Initial Condition Assessment for Reaction-Diffusion Glioma Growth Models: A Translational MRI-Histology (In)Validation Study.

Reaction-diffusion models have been proposed for decades to capture the growth of gliomas. Nevertheless, these models require an initial condition: the tumor cell density distribution over the whole brain at diagnosis time. Several works have proposed to relate this distribution to abnormalities visible on magnetic resonance imaging (MRI). In this work, we verify these hypotheses by stereotactic histological analysis of a non-operated brain with glioblastoma using a 3D-printed slicer. Cell density maps are computed from histological slides using a deep learning approach. The density maps are then registered to a postmortem MR image and related to an MR-derived geodesic distance map to the tumor core. The relation between the edema outlines visible on T2-FLAIR MRI and the distance to the core is also investigated. Our results suggest that (i) the previously proposed exponential decrease of the tumor cell density with the distance to the core is reasonable but (ii) the edema outlines would not correspond to a cell density iso-contour and (iii) the suggested tumor cell density at these outlines is likely overestimated. These findings highlight the limitations of conventional MRI to derive glioma cell density maps and the need for other initialization methods for reaction-diffusion models to be used in clinical practice.

Assessment of cardiac-driven liver movements with filtered harmonic phase image representation, optical flow quantification, and motion amplification.

PURPOSE: To characterize cardiac-driven liver movements using a harmonic phase image representation (HARP) with an optical flow quantification and motion amplification method. The method was applied to define the cardiac trigger delay providing minimal signal losses in liver DWI images. METHODS: The 16-s breath-hold balanced-SSFP time resolved 20 images/s were acquired at 3T in coronal and sagittal orientations. A peripheral pulse unit signal was recorded. Cardiac-triggered DWI images were acquired after different peripheral pulse unit delays. A steerable pyramid decomposition with multiple orientations and spatial frequencies was applied. The liver motion field-map was derived from temporal variations of the HARP representation filtered around the cardiac frequency. Liver displacements were quantified with an optical flow method; moreover the right liver motion was amplified. RESULTS: The largest displacements were observed in the left liver (feet-head:3.70 ± 1.06 mm; anterior-posterior: 2.35 ± 0.51 mm). Displacements were statistically significantly weaker in the middle right liver (0.47 ± 0.11 mm; P = 0.0156). The average error was 0.013 ± 0.022 mm (coronal plane) and 0.021 ± 0.041 mm (sagittal plane). The velocity field demonstrated opposing movements of the right liver extremities during the cardiac cycle. DWI signal loss was minimized in regions and instants of smallest amplitude of both velocity and velocity gradient. CONCLUSION: Cardiac-driven liver movements were quantified with combined cardiac frequency-filtered HARP and optical flow methods. A motion phase opposition between right liver extremities was demonstrated. Displacement amplitude and velocity were larger in the left liver especially along the vertical direction. Motion amplification visually emphasized cardiac-driven right liver displacements. The optimal cardiac timing minimizing signal loss in liver DWI images was derived.

In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy.

The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79% were compatible with the human respirable size range, and this formulation retained 100% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs.