Performance of a Nonlinear Magnetic Handheld Probe for Intraoperative Sentinel Lymph Node Detection: A Phantom Study.

OBJECTIVE: This study investigates the performance of the DiffMag handheld probe (nonlinear magnetometry), to be used for sentinel lymph node detection. Furthermore, the performance of DiffMag is compared with a gamma probe and a first-order magnetometer (Sentimag®, linear magnetometry). METHODS: The performance of all three probes was evaluated based on longitudinal distance, transverse distance, and resolving power for two tracer volumes. A phantom was developed to investigate the performance of the probes for a clinically relevant situation in the floor of the mouth (FOM). RESULTS: Considering the longitudinal distance, both DiffMag handheld and Sentimag® probe had comparable performance, while the gamma probe was able to detect at least a factor of 10 deeper. Transverse distances of 13, 11, and 51 mm were measured for the small tracer volume by the DiffMag handheld, Sentimag®, and the gamma probe, respectively. For the large tracer volume this was 21, 18, and 55 mm, respectively. The full width at half maximum, at 7 mm probe height from the phantom surface, was 14, 12, and 18 mm for the small tracer volume and 15, 18, and 25 mm for the large tracer volume with the DiffMag handheld, Sentimag®, and gamma probe, respectively. CONCLUSIONS: With a high resolving power but limited longitudinal distance, the DiffMag handheld probe seems suitable for detecting SLNs which are in close proximity to the primary tumor. In this study, comparable results were shown using linear magnetometry. The gamma probe reached 10 times deeper, but has a lower resolving power compared with the DiffMag handheld probe.

Triaxial detection of the neuromagnetic field using optically-pumped magnetometry: feasibility and application in children.

Optically-pumped magnetometers (OPMs) are an established alternative to superconducting sensors for magnetoencephalography (MEG), offering significant advantages including flexibility to accommodate any head size, uniform coverage, free movement during scanning, better data quality and lower cost. However, OPM sensor technology remains under development; there is flexibility regarding OPM design and it is not yet clear which variant will prove most effective for MEG. Most OPM-MEG implementations have either used single-axis (equivalent to conventional MEG) or dual-axis magnetic field measurements. Here we demonstrate use of a triaxial OPM formulation, able to characterise the full 3D neuromagnetic field vector. We show that this novel sensor is able to characterise magnetic fields with high accuracy and sensitivity that matches conventional (dual-axis) OPMs. We show practicality via measurement of biomagnetic fields from both the heart and the brain. Using simulations, we demonstrate how triaxial measurement offers improved cortical coverage, especially in infants. Finally, we introduce a new 3D-printed child-friendly OPM-helmet and demonstrate feasibility of triaxial measurement in a five-year-old. In sum, the data presented demonstrate that triaxial OPMs offer a significant improvement over dual-axis variants and are likely to become the sensor of choice for future MEG systems, particularly for deployment in paediatric populations.

Sentinel lymph node localization and staging with a low-dose of superparamagnetic iron oxide (SPIO) enhanced MRI and magnetometer in patients with cutaneous melanoma of the extremity - The MAGMEN feasibility study.

BACKGROUND: In patients with melanoma, sentinel lymph node (SLN) status is pivotal for treatment decisions. Current routine for SLN detection combines Technetium99m (Tc99) lymphoscintigraphy and blue dye (BD). The primary aim of this study was to examine the feasibility of using a low dose of superparamagnetic iron oxide (SPIO) injected intracutaneously to detect and identify the SLN, and the secondary aim was to investigate if a low dose of SPIO would enable a preoperative MRI-evaluation of SLN status. METHODS: Patients with melanoma of the extremities were eligible. Before surgery, a baseline MRI of the nodal basin was followed by an injection of a low dose (0.02-0.5 mL) of SPIO and then a second MRI (SPIO-MRI). Tc99 and BD was used in parallel and all nodes with a superparamagnetic and/or radioactive signal were harvested and analyzed. RESULTS: Fifteen patients were included and the SLNB procedure was successful in all patients (27 SLNs removed). All superparamagnetic SLNs were visualized by MRI corresponding to the same nodes on scintigraphy. Micrometastatic deposits were identified in four SLNs taken from three patients, and SPIO-MRI correctly predicted two of the metastases. There was an association between MRI artefacts in the lymph node and the dose SPIO given. DISCUSSION: It is feasible to detect SLN in patients with melanoma using a low dose of SPIO injected intracutaneously compared with the standard dual technique. A low dose of SPIO reduces the lymph node MRI artefacts, opening up for a non-invasive assessment of SLN status in patients with cancer.

