Super-Resolution Ultrasound Imaging for Monitoring the Therapeutic Efficacy of a Vascular Disrupting Agent in an Animal Model of Breast Cancer.

Objective: Evaluate the use of super-resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular-disrupting agent (VDA).

Methods: A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA-MB-231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein.

Critical Advances for Democratizing Ultrasound Diagnostics in Human and Veterinary Medicine.

The democratization of ultrasound imaging refers to the process of making ultrasound technology more accessible. Traditionally, ultrasound imaging has been predominately used in specialized medical facilities by trained professionals. Advancements in technology and changes in the health-care landscape have inspired efforts to broaden the availability of ultrasound imaging to various settings such as remote and resource-limited areas.

A single photodynamic priming protocol augments delivery of ⍺-PD-L1 mAbs and induces immunogenic cell death in head and neck tumors.

Photodynamic priming (PDP) leverages the photobiological effects of subtherapeutic photodynamic therapy (PDT) regimens to modulate the tumor vasculature and stroma. PDP also sensitizes tumors to secondary therapies, such as immunotherapy by inducing a cascade of molecular events, including immunogenic cell death (ICD). We and others have shown that PDP improves the delivery of antibodies, among other theranostic agents.

Endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle.

The estrogen receptor (ER) designated ERα has actions in many cell and tissue types that impact glucose homeostasis. It is unknown if these include mechanisms in endothelial cells, which have the potential to influence relative obesity, and processes in adipose tissue and skeletal muscle that impact glucose control. Here we show that independent of impact on events in adipose tissue, endothelial ERα promotes glucose tolerance by enhancing endothelial insulin transport to skeletal muscle.

Optical blood-brain-tumor barrier modulation expands therapeutic options for glioblastoma treatment.

The treatment of glioblastoma has limited clinical progress over the past decade, partly due to the lack of effective drug delivery strategies across the blood-brain-tumor barrier. Moreover, discrepancies between preclinical and clinical outcomes demand a reliable translational platform that can precisely recapitulate the characteristics of human glioblastoma. Here we analyze the intratumoral blood-brain-tumor barrier heterogeneity in human glioblastoma and characterize two genetically engineered models in female mice that recapitulate two important glioma phenotypes, including the diffusely infiltrative tumor margin and angiogenic core.

Multiparametric ultrasound imaging for early-stage steatosis: Comparison with magnetic resonance imaging-based proton density fat fraction.

Background: The prevalence of liver diseases, especially steatosis, requires a more convenient and noninvasive tool for liver diagnosis, which can be a surrogate for the gold standard biopsy. Magnetic resonance (MR) measurement offers potential, however ultrasound (US) has better accessibility than MR.

Purpose: This study aims to suggest a multiparametric US approach which demonstrates better quantification and imaging performance than MR imaging-based proton density fat fraction (MRI-PDFF) for hepatic steatosis assessment.

Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model.

Tumors become inoperable due to their size or location, making neoadjuvant chemotherapy the primary treatment. However, target tissue accumulation of anticancer agents is limited by the physical barriers of the tumor microenvironment. Low-intensity focused ultrasound (FUS) in combination with microbubble (MB) contrast agents can increase microvascular permeability and improve drug delivery to the target tissue after systemic administration.

Simultaneous imaging of ultrasonic relative backscatter and attenuation coefficients for quantitative liver steatosis assessment.

Prevalence of liver disease is continuously increasing and nonalcoholic fatty liver disease (NAFLD) is the most common etiology. We present an approach to detect the progression of liver steatosis based on quantitative ultrasound (QUS) imaging. This study was performed on a group of 55 rats that were subjected to a control or methionine and choline deficient (MCD) diet known to induce NAFLD.

Assessment of Transarterial Chemoembolization Using Super-resolution Ultrasound Imaging and a Rat Model of Hepatocellular Carcinoma.

Objective: Hepatocellular carcinoma (HCC) is a highly prevalent form of liver cancer diagnosed annually in 600,000 people worldwide. A common treatment is transarterial chemoembolization (TACE), which interrupts the blood supply of oxygen and nutrients to the tumor mass. The need for repeat TACE treatments may be assessed in the weeks after therapy with contrast-enhanced ultrasound (CEUS) imaging.

