Volumetric and Simultaneous Photoacoustic and Ultrasound Imaging With a Conventional Linear Array in a Multiview Scanning Scheme.

Volumetric, multimodal imaging with precise spatial and temporal coregistration can provide valuable and complementary information for diagnosis and monitoring. Considerable research has sought to combine 3-D photoacoustic (PA) and ultrasound (US) imaging in clinically translatable configurations; however, technical compromises currently result in poor image quality either for PA or ultrasonic modes. This work aims to provide translatable, high-quality, simultaneously coregistered dual-mode PA/US 3-D tomography.

Non-Invasive Ultrasonic Description of Tumor Evolution.

Purpose: There is a clinical need to better non-invasively characterize the tumor microenvironment in order to reveal evidence of early tumor response to therapy and to better understand therapeutic response. The goals of this work are first to compare the sensitivity to modifications occurring during tumor growth for measurements of tumor volume, immunohistochemistry parameters, and emerging ultrasound parameters (Shear Wave Elastography (SWE) and dynamic Contrast-Enhanced Ultrasound (CEUS)), and secondly, to study the link between the different parameters.

Methods: Five different groups of 9 to 10 BALB/c female mice with subcutaneous CT26 tumors were imaged using B-mode morphological imaging, SWE, and CEUS at different dates.

Monitoring Dual VEGF Inhibition in Human Pancreatic Tumor Xenografts With Dynamic Contrast-Enhanced Ultrasound.

Background: Association of drugs acting against different antiangiogenic mechanisms may increase therapeutic effect and reduce resistance. Noninvasive monitoring of changes in the antiangiogenic response of individual tumors could guide selection and administration of drug combinations. Noninvasive detection of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway was investigated in an ectopic subcutaneous xenograft model for human pancreatic tumor.

3-D Longitudinal Imaging of Tumor Angiogenesis in Mice in Vivo Using Ultrafast Doppler Tomography.

Angiogenesis, the formation of new vessels, is one of the key mechanisms in tumor development and an appealing target for therapy. Non-invasive, high-resolution, high-sensitivity, quantitative 3-D imaging techniques are required to correctly depict tumor heterogeneous vasculature over time. Ultrafast Doppler was recently introduced and provides an unprecedented combination of resolution, penetration depth and sensitivity without requiring any contrast agents.

In Vivo Multiparametric Ultrasound Imaging of Structural and Functional Tumor Modifications during Therapy.

Longitudinal imaging techniques are needed that can meaningfully probe the tumor microenvironment and its spatial heterogeneity. Contrast-enhanced ultrasound, shear wave elastography and quantitative ultrasound are ultrasound-based techniques that provide information on the vascular function and micro-/macroscopic tissue structure. Modifications of the tumor microenvironment induced by cytotoxic and anti-angiogenic molecules in ectopic murine Lewis lung carcinoma tumors were monitored.

Local Transverse-Slice-Based Level-Set Method for Segmentation of 3-D High-Frequency Ultrasonic Backscatter From Dissected Human Lymph Nodes.

Objective: To detect metastases in freshly excised human lymph nodes (LNs) using three-dimensional (3-D), high-frequency, quantitative ultrasound (QUS) methods, the LN parenchyma (LNP) must be segmented to preclude QUS analysis of data in regions outside the LNP and to compensate ultrasound attenuation effects due to overlying layers of LNP and residual perinodal fat (PNF).

Methods: After restoring the saturated radio-frequency signals from PNF using an approach based on smoothing cubic splines, the three regions, i.e.

Quantification of tumor perfusion using dynamic contrast-enhanced ultrasound: impact of mathematical modeling.

Dynamic contrast-enhanced ultrasound has been proposed to monitor tumor therapy, as a complement to volume measurements. To assess the variability of perfusion parameters in ideal conditions, four consecutive test-retest studies were acquired in a mouse tumor model, using controlled injections. The impact of mathematical modeling on parameter variability was then investigated.

Imaging Reactive Oxygen Species-Induced Modifications in Living Systems.

Significance: Reactive Oxygen Species (ROS) may regulate signaling, ion channels, transcription factors, and biosynthetic processes. ROS-related diseases can be due to either a shortage or an excess of ROS.

