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Purpose Fluorescence-guided surgery applying 5-aminolevulinic acid (5-ALA) in high-grade gliomas is an established method in adults. In children, results have so far been ambiguous. The aim of this study was to investigate 5-ALA-induced fluorescence in pediatric brain tumors by using the surgical microscope and a spectroscopic hand-held probe. Methods Fourteen randomly selected children (age 4–17) with newly MRI-verified brain tumors were included. No selection was based on the suspected diagnosis prior to surgery. All patients received 5-ALA (20 mg /kg) either orally or via a gastric tube prior to surgery. Intratumoral fluorescence was detected with the microscope and the probe. Moreover, fluorescence in the skin of the forearm was measured. Histopathology samples revealed seven low-grade gliomas, four medulloblastomas, one diffuse intrinsic pontine glioma, one glioblastoma and one atypical meningioma. Blood samples were analyzed, and potential clinical side effects were monitored. Results Microscopically, vague fluorescence was visible in two patients. Intratumoral fluorescence could be detected in five patients with the probe, including the two patients with vague microscopic fluorescence. Three of the oldest children had PpIX fluorescence in the skin. Nine children did not show any fluorescence in the tumor or in the skin. No clinical side effects or laboratory adverse events were observed. Conclusion Fluorescence could not be used to guide surgery in this study, neither with the surgical microscope nor with the hand-held probe. In nine children, no fluorescence was discerned and children with noticeable fluorescence were all older than nine years. 5-ALA was considered safe to apply in children.

Objective To evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinsons disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field. Materials and Methods We report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinsons Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinsons Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III, and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for creation of improvement maps and anatomical evaluation. Results Median UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change but the subdomains activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29% respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation. Conclusions Bilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief. Funding Agencies|Umea Universitet Funding Source: Medline; Umea University Hospital [Spjutspetsmedel] Funding Source: Medline; Parkinsonfonden Funding Source: Medline; Stiftelsen for Strategisk Forskning [SSF BD150032] Funding Source: Medline; Vetenskapsradet [VR 2016-03564] Funding Source: Medline

Background Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle, and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS. Methods In a pilot study of eleven participants with DBS of the BNST, we investigate through patient-specific simulation of electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Our study combined individual patient’s stimulation parameters at 12- and 24-month follow-up with image data from the preoperative MRI and postoperative CT. These data were used to calculate the distribution of electric field and create individual anatomical models of the field of stimulation. Results The individual electric stimulation fields by stimulation in the BNST were similar at both the 12- and 24-month follow-up, involving mainly anterior limb of the internal capsule (ALIC), genu of the internal capsule (IC), BNST, fornix, anteromedial globus pallidus externa (GPe), and the anterior commissure. A statistical significant correlation (p Conclusions Many of the targets under investigation for OCD are in anatomical proximity. As seen in our study, off-target effects are overlapping. Therefore, DBS in the region of ALIC, NAc, and BNST may perhaps be considered to be stimulation of the same target.

Deep brain stimulation (DBS) is a well-established neurosurgical procedure for movement disorders that is also being explored for treatment-resistant psychiatric conditions. This review highlights important consideration for DBS simulation and data analysis. The literature on DBS has expanded considerably in recent years, and this article aims to identify important trends in the field. During DBS planning, surgery, and follow up sessions, several large data sets are created for each patient, and it becomes clear that any group analysis of such data is a big data analysis problem and has to be handled with care. The aim of this review is to provide an update and overview from a neuroengineering perspective of the current DBS techniques, technical aids, and emerging tools with the focus on patient-specific electric field (EF) simulations, group analysis, and visualization in the DBS domain. Examples are given from the state-of-the-art literature including our own research. This work reviews different analysis methods for EF simulations, tractography, deep brain anatomical templates, and group analysis. Our analysis highlights that group analysis in DBS is a complex multi-level problem and selected parameters will highly influence the result. DBS analysis can only provide clinically relevant information if the EF simulations, tractography results, and derived brain atlases are based on as much patient-specific data as possible. A trend in DBS research is creation of more advanced and intuitive visualization of the complex analysis results suitable for the clinical environment.

