Detection of magnetomotive ultrasound signals from human tissue.

Rectal cancer is a common cancer, with presently a 5-year survival of 67 %. Treatment is based on tumor stage, but current staging methods, such as magnetic resonance imaging (MRI) or ultrasound, are limited in the ability to correctly stage the disease. Magnetomotive ultrasound is a developing modality that has a potential to improve rectal cancer staging. Magnetic nanoparticles are set in motion by an external magnetic field, and the resulting motion signature is detected by ultrasound. Here, we report on magnetomotive images of magnetic nanoparticles in human tissue, using a prototype system where a rotating permanent magnet provides the varying magnetic field, and an ultrasound transducer array encircling the magnet, detects the induced motion. Prior to surgery, a patient with a low rectal tumor was injected at three sites close to the tumor with magnetic nanoparticles. Postsurgical magnetomotive ultrasound scanning revealed the three injection sites, with no obvious artefactual signals. A phantom study showed detection of nanoparticles beyond 40 mm, where 30 mm is the expected maximum distance to mesorectal lymph nodes. Magnetomotive ultrasound image of iron oxide nanoparticles in human tissue. Prior to surgery a patient was injected with nanoparticles, and the excised tissue specimen was imaged with a prototype magnetomotive ultrasound system. The three colored areas overlaid on the standard B-mode greyscale image, correspond to the three injection sites.

Histopathological dimensions differ between aganglionic and ganglionic bowel wall in children with Hirschsprung's disease.

BACKGROUND: In the validation of new imaging technology for children with Hirschsprung's disease (HSCR), basic anatomical parameters of the bowel wall must be established specifically for this patient group. AIM: To explore differences in histoanatomical layers of bowel wall, comparing ganglionic and aganglionic bowel walls, and to examine if the bowel wall thickness is linked to patient weight. METHODS: This was an observational study of bowel specimens from children weighing 0-10 kg, operated on consecutively during 2018-2020. Ganglionic and aganglionic bowel walls were measured in digitalized microscopy images from 10 sites per trans-sectional specimen and compared regarding the thickness of their histoanatomical layers. RESULTS: Bowel walls were measured in 21 children. Full bowel wall thickness did not differ between aganglionic and ganglionic bowel (2.20 vs 2.04; p = 0.802) while weight at surgery correlated positively with both ganglionic and aganglionic bowel wall thickness (r = 0.688 and 0.849, respectively), and age at surgery with ganglionic bowel wall thickness (r = 0.517). In aganglionic segments, the muscularis externa layer was thicker compared to that in ganglionosis (0.45 vs 0.31 mm, p = 0.012) whereas the muscularis interna was thinner (0.45 vs 0.62 mm, p < 0.001). A diagnostic index was identified whereby a lower ratio of muscularis interna/externa thickness followed by a thinner muscularis interna differed between aganglionic and ganglionic bowel in all specimens. CONCLUSION: Thicknesses of the bowel wall's muscle layers differ between aganglionic and ganglionic bowel walls in children with HSCR. These findings support a diagnostic index that could be validated for transfer to instant diagnostic imaging techniques. LEVEL OF EVIDENCE: Diagnostic: 3.

Closed-loop regulation of arterial pressure after acute brain death.

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.

Doppler Audio Signal Analysis as an Additional Tool in Evaluation of Umbilical Artery Circulation.

Purpose To investigate the predictive capacity of a new method for sound spectrum analysis of Doppler signals recorded from the umbilical artery in high-risk pregnancies. Material and Methods The retrospective study comprised 127 pregnant women with various pregnancy complications between 23 and 39 gestational weeks. Umbilical artery blood flow velocity waveforms were recorded with Doppler ultrasound and characterized by pulsatility index (PI) and blood flow class (BFC). Doppler audio signals were stored on a digital video recorder and the sound frequency at the energy level 15 dB below its peak (MAXpeak-15 dB) was estimated off-line. The prediction of probability for composite adverse pregnancy outcome (operative delivery for fetal distress, admission to neonatal intensive care unit, perinatal death) was evaluated using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. Results With increasing umbilical artery BFC, the MAXpeak-15 dB frequencies decreased (p < 0.0001) and the PI increased (p < 0.0001). The ROC AUCs for adverse outcome for MAXpeak-15 dB and for PI were 0.842 and 0.836 (p = 0.88), respectively. For the combination of MAXpeak-15 dB and PI, the corresponding AUC was 0.894, significantly higher than that of PI (p < 0.03) and of MAXpeak-15 dB (p < 0.05). Conclusion Umbilical artery Doppler sound spectrum analysis might be a useful supplement to PI in the clinical evaluation of fetoplacental circulation.