Recent Advances: Since the biological activity of ROS depends on not only concentration but also spatiotemporal distribution, real-time imaging of ROS, possibly in vivo, has become a need for scientists, with potential for clinical translation.

Reproducibility of Contrast-Enhanced Ultrasound in Mice with Controlled Injection.

Purpose: Sensitivity of contrast-enhanced ultrasound (CEUS) to microvascular flow modifications can be limited by intra-injection variability (injected dose, rate, volume).

Procedures: To evaluate the effect of injection variability on microvascular flow evaluation, CEUS was compared between controlled and manual injections where enhancement was assessed in vitro within a flow phantom, in normal murine kidney (N = 12) and in murine ectopic tumors (N = 10).

Results: For both in vitro and in vivo measurements in the renal cortex, controlled injections significantly improved reproducibility of functional parameter estimation.

VEGFR2-Targeted Contrast-Enhanced Ultrasound to Distinguish between Two Anti-Angiogenic Treatments.

The aim of this study was to evaluate the capacity of BR55, an ultrasound contrast agent specifically targeting vascular endothelial growth factor receptor 2 (VEGFR2), to distinguish the specific anti-VEGFR2 therapy effect of sunitinib from other anti-angiogenic effects of a therapy (imatinib) that does not directly inhibit VEGFR2. Sunitinib, imatinib and placebo were administered daily for 11 d (264 h) to 45 BalbC mice bearing ectopic CT26 murine colorectal carcinomas. During the course of therapy, B-mode ultrasound, contrast-enhanced ultrasound and VEGFR2-targeted contrast-enhanced ultrasound were performed to assess tumor morphology, vascularization and VEGFR2 expression, respectively.

Automatic motion estimation using flow parameters for dynamic contrast-enhanced ultrasound.

Dynamic contrast-enhanced ultrasound (DCE-US) sequences are subject to motion which can disturb functional flow quantification. This can make estimated parameters more variable or unreliable. Methods that compensate for motion are therefore desirable.

Modeling the envelope statistics of three-dimensional high-frequency ultrasound echo signals from dissected human lymph nodes.

This work investigates the statistics of the envelope of three-dimensional (3D) high-frequency ultrasound (HFU) data acquired from dissected human lymph nodes (LNs). Nine distributions were employed, and their parameters were estimated using the method of moments. The Kolmogorov Smirnov (KS) metric was used to quantitatively compare the fit of each candidate distribution to the experimental envelope distribution.

Dual-mode registration of dynamic contrast-enhanced ultrasound combining tissue and contrast sequences.

This study proposes a new method for automatic, iterative image registration in the context of dynamic contrast-enhanced ultrasound (DCE-US) imaging. By constructing a cost function of image registration using a combination of the tissue and contrast-microbubble responses, this new method, referred to as dual-mode registration, performs alignment based on both tissue and vascular structures. Data from five focal liver lesions (FLLs) were used for the evaluation.

High-frequency (20 to 40 MHz) acoustic response of liquid-filled nanocapsules.

Liquid-core nanoparticles are promising candidates for targeted ultrasound-controlled therapy, but their acoustic detection remains challenging. High-frequency (20 to 40 MHz) tone burst sequences were implemented with a programmable ultrasound biomicroscope to characterize acoustic response from perfluorooctyl bromide-core nanoparticles with thick poly(lactide-coglycolide) (PLGA) shells. Radio-frequency signals were acquired from flowing solutions of nanoparticles with two different shell-thickness-to-particle-radius ratios, solid PLGA nanoparticles, and latex nanobeads (linear controls).

A multiplicative model for improving microvascular flow estimation in dynamic contrast-enhanced ultrasound (DCE-US): theory and experimental validation.

Perfusion parameter estimation from dynamic contrast-enhanced ultrasound (DCE-US) data relies on fitting parametric models of flow to curves describing linear echo power as a function of time. The least squares criterion is generally used to fit these models to data. This criterion is optimal in the sense of maximum likelihood under the assumption of an additive white Gaussian noise.

Echo-power estimation from log-compressed video data in dynamic contrast-enhanced ultrasound imaging.

Ultrasound (US) scanners typically apply lossy, non-linear modifications to the US data for visualization purposes. The resulting images are then stored as compressed video data. Some system manufacturers provide dedicated software for quantification purposes to eliminate such processing distortions, at least partially.