Laparoscopic Probe for Sentinel Lymph Node Harvesting Using Magnetic Nanoparticles.

OBJECTIVE: Sentinel lymph node harvesting is an essential step in the surgical treatment of a growing number of malignancies. Various techniques are available to facilitate this purpose. The present study reports a new laparoscopic technique for lymph node harvesting using magnetic nanoparticles containing a superparamagnetic iron-oxide core and dextran coating. This study assesses the clinical relevance of the prototype and provides input for further technological development on the way to clinical implementation. METHODS: A laparoscopic differential magnetometer prototype was built, utilizing a nonlinear detection principle (differential magnetometry) for magnetic identification of lymph nodes. The iron content sensitivity, depth & spatial sensitivity, and angular sensitivity were analyzed to investigate clinical options. RESULTS: The minimum detectable amount of iron was 9.8 µg at a distance of 1 mm. The detection depth was 5, 8, and 10 mm for samples containing 126, 252, and 504 µg iron, respectively. The maximum lateral detection distance was 5, 7, and 8 mm for samples containing 126, 252, and 504 µg iron, respectively. A sample containing 504 µg iron was detectable at all angulations assessed (0°, 30°, 60° and 90°). CONCLUSION: The laparoscopic differential magnetometer demonstrates promising results for further investigation and development towards laparoscopic lymph node harvesting using magnetic nanoparticles. SIGNIFICANCE: The laparoscopic differential magnetometer facilitates a novel method for sentinel lymph node harvesting, which helps to determine prognosis and treatment of cancer patients.

New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives with MI-Crobicidal and Antibiofilm Activity Enhanced by Combination with Iron Oxide Nanoparticles.

Antimicrobial resistance is one of the major public health threats at the global level, urging the search for new antimicrobial molecules. The fluorene nucleus is a component of different bioactive compounds, exhibiting diverse pharmacological actions. The present work describes the synthesis, chemical structure elucidation, and bioactivity of new O-aryl-carbamoyl-oxymino-fluorene derivatives and the contribution of iron oxide nanoparticles to enhance the desired biological activity. The antimicrobial activity assessed against three bacterial and fungal strains, in suspension and biofilm growth state, using a quantitative assay, revealed that the nature of substituents on the aryl moiety are determinant for both the spectrum and intensity of the inhibitory effect. The electron-withdrawing inductive effect of chlorine atoms enhanced the activity against planktonic and adhered Staphylococcus aureus, while the +I effect of the methyl group enhanced the anti-fungal activity against Candida albicans strain. The magnetite nanoparticles have substantially improved the antimicrobial activity of the new compounds against planktonic microorganisms. The obtained compounds, as well as the magnetic core@shell nanostructures loaded with these compounds have a promising potential for the development of novel antimicrobial strategies.

Using Magnetometry to Monitor Cellular Incorporation and Subsequent Biodegradation of Chemically Synthetized Iron Oxide Nanoparticles.

Magnetic nanoparticles, made of iron oxide, present a peculiar interest for a wide range of biomedical applications for which they are often internalized in cells and then left within. One challenge is to assess their fate in the intracellular environment with reliable and precise methodologies. Herein, we introduce the use of the vibrating sample magnetometer (VSM) to precisely quantify the integrity of magnetic nanoparticles within cells by measuring their magnetic moment. Stem cells are first labeled with two types of magnetic nanoparticles; the nanoparticles have the same core produced via a fast and efficient microwave-based nonaqueous sol gel synthesis and differ in their coating: the commonly used citric acid molecule is compared to polyacrylic acid. The formation of 3D cell-spheroids is then achieved via centrifugation and the magnetic moment of these spheroids is measured at different times with the VSM. The obtained moment is a direct fingerprint of the nanoparticles' integrity, with decreasing values indicative of a nanoparticle degradation. For both nanoparticles, the magnetic moment decreases over culture time revealing their biodegradation. A protective effect of the polyacrylic acid coating is also shown, when compared to citric acid.

Safety and efficacy of magnetic seed localisation of non-palpable breast lesions: pilot study in a Chinese population.

