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Endovascular revascularization is the preferred treatment for peripheral arterial disease. Restenosis often occurs as a response to procedure-induced arterial damage. Reducing vascular injury during endovascular revascularization may improve its success rate. This study developed and validated an ex vivo flow model using porcine iliac arteries, obtained from a local abattoir. Twenty arteries (of 10 pigs) were equally allocated to two groups: a mock-treated control group and an endovascular intervention group. Arteries of both groups were perfused with porcine blood for 9 min, including 3 min of balloon angioplasty in the intervention group. Vessel injury was assessed by calculating the presence of endothelial cell denudation, vasomotor function, and histopathological analysis. MR imaging displayed balloon positioning and inflation. Endothelial cell staining showed 76% of denudation after ballooning compared to 6% in the control group (p < 0.001). This was confirmed by histopathological analysis, showing a significantly reduced endothelial nuclei count after ballooning compared to the controls (median: 22 vs. 37 nuclei/mm, p = 0.022). In the intervention group, vasoconstriction and endothelium-dependent relaxation were significantly reduced (p < 0.05).We present an ex vivo flow model to test the effects of endovascular therapy on the vessel’s wall morphology, endothelial denudation, and endothelial-dependent vasomotor function under physiological conditions. Additionally, it allows the future testing of human arterial tissue.

Objective Intracerebral hemorrhage (ICH) volume is a strong predictor of outcome in patients presenting with acute hemorrhagic stroke. It is necessary to segment the hematoma for ICH volume estimation and for computerized extraction of features, such as spot sign, texture parameters, or extravasated iodine content at dual-energy computed tomography. Manual and semiautomatic segmentation methods to delineate the hematoma are tedious, user dependent, and require trained personnel. This article presents a convolutional neural network to automatically delineate ICH from noncontrast computed tomography scans of the head. Methods A model combining a U-Net architecture with a masked loss function was trained on standard noncontrast computed tomography images that were down sampled to 256 × 256 size. Data augmentation was applied to prevent overfitting, and the loss score was calculated using the soft Dice loss function. The Dice coefficient and the Hausdorff distance were computed to quantitatively evaluate the segmentation performance of the model, together with the sensitivity and specificity to determine the ICH detection accuracy. Results The results demonstrate a median Dice coefficient of 75.9% and Hausdorff distance of 2.65 pixels in segmentation performance, with a detection sensitivity of 77.0% and specificity of 96.2%. Conclusions The proposed masked loss U-Net is accurate in the automatic segmentation of ICH. Future research should focus on increasing the detection sensitivity of the model and comparing its performance with other model architectures.

Introduction and hypothesis Pelvic organ prolapse quantification by means of upright magnetic resonance imaging (MRI) is a promising research field. This study determines the angle for the pelvic inclination correction system (PICS) for upright patient position, which is hypothesized to deviate from the supine PICS angle. The necessity of different PICS angles for various patient positions will also be discussed. Methods Magnetic resonance scans of 113 women, acquired in an upright patient position, were used to determine the upright PICS angle, defined as the angle between the sacrococcygeal–inferior pubic point (SCIPP) line and the horizontal line. The difference and correlation between the upright and supine PICS angles were calculated using the paired Student’s t-test and the Pearson’s correlation coefficient (r) respectively. The effect of the difference between the upright and supine PICS angle on the measured pelvic organ extent was calculated using goniometry. Results The mean (interquartile range) PICS angles were 29° (26–35°) for the upright and 33° (30–37°) for the supine patient position. They were significantly different (pr = 0.914, p Conclusions The PICS angle for the upright patient position is 29°. The use of a dedicated PICS angle for different patient positions allows for more accurate pelvic organ extent analysis in patients with prolapse.

Introduction and hypothesis Symptoms of pelvic organ prolapse (POP) can affect quality of life and are reported to progress during the day, although this was never objectified. The aim of this study is to determine whether the pelvic anatomy changes during the day using upright magnetic resonance imaging (MRI), in POP patients and asymptomatic women. Methods In this prospective study 15 POP patients and 45 asymptomatic women were included. Upright MRI scans were obtained three times per day. The distances from the lowest points of the bladder and cervix to a standardized reference (pelvic inclination correction system) line were determined. A principal component analysis was performed on the levator plate (LP) shape. Statistical differences between time points and the groups were determined for the bladder, cervix, and LP shape. Results For all women a significant decrease in bladder and cervix height of −0.2 cm (pp=0.004). Individual differences in bladder position in the POP group of up to 2.2 cm between the morning and afternoon scan were reported. There was a significant difference in LP shape (p Conclusions This study found no clinically relevant pelvic anatomy changes during the day. Still, on an individual level differences can be large, so repeating clinical examination at the end of the day can be recommended in patients when anamnesis and physical examination do not match.

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.

Background There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing. Methods In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation. Results A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)). Conclusion RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies.

Magnetic nanoparticles (MNPs) are used in many biomedical applications, including sentinel lymph node biopsy (SLNB) and magnetic particle imaging (MPI). University of Twente has developed DiffMag handheld probe for a magnetic SLNB utilising MNPs. This probe is based upon differential magnetometry employing nonlinear magnetic response of superparamagnetic MNPs. The DiffMag handheld probe consists of an excitation coil to activate the MNPs, and a set of detection coils to acquire the signal generated by MNPs. The hydrodynamic size and surface properties of MNPs may change when introduced to a new environment. This alteration in mechanical properties will have an effect on their magnetic behaviour. In this study, the protocol settings for the nonlinear handheld detection probe during the SLNB procedure is optimized. The observed detection depth of DiffMag handheld probe decreases slightly by increasing the environment viscosity.

Background: In vivo diffuse reflectance spectroscopy provides additional contrast in discriminating nerves embedded in adipose tissue during surgery. However, large datasets are required to achieve clinically acceptable classification levels. This study assesses the spectral similarity between ex vivo porcine and in vivo human spectral data of nerve and adipose tissue, as porcine tissue could contribute to generate large datasets. Methods: Porcine diffuse reflectance spectra were measured at 124 nerve and 151 adipose locations. A previously recorded dataset of 32 in vivo human nerve and 23 adipose tissue locations was used for comparison. In total, 36 features were extracted from the raw porcine to generate binary logistic regression models for all combinations of two, three, four and five features. Feature selection was performed by assessing similar means between normalized features of nerve and of adipose tissue (Kruskal–Wallis test, p < 0.05) and for models performing best on the porcine cross validation set. The human test set was used to assess classification performance. Results: The binary logistic regression models with selected features showed an accuracy of 60% on the test set. Conclusions: Spectral similarity between ex vivo porcine and in vivo human adipose and nerve tissue was present, but further research is required.

