Short-wave Infrared Neural Stimulation Drives Graded Sciatic Nerve Activation Across A Continuum of Wavelengths.

Infrared neural stimulation (INS) is an optical stimulation technique which uses coherent light to stimulate nerves and neurons and which shows increased spatial selectivity compared to electrical stimulation. This could improve deep brain, high channel count, or vagus nerve stimulation. In this study, we seek to understand the wavelength dependence of INS in the near-infrared optical window. Rat sciatic nerves were excised ex vivo and stimulated with wavelengths between 700 and 900 nm. Recorded compound nerve action potentials (CNAPs) showed that stimulation was maximized in the 700 nm window despite comparable laser power levels across wavelengths. Computational models demonstrated that wavelength-based activation dependencies were not a result of passive optical properties. This data demonstrates that INS is both wavelength and power level dependent, which inform stimulation systems to actively target neural microcircuits in humans.

Interplay effects in highly modulated stereotactic body radiation therapy lung cases treated with volumetric modulated arc therapy.

Interplay effects in highly modulated stereotactic body radiation therapy lung cases treated with volumetric modulated arc therapy. PURPOSE: To evaluate the influence of tumor motion on dose delivery in highly modulated stereotactic body radiotherapy (SBRT) of lung cancer using volumetric modulated arc therapy (VMAT). METHODS: 4D-CT imaging data of the quasar respiratory phantom were acquired, using a GE Lightspeed 16-slice CT scanner, while the phantom reproduced patient specific respiratory traces. Flattening filter-free (FFF) dual-arc VMAT treatment plans were created on the acquired images in Pinnacle3 treatment planning system. Each plan was generated with varying levels of complexity characterized by the modulation complexity score. Static and dynamic measurements were delivered to GafChromic EBT3 film inside the respiratory phantom using an Elekta Versa HD linear accelerator. The treatment prescription was 10 Gy per fraction for 5 fractions. Comparisons of the planned and delivered dose distribution were performed using Radiological Imaging Technology (RIT) software. RESULTS: For the motion amplitudes and periods studied, the interplay effect is insignificant to the GTV coverage. The mean dose deviations between the planned and delivered dose distribution never went below -2.00% and a minimum dose difference of -5.05% was observed for a single fraction. However for amplitude of 2 cm, the dose error could be as large as 20.00% near the edges of the PTV at increased levels of complexity. Additionally, the modulation complexity score showed an ability to provide information related to dose delivery. A correlation value (R) of 0.65 was observed between the complexity score and the gamma passing rate for GTV coverage. CONCLUSIONS: As expected, respiratory motion effects are most evident for large amplitude respirations, complex fields, and small field margins. However, under all tested conditions target coverage was maintained.

An ultrasound based platform for image-guided radiotherapy in canine bladder cancer patients.

BACKGROUND AND PURPOSE: Ultrasound (US) is a non-invasive, non-radiographic imaging technique with high spatial and temporal resolution that can be used for localizing soft-tissue structures and tumors in real-time during radiotherapy (RT) (inter- and intra-fraction). A comprehensive approach incorporating an in-house 3D-US system within RT is presented. This system is easier to adopt into existing treatment protocols than current US based systems, with the aim of providing millimeter intra-fraction alignment errors and sensitivity to track intra-fraction bladder movement. MATERIALS AND METHODS: An in-house integrated US manipulator and platform was designed to relate the computed tomographic (CT) scanner, 3D-US and linear accelerator coordinate systems. An agar-based phantom with measured speed of sound and densities consistent with tissues surrounding the bladder was rotated (0-45°) and translated (up to 55 mm) relative to the US and CT coordinate systems to validate this device. After acquiring and integrating CT and US images into the treatment planning system, US-to-US and US-to-CT images were co-registered to re-align the phantom relative to the linear accelerator. RESULTS: Statistical errors from US-to-US registrations for various patient orientations ranged from 0.1 to 1.7 mm for x, y, and z translation components, and 0.0-1.1° for rotational components. Statistical errors from US-to-CT registrations were 0.3-1.2 mm for the x, y and z translational components and 0.1-2.5° for the rotational components. CONCLUSIONS: An ultrasound-based platform was designed, constructed and tested on a CT/US tissue-equivalent phantom to track bladder displacement with a statistical uncertainty to correct and track inter- and intra-fractional displacements of the bladder during radiation treatments.

The role of brachytherapy in the treatment of glioblastoma multiforme.

