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DOI: 10.1148/radiol.2391041990
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(Radiology 2006;239:209-216.)
© RSNA, 2006

Neuroradiology

Parkinson Disease: Pattern of Functional MR Imaging Activation during Deep Brain Stimulation of Subthalamic Nucleus—Initial Experience1

Micheal D. Phillips, MD, Kenneth B. Baker, PhD, Mark J. Lowe, PhD, Jean A. Tkach, PhD, Scott E. Cooper, MD, PhD, Brian H. Kopell, MD and Ali R. Rezai, MD

1 From the Departments of Radiology (M.D.P., M.J.L., J.A.T.), Neurology (S.E.C.), and Neurosurgery (K.B.B., A.R.R.), Cleveland Clinic Foundation, Mellen Center/U-15, 9500 Euclid Ave, Cleveland, OH 44195; and Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wis (B.H.K.). Received November 23, 2004; revision requested January 27, 2005; revision received April 26; final version accepted June 3. Supported in part by State of Ohio Biomedical Research and Technology Transfer Grant. Address correspondence to M.D.P. (e-mail: phillim{at}ccf.org).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Purpose: To prospectively determine the pattern of functional magnetic resonance (MR) imaging activation at 3 T produced by deep brain stimulation (DBS) of subthalamic nucleus (STN) for treatment of Parkinson disease and to determine the safety of DBS electrode stimulation during functional MR imaging at 3 T.

Materials and Methods: Informed consent was obtained from all subjects participating in the study, and the study protocol was approved by the institutional review board at the Cleveland Clinic Foundation and was HIPAA compliant. After extensive phantom safety testing of DBS lead systems, five patients (three men, two women; mean age, 49.4 years ± 14.5 [standard deviation]; range, 31–74 years) with percutaneously extended bilateral DBS electrodes placed in the STN for treatment of Parkinson disease were examined at 3 T on the 1st or 2nd postoperative day. Imaging consisted of a three-dimensional anatomic data set with leads disconnected and a blood oxygen level–dependent functional MR image with a single lead connected to the external pulse generator in the MR imaging control room by using stimulation parameters previously determined to produce optimal stimulation for alleviation of symptoms. A total of nine leads were tested with the functional MR imaging protocol. Subjects underwent neurologic examination immediately before and after MR imaging.

Results: All five patients completed the study without change in their neurologic examination and with activation seen in eight of nine electrodes stimulated. Activation was seen in the ipsilateral basal ganglia in all subjects and ipsilateral thalamus in six of the electrodes tested. Two of the electrode stimulations demonstrated additional activation in the STN and/or substantia nigra region adjacent to the electrode tip. For three electrode stimulations, activation was seen in the contralateral superior cerebellum.

Conclusion: Therapeutically effective DBS of STN can be performed safely during functional MR imaging at 3 T and produces a consistent pattern of ipsilateral activation of deep brain motor structures.

© RSNA, 2006


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become part of the standard of care for the treatment of Parkinson disease. Despite the frequency of DBS use, several questions remain about the exact mechanism of action of DBS in Parkinson disease. Functional magnetic resonance (MR) imaging has the potential to address several of the questions regarding mechanisms of action of DBS. Unfortunately, relatively few MR imaging examinations have been performed to evaluate the function of DBS. To date, researchers in three studies about functional MR imaging at 1.5 T have examined a total of five patients with DBS electrodes in place for the treatment of Parkinson disease (1–3). The studies have largely focused on unilaterally placed electrodes for the treatment of Parkinson disease. In one of the studies in which a single subject was used, the focus was on evaluation of changes in functional MR imaging activation during motor task performance with DBS rather than on evaluation of the pattern of activation produced during DBS (3). Thus, only a total of four subjects with DBS for Parkinson disease have been examined to determine the functional MR imaging activation pattern produced by unilateral electrode stimulation of the STN. Initial results suggest a pattern of ipsilateral basal ganglia and thalamic activation in response to electrode stimulation.