Purpose: High permittivity dielectric pads are known to be effective for tailoring the RF field and improving image quality in high field MRI. Despite a number of studies reporting benign specific absorption rate (SAR) effects, their “universal” safety remains an open concern. In this work, we evaluate the impact of the insulation material in between the pad and the body, using both RF simulations as well as phantom experiments. Methods: A 3T configuration with high permittivity material was simulated and characterized experimentally in terms of B1+ fields and RF power absorption, both with and without electrical insulation in between the high permittivity material and the sample. Different insulation conditions were compared, and electromagnetic analyses on the induced current density were performed to elucidate the effect. Results: Increases in RF heating of up to 49% were observed experimentally in a tissue-mimicking phantom after removing the material insulation. The B1+ magnitude and RF transceive phase were not affected. Simulations indicated that an insulation thickness of 0.5–2 mm should be accounted for in numerical models in order to ensure reliable results. Conclusion: A reliable RF safety assessment of high permittivity dielectric pads requires accounting for the insulating properties of the plastic encasing. Ignoring the electrical insulation can lead to erroneous results with substantial increases in local SAR at the interface. Conversely, the material insulation does not need to be modeled to predict the B1+ effects during the design of the pad geometry.

Background Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions. Methods This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance. The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events. Discussion This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery. Trial registration Netherlands National Trial Register, NL8019, registered on September 12th 2019.

Background: Cerebral venous pathways are subjected to geometrical and patency changes due to body position. The internal jugular veins (IJVs) are the main venous drainage pathway in supine position. Their patency and geometry should be evaluated under different body inclination angles over a three-dimensional (3D) volume in the healthy situation to better understand pathological cases. Purpose: To investigate whether positional changes in the body can affect the geometrical properties and patency of the venous system. Study Type: Prospective. Population: 15 healthy volunteers, of which seven males and median age 22 years in a range of 19–59. Field Strength/Sequence: A 0.25-T tiltable MRI system was used to scan volunteers in 90° (sitting position), 69°, 45°, 21°, and 0° (supine position) in the transverse plane with the top at vertebra C2. A gradient echo sequence was used. Assessment: Three observers assessed IJVs on patency and created automatic centerlines from which diameter and patency were analysed perpendicular to the vessel at every 4 mm starting at the level of C2. Statistical Tests: A Student's t test was used to find statistical difference (p < 0.05) in average IJV diameters per inclination angle. Results: The amount of fully collapsed IJVs increased from 33% to 93% (left IJV) and 14% to 80% (right IJV) when increasing the inclination angle from 0° to 90°. In both IJVs, the mean diameter (±SD) of the open vessels was significantly higher at 0° than 90° with 6.3 ± 0.5 mm vs. 4.4 ± 0.1 mm (left IJV) and 6.6 ± 0.6 mm vs. 4.3 ± 0.4 mm (right IJV). Data Conclusion: Tiltable low-field MRI can be used to assess IJV geometry and its associated venous pathways in 3D under multiple inclination angles. Next to a higher amount of collapsed vessels, the average diameter of noncollapsed vessels decreases with increasing inclination angles for both left and right IJVs. Level of Evidence: 2. Technical Efficacy Stage: 1.

In the last 2 decades, multiple robotic camera holders have been developed to improve camera steering during laparoscopic surgery. A new image-based steering method has been developed for more intuitive camera control. In this article, the efficiency and user experience of image-based steering were compared to conventional steering methods. Four participants (two senior surgical registrars, one junior surgical registrar and a technical medicine student) were enrolled in this study. All participants performed multiple camera steering exercises with three different steering modalities in randomized order: image-based, joystick and manual camera steering. Steering of the laparoscope was evaluated by execution time and with the SMEQ and NASA-TLX questionnaires to analyze user experience. A total of 267 camera steering exercises were performed. The analyzed data showed a significantly shorter execution time for manual camera steering compared to image-based robotic steering (p = 0.001) and joystick robotic steering (p = 0.001). The participants reported the lowest user experience with joystick camera steering. The results of the questionnaires showed no significant difference in all subscales of user experience for image-based and manual camera steering. Manual camera steering resulted in significantly higher perceived physiological workload scores (M = 30.0, IQR = 27.5) compared to image-based (M = 10, IQR = 5.0) and joystick camera steering (M = 15.0, IQR = 10.0). Manual control of the laparoscope remains the fastest steering method at the expense of a high physical workload. Using image-based camera steering is a viable alternative to the current joystick control of robotic camera holders, as it improves speed and user experience. The study results suggest that optimisation of robotic camera steering with algorithms based on image analysis is a promising technology.

Purpose Sentinel lymph node biopsy is a routine procedure for nodal staging in penile cancer. Most commonly, this procedure is guided by radioactive tracers, providing various forms of preoperative and intraoperative guidance. This is further extended with fluorescence imaging using hybrid radioactive–fluorescence tracers. Alternatively, a magnetic-based approach has become available using superparamagnetic iron-oxide nanoparticles (SPIONs). This study investigates a novel freehand magnetic particle imaging and navigation modality (fhMPI) for intraoperative localization, along with a hybrid approach, combining magnetic and fluorescence guidance. Materials and methods The fhMPI set-up was built with a surgical navigation device, optical tracking system and magnetometer probe. A dedicated reconstruction software based on a look-up-table method was used to reconstruct a superficial 3D volume of the SPION distribution in tissue. For fluorescence guidance, indocyanine green (ICG) was added to the SPIONs. The fhMPI modality was characterized in phantoms, ex vivo human skin and in vivo porcine surgery. Results Phantom and human skin explants illustrated that the current fhMPI modality had a sensitivity of 2.2 × 10–2 mg/mL SPIONs, a resolving power of at least 7 mm and a depth penetration up to 1.5 cm. Evaluation during porcine surgery showed that fhMPI allowed for an augmented reality image overlay of the tracer distribution in tissue, as well as 3D virtual navigation. Besides, using the hybrid approach, fluorescence imaging provided a visual confirmation of localized nodes. Conclusion fhMPI is feasible in vivo, providing 3D imaging and navigation for magnetic nanoparticles in the operating room, expanding the guidance possibilities during magnetic sentinel lymph node procedures. Furthermore, the integration of ICG provides the ability to visually refine and confirm correct localization. Further clinical evaluation should verify these findings in human patients as well.

A recently developed prototype (Laparoscopic Differential Magnetometer, in short LapDiffMag) identifies magnetic tracer accumulated inside sentinel lymph nodes (SLNs) during clinical laparoscopic procedures. The LapDiffMag relies on excitation of superparamagnetic iron oxide nanoparticles (SPIONs) and subsequent laparoscopic detection based on a nonlinear detection principle. The prototype uses an excitation coil to generate a magnetic field needed to activate SPIONs. This study reports on the process of developing a new excitation coil by describing the design choices based upon clinical requirements, by modeling delivered magnetic field using digital twin, and by comparing the magnetic fields of modeled and manufactured prototype. Digital twin technology was used to produce relevant and reliable data to demonstrate the safety and effectiveness of the excitation coil. The magnetic field originating from manufactured prototype was validated at two different heights above the excitation coil and have shown a good concordance to the data generated by its digital twin. Clinical Relevance- Current standard-of-care for a variety of tumor types consists of minimally invasive radical resection of primary tumor and regional lymph nodes (LNs). The newly introduced excitation coil will (after full validation) enable minimally invasive harvesting of sentinel LNs by means of magnetic tracer detection.

