Ultrasound-guided hepatic portal vein injection is not a reproducible technique for delivery of cell therapies to the liver in mice.

AIMS: Our aim was to determine if ultrasound-guided HPV injection in mice would provide reproducible and reliable results, as is currently obtained via open laparotomy techniques, and offer a surgical refinement to emulate islet transplantation in humans. METHODS: Fluorescent-polymer microparticles (20 µm) were injected (27G-needle) into the HPV via open laparotomy (n = 4) or under ultrasound-guidance (n = 4) using an MX550D-transducer with a Vevo3100-scanner (FUJIFILM VisualSonics, Inc.). Mice were culled 24-h post injection; organs were frozen, step sectioned (10 µm-slices) and 10 sections/mouse (50 µm-spacing) were quantified for microparticles in the liver and other organs by fluorescent microscopy. RESULTS: Murine HPV injection, via open laparotomy-route, resulted in widespread distribution of microparticles in the liver, lungs and spleen; ultrasound-guided injection resulted in reduced microparticle delivery (p < 0.0001) and microparticle clustering in distinct areas of the liver at the site of needle penetration, with very few/no microparticles being seen in lung and spleen tissues, hypothesised to be due to flow into the body cavity: liver median (interquartile range) 4.15 (0.00-4.15) versus 0.00 (0.00-0.00) particle-count mm-2 , respectively. CONCLUSIONS: Ultrasound-guided injection results in microparticle clustering in the liver, with an overall reduction in microparticle number when compared to open laparotomy HPV injection, and high variability in microparticle-counts detected between mice. Ultrasound-guided injection is not currently a technique that can replace open laparotomy HPV of islet transplantation in mice.

Best Practice Recommendations for the Safe use of Lung Ultrasound.

The safety of ultrasound is of particular importance when examining the lungs, due to specific bioeffects occurring at the alveolar air-tissue interface. Lung is significantly more sensitive than solid tissue to mechanical stress. The causal biological effects due to the total reflection of sound waves have also not been investigated comprehensively.On the other hand, the clinical benefit of lung ultrasound is outstanding. It has gained considerable importance during the pandemic, showing comparable diagnostic value with other radiological imaging modalities.Therefore, based on currently available literature, this work aims to determine possible effects caused by ultrasound on the lung parenchyma and evaluate existing recommendations for acoustic output power limits when performing lung sonography.This work recommends a stepwise approach to obtain clinically relevant images while ensuring lung ultrasound safety. A special focus was set on the safety of new ultrasound modalities, which had not yet been introduced at the time of previous recommendations.Finally, necessary research and training steps are recommended in order to close knowledge gaps in the field of lung ultrasound safety in the future.These recommendations for practice were prepared by ECMUS, the safety committee of the EFSUMB, with participation of international experts in the field of lung sonography and ultrasound bioeffects.

The Imaging Performance of Diagnostic Ultrasound Scanners Using the Edinburgh Pipe Phantom to Measure the Resolution Integral - 15 Years of Experience.

The grayscale imaging performance of a total of 368 different scanner/transducer combinations from 39 scanner manufacturers measured over a period of 15 years is presented. Performance was measured using the resolution integral, a single figure-of-merit to quantify ultrasound imaging performance. The resolution integral was measured using the Edinburgh Pipe Phantom. Transducers included single element, linear, phased, curvilinear and multi-row arrays. Our results demonstrate that the resolution integral clearly differentiates between transducers with varying levels of performance. Two further parameters were also derived from the resolution integral: characteristic resolution and depth of field. We demonstrate that these two parameters can successfully characterize individual transducer performance and differentiate between transducers designed for different clinical and preclinical applications. In conclusion, the resolution integral is an effective metric to quantify and monitor grayscale imaging performance in clinical practice.

Safety Aspects of Perinatal Ultrasound.

Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable. The perinatal period is probably less vulnerable than the first and second trimesters of pregnancy, and ultrasound is often a safer alternative to other diagnostic imaging modalities. Here we present step-by-step procedures for obtaining clinically relevant images while maintaining ultrasound safety. We briefly discuss the current status of the field of ultrasound safety, with special attention to the safety of novel modalities, safety considerations when ultrasound is employed for research and education, and ultrasound of particularly vulnerable tissues, such as the neonatal lung. This CME is prepared by ECMUS, the safety committee of EFSUMB, with contributions from OB/GYN clinicians with a special interest in ultrasound safety.

