Excitation coil for sentinel lymph node harvesting: design, digital twin and prototype.

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.

High incidence of (ultra)low oesophageal temperatures during cryoballoon pulmonary vein isolation for atrial fibrillation.

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 <16 °C. Low and ultralow OT were defined as OT <20 and <16 °C respectively. 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 <19 mm was present in all patients in at least one PV, we recommend routine OT measurement during PVI cryoballoon therapy to prevent oesophagus-related complications.

Experimental comparison of four nonlinear magnetic detection methods and considerations on clinical usability.

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.

A novel characterization technique for superparamagnetic iron oxide nanoparticles: The superparamagnetic quantifier, compared with magnetic particle spectroscopy.

Superparamagnetic iron oxide nanoparticles (SPIONs) are used as a tracer material in sentinel node biopsies. The latter is a procedure to analyze if cancer cells have spread to lymph nodes, helping to personalize patient care. To predict SPION behavior in vivo, it is important to analyze their magnetic properties in biological environments. The superparamagnetic quantifier (SPaQ) is a new device to measure the dynamic magnetization curve of SPIONs. The magnetization curve was measured for two types of SPIONs: Resovist and SHP-25. We used three techniques: Vibrating Sample Magnetometry (VSM), Magnetic Particle Spectroscopy (MPS), and our new SPaQ. Furthermore, AC susceptibility (ACS) measurements were performed as part of the evaluation of the three techniques. SPaQ and VSM results were found to be similar. Measurement results were nearly identical in both directions, indicating minor hysteresis. However, in MPS measurements, a clear hysteresis loop was observed. Furthermore, the ACS measurements showed a pronounced Brownian maximum, indicating an optimal response for an AC frequency below 10 kHz for both particle systems. Both the SPaQ and MPS were found to be superior to VSM since measurements are faster, can be performed at room temperature, and are particularly sensitive to particle dynamics. The main difference between the SPaQ and MPS lies in the excitation sequence. The SPaQ combines an alternating magnetic field that has a low amplitude with a gradual DC offset, whereas MPS uses only an alternating field that has a large amplitude. In conclusion, both the SPaQ and MPS are highly suited to improve understanding SPION behavior, which will lead to the radical improvement of sentinel node biopsy accuracy.

Surgical removal of the index node marked using magnetic seed localization to assess response to neoadjuvant immunotherapy in patients with stage III melanoma.

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.

Low-field magnetic resonance imaging offers potential for measuring tibial component migration.

BACKGROUND: Roentgen stereophotogrammetric analysis (RSA) is used to measure early prosthetic migration and to predict future implant failure. RSA has several disadvantages, such as the need for perioperatively inserted tantalum markers. Therefore, this study evaluates low-field MRI as an alternative to RSA. The use of traditional MRI with prostheses induces disturbing metal artifacts which are reduced by low-field MRI. The purpose of this study is to assess the feasibility to use low-field (0.25 Tesla) MRI for measuring the precision of zero motion. This was assessed by calculating the virtual prosthetic motion of a zero-motion prosthetic reconstruction in multiple scanning sessions. Furthermore, the effects of different registration methods on these virtual motions were tested. RESULTS: The precision of zero motion for low-field MRI was between 0.584 mm and 1.974 mm for translation and 0.884° and 3.774° for rotation. The manual registration method seemed most accurate, with µ ≤ 0.13 mm (σ ≤ 0.931 mm) for translation and µ ≤ 0.15° (σ ≤ 1.63°) for rotation. CONCLUSION: Low-field MRI is not yet as precise as today's golden standard (marker based RSA) as reported in the literature. However, low-field MRI is feasible of measuring the relative position of bone and implant with comparable precision as obtained with marker-free RSA techniques. Of the three registration methods tested, manual registration was most accurate. Before starting clinical validation further research is necessary and should focus on improving scan sequences and registration algorithms.

Feasibility of magnetic marker localisation for non-palpable breast cancer.

OBJECTIVES: Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. MATERIALS AND METHODS: Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. RESULTS: Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. CONCLUSION: Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies.

A handheld SPIO-based sentinel lymph node mapping device using differential magnetometry.

