A better understanding of ultrasound transmission through human skull is fundamental to develop optimal imaging and therapeutic applications. In this study, we present global attenuation values and functions that correlate apparent density calculated from computed tomography (CT) scans to shear speed of sound. For this purpose, we used a model for sound propagation based on the viscoelastic wave equation (VWE) assuming isotropic conditions. The model was validated using a series of measurements with plates of different plastic materials and angles of incidence of 0°, 15° and 50°. The optimal functions for transcranial ultrasound propagation were established using the VWE, scan measurements of transcranial propagation with an angle of incidence of 40° and a genetic optimization algorithm. Ten (10) locations over three (3) skulls were used for ultrasound frequencies of 270 kHz and 836 kHz. Results with plastic materials demonstrated that the viscoelastic modeling predicted both longitudinal and shear propagation with an average (± s.d.) error of 9(±7)% of the wavelength in the predicted delay and an error of 6.7(±5)% in the estimation of transmitted power. Using the new optimal functions of speed of sound and global attenuation for the human skull, the proposed model predicted the transcranial ultrasound transmission for a frequency of 270 kHz with an expected error in the predicted delay of 5(±2.7)% of the wavelength. The sound propagation model predicted accurately sound propagation regardless either shear or longitudinal sound transmission dominated. For 836 kHz, the model predicted accurately in average with an error in the predicted delay of 17(±16)% of the wavelength. Results indicated the high importance of the specificity of the information at a voxel level to better understand ultrasound transmission through the skull. These results and new model will be very valuable tools for the future development of transcranial applications of ultrasound therapy and imaging.

Finite-difference time domain (FDTD) techniques are widely used to model the propagation of viscoelastic waves through complex and heterogeneous structures. However, in the specific case of media mixing liquid and solid, attempts to model continuous media onto a Cartesian grid produces errors when the liquid-solid interface between different media do not align precisely with the Cartesian grid. The increase in spatial resolution required to eliminate this grid staircasing effect can be computationally prohibitive. Here, a modification to the Virieux staggered-grid FDTD scheme called the superposition method is presented. This method is intended to reduce this staircasing effect while keeping a manageable computational time. The method was validated by comparing low-spatial-resolution simulations against simulations with sufficiently high resolution to provide reasonably accurate results at any incident angle. The comparison of the root-mean-square of the stress amplitude maps showed that the amplitude of artifactual waves could be reduced by several orders of magnitude when compared to the Virieux staggered-grid FDTD method and that the superposition method helped to significantly reduce the staircasing effect in FDTD simulations.

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment (TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy - most commonly using a local high single dose - are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.

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Pancreatic ductal adenocarcinoma (PDAC) diagnosis accompanies a somber prognosis for the patient, with dismal survival odds: 5% at 5 years. Despite extensive research, PDAC is expected to become the second leading cause of mortality by cancer by 2030. Ultrasound (US) has been used successfully in treating other types of cancer and evidence is flourishing that it could benefit PDAC patients. High-intensity focused US (HIFU) is currently used for pain management in palliative care. In addition, clinical work is being performed to use US to downstage borderline resectable tumors and increase the proportion of patients eligible for surgical ablation. Focused US (FUS) can also induce mechanical effects, which may elicit an anti-tumor response through disruption of the stroma and can be used for targeted drug delivery. More recently, sonodynamic therapy (akin to photodynamic therapy) and immunomodulation have brought new perspectives in treating PDAC. The aim of this review is to summarize the current state of those techniques and share our opinion on their future and challenges.