The Influence of Etiology and Stimulation Target on the Outcome of Deep Brain Stimulation for Chronic Neuropathic Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Deep brain stimulation (DBS) to treat chronic neuropathic pain has shown variable outcomes. Variations in pain etiologies and DBS targets are considered the main contributing factors, which are, however, underexplored owing to a paucity of patient data in individual studies. An updated meta-analysis to quantitatively assess the influence of these factors on the outcome of DBS for chronic neuropathic pain is warranted, especially considering that the anterior cingulate cortex (ACC) has emerged recently as a new DBS target. MATERIALS AND METHODS: A comprehensive literature review was performed in PubMed, Embase, and Cochrane data bases to identify studies reporting quantitative outcomes of DBS for chronic neuropathic pain. Pain and quality of life (QoL) outcomes, grouped by etiology and DBS target, were extracted and analyzed (α = 0.05). RESULTS: Twenty-five studies were included for analysis. Patients with peripheral neuropathic pain (PNP) had a significantly greater initial stimulation success rate than did patients with central neuropathic pain (CNP). Both patients with CNP and patients with PNP with definitive implant, regardless of targets, gained significant follow-up pain reduction. Patients with PNP had greater long-term pain relief than did patients with CNP. Patients with CNP with ACC DBS gained less long-term pain relief than did those with conventional targets. Significant short-term QoL improvement was reported in selected patients with CNP after ACC DBS. However, selective reporting bias was expected, and the improvement decreased in the long term. CONCLUSIONS: Although DBS to treat chronic neuropathic pain is generally effective, patients with PNP are the preferred population over patients with CNP. Current data suggest that ACC DBS deserves further investigation as a potential way to treat the affective component of chronic neuropathic pain.

High-speed k-linear swept laser using acousto-optic deflectors with Doppler shift compensation for optical coherence tomography.

Swept laser based on the acousto-optic deflector (AOD) is a promising swept source in optical coherence tomography (OCT) applications for its high wavenumber linear sweep without mechanical motion. However, the poor coherence length and the elongated cavity of the laser imposed limitations on the acquisition of high-quality images with adequate imaging depth and high imaging speed. In this Letter, we demonstrate a compact high-speed wavenumber linear swept laser based on AOD using Doppler shift compensation, achieving a high linearity of Pearson's R of 0.999991, a duty cycle of ∼100%, an extended coherence length of 5.7 mm, an output power of 18 mW, and excellent phase stability at a sweep speed of 500 kHz. OCT structural images with a system sensitivity of 103.2 dB and OCT angiography (OCTA) of human palm in vivo have been successfully performed, serving as a compelling demonstration of the excellent performance of this swept laser. We believe that the proposed laser will be of high potential in various clinical and industrial applications in the future.

Precise management system for chronic intractable pain patients implanted with spinal cord stimulation based on a remote programming platform: study protocol for a randomized controlled trial (PreMaSy study).

BACKGROUND: Spinal cord stimulation (SCS) is a surgical technique used in patients with chronic intractable pain, and its effectiveness and safety have been validated by multiple studies. However, to maintain an optimal and steady long-term effect is still challenging. Here, we report a new management paradigm integrating smartphone application and remote programming. Chronic pain patients with SCS implants can monitor their pain status on the phone and change stimulation parameters accordingly. The PreMaSy study is a randomized controlled trial to evaluate the clinical effectiveness and safety of this precise management system. METHODS: Patients with chronic intractable pain will be screened for eligibility, and 82 participants are anticipated to be enrolled in this trial. After the electrode implantation, the stimulation effectiveness will be tested. Participants with a reduction of more than 50% in the visual analog scale (VAS) will receive implantation of an implantable pulse generator and randomized (1:1) into the experimental group or control group. All participants will be asked to take online follow-ups and complete assessments using a smartphone application. Daily pain characteristic assessments and monthly quality of life questionnaires are integrated into the App, and participants will be required to complete these assessments. The daily VAS for pain intensity will be monitored and a threshold will be set based on baseline VAS score. The interventional appointment will be scheduled once the threshold is reached. The primary outcome is the health condition and quality of life assessed by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). Utility values of EQ-5D-5L will be assessed at baseline and 1, 3, and 6 months post-operative. DISCUSSION: The PreMaSy study aims to evaluate the effectiveness and safety of a novel App-based, patient-centered, self-assessment management system for chronic intractable pain. A randomized controlled trial is designed to test the non-inferiority of this precise management system compared to the monthly online follow-ups. It is also expected to yield valuable experiences regarding precision medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT05761392. Registered on March 07, 2023.

Polarization-isolated stretched-pulse mode-locked swept laser for 10.3-MHz A-line rate optical coherence tomography.

Stretched-pulse mode-locked (SPML) lasing based on a chirped fiber Bragg grating (CFBG) has proven to be a powerful method to generate wavelength-swept lasers at speeds of tens of megahertz. However, light transmitted through the CFBG may lead to undesirable laser oscillation that disrupts the mechanism of the laser active mode locking in the theta ring cavity. In this Letter, we demonstrate a simple and low-cost approach to suppress the transmitted light and achieve an effective duty cycle of ∼100% with only one CFBG and no need for intra-cavity semiconductor optical amplifier (SOA) modulation, extra-cavity optical buffering, and post amplification. By utilizing polarization isolation of the bi-directional CFBG, a swept laser centered at 1305 nm, with repetition rate of 10.3 MHz, optical power of 84 mW, and 3 dB bandwidth of 109 nm, is demonstrated. Ultrahigh speed 3D optical coherence tomography (OCT) structural imaging of a human palm in vivo using this swept laser is also demonstrated. We believe that this ultrahigh speed swept laser will greatly promote the OCT technique for industrial and biomedical applications.

External magnetic field non-invasively stimulates spinal cord regeneration in rat via a magnetic-responsive aligned fibrin hydrogel.

Magnetic stimulation is becoming an attractive approach to promote neuroprotection, neurogenesis, axonal regeneration, and functional recovery in both the central nervous system and peripheral nervous system disorders owing to its painless, non-invasive, and deep penetration characteristics. Here, a magnetic-responsive aligned fibrin hydrogel (MAFG) was developed to import and amplify the extrinsic magnetic field (MF) locally to stimulate spinal cord regeneration in combination with the beneficial topographical and biochemical cues of aligned fibrin hydrogel (AFG). Magnetic nanoparticles (MNPs) were embedded uniformly in AFG during electrospinning to endow it magnetic-responsive feature, with saturation magnetization of 21.79 emu g-1. It is found that the MNPs under the MF could enhance cell proliferation and neurotrophin secretion of PC12 cellsin vitro. The MAFG that was implanted into a rat with 2 mm complete transected spinal cord injury (SCI) effectively enhanced neural regeneration and angiogenesis in the lesion area, thus leading to significant recovery of motor function under the MF (MAFG@MF). This study suggests a new multimodal tissue engineering strategy based on multifunctional biomaterials that deliver multimodal regulatory signals with the integration of aligned topography, biochemical cues, and extrinsic MF stimulation for spinal cord regeneration following severe SCI.

Multimodal-based machine learning strategy for accurate and non-invasive prediction of intramedullary glioma grade and mutation status of molecular markers: a retrospective study.