INTRODUCTION: A magnetic seed marker system (Magseed, Endomagnetics, Cambridge, United Kingdom) is used as a localisation method for non-palpable breast lesions in the United States, Europe, and Hong Kong. It overcomes many limitations of conventional techniques and allows scheduling flexibility. We sought to evaluate its efficacy and safety in the Chinese population. METHODS: We retrospectively reviewed all Chinese women who underwent magnetic seed marker-guided breast lesion excision from June 2019 to February 2020 at a single institution. Placement success (final target-to-seed distance <10 mm) was evaluated by imaging on the day of surgery. Specimen radiographs and pathology reports were reviewed for magnetic seed markers and target removal. Margin clearance and re-excision rates were analysed. RESULTS: Twenty two magnetic seed markers were placed in 21 patients under sonographic or stereotactic guidance to localise 21 target lesions. One target lesion required two magnetic seed markers for bracketing. There was no migration of nine markers placed 6 to 56 days before the day of surgery. Placement success was achieved in 20 (90.9%) cases. Mean final target-to-seed distance was 3.1 mm. Two out of 21 (9.5%) lesions required alternative localisation due to marker migration ≥10 mm, while 19 (90.5%) lesions underwent successful magnetic seed marker-guided excision. Three of these 19 lesions (15.8%) were excised with therapeutic intent, one of which (33%) required re-excision due to a close margin. All 22 magnetic seed markers were successfully removed. No complications were reported. CONCLUSION: Magnetic seed markers demonstrated safety and efficacy in Chinese women for breast lesion localisation and excision.

Biomagnetism of tumor in rats with Guerin's carcinoma after injection of ferromagnetic nanocomposite (Ferroplat): contactless measurement.

AIM: In order to develop fundamentally new technologies for non-invasive and safer diagnosis of cancer, we aimed to detect non-contact magnetic signals from a malignant tumor in animals treated or not-treated with the ferromagnetic nanocomposite Ferroplat. MATERIALS AND METHODS: Guerin's carcinoma was used as a model of tumor growth. The biomagnetism of the tumor was evaluated in the dynamics of its growth. Ten days after tumor transplantation, Ferroplat was administered intravenously to half of the animals with the tumor and to half of the control animals. The magnitude of the magnetic signals was determined 1 h and every two days after administration of the nanocomposite using a Superconducting Quantum Interference Device magnetometer of the original design. RESULTS: We have found that the magnetic signals coming from the tumor are significantly higher compared to control tumor-free animals. Intravenous administration of a ferromagnetic nanocomposite (Ferroplat: Fe3O4 + cisplatinum) led to a significant increase of the magnetic signal, especially in the tumor tissue, and inhibition of Guerin's carcinoma growth. Ferromagnetic nanoparticles (32.7 nm) are retained in malignant cells for a longer time than in normal ones. CONCLUSION: Tumor cells accumulate iron nanoparticles more intensively than normal ones. Nanocomposite Ferroplat can be used for a targeted delivery of cisplatin to malignant cells.

Highly Reproducible Hyperthermia Response in Water, Agar, and Cellular Environment by Discretely PEGylated Magnetite Nanoparticles.

Local heat generation from magnetic nanoparticles (MNPs) exposed to alternating magnetic fields can revolutionize cancer treatment. However, the application of MNPs as anticancer agents is limited by serious drawbacks. Foremost among these are the fast uptake and biodegradation of MNPs by cells and the unpredictable magnetic behavior of the MNPs when they accumulate within or around cells and tissues. In fact, several studies have reported that the heating power of MNPs is severely reduced in the cellular environment, probably due to a combination of increased viscosity and strong NP agglomeration. Herein, we present an optimized protocol to coat magnetite (Fe3O4) NPs larger than 20 nm (FM-NPs) with high molecular weight PEG molecules that avoid collective coatings, prevent the formation of large clusters of NPs and keep constant their high heating performance in environments with very different ionic strengths and viscosities (distilled water, physiological solutions, agar and cell culture media). The great reproducibility and reliability of the heating capacity of this FM-NP@PEG system in such different environments has been confirmed by AC magnetometry and by more conventional calorimetric measurements. The explanation of this behavior has been shown to lie in preserving as much as possible the magnetic single domain-type behavior of nearly isolated NPs. In vitro endocytosis experiments in a colon cancer-derived cell line indicate that FM-NP@PEG formulations with PEGs of higher molecular weight (20 kDa) are more resistant to endocytosis than formulations with smaller PEGs (5 kDa), showing quite large uptake mean-life (τ > 5 h) in comparison with other NP systems. The in vitro magnetic hyperthermia was performed at 21 mT and 650 kHz during 1 h in a pre-endocytosis stage and complete cell death was achieved 48 h posthyperthermia. These optimal FM-NP@PEG formulations with high resistance to endocytosis and predictable magnetic response will aid the progress and accuracy of the emerging era of theranostics.