Scatterer size estimation using the center frequency assessed from ultrasound time domain data.

Scatterer size estimation is useful when characterizing tissue using ultrasound. In all previous studies on scatterer size, the estimations are performed in the frequency domain and are thus subjected to a trade off in time-frequency resolution. This study focused on the feasibility of estimating scatterer size in the time domain using only the ultrasound center frequency, assuming a Gaussian-shaped pulse. A model for frequency normalization was derived and the frequency-dependent attenuation was compensated. Five phantoms with well-defined sizes of spherical glass beads were made and scanned with two different linear array transducers with variable center frequencies. A strong correlation (r = 0.99, p < 10-19) between the backscattered center frequency and the product between the wave number and scatterer radius was demonstrated. On average the scatterer diameter was underestimated by 6% ± 24%. These results suggest that estimation of scatterer size is possible using only the center frequency assessed in the time domain.

Audio spectrum analysis of umbilical artery Doppler ultrasound signals applied to a clinical material.

Analysis of umbilical artery flow velocity waveforms characterized by pulsatility index (PI) is used to evaluate fetoplacental circulation in high-risk pregnancies. However, an experienced sonographer may be able to further differentiate between various timbres of Doppler audio signals. Recently, we have developed a method for objective audio signal characterization; the method has been tested in an animal model. In the present pilot study, the method was for the first time applied to human pregnancies. Doppler umbilical artery velocimetry was performed in 13 preterm fetuses before and after two doses of 12 mg betamethasone. The auditory measure defined by the frequency band where the spectral energy had dropped 15 dB from its maximum level (MAXpeak-15 dB ), increased two days after betamethasone administration (p = 0.001) parallel with a less pronounced decrease in PI (p = 0.04). The new auditory parameter MAXpeak-15 dB reflected the changes more sensitively than the PI did.

Deep Learning on Ultrasound Images Visualizes the Femoral Nerve with Good Precision.

The number of hip fractures per year worldwide is estimated to reach 6 million by the year 2050. Despite the many advantages of regional blockades when managing pain from such a fracture, these are used to a lesser extent than general analgesia. One reason is that the opportunities for training and obtaining clinical experience in applying nerve blocks can be a challenge in many clinical settings. Ultrasound image guidance based on artificial intelligence may be one way to increase nerve block success rate. We propose an approach using a deep learning semantic segmentation model with U-net architecture to identify the femoral nerve in ultrasound images. The dataset consisted of 1410 ultrasound images that were collected from 48 patients. The images were manually annotated by a clinical professional and a segmentation model was trained. After training the model for 350 epochs, the results were validated with a 10-fold cross-validation. This showed a mean Intersection over Union of 74%, with an interquartile range of 0.66-0.81.

A Computer Program for Assessing Histoanatomical Morphometrics in Ultra-High-Frequency Ultrasound Images of the Bowel Wall in Children: Development and Inter-Observer Variability.

Ultra-high-frequency ultrasound (UHFUS) has a reported potential to differentiate between aganglionic and ganglionic bowel wall, referred to as histoanatomical differences. A good correlation between histoanatomy and UHFUS of the bowel wall has been proven. In order to perform more precise and objective histoanatomical morphometrics, the main research objective of this study was to develop a computer program for the assessment and automatic calculation of the histoanatomical morphometrics of the bowel wall in UHFUS images. A computer program for UHFUS diagnostics was developed and presented. A user interface was developed in close collaboration between pediatric surgeons and biomedical engineers, to enable interaction with UHFUS images. Images from ex vivo bowel wall samples of 23 children with recto-sigmoid Hirschsprung's disease were inserted. The program calculated both thickness and amplitudes (image whiteness) within different histoanatomical bowel wall layers. Two observers assessed the images using the program and the inter-observer variability was evaluated. There was an excellent agreement between observers, with an intraclass correlation coefficient range of 0.970-0.998. Bland-Altman plots showed flat and narrow distributions. The mean differences ranged from 0.005 to 0.016 mm in thickness and 0 to 0.7 in amplitude units, corresponding to 1.1-3.6% and 0.0-0.8% from the overall mean. The computer program enables and ensures objective, accurate and time-efficient measurements of histoanatomical thicknesses and amplitudes in UHFUS images of the bowel wall. The program can potentially be used for several bowel wall conditions, accelerating research within UHFUS diagnostics.