High-Resolution Ultrasound Characterization of Local Scattering in Cancer Tissue.

Ultrasound (US) has afforded an approach to tissue characterization for more than a decade. The challenge is to reveal hidden patterns in the US data that describe tissue function and pathology that cannot be seen in conventional US images. Our group has developed a high-resolution analysis technique for tissue characterization termed H-scan US, an imaging method used to interpret the relative size of acoustic scatterers.

Generalized mathematical framework for contrast-enhanced ultrasound imaging with pulse inversion spectral deconvolution.

A generalized mathematical framework for performing contrast-enhanced ultrasound (CEUS) imaging is introduced. Termed pulse inversion spectral deconvolution (PISD), this CEUS approach is founded on Gaussian derivative functions (GDFs). PISD pulses are used to form two inverted pulse sequences, which are then used to filter backscattered ultrasound (US) data for isolation of the nonlinear (NL) microbubble (MB) signal component.

Towards Photodynamic Image-Guided Surgery of Head and Neck Tumors: Photodynamic Priming Improves Delivery and Diagnostic Accuracy of Cetuximab-IRDye800CW.

Fluorescence image-guided surgery (IGS) using antibody conjugates of the fluorophore IRDye800CW have revolutionized the surgical debulking of tumors. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, conjugated to IRDye800CW (Cet-IRDye800) is the first molecular targeted antibody probe to be used for IGS in head and neck cancer patients. In addition to surgical debulking, Cetuximab-targeted photodynamic therapy (photoimmunotherapy; PIT) is emerging in the clinic as a powerful modality for head and neck tumor photodestruction.

Photoacoustic graphic equalization and application in characterization of red blood cell aggregates.

A photoacoustic (PA) graphic equalization (PAGE) algorithm was developed to characterize the relative size of optical absorbing aggregates. This technique divides the PA signal into frequency bands related to different-sized optical absorbers. Simulations of a material containing optical absorbing microparticles of varying size were used to assess PAGE performance.

Disease-Specific Imaging Utilizing Support Vector Machine Classification of H-Scan Parameters: Assessment of Steatosis in a Rat Model.

In medical imaging, quantitative measurements have shown promise in identifying diseases by classifying normal versus pathological parameters from tissues. The support vector machine (SVM) has shown promise as a supervised classification algorithm and has been widely used. However, the classification results typically identify a category of abnormal tissues but do not necessarily differentiate progressive stages of a disease.

Three-Dimensional H-Scan Ultrasound Imaging of Early Breast Cancer Response to Neoadjuvant Therapy in a Murine Model.

Objectives: Three-dimensional (3D) H-scan is a new ultrasound (US) technique that images the relative size of acoustic scatterers. The goal of this research was to evaluate use of 3D H-scan US imaging for monitoring early breast cancer response to neoadjuvant therapy using a preclinical murine model of breast cancer.

Materials And Methods: Preclinical studies were conducted using luciferase-positive breast cancer-bearing mice (n = 40).

Multiscale computational modeling of cancer growth using features derived from microCT images.

Advances in medical imaging technologies now allow noninvasive image acquisition from individual patients at high spatiotemporal resolutions. A relatively new effort of predictive oncology is to develop a paradigm for forecasting the future status of an individual tumor given initial conditions and an appropriate mathematical model. The objective of this study was to introduce a comprehensive multiscale computational method to predict cancer and microvascular network growth patterns.

Intercellular Arc Signaling Regulates Vasodilation.

Injury responses require communication between different cell types in the skin. Sensory neurons contribute to inflammation and can secrete signaling molecules that affect non-neuronal cells. Despite the pervasive role of translational regulation in nociception, the contribution of activity-dependent protein synthesis to inflammation is not well understood.

Evaluation of Nonlinear Contrast Pulse Sequencing for Use in Super-Resolution Ultrasound Imaging.

The use of super-resolution ultrasound (SR-US) imaging greatly improves visualization of microvascular structures, but clinical adoption is limited by long imaging times. This method depends on detecting and localizing isolated microbubbles (MBs), forcing the use of a dilute contrast agent concentration. Contrast-enhanced ultrasound (CEUS) image acquisition times as long as minutes arise as the localization of thousands of MBs are acquired to form a complete SR-US image.