BACKGROUND: Determining the grade and molecular marker status of intramedullary gliomas is important for assessing treatment outcomes and prognosis. Invasive biopsy for pathology usually carries a high risk of tissue damage, especially to the spinal cord, and there are currently no non-invasive strategies to identify the pathological type of intramedullary gliomas. Therefore, this study aimed to develop a non-invasive machine learning model to assist doctors in identifying the intramedullary glioma grade and mutation status of molecular markers. METHODS: A total of 461 patients from two institutions were included, and their sagittal (SAG) and transverse (TRA) T2-weighted magnetic resonance imaging scans and clinical data were acquired preoperatively. We employed a transformer-based deep learning model to automatically segment lesions in the SAG and TRA phases and extract their radiomics features. Different feature representations were fed into the proposed neural networks and compared with those of other mainstream models. RESULTS: The dice similarity coefficients of the Swin transformer in the SAG and TRA phases were 0.8697 and 0.8738, respectively. The results demonstrated that the best performance was obtained in our proposed neural networks based on multimodal fusion (SAG-TRA-clinical) features. In the external validation cohort, the areas under the receiver operating characteristic curve for graded (WHO I-II or WHO III-IV), alpha thalassemia/mental retardation syndrome X-linked (ATRX) status, and tumor protein p53 (P53) status prediction tasks were 0.8431, 0.7622, and 0.7954, respectively. CONCLUSIONS: This study reports a novel machine learning strategy that, for the first time, is based on multimodal features to predict the ATRX and P53 mutation status and grades of intramedullary gliomas. The generalized application of these models could non-invasively provide more tumor-specific pathological information for determining the treatment and prognosis of intramedullary gliomas.

Real-Time Navigation with Guide Template for Pedicle Screw Placement Using an Augmented Reality Head-Mounted Device: A Proof-of-Concept Study.

Objective: This study aims to explore the real-time navigation with guide template using an augmented reality head-mounted device (ARHMD) for pedicle screw placement. Methods: The spatial coordinate relationships between augmented reality images and real objects were established through the custom-made guide template, and the registration and tracking were completed using an ARHMD. The feasibility and accuracy of this method were verified by pedicle screw placement in 2 lumbar models. According to the Gertzbein-Robbins grading scale, the accuracy of pedicle screw placement was assessed. The navigation errors were estimated by measuring the deviation values of entry point and trajectory angle. Results: A total of 20 pedicle K-wires were placed into L1-L5 in 2 lumbar models, which were successfully completed, with an average time of 11.5 min per model and 69 s per screw. The overall K-wires placement accuracy was 100% (20 screws). The navigation error was 2.77 ± 0.82 mm for the deviation value of entry point, and 3.03° ± 0.94° for the deviation value of trajectory angle. Conclusions: The application of an ARHMD combined with guide template for pedicle screw placement is a promising navigation approach.

Emotional Problems, Quality of Life and Symptom Burden in Patients with Chordoma.

Chordomas are very rare malignant bone tumors. Following surgery, their effects on neurological, physical, psychological, social, and emotional functioning are substantial and can have a major impact on a patients' quality of life (QOL). In this survey, we aimed to characterize the postoperation health-related QOL and emotional problem in patients with chordoma using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and Hamilton Depression Rating Scale (HAMD). The cohort included 100 patients who underwent resection surgery between 2014 and 2020. Being single or divorced, living in a rural area, receiving a diagnosis of sacrococcygeal chordoma, Karnofsky performance status (KPS) ≤ 70, and weight loss were associated with increased likelihood of depression (p < 0.05). Patients who were single or divorced, with KPS ≤ 70, and experiencing weight loss had a higher likelihood of a worse QOL (p < 0.05). The uni- and multivariate logistic regression analyses indicated that the KPS level (p = 0.000) and postoperative radiation therapy (p = 0.009) were related to depression; marital status (p = 0.029), KPS level (p = 0.006), and tumor location (p = 0.033) were related to worse QOL. Certain characteristics placed patients with chordoma at increased risk of emotional problems, which are associated with a lowered QOL and a higher symptom burden. Further knowledge regarding emotional problems is key to improving the QOL for patients with chordoma.

3D bio-printed living nerve-like fibers refine the ecological niche for long-distance spinal cord injury regeneration.

3D bioprinting holds great promise toward fabricating biomimetic living constructs in a bottom-up assembly manner. To date, various emergences of living constructs have been bioprinted for in vitro applications, while the conspicuous potential serving for in vivo implantable therapies in spinal cord injury (SCI) has been relatively overlooked. Herein, living nerve-like fibers are prepared via extrusion-based 3D bioprinting for SCI therapy. The living nerve-like fibers are comprised of neural stem cells (NSCs) embedded within a designed hydrogel that mimics the extracellular matrix (ECM), assembled into a highly spatial ordered architecture, similar to densely arranged bundles of the nerve fibers. The pro-neurogenesis ability of these living nerve-like fibers is tested in a 4 mm-long complete transected SCI rat model. Evidence shows that living nerve-like fibers refine the ecological niche of the defect site by immune modulation, angiogenesis, neurogenesis, neural relay formations, and neural circuit remodeling, leading to outstanding functional reconstruction, revealing an evolution process of this living construct after implantation. This effective strategy, based on biomimetic living constructs, opens a new perspective on SCI therapies.

Intratumor Injection of Thermosensitive Polypeptide with Resveratrol Inhibits Glioblastoma Growth.

Local tumor treatment is a feasible measure for patients with glioblastoma (GBM) who are unsuitable for surgical resection. Interferon-elastin-like polypeptide [IFN-ELP(V)] is a slow-release, biodegradable, thermosensitive fusion protein with antitumor immunity, and resveratrol (Res) is a polyphenolic compound with an antitumor effect. In this study, we found that intratumor injection of IFN-ELP(V) combined with intraperitoneal injection of Res is more effective in delaying GBM growth in mice. Specifically, in an orthotopic GBM model, we found a significant improvement in the median survival with this strategy. Our results suggested that the combined use of IFN-ELP(V) and Res has a dramatic synergistic effect on GBM, thus providing a novel and effective therapeutic strategy for tumors. Impact statement We report a novel and effective strategy in which the combined use of interferon-elastin-like polypeptide [IFN-ELP(V)] and Res effectively inhibits glioblastoma growth. IFN-ELP(V) can create a reservoir in the tumor and continuously release IFN to produce a powerful in situ antitumor immune response; furthermore, the combination of IFN-ELP(V) and Res is more effective in inhibiting tumor growth.

Optical coherence tomography angiography with adaptive multi-time interval.

Optical coherence tomography angiography (OCTA) can provide in vivo three-dimensional microvasculature information of bio-tissues, but it is sensitive to motion and time-consuming. To overcome these limitations, we propose an adaptive multiple time interval correlation mapping OCTA with a time-efficient scanning protocol and motion compensation algorithms. A spectral-domain OCT with a center wavelength of 850 nm, A-scan rate of 120 kHz and spatial resolution of 4.1 µm (axial) × 6.9 µm (lateral) is built to reconstruct the microvascular networks in the human arm. By adaptive optimization of the weights of different time interval B-scan angiograms, our novel OCTA technique achieves better performance with a visible vascular density increase of ~67% and a signal-to-noise ratio enhancement of ~11.6%.

Automatic and Efficient Prediction of Hematoma Expansion in Patients with Hypertensive Intracerebral Hemorrhage Using Deep Learning Based on CT Images.

Patients with hypertensive intracerebral hemorrhage (ICH) have a high hematoma expansion (HE) incidence. Noninvasive prediction HE helps doctors take effective measures to prevent accidents. This study retrospectively analyzed 253 cases of hypertensive intraparenchymal hematoma. Baseline non-contrast-enhanced CT scans (NECTs) were collected at admission and compared with subsequent CTs to determine the presence of HE. An end-to-end deep learning method based on CT was proposed to automatically segment the hematoma region, region of interest (ROI) feature extraction, and HE prediction. A variety of algorithms were employed for comparison. U-Net with attention performs best in the task of segmenting hematomas, with the mean Intersection overUnion (mIoU) of 0.9025. ResNet-34 achieves the most robust generalization capability in HE prediction, with an area under the receiver operating characteristic curve (AUC) of 0.9267, an accuracy of 0.8827, and an F1 score of 0.8644. The proposed method is superior to other mainstream models, which will facilitate accurate, efficient, and automated HE prediction.

White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in canine T12 spinal cord injury.

A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.