Although DBS electrode placement is relatively common, very few functional MR imaging studies have been performed in patients with implanted DBS systems because of potential safety concerns. Evaluation of DBS by using MR imaging is potentially very dangerous, with several injuries having been reported in the literature (4,5). Findings in studies suggest that MR imaging can be performed at 1.5 T in the presence of a DBS system with very specific conditions (4,6–8). Safety data appear to be specific for the pulse sequences and imaging platform (ie, a specific imaging system and operating software) used and are not generalizable to other imaging platforms (4,8). Therefore, safety testing of each platform must be performed prior to imaging in humans.

We hypothesized that functional MR imaging can be performed safely at 3 T with the DBS electrodes in place and that electrode stimulation optimized for symptom relief will produce a consistent pattern of activation in patients who have Parkinson disease with DBS leads placed in the STN. Thus, the purpose of our study was to prospectively determine the pattern of functional MR imaging activation at 3 T produced by DBS of the STN for the treatment of Parkinson disease and to determine the safety of DBS electrode stimulation during functional MR imaging at 3 T.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Safety Testing
All examinations were performed with a 3-T MR imaging system (Allegra; Siemens, Erlangen, Germany). Prior to any studies in humans, safety testing was performed by using a previously described gel phantom (6,9). DBS electrodes (quadripolar lead models 3387 and 3389 from Activa Tremor Control Systems; Medtronic, Minneapolis, Minn) were placed in the phantom in the approximate position in which they would be placed during implantation in the STN. The leads were then coiled on the surface of the phantom in a similar fashion to that performed for DBS placement during surgery. The leads were then attached to lead extenders, which ran around the periphery of the imaging room and out the waveguide to an implantable pulse generator (Soletra, model 7426; Medtronic) in the MR imaging control room. Temperature measurements were performed by using an MR imaging–compatible fluoroptic thermometry system (model 790; Luxtron, Santa Clara, Calif), with the temperature-sensing probe placed within 1 mm of the electrode lead tip in a fashion similar to that used in previously described safety experiments (6–10).

All of the imaging sequences (described later) that were used during the experiments in humans were tested for potential excess heating. Electrodes were tested simulating a bilateral DBS placement. Heating measurements were acquired from each electrode during each imaging sequence. In the case of the functional MR imaging sequence, each probe (right and left probes separately) was also tested in both the stimulus-on and stimulus-off condition. All measurements for each potential combination of conditions (image sequence and stimulus condition) were tested for heating a minimum of five times. Sequences were deemed safe if the observed temperature increases were less than 2°C during imaging according to the guidelines for acceptable heating of implanted devices determined by the European Committee for Standardization (11).

Subjects
Five patients (three men and two women; mean age, 49.4 years ± 14.5 [standard deviation]; range, 31–74 years), who had undergone placement of bilateral DBS electrodes in the STN (one in each brain hemisphere) for treatment of Parkinson disease, were examined. The range of disease duration was 11–20 years (mean, 15.6 years ± 3.2). Subjects were examined by using functional MR imaging on postoperative day 1 or 2 after the brain stimulator placement. At the time of surgery, optimal settings for symptom relief for each of the brain stimulator electrodes were determined. Subjects underwent a neurologic examination immediately prior to and immediately after MR imaging. Neurologic examinations were performed by an experienced fellowship-trained motion disorders neurologist (S.E.C.) with 4 years of postfellowship staff experience. The neurologic examination consisted of evaluations of motor, sensory, and cranial nerve function, as well as of assessment of orientation. Informed consent was obtained from all subjects prior to their participation in the study. All studies were approved by our local institutional review board and were performed in compliance with Health Insurance Portability and Accountability Act guidelines.