Sentinel lymph node biopsy has become a staple tool in the diagnosis of breast cancer. By replacing the morbidity-plagued axillary node clearance with removing only those nodes most likely to contain metastases, it has greatly improved the quality of life of many breast cancer patients. However, due to the use of ionizing radiation emitted by the technetium-based tracer material, the current sentinel lymph node biopsy has serious drawbacks. Most urgently, the reliance on radioisotopes limits the application of this procedure to small parts of the developed world, and it imposes restrictions on patient planning and hospital logistics. Magnetic alternatives have been tested in recent years, but all have their own drawbacks, mostly related to interference from metallic instruments and electromagnetic noise coming from the human body. In this paper, we demonstrate an alternative approach that utilizes the unique nonlinear magnetic properties of superparamagnetic iron oxide nanoparticles to eliminate the drawbacks of both the traditional gamma-radiation centered approach and the novel magnetic techniques pioneered by others. Contrary to many other nonlinear magnetic approaches however, field amplitudes are limited to 5 mT, which enables handheld operation without additional cooling. We show that excellent mass sensitivity can be obtained without the need for external re-balancing of the probe to negate any influences from the human body. Additionally, we show how this approach can be used to suppress artefacts resulting from the presence of metallic instruments, which are a significant dealbreaker when using conventional magnetometry-based approaches.

Meta-analysis of sentinel lymph node biopsy in breast cancer using the magnetic technique.

BACKGROUND: The standard for sentinel lymph node biopsy (SLNB), the dual technique (radiolabelled tracer and blue dye), has several drawbacks. A novel magnetic technique without these drawbacks has been evaluated in a number of clinical trials. It uses a magnetic tracer and a handheld magnetometer to identify and excise sentinel lymph nodes. A systematic review and meta-analysis was performed to assess the performance and utility of the magnetic in comparison to the standard technique. METHODS: MEDLINE, PubMed, Embase and the Cochrane online literature databases were used to identify all original articles evaluating the magnetic technique for SLNB published up to April 2016. Studies were included if they were prospectively conducted clinical trials comparing the magnetic with the standard technique for SLNB in patients with breast cancer. RESULTS: Seven studies were included. The magnetic technique was non-inferior to the standard technique (z = 3·87, P < 0·001), at a 2 per cent non-inferiority margin. The mean identification rates for the standard and magnetic techniques were 96·8 (range 94·2-99·0) and 97·1 (94·4-98·0) per cent respectively (risk difference (RD) 0·00, 95 per cent c.i. -0·01 to 0·01; P = 0·690). The total lymph node retrieval was significantly higher with the magnetic compared with the standard technique: 2113 (1·9 per patient) versus 2000 (1·8 per patient) (RD 0·05, 0·03 to 0·06; P = 0·003). False-negative rates were 10·9 (range 6-22) per cent for the standard technique and 8·4 (2-22) per cent for the magnetic technique (RD 0·03, 0·00 to 0·06; P = 0·551). The mean discordance rate was 3·9 (range 1·7-6·9) per cent. CONCLUSION: The magnetic technique for SLNB is non-inferior to the standard technique, with a high identification rate but with a significantly higher lymph node retrieval rate.

Ex vivo sentinel lymph node mapping in colorectal cancer using a magnetic nanoparticle tracer to improve staging accuracy: a pilot study.

AIM: Nodal status is the most important prognostic factor in colorectal cancer (CRC). Small occult metastases may remain undetected on conventional histopathological examination, potentially resulting in undertreatment. Ex vivo sentinel lymph node mapping (SLNM) can be used to improve the accuracy of nodal staging, but the currently used tracers suffer from drawbacks, which hamper implementation of the technique in routine clinical practice. Magnetic tracers are the optimal size for sentinel lymph node (SLN) retention and allow objective quantitative selection of SLNs; they therefore have great potential for SLNM in CRC. The study evaluates the feasibility of ex vivo magnetic SLNM and compares the performance of this technique with blue dye SLNM. METHOD: Twenty-eight ex vivo SLNM procedures were performed in 27 histological node-negative patients with CRC using a magnetic tracer and blue dye. A magnetometer was used to select magnetic SLNs after formalin fixation of the CRC specimen. Both magnetic and blue SLNs were subjected to serial sectioning and immunohistochemical staining to reveal occult metastases. RESULTS: At least one SLN was successfully identified in 27/28 (96%) and 25/28 (89%) of the cases with the magnetic technique and blue dye. Isolated tumour cells were detected in 10 patients. This was predicted with 100% sensitivity and accuracy using the magnetic technique, and with 91% sensitivity and 96% accuracy using the blue dye technique. CONCLUSION: This study demonstrates that ex vivo magnetic SLNM is a feasible technique for use in routine clinical practice, improving nodal staging accuracy of CRC patients.