EFSUMB Clinical Safety Statement for Diagnostic Ultrasound - (2019 revision).

This document is the updated 2019 revision of the EFSUMB Clinically Safety Statement. A Safety Statement has been published by EFSUMB annually since 1994 by the Safety Committee (ECMUS) of the federation. The text is deliberately brief and gives a concise overview of safety in the use of diagnostic ultrasound.

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11ß-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11ß-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.

Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial.

BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension. METHODS AND FINDINGS: To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 µg/kg/d and then 60 min at 30 µg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT/eNOS/NO signaling pathway in the kidney. In the randomized clinical study, infusion of serelaxin for 120 min increased total renal arterial blood flow by 65% (95% CI 40%, 95%; p < 0.001) from baseline. Administration of serelaxin was safe and well tolerated, with no detrimental effect on systemic blood pressure or hepatic perfusion. The clinical study's main limitations were the relatively small sample size and stable, well-compensated population. CONCLUSIONS: Our mechanistic findings in rat models and exploratory study in human cirrhosis suggest the therapeutic potential of selective renal vasodilation using serelaxin as a new treatment for renal dysfunction in cirrhosis, although further validation in patients with more advanced cirrhosis and renal dysfunction is required. TRIAL REGISTRATION: ClinicalTrials.gov NCT01640964.

Ultrasound-guided intrauterine injection of lipopolysaccharide as a novel model of preterm birth in the mouse.

Mouse models are used to study mechanisms that link intrauterine infection and preterm birth (PTB). To mimic intrauterine infection, lipopolysaccharide (LPS) is commonly injected into the uterus via minilaparotomy, which is invasive, and can cause PTB in control animals. We hypothesized that less-invasive ultrasound-guided intrauterine LPS injection or intravaginal LPS administration could induce PTB by stimulating an inflammatory response of the uteroplacental tissues, while minimizing PTB in control animals. On day 17 of gestation mice received LPS intravaginally (10 to 240 µg; n = 3 to 8) or into the uterus (20 µg) under ultrasound guidance (n = 7) or via laparotomy (n = 7). Control animals received phosphate-buffered saline (PBS; n = 5 to 7). Intrauterine administration of LPS, both under ultrasound guidance and via laparotomy, induced delivery earlier than in PBS control groups (P < 0.01). Intravaginal LPS administration did not stimulate PTB. Quantitative real-time PCR and immunohistochemistry of tissues harvested 6 hours after treatment confirmed that ultrasound-guided LPS administration induced a localized inflammatory response. Ultrasound-guided intrauterine LPS injection reliably induces PTB in the mouse and mimics the local inflammatory and immune responses observed in the more-invasive laparotomy model of inflammation-induced PTB. Ultrasound-guided intrauterine LPS injection is a useful novel model of PTB for future studies and concords with the principles of reduction, replacement, and refinement.

Focused ultrasound as a non-invasive intervention for neurological disease: a review.

Focused ultrasound (FUS) is an incision-less intervention that is a Food and Drug Association (FDA) approved surgical treatment for various pathologies including uterine fibroids and bone metastases. Recent advances in magnetic resonance imaging thermometry and ability to use FUS across the intact calvarium have re-opened interest in the use of FUS in the treatment of neurological diseases. FUS currently has a European CE mark for use in movement disorders. However, it shows potential in the treatment of other neuropathologies including tumours and as a lesional tool in epilepsy. FUS may exert its therapeutic effect through thermal or mechanical fragmentation of intracranial lesions, or by enhancing delivery of pharmaceutical agents across the blood-brain barrier. In this review, we summarise the mechanisms, clinical applications and potential future of FUS for the treatment of neurological disease. We have searched for and described the recently completed and on-going clinical trials investigating FUS for the treatment of neurological disorders. We identified phase one trials investigating utility of FUS in: movement disorders (including essential tremor and Parkinson's disease), chronic pain, obsessive-compulsive disorder and cerebral tumours. Current literature also reports pre-clinical work exploring utility in epilepsy, neurodegenerative conditions (such as Alzheimer's disease) and thrombolysis. Safety and early efficacy data are now emerging, suggesting that transcalvarial FUS is a feasible and safe intervention. Further evidence is required to determine whether FUS is an effective alternative in comparison to current neurosurgical interventions. The cost of requisite hardware is currently a barrier to widespread uptake in UK neurosurgical centres.