Metallic iron in cornflakes.

Iron is an essential element, and cornflake-style cereals are typically fortified with iron to a level up to 14 mg iron per 100 g. Even single cornflakes exhibit magnetic behaviour. We extracted iron microparticles from samples of two own-brand supermarket cornflakes using a strong permanent magnet. Synchrotron iron K-edge X-ray absorption near-edge spectroscopic data were consistent with identification as metallic iron, and X-ray diffraction studies provided unequivocal identification of the extracted iron as body-centred cubic (BCC) α-iron. Magnetometry measurements were also consistent with ca. 14 mg per 100 g BCC iron. These findings emphasise that attention must be paid to the speciation of trace elements, in relation to their bioavailability. To mimic conditions in the stomach, we suspended the iron extract in dilute HCl (pH 1.0-2.0) at 310 K (body temperature) and found by ICP-MS that over a period of 5 hours, up to 13% of the iron dissolved. This implies that despite its metallic form in the cornflakes, the iron is potentially bioavailable for oxidation and absorption into the body.

Electromagnetic navigational bronchoscopy-directed dye marking for locating pulmonary nodules.

BACKGROUND: Small peripheral pulmonary nodules, which are usually deep-seated with no visual markers on the pleural surface, are often difficult to locate during surgery. At present, CT-guided percutaneous techniques are used to locate pulmonary nodules, but this method has many limitations. Thus, we aimed to evaluate the accuracy and feasibility of electromagnetic navigational bronchoscopy (ENB) with pleural dye to locate small peripheral pulmonary nodules before video-associated thoracic surgery (VATS). METHODS: The ENB localisation procedure was performed under general anaesthesia in an operating room. Once the locatable guide wire, covered with a sheath, reached the ideal location, it was withdrawn and 0.2-1.0 mL of methylene blue/indocyanine green was injected through the guide sheath. Thereafter, 20-60 mL of air was instilled to disperse the dye to the pleura near the nodules. VATS was then performed immediately. RESULTS: Study subjects included 25 patients with 28 nodules. The mean largest diameter of the pulmonary nodules was 11.8 mm (range, 6.0-24.0 mm), and the mean distance from the nearest pleural surface was 13.4 mm (range, 2.5-34.9 mm). After the ENB-guided localisation procedure was completed, the dye was visualised in 23 nodules (82.1%) using VATS. The average duration of the ENB-guided pleural dye marking procedure was 12.6 min (range, 4-30 min). The resection margins were negative in all malignant nodules. Complications unrelated to the ENB-guided localisation procedure occurred in two patients, including one case of haemorrhage and one case of slow intraoperative heart rate. CONCLUSION: ENB can be used to safely and accurately locate small peripheral pulmonary nodules and guide surgical resection. TRIAL REGISTRATION NUMBER: ChiCTR1900021963.

End-expiratory lung volume decreases during REM sleep despite continuous positive airway pressure.

PURPOSE: Patients with obstructive sleep apnea (OSA) may experience apneas and hypopneas primarily during stage R (REM) sleep when end-expiratory lung volume (EELV) reaches its nadir. The purpose of this study was to determine if REM-related reductions in EELV persist in the presence of continuous positive airway pressure (CPAP) prescribed during non-stage REM (NREM) sleep. METHODS: We prospectively recruited 17 subjects referred to the sleep laboratory for CPAP titration. CPAP was titrated per AASM protocol to control respiratory events. The change in EELV was measured using magnetometry. RESULTS: Of the 17 subjects, 12 (71%) had moderate to severe OSA. Despite the application of CPAP, there was a significant reduction in EELV between NREM and REM sleep (- 105.9 ± 92.2 to - 325.0 ± 113.1 mL, respectively, p < 0.01). The change in EELV between non-stage R (NREM) and REM significantly correlated with overall apnea-hypopnea index (AHI) (r = 0.5, p = 0.04), the number of respiratory arousals during REM (r = 0.5, p = 0.04), and prescribed level of CPAP (r = 0.7, p < 0.01). CONCLUSION: REM-related reductions in EELV are associated with worsening sleep disordered breathing and occur despite the presence of CPAP.

