Molecular Detection of Venous Thrombosis in Mouse Models Using SPECT/CT.

The efficacy of thrombolysis is inversely correlated with thrombus age. During early thrombogenesis, activated factor XIII (FXIIIa) cross-links α2-AP to fibrin to protect it from early lysis. This was exploited to develop an α2-AP-based imaging agent to detect early clot formation likely susceptible to thrombolysis treatment.

Inter-observer variability of organ contouring for preclinical studies with cone beam Computed Tomography imaging.

Background And Purpose: In preclinical radiation studies, there is great interest in quantifying the radiation response of healthy tissues. Manual contouring has significant impact on the treatment-planning because of variation introduced by human interpretation. This results in inconsistencies when assessing normal tissue volumes.

Automatic contouring of normal tissues with deep learning for preclinical radiation studies.

Delineation of relevant normal tissues is a bottleneck in image-guided precision radiotherapy workflows for small animals. A deep learning (DL) model for automatic contouring using standardized 3D micro cone-beam CT (CBCT) volumes as input is proposed, to provide a fully automatic, generalizable method for normal tissue contouring in preclinical studies.A 3D U-net was trained to contour organs in the head (whole brain, left/right brain hemisphere, left/right eye) and thorax (complete lungs, left/right lung, heart, spinal cord, thorax bone) regions.

Dose painting by dynamic irradiation delivery on an image-guided small animal radiotherapy platform.

Objective:: Using synchronized three-dimensional stage translation and multiangle radiation delivery to improve conformality and homogeneity of radiation delivery to complexly shaped target volumes for precision preclinical radiotherapy.

Methods:: A CT image of a mouse was used to design irradiation plans to target the spinal cord and an orthotopic lung tumour. A dose painting method is proposed that combines heterogeneous two-dimensional area irradiations from multiple beam directions.

An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms.

Methods:: An orthotopic non-small cell lung cancer model in NMRI-nude mice was established to investigate the complementary information acquired from 80 kVp microcone-beam CT (micro-CBCT) and bioluminescence imaging (BLI) using different angles and filter settings. Different micro-CBCT-based radiation-delivery plans were evaluated based on their dose-volume histogram metrics of tumor and organs at risk to select the optimal treatment plan.

Results:: H1299 cell suspensions injected directly into the lung render exponentially growing single tumor nodules whose CBCT-based volume quantification strongly correlated with BLI-integrated intensity.

Altered protein turnover signaling and myogenesis during impaired recovery of inflammation-induced muscle atrophy in emphysematous mice.

Exacerbations in Chronic obstructive pulmonary disease (COPD) are often accompanied by pulmonary and systemic inflammation, and are associated with an increased susceptibility to weight loss and muscle wasting. As the emphysematous phenotype in COPD appears prone to skeletal muscle wasting, the aims of this study were to evaluate in emphysematous compared to control mice following repetitive exacerbations (1) changes in muscle mass and strength and, (2) whether muscle mass recovery and its underlying processes are impaired. Emphysema was induced by intra-tracheal (IT) elastase instillations, followed by three weekly IT-LPS instillations to mimic repetitive exacerbations.

On the determination of planning target margins due to motion for mice lung tumours using a four-dimensional MOBY phantom.

Objective:: This work aims to analyse the effect of respiratory motion on optimal irradiation margins for murine lung tumour models.

Methods:: Four-dimensional mathematical phantoms with different lung tumour locations affected by respiratory motion were created. Two extreme breathing curves were adopted and divided into time-points.

Automatic multiatlas based organ at risk segmentation in mice.

Objective:: During the treatment planning of a preclinical small animal irradiation, which has time limitations for reasons of animal wellbeing and workflow efficiency, the time consuming organ at risk (OAR) delineation is performed manually. This work aimed to develop, demonstrate, and quantitatively evaluate an automated contouring method for six OARs in a preclinical irritation treatment workflow.

Methods:: Microcone beam CT images of nine healthy mice were contoured with an in-house developed multiatlas-based image segmentation (MABIS) algorithm for six OARs: kidneys, eyes, heart, and brain.