Intraoperative application of yellow fluorescence in resection of intramedullary spinal canal ependymoma.

BACKGROUND: Spinal ependymoma is the most common intramedullary tumor in adults. This study was performed to evaluate whether intraoperative yellow fluorescence use enhances our ability to identify the tumor margin and residual tumor tissue in intramedullary spinal cord ependymoma resection. We also evaluated patients' clinical conditions at a 3-month follow-up. METHODS: We retrospectively evaluated 56 patients with intramedullary ependymoma. Thirty minutes before anesthesia, the patients received intravenous sodium fluorescein injections. Tumor resection was performed under two illumination modes, traditional white light and yellow fluorescence, and the residual tumor tissue was detected. Magnetic resonance imaging was performed 3 months postoperatively to observe the tumor resection outcome and residual tumor tissue. The McCormick spinal cord function grade was evaluated preoperatively and 3 months postoperatively. RESULTS: The total resection rate was 100.0% in all patients. Nine patients had no significant fluorescence imaging. After 3 months, patients with a spinal function grade of I to IV showed significant spinal function improvement. Magnetic resonance imaging showed no residual tumor tissue or recurrence. CONCLUSION: Sodium fluorescein aids in total excision of intramedullary spinal cord ependymoma and intraoperative residual tumor tissue identification. At the 3-month follow-up, the patients' functional outcome in the fluorescein group was good.

Improved Ultrafast Power Doppler Imaging by Using Spatiotemporal Non-Local Means Filtering.

The change of microvasculature is associated with the occurrence and development of many diseases. Ultrafast power Doppler imaging (uPDI) is an emerging technology for the visualization of microvessels due to the development of ultrafast plane wave (PW) imaging and advanced clutter filters. However, the low signal-to-noise ratio (SNR) caused by unfocused transmit of PW imaging deteriorates the subsequent imaging of microvasculature. Nonlocal means (NLM) filtering has been demonstrated to be effective in the denoising of both natural and medical images, including ultrasound power Doppler images. However, the feasibility and performance of applying an NLM filter on the ultrasound radio frequency (RF) data have not been investigated so far. In this study, we propose to apply an NLM filter on the spatiotemporal domain of clutter filtered blood flow RF data (St-NLM) to improve the quality of uPDI. Experiments were conducted to compare the proposed method with three different methods (under various similarity window sizes), including conventional uPDI without NLM filtering (Non-NLM), NLM filtering on the obtained power Doppler images (PD-NLM), and NLM filtering on the spatial domain of clutter filtered blood flow RF data (S-NLM). Phantom experiments, in vivo contrast-enhanced human spinal cord tumor experiments, and in vivo contrast-free human liver experiments were performed to demonstrate the superiority of the proposed St-NLM method over the other three methods. Qualitative and quantitative results show that the proposed St-NLM method can effectively suppress the background noise, improve the contrast between vessels and background, and preserve the details of small vessels at the same time. In the human liver study, the proposed St-NLM method achieves 31.05-, 24.49-, and 11.15-dB higher contrast-to-noise ratios (CNRs) and 36.86-, 36.86-, and 15.22-dB lower noise powers than Non-NLM, PD-NLM, and S-NLM, respectively. In the human spinal cord tumor, the full-width at half-maximums (FWHMs) of vessel cross Section are 76, 201, and [Formula: see text] for St-NLM, Non-NLM, and S-NLM, respectively. The proposed St-NLM method can enhance the microvascular visualization in uPDI and has the potential for the diagnosis of many microvessel-change-related diseases.

Ultrafine Flexible Endoscope Visualization to Assist in the Removal of a Huge Spinal Extradural Arachnoid Cyst: Case Report and Literature Review.

Arachnoid cysts are one of the benign spinal cystic lesions. Multiple nerve roots and spinal cord may be compressed by it, and operating is often recommended. Traditional surgical procedures often choose the posterior median approach, separating the paravertebral muscles, milling the lamina, fully exposing the cyst, partially or completely removing the cyst wall, looking for the leak, and then suturing and sealing. Here we present a case of giant spinal extradural arachnoid cyst in which a ultrafine flexible endoscope was used to visualize cystic spaces and identity the leaks. We repaired the leak after removing part of the cyst wall under the operating microscope, and the patient had an excellent recovery.