Imaging Protocol
Subjects were placed inside the MR imager. A three-plane scout gradient-echo sequence was performed with the following parameters: repetition time msec/echo time msec, 18/4.28; flip angle, 25°; field of view, 300 x 300 mm; section thickness, 5 mm; number of sections, three (one each in the transverse, sagittal, and coronal planes), collected as three concatenations; matrix, 256 x 256; and receive bandwidth, 46 KHz. Imaging with a three-dimensional data set for the purpose of anatomic localization was performed with a three-dimensional magnetization-prepared rapid acquisition gradient-echo transverse acquisition. Parameters were as follows: repetition time msec/echo time msec/inversion time msec, 1900/1.74/900; flip angle, 8°; number of sections acquired, 120; section thickness, 1.2 mm; matrix, 128 x 256; field of view, 240 mm x 240 mm; and receive bandwidth, 125 KHz. Anatomic imaging was performed without the DBS leads attached to the external pulse generator. After completion of the anatomic imaging data set, a single DBS lead was attached to the pulse generator, and functional MR imaging acquisitions were performed. Functional MR imaging acquisitions were performed by using prospectively motion-corrected two-dimensional gradient-echo echo-planar imaging with the following imaging parameters: 2000/29; flip angle, 90°; number of volumes acquired, 180; sections per volume, 32; section thickness, 3.8 mm; matrix, 64 x 64; field of view, 240 x 240 mm; receive bandwidth, 125 KHz. All subjects were able to successfully complete the functional MR imaging examination. None of the subjects complained of any abnormal sensations or discomfort caused by MR imaging with DBS electrodes in place.

Imaging Paradigm
Functional MR imaging examinations were performed by using a simple block-style paradigm that alternated between the stimulator-off condition and the stimulator-on condition with optimal stimulation parameters. There were five 32-second stimulator-off epochs and four 32-second stimulator-on epochs. A 10-second ramping phase was placed between each of the stimulator-off and stimulator-on conditions. This allows the operator to slowly ramp the stimulator to optimal stimulation conditions. The slow ramping process is similar to that which is used clinically and greatly increases patient comfort, and thereby reduces patient motion. The paradigm was performed separately for left- and right-hemisphere DBS electrodes in all subjects, with the exception of one subject (subject 1) in whom only left-hemisphere DBS was performed during functional MR imaging. The study was stopped after unilateral testing because the subject complained of fatigue and did not wish to continue. Thus, a total of nine rather than 10 electrodes were tested. The functional MR imaging acquisitions were performed only during unilateral stimulation to allow the contralateral electrode to act as a control for potential susceptibility artifacts, as well as to offer a better estimation of the degree of both ipsilateral and contralateral activation produced by individual electrode stimulation. Note that this method also more closely approximates the DBS programming for optimal stimulation, which is often performed one electrode at a time.

Image Analysis
Images acquired during the ramping process were discarded prior to image analysis. All data were spatially filtered with a Hamming filter that has been demonstrated to provide a threefold increase in signal-to-noise ratio (12). The MR imaging time series at each pixel was fit by using least squares to a boxcar reference function plus a slope and intercept to generate Student t maps (13). All data sets were transformed to the coordinate system of Talairach and Tournoux (14). Student t maps were then overlaid on the anatomic data sets and analyzed by a board-certified neuroradiologist (M.D.P.) with 8 years of experience in functional MR imaging for areas of inactivation. A threshold Student t value 5 (P < 10–6) was used to determine voxels of substantial activation. The Talairach coordinates of the centroid for regions of significant activation were used to determine the location and pattern of activation produced by stimulation.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Safety
The combined results for the heating and safety experiments (Table 1) showed that none of the imaging sequences produced a temperature increase greater than 1.4°C. Therefore, this specific configuration, which included the specific pulse sequences, wiring of the electrodes and lead extenders, and imaging platform (Siemens Allegra 3T, Numaris Syngo, running software version VA21C; Siemens), was deemed safe for imaging in humans.


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  		Table 1. Temperature Changes Associated with Each Sequence

 
Functional MR Imaging
None of the subjects had any change in the results of their neurologic examination performed before MR imaging compared with those of the neurologic examination performed after MR imaging. Eight of the nine DBS electrodes tested produced activation that was significantly correlated with the on cycle of the stimulator at the P < 10–6 level (Student t > 5). In one of the subjects (subject 4), data from one of the electrode stimulations were corrupted by subject motion.