The impact of dual energy CT imaging on dose calculations for pre-clinical studies.

Background: To investigate the feasibility of using dual-energy CT (DECT) for tissue segmentation and kilovolt (kV) dose calculations in pre-clinical studies and assess potential dose calculation accuracy gain.

Methods: Two phantoms and an ex-vivo mouse were scanned in a small animal irradiator with two distinct energies. Tissue segmentation was performed with the single-energy CT (SECT) and DECT methods.

Differential regulation of muscle protein turnover in response to emphysema and acute pulmonary inflammation.

Background: Exacerbations in COPD are often accompanied by pulmonary and systemic inflammation, and associated with increased susceptibility to and prevalence of weight loss and muscle wasting. Muscle mass loss during disease exacerbations may contribute to emphysema-associated muscle atrophy. However, whether pulmonary inflammation in presence of emphysema differentially affects skeletal muscle, including protein synthesis and degradation signaling pathways has not previously been addressed.

Optimizing dual energy cone beam CT protocols for preclinical imaging and radiation research.

Objective: The aim of this work was to investigate whether quantitative dual-energy CT (DECT) imaging is feasible for small animal irradiators with an integrated cone-beam CT (CBCT) system.

Methods: The optimal imaging protocols were determined by analyzing different energy combinations and dose levels. The influence of beam hardening effects and the performance of a beam hardening correction (BHC) were investigated.

The influence of respiratory motion on dose delivery in a mouse lung tumour irradiation using the 4D MOBY phantom.

Objective: During precision irradiation of a preclinical lung tumour model, the tumour is subject to breathing motion and it can partially move out of the irradiation field. This work aimed to perform a quantitative analysis of the impact of respiratory motion on a mouse lung tumour irradiation with small fields.

Methods: A four-dimensional digital mouse whole body phantom (MOBY) with a virtual 4-mm spherical lung tumour at different locations in both lungs is used to simulate a breathing anaesthetized mouse in different breathing phases representing a full breathing cycle.

NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation resistance and intrinsic or acquired TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC).

An image guided small animal radiation therapy platform (SmART) to monitor glioblastoma progression and therapy response.

Background And Purpose: Glioblastoma multiforme is the most common malignant brain tumor. Standard treatment including surgery, radiotherapy and chemotherapy with temozolomide is not curative. There is a great need for in vitro and in vivo models closely mimicking clinical practice to ensure better translation of novel preclinical findings.

A framework for inverse planning of beam-on times for 3D small animal radiotherapy using interactive multi-objective optimisation.

Advances in precision small animal radiotherapy hardware enable the delivery of increasingly complicated dose distributions on the millimeter scale. Manual creation and evaluation of treatment plans becomes difficult or even infeasible with an increasing number of degrees of freedom for dose delivery and available image data. The goal of this work is to develop an optimisation model that determines beam-on times for a given beam configuration, and to assess the feasibility and benefits of an automated treatment planning system for small animal radiotherapy.

A longitudinal evaluation of partial lung irradiation in mice by using a dedicated image-guided small animal irradiator.

Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging.

Development and validation of a treatment planning system for small animal radiotherapy: SmART-Plan.

Background And Purpose: Image-guided equipment for precision irradiation of small animals for pre-clinical radiotherapy research became recently available. To enable downscaled radiotherapy studies that can be translated into human radiotherapy knowledge, a treatment planning system for pre-clinical studies is required.

Material And Methods: A dedicated treatment planning system (SmART-Plan) for small animal radiotherapy studies was developed.

Evaluation of a novel triple-channel radiochromic film analysis procedure using EBT2.

A novel approach to read out radiochromic film was introduced recently by the manufacturer of GafChromic film. In this study, the performance of this triple-channel film dosimetry method was compared against the conventional single-red-channel film dosimetry procedure, with and without inclusion of a pre-irradiation (pre-IR) film scan, using EBT2 film and kilo- and megavoltage photon beams up to 10 Gy. When considering regions of interest averaged doses, the triple-channel method and both single-channel methods produced equivalent results.