Harmonic Contrast-Enhanced Ultrasound (CEUS) of Kidney Tumors

Nowadays, kidney tumor diagnosis benefits from large and highly accurate imagistic methods. A new imagistic method is contrast-enhanced ultrasound (CEUS) that accurately depicts the circulatory pattern of tumors. In kidney pathology, any mass or even capsular deformation depicted by B mode ultrasound represents an indication for CEUS. The kidney is completely and uniformly vascularized. In cystic tumors, there is a lack of contrast loading. In “impure” cystic masses (Bosnian 3 and 4), CEUS reveals vascularized septa and walls. In malignant tumors, accelerated and heterogeneous loading of contrast agent is observed in arterial phase followed by early, inhomogeneous washout of the contrast agent compared to normal renal parenchyma. In the abscesses, the appearance is the early loading of the walls associated with moderate hyperemia of the normal circulatory bed. This chapter details the CEUS in kidney tumor pathology, emphasizing the accurate information for the circulatory pattern of renal masses. It requires correlations with clinical data and information provided by other imaging explorations to make a final diagnosis

Metabolism

Access to the CNS and delivery of therapeutics across the blood-brain barrier remains a challenge for most treatments of major neurological diseases such as AD or PD. Focused ultrasound represents a potential approach for overcoming these barriers to treating AD and PD and perhaps other neurological diseases. Ultrasound (US) is best known for its imaging capabilities of organs in the periphery, but various arrangements of the transducers producing the acoustic signal allow the energy to be precisely focused (F) within the skull. Using FUS in combination with MRI and contrast agents further enhances accuracy by providing clear information on location. Varying the acoustic power allows FUS to be used in applications ranging from imaging, stimulation of brain circuits, to ablation of tissue. In several transgenic mouse models of AD, the use of FUS with microbubbles reduces plaque load and improves cognition and suggests the need to investigate this technology for plaque removal in AD. In PD, FUS is being explored as a way to non-invasively ablate the brain areas responsible for the tremor and dyskinesia associated with the disease, but has yet to be utilized for non-invasive delivery of putative therapeutics. The FUS approach also greatly increases the range of possible CNS therapeutics as it overcomes the issues of BBB penetration. In this review we discuss how the characteristics and various applications of FUS may advance the therapeutics available for treating or preventing neurodegenerative disorders with an emphasis on treating AD and PD.CC999999/Intramural CDC HHS/United States2019-05-10T00:00:00Z28159329PMC65102416242vault:3213

Untargeted Contrast-Enhanced Ultrasound Versus Contrast-Enhanced Computed Tomography: A Differential Diagnostic Performance (DDP) Study for Kidney Lesions

OBJECTIVES: Histopathology is the ‘gold standard’ for diagnosing renal cell carcinoma but is limited by sample size. Contrast-enhanced ultrasound can differentiate malignant and benign lesions, but the Chinese guidelines on the management of renal cell carcinoma do not include this method. The purpose of this study was to compare the diagnostic parameters of contrast-enhanced ultrasound against those of contrast-enhanced computed tomography for detecting kidney lesions, with histopathology considered the reference standard. METHODS: Patients with suspected kidney lesions from prior grayscale ultrasonography and computed tomography were included in the analysis (n=191). The contrast-enhanced ultrasound, contrast-enhanced computed tomography, and histopathology data were collected and analyzed. A solid, enhanced mass was considered a malignant lesion, and an unenhanced mass or cyst was considered a benign lesion. The Bosniak criteria were used to characterize the lesions. RESULTS: Contrast-enhanced ultrasound and contrast-enhanced computed tomography both detected that 151 patients had malignant tumors and 40 patients had benign tumors. No significant differences in the tumors and their subtypes were reported between contrast-enhanced ultrasound and histopathology (p=0.804). Chromophobe renal cell carcinoma was detected through contrast-enhanced computed tomography (n=1), but no such finding was reported by contrast-enhanced ultrasound. A total of 35 cases of papillary renal cell carcinoma were reported through contrast-enhanced ultrasound while 32 were reported through histopathology. CONCLUSIONS: Contrast-enhanced ultrasound might be safe and as accurate as histopathology in diagnosing kidney lesions, especially renal cell carcinoma. Additionally, this study provides additional information over histopathology and has an excellent safety profile. Level of evidence: III

