Months

3 Months vs Baseline

6 Months vs Baseline

PF

45.13 ⫾ 28.49

51.97 ⫾ 26.75

48.02 ⫾ 26.21

0.128

0.503

RP

17.76 ⫾ 31.79

44.08 ⫾ 36.96

26.97 ⫾ 38.72

0.002*

0.173

BP

51.45 ⫾ 26.85

73.88 ⫾ 23.63

68.16 ⫾ 23.41

⬍0.001*

GH

46.95 ⫾ 19.47

59.11 ⫾ 21.49

53.42 ⫾ 20.21

0.001*

0.043

VT

42.63 ⫾ 19.34

53.95 ⫾ 21.06

50.13 ⫾ 19.29

0.002*

0.091

SF

44.80 ⫾ 26.07

64.14 ⫾ 26.75

62.30 ⫾ 24.70

0.001*

0.001*

RE

20.18 ⫾ 35.97

52.63 ⫾ 42.89

29.82 ⫾ 39.36

0.001*

0.208

MH

56.11 ⫾ 17.53

64.74 ⫾ 18.83

62.11 ⫾ 21.69

⬍0.001*

0.071

PCS

161.29 ⫾ 76.46

229.04 ⫾ 80.71

196.58 ⫾ 86.11

⬍0.001*

0.015

MCS

163.71 ⫾ 77.35

235.46 ⫾ 89.97

204.36 ⫾ 84.37

⬍0.001*

0.007*

Scales

0.005*

Summary scales

PF, Physical Functioning; RP, Role Physical; BP, Bodily Pain; GH, General Health; VT, Vitality; SF, Social Functioning; RE, Role Emotional; MH, Mental Health; PCS, Physical Component Summary; MCS, Mental Component Summary. *P ⬍ 0.01 and statistical significance with use of the Bonferroni correction method to avoid a type I error when conducting multiple analyses over time.

387.2 at 3 months (P ⬍ 0.001), and 246.5 mg/day ⫾ 322.1 at 6 months (P ⬍ 0.001) after STN stimulation (Figure 2). Among the off-medication motor subscores on part III of the UPDRS, the motor symptoms tremor and rigidity exhibited the most significant improvement after STN DBS surgery (Table 3). The other off-medication motor subscores, with the exception of speech, also improved significantly after STN DBS. The SF-36 outcomes of the 38 patients are summarized in Table 4. The scores of all subscales, with the exceptions of the physical functioning scale and of the physical and mental component summary scales of the SF36, were improved significantly at 3 months after surgery. The scores of bodily pain and social functioning among the eight scales and the mental component summary scales of the SF-36 were improved significantly at 6 months after surgery. Neuropsychological tests were performed before and 6 months after STN DBS. A significant decline in minimental status examination (MMSE) scores was noted at 6 months (27.86 ⫾ 1.85 vs 26.62 ⫾ 2.70, P ⫽ 0.002). Although MMSE scores showed a decline at 6 months postoperatively, the changes were small. In addition, some of the tests, such as the nonverbal memory test and sensorimotor coordination on the left (grooved

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pegboard test), revealed an improvement in performance. These results suggest that STN DBS has no major detrimental impact on cognitive function (Table 5).

DISCUSSION To our knowledge, this is the first report to propose a new approach to programming after STN DBS based on fused images of preoperative MRI and postoperative CT acquired 1 month after STN DBS, rather than adopting the traditional algorithm of stimulation programming after STN DBS. Clinical outcomes after STN DBS in our 38 patients with advanced PD were comparable to outcomes of previous reports from many institutions (1-3, 8, 14, 17). Previously, we compared UPDRS scores before and after reprogramming guided by fused images of preoperative MRI and postoperative CT acquired 6 months after surgery in 51 patients who had bilateral STN DBS surgery and were managed for at least 6 months using a traditional programming algorithm (10). We found that CT/MRI fusion images resulted in better clinical improvement in the patients who had been adjusted to best clinical status using the traditional method, with ease and confidence and in a time-saving manner. We confirmed

that the patients in the good locator group, with electrodes located within the STN, had a better clinical improvement after reprogramming guided by CT/MRI fused images compared with patients in the poor locator group, with electrodes located off the STN. Together with the previous experience, the data presented here suggest that programming based on the fused images of preoperative MRI and postoperative CT acquired 1 month after surgery results in symptomatic improvement that is comparable to improvement previously reported by many institutions in the short-term after STN DBS (1-3, 8, 14, 17). For the sake of the patients, the time spent selecting the stimulation contacts with appropriate stimulation parameters was markedly shortened based on the information from the fused images of preoperative MRI and postoperative CT, without prolonged experience of the unnecessary adverse effects caused by the selection of inappropriate contacts far from the STN target. With this approach, the selection of stimulation contacts with appropriate stimulation parameters in harmony with the reduced antiparkinsonian drugs can be achieved soon after surgery. For the sake of the physicians, the time and effort spent in the selection of the stimulation contacts with appropriate stimulation parameters