Glucocorticoid receptor is required for foetal heart maturation.

Glucocorticoids are vital for the structural and functional maturation of foetal organs, yet excessive foetal exposure is detrimental to adult cardiovascular health. To elucidate the role of glucocorticoid signalling in late-gestation cardiovascular maturation, we have generated mice with conditional disruption of glucocorticoid receptor (GR) in cardiomyocytes and vascular smooth muscle cells using smooth muscle protein 22-driven Cre recombinase (SMGRKO mice) and compared them with mice with global deficiency in GR (GR(-/-)). Echocardiography shows impaired heart function in both SMGRKO and GR(-/-) mice at embryonic day (E)17.5, associated with generalized oedema. Cardiac ultrastructure is markedly disrupted in both SMGRKO and GR(-/-) mice at E17.5, with short, disorganized myofibrils and cardiomyocytes that fail to align in the compact myocardium. Failure to induce critical genes involved in contractile function, calcium handling and energy metabolism underpins this common phenotype. However, although hearts of GR(-/-) mice are smaller, with 22% reduced ventricular volume at E17.5, SMGRKO hearts are normally sized. Moreover, while levels of mRNA encoding atrial natriuretic peptide are reduced in E17.5 GR(-/-) hearts, they are normal in foetal SMGRKO hearts. These data demonstrate that structural, functional and biochemical maturation of the foetal heart is dependent on glucocorticoid signalling within cardiomyocytes and vascular smooth muscle, though some aspects of heart maturation (size, ANP expression) are independent of GR at these key sites.

An Assessment of the Imaging Performance of Hand-Held Ultrasound Scanners Using the Edinburgh Pipe Phantom.

OBJECTIVE: Although hand-held ultrasound devices (HHUSDs) are currently used for a diverse range of diagnostic and interventional applications the imaging performance of such scanners is rarely considered. The aim of this study was to assess the imaging performance of a wide-range of HHUSDs and compare their imaging performance to cart-based systems utilized for the same clinical applications. METHODS: The grayscale imaging performances of 19 HHUSDs from eight different manufacturers, manufactured between 2016 and 2021, were measured using a figure-of-merit known as the resolution integral. The imaging performance of the HHUSDs were compared to 142 cart-based ultrasound scanners. RESULTS: The HHUSD with the overall highest resolution integral (66) was a Butterfly (Burlington, MA, USA) wired phased array for small parts applications, followed by a Philips (Bothell, WA, USA) Lumify wired curvilinear transducer (57) for abdominal applications, a Butterfly wired phased array (56) for abdominal applications, a GE (Freiburg, Baden-Wurttemberg, Germany) VScan Air wireless linear array (56) for small parts applications, and a Healcerion (Seoul, Korea) Sonon 300L wireless linear array (56) for small parts applications. A GE VScan Extend wired phased array had the highest resolution integral (44) for cardiac applications. CONCLUSIONS: The Butterfly phased array had the highest resolution integral of all the 19 HHUSDs, although this value is still less than the majority of cart-based cardiac and abdominal ultrasound scanners manufactured from 2010 to 2017. Clinical users of HHUSDs should be mindful of the limitations in imaging performance of hand-held ultrasound devices.

Feto-placental vascular structure and in silico haemodynamics: Of mice, rats, and human.

INTRODUCTION: The complex arborization of the feto-placental vasculature is crucial for optimal fetal nutrition, waste exchange and ultimately, development. Ethical and experimental limitations constrain research into the human placenta, hence experimental animal models such as mice and rats, are crucial to understand placental function. It is unclear how well the mouse and rat feto-placental vascular structure emulates human. Moreover, the implications of differences in vascular structure, especially in arborization, for placental function remain unclear. METHODS: We use micro-computed tomography imaging, high frequency Doppler ultrasound and computational fluid dynamics to characterize feto-placental vasculature structure and haemodynamics in mice, rats, and human. RESULTS: Our data suggest that despite structural differences between rat and mouse placenta, haemodynamics are similar and that both hold applicability to investigating feto-placental structure and function. We show that human cotyledons demonstrate vascularity-dependent haemodynamic behaviour (including flow deceleration and oxygen exchange) similar to rodents and can be analysed in the same spectrum as rodents. Finally, we show strong structure-function relationships when interspecies datasets are combined; notably, we demonstrate that surrogate measures such as vascularity, can be used to estimate placental oxygen exchange function. DISCUSSION: Pre-clinical placental research utilising rat and mouse placentae to understand the impact of feto-placental arborization on placental function and fetal development can inform the human context.