Diagnostic vascular ultrasonography with the help of color Doppler and contrast-enhanced ultrasonography

The use of ultrasonography and especially of contrast-enhanced ultrasonography (CEUS) in the diagnosis of vascular pathologies before and after interventions has significantly increased over the past years due to the broader availability of modern ultrasound systems with CEUS capabilities and more trained user experience in this imaging modality. For the preinterventional and postinterventional work-up of carotid diseases, duplex ultrasound as well as CEUS have been established as the standard-of-care examination procedures for diagnosis, evaluation, and follow-up. In addition to its use for carotid arterial diseases, ultrasonography has also become the primary modality for the screening of vascular pathologies. This review describes the most common pathologies found in ultrasonography of the carotid arteries, the abdominal aorta, and the femoral arteries

EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound - Part 1: Examination Techniques and Normal Findings (Long version).

Abstract ▼ In October 2014 the European Federation of Societies for Ultrasound in Medicine and Biology formed a Gastrointestinal Ultrasound (GIUS) task force group to promote the use of GIUS in a clinical setting. One of the main objectives of the task force group was to develop clinical recommendations and guidelines for the use of GIUS under the auspices of EFSUMB. The first part, gives an overview of the examination techniques for GIUS recommended by experts in the field. It also presents the current evidence for the interpretation of normal sonoanatomical and physiological features as examined with different ultrasound modalities

Imaging characteristics of intravascular spherical contrast agents for grating-based x-ray dark-field imaging - effects of concentrations, spherical sizes and applied voltage

This study investigates the x-ray scattering characteristics of microsphere particles in x-ray-grating-based interferometric imaging at different concentrations, bubble sizes and tube voltages (kV). Attenuation (ATI), dark-field (DFI) and phase-contrast (PCI) images were acquired. Signal-to-noise (SNR) and contrast-to-noise ratios with water (CNRw) and air as reference (CNRa) were determined. In all modalities, a linear relationship between SNR and microbubbles concentration, respectively, microsphere size was found. A significant gain of SNR was found when varying kV. SNR was significantly higher in DFI and PCI than ATI. The highest gain of SNR was shown at 60kV for all media in ATI and DFI, at 80kV for PCI. SNR for all media was significantly higher compared to air and was slightly lower compared to water. A linear relationship was found between CNRa, CNRw, concentration and size. With increasing concentration and decreasing size, CNRa and CNRw increased in DFI, but decreased in PCI. Best CNRa and CNRw was found at specific combination of kV and concentration/size. Highest average CNRa and CNRw was found for microspheres in ATI and PCI, for microbubbles in DFI. Microspheres are a promising contrast-media for grating-based-interferometry, if kV, microsphere size and concentration are appropriately combined

Diagnostic Workup for Patients with Solid Renal Masses: A Cost-Effectiveness Analysis

Simple Summary There are several benign and malignant types of solid renal masses. For diagnostic and characterization of these masses, a few imaging methods such as magnetic resonance imaging (MRI), computed tomography (CT) or (contrast-enhanced) ultrasound (CEUS) are established in the clinical routine. The aim of our study was to assess the most economical approach for detecting and characterizing these masses. As a result, contrast-enhanced ultrasound turned out to be a cost-effective diagnostic method. Therefore, if available, this method should be considered in the routine. Alternatively, MRI also offers excellent diagnostic accuracy, but it is associated with higher costs. This result may lead to a change in the diagnostic workup of solid renal masses in clinical routine, as contrast-enhanced ultrasound should be considered as an appropriate method for the first analysis compared to CT and MRI. Background: For patients with solid renal masses, a precise differentiation between malignant and benign tumors is crucial for forward treatment management. Even though MRI and CT are often deemed as the gold standard in the diagnosis of solid renal masses, CEUS may also offer very high sensitivity in detection. The aim of this study therefore was to evaluate the effectiveness of CEUS from an economical point of view. Methods: A decision-making model based on a Markov model assessed expenses and utilities (in QALYs) associated with CEUS, MRI and CT. The utilized parameters were acquired from published research. Further, a Monte Carlo simulation-based deterministic sensitivity analysis of utilized variables with 30,000 repetitions was executed. The willingness-to-pay (WTP) is at USD 100,000/QALY. Results: In the baseline, CT caused overall expenses of USD 10,285.58 and an efficacy of 11.95 QALYs, whereas MRI caused overall expenses of USD 7407.70 and an efficacy of 12.25. Further, CEUS caused overall expenses of USD 5539.78, with an efficacy of 12.44. Consequently, CT and MRI were dominated by CEUS, and CEUS remained cost-effective in the sensitivity analyses. Conclusions: CEUS should be considered as a cost-effective imaging strategy for the initial diagnostic workup and assessment of solid renal masses compared to CT and MRI

Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.

Measuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths, OT can interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.Significance: Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg Cancer Res; 78(20); 5980-91. ©2018 AACR

Intracellular signaling in key pathways is induced by treatment with ultrasound and microbubbles in a leukemia cell line, but not in healthy peripheral blood mononuclear cells

Treatment with ultrasound and microbubbles (sonoporation) to enhance therapeutic efficacy in cancer therapy is rapidly expanding, but there is still very little consensus as to why it works. Despite the original assumption that pore formation in the cell membrane is responsible for increased uptake of drugs, the molecular mechanisms behind this phenomenon are largely unknown. We treated cancer cells (MOLM-13) and healthy peripheral blood mononuclear cells (PBMCs) with ultrasound at three acoustic intensities (74, 501, 2079 mW/cm2) ± microbubbles. We subsequently monitored the intracellular response of a number of key signaling pathways using flow cytometry or western blotting 5 min, 30 min and 2 h post-treatment. This was complemented by studies on uptake of a cell impermeable dye (calcein) and investigations of cell viability (cell count, Hoechst staining and colony forming assay). Ultrasound + microbubbles resulted in both early changes (p38 (Arcsinh ratio at high ultrasound + microbubbles: +0.5), ERK1/2 (+0.7), CREB (+1.3), STAT3 (+0.7) and AKT (+0.5)) and late changes (ribosomal protein S6 (Arcsinh ratio at low ultrasound: +0.6) and eIF2α in protein phosphorylation). Observed changes in protein phosphorylation corresponded to changes in sonoporation efficiency and in viability, predominantly in cancer cells. Sonoporation induced protein phosphorylation in healthy cells was pronounced (p38 (+0.03), ERK1/2 (−0.03), CREB (+0.0), STAT3 (−0.1) and AKT (+0.04) and S6 (+0.2)). This supports the hypothesis that sonoporation may enhance therapeutic efficacy of cancer treatment, without causing damage to healthy cells.publishedVersio

Noninvasive Evaluation of Microcirculation under Normal and Pathological Conditions Using Contrast-Enhanced Ultrasonography (CEUS)

The present chapter highlights the most important information about microcirculation and its evaluation using contrast-enhanced ultrasonography (CEUS). In the beginning it outlines some general considerations about microcirculation, together with its morphological and physiological particularities under normal and pathological circumstances. The ultrasonographic (US) evaluation of vascularity is based on the Doppler technique and the harmonic technique using contrast agents. Then it presents briefly the Doppler ultrasound (DUS) and discusses its most important current and emerging indications. CEUS is presented extensively, covering the fundamentals of sonographic contrast agents, harmonic imaging and quantification techniques. A special focus is placed not only on the current and emerging indications of CEUS but also on the advantages and limitations of the method. This chapter also incorporates information about experimental CEUS applications and future perspectives. CEUS is the recommended US method for the characterization of microcirculation. The results of the examination are displayed in real-time, under the eyes of the examiner, while the quantitative assessment of the contrast agent kinetics parameters is easy to perform. This method allows a precise definition of the healthy or pathologic state of an organ and the follow-up of treatment response