Background: Optics can be used for guidance in deep brain stimulation (DBS) surgery. The aim was to use laser Doppler flowmetry (LDF) to investigate the intraoperative optical trajectory along the ventral intermediate nucleus (VIM) and zona incerta (Zi) regions in patients with essential tremor during asleep DBS surgery, and whether the Zi region could be identified. Methods: A forward-looking LDF guide was used for creation of the trajectory for the DBS lead, and the microcirculation and tissue greyness, i.e., total light intensity (TLI) was measured along 13 trajectories. TLI trajectories and the number of high-perfusion spots were investigated at 0.5-mm resolution in the last 25 mm from the targets. Results: All implantations were done without complications and with significant improvement of tremor (p < 0.01). Out of 798 measurements, 12 tissue spots showed high blood flow. The blood flow was significantly higher in VIM than in Zi (p < 0.001). The normalized mean TLI curve showed a significant (p < 0.001) lower TLI in the VIM region than in the Zi region. Conclusion: Zi DBS performed asleep appears to be safe and effective. LDF monitoring provides direct in vivomeasurement of the microvascular blood flow in front of the probe, which can help reduce the risk of hemorrhage. LDF can differentiate between the grey substance in the thalamus and the transmission border entering the posterior subthalamic area where the tissue consists of more white matter tracts.

BACKGROUND Accurate stereotactic biopsies of brain tumors are imperative for diagnosis and tailoring of the therapy. Repetitive needle insertions enhance risks of brain lesioning, hemorrhage, and complications due to prolonged procedure. OBJECTIVE To investigate clinical benefits of a combined 5-aminolaevulinic acid (5-ALA) fluorescence and laser Doppler flowmetry system for the detection of malignant brain tumor and blood vessels in stereotactic biopsies. METHODS Planning of targets and trajectories was followed by optical measurements in 20 patients, using the Leksell Stereotactic System and a manual insertion device. Fluorescence spectra, microvascular blood flow, and tissue grayness were recorded each millimeter along the paths. Biopsies were taken at preplanned positions. The diagnoses were compared with the fluorescence signals. The recordings were plotted against measurement positions and compared. Sites indicating a risk of hemorrhage were counted as well as the time for the procedures. RESULTS Signals were recorded along 28 trajectories, and 78 biopsies were collected. The final diagnosis showed 17 glioblastomas, 2 lymphomas, and 1 astrocytoma grade III. Fluorescence was seen along 23 of the paths with 4 having the peak of 5-ALA fluorescence 3 mm or more from the precalculated target. There was increased microcirculation in 40 of 905 measured positions. The measurement time for each trajectory was 5 to 10 min. CONCLUSION The probe provided direct feedback of increased blood flow along the trajectory and of malignant tissue in the vicinity of the target. The method can increase the precision and the safety of the biopsy procedure and reduce time. Funding: LiU Cancer Strategic Research Grant; Swedish Childhood Cancer FoundationEuropean Commission [MT 20130043]; ALF Grants Region Ostergotland; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [RMX18-0056]

Deep brain stimulation (DBS) is an intervention used for several neurological conditions such as Parkinson’s disease. To evaluate the clinical response in relation to anatomical location, electric field simulation using the finite element method is commonly used. The models presented in different studies are varying in complexity and this study aims to evaluate the effect of including anisotropy in the tissue model using homogenous tissue with varying level of anisotropy both parallel and perpendicular to the DBS lead. As a benchmark, data from one patient was included and simulations was performed in zona incerta (Zi) and the internal capsule (IC). The parameters investigated were impedance, volume within the 0.2 V/mm isosurface, radial and longitudinal expansion as well as visual representation of the isosurface. The investigations show that both the impedance and volume are increasing with increasing anisotropy together with the electric field isosurface in the principal direction of the anisotropy. When comparing different stimulation modes, current control (CC) stimulation had a steeper increase with increasing anisotropy for all parameters compared to voltage control (VC) stimulation. This could be due to a joint effect of the anisotropy and the increasing impedance. The result from the patient simulations are in the anisotropy range where simulations from the homogenous models starts to have a higher slope for all parameters. This indicates that including anisotropy in computer models will be of importance in areas of high anisotropy.

