Human brain tissue identification using coherent anti-Stokes Raman scattering spectroscopy and diffuse reflectance spectroscopy for deep brain stimulation surgery.

Significance: We assess the feasibility of using diffuse reflectance spectroscopy (DRS) and coherent anti-Stokes Raman scattering spectroscopy (CARS) as optical tools for human brain tissue identification during deep brain stimulation (DBS) lead insertion, thereby providing a promising avenue for additional real-time neurosurgical guidance. Aim: We developed a system that can acquire CARS and DRS spectra during the DBS surgery procedure to identify the tissue composition along the lead trajectory. Approach: DRS and CARS spectra were acquired using a custom-built optical probe integrated in a commercial DBS lead. The lead was inserted to target three specific regions in each of the brain hemispheres of a human cadaver. Spectra were acquired during the lead insertion at constant position increments. Spectra were analyzed to classify each spectrum as being from white matter (WM) or gray matter (GM). The results were compared with tissue classification performed on histological brain sections. Results: DRS and CARS spectra obtained using the optical probe can identify WM and GM during DBS lead insertion. The tissue composition along the trajectory toward a specific target is unique and can be differentiated by the optical probe. Moreover, the results obtained with principal component analysis suggest that DRS might be able to detect the presence of blood due to the strong optical absorption of hemoglobin. Conclusions: It is possible to use optical measurements from the DBS lead during surgery to identify WM and GM and possibly the presence of blood in human brain tissue. The proposed optical tool could inform the surgeon during the lead placement if the lead has reached the target as planned. Our tool could eventually replace microelectrode recordings, which would streamline the process and reduce surgery time. Further developments are required to fully integrate these tools into standard clinical procedures.

The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo.

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mouse revealed that decreases in ATP levels force cells into the stationary phase and induce autophagy. Pharmacological or genetic impairments of autophagy in neuroblasts using either bafilomycin, inducible conditional mice, or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases to sustain neuronal migration.

Intraoperative fiber optic guidance during chronic electrode implantation in deep brain stimulation neurosurgery: proof of concept in primates.

OBJECTIVE: The clinical outcome of deep brain stimulation (DBS) surgery relies heavily on the implantation accuracy of a chronic stimulating electrode into a small target brain region. Most techniques that have been proposed to precisely target these deep brain regions were designed to map intracerebral electrode trajectory prior to chronic electrode placement, sometimes leading to positioning error of the final electrode. This study was designed to create a new intraoperative guidance tool for DBS neurosurgery that can improve target detection during the final implantation of the chronic electrode. METHODS: Taking advantage of diffuse reflectance spectroscopy, the authors developed a new surgical tool that senses proximal brain tissue through the tip of the chronic electrode by means of a novel stylet, which provides rigidity to DBS leads and houses fiber optics. RESULTS: As a proof of concept, the authors demonstrated the ability of their noninvasive optical guidance technique to precisely locate the border of the subthalamic nucleus during the implantation of commercially available DBS electrodes in anesthetized parkinsonian monkeys. Innovative optical recordings combined to standard microelectrode mapping and detailed postmortem brain examination allowed the authors to confirm the precision of optical target detection. They also show the optical technique's ability to detect, in real time, upcoming blood vessels, reducing the risk of hemorrhage during the chronic lead implantation. CONCLUSIONS: The authors present a new optical guidance technique that can detect target brain regions during DBS surgery from within the implanted electrode using a proof of concept in nonhuman primates. The technique discriminates tissue in real time, contributes no additional invasiveness to the procedure by being housed within the electrode, and can provide complementary information to microelectrode mapping during the implantation of the chronic electrode. The technique may also be a powerful tool for providing direct anatomical information in the case of direct implantations wherein microelectrode mapping is not performed.

Potentiation of response to low doses of levodopa in MPTP-injected monkeys by chemical unilateral subthalamotomy.

OBJECT: Subthalamotomy is a stereotactic surgery performed in patients with disabling dyskinesias due to Parkinson disease. The authors set out to model this human condition in MPTP monkeys and determine if subthalamotomy allowed a reduction of levodopa for similar benefit. METHODS: The authors performed unilateral subthalamotomy in 4 parkinsonian dyskinetic monkeys by stereotactic injection of ibotenic acid. An optimal dose, defined as the highest dose of levodopa improving parkinsonian motor symptoms while inducing low or no dyskinesias, was established in these animals. Each monkey was scored for the antiparkinsonian and dyskinetic effects of the optimal dose of levodopa, as well as suboptimal and dyskinesia-inducing doses (60% and 140% of the optimal dose, respectively), and these scores were compared with those obtained at baseline before and after subthalamotomy. Bradykinesia was assessed by a prehension task. RESULTS: Unilateral subthalamotomy had a positive effect on the antiparkinsonian response for all doses of levodopa as well as the baseline. There were no differences in the antiparkinsonian response between the suboptimal dose postsurgery and the optimal dose presurgery. Dyskinesias were increased at the suboptimal and the optimal doses. After surgery, the duration of response to levodopa increased between 20% and 25% in the suboptimal dose, whereas it remained unchanged with higher doses. Bradykinesia was significantly reduced after surgery only at the suboptimal dose. CONCLUSIONS: Subthalamotomy potentiated the response to suboptimal doses of levodopa. Thus, levodopa can be reduced by 40% after surgery for similar beneficial antiparkinsonian response and less dyskinesia than with an optimal dose before surgery.

Substantia nigra and Parkinson's disease: a brief history of their long and intimate relationship.

The substantia nigra was discovered in 1786 by Félix Vicq d'Azyr, but it took more than a century before Paul Blocq and Georges Marinesco alluded to a possible link between this structure and Parkinson's disease. The insight came from the study of a tuberculosis patient admitted in Charcot's neurology ward at la Salpêtrière because he was suffering from unilateral parkinsonian tremor. At autopsy, Blocq and Marinesco discovered an encapsulated tumor confined to the substantia nigra, contralateral to the affected side, and concluded that tremor in that particular case resulted from a midbrain lesion. This pioneering work, published in 1893, led Edouard Brissaud to formulate, in 1895, the hypothesis that the substantia nigra is the major pathological site in Parkinson's disease. Brissaud's hypothesis was validated in 1919 by Constantin Trétiakoff in a remarkable thesis summarizing a post-mortem study of the substantia nigra conducted in Marinesco's laboratory. Despite highly convincing evidence of nigral cell losses in idiopathic and post-encephalitic Parkinsonism, Trétiakoff's work raised considerable doubts among his colleagues, who believed that the striatum and pallidum were the preferential targets of parkinsonian degeneration. Trétiakoff's results were nevertheless confirmed by detailed neuropathological studies undertaken in the 1930s and by the discovery, in the 1960s, of the dopaminergic nature of the nigrostriatal neurons that degenerate in Parkinson's disease. These findings have strengthened the link between the substantia nigra and Parkinson's disease, but modern research has uncovered the multifaceted nature of this neurodegenerative disorder by identifying other brain structures and chemospecifc systems involved in its pathogenesis.