Fluorescence-Guided Stereotactic Biopsy: A Proof-of-Concept Study

Introduction: Histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in approximately 10% of cases. This can delay initiation of treatment and may result in further invasive procedures for patients. Here, we evaluate if coupling in vivo optical imaging with a STB system can identify diagnostic tissue at the time of biopsy. Methods: A minimally invasive fiber optic imaging system was developed by coupling a 0.65mm diameter fiber optic fluorescence microendoscope to a STB system. Human glioma cells were transduced for stable expression of blue fluorescent protein (U251-BFP) and utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by sodium fluorescein (FNa) was quantified with fluorescence microscopy. Rodent xenografts implanted with U251-BFP cells (n=4) were utilized for in vivo experiments. Five weeks post-implantation, xenografts received 5-10mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest (ROI) ipsilateral and contralateral to tumor implantation were analyzed. Results: Live-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2=0.91, p\u3c0.001). Normalized to background, in vivo FNa fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (60.65± 17.35 %, p\u3c0.001). Fluorescein fluorescence was not significantly greater from the tumor margin compared to normal brain (p =0.096). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor. Conclusion: We found in vivo fluorescence imaging with a STB needle containing a submillimeter diameter fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. This was confirmed in vivo and by post-hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies

Epithelioid Glioblastoma Presenting as Aphasia in a Young Adult with Ovarian Cancer: A Case Report

Background: Epithelioid glioblastoma (eGBM) is a recent addition to the World Health Organization’s classification of central nervous system (CNS) tumors. This rare lesion has a predilection for younger patients, can mimic metastatic disease on preoperative imaging and intraoperative pathology, and portends a poor prognosis due to propensity for leptomeningeal dissemination. Case Description: We discuss a case of a young woman with a history of ovarian cancer who presented with seizure and a new ring-enhancing left temporal brain lesion. The patient underwent gross-total surgical resection of this lesion, during which frozen section suggested metastasis. However, pathologic interrogation showed pleomorphic epithelioid cells and glial fibrillary acid positivity, suggesting eGBM. The patient has since completed radiotherapy and six-month post-operative imaging has not revealed recurrence or leptomeningeal dissemination. Conclusion: Our patient\u27s clinical history and pre-operative radiographic evaluation suggested CNS metastatic disease. Ultimately, final pathology revealed eGBM, a newly classified CNS primary tumor. This reinforces the importance of direct tissue sampling and including eGBM on the differential for young patients with histories of systemic cancer presenting with new CNS lesions

Epithelioid Glioblastoma Presenting as Aphasia in a Young Adult with Ovarian Cancer: A Case Report

Our patient\u27s clinical history and preoperative radiographic evaluation suggested central nervous system (CNS) metastatic disease. Ultimately, final pathology revealed epithelioid glioblastoma (eGBM), a newly classified CNS primary tumor. This reinforces the importance of direct tissue sampling and including eGBM on the differential for young patients with histories of systemic cancer presenting with new CNS lesions

Minimally Invasive In Vivo Real-Time Identification of Human Astrocytoma with Sulforhodamine 101

Abstract and poster under embargo until May 31, 2019

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials.

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources

Home Range Use and Movement Patterns of Non-Native Feral Goats in a Tropical Island Montane Dry Landscape

Advances in wildlife telemetry and remote sensing technology facilitate studies of broad-scale movements of ungulates in relation to phenological shifts in vegetation. In tropical island dry landscapes, home range use and movements of non-native feral goats (Capra hircus) are largely unknown, yet this information is important to help guide the conservation and restoration of some of the world’s most critically endangered ecosystems. We hypothesized that feral goats would respond to resource pulses in vegetation by traveling to areas of recent green-up. To address this hypothesis, we fitted six male and seven female feral goats with Global Positioning System (GPS) collars equipped with an Argos satellite upload link to examine goat movements in relation to the plant phenology using the Normalized Difference Vegetation Index (NDVI). Movement patterns of 50% of males and 40% of females suggested conditional movement between non-overlapping home ranges throughout the year. A shift in NDVI values corresponded with movement between primary and secondary ranges of goats that exhibited long-distance movement, suggesting that vegetation phenology as captured by NDVI is a good indicator of the habitat and movement patterns of feral goats in tropical island dry landscapes. In the context of conservation and restoration of tropical island landscapes, the results of our study identify how non-native feral goats use resources across a broad landscape to sustain their populations and facilitate invasion of native plant communities