En-bloc tumor resection is the standard treatment for locally advanced colorectal cancer (CRC). An extensive histopathological assessment is necessary to evaluate the metastatic spread and adjuvant therapy. Sentinel lymph node biopsy decreases the histopathological burden when only sentinel lymph nodes (SLNs) are examined. This study aims to evaluate the spread of a magnetic tracer throughout the lymphatic system after ex vivo injection in en-bloc resected specimens of patients with CRC. To achieve this, lymph nodes (LNs) were quantified using a new magnetic detection method. Fifteen patients with CRC diagnosed with clinically negative LNs were included in this study and received 2–4 ex vivo magnetic tracer injections (total volume of 2[Formula: see text]mL). Magnetic sample series were acquired to create a look-up table for magnetic tracer quantification. In 80% of the patients, at least one magnetic LN was detected. A total of 33 LNs were marked as magnetic, containing an average of 8.1[Formula: see text][Formula: see text]g iron. In 71% of the patients, metastases were found in nonmagnetic LNs. Ex vivo injection leads to sub-optimal tracer spread and therefore inaccurate diagnosis. This study presents a novel magnetic detection method to quantify magnetic tracer in lymph nodes. Detecting the SLNs in en-bloc resected specimens and involving only these LNs in histopathological investigation enable a decrease in healthcare costs or an increased diagnostic potential.

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom’s potential.

In order to improve the accuracy of SLNB in FOM cancer patients, and explore the magnetic approach as alternative to the conventional technique using radioisotopes. The aim of this thesis is twofold: At first, gain insight in the magnetic SLNB procedure in oral cancer patients, using a clinically available magnetic probe (Sentimag®). Second, establish a safe DiffMag handheld probe prototype for clinical investigation. The first part of this thesis discusses the clinical application of magnetic SLNB in OSCC patients. In Chapter 2 an evaluation on novel SLNB imaging techniques for early-stage OSCC is given, one of them is MR lymphography. An overview is given on their diagnostic accuracy, relative merits, disadvantages and potential applications. In Chapter 3 we present a clinical feasibility study, using Sentimag®, covering a complete magnetic SLNB procedure in ten OSCC patients: injection, preoperative imaging to surgical removal of the lymph nodes, and histopathological examination. Which is followed by an additional analysis to the lymphatic drainage of the magnetic tracer for eight OSCC patients of the feasibility study. Based on these initial results, the iron content in SLNs is determined and a proposal is made for the iron grading of SLNs on MRI and histopathological examination in Chapter 4. The second part focuses on the technical aspects of DiffMag handheld probe development and how to get it safe for clinical application. For this purpose in Chapter 5 specifications (detection depth, lateral detection distance and resolving power) are determined for DiffMag handheld probe in a comparison study with Sentimag® and a gamma probe. Chapter 6 gives an overview of the process of qualifying a medical device (in this case DiffMag handheld probe) for clinical use, encountering the new MDR, applicable standards, analyzed risks and adaptations made to the system. Furthermore lessons learned during this process and advice to others to support their development process is given. Chapter 7 provides a general conclusion and future perspectives regarding the magnetic SLNB procedure in OSCC patients and the use of DiffMag handheld probe

The overall aim of this thesis is to explore the usage of magnetic nanoparticles for sentinel lymph node biopsies in the abdomen, and further develop a new magnetic detection prototype for laparoscopic surgery. The central medical problem which a sentinel lymph node biopsy (SLNB) tries to solve can be split into two parts. First, when a primary tumour is surgically treated by radical removal of the tumour and surrounding lymph nodes (LNs), unneeded tissue damage is caused if all removed LNs did not contain tumour cells. Second, if tumour cells spread to LNs outside the selected resection area, chance of tumour recurrence is high, leading to a worse patient prognosis. By using a tracer to select the primary draining lymph nodes (sentinel lymph nodes, SLNs) and removing those regardless of the anatomical area, less tissue damage is expected but with still a high accuracy to detect possible tumour cells. The used tracer in this thesis consists of superparamagnetic iron oxide nanoparticles. With a magnetic core and polymer coating, the tracer is seen as inert by the human body and is encapsuled by white blood cells in LNs, resulting in a good biocompatibility. The main parameter of interest of this tracer is it superparamagnetic (nonlinear) magnetic behaviour. Because of this, it is possible to automatically remove linear signals (e.g. surgical steel and the human body) with the used differential magnetometry method. To find this tracer, a magnetometer is necessary. Currently, there is only one commercially available magnetometer, which senses magnetic tracer, surgical steel and even the human body. To compensate, manual balancing between every measurement is necessary, which is time consuming. A novel magnetometer is further developed and described in this thesis which does not need balancing and can also be used during laparoscopic surgery. This thesis successfully demonstrates ways of using magnetic nanoparticles for SLNB. It also describes the development of a novel prototype for laparoscopic magnetic detection.

In this paper the focus is on thermal and electrical design aspects of a NbTi-based demonstrator magnet for magnetic density separation (MDS) that is being constructed at the University of Twente. MDS is a recycling technology that allows the separation of non-magnetic particles based on their mass density, using a vertical magnetic field gradient and a ferrofluid. To minimize the distance between the planar array of racetrack coils and the ferrofluid bath, the system is conduction-cooled. First the thermal design is presented, which shows that the coils can operate below 4.5 K with sufficient margin using a single cryocooler. High-purity aluminium heat drains enable a low thermal gradient across the cold mass. The current path is introduced, as well as the adopted protection scheme. The magnet’s stored energy can safely be dumped in the coils. Diodes are placed (anti-)parallel to the coils in the cold to prevent high terminal voltages. In the case of a quench in the superconducting part of the current leads or an external anomaly, a switch is opened and the current is forced through a resistor in series with the diodes, causing a deliberate transition of the coils to the normal state and thus a fast ramp-down.

Background: Robotic camera steering systems have been developed to facilitate endoscopic surgery. In this study, a randomized controlled trial was conducted to compare conventional human camera control with the AutoLap™ robotic camera holder in terms of efficiency and user experience when performing routine laparoscopic procedures. Novelty of this system relates to the steering method, which is image based. Methods: Patients undergoing an elective laparoscopic hemicolectomy, sigmoid resection, fundoplication and cholecystectomy between September 2016 and January 2018 were included. Stratified block randomization was used for group allocation. The primary aim of this study was to compare the efficiency of robotic and human camera control, measured with surgical team size and total operating time. Secondary outcome parameters were number of cleaning moments of the laparoscope and the post-study system usability questionnaire. Results: A total of 100 patients were randomized to have robotic (50) versus human (50) camera control. Baseline characteristics did not differ significantly between groups. In the robotic group, 49/50 (98%) of procedures were carried out without human camera control, reducing the surgical team size from four to three individuals. The median total operative time (60.0 versus 53.0 min, robotic vs. control) was not significantly different, p = 0.122. The questionnaire showed a positive user satisfaction and easy control of the robotic camera holder. Conclusion: Image-based robotic camera control can reduce surgical team size and does not result in significant difference in operative time compared to human camera control. Moreover, robotic image-guided camera control was associated with positive user experience.

Background: In the 123-study, we prospectively assessed, in a randomized fashion, the minimal cryoballoon application time necessary to achieve pulmonary vein (PV) isolation (PVI) in patients with paroxysmal atrial fibrillation (AF) with the aim to reduce complications by shortening the application duration. The first results of this study demonstrated that shortened cryoballoon applications (

BACKGROUND AND PURPOSE: Identification of a partial/complete chemotherapy response in pediatric patients with intracranial germ cell tumors is clinically important for radiation treatment and management. Partial/complete response is conventionally determined on postcontrast MR imaging sequences. The purpose of this study was to assess the diagnostic utility of a balanced steady-state free precession sequence as an adjunct to standard MR imaging sequences for the detection of residual tumor in pediatric patients on postchemoreduction pre–radiation planning MR imaging. MATERIALS AND METHODS: This was a retrospective study of pediatric patients with intracranial germ cell tumors undergoing postchemotherapy, preradiotherapy MR imaging. Patients underwent 1.5T or 3T MR imaging with pre- and postcontrast T1WIs, T2WIs, and a balanced steady-state free precession sequence. Two neuroradiologists independently reviewed standard MR imaging sequences without the balanced steady-state free precession sequence, then with the balanced steady-state free precession sequence 1 week later. Assessment for partial/complete response was determined using Response Assessment in Neuro-Oncology criteria. A 5-point Likert scale scored the diagnostic confidence of the neuroradiologist rating each study without/with the balanced steady-state free precession sequence. Rates of residual disease concordance and diagnostic confidence levels without/with the balanced steady-state free precession sequence were calculated. RESULTS: Thirty-nine patients were included with 31 males and 8 females (mean age, 14.15 ± 4.26 years). Thirty-one patients had single-site disease; 8 patients had multisynchronous disease (47 sites in total). Compared to review of the standard MR sequences alone, the addition of the balanced steady state free precession sequence resulted in higher rates of tumor partial response categorization and greater diagnostic confidence levels (P

Summary The droplet digital polymerase chain reaction (ddPCR) is a novel molecular technique that allows rapid quantification of rare target DNA sequences. Aim of this study was to explore the feasibility of the ddPCR technique to detect pathogen DNA in whole blood and to assess the diagnostic accuracy of ddPCR to detect bloodstream infections (BSIs), benchmarked against blood cultures. Broad‐range primers and probes were designed to detect bacterial 16S rRNA (and Gram stain for differentiation) and fungal 28S rRNA. To determine the detection limit of ddPCR, 10‐fold serial dilutions of E. coli and C. albicans were spiked in both PBS and whole blood. The diagnostic accuracy of ddPCR was tested in historically collected frozen blood samples from adult patients suspected of a BSI and compared with blood cultures. Analyses were independently performed by two research analysts. Outcomes included sensitivity and specificity of ddPCR. Within 4 h, blood samples were drawn, and DNA was isolated and analysed. The ddPCR detection limit was approximately 1–2 bacteria or fungi per ddPCR reaction. In total, 45 blood samples were collected from patients, of which 15 (33%) presented with positive blood cultures. The overall sensitivity of ddPCR was 80% (95% CI 52–96) and specificity 87% (95% CI 69–96). In conclusion, the ddPCR technique has considerable potential and is able to detect very low amounts of pathogen DNA in whole blood within 4 h. Currently, ddPCR has a reasonable sensitivity and specificity, but requires further optimization to make it more useful for clinical practice., The droplet digital polymerase chain reaction (ddPCR) is a novel molecular technique that allows rapid quantification of rare target DNA sequences. Aim of this study was to explore the feasibility of the ddPCR technique to detect pathogen DNA in whole blood, and to assess the diagnostic accuracy of ddPCR to detect bloodstream infections, benchmarked against blood cultures. The ddPCR technique showed considerable potential and was able to detect very low amounts of pathogen DNA in whole blood within 4 h. Currently, ddPCR has a reasonable sensitivity and specificity, but requires further optimization to make it more useful for clinical use.

To investigate the relationship between dynamic changes of coronary artery geometry and coronary artery disease (CAD) using computed tomography (CT). Seventy-one patients underwent coronary CT angiography with retrospective electrocardiographic gating. End-systolic (ES) and end-diastolic (ED) phases were automatically determined by dedicated software. Centerlines were extracted for the right and left coronary artery. Differences between ES and ED curvature and tortuosity were determined. Associations of change in geometrical parameters with plaque types and degree of stenosis were investigated using linear mixed models. The differences in number of inflection points were analyzed using Wilcoxon signed-rank tests. Tests were done on artery and segment level. One hundred thirty-seven arteries (64.3%) and 456 (71.4%) segments were included. Curvature was significantly higher in ES than in ED phase for arteries (p= 0.002) and segments (p< 0.001). The difference was significant only at segment level for tortuosity (p= 0.005). Number of inflection points was significantly higher in ES phase on both artery and segment level (p< 0.001). No significant relationships were found between degree of stenosis and plaque types and dynamic change in geometrical parameters. Non-invasive imaging by cardiac CT can quantify change in geometrical parameters of the coronary arteries during the cardiac cycle. Dynamic change of vessel geometry through the cardiac cycle was not found to be related to the presence of CAD.

The inter-strand contact resistance and AC losses were measured on an International Thermonuclear Experimental Reactor (ITER) poloidal field (PF) coil joint in a parallel applied AC magnetic field. In addition, the hysteresis loss was measured as a function of the angle with the applied magnetic field on a niobium-titanium (NbTi) strand of the same type as in the joint with a vibrating sample magnetometer. The AC loss measurements were performed at four applied field conditions for combinations of 0 or 1 T offset field and 0.2 or 0.4 T sinusoidal amplitude. The hysteresis loss of the joint was compared with the measured AC loss density of the NbTi strand for the same field conditions as the joint AC loss measurement but with varying the angle of the applied field. The subsequent cable twist angles affect the hysteresis loss since the critical current and penetration field depend on the angle of the applied field. It is found that 15.5° is an effective angle for the calculation of the hysteresis loss of joint when compared to the single strand measurement. The inter-strand contact resistance measurements cover all the typical strand combinations from the five cabling stages of the individual conductors, as well as the strand combinations across the two conductors to characterize the inter-strand including the copper sole resistivity. It is the first time to measure the contact resistances and AC losses of the full-size ITER PF joint. By comparing the measured and simulated data in the JackPot-ACDC model, it is also the first time to obtain the accurate inter-strand, inter-petal and strand to copper sole contact resistivities, which are the main input parameters for the further quantitative numerical analysis of the PF joints, in any current and magnetic field conditions.