Thinner Regions of Intracranial Aneurysm Wall Correlate with Regions of Higher Wall Shear Stress: A 7T MRI Study.

BACKGROUND AND PURPOSE: Both hemodynamics and aneurysm wall thickness are important parameters in aneurysm pathophysiology. Our aim was to develop a method for semi-quantitative wall thickness assessment on in vivo 7T MR images of intracranial aneurysms for studying the relation between apparent aneurysm wall thickness and wall shear stress. MATERIALS AND METHODS: Wall thickness was analyzed in 11 unruptured aneurysms in 9 patients who underwent 7T MR imaging with a TSE-based vessel wall sequence (0.8-mm isotropic resolution). A custom analysis program determined the in vivo aneurysm wall intensities, which were normalized to the signal of nearby brain tissue and were used as measures of apparent wall thickness. Spatial wall thickness variation was determined as the interquartile range in apparent wall thickness (the middle 50% of the apparent wall thickness range). Wall shear stress was determined by using phase-contrast MR imaging (0.5-mm isotropic resolution). We performed visual and statistical comparisons (Pearson correlation) to study the relation between wall thickness and wall shear stress. RESULTS: 3D colored apparent wall thickness maps of the aneurysms showed spatial apparent wall thickness variation, which ranged from 0.07 to 0.53, with a mean variation of 0.22 (a variation of 1.0 roughly means a wall thickness variation of 1 voxel [0.8 mm]). In all aneurysms, apparent wall thickness was inversely related to wall shear stress (mean correlation coefficient, -0.35; P < .05). CONCLUSIONS: A method was developed to measure the wall thickness semi-quantitatively, by using 7T MR imaging. An inverse correlation between wall shear stress and apparent wall thickness was determined. In future studies, this noninvasive method can be used to assess spatial wall thickness variation in relation to pathophysiologic processes such as aneurysm growth and rupture.

Systematic review of high-intensity focused ultrasound ablation in the treatment of breast cancer.

BACKGROUND: A systematic review was undertaken to assess the clinical efficacy of non-invasive high-intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer. METHODS: MEDLINE/PubMed library databases were used to identify all studies published up to December 2013 that evaluated the role of HIFU ablation in the treatment of breast cancer. Studies were eligible if they were performed on patients with breast cancer and objectively recorded at least one clinical outcome measure of response (imaging, histopathological or cosmetic) to HIFU treatment. RESULTS: Nine studies fulfilled the inclusion criteria. The absence of tumour or residual tumour after treatment was reported for 95·8 per cent of patients (160 of 167). No residual tumour was found in 46·2 per cent (55 of 119; range 17-100 per cent), less than 10 per cent residual tumour in 29·4 per cent (35 of 119; range 0-53 per cent), and between 10 and 90 per cent residual tumour in 22·7 per cent (27 of 119; range 0-60 per cent). The most common complication associated with HIFU ablation was pain (40·1 per cent) and less frequently oedema (16·8 per cent), skin burn (4·2 per cent) and pectoralis major injury (3·6 per cent). MRI showed an absence of contrast enhancement after treatment in 82 per cent of patients (31 of 38; range 50-100 per cent), indicative of coagulative necrosis. Correlation of contrast enhancement on pretreatment and post-treatment MRI successfully predicted the presence of residual disease. CONCLUSION: HIFU treatment can induce coagulative necrosis in breast cancers. Complete ablation has not been reported consistently on histopathology and no imaging modality has been able confidently to predict the percentage of complete ablation. Consistent tumour and margin necrosis with reliable follow-up imaging are required before HIFU ablation can be evaluated within large, prospective clinical trials.