Photoacoustic-Guided Surgery with Indocyanine Green-Coated Superparamagnetic Iron Oxide Nanoparticle Clusters.

A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real-time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles-with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20-30% of the total weight (ICG + SPIO). The ICG-SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG-SPIO clusters, animals undergoing PA-guided surgery demonstrate increased progression-free survival compared to animals undergoing microscopic surgery.

Myofascial Closure of Intradural Inclusion Cysts following in utero Myelomeningocele Repair.

Myelomeningocele is one of the most common congenital malformations. A randomized controlled trial, known as the Management of Myelomeningocele Study (MOMS), demonstrated that closure during the fetal period can be performed relatively safely and be of significant benefit to patients. However, postnatally, patients can develop resultant symptoms from a tethered cord and inclusion cysts; this often requires surgical treatment. Repeat surgery in this population can be challenging due to the age of the patients, the extent of surgical exposure needed and the need for resection of dermal and epidermal tissues in the midline. We describe our approach for closure of these complex defects using lateral fasciocutaneous flaps with relaxing incisions made in the posterior axillary line, in order to minimize tension and maximize soft tissue coverage of the midline.

Seizure outcomes and mesial resection volumes following selective amygdalohippocampectomy and temporal lobectomy.

OBJECT: Anterior temporal lobectomy (ATL) and selective amygdalohippocampectomy (SelAH) are the preferred surgical approaches for the treatment of medically refractory epilepsy involving the nondominant and dominant temporal lobes, respectively. Both techniques provide access to mesial structures-with the ATL providing a wider surgical corridor than SelAH. Because the extent of mesial temporal resection potentially impacts seizure outcome, the authors examined mesial resection volumes, seizure outcomes, and neuropsychiatric test scores in patients undergoing either ATL or transcortical SelAH at a single institution. METHODS: A retrospective study was conducted in 96 patients with medically refractory mesial temporal lobe epilepsy. Fifty-one patients who had nondominant temporal lobe epilepsy underwent standard ATL, and 45 patients with language-dominant temporal lobe epilepsy underwent transcortical SelAH. Volumetric MRI analysis was used to quantify the mesial resection in both groups. In addition, the authors examined seizure outcomes and the change in neuropsychiatric test scores. RESULTS: Seizure-free outcome in the entire patient cohort was 94% at a mean follow-up of 44 months. There was no significant difference in the seizure outcome between the 2 groups. The extent of resection of the mesial structures following ATL was slightly higher than for SelAH (98% vs. 91%, p < 0.0001). The change in neuropsychiatric test scores largely reflected the side of surgery, but overall IQ and memory function did not change significantly in either group. CONCLUSIONS: Transcortical SelAH provides adequate access to the mesial structures, and allows for a resection that is nearly as extensive as that achieved with standard ATL. Seizure outcomes and neuropsychiatric sequelae are similar in both procedures.

Cost-effectiveness of confirmatory techniques for the placement of lumbar pedicle screws.

OBJECT: There is considerable variation in the use of adjunctive technologies to confirm pedicle screw placement. Although there is literature to support the use of both neurophysiological monitoring and isocentric fluoroscopy to confirm pedicle screw positioning, there are no studies examining the cost-effectiveness of these technologies. This study compares the cost-effectiveness and efficacy of isocentric O-arm fluoroscopy, neurophysiological monitoring, and postoperative CT scanning after multilevel instrumented fusion for degenerative lumbar disease. METHODS: Retrospective data were collected from 4 spine surgeons who used 3 different strategies for monitoring of pedicle screw placement in multilevel lumbar degenerative disease. A decision analysis model was developed to analyze costs and outcomes of the 3 different monitoring strategies. A total of 448 surgeries performed between 2005 and 2010 were included, with 4 cases requiring repeat operation for malpositioned screws. A sample of 64 of these patients was chosen for structured interviews in which the EuroQol-5D questionnaire was used. Expected costs and quality-adjusted life years were calculated based on the incidence of repeat operation and its negative effect on quality of life and costs. RESULTS: The decision analysis model demonstrated that the O-arm monitoring strategy is significantly (p < 0.001) less costly than the strategy of postoperative CT scanning following intraoperative uniplanar fluoroscopy, which in turn is significantly (p < 0.001) less costly than neurophysiological monitoring. The differences in effectiveness of the different monitoring strategies are not significant (p = 0.92). CONCLUSIONS: Use of the O-arm for confirming pedicle screw placement is the least costly and therefore most cost-effective strategy of the 3 techniques analyzed.

Predicting pediatric optic pathway glioma progression using advanced magnetic resonance image analysis and machine learning.