A magnetic sentinel lymph node biopsy ((SLN)B) procedure has recently been shown feasible in oral cancer patients. However, a grading system is absent for proper identification and classification, and thus for clinical reporting. Based on data from eight complete magnetic SLNB procedures, we propose a provisional grading system. This grading system includes: (1) a qualitative five-point grading scale for MRI evaluation to describe iron uptake by LNs; (2) an ex vivo count of resected SLN with a magnetic probe to quantify iron amount; and (3) a qualitative five-point grading scale for histopathologic examination of excised magnetic SLNs. Most SLNs with iron uptake were identified and detected in level II. In this level, most variance in grading was seen for MRI and histopathology; MRI and medullar sinus were especially highly graded, and cortical sinus was mainly low graded. On average 82 ± 58 µg iron accumulated in harvested SLNs, and there were no significant differences in injected tracer dose (22.4 mg or 11.2 mg iron). In conclusion, a first step was taken in defining a comprehensive grading system to gain more insight into the lymphatic draining system during a magnetic SLNB procedure.

Background A procedure for sentinel lymph node biopsy (SLNB) using superparamagnetic iron-oxide (SPIO) nanoparticles and intraoperative sentinel lymph node (SLN) detection was developed to overcome drawbacks associated with the current standard-of-care SLNB. However, residual SPIO nanoparticles can result in void artefacts at follow-up magnetic resonance imaging (MRI) scans. We present a grading protocol to quantitatively assess the severity of these artefacts and offer an option to minimise the impact of SPIO nanoparticles on diagnostic imaging. Methods Follow-up mammography and MRI of two patient groups after a magnetic SLNB were included in the study. They received a 2-mL subareolar dose of SPIO (high-dose, HD) or a 0.1-mL intratumoural dose of SPIO (low-dose, LD). Follow-up mammography and MRI after magnetic SLNB were acquired within 4 years after breast conserving surgery (BCS). Two radiologists with over 10-year experience in breast imaging assessed the images and analysed the void artefacts and their impact on diagnostic follow-up. Results A total of 19 patients were included (HD, n = 13; LD, n = 6). In the HD group, 9/13 patients displayed an artefact on T1-weighted images up to 3.6 years after the procedure, while no impact of the SPIO remnants was observed in the LD group. Conclusions SLNB using a 2-mL subareolar dose of magnetic tracer in patients undergoing BCS resulted in residual artefacts in the breast in the majority of patients, which may hamper follow-up MRI. This can be avoided by using a 0.1-mL intratumoural dose.

Magnetic nanoparticles (MNPs) are widely used to facilitate magnetic particle imaging (MPI) which has the potential to become the leading diagnostic instrument for biomedical imaging. This comparative study assesses the effects of changing iron content and excitation frequency on point-spread function (PSF) representing the effect of magnetization reversal. PSF is quantified by features of interest for MPI: i.e. gradient amplitude and full-width-at-half-maximum (FWHM). A superparamagnetic quantifier (SPaQ) is used to assess differential magnetic susceptibility of two commercially available MNPs: Synomag��-D50 and Synomag��-D70. For both MNPs, the signal output depends on increase in drive field frequency and amount of iron-oxide, which might be hampering the sensitivity of MPI systems that perform on higher frequencies. Nevertheless, there is a clear potential of Synomag��-D for a stable MPI resolution, especially in case of 70 nm version, that is independent of either drive field frequency or amount of iron-oxide., International Journal on Magnetic Particle Imaging, Vol 8 No 1 Suppl 1 (2022)

Contains fulltext : 244201.pdf (Publisher’s version ) (Open Access) Recent studies suggest that a subset of cortical microinfarcts may be identifiable on T2* but invisible on T1 and T2 follow-up images. We aimed to investigate whether cortical microinfarcts are associated with iron accumulation after the acute stage. The RUN DMC - InTENse study is a serial MRI study including individuals with cerebral small vessel disease (SVD). 54 Participants underwent 10 monthly 3 T MRIs, including diffusion-weighted imaging, quantitative R1 (=1/T1), R2 (=1/T2), and R2* (=1/T2*) mapping, from which MRI parameters within areas corresponding to microinfarcts and control region of interests (ROIs) were retrieved within 16 participants. Finally, we compared pre- and post-lesional values with repeated measures ANOVA and post-hoc paired t-tests using the mean difference between lesion and control ROI values. We observed 21 acute cortical microinfarcts in 7 of the 54 participants (median age 69 years [IQR 66-74], 63% male). R2* maps demonstrated an increase in R2* values at the moment of the last available follow-up MRI (median [IQR], 5 [5-14] weeks after infarction) relative to prelesional values (p = .08), indicative of iron accumulation. Our data suggest that cortical microinfarcts are associated with increased R2* values, indicative of iron accumulation, possibly due to microhemorrhages, neuroinflammation or neurodegeneration, awaiting histopathological verification.

Recently, there has been a renewed interest in low-field MRI. Contrast agents (CA) in MRI have magnetic behavior dependent on magnetic field strength. Therefore, the optimal contrast agent for low-field MRI might be different from what is used at higher fields. Ultra-small superparamagnetic iron-oxides (USPIOs), commonly used as negative CA, might also be used for generating positive contrast in low-field MRI. The purpose of this study was to determine whether an USPIO or a gadolinium based contrast agent is more appropriate at low field strengths. Relaxivity values of ferumoxytol (USPIO) and gadoterate (gadolinium based) were used in this research to simulate normalized signal intensity (SI) curves within a concentration range of 0–15 mM. Simulations were experimentally validated on a 0.25T MRI scanner. Simulations and experiments were performed using spin echo (SE), spoiled gradient echo (SGE), and balanced steady-state free precession (bSSFP) sequences. Maximum achievable SIs were assessed for both CAs in a range of concentrations on all sequences. Simulations at 0.25T showed a peak in SIs at low concentrations ferumoxytol versus a wide top at higher concentrations for gadoterate in SE and SGE. Experiments agreed well with the simulations in SE and SGE, but less in the bSSFP sequence due to overestimated relaxivities in simulations. At low magnetic field strengths, ferumoxytol generates similar signal enhancement at lower concentrations than gadoterate.