All of the successful electrode stimulations produced activation (five [100%] of five patients; eight [100%] of eight electrodes) in the ipsilateral basal ganglia, typically in the globus pallidus externa posteriorly or at the border of the globus pallidus externa and putamen posteriorly (Table 2). Six (75%) of eight electrode stimulations in four of five patients also produced activation in the ipsilateral thalamus (Figs 1–3). In three (38%) of eight electrode stimulations in three of five patients, activation also was seen in the contralateral cerebellum. One (12%) of eight electrode stimulations in one of five patients (electrode placement in right side of the brain in subject 5) produced activation in the contralateral basal ganglia and ipsilateral cerebellum (Fig 3). In this subject, the activation was much more prominent on the ipsilateral side of the basal ganglia and the contralateral cerebellum. Additionally, two (25%) of eight electrode stimulations in one of five patients produced some activation within the midbrain region either in the area of the STN or the substantia nigra.


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  		Table 2. Talairach Position Data

 

Figure 1
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  		Figure 1: Subject 1. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images displayed in transverse, coronal, and transverse planes from left to right. Only left-sided DBS was performed. Arrows point to bilateral DBS electrodes. Areas of activation were identified within left posterior globus pallidus externa (left and middle images), posterior putamen (left and middle images), left thalamus (middle image), and right cerebellum (right image).

 

Figure 2
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  		Figure 2a: Subject 3. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in transverse plane. Foci of activation within (a) right thalamus and (b) right globus pallidus externa during right-sided DBS. (c) Foci of activation within left globus pallidus externa and left thalamus during left-sided DBS.

 

Figure 2
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  		Figure 2b: Subject 3. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in transverse plane. Foci of activation within (a) right thalamus and (b) right globus pallidus externa during right-sided DBS. (c) Foci of activation within left globus pallidus externa and left thalamus during left-sided DBS.

 

Figure 2
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  		Figure 2c: Subject 3. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in transverse plane. Foci of activation within (a) right thalamus and (b) right globus pallidus externa during right-sided DBS. (c) Foci of activation within left globus pallidus externa and left thalamus during left-sided DBS.

 

Figure 3
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  		Figure 3a: Subject 5. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in (a, d, e) transverse and (b, c) coronal planes. (a–c) Pattern of activation during right-sided DBS. Foci of activation were identified within the (a, b) ipsilateral posterior globus pallidus externa and posterior putamen with a smaller focus of activation identified in the contralateral globus pallidus externa and putamen and in the (c) contralateral cerebellum with a smaller focus of activation in the ipsilateral cerebellum. (d, e) Pattern of activation during left-sided DBS. Foci of activation were identified within (d) ipsilateral globus pallidus externa and (e) thalamus.

 

Figure 3
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  		Figure 3b: Subject 5. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in (a, d, e) transverse and (b, c) coronal planes. (a–c) Pattern of activation during right-sided DBS. Foci of activation were identified within the (a, b) ipsilateral posterior globus pallidus externa and posterior putamen with a smaller focus of activation identified in the contralateral globus pallidus externa and putamen and in the (c) contralateral cerebellum with a smaller focus of activation in the ipsilateral cerebellum. (d, e) Pattern of activation during left-sided DBS. Foci of activation were identified within (d) ipsilateral globus pallidus externa and (e) thalamus.

 

Figure 3
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  		Figure 3c: Subject 5. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in (a, d, e) transverse and (b, c) coronal planes. (a–c) Pattern of activation during right-sided DBS. Foci of activation were identified within the (a, b) ipsilateral posterior globus pallidus externa and posterior putamen with a smaller focus of activation identified in the contralateral globus pallidus externa and putamen and in the (c) contralateral cerebellum with a smaller focus of activation in the ipsilateral cerebellum. (d, e) Pattern of activation during left-sided DBS. Foci of activation were identified within (d) ipsilateral globus pallidus externa and (e) thalamus.

