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.

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.

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.

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.

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.

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.

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.

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.

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.

Desire of Use: A Hierarchical Decomposition of Activities and its Application on Mobility of Blind and Low-Vision Individuals.

OBJECTIVE: Blind and low-vision individuals often have severely reduced mobility, affecting their quality of life and associated socioeconomic cost. Despite numerous efforts and great technological progress, the only used primary mobility aids are still white canes and seeing-eye dogs. Furthermore, there is a permeating tendency in the field to ignore knowledge of both mobility and the target group, as well as constantly design new metrics and tests that makes comparisons between solutions markedly more difficult. METHOD: The Desire of Use model is introduced in an effort to promote a more holistic approach; it should be generalizable for any activity by any user, but is here applied on mobility of blind and low-vision individuals by a proposal and integration of parameters. RESULTS: An embodiment of the model is presented and with it we show why popular mobility metrics of today are insufficient to guide design; what tasks and metrics that should provide better understanding; as well as which fundamental properties determine them and are critical to discuss. CONCLUSION: Desire of Use has been introduced as a tool and a theoretical framework, and a realization has been proposed. SIGNIFICANCE: Desire of Use offers both a structured perspective of pertinent design challenges facing a given solution, as well as a platform from which to compare test results and properties of existing solutions; in for example the field of electronic travel aids it should prove valuable for designing and evaluating new tests and devices.

Audomni: Super-Scale Sensory Supplementation to Increase the Mobility of Blind and Low-Vision Individuals-A Pilot Study.

OBJECTIVE: Blindness and low vision have severe effects on individuals' quality of life and socioeconomic cost; a main contributor of which is a prevalent and acutely decreased mobility level. To alleviate this, numerous technological solutions have been proposed in the last 70 years; however, none has become widespread. METHOD: In this paper, we introduce the vision-to-audio, super-scale sensory substitution/supplementation device Audomni; we address the field-encompassing issues of ill-motivated and overabundant test methodologies and metrics; and we utilize our proposed Desire of Use model to evaluate proposed pilot user tests, their results, and Audomni itself. RESULTS: Audomni holds a spatial resolution of 80 x 60 pixels at ~1.2° angular resolution and close to real-time temporal resolution, outdoor-viable technology, and several novel differentiation methods. The tests indicated that Audomni has a low learning curve, and several key mobility subtasks were accomplished; however, the tests would benefit from higher real-life motivation and data collection affordability. CONCLUSION: Audomni shows promise to be a viable mobility device - with some addressable issues. Employing Desire of Use to design future tests should provide both high real-life motivation and relevance to them. SIGNIFICANCE: As far as we know, Audomni features the greatest information conveyance rate in the field, yet seems to offer comprehensible and fairly intuitive sonification; this work is also the first to utilize Desire of Use as a tool to evaluate user tests, a device, and to lay out an overarching project aim.

Clinical Translation of a Novel Photoacoustic Imaging System for Examining the Temporal Artery.

The objective was to provide a clinical setup for photoacoustic imaging (PAI) of the temporal artery in humans and to describe the challenges encountered and methods of overcoming them. The temporal artery was examined in seven patients with suspect giant-cell arteritis (GCA), both in vivo and ex vivo, and the results were compared to that of histology. To adapt PAI to the human studies, the transducer was fixed to an adjustable arm to reduce motion artifacts, and a stepping motor was developed to enable 3-D scanning. Risks associated with the use of lasers, ultrasound, and electrical equipment were evaluated by measuring energy levels, and safety precautions were undertaken to prevent injury to the patients and staff. The PAI spectra obtained clearly delineated the artery wall, both in vivo and ex vivo, although the latter was of high quality due to the lack of artifacts. The results could be compared to that of histology. The involved energy levels were found to be below the limits given in regulatory standards. Eye protectors prevented irradiation of the patient's eyes, and visual function after the procedure was found not to be affected. The patients reported no discomfort during the investigations. PAI provides images of the temporal artery wall that may be used for the future diagnosis of GCA in humans. The technique could be further refined by addressing the specific problems of motion artifacts and interference from blood and other chromophores. This study paves the way for other clinical applications of PAI.

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.

Combined Magnetomotive ultrasound, PET/CT, and MR imaging of 68Ga-labelled superparamagnetic iron oxide nanoparticles in rat sentinel lymph nodes in vivo.

Current methods for intra-surgical guidance to localize metastases at cancer surgery are based on radioactive tracers that cause logistical challenges. We propose the use of a novel ultrasound-based method, magnetomotive ultrasound (MMUS) imaging that employ a nanoparticle-based contrast agent that also may be used for pre-operative PET/MRI imaging. Since MMUS is radiation free, this eliminates the dependence between pre- and intra-operative imaging and the radiation exposure for the surgical staff. This study investigates a hypothetical clinical scenario of pre-operative PET imaging, combined with intra-operative MMUS imaging, implemented in a sentinel lymph node (SLN) rat model. At one-hour post injection of 68Ga-labelled magnetic nanoparticles, six animals were imaged with combined PET/CT. After two or four days, the same animals were imaged with MMUS. In addition, ex-vivo MRI was used to evaluate the amount of nanoparticles in each single SLN. All SLNs were detectable by PET. Four out of six SLNs could be detected with MMUS, and for these MMUS and MRI measurements were in close agreement. The MRI measurements revealed that the two SLNs undetectable with MMUS contained the lowest nanoparticle concentrations. This study shows that MMUS can complement standard pre-operative imaging by providing bedside real-time images with high spatial resolution.