Contains fulltext : 212564.pdf (Publisher’s version ) (Closed access) Laminar resolution, functional MRI (lfMRI) is a noninvasive technique with the potential to distinguish top-down and bottom-up signal contributions on the basis of laminar specific interactions between distal regions. Hitherto, lfMRI could not be demonstrated for either whole-brain distributed networks or for complex cognitive tasks. We show that lfMRI can reveal whole-brain directed networks during word reading. We identify distinct, language-critical regions based on their association with the top-down signal stream and establish lfMRI for the noninvasive assessment of directed connectivity during task performance.Interactions between top-down and bottom-up information streams are integral to brain function but challenging to measure noninvasively. Laminar resolution, functional MRI (lfMRI) is sensitive to depth-dependent properties of the blood oxygen level-dependent (BOLD) response, which can be potentially related to top-down and bottom-up signal contributions. In this work, we used lfMRI to dissociate the top-down and bottom-up signal contributions to the left occipitotemporal sulcus (LOTS) during word reading. We further demonstrate that laminar resolution measurements could be used to identify condition-specific distributed networks on the basis of whole-brain connectivity patterns specific to the depth-dependent BOLD signal. The networks corresponded to top-down and bottom-up signal pathways targeting the LOTS during word reading. We show that reading increased the top-down BOLD signal observed in the deep layers of the LOTS and that this signal uniquely related to the BOLD response in other language-critical regions. These results demonstrate that lfMRI can reveal important patterns of activation that are obscured at standard resolution. In addition to differences in activation strength as a function of depth, we also show meaningful differences in the interaction between signals originating from different depths both within a region and with the rest of the brain. We thus show that lfMRI allows the noninvasive measurement of directed interaction between brain regions and is capable of resolving different connectivity patterns at submillimeter resolution, something previously considered to be exclusively in the domain of invasive recordings. 6 p.

Contains fulltext : 209018.pdf (Publisher’s version ) (Closed access) Type 2 diabetes (T2D) is associated with an accelerated episodic memory decline, but the underlying pathophysiological mechanisms are not well understood. Hallmarks of T2D comprise impairment of insulin secretion and insulin sensitivity. Insulin signaling modulates cerebral neurotransmitter activity, including the excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) systems. Here we tested the hypothesis that the glutamate and GABA systems are altered in T2D patients and this relates to memory decline and insulin resistance. Using (1) H-magnetic resonance spectroscopy (MRS), we examined glutamate and GABA concentrations in episodic memory relevant brain regions (medial prefrontal cortex and precuneus) of T2D patients and matched controls. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps and memory performance was assessed using a face-profession associations test. T2D patients exhibited peripheral insulin resistance and had a decreased memory for face-profession associations as well as elevated GABA concentration in the medial prefrontal cortex but not precuneus. In addition, medial prefrontal cortex GABA concentration was negatively associated with memory performance suggesting that abnormal GABA levels in the medial prefrontal cortex are linked to the episodic memory decline that occurs in T2D patients.

Good B0 field homogeneity is considered an essential requirement to obtain high-quality MRS data. Many commonly used spectral fitting methods assume that all metabolite signals have Lorentzian or Gaussian shapes. However, B0 inhomogeneity can both broaden the linewidth and modify the lineshape. In this study, it is hypothesized that a realistic metabolite fitting model, which accounts for B0 homogeneity on the basis of the water lineshape, will improve the accuracy of estimation of metabolite concentrations. In-vivo water suppressed/unsuppressed single voxel spectroscopy signals were acquired under three different B0 field homogeneity regimes. Individual realistic basis sets were created for each acquisition. Frequency-domain spectral fitting with LCModel was used to quantify the metabolite concentrations with fitting uncertainties given in terms of the Cramer-Rao lower bound. The quantification results obtained using the water lineshape basis set yielded similar concentrations independent of linewidth and showed a larger fitting error as the linewidth increased. The conventional approach, however quantifies metabolite concentrations with greater variations despite showing a supposedly improved fitting quality. The water lineshape basis set achieved single voxel spectroscopy accuracy that is less sensitive to the linewidth compared to the conventional spectral fitting method for the range of linewidths used in this study, but the precision deteriorated with worsening B0 field inhomogeneity. The beneficial effect was ascribed to a reduction in the number of degrees of freedom when using the water lineshape to generate the basis set.

A novel probe for laparoscopic in vivo detection of superparamagnetic iron oxide nanoparticles (SPIONs) has been developed. The main application for in vivo detection of SPIONs our research group aims at is sentinel node biopsy. This is a method to determine if a tumor has spread through the body, which helps to improve cancer patient care. The method we use to selectively detect SPIONs is Differential Magnetometry (DiffMag). DiffMag makes use of small magnetic field strengths in the mT range. For DiffMag, a handheld probe is used that contains excitation and detection coils. However, depth sensitivity of a handheld probe is restricted by the diameter of the coils. Therefore, excitation and detection coils are separated in our novel probe. As a result, excitation coils can be made large and placed underneath a patient to generate a sufficiently large volume for the excitation field. Detection coils are made small enough to be used in laparoscopic surgery. The main challenge of this setup is movement of detection coils with respect to excitation coils. Consequently, the detector signal is obscured by the excitation field, making it impossible to measure the tiny magnetic signature from SPIONs. To measure SPIONs, active compensation is used, which is a way to cancel the excitation field seen by the detection coils. SPIONs were measured in various amounts and at various distances from the excitation coils. Furthermore, SPIONs were measured in proximity to a surgical steel retractor, and 3 L water. It is shown that small amounts of SPIONs (down to 25 μg Fe) can be measured, and SPIONs can be measured up to 20 cm from the top of the excitation coil. Also, surgical steel, and diamagnetism of water – and thus of tissue – have minor influence on DiffMag measurements. In conclusion, these results make this novel probe geometry combined with DiffMag promising for laparoscopic sentinel node biopsy.

This pilot study explored the value of localized index node removal after neoadjuvant immunotherapy in patients with stage III melanoma, for use as a response indicator to guide the extent of completion lymph node dissection. Promising technology.

