Chris Kao

Application of infrared light for in vivo neural stimulation

A novel method for damage-free, artifact-free stimulation of neural tissue using pulsed, low-energy infrared laser light is presented. Optical stimulation elicits compound nerve and muscle potentials similar to responses obtained with conventional electrical neural stimulation in a rat sciatic nerve model. Stimulation and damage thresholds were determined as a function of wavelength using a tunable free electron laser source (lambda = 2 to 10 microm) and a solid state holmium:YAG laser (lambda = 2.12 microm). Threshold radiant exposure required for stimulation varies with wavelength from 0.312 Jcm2 (lambda = 3 microm) to 1.22 Jcm2 (lambda = 2.1 microm). Histological analysis indicates no discernable thermal damage with suprathreshold stimulation. The largest damage/stimulation threshold ratios (>6) were at wavelengths corresponding to valleys in the IR spectrum of soft tissue absorption (4 and 2.1 microm). Furthermore, optical stimulation can be used to generate a spatially selective response in small fascicles of the sciatic nerve that has significant advantages (e.g., noncontact, spatial resolution, lack of stimulation artifact) over conventional electrical methods in diagnostic and therapeutic procedures in neuroscience, neurology, and neurosurgery.

Optical stimulation of neural tissue in vivo.

For more than a century, the traditional method of stimulating neural activity has been based on electrical methods, and it remains the gold standard to date. We report a technological breakthrough in neural activation in which low-level, pulsed infrared laser light is used to elicit compound nerve and muscle potentials in mammalian peripheral nerve in vivo. Optically induced neural action potentials are spatially precise, artifact free, and damage free and are generated by use of energies well below tissue ablation threshold. Thus optical stimulation presents a simple yet novel approach to contact-free in vivo neural activation that has major implications for clinical neurosurgery, basic neurophysiology, and neuroscience.

Pulsed laser versus electrical energy for peripheral nerve stimulation

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods result in highly selective functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits distinct advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future.

Computer-aided placement of deep brain stimulators: from planningto intraoperative guidance

In current practice, optimal placement of deep-brain stimulators (DBSs) used to treat movement disorders in patients with Parkinsons disease and essential tremor is an iterative procedure. A target is chosen preoperatively based on anatomical landmarks identified on magnetic resonance images. This point is used as an initial position that is refined intraoperatively using both microelectrode recordings and macrostimulation. In this paper, we report on our current progress toward developing a system for the computer-assisted preoperative selection of target points and for the intraoperative adjustment of these points. The system consists of a deformable atlas of optimal target points that can be used to select automatically the preoperative target, of an electrophysiological atlas, and of an intraoperative interface. Results we have obtained show that automatic prediction of target points is an achievable goal. Our results also indicate that electrophysiological information could be used to resolve structures not visible in anatomic images, thus improving both preoperative and intraoperative guidance. Our intraoperative system has reached the stage of a working prototype and we compare targeting accuracy as well as the number of paths needed to reach the targets with our system and with the method in current clinical use.

Accuracy of customized miniature stereotactic platforms.

In this study, a new system was evaluated for implanting deep-brain stimulators based on a one-piece platform for each trajectory customized from a preoperative planning image. During surgery, the platform is attached to skull-implanted posts that extend through the scalp. The platform acts as a miniature stereotactic frame to provide guidance for parallel cannulas as they are advanced through a burr hole to the target. Accuracy is determined from a postoperative CT. For each implantation, the distance between the position observed in the postoperative image and the position calculated relative to the platform from the preoperative image is our measure of error. Because this measure incorporates the surgical error of electrode anchoring, brain shift between preoperative and postoperative scanning, and error in the measurement of the position of the electrode in CT, it will tend to overestimate the true error. The mean error was 2.8 mm for 20 implantations. These data reflect favorably the accuracy of this system when compared with others.

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

BACKGROUND Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinsons disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. METHODS Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. RESULTS As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. CONCLUSIONS This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.

CranialVault and its CRAVE tools: A clinical computer assistance system for deep brain stimulation (DBS) therapy

A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAnialVault Explorer (CRAVE) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information.

Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial

Background Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinsons disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. Objectives/methods 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. Results 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior −1.1±1.7 mm, lateral 10.7±1.7 mm and superior −3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. Conclusions The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

Neuromodulation of the cingulum for neuropathic pain after spinal cord injury. Case report.

The authors present a case in which high-frequency electrical stimulation of the cingulum using standard deep brain stimulation (DBS) technology resulted in pain relief similar to that achieved with cingulotomy and superior to that achieved with periventricular gray matter (PVG) stimulation. This patient had a complete spinal cord injury at the C-4 level and suffered from medically refractory neuropathic pain. He underwent placement of bilateral cingulum and unilateral PVG DBS electrodes and a 1-week blinded stimulation trial prior to permanent implantation of a pulse generator. During the stimulation trial, the patients pain level was assessed using a visual analog scale, and pain medication usage was recorded. During this period the patient was blinded to stimulation parameters. Stimulation of the cingulum provided better pain control than PVG stimulation or medication alone. The authors believe that cingulum stimulation can benefit patients with severe neuropathic pain that is refractory to other treatments. Advantages over cingulotomy include reversibility and the ability to adjust stimulation parameters for optimum efficacy.

Customized, miniature rapid-prototype stereotactic frames for use in deep brain stimulator surgery: initial clinical methodology and experience from 263 patients from 2002 to 2008.

Background: The microTargeting™ platform (MTP) stereotaxy system (FHC Inc., Bowdoin, Me., USA) was FDA approved in 2001 utilizing rapid-prototyping technology to create custom platforms for human stereotaxy procedures. It has also been called the STarFix (surgical targeting fixture) system since it is based on the concept of a patient- and procedure-specific surgical fixture. This is an alternative stereotactic method by which planned trajectories are incorporated into custom-built, miniature stereotactic platforms mounted onto bone fiducial markers. Our goal is to report the clinical experience with this system over a 6-year period. Methods: We present the largest reported series of patients who underwent deep brain stimulation (DBS) implantations using customized rapidly prototyped stereotactic frames (MTP). Clinical experience and technical features for the use of this stereotactic system are described. Final lead location analysis using postoperative CT was performed to measure the clinical accuracy of the stereotactic system. Results: Our series included 263 patients who underwent 284 DBS implantation surgeries at one institution over a 6-year period. The clinical targeting error without accounting for brain shift in this series was found to be 1.99 mm (SD 0.9). Operating room time was reduced through earlier incision time by 2 h per case. Conclusion: Customized, miniature stereotactic frames, namely STarFix platforms, are an acceptable and efficient alternative method for DBS implantation. Its clinical accuracy and outcome are comparable to those associated with traditional stereotactic frame systems.