Fast in vivo imaging of amyloid plaques using μ-MRI Gd-staining combined with ultrasound-induced blood-brain barrier opening.

Amyloid plaques are one of the major microscopic lesions that characterize Alzheimer's disease. Current approaches to detect amyloid plaques by using magnetic resonance imaging (MRI) contrast agents require invasive procedures to penetrate the blood-brain barrier (BBB) and to deliver the contrast agent into the vicinity of amyloid plaques. Here we have developed a new protocol (US-Gd-staining) that enables the detection of amyloid plaques in the brain of an APP/PS1 transgenic mouse model of amyloidosis after intra-venous injection of a non-targeted, clinically approved MRI contrast agent (Gd-DOTA, Dotarem®) by transiently opening the BBB with unfocused ultrasound (1 MHz) and clinically approved microbubbles (Sonovue®, Bracco).

Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation.

Objective: To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE).

Methods: In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour.

Correlation and agreement between contrast-enhanced ultrasonography and perfusion computed tomography for assessment of liver metastases from endocrine tumors: normalization enhances correlation.

We studied correlation and agreement between perfusion parameters derived from contrast-enhanced ultrasonography (CEUS) and computed tomography (CT). Both techniques were performed in 16 patients with proven liver metastases from endocrine tumor. Replenishment study after ultrasound-induced destruction of microbubbles was used for CEUS quantification.

RANKL induces organized lymph node growth by stromal cell proliferation.

RANK and its ligand RANKL play important roles in the development and regulation of the immune system. We show that mice transgenic for Rank in hair follicles display massive postnatal growth of skin-draining lymph nodes. The proportions of hematopoietic and nonhematopoietic stromal cells and their organization are maintained, with the exception of an increase in B cell follicles.

Noninvasive contrast-enhanced US quantitative assessment of tumor microcirculation in a murine model: effect of discontinuing anti-VEGF therapy.

Purpose: To determine, by using contrast material-enhanced ultrasonography (US), how quickly renal tumors grafted in mice begin to revascularize after stopping bevacizumab treatment.

Materials And Methods: All experiments were approved by the regional ethics committee. A human tumor cell line SK-NEP-1 was grafted at day 0 in the left kidney of 50 nude mice.

Real-time chirp-coded imaging with a programmable ultrasound biomicroscope.

Ultrasound biomicroscopy (UBM) of mice can provide a testing ground for new imaging strategies. The UBM system presented in this paper facilitates the development of imaging and measurement methods with programmable design, arbitrary waveform coding, broad bandwidth (2-80 MHz), digital filtering, programmable processing, RF data acquisition, multithread/multicore real-time display, and rapid mechanical scanning ( View Article and Find Full Text PDF

Clinical relevance of contrast-enhanced ultrasound in monitoring anti-angiogenic therapy of cancer: current status and perspectives.

Angiogenesis regulation is one of the newest fronts in the fight against cancer. Anti-angiogenic therapy is based on inhibiting factors required to solicit vessel formation thus cutting-off the tumor's supply of nutriments and oxygen. Initial vascular response is followed by formation of necrosis.

Ultrasound biomicroscopy: a powerful tool probing murine lymph node size in vivo.

Invasive cell-counting in lymph node (LN) is the current reference to assess LN changes due to inflammation, immunodeficiency and cancer in murine models. This work evaluates whether ultrasound biomicroscopy (UBM) can measure LN size alterations noninvasively for a large range of sizes (0.1 mm3 to 22 mm3).

Ultrasonic backscatter and attenuation (11-27 MHz) variation with collagen fiber distribution in ex vivo human dermis.

This ex vivo study explores the relationship of ultrasonic attenuation and backscatter to dermal microarchitecture by comparing ultrasonic measurements of these parameters (11-27 MHz) to a microscopic analysis of three parameters describing the collagen distribution (mean thickness and spacing of collagen bundles along the insonification direction and the percent area occupied by collagen). Skin samples (N= 31) were obtained from patients undergoing breast or abdominal reduction surgery. Radio-frequency (rf) signals were acquired in a B-scan format using an ultrasound system developed for skin imaging (Ultrasons Technologies, Tours, France).