Objective: Pelvic organ prolapse (POP) is clinically diagnosed in the supine position, where the effect of gravity is simulated by having the patients put strain on their pelvic floor. The objective of this study was to determine the degree of POP underestimation in the supine position based on magnetic resonance imaging (MRI) findings. Methods: This prospective study was conducted with symptomatic POP grade ≥ 2 patients. Fifteen female patients were examined with an MRI system that allows supine and upright imaging. The differences between supine and upright in distances of the bladder neck, cervix, and pouch of Douglas from the pubococcygeal line (PCL) were estimated, together with changes in the genital hiatal area. Patients were scanned at rest and during straining. All distances were compared using the Wilcoxon ranking test. Results: All mean distances from the PCL increased from the supine–strain to the upright–rest and from the supine–strain to the upright–strain position. These distances were found in the supine and upright positions: the bladder descended 1.3 cm to 1.4 cm, the cervix 1.1 cm to 2.2 cm, and the pouch of Douglas 0.8 cm to 1.5 cm respectively (all p values

Purpose To obtain whole-brain high-resolution T-2 maps in 2 minutes by combining simultaneous multislice excitation and low-power PINS (power independent of number of slices) refocusing pulses with undersampling and a model-based reconstruction. Methods A multi-echo spin-echo sequence was modified to acquire multiple slices simultaneously, ensuring low specific absorption rate requirements. In addition, the acquisition was undersampled to achieve further acceleration. Data were reconstructed by subsequently applying parallel imaging to separate signals from different slices, and a model-based reconstruction to estimate quantitative T-2 from the undersampled data. The signal model used is based on extended phase graph simulations that also account for nonideal slice profiles and B-1 inhomogeneity. In vivo experiments with 3 healthy subjects were performed to compare accelerated T-2 maps to fully sampled single-slice acquisitions. The accuracy of the T-2 values was assessed with phantom experiments by comparing the T-2 values to single-echo spin-echo measurements. Results In vivo results showed that conventional multi-echo spin-echo, simultaneous multislice, and undersampling result in similar mean T-2 values within regions of interest. However, combining simultaneous multislice and undersampling results in higher SDs (about 7 ms) in comparison to a conventional sequence (about 3 ms). The T-2 values were reproducible between scan and rescan (SD < 1.2 ms) within subjects and were in similar ranges across subjects (SD < 4.5 ms). Conclusion The proposed method is a fast T-2 mapping technique that enables whole-brain acquisitions at 0.7-mm in-plane resolution, 3-mm slice thickness, and low specific absorption rate in 2 minutes.

Wire-guided localization (WGL) is the standard of care in the surgical treatment of nonpalpable breast tumors. In this study, we compare the use of a new magnetic marker localization (MaMaLoc) technique to WGL in the treatment of early-stage breast cancer patients. Open-label, single-center, randomized controlled trial comparing MaMaLoc (intervention) to WGL (control) in women with early-stage breast cancer. Primary outcome was surgical usability measured using the System Usability Scale (SUS, 0-100 score). Secondary outcomes were patient reported, clinical, and pathological outcomes such as retrieval rate, operative time, resected specimen weight, margin status, and reoperation rate. Thirty-two patients were analyzed in the MaMaLoc group and 35 in the WGL group. Patient and tumor characteristics were comparable between groups. No in situ complications occurred. Retrieval rate was 100% in both groups. Surgical usability was higher for MaMaLoc: 70.2 ± 8.9 vs. 58.1 ± 9.1, p < 0.001. Patients reported higher overall satisfaction with MaMaLoc (median score 5/5) versus WGL (score 4/5), p < 0.001. The use of magnetic marker localization (MaMaLoc) for early-stage breast cancer is effective and has higher surgical usability than standard WGL.

Objectives To assess the feasibility and merits of a complete magnetic approach for a sentinel lymph node biopsy (SLNB) procedure in oral cancer patients. Materials and methods This study included ten oral cancer patients (stage cT1-T2N0M0) scheduled for elective neck dissection (END). Superparamagnetic iron oxide nanoparticles (SPIO) were administered peritumorally prior to surgery. A preoperative MRI was acquired to identify lymph nodes (LNs) with iron uptake. A magnetic detector was used to identify magnetic hotspots prior, during, and after the SLNB procedure. The resected sentinel LNs (SLNs) were evaluated using step-serial sectioning, and the neck dissection specimen was assessed by routine histopathological examination. A postoperative MRI was acquired to observe any residual iron. Results Of ten primary tumors, eight were located in the tongue, one floor-of-mouth (FOM), and one tongue-FOM transition. SPIO injections were experienced as painful by nine patients, two of whom developed a tongue swelling. In eight patients, magnetic SLNs were successfully detected and excised during the magnetic SLNB procedure. During the END procedure, additional magnetic SLNs were identified in three patients. Histopathology confirmed iron deposits in sinuses of excised SLNs. Three SLNs were harboring metastases, of which one was identified only during the END procedure. The END specimens revealed no further metastases. Conclusion A complete magnetic SLNB procedure was successfully performed in eight of ten patients (80% success rate), therefore the procedure seems feasible. Recommendations for further investigation are made including: use of anesthetics, magnetic tracer volume, planning preoperative MRI, comparison to conventional technique and follow-up.

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising for clinical applications, because they have a characteristic nonlinear magnetic response when an external magnetic field is applied. This nonlinearity enables the distinct detection of SPIONs and makes measurements less sensitive to the human body and surgical steel instruments. In clinical applications, only a limited field strength for the magnetic detection is allowed. The signal to noise ratios (SNRs) of four nonlinear magnetic detection methods are compared. These methods include differential magnetometry and three variations of magnetic particle spectroscopy: frequency mixing, second harmonic detection and third harmonic detection. All methods were implemented on the same hardware and experimentally compared for various field strengths. To make the comparison fair, the same power was supplied to the excitation coil each time. In general, the SNR increases with increasing field strength. The SNR per drive field of all methods stabilizes or even decreases for field strengths above 6 mT. The second harmonic detection has the best SNR and the most room for improvement.

Urinary incontinence (UI) is a common problem in children. It is important to treat UI effectively, because of the major social impact on the child’s quality of life. Children rated ‘wetting their pants in class’ repeatedly in the top 5 of most stressful life events between ‘losing my mother or father’ or ‘going blind’. To support these children, it could be beneficial to continuously monitor the fullness of the bladder for both diagnostics – and treatment purposes by means of wearable ultrasonography. The first part of this thesis focusses on the design, the (safety) verification, and clinical validation of the initial clinical prototype, the URIKA Bladder Monitor, and the new redesigned, commercialized device: the SENS-U. The main objective of the first part is to determine the safety and performance of these new ultrasound devices, under normal conditions of use, in order to obtain CE-marking. After CE-marking was obtained, the second part of the thesis started focusing on the clinical implementation and valorization of the SENS-U. The clinical results reported are directly derived from using this device for children with urinary incontinence. The main objectives of the second part are (1) to evaluate the performance of the SENS-U during regular daily life activities, (2) to verify the accuracy for nighttime registration of the bladder filling and (3) to establish and verify the clinical benefits of the device. Finally, this thesis discussed the first steps towards a broader clinical implementation, presenting the first potential clinical benefits of SENS-U: increasing the awareness of a full bladder through direct biofeedback, being able to become and stay dry, providing insight regarding possible residual volume, producing better voided or catheterized volumes, increasing the quality of life, supporting central inhibition and becoming more independent. However, there was several technological opportunities were identified which could be beneficial for a broader clinical implementation and valorization of the SENS-U.