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FUSION IMAGE–BASED PROGRAMMING AFTER STN DBS

Table 5. Neuropsychological Tests Before and at 6 Months of Patients with Parkinson Disease After Subthalamic Nucleus Deep Brain Stimulation (n ⫽ 29)

MMSE Attention

TMT (seconds)

Language

K-BNT

Memory

Verbal

Part A

Sensorimotor coordination (seconds)

Frontal lobe function

Stroop test (seconds)

6 Months

P Value

27.86 (1.85)

26.62 (2.70)

0.002*

59.86 (48.58)

74.25 (80.00)

0.122

Part B

57.33 (32.92)

62.89 (44.20)

0.460

Part C

134.22 (75.72)

150.61 (94.33)

0.307

49.04 (7.22)

49.08 (7.55)

0.962

37.05 (14.39)

35.23 (10.58)

0.619

Immediate recall Delayed recall

Nonverbal

Baseline

6.05 (2.52)

6.81 (2.54)

0.198

Recognition

10.62 (2.27)

10.57 (2.25)

0.915

Immediate recall

11.97 (7.44)

16.52 (8.70)

0.005*

Delayed recall

13.33 (8.93)

15.44 (8.77)

0.126

Right

154.57 (96.11)

125.35 (41.86)

0.157

Left

147.87 (55.43)

125.70 (44.02)

0.037

Color dot

18.70 (5.36)

19.85 (6.31)

0.218

Neutral word

26.71 (10.08)

27.89 (11.20)

0.444

Color-word

37.33 (14.85)

40.52 (15.91)

0.281

26.54 (8.57)

24.68 (8.54)

0.213

18.46 (7.74)

18.00 (11.28)

0.824

Fluency BDI

Note: Values are presented as mean (standard deviation) scores. BDI, Beck Depression Inventory; K-BNT, Korean Boston Naming Test; MMSE, Mini-mental status examination; TMT, Trail-Making Test. *P ⬍ .01 and statistical significance with use of the Bonferroni correction method to avoid a type I error when conducting multiple analyses over time.

were also markedly reduced using the fused images, without long-term trial-and errorrounds caused by the step-by-step selection of the contacts, even with experienced specialists (5, 14, 19). In this study, we chose postoperative CT scans acquired 1 month after STN DBS to estimate the electrode position for programming by fusing them with preoperative MRI. Although postoperative brain CT scans acquired 6 months after STN DBS were used for the estimation of electrode positioning in the previous study (15), 1 month after STN DBS seems to be sufficient for the turning back of the shifted brain at the immediate postoperative period to its original position (7). Previously, we compared the discrepancy of the center of the electrodes between the immediate postoperative period and 1 month and 3 months after surgery in 15 PD patients treated with STN DBS. We found that there was no significant discrepancy in the center of electrodes estimated in brain CT scans acquired 1 month and 3 months after STN DBS surgery, although there was a significant dif-

ference in the center of electrodes in the brain CT scans acquired during the immediate postoperative period and 1 month after STN DBS surgery (7). A microlesional effect has been reported for the implantation of DBS, which is believed to reflect the traumatic tissue reaction within the STN (12, 13). Mann et al. (13) found that a significant improvement in motor scores (tremor, rigidity, and bradykinesia) was observed as a result of acute collision and implantation with MER and lead placement, which is similar in magnitude to what was observed 4 months and 6 months after DBS following programming and optimization of medication. Thus, 1 month after STN DBS would be enough to be free from microlesional effect. This study had several limitations. First, there was no control group to compare the surgical outcome after STN DBS between fusion image– based programming and the traditional method. Additional prospective analyses of a randomized controlled study are needed to validate the practical usability and the efficacy in application of fusion im-

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age– based programming after STN DBS. Second, it is likely that there were several unavoidable errors in this study regarding the estimation of the positions of the electrodes based on the fused images of MRI/ CT, such as errors in image fusion, interevaluator or intraevaluator errors, and errors in plotting the electrodes in the brain atlas based on the fused images. The wellknown individual variations of the anatomy of the STN and related structures may also have caused inevitable errors in the estimation of electrodes via the plotting of the leads and contacts onto the human brain atlas of Schaltenbrandt and Wahren. Finally, the long-term outcome of the patients who underwent programming based on the information from MRI/CT fused images after STN DBS needs to be assessed.

CONCLUSIONS We developed a new approach for programming after STN DBS that consisted of fusing images of preoperative MRI and postop-

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erative CT using the mutual information technique, which enabled the identification of the three-dimensional location of the leads and of each contact in relation to the STN. Using the information of the threedimensional location of the electrodes and their contacts based on the fused images of preoperative MRI and postoperative CT acquired 1 month after surgery, programming after STN DBS may be quickly, easily, and efficiently performed after STN DBS.

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Conflict of interest statement: This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092052-0911-0000100). received 16 February 2010; accepted 01 December 2010 Citation: World Neurosurg. (2011) 75, 3/4:517-524. DOI: 10.1016/j.wneu.2010.12.003 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter © 2011 Elsevier Inc. All rights reserved.

WORLD NEUROSURGERY, DOI:10.1016/j.wneu.2010.12.003