Ultra-High Frequency Ultrasound Imaging of Bowel Wall in Hirschsprung's Disease-Correlation and Agreement Analyses of Histoanatomy.

Hirschsprung's disease (HD) is characterized by aganglionosis in the bowel wall, requiring resection. Ultra-high frequency ultrasound (UHFUS) imaging of the bowel wall has been suggested to be an instantaneous method of deciding resection length. The aim of this study was to validate UHFUS imaging of the bowel wall in children with HD by exploring the correlation and systematic differences between UHFUS and histopathology. Resected fresh bowel specimens of children 0-1 years old, operated on for rectosigmoid aganglionosis at a national HD center 2018-2021, were examined ex vivo with UHFUS center frequency 50 MHz. Aganglionosis and ganglionosis were confirmed by histopathological staining and immunohistochemistry. Histoanatomical layers of bowel wall in histopathological and UHFUS images, respectively, were outlined using MATLAB programs. Both histopathological and UHFUS images were available for 19 aganglionic and 18 ganglionic specimens. The thickness of muscularis interna correlated positively between histopathology and UHFUS in both aganglionosis (R = 0.651, p = 0.003) and ganglionosis (R = 0.534, p = 0.023). The muscularis interna was systematically thicker in histopathology than in UHFUS images in both aganglionosis (0.499 vs. 0.309 mm; p < 0.001) and ganglionosis (0.644 versus 0.556 mm; p = 0.003). Significant correlations and systematic differences between histopathological and UHFUS images support the hypothesis that UHFUS reproduces the histoanatomy of the bowel wall in HD accurately.

Quantification of left-to-right shunt through patent ductus arteriosus by colour Doppler in children admitted for a device closure.

PURPOSE: Our animal model suggests that quantification of ductal flow from colour Doppler pixels is possible. We aimed to clarify whether this method can be used to determine a clinically significant ductal shunt in children. METHODS: We retrospectively quantified ductal flow from saved images from 20 children who had been admitted for device occlusion of patent ductus arteriosus. Colour Doppler images over the main stem of the pulmonary artery were obtained in longitudinal cross-sections. The colour pixel percentages during diastole, representing ductal flow, were correlated with the documented shunt, measured invasively according to Fick's principle. RESULTS: The ratio of pulmonary to systemic flow correlated best with the sum of the percentages of green colour pixels (r = 0.73, r2 = 0.54, p < 0.001). When the shunt was 1.5:1 or more, 12 out of 13 infants had 50% or more of the region of interest covered with green pixels--sensitivity 92%, specificity 71%. The correlation between ductal diameter and pulmonary-to-systemic flow ratio was less significant (r = 0.6, r2 = 0.37, p < 0.03). CONCLUSIONS: We conclude that clinically significant shunts with pulmonary-to-systemic flow ratio over 1.5 can be diagnosed with this method where neither the size of the patient nor echocardiographic settings seem to be critical. The method could be used to provide an objective indication for ductal closure, but further prospective studies in children are needed to verify the power of the method.

Evaluation of cellular stress responses in magnetomotive ultrasound.

Early and accurate diagnoses are important for successful cancer treatment. Lymph node involvement is often critical, and magnetomotive ultrasound (MMUS) has been proposed for its detection and characterization. MMUS relies on a magnetic contrast agent, for example, iron oxide nanoparticles, delivered to the tissue of interest, magnetically set in motion and detected using ultrasound. The magneto-mechanical interaction has not previously been evaluated on a cellular level. Here we demonstrate uptake and dose-dependent retention of magnetic nanoparticles in two human adenocarcinoma cell lines, with <10% cytotoxicity which did not increase following magnetic excitation. Further, the oxidative stress levels were not affected by magnetic particles or force. Thus, we found no evidence of adverse effects from the magneto-mechanical interactions under these conditions.