 

Figure 3
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  		Figure 3d: Subject 5. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in (a, d, e) transverse and (b, c) coronal planes. (a–c) Pattern of activation during right-sided DBS. Foci of activation were identified within the (a, b) ipsilateral posterior globus pallidus externa and posterior putamen with a smaller focus of activation identified in the contralateral globus pallidus externa and putamen and in the (c) contralateral cerebellum with a smaller focus of activation in the ipsilateral cerebellum. (d, e) Pattern of activation during left-sided DBS. Foci of activation were identified within (d) ipsilateral globus pallidus externa and (e) thalamus.

 

Figure 3
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  		Figure 3e: Subject 5. Colorized functional MR imaging activation data displayed in yellow, orange, and red on anatomic magnetization-prepared rapid acquisition gradient-echo images in (a, d, e) transverse and (b, c) coronal planes. (a–c) Pattern of activation during right-sided DBS. Foci of activation were identified within the (a, b) ipsilateral posterior globus pallidus externa and posterior putamen with a smaller focus of activation identified in the contralateral globus pallidus externa and putamen and in the (c) contralateral cerebellum with a smaller focus of activation in the ipsilateral cerebellum. (d, e) Pattern of activation during left-sided DBS. Foci of activation were identified within (d) ipsilateral globus pallidus externa and (e) thalamus.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Several potential hazards are associated with MR imaging with DBS electrodes in place. These include movement of DBS leads caused by the magnetic field of the MR imager, damage to the DBS implanted pulse generator, induced currents within the lead system, and heating within DBS leads. Researchers in several studies have demonstrated significant heating within DBS leads by using standard pulse sequences (6,7,9). Rezai et al (6) demonstrated significant heating to temperatures as high as 25.3°C by using MR imaging sequences that were within the accepted limits for a specific absorption rate. More important, most of the heating occurred within the first 90 seconds of imaging (6,7,9). This degree of rapid heating without adequate time for dispersion is sufficient to cause a focal brain lesion. Clearly, evaluation of DBS by using MR imaging is potentially dangerous. Findings in a recent study, however, suggest that, because of differences in specific absorption rate reporting and monitoring, safety data appear to be specific for the pulse sequences and imaging platform (ie, a specific imaging system and operating software) used and that these data cannot be generalized to other imaging platforms (8). These findings have led investigators to recommend that safety testing of each platform be performed prior to imaging in humans (4,8).

The results of our study demonstrate that, with carefully controlled specific conditions, functional MR imaging can be performed safely at 3 T during DBS. With the phantom data from the present study, imaging with all of the pulse sequences used produced less than a 1.4°C increase in temperature in DBS leads, and none of the subjects experienced abnormal sensations or changes in the results of their neurologic examinations. As mentioned previously, these results are specific to our imaging platform with the sequences outlined previously and are not clearly generalizable to other 3-T systems or other imaging conditions (4,8). Performance of MR imaging studies with any other platform would require phantom testing of the system prior to studies in humans (4,8).

We believe that the series of patients who underwent DBS in our study is the largest series of those who have been examined with functional MR imaging and the first study performed at 3 T. The results suggest a consistent pattern of activation within the ipsilateral basal ganglia, primarily in the globus pallidus externa and in the thalamus, in response to DBS. The findings in the presence of bilateral DBS placement suggest that areas of activation are unlikely to reflect susceptibility artifacts. One subject (subject 5) demonstrated bilateral activity. This was not seen in any of the other functional MR imaging examinations (1–3). Investigators in some studies (15–17) have shown that some subjects demonstrate a bilateral benefit from unilateral DBS of the STN in Parkinson disease. Findings may reflect a patient who received a substantial bilateral benefit from unilateral DBS. Note that, in the present study, areas of activation identified in the globus pallidus, putamen, thalamus, and cerebellum have been implicated in models for Parkinson disease and effectiveness of DBS (1,18–32).