Ion Waves in an Inhomogeneous Plasma

Object: Thoracolumbar instrumentation has experienced a dramatic increase in utilization over the last 2 decades. However, pedicle screw fixation remains a challenging undertaking, with suboptimal placement contributing to postoperative pain, neurological deficit, vascular complications, and return to the operating suite. Image-guided spinal surgery has substantially improved the accuracy rates for these procedures. However, it is not without technical challenges and a learning curve for novice operators. The authors present their experience with the O-arm intraoperative imaging system and share the lessons they learned over nearly 5 years. Methods: The authors performed a retrospective chart review of 270 consecutive patients who underwent thoracolumbar pedicle screw fixation utilizing the O-arm imaging system in conjunction with StealthStation navigation between April 2009 and September 2013 at a single tertiary care center; 266 of the patients underwent CT scanning on postoperative Day 1 to evaluate hardware placement. The CT scans were interpreted prospectively by 3 neuroradiologists as part of standard work flow and retrospectively by 2 neurosurgeons and a senior resident. Pedicle screws were evaluated for breaches according to the 3-tier classification proposed by Mirza et al. Results: Of 270 patients, 266 (98.5%) were included in the final analysis based on the presence of a postoperative CT scan. Overall, 1651 pedicle screws were placed in 266 patients and yielded a 5.3% breach rate; 213 thoracic and 1438 lumbosacral pedicle screws were inserted with 6.6% and 5.1% breach rates, respectively. Of the 87 suboptimally placed screws, there were 13 Grade 1, 16 Grade 2, and 12 Grade 3 misses as well as 46 anterolateral or tipout perforations at L-5. Four patients (1.5%) required a return to the operating room for pedicle screw revision, 2 of whom experienced transient radicular symptoms and 2 remained asymptomatic. Interestingly, the pedicle breach rate was higher than anticipated at 13.21% for the 30 patients over the initial 6-month period with the O-arm. After certain modifications to the authors\u27 technique, the subsequent 30 patients experienced a statistically significant decrease in breach rate at 5.6% (p = 0.014). Conclusions: Image-guided spinal surgery can be a great option in the operating room and provides high pedicle screw accuracy rates. With numerous systems commercially available, it is important to develop a systematic approach regardless of the technology in question. There is a learning curve for surgeons unfamiliar with image guidance that should be recognized and appreciated when transitioning to navigation-assisted spinal surgery. In fact, the authors\u27 experience with a large patient cohort suggests that this learning curve may be more significant than previously reported. ©AANS, 2014

Dependence of 3 Nebraska Sandhills Warm-Season Grasses on Vesicular-Arbuscular Mycorrhizae

Vesicular-arbuscular mycorrhizae (VAM) are rare or absent in actively eroding soils of the Sandhills. The objective of this study was to determine if 3 major Sandhills warm-season grasses used in reseeding eroded Sandhills sites are highly mycorrhizal dependent, and evaluate the response of VAM at different phosphorus (P) levels. In 2 greenhouse experiments, sand bluestem [Andropogon gerardii var. paucipilus (Nash) Fern.], switchgrass, (Panicum virgatum L.), and prairie sandreed [Calamovilfa longifolio (Hook) Scribn.] were grown in steam-sterilized sand in pots and inoculated with either indigenous Sandhills VAM, Glomus deserticola, or noninoculated. In the second experiment, VAM inoculated and control plants were treated with 5 P levels ranging from 5.4 to 27.0 mg P pot1. Increasing levels of P fertilizer caused an initial increase, then dramatic decrease, in percentage colonization by Glomus deserticola but had no effect on percentage colonization by indigenous Sandhills VAM. Mycorrhizal inoculated plants had a greater number of tillers, greater shoot weight, root weight, tissue P concentration and percentage P recovered, and a lower root/- shoot ratio and P efficiency than noninoculated plants. Non-inoculated sand bluestem had significantly lower shoot P concentration but greater P efficiency over all P levels than any other grass-VAM treatment combination. Phosphorus fertilizer and VAM effects were often complementary at P levels up to 16.2 to 21.6 mg P pot-1, with no change or a decrease in plant responses at higher P levels. These 3 major Sandhills warm-season grasses were highly mycorrhizal dependent. Successful reestablishment of these on eroded sites in the Sandhills may be greatly improved if soil reinoculation with VAM occurred prior to revegetation