Displacement Patterns in Magnetomotive Ultrasound Explored by Finite Element Analysis.

Magnetomotive ultrasound is an emerging technique that enables detection of magnetic nanoparticles. This has implications for ultrasound molecular imaging, and potentially addresses clinical needs regarding determination of metastatic infiltration of the lymphatic system. Contrast is achieved by a time-varying magnetic field that sets nanoparticle-laden regions in motion. This motion is governed by vector-valued mechanical and magnetic forces. Understanding how these forces contribute to observed displacement patterns is important for the interpretation of magnetomotive ultrasound images. Previous studies have captured motion adjacent to nanoparticle-laden regions that was attributed to diamagnetism. While diamagnetism could give rise to a force, it cannot fully account for the observed displacements in magnetomotive ultrasound. To isolate explanatory variables of the observed displacements, a finite element model is set up. Using this model, we explore potential causes of the unexplained motion by comparing numerical models with earlier experimental findings. The simulations reveal motion outside particle-laden regions that could be attributed to mechanical coupling and the principle of mass conservation. These factors produced a motion that counterbalanced the time-varying magnetic excitation, and whose extent and distribution was affected by boundary conditions as well as compressibility and stiffness of the surroundings. Our findings emphasize the importance of accounting for the vector-valued magnetic force in magnetomotive ultrasound imaging. In an axisymmetric geometry, that force can be represented by a simple scalar expression, an oversimplification that rapidly becomes inaccurate with distance from the symmetry axis. Additionally, it results in an underestimation of the vertical force component by up to 30%. We therefore recommend using the full vector-valued force to capture the magnetic interaction. This study enhances our understanding of how forces govern magnetic nanoparticle displacement in tissue, contributing to accurate analysis and interpretation of magnetomotive ultrasound imaging.

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.

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.

Fusion imaging in brain structure measurements on a fetus phantom, combining real-time ultrasound with magnetic resonance imaging.

OBJECTIVES: To assess synchronisation of MRI and US in measuring foetus phantom head structures; inter-method, intra- and inter-observer differences on biparietal diameter (BPD), head diameter, anterio-posterior head diameter (HAP) and lateral ventricle structures (VS). METHODS: Fusion Imaging (FI) has been performed by combining MRI and US simultaneously. Axial scans of 1.5 Tesla MRI on a foetus phantom were acquired and uploaded on a US machine (EPIQ 7G, Philips). A PercuNav US tracker allowed the system to recognise and display the position of the transducer. A fetal phantom tracker was used as a phantom reference. Real-time US of the phantom head was performed by synchronising the uploaded MRI images using different landmarks. Synchronisation has been assessed by taking measurements after rotating the US probe by 90. Measurements were taken by three different observers twice. Differences in measurements between MRI and US, inter-, intra-observer differences in all measurements were assessed. RESULTS: BPD, HAP and VS measurements before rotation were 0.13 ± 0.06 cm, 0.46 ± 0.09 cm and 0.4 ± 0.23 cm (width) and mean 0.6 ± 0.25 cm (length) larger at MRI than at US using any number of landmarks. After US probe rotation VS were 0.3 ± 0.24 cm in width and 0.3 ± 0.27 cm in length. Intra- and inter-observer differences in all measurements were small. CONCLUSIONS: FI showed good synchronisation in measurements. BPD, HAP and VS were larger at MRI than US, likely a result of the way images are generated. Intra-, inter-observer differences between measurements were small. This can be important when reporting geometric measures from FI.

Ultra high frequency ultrasonography to distinguish ganglionic from aganglionic bowel wall in Hirschsprung disease: A first report.