Researchers in three prior studies (1–3) with a total of five patients have looked at functional MR imaging for unilateral effective DBS in the STN in Parkinson disease. Hesselmann et al (3) performed functional MR imaging with a finger tapping task in one subject with unilateral placement of DBS. This paradigm differs from the passive comparison of stimulator-on and stimulator-off DBS conditions. Hesselmann et al found that there was decreased activity during active motor task performance with the stimulator on in the contralateral sensorimotor cortex and ipsilateral cerebellum, with increased activity in the contralateral basal ganglia (3). It is unclear how these findings relate to the results of our study because of the marked differences in the paradigms used; however, the pattern appears to be the mirror opposite of the present results, with increased activity in the ipsilateral cerebellum and basal ganglia. This discrepancy may reflect differences between the active and passive paradigms used.

Stefurak et al (2) performed functional MR imaging in one subject with bilateral DBS; however, only one of the leads produced motor symptom relief with stimulation. Stimulation with that lead produced areas of increased activation in the thalamus, putamen, cerebellum, and primary motor cortex. The findings were more prominent ipsilaterally. Similar areas of activation were seen in our study. Images from our study suggest that some areas of activation were observed over the globus pallidus as well. It should be noted that Stefurak et al also observed several areas of activation that are of uncertain importance, including the parietal, dorsolateral prefrontal cortex, insula, and inferior and superior temporal gyri (2). Activation was not seen in these regions in our study. This observation may have been caused by technical differences with the relatively lower significance threshold used by Stefurak et al (2). The findings were more prominent ipsilaterally. Jech et al (1) examined three patients with unilaterally placed DBS and saw a pattern of activation similar to that seen in the present study with activation of the ipsilateral globus pallidus in two subjects and thalamic activation in all three subjects. Talairach coordinates suggest that the activation was primarily in the globus pallidus externa. Thalamic activation was seen in the anterior and ventrolateral thalamus. Jech et al (1) did not see activation in the contralateral cerebellum, as was observed in the present study. This may reflect differences in sensitivity between the 3- and 1.5-T platforms. Jech et al also showed activation in the dorsal lateral prefrontal cortex, which was not seen in our study. This observation may have been caused by technical factors discussed later.

Electrophysiologic data demonstrate increased firing rates in the globus pallidus interna and globus pallidus externa during DBS in animal models of Parkinson disease (32,33). Although in some cases activation did extend to the lateral aspect of the globus pallidus interna, our data did not show a clear activation centered in the globus pallidus interna during stimulation. Regions of activation were centered more consistently more consistently within the globus pallidus externa. This may have been caused by the relative smaller size of the globus pallidus interna, which may limit the sensitivity of functional MR imaging for detection of these changes. Alternatively, this finding may reflect relative differences in a change of firing produced by DBS in the globus pallidus externa in comparison with that produced in the globus pallidus interna. Hashimoto et al (33) observed a larger percentage increase in the mean firing rate in the globus pallidus externa compared with that in the globus pallidus interna. The larger increase in firing rate may produce a greater change in relative blood flow, which is more readily detected with functional MR imaging. The increased mean discharge rates in the globus pallidus interna would also be expected to produce increased blood flow in the thalamus caused by increased activity in the pallidothalamic projection (33). These data also support the present observations.

There were several limitations to our study. Although stimulation parameters were optimized at the time of surgery, the optimization procedure was largely based on the experience of the neurologist and neurosurgeons who performed the procedure. This procedure is an abbreviated version of the usual programming session and was performed in the surgical and immediate postsurgical setting. Typically, the experience at our institution is that these parameters are relatively close to those finally chosen after a more thorough programming session.