Spinal Angiolipomas : Clinical Characteristics, Surgical Strategies and Prognosis.

OBJECTIVE: Angiolipomas are usually found in the subcutaneous tissue of the trunk and limbs. Spinal angiolipomas (SALs) are uncommon and have rarely been reported. We report a series of nine SALs patients who received surgical treatment in our department. To summarize the clinical characteristics of SALs, propose our surgical strategies, and evaluate the effects of the operation. METHODS: This was a retrospective review of nine SALs patients who received surgical treatment from August 2015 to March 2020. Total or subtotal resection was determined by the axial localization (dorsal or ventral) and the extent of intervertebral foramen involvement. The outcomes were assessed based on the modified Japanese Orthopaedic Association (mJOA) scoring system utilized before surgery and at various follow-up points. RESULTS: Among the nine patients, the mean mJOA score before surgery was 6.6±2.3, compared with 10.1±1.1 at the last follow-up time point (33.4±11.8 months). All patients achieved good outcomes, even in cases of subtotal resection. CONCLUSION: Early surgical resection of SALs is recommended, and the specific procedures should be determined by the axial localization (dorsal or ventral) and the extent of intervertebral foramen involvement. Most of the patients had a good prognosis, even in cases of subtotal resection.

A multi-modal delivery strategy for spinal cord regeneration using a composite hydrogel presenting biophysical and biochemical cues synergistically.

Extensive tissue engineering studies have supported the enhanced spinal cord regeneration by implantable scaffolds loaded with bioactive cues. However, scaffolds with single-cue delivery showed unsatisfactory effects, most likely due to the complex nature of hostile niches in the lesion area. In this regard, strategies of multi-modal delivery of multiple heterogeneous cell-regulatory cues are unmet needs for enhancing spinal cord repair, which requires a thorough understanding of the regenerative niche associated with spinal cord injury. Here, by combining hierarchically aligned fibrin hydrogel (AFG) and functionalized self-assembling peptides (fSAP), a novel multifunctional nanofiber composite hydrogel AFG/fSAP characterized with interpenetrating network is designed. Serving as a source of both biophysical and biochemical cues, AFG/fSAP can facilitate spinal cord regeneration via guiding regenerated tissues, accelerating axonal regrowth and remyelination, and promoting angiogenesis. Giving the synergistic effect of multiple cues, AFG/fSAP implantation contributes to anatomical, electrophysiological, and motor functional restorations in rats with spinal cord hemisection. This study provides a novel multi-modal approach for regeneration in central nervous system, which has potentials for clinical practice of spinal cord injury.

LINC01158 works as an oncogene in glioma via sponging miR-6734-3p to boost CENPK expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been certified to play vital biological functions in glioma and have received considerable attention in the recent literature. Nonetheless, the role of LINC01158 in glioma remains to be elucidated. METHODS: qRT-PCR, western blot and GEPIA database were applied for reporting the expression of CENPK and LINC01158 in glioma and the correlation between LINC01158 and CENPK expression. EdU, colony formation, CCK-8, caspase-3 activity and TUNEL assays probed the impacts of LINC01158 on glioma cell growth. Subcellular fractionation and FISH assays revealed the cellular distribution of LINC01158. Luciferase reporter and RIP assays examined ceRNA network of LINC01158, CENPK and miR-6734-3p. RESULTS: LINC01158 and CENPK were both overexpressed in glioma and a positive regulation of LINC01158 on CENPK was corroborated. LINC01158 served a pro-proliferative and anti-apoptotic part in glioma by sponging miR-6734-3p to augment CENPK. CONCLUSION: LINC01158 enhances CENPK by serving as sponge for miR-6734-3p to facilitate glioma development, proposing LINC01158 as a new player in glioma.