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Introduction: Lead movement after deep brain stimulation may occur and influence the affected volume of stimulation. The aim of the study was to investigate differences in lead position between the day after surgery and approximately 1 month postoperatively and also simulate the electric field (EF) around the active contacts in order to investigate the impact of displacement on affected volume. Methods: Twenty-three patients with movement disorders underwent deep brain stimulation surgery (37 leads). Computed tomography at the 2 time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, and z) of the lead tips were compared between the 2 dates. Eleven of these patients were selected for the EF simulation in Comsol Multiphysics. Postoperative changes of EF spread in the tissue due to conductivity changes in perielectrode space and due to displacement were evaluated by calculating the coverage coefficient and the Sørensen-Dice coefficient. Results: There was a significant displacement (mean ± SD) on the left lead: x (0.44 ± 0.72, p < 0.01), y (0.64 ± 0.54, p < 0.001), and z (0.62 ± 0.71, p < 0.001). On the right lead, corresponding values were: x (−0.11 ± 0.61, ns), y (0.71 ± 0.54, p < 0.001), and z (0.49 ± 0.81, p < 0.05). The anchoring technique was a statistically significant variable associated with displacement. No correlation was found between bilateral (n = 14) versus unilateral deep brain stimulation, gender (n = 17 male), age n = 8), and calculated air volume. The simulated stimulation volume was reduced after 1 month because of the perielectrode space. When considering perielectrode space and displacement, the volumes calculated the day after surgery and approximately 1 month later were partly overlapped. Conclusion: The left lead tip displayed a tendency to move lateral, anterior, and inferior and the right a tendency to move anterior and inferior. The anchoring technique was associated to displacement. New brain territory was affected due to the displacement despite considering the reduced stimulated volume after 1 month. Postoperative changes in perielectrode space and small lead movements are reasons for delaying programming to 4 weeks following surgery.

Highlights: • Non-linear iterative structural normalization method focused on the deep brain. • Multi-modality image data from deep brain stimulation patients. • Comparison of ANTS, FNIRT and DRAMMS for the non-linear registrations using different settings for each. • Evaluation of the registration tools based on the analysis of 58 structures of the deep brain segmented manually by a single expert. • ANTS was identified as the best performing non-linear registration tool., Deep brain stimulation (DBS) therapy requires extensive patient-specific planning prior to implantation to achieve optimal clinical outcomes. Collective analysis of patient’s brain images is promising in order to provide more systematic planning assistance. In this paper the design of a normalization pipeline using a group specific multi-modality iterative template creation process is presented. The focus was to compare the performance of a selection of freely available registration tools and select the best combination. The workflow was applied on 19 DBS patients with T1 and WAIR modality images available. Non-linear registrations were computed with ANTS, FNIRT and DRAMMS, using several settings from the literature. Registration accuracy was measured using single-expert labels of thalamic and subthalamic structures and their agreement across the group. The best performance was provided by ANTS using the High Variance settings published elsewhere. Neither FNIRT nor DRAMMS reached the level of performance of ANTS. The resulting normalized definition of anatomical structures were used to propose an atlas of the diencephalon region defining 58 structures using data from 19 patients.

