Evaluating and reporting LET and RBE-weighted dose in proton therapy for glioma - The Dutch approach.

Background And Purpose: With proton therapy, the relative biological effectiveness (RBE) accounts for increased DNA damage caused by higher linear energy transfer (LET) compared to photons. However, the LET and hence the RBE varies along the proton range, particularly at the Bragg peak, introducing challenges in proton treatment planning for brain tumors. The aim of this paper is to standardize evaluating and reporting LET and RBE in proton therapy for patients with grade 2 and 3 IDH mutant gliomas among the Dutch proton therapy centers.

Kilohertz volumetric imaging of in-vivo dynamics using squeezed light field microscopy.

Volumetric functional imaging of transient cellular signaling and motion dynamics poses a significant challenge to current microscopy techniques, primarily due to limitations in hardware bandwidth and the restricted photon budget within short exposure times. In response to this challenge, we present squeezed light field microscopy (SLIM), a computational imaging method that enables rapid detection of high-resolution three-dimensional (3D) light signals using only a single, low-format camera sensor area. SLIM pushes the boundaries of 3D optical microscopy, achieving over one thousand volumes per second across a large field of view of 550 μm in diameter and 300 μm in depth with a spatial resolution of 3.

Flow-tub model: A modified bathtub flood model with hydraulic connectivity and path-based attenuation.

Global climate change and sea level rise are increasing the risks of flooding for coastal communities. Probabilistic coastal flood risk analysis at regional or global scales requires flood models with relatively low data requirements and low computational costs. Bathtub inundation models, which compute flood depth as the difference between water level and ground elevation, are well-suited for large-scale flood risk analysis.

Feasibility of Monte Carlo dropout-based uncertainty maps to evaluate deep learning-based synthetic CTs for adaptive proton therapy.

Background: Deep learning has shown promising results to generate MRI-based synthetic CTs and to enable accurate proton dose calculations on MRIs. For clinical implementation of synthetic CTs, quality assurance tools that verify their quality and reliability are required but still lacking.

Purpose: This study aims to evaluate the predictive value of uncertainty maps generated with Monte Carlo dropout (MCD) for verifying proton dose calculations on deep-learning-based synthetic CTs (sCTs) derived from MRIs in online adaptive proton therapy.

Assessment of residual geometrical errors of clinical target volumes and their impact on dose accumulation for head and neck radiotherapy.

Purpose: To assess the residual geometrical errors (dr) and their impact on the clinical target volumes (CTV) dose coverage for head and neck cancer (HNC) proton therapy patients.

Methods: We analysed 28 HNC patients treated with 70 Gy (RBE) and 54.25 Gy (RBE) to the therapeutic CTV and prophylactic CTV, respectively.

Large-scale high-density brain-wide neural recording in nonhuman primates.

High-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.

Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients.

Background: Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arc plan.

Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses.

Optical implants to control and monitor neuronal activity in vivo have become foundational tools of neuroscience. Standard two-dimensional histology of the implant location, however, often suffers from distortion and loss during tissue processing. To address that, we developed a three-dimensional post hoc histology method called "light-guided sectioning" (LiGS), which preserves the tissue with its optical implant in place and allows staining and clearing of a volume up to 500 μm in depth.

Can the mean linear energy transfer of organs be directly related to patient toxicities for current head and neck cancer intensity-modulated proton therapy practice?

Background And Purpose: The relative biological effectiveness (RBE) of proton therapy is predicted to vary with the dose-weighted average linear energy transfer (LET). However, RBE values may substantially vary for different clinical endpoints. Therefore, the aim of this study was to assess the feasibility of relating mean D⋅LET parameters to patient toxicity for HNC patients treated with proton therapy.

Anatomy and activity patterns in a multifunctional motor neuron and its surrounding circuits.

Dorsal Excitor motor neuron DE-3 in the medicinal leech plays three very different dynamical roles in three different behaviors. Without rewiring its anatomical connectivity, how can a motor neuron dynamically switch roles to play appropriate roles in various behaviors? We previously used voltage-sensitive dye imaging to record from DE-3 and most other neurons in the leech segmental ganglion during (fictive) swimming, crawling, and local-bend escape (Tomina and Wagenaar, 2017). Here, we repeated that experiment, then re-imaged the same ganglion using serial blockface electron microscopy and traced DE-3's processes.

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State, Expectation, and Behavioral Context.

The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRN neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues.

Label-free imaging of lipid-rich biological tissues by mid-infrared photoacoustic microscopy.