Brachytherapy (BT) for glioblastoma multiforme (GBM) involves the use of radioactive isotopes to deliver ionizing radiation directly into the tumor bed. Its application as a means to prolong survival in GBM patients over the past few decades has come with variable success. The objective of this review is to describe the utility of BT in GBM, and to report the outcomes and adverse events associated with its use in different multimodal treatment approaches. A search of the literature was conducted using the PubMed database. The most recent search was performed in September 2015. Thirty-two series involving 1571 patients were included in our review. The longest median overall survival (MOS) following BT for newly diagnosed GBM reached 28.5 months. Overall, 1-, 2-, and 3-year survival rates were 46-89 %, 20-57 %, and 14-27 %. For recurrent GBM, the longest reported MOS after BT was 15.9 months. One-, 2- and 3-year survival rates for recurrent GBM were 10-66 %, 3-23 %, and 9-15 %. Adverse events were reported in 27 % of patients. Reoperation for radiation necrosis occurred in 4 and 27 % of patients following low- and high-dose rate BT, respectively. BT is a feasible option for extending survival in carefully selected GBM patients. As patient outcomes and overall survival improve with more aggressive radiotherapy, so does the risk of radiation-related complications. The most effective use of BT is likely as a part of multimodal treatment with other novel therapies.

Chronic nicotine exposure inhibits estrogen-mediated synaptic functions in hippocampus of female rats.

Nicotine, the addictive agent in cigarettes, reduces circulating estradiol-17ß (E2) and inhibits E2-mediated intracellular signaling in hippocampus of female rats. In hippocampus, E2-signaling regulates synaptic plasticity by phosphorylation of the N-methyl-D-aspartic acid receptor subunit NR2B and cyclic-AMP response element binding protein (pCREB). Therefore, we hypothesized that chronic nicotine exposure induces synaptic dysfunction in hippocampus of female rats. Female rats were exposed to nicotine or saline for 16 days followed by electrophysiological analysis of hippocampus. Briefly, population measurements of excitatory post-synaptic field potentials (fEPSPs) were recorded from stratum radiatum of the CA1 hippocampal slice subfield. A strict software-controlled protocol was used which recorded 30 min of baseline data (stimulation rate of 1/min), a paired-pulse stimulation sequence followed by tetanic stimulation, and 1h of post-tetanus recording. EPSP amplitude and the initial EPSP slope were measured off-line. We then investigated by Western blot analysis the effects of nicotine on hippocampal estrogen receptor-beta (ER-ß), NR2B and pCREB. The results demonstrated significantly decreased post-tetanic potentiation and paired-pulse facilitation at the 40, and 80 ms interval in nicotine-exposed rats compared to the saline group. Western blot analysis revealed that nicotine decreased protein levels of ER-ß, NR2B, and pCREB. We also confirmed the role of E2 in regulating NR2B and pCREB phosphorylation by performing Western blots in hippocapmal tissue obtained from E2-treated ovariectomized rats. In conclusion, chronic nicotine exposure attenuates short-term synaptic plasticity, and the observed synaptic defects might be a consequence of loss of estradiol-17ß-signaling. However, determining the exact molecular mechanisms of chronic nicotine exposure on synaptic plasticity specific to the female brain require further investigation.

EphrinBs regulate D-serine synthesis and release in astrocytes.

There is growing evidence that astrocytes play critical roles in neuron-glial interactions at the synapse. Astrocytes are believed to regulate presynaptic and postsynaptic structures and functions, in part, by the release of gliotransmitters such as glutamate, ATP, and d-serine; however, little is known of how neurons and astrocytes communicate to regulate these processes. Here, we investigated a family of transmembrane proteins called ephrinBs and Eph receptors that are expressed in the synapse and are known to regulate synaptic transmission and plasticity. In addition to their presence on CA1 hippocampal neurons, we determined that ephrins and Eph receptors are also expressed on hippocampal astrocytes. Stimulation of hippocampal astrocytes with soluble ephrinB3, known to be expressed on CA1 postsynaptic dendrites, enhanced d-serine synthesis and release in culture. Conversely, ephrinB3 had no effect on d-serine release from astrocytes deficient in EphB3 and EphA4, which are the primary receptors for ephrinB3. Eph receptors mediate this response through interactions with PICK1 (protein interacting with C-kinase) and by dephosphorylating protein kinase C α to activate the conversion of l-serine to d-serine by serine racemase. These findings are supported in vivo, where reduced d-serine levels and synaptic transmissions are observed in the absence of EphB3 and EphA4. These data support a role for ephrins and Eph receptors in regulating astrocyte gliotransmitters, which may have important implications on synaptic transmission and plasticity.