High-resolution echocardiography in the assessment of cardiac physiology and disease in preclinical models.

The high temporal and spatial resolution of echocardiography makes it a powerful and reliable tool for the non-invasive study of cardiac phenotype and disease in both adult and embryonic preclinical models. This overview of the use of high-resolution ultrasound for echocardiography highlights the present and potential applications of the technique.

Community Survey Results Show that Standardisation of Preclinical Imaging Techniques Remains a Challenge.

PURPOSE: To support acquisition of accurate, reproducible and high-quality preclinical imaging data, various standardisation resources have been developed over the years. However, it is unclear the impact of those efforts in current preclinical imaging practices. To better understand the status quo in the field of preclinical imaging standardisation, the STANDARD group of the European Society of Molecular Imaging (ESMI) put together a community survey and a forum for discussion at the European Molecular Imaging Meeting (EMIM) 2022. This paper reports on the results from the STANDARD survey and the forum discussions that took place at EMIM2022. PROCEDURES: The survey was delivered to the community by the ESMI office and was promoted through the Society channels, email lists and webpages. The survey contained seven sections organised as generic questions and imaging modality-specific questions. The generic questions focused on issues regarding data acquisition, data processing, data storage, publishing and community awareness of international guidelines for animal research. Specific questions on practices in optical imaging, PET, CT, SPECT, MRI and ultrasound were further included. RESULTS: Data from the STANDARD survey showed that 47% of survey participants do not have or do not know if they have QC/QA guidelines at their institutes. Additionally, a large variability exists in the ways data are acquired, processed and reported regarding general aspects as well as modality-specific aspects. Moreover, there is limited awareness of the existence of international guidelines on preclinical (imaging) research practices. CONCLUSIONS: Standardisation of preclinical imaging techniques remains a challenge and hinders the transformative potential of preclinical imaging to augment biomedical research pipelines by serving as an easy vehicle for translation of research findings to the clinic. Data collected in this project show that there is a need to promote and disseminate already available tools to standardise preclinical imaging practices.

A Comparison of the Sensitivity of Contrast-Specific Imaging Modes on Clinical and Preclinical Ultrasound Scanners.

Ultrasonic contrast agents are used routinely to aid clinical diagnosis. All premium- and mid-range scanners utilise contrast-specific imaging techniques to preferentially isolate and display the nonlinear signals generated from the microbubbles when insonated with a series of ultrasound pulses. In this manuscript the abilities of four premium ultrasound scanners to detect and display the ultrasound signal from two commercially available contrast agents-SonoVue and DEFINITY®-are compared. A flow phantom was built using tubes with internal diameters of 1.6 mm and 3.2 mm, suspended at depths of 1, 5 and 8 cm and embedded in tissue-mimicking material. Dilute solutions of SonoVue and DEFINITY® were pumped through the phantom at 0.25 mL/s and 1.5 mL/s. Four transducers were used to scan the tubes-a GE Logiq E9 (C2-9) curvilinear probe, a Philips iU22 L9-3 linear array probe, an Esaote MyLab Twice linear array LA523 (4-13 MHz) and a Fujifilm VisualSonics Vevo3100 MX250 (15-30 MHz) linear array probe. We defined a new parameter to compare the ability of the ultrasound scanners to display the contrast enhancement. This was defined as the ratio of grey-scale intensity ratio in contrast-specific imaging mode relative to the B-mode intensity from the same region-of-interest within the corresponding B-mode image. The study demonstrated that the flow rates used in this study had no effect on the contrast-specific imaging mode to B-mode (CSIM-BM) ratio for the three clinical scanners studied, with SonoVue demonstrating broadly similar CSIM-BM ratios across all 3 clinical scanners. DEFINITY® also displayed similar results to SonoVue except when insonated with the Esaote MyLab Twice LA523 transducer, where it demonstrated significantly higher CSIM-BM ratios at superficial depths.