Significance: Mid-infrared (IR) imaging based on the vibrational transition of biomolecules provides good chemical-specific contrast in label-free imaging of biology tissues, making it a popular tool in both biomedical studies and clinical applications. However, the current technology typically requires thin and dried or extremely flat samples, whose complicated processing limits this technology's broader translation.

Aim: To address this issue, we report mid-IR photoacoustic microscopy (PAM), which can readily work with fresh and thick tissue samples, even when they have rough surfaces.

Stimulus-specific hypothalamic encoding of a persistent defensive state.

Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial hypothalamus (VMHdm/c) that express the nuclear receptor protein NR5A1 (also known as SF1) are necessary for defensive responses to predators in mice.

Head and neck IMPT probabilistic dose accumulation: Feasibility of a 2 mm setup uncertainty setting.

Objective: To establish optimal robust optimization uncertainty settings for clinical head and neck cancer (HNC) patients undergoing 3D image-guided pencil beam scanning (PBS) proton therapy.

Methods: We analyzed ten consecutive HNC patients treated with 70 and 54.25 Gy to the primary and prophylactic clinical target volumes (CTV) respectively using intensity-modulated proton therapy (IMPT).

Improved Transferability of Data-Driven Damage Models Through Sample Selection Bias Correction.

Damage models for natural hazards are used for decision making on reducing and transferring risk. The damage estimates from these models depend on many variables and their complex sometimes nonlinear relationships with the damage. In recent years, data-driven modeling techniques have been used to capture those relationships.

Validation of the proton range accuracy and optimization of CT calibration curves utilizing range probing.

Proton therapy is affected by range uncertainty, which is partly caused by an ambiguous conversion from x-ray attenuation to proton stopping power. CT calibration curves, or Hounsfield look-up tables (HLUTs), are institution-specific and may be a source of systematic errors in treatment planning. A range probing method to verify, optimize and validate HLUTs for proton treatment is proposed.

Validation of linear energy transfer computed in a Monte Carlo dose engine of a commercial treatment planning system.

The relative biological effectiveness (RBE) of protons is highly variable and difficult to quantify. However, RBE is related to the local ionization density, which can be related to the physical measurable dose weighted linear energy transfer (LET). The aim of this study was to validate the LET calculations for proton therapy beams implemented in a commercially available treatment planning system (TPS) using microdosimetry measurements and independent LET calculations (Open-MCsquare (MCS)).

Electrophysiology and transcriptomics reveal two photoreceptor classes and complex visual integration in .

Among animals with visual processing mechanisms, the leech is a rare example in which all neurons can be identified. However, little is known about its visual system, which is composed of several pigmented head eyes and photosensitive non-pigmented sensilla that are distributed across its entire body. Although several interneurons are known to respond to visual stimuli, their response properties are poorly understood.

Composite minimax robust optimization of VMAT improves target coverage and reduces non-target dose in head and neck cancer patients.

Background And Purpose: To assess the potential of composite minimax robust optimization (CMRO) compared to planning target volume (PTV)-based optimization for head and neck cancer (HNC) patients treated with volumetric modulated arc therapy (VMAT).

Materials And Methods: Ten HNC patients previously treated with a PTV-based VMAT plan were studied. In addition to the PTV-plan a VMAT plan was created with CMRO.

Two-Photon Microscopy with a Double-Wavelength Metasurface Objective Lens.

Two-photon microscopy is a key imaging technique in life sciences due to its superior deep-tissue imaging capabilities. Light-weight and compact two-photon microscopes are of great interest because of their applications for in vivo deep brain imaging. Recently, dielectric metasurfaces have enabled a new category of small and lightweight optical elements, including objective lenses.

Dual-sided Voltage-sensitive Dye Imaging of Leech Ganglia.

In this protocol, we introduce an effective method for voltage-sensitive dye (VSD) loading and imaging of leech ganglia as used in Tomina and Wagenaar (2017). Dissection and dye loading procedures are the most critical steps toward successful whole-ganglion VSD imaging. The former entails the removal of the sheath that covers neurons in the segmental ganglion of the leech, which is required for successful dye loading.

Responses to mechanically and visually cued water waves in the nervous system of the medicinal leech.

Sensitivity to water waves is a key modality by which aquatic predators can detect and localize their prey. For one such predator - the medicinal leech, - behavioral responses to visual and mechanical cues from water waves are well documented. Here, we quantitatively characterized the response patterns of a multisensory interneuron, the S cell, to mechanically and visually cued water waves.