Over the past decade, cryoballoon therapy has evolved into a well-recognized and recommended ablation method to perform pulmonary vein isolation (PVI) in the treatment of atrial fibrillation (AF)1. This thesis describes the search for a balance between safety and efficacy in cryoballoon PVI and focusses primarily on the improvement of safety aspects. In the early stage of cryoballoon PVI, the main goal of cryoballoon ablation was to reach similar outcomes compared to the traditional “gold standard” point by point radiofrequency (RF) ablation. The safety aspect was not mentioned regularly in global research. Over the last years, the paradigm has shifted. After the introduction of the second-generation cryoballoon and the proven non-inferiority to RF ablation, more attention was pointed to the safety aspect. During the years in which the research of this dissertation was performed, the number of studies on safety aspects showed a sharp increase. Original promotion date was June 19, 2020 (COVID-19)

Introduction Magnetic resonance spectroscopic imaging (MRSI) has the potential to add a layer of understanding of the neurobiological mechanisms underlying brain diseases, disease progression, and treatment efficacy. Limitations related to metabolite fitting of low signal‐to‐noise ratios data, signal variations due to partial‐volume effects, acquisition and extracranial lipid artifacts, along with clinically relevant aspects such as scan time constraints, are among the challenges associated with in vivo MRSI. Methods The aim of this work was to address some of these factors and to develop an acquisition, reconstruction, and postprocessing pipeline to derive lipid‐suppressed metabolite values of central brain structures based on free‐induction decay measurements made using a 7 T MR scanner. Anatomical images were used to perform high‐resolution (1 mm3) partial‐volume correction to account for gray matter, white matter (WM), and cerebral‐spinal fluid signal contributions. Implementation of automatic quality control thresholds and normalization of metabolic maps from 23 subjects to the Montreal Neurological Institute (MNI) standard atlas facilitated the creation of high‐resolution average metabolite maps of several clinically relevant metabolites in central brain regions, while accounting for macromolecular distributions. Partial‐volume correction improved the delineation of deep brain nuclei. We report average metabolite values including glutamate + glutamine (Glx), glycerophosphocholine, choline and phosphocholine (tCho), (phospo)creatine, myo‐inositol and glycine (mI‐Gly), glutathione, N‐acetyl‐aspartyl glutamate(and glutamine), and N‐acetyl‐aspartate in the basal ganglia, central WM (thalamic radiation, corpus callosum) as well as insular cortex and intracalcarine sulcus. Conclusion MNI‐registered average metabolite maps facilitate group‐based analysis, thus offering the possibility to mitigate uncertainty in variable MRSI data., We use a 7 T MRI scanner along with a combination of advanced acquisition, reconstruction, and postprocessing techniques to derive metabolic distribution in deep brain structures.

The nonlinear magnetic behaviour of superparamagnetic iron-oxide nanoparticles (SPIONs) has attracted interest as a valuable feature for upcoming medical applications. Injecting SPIONs into the human body affects their magnetic properties through the formation of protein corona or cell immobilisation. It is therefore important to study the effects of environmental changes on the magnetic susceptibility of SPIONs. A superparamagnetic quantifier (SPaQ) is used here to assess the differential magnetic susceptibility of three commercially available SPIONs: Synomag®, Resovist® and Sienna+®. The following experiments were carried out to mimic the influence of the biological environment on the magnetic responses of SPIONs: (i) varying the viscosity of the medium; and (ii) immobilising the nanoparticles by freeze-drying. Differential magnetisation curves as a function of the applied magnetic field were visualised to reveal the dynamic magnetic behaviour of SPIONs in both experiments. Synomag® displayed the lowest decrease (~5%) in differential magnetic susceptibility compared to Resovist® (~33%) and Sienna+® (~21%), for a change from water to a high-viscosity fluid. Although Synomag® showed a clear drop in differential magnetic susceptibility (~58%) after freeze-drying, it still appears to be a promising candidate for clinical applications due to its low sensitivity to changes in viscosity.

Background Low oesophageal temperatures (OTs) during cryoballoon pulmonary vein isolation (PVI) have been associated with complications. This study assessed the incidence of low OT in clinical practice during cryoballoon PVI and verified possible predictive values for low OT. Methods Consecutive patients who underwent PVI using the second-generation cryoballoon were retrospectively included. The distance from the oesophagus to the different pulmonary veins (PVs) (OP distance), body mass index (BMI), sex, age, balloon temperature and application time were studied as potential predictors of low OTs. Computed tomography was performed before the procedure to determine the OP distance. OT was measured using an oesophageal temperature probe. Applications were ended prematurely if the OT reached Results Two hundred and four patients were included. Low OT was observed in 54 patients (26%) and 27 patients (13%) reached ultralow OTs. OP distance was the only predictor of low OTs after multivariate analysis. A cut-off value of 19 mm showed 96.2% sensitivity and 37.8% specificity in predicting low OTs. No clinically relevant relation was found between low OTs and BMI, age, sex, balloon temperature or application duration. Conclusions The incidence of low OT was 26% for cryoballoon PVI. OP distance was the only predictor of low OTs. Since an OP distance

This work is an assessment of changes in magnetic properties of magnetic nanoparticles in various biological environments. To mimic variations in biological conditions, we have evaluated magnetic performance of Synomag® nanoparticles in two experiments: the effect of viscosity by varying the ratio of glycerol/water mixture and the effect of immobilization after blocking the Brownian relaxation by freeze-drying (to mimic uptake in macrophages). The magnetic response was measured with the Superparamagnetic quantifier. Synomag® exhibits a slight decrease (7.9%) of magnetic response under increased viscosity from η1=0.95 to η6=259.71 mPa.s, and a dramatic magnetic signal drop (78.2%) after freeze-drying. Synomag® nanoparticles are less sensitive to viscosity due to an additional relaxation mechanism of disordered spins within the nanoflowers. However, the magnetic performance has been reduced due to the blocking of Brownian relaxation after immobilization. Int. J. Mag. Part. Imag. 6(2), Suppl. 1, 2020, Article ID: 2009022, DOI: 10.18416/IJMPI.2020.2009022, International Journal on Magnetic Particle Imaging, Vol 6 No 2 Suppl. 1 (2020)

During surgery, surgeons must identify vital anatomical structures (nerves and lymph nodes) to prevent damage. Correct identification remains enormously challenging and surgeons require high-tech intra-operative imaging. Our team worked on developing a demonstrator of H3D-VISIOnAiR that enables visualizing the invisible by combining a commercial spectral + RGB camera, advanced image analytics and near eye display. Tests were performed with a simulated surgical task consisting of positioning beads in a nailbed with very low contrast. The results show proof of concept by real-time 2D high-resolution image acquisition, processing of hyperspectral images and displaying augmented reality overlay of processed hyperspectral images.