Sonoporation of Human Renal Proximal Tubular Epithelial Cells In Vitro to Enhance the Liberation of Intracellular miRNA Biomarkers.

Ultrasound has previously been demonstrated to non-invasively cause tissue disruption. Small animal studies have demonstrated that this effect can be enhanced by contrast microbubbles and has the potential to be clinically beneficial in techniques such as targeted drug delivery or enhancing liquid biopsies when a physical biopsy may be inappropriate. Cavitating microbubbles in close proximity to cells increases membrane permeability, allowing small intracellular molecules to leak into the extracellular space. This study sought to establish whether cavitating microbubbles could liberate cell-specific miRNAs, augmenting biomarker detection for non-invasive liquid biopsies. Insonating human polarized renal proximal tubular epithelial cells (RPTECs), in the presence of SonoVue microbubbles, revealed that cellular health could be maintained while achieving the release of miRNAs, miR-21, miR-30e, miR-192 and miR-194 (respectively, 10.9-fold, 7.17-fold, 5.95-fold and 5.36-fold). To examine the mechanism of release, RPTECs expressing enhanced green fluorescent protein were generated and the protein successfully liberated. Cell polarization, cellular phenotype and cell viability after sonoporation were measured by a number of techniques. Ultrastructural studies using electron microscopy showed gap-junction disruption and pore formation on cellular surfaces. These studies revealed that cell-specific miRNAs can be non-specifically liberated from RPTECs by sonoporation without a significant decrease in cell viability.

Contrast enhanced magneto-motive ultrasound in lymph nodes - modelling and pre-clinical imaging using magnetic microbubbles.

Despite advances in MRI, the detection and characterisation of lymph nodes in rectal cancer remains complex, especially when assessing the response to neo-adjuvant treatment. An alternative approach is functional imaging, previously shown to aid characterization of cancer tissues. We report proof-of-concept of the novel technique Contrast-Enhanced Magneto-Motive Ultrasound (CE-MMUS) to recover information relating to local perfusion and lymphatic drainage, and interrogate tissue mechanical properties through magnetically induced tissue deformations. The feasibility of the proposed application was explored using a combination of pre-clinical ultrasound imaging and finite element analysis. First, contrast enhanced ultrasound imaging on one wild type mouse recorded lymphatic drainage of magnetic microbubbles after bolus injection. Second, preliminary CE-MMUS data were acquired as a proof of concept. Third, the magneto-mechanical interactions of a magnetic microbubble with an elastic solid were simulated using finite element software. Accumulation of magnetic microbubbles in the inguinal lymph node was verified using contrast enhanced ultrasound, with peak enhancement occurring 3.7 s post-injection. Preliminary CE-MMUS indicates the presence of magnetic contrast agent in the lymph node. The finite element analysis explores how the magnetic force is transferred to motion of the solid, which depends on elasticity and bubble radius, indicating an inverse relation with displacement. Combining magnetic microbubbles with MMUS could harness the advantages of both techniques, to provide perfusion information, robust lymph node delineation and characterisation based on mechanical properties. Clinical Relevance- Robust detection and characterisation of lymph nodes could be aided by visualising lymphatic drainage of magnetic microbubbles using contrast enhanced ultrasound imaging and magneto-motion, which is dependent on tissue mechanical properties.

Modelling of magnetic microbubbles to evaluate contrast enhanced magnetomotive ultrasound in lymph nodes - a pre-clinical study.