BACKGROUND/PURPOSE: In Hirschsprung disease (HD) surgery, confirming ganglionic bowel is essential. A faster diagnostic method than the current frozen biopsy is desirable. This study investigated whether aganglionic and ganglionic intestinal wall can be distinguished from each other by ultra high frequency ultrasound (UHF ultrasound). METHODS: In an HD center during 2019, intestinal walls of recto-sigmoid specimens from HD patients were examined ex vivo with a 70 MHz UHF ultrasound transducer. Data from four sites were described. Histopathologic analysis was compared to the ultrasonography outcome at each site. Each patient's specimen served as its own control. RESULTS: 11 resected recto-sigmoid specimens (median 20 cm long [range 6.5-33]) with transition zones of 5 cm (2-11 cm) were taken from children aged 22 days (13-48) weighing 3668 g (3500-5508); 44 key sites were analyzed. There was full concordance for 42/44 (95%) key sites and 10 of 11 (91%) specimens. The specimen with discordance of two key sites contained a segment of aganglionosis (3 cm) and a transition zone (1 cm): the site discordance was limited to the transition zone ends. CONCLUSIONS: This first report on UHF ultrasound in recto-sigmoid HD shows promising results in identifying aganglionosis, transition zones and ganglionic bowel. Further in vivo studies are required.

Gemcitabine and capecitabine in combination for advanced anthracycline and taxane pre-treated breast cancer patients: A phase II study.

AIM: The aim of this study was to explore the clinical value of gemcitabine combined with capecitabine (GC) in heavily pre-treated patients with metastatic breast cancer. MATERIAL AND METHODS: All patients had failed anthracyclines and taxanes. In 14 patients (41%), more than two metastatic sites were diagnosed with bone (68%) and liver (62%) being the most prominent. Gemcitabine (1,250 mg/m(2), d1+8) and capecitabine (800 mg/m(2) twice daily, d1-14) were administered according to a 3-week schedule. The majority of patients received GC as 3rd or 4th line chemotherapy for metastatic disease. Laboratory tests were done on day 1+8 in cycles. Subjective toxicity was recorded according to the NCI-CTC v. 2.0 criteria. Tumour evaluations were done every 12th week according to the RECIST criteria. The primary objective was to investigate time to progression. Secondary objectives were response rate with special focus on the proportion of patients achieving PR or SD of at least three months, toxicity and survival. RESULTS: A total of 34 patients were enrolled. All subjects are eligible for toxicity, response and time to event analyses. Treatment was given until progressive disease, severe toxicity or until the patient wanted to withdraw. The Kaplan-Meier median time to progression was estimated to 4.3 months and the overall survival time to 13.7 months. Partial response was noted in 12 of 29 evaluable patients (41%). The best outcome amongst remaining patients was stable disease in nine (31%) or tumour progression in eight (28%). A delay of disease progression of more than three months was noted in 53% of the study population. The main side effect was granulocytopenia with 44% and 15% of patients suffering from grade 3 or grade 4 events respectively however, no neutropenic infections were observed. Pre-dominant grade 3 subjective toxicities were: fatigue (21% of patients) and hand-foot syndrome (15% of patients). DISCUSSIONS: We investigated the value of the GC combination as a treatment for late stage breast cancer patients. Tumour progression was delayed and the treatment was well tolerated. We believe that the GC therapy can achieve meaningful palliation.

Corrections to "Desire of Use: A Hierarchical Decomposition of Activities and Its Application on Mobility of by Blind and Low-Vision Individuals".

The title of [1] contains a typo. "Desire of Use: A Hierarchical Decomposition of Activities and Its Application on Mobility of Blind and Low-Vision Individuals" is the correct title.

Magnetomotive Ultrasound Imaging Systems: Basic Principles and First Applications.

This review discusses magnetomotive ultrasound, which is an emerging technique that uses superparamagnetic iron oxide nanoparticles as a contrast agent. The key advantage of using nanoparticle-based contrast agents is their ability to reach extravascular targets, whereas commercial contrast agents for ultrasound comprise microbubbles confined to the blood stream. This also extends possibilities for molecular imaging, where the contrast agent is labeled with specific targeting molecules (e.g., antibodies) so that pathologic tissue may be visualized directly. The principle of action is that an external time-varying magnetic field acts to displace the nanoparticles lodged in tissue and thereby their immediate surrounding. This movement is then detected with ultrasound using frequency- or time-domain analysis of echo data. As a contrast agent already approved for magnetic resonance imaging (MRI) by the US Food and Drug Administration, there is a shorter path to clinical translation, although safety studies of magnetomotion are necessary, especially if particle design is altered to affect biodistribution or signal strength. The external modulated magnetic field may be generated by electromagnets, permanent magnets, or a combination of the two. The induced nanoparticle motion may also reveal mechanical material properties of tissue, healthy or diseased, one of several interesting potential future aspects of the technique.