The Feasibility of Using a Smartphone Magnetometer for Assisting Needle Placement.

Minimally invasive surgical procedures often require needle insertion. For these procedures, efficacy greatly depends on precise needle placement. Many methods, such as optical tracking and electromagnetic tracking, have been applied to assist needle placement by tracking the real-time position information of the needle. Compared with the optical tracking method, electromagnetic tracking is more suitable for minimally invasive surgery since it has no requirement of line-of-sight. However, the devices needed for electromagnetic tracking are usually expensive, which will increase the cost of surgery. In this study, we presented a low-cost smartphone-based permanent magnet tracking method compatible with CT imaging and designed a 3D printed operation platform to assist with needle placement prior to needle insertion during minimally invasive surgery. The needle positioning accuracy of this method was tested in an open air test and a prostate phantom test in a CT environment. For these two tests, the average radial errors were 0.47 and 2.25 mm, respectively, and the standard deviations were 0.29 and 1.63, respectively. The materials and fabrication required for the presented method are inexpensive. Thus, many image-guided therapies may benefit from the presented method as a low-cost option for needle positioning prior to needle insertion.

Multicenter clinical trial on sentinel lymph node biopsy using superparamagnetic iron oxide nanoparticles and a novel handheld magnetic probe.

BACKGROUND: Sentinel lymph node biopsy is a standard staging procedure for early axillary lymph node-negative breast cancer. As an alternative to the currently used radioactive tracers for sentinel lymph node (SLN) detection during the surgical procedure, a number of studies have shown promising results using superparamagnetic iron oxide (SPIO) nanoparticles. Here, we developed a new handheld, cordless, and lightweight magnetic probe for SPIO detection. METHODS: Resovist (SPIO nanoparticles) were detected by the newly developed handheld probe, and the SLN detection rate was compared to that of the standard radioisotope (RI) method using radioactive colloids (99m Tc) and a blue dye (indigo carmine). This was a multicenter prospective clinical trial that included 220 patients with breast cancer scheduled for sentinel node biopsy after a clinical diagnosis of negative axillary lymph node from three facilities in Japan. RESULTS: Of the 210 patients analyzed, SLN was detected in 94.8% (199/210 cases, 90% confidence interval [CI]) with our magnetic method and in 98.1% (206/210 cases, 90% CI) with the RI method. The magnetic method exceeded the threshold identification rate of 90%. CONCLUSION: This was the first clinical study to use a novel handheld magnetometer to detect SLN, which we demonstrate to be not inferior to the RI method.

Novel functional imaging technique for the brachial plexus based on magnetoneurography.

OBJECTIVE: To visualize neural activity in the brachial plexus using magnetoneurography (MNG). METHODS: Using a 124- or 132-channel biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields above the clavicle and neck region were recorded in response to electrical stimulation of the median and ulnar nerves in five asymptomatic volunteers (four men and one woman; age, 27-45 years old). Equivalent currents were computationally reconstructed from neuromagnetic fields and visualized as pseudocolor maps. Reconstructed currents at the depolarization site and compound nerve action potentials (CNAPs) at Erb's point were compared. RESULTS: Neuromagnetic fields were recorded in all subjects. The reconstructed equivalent currents propagated into the vertebral foramina, and the main inflow levels differed between the median nerve (C5/C6-C7/T1 vertebral foramen) and the ulnar nerve (C7/T1-T1/T2). The inward current peaks at the depolarization site and CNAPs showed high linear correlation. CONCLUSIONS: MNG visualizes neural activity in the brachial plexus and can differentiate the conduction pathways after median and ulnar nerve stimulations. In addition, it can visualize not only the leading and trailing components of intra-axonal currents, but also inward currents at the depolarization site. SIGNIFICANCE: MNG is a novel and promising functional imaging modality for the brachial plexus.

Citric acid functionalized silane coupling versus post-grafting strategy for dual pH and saline responsive delivery of cisplatin by Fe3O4/carboxyl functionalized mesoporous SiO2 hybrid nanoparticles: A-synthesis, physicochemical and biological characterization.