OBJECTIVES: Despite advances in MRI the detection and characterisation of lymph nodes in rectal cancer remains complex, especially when assessing the response to neoadjuvant treatment. An alternative approach is functional imaging, previously shown to aid characterisation of cancer tissues. We report proof of concept of the novel technique Contrast-Enhanced Magneto-Motive Ultrasound (CE-MMUS) to recover information relating to local perfusion and lymphatic drainage, and interrogate tissue mechanical properties through magnetically induced deformations. METHODS: The feasibility of the proposed application was explored using a combination of experimental animal and phantom ultrasound imaging, along with finite element analysis. First, contrast-enhanced ultrasound imaging on one wild type mouse recorded lymphatic drainage of magnetic microbubbles after bolus injection. Second, tissue phantoms were imaged using MMUS to illustrate the force- and elasticity dependence of the magnetomotion. Third, the magnetomechanical interactions of a magnetic microbubble with an elastic solid were simulated using finite element software. RESULTS: Accumulation of magnetic microbubbles in the inguinal lymph node was verified using contrast enhanced ultrasound, with peak enhancement occurring 3.7 s post-injection. The magnetic microbubble gave rise to displacements depending on force, elasticity, and bubble radius, indicating an inverse relation between displacement and the latter two. CONCLUSION: Combining magnetic microbubbles with MMUS could harness the advantages of both techniques, to provide perfusion information, robust lymph node delineation and characterisation based on mechanical properties. ADVANCES IN KNOWLEDGE: (a) Lymphatic drainage of magnetic microbubbles visualised using contrast-enhanced ultrasound imaging and (b) magnetomechanical interactions between such bubbles and surrounding tissue could both contribute to (c) robust detection and characterisation of lymph nodes.

Development of Preclinical Ultrasound Imaging Techniques to Identify and Image Sentinel Lymph Nodes in a Cancerous Animal Model.

Lymph nodes (LNs) are believed to be the first organs targeted by colorectal cancer cells detached from a primary solid tumor because of their role in draining interstitial fluids. Better detection and assessment of these organs have the potential to help clinicians in stratification and designing optimal design of oncological treatments for each patient. Whilst highly valuable for the detection of primary tumors, CT and MRI remain limited for the characterization of LNs. B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) can improve the detection of LNs and could provide critical complementary information to MRI and CT scans; however, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines advise that further evidence is required before US or CEUS can be recommended for clinical use. Moreover, knowledge of the lymphatic system and LNs is relatively limited, especially in preclinical models. In this pilot study, we have created a mouse model of metastatic cancer and utilized 3D high-frequency ultrasound to assess the volume, shape, and absence of hilum, along with CEUS to assess the flow dynamics of tumor-free and tumor-bearing LNs in vivo. The aforementioned parameters were used to create a scoring system to predict the likelihood of a disease-involved LN before establishing post-mortem diagnosis with histopathology. Preliminary results suggest that a sum score of parameters may provide a more accurate diagnosis than the LN size, the single parameter currently used to predict the involvement of an LN in disease.

Comparative imaging study in ultrasound, MRI, CT, and DSA using a multimodality renal artery phantom.

PURPOSE: A range of anatomically realistic multimodality renal artery phantoms consisting of vessels with varying degrees of stenosis was developed and evaluated using four imaging techniques currently used to detect renal artery stenosis (RAS). The spatial resolution required to visualize vascular geometry and the velocity detection performance required to adequately characterize blood flow in patients suffering from RAS are currently ill-defined, with the result that no one imaging modality has emerged as a gold standard technique for screening for this disease. METHODS: The phantoms, which contained a range of stenosis values (0%, 30%, 50%, 70%, and 85%), were designed for use with ultrasound, magnetic resonance imaging, x-ray computed tomography, and x-ray digital subtraction angiography. The construction materials used were optimized with respect to their ultrasonic speed of sound and attenuation coefficient, MR relaxometry (T1, T2) properties, and Hounsfield number/x-ray attenuation coefficient, with a design capable of tolerating high-pressure pulsatile flow. Fiducial targets, incorporated into the phantoms to allow for registration of images among modalities, were chosen to minimize geometric distortions. RESULTS: High quality distortion-free images of the phantoms with good contrast between vessel lumen, fiducial markers, and background tissue to visualize all stenoses were obtained with each modality. Quantitative assessments of the grade of stenosis revealed significant discrepancies between modalities, with each underestimating the stenosis severity for the higher-stenosed phantoms (70% and 85%) by up to 14%, with the greatest discrepancy attributable to DSA. CONCLUSIONS: The design and construction of a range of anatomically realistic renal artery phantoms containing varying degrees of stenosis is described. Images obtained using the main four diagnostic techniques used to detect RAS were free from artifacts and exhibited adequate contrast to allow for quantitative measurements of the degree of stenosis in each phantom. Such multimodality phantoms may prove useful in evaluating current and emerging US, MRI, CT, and DSA technology.