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.

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.

It has been shown that ultra-high frequency (UHF) ultrasound applied to the external bowel wall can delineate the histo-anatomic layers in detail and distinguish normal bowel from aganglionosis. This would potentially reduce or lessen the need for biopsies that are currently mandatory for the diagnosis of Hirschsprung’s disease. However, to our knowledge, no suitable rectal probes for such a use are on the market. The aim was to define the specifications of an UHF transrectal ultrasound probe (50 MHz center frequency) suitable for use in infants. Probe requirements according to patient anatomy, clinicians’ requests, and biomedical engineering UHF prerequisites were collected within an expert group. Suitable probes on the market and in clinical use were reviewed. The requirements were transferred into the sketching of potential UHF ultrasound transrectal probes followed by their 3D prototype printing. Two prototypes were created and tested by five pediatric surgeons. The larger and straight 8 mm head and shaft probe was preferred as it facilitated stability, ease of anal insertion, and possible UHF technique including 128 piezoelectric elements in a linear array. We hereby present the procedure and considerations behind the development of a proposed new UHF transrectal pediatric probe. Such a device can open new possibilities for the diagnostics of pediatric anorectal conditions.

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.

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.

Background/Objectives: Intraoperative frozen biopsies are essential during surgery for Hirschsprung’s disease (HD). However, this method has several limitations with the need for a faster and real-time diagnostic alternative. For this, consistent histoanatomical and morphometric differences between aganglionic and ganglionic bowel must be established. The primary objective was to compare dimensions of bowel wall layers between aganglionic and ganglionic segments histopathologically in resected rectosigmoid specimens from children with HD. Secondary objectives were to design a diagnostic algorithm to distinguish aganglionosis from ganglionosis and assess whether full bowel wall thickness correlates with patient weight and age. Methods: Each histoanatomic bowel wall layer—mucosa, submucosa, and muscularis propria’s layers—was delineated manually on histopathological images. Mean thicknesses were calculated automatically using an in-house image analysis software. Paired parametric tests compared measurements in aganglionic and ganglionic segments. Results: Resected specimens from 30 children with HD were included. Compared to aganglionic bowel, ganglionic bowel showed a thicker muscularis interna (mean 0.666 mm versus 0.461 mm, CI −0.257–(−0.153), p < 0.001), and a higher muscularis interna/muscularis externa ratio (2.047 mm versus 1.287 mm, CI −0.954–(−0.565), p < 0.001). An algorithm based on these features achieved 100% accuracy in distinguishing aganglionosis from ganglionosis. No significant difference in full bowel wall thickness was found between aganglionic and ganglionic segments, nor any correlation with patient weight or age. Conclusions: Histoanatomic layer thickness differs between aganglionic and ganglionic bowel, forming the basis of a diagnostic algorithm. Full bowel wall thickness was independent of patient weight and age.