Synthesis of monodisperse carboxylic acid-functionalized magnetic mesoporous silica nanoparticles is performed by either two-step sol-gel process or post-grafting using citric acid modified isocyanate silane coupling agent (MMSN-NCO-CA) or succinic anhydride modified magnetic mesoporous silica (MMSN-NH-SA). Morphology, structure and magnetic properties of bare and mesoporous silica coated Fe3O4 core were studied using various techniques such as FTIR, VSM, TEM, FESEM, XRD and N2 adsorption-desorption isotherms (BET). Cisplatin (cis-Pt) adsorption isotherms and its release profile in various media were investigated by ICP-OES. MMSN-NCO-CA with mean particle size 107 nm had lower surface area (87.5 m2/g) and larger pore size (6.9 nm) in comparison with MMSN-NH-SA (respective values of 151.2 m2/g and 3.5 nm). cis-Pt loading into particles followed a saturable adsorption with respect to the drug to particle mass ratios. More sustained release of cis-Pt was observed for MMSN-NCO-CA, though both nanoparticles exhibited a pH- and saline concentration-dependent drug release. In addition, general and cis-Pt specific cytotoxicity were examined by MTT assay in MDA-MB-231 breast cancer cell line, and to further detect apoptosis, acridine orange/ethidium bromide dual cell staining was investigated by fluorescence microscopy. In-vitro anti-tumor efficiency of cis-Pt loaded MMSN-NCO-CA and MMSN-NH-SA were similarly enhanced in comparison to free cis-Pt; however, more specific apoptotic death occurred for cis-Pt loaded MMSN-NCO-CA. Therefore, the as-synthesized citric acid functionalized core-shell magnetic mesoporous hybrid nanoparticles could be used as a promising drug carriers for cancer therapy in-vivo.

Synthetic aperture magnetometry and excess kurtosis mapping of Magnetoencephalography (MEG) is predictive of epilepsy surgical outcome in a large pediatric cohort.

OBJECTIVE: Resective surgery is the most effective treatment option for patients with refractory epilepsy; however identification of patients who will benefit from epilepsy surgery remains challenging. Synthetic aperture magnetometry and excess kurtosis mapping (SAM(g2)) of magnetoencephalography (MEG) is a non-invasive tool that warrants further examination in the pediatric epilepsy population. Here, we examined the utility of MEG with SAM(g2) to determine if MEG epileptiform foci correlates with surgical outcome and to develop a predictive model incorporating MEG information to best assess likelihood of seizure improvement/freedom from resective surgery. METHODS: 564 subjects who had MEG at the Children's Hospital of Philadelphia between 2010-2015 were screened. Clinical epilepsy history and prior electrographic records were extracted and reviewed and correlated with MEG findings. MEG assessments were made by both a neurologist and neuroradiologist. Predictive models were developed to assess the utility of MEG in determining Engel class at one year and five years after resective epilepsy surgery. RESULTS: The number of MEG spike foci was highly associated with Engel class outcome at both one year and five years; however, using MEG data in isolation was not significantly predictive of 5 year surgical outcome. When combined with clinical factors; scalp EEG (single ictal onset zone), MRI (lesional or not), age and sex in a logistic regression model MEG foci was significant for Engel class outcome at both 1 year (p = 0.03) and 5 years (0.02). The percent correctly classified for Engel class at one year was 78.43% and the positive predictive value was 71.43. SIGNIFICANCE: MEG using SAM(g2) analysis in an important non-invasive tool in the identification of those patients who will benefit most from surgery. Integrating MEG data analysis into pre-surgical evaluation can help to predict epilepsy outcome after resective surgery in the pediatric population if utilized with skilled interpretation.

Sound analysis of the magnetically levitated left ventricular assist device HeartMate 3™.