Although patients typically received bilateral stimulations simultaneously, our functional MR imaging experiments were performed only with unilateral stimulation. This method was chosen to understand the potential contralateral and ipsilateral activation produced by electrode stimulation. The unilateral stimulation approach also allows the contralateral electrode without stimulation to act as a control to ensure that the appearance of activation is not caused by susceptibility artifacts. Last, programming for individual leads is typically performed separately; hence, the unilateral stimulation approach may more closely mimic the clinical process for assessment of stimulation effectiveness. Potential future experiments may be useful to study the potential synergistic effects of bilateral stimulation on functional MR imaging activation.

Functional MR imaging examinations were performed on the 1st and 2nd postoperative day, as noted in our preliminary data. The authors recognize that this is not an optimal time for functional imaging. Residual effects from anesthesia, edema surrounding the lead, and microlesional effects of lead placement may limit or alter the results of functional MR imaging evaluation. Functional MR imaging was performed at this time to use the externalized leads for the DBS. The externalized lead system can be more easily safety tested and offers a more controlled method of delivery of stimuli in the MR imaging environment. After completion of functional MR imaging, the DBS leads are internalized, and the patient is discharged. All of our safety and phantom work was performed with externalized DBS leads. There are extensive additional safety concerns related to performing functional MR imaging with the implanted pulse generator in place. Although MR imaging has been performed in patients with the DBS implanted pulse generator in place, the pulse generator is always turned off for the examination. Functional MR imaging performed by using the implanted pulse generator would require the device to be actively firing during the examination. This would require documentation of the safety both with respect to heating and appropriate function of the implanted pulse generator. Further, it is unclear whether performance of functional MR imaging with the pulse generator turned on would damage the implanted pulse generator, requiring replacement (additional surgery for the patient). Even if safety concerns could be addressed, there would be no direct control of the implanted pulse generator during the functional MR imaging examination. This raises concerns with regard to the time of firing of the implanted pulse generator with respect to the functional MR imaging acquisition. Additionally, a method for documenting the amplitude and pattern of the implanted pulse generator–driven DBS would need to be developed for the functional MR imaging environment to ensure that appropriate stimulation was being delivered during the examination. Therefore, despite the drawbacks of imaging in the perioperative period, use of an external pulse generator remains the most viable method available for functional MR imaging in DBS.

Findings in the present study indicate that functional MR imaging during DBS of the STN can be performed safely at 3 T with carefully specified conditions and that therapeutically effective DBS of the STN produces a consistent pattern of activation (ipsilateral basal ganglionic and thalamic activation) in deep brain motor structures.


   ACKNOWLEDGMENTS
 
We are grateful to Jian Lin, MS, for her help in processing functional MR imaging data sets. We also express our gratitude to Derrek I. Tew, RT, for his help in MR data acquisitions.


   FOOTNOTES
 

Abbreviations: DBS = deep brain stimulation • STN = subthalamic nucleus

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, M.D.P., A.R.R.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, M.D.P., K.B.B., J.A.T., A.R.R.; clinical studies, M.D.P., K.B.B., J.A.T., B.H.K., A.R.R.; experimental studies, M.D.P., K.B.B., M.J.L., J.A.T., S.E.C.; statistical analysis, M.D.P., M.J.L.; and manuscript editing, M.D.P., K.B.B., M.J.L., J.A.T., A.R.R.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Jech R, Urgosik D, Tintera J, et al. Functional magnetic resonance imaging during deep brain stimulation: a pilot study in four patients with Parkinson's disease. Mov Disord 2001;16:1126–1132.[CrossRef][Medline]
  2. Stefurak T, Mikulis D, Mayberg H, et al. Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study. Mov Disord 2003;18:1508–1516.[CrossRef][Medline]
  3. Hesselmann V, Sorger B, Girnus R, et al. Intraoperative functional MRI as a new approach to monitor deep brain stimulation in Parkinson's disease. Eur Radiol 2004;14:686–690.[CrossRef][Medline]
  4. Rezai AR, Phillips M, Baker KB, et al. Neurostimulation system used for deep brain stimulation (DBS): MR safety issues and implications of failing to follow safety recommendations. Invest Radiol 2004;39:300–303.[CrossRef][Medline]
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