BACKGROUND: Optic pathway gliomas (OPGs) are low-grade tumors of the white matter of the visual system with a highly variable clinical course. The aim of the study was to generate a magnetic resonance imaging (MRI)-based predictive model of OPG tumor progression using advanced image analysis and machine learning techniques. METHODS: We performed a retrospective case-control study of OPG patients managed between 2009 and 2015 at an academic children's hospital. Progression was defined as radiographic tumor growth or vision decline. To generate the model, optic nerves were manually highlighted and optic radiations (ORs) were segmented using diffusion tractography tools. For each patient, intensity distributions were obtained from within the segmented regions on all imaging sequences, including derivatives of diffusion tensor imaging (DTI). A machine learning algorithm determined the combination of features most predictive of progression. RESULTS: Nineteen OPG patients with progression were matched to 19 OPG patients without progression. The mean time between most recent follow-up and most recently analyzed MRI was 3.5 ± 1.7 years. Eighty-three MRI studies and 532 extracted features were included. The predictive model achieved an accuracy of 86%, sensitivity of 89%, and specificity of 81%. Fractional anisotropy of the ORs was among the most predictive features (area under the curve 0.83, P < 0.05). CONCLUSIONS: Our findings show that image analysis and machine learning can be applied to OPGs to generate a MRI-based predictive model with high accuracy. As OPGs grow along the visual pathway, the most predictive features relate to white matter changes as detected by DTI, especially within ORs.

On-Demand Prolongation of Peripheral Nerve Blockade through Bupivacaine-Loaded Hydrogels with Suitable Residence Periods.

Peripheral nerve blockade is an important perioperative intervention for pain management. However, this management always results in a limited analgesia effect due to the rapid elimination of local anesthetic drugs after a single injection, while continuous infusion leads to multiple side effects associated with catheter insertion. In this study, three thermosensitive hydrogels, i.e., Pluronic F127, and poly(l-alanine)-block-poly(ethylene glycol)-block-poly(l-alanine) (PAla-PEG-PAla), and poly(lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA), with distinct properties were applied to encapsulate bupivacaine (BUP) for prolonged analgesia with one single injection. All three hydrogel platforms exhibited a homogeneous three-dimensional structure with thermosensitive properties and high BUP encapsulation efficiency. The BUP loaded in PAla-PEG-PAla showed a sustained drug release profile, which was advantageous over those from Pluronic F127 and PLGA-PEG-PLGA with either burst release or inadequate release. The hydrogel platforms exhibited prolonged nerve blockade duration compared with BUP·HCl in vivo. Furthermore, the in vivo residence period of PAla-PEG-PAla/BFB was shorter than that of PLGA-PEG-PLGA/BFB while longer than that of Pluronic F127/BFB. All the hydrogels induced reversible inflammatory response without neurotoxicity. Overall, in comparison with the other two hydrogel platforms, PAla-PEG-PAla exhibited controlled drug release, appropriate residence period, and long-acting analgesia effect. Moreover, it might be a potential method to meet the different demands of regional nerve blockade and guide clinical pain management.

Polymer scaffolds facilitate spinal cord injury repair.

During the past decades, improving patient neurological recovery following spinal cord injury (SCI) has remained a challenge. An effective treatment for SCI would not only reduce fractured elements and isolate developing local glial scars to promote axonal regeneration but also ameliorate secondary effects, including inflammation, apoptosis, and necrosis. Three-dimensional (3D) scaffolds provide a platform in which these mechanisms can be addressed in a controlled manner. Polymer scaffolds with favorable biocompatibility and appropriate mechanical properties have been engineered to minimize cicatrization, customize drug release, and ensure an unobstructed space to promote cell growth and differentiation. These properties make polymer scaffolds an important potential therapeutic platform. This review highlights the recent developments in polymer scaffolds for SCI engineering. STATEMENT OF SIGNIFICANCE: How to improve the efficacy of neurological recovery after spinal cord injury (SCI) is always a challenge. Tissue engineering provides a promising strategy for SCI repair, and scaffolds are one of the most important elements in addition to cells and inducing factors. The review highlights recent development and future prospects in polymer scaffolds for SCI therapy. The review will guide future studies by outlining the requirements and characteristics of polymer scaffold technologies employed against SCI. Additionally, the peculiar properties of polymer materials used in the therapeutic process of SCI also have guiding significance to other tissue engineering approaches.

Transcriptome signatures associated with meningioma progression.

Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. RNA-seq was used to profile the transcriptome of grade I, II, and III meningiomas and to identify genes that may be involved in progression. Bioinformatic analyses showed that grade I meningiomas that progress to a higher grade are molecularly different from those that do not. As such, we identify GREM2, a regulator of the BMP pathway, and the snoRNAs SNORA46 and SNORA48, as being significantly reduced in meningioma progression. Additionally, our study has identified several novel fusion transcripts that are differentially present in meningiomas, with grade I tumors that did not progress presenting more fusion transcripts than all other tumors. Interestingly, our study also points to a difference in the tumor immune microenvironment that correlates with histopathological grade.