INTRODUCTION: The HeartMate 3™ has shown lower rates of adverse events compared to previous devices due to the design and absence of mechanical bearings. For previous devices, sound analysis emerged as a way to assess pump function. The aims of this study were to determine if sound analysis can be applied to the HeartMate 3 in vivo and in vitro and to evaluate an electronic stethoscope. METHOD: Sound recordings were performed with microphones and clinical accessible electronic stethoscope. The recordings were studied in both the time and the frequency domains. Recordings from four patients were performed to determine if in vivo and in vitro recordings are comparable. RESULTS: The results show that it is possible to detect sound from HeartMate 3 and the sound spectrum is clear. Pump frequency and frequency of the pulsatile mode are easily determined. Frequency spectra from in vitro and in vivo recordings have the same pattern, and the major proportion (96.7%) of signal power is located at the pump speed frequency ±40 Hz. The recordings from the patients show low inter-individual differences except from location of peaks originating from pump speed and harmonics. Electronic stethoscopes could be used for sound recordings, but the dedicated equipment showed a clearer sound spectrum. DISCUSSION: The results show that acoustic analysis can also be performed with the HeartMate 3 and that in vivo and in vitro sound spectrum is similar. The frequency spectra are different from previous devices, and methods for assessing pump function or thrombosis need further evaluation.

Mesoporous superparamagnetic hydroxyapatite nanocomposite: A multifunctional platform for synergistic targeted chemo-magnetotherapy.

In the present study, the aim was to develop a magneto-responsive nanocomposite for application in drug delivery by the integration of magnetic nanoparticles into an inorganic architecture, hydroxyapatite. The magnetic mesoporous hydroxyapatite nanocomposites, MMHAPs, were synthesized using a template-free method and fully characterized by XRD, FT-IR, TEM, FE-SEM, VSM, ICP, BET, and UV-Vis spectroscopy. MMHAPs exhibited a rod-like shape with a structure of large mesopores and high surface area. A sample of the nanocomposites with well-defined properties, MMHAP(2), was selected as a carrier for delivery of chemotherapy drug, doxorubicin (Dox). Then, it was coated with polyethylene glycol (P) and folic acid (F), providing aqueous stability and tumor targeting, respectively. The evaluation of drug release profile revealed that the release of drug occurs in a time-staggered manner under low pH conditions, which simulate the internal condition of lysosome. More important, a significant drug release was observed under a static magnetic field (SMF), displaying a magnetically triggered release. According to the toxicity assessment, MMHAP(2) did not show any noticeable toxic effect against the tumor cells (Saos-2) and normal cells (HEK-293) up to 100 µg ml-1 in the presence or absence of SMF. In contrast, the drug-loaded nanocomposite, F.P.D@MMHAP(2), possesses high antitumor efficacy particularly in the presence of SMF. Moreover, it was found that the cellular internalization of F.P.D@MMHAP(2) could be increased by SMF, providing therapeutic efficiency enhancement. The high cytotoxic effect of F.P.D@MMHAP(2) with the help of SMF caused apoptosis in the tumor cells, which was preceded by a disturbance in the intracellular redox state and then caspase activation. Based on the data obtained, F.P.D@MMHAP(2) is a pH- and magneto-responsive platform opening up a new perspective in terms of its exploitation in cancer therapy.

Magnetic detection of sentinel lymph node in papillary thyroid carcinoma: The MAGIC-PAT study results.

INTRODUCTION: Despite the controversy concerning sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC), successful detection rates can be achieved by radioguidance and vital dyeing. However, the drawbacks in both techniques are notable. Magnetic-guided SLNB (mSLNB) using superparamagnetic iron oxide (SPIO) nanoparticles is appealing as an alternative procedure. MATERIALS AND METHODS: mSLNB using the Sentimag-Sienna System®, total thyroidectomy and central compartment dissection (CCD) were performed on all PTC patients. Lymph node involvement was assessed by postoperative pathological examination. RESULTS: From 2014 to 2016, 33 consecutive patients with PTC were enrolled in the study. A total of 20 patients met the eligibility. mSLNB succeeded in 16 patients, with a detection rate of 80%. A median of two SLN per patient were detected. A median of 10.5 non-sentinel lymph nodes (NSLN) from CCD were examined. Among the patients, 56.25% (9/16) had no metastatic nodes, while 12.5% (2/16) had exclusively SLN involvement. No false negative cases were found. The agreement between SLN and NSLN status was 87.5%. The prediction of NSLN involvement by SLN status showed 100% sensitivity, 81.8% specificity, 71.4% PPV and 100% NPV. Subsequently, mSLNB and the final pathological analysis would discriminate 43.75% (7/16) of patients who would certainly benefit from CCD whilst 56.25% of the total would confirm an unnecessary lymphadenectomy and avoid morbidity. CONCLUSION: mSLNB showed satisfactory performance in PTC with clinical-negative nodes. We have shown mSLNB to be a good predictor of central compartment status that can improve the staging and management of PTC patients.