Deep brain stimulation (DBS) is an established technique for reduction of symptoms in movement disorders. Finite element method (FEM) simulations of the electric field magnitude (EF) are useful for estimating the affected tissue around the DBS lead and this can help optimize the therapy. This paper describes how patient-specific FEM models can be set up with the aid of the Matlab-based in-house software tool ELMA. Electrode placement is determined from two coordinates in postoperative medical imaging and electric conductivity is assigned from preoperative magnetic resonance imaging (MRI) and patient-specific DBS data. Simulations are performed using the equation for steady currents in Comsol Multiphysics (CM). The simulated EF is superimposed on the preoperative MRI for evaluation of affected structures. The method is demonstrated with patient-specific simulations in the zona incerta and a globus pallidus example containing cysts with higher conductive which causes considerable distortion of the EF. The improved software modules and precise lead positioning simplifies and reduces the time for DBS EF modelling and simulation. Funding agencies: Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [BD15-0032]; Swedish Research Council (Vetenskapsriddet)Swedish Research Council [2016-03564]; Knut and Alice Wallenberg Foundation (Project Seeing Organ Function)

Deep brain stimulation (DBS) is an established therapy for movement disorders such as essential tremor (ET). Positioning of the DBS lead in the patients brain is crucial for effective treatment. Extensive evaluations of improvement and adverse effects of stimulation at different positions for various current amplitudes are performed intraoperatively. However, to choose the optimal position of the lead, the information has to be "mentally" visualized and analyzed. This paper introduces a new technique called "stimulation maps," which summarizes and visualizes the high amount of relevant data with the aim to assist in identifying the optimal DBS lead position. It combines three methods: outlines of the relevant anatomical structures, quantitative symptom evaluation, and patient-specific electric field simulations. Through this combination, each voxel in the stimulation region is assigned one value of symptom improvement, resulting in the division of stimulation region into areas with different improvement levels. This technique was applied retrospectively to five ET patients in the University Hospital in Clermont-Ferrand, France. Apart from identifying the optimal implant position, the resultant nine maps show that the highest improvement region is frequently in the posterior subthalamic area. The results demonstrate the utility of the stimulation maps in identifying the optimal implant position. Graphical abstract Funding Agencies|Swiss National Science FoundationSwiss National Science Foundation (SNSF) [CR3212_153370]; Germaine de Stael program of the Swiss Academy of Engineering Sciences; French Ministry of Health [2011-A00774-37]; Swedish Research CouncilSwedish Research Council [2016-03564]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [BD15-0032]

Patient MRI from DBS implantations in the subthalamic nucleus (STN) were reviewed and it was found that around 10% had Virchow-Robin spaces (VRS). Patient-specific models were developed to evaluate changes in the electric field (EF) around DBS leads. The patients (n = 7) were implanted bilaterally either with the standard voltage-controlled lead 3389 or with the directional current-controlled lead 6180. The EF distribution was evaluated by comparing simulations using patient-specific models with homogeneous models without VRS. The EF, depicted with an isocontour of 0.2 V/mm, showed a deformation in the presence of the VRS around the DBS lead. For patient-specific models, the radial extension of the EF isocontours was enlarged regardless of the operating mode or the DBS lead used. The location of the VRS in relation to the active contact and the stimulation amplitude, determined the changes in the shape and extension of the EF. It is concluded that it is important to take the patients? brain anatomy into account as the high conductivity in VRS will alter the electric field if close to the DBS lead. This can be a cause of unexpected side effects. Funding Agencies|Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [SSF BD15-0032]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [VR 201603654]

Continuous measurement of local brain oxygen saturation (SO2) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are consi ...

There are many techniques using sensors and wearable devices for detecting and monitoring patients with Parkinson&#x02BC s disease &#x0028 PD &#x0029. A recent development is the utilization of human interaction with computer keyboards for analyzing and identifying motor signs in the early stages of the disease. Current designs for classification of time series of computer-key hold durations recorded from healthy control and PD subjects require the time series of length to be considerably long. With an attempt to avoid discomfort to participants in performing long physical tasks for data recording, this paper introduces the use of fuzzy recurrence plots of very short time series as input data for the machine training and classification with long short-term memory &#x0028 LSTM &#x0029 neural networks. Being an original approach that is able to both significantly increase the feature dimensions and provides the property of deterministic dynamical systems of very short time series for information processing carried out by an LSTM layer architecture, fuzzy recurrence plots provide promising results and outperform the direct input of the time series for the classification of healthy control and early PD subjects.