Self-powered ultra-flexible electronics via nano-grating-patterned organic photovoltaics.

Next-generation biomedical devices1-9 will need to be self-powered and conformable to human skin or other tissue. Such devices would enable the accurate and continuous detection of physiological signals without the need for an external power supply or bulky connecting wires. Self-powering functionality could be provided by flexible photovoltaics that can adhere to moveable and complex three-dimensional biological tissues1-4 and skin5-9. Ultra-flexible organic power sources10-13 that can be wrapped around an object have proven mechanical and thermal stability in long-term operation13, making them potentially useful in human-compatible electronics. However, the integration of these power sources with functional electric devices including sensors has not yet been demonstrated because of their unstable output power under mechanical deformation and angular change. Also, it will be necessary to minimize high-temperature and energy-intensive processes10,12 when fabricating an integrated power source and sensor, because such processes can damage the active material of the functional device and deform the few-micrometre-thick polymeric substrates. Here we realize self-powered ultra-flexible electronic devices that can measure biometric signals with very high signal-to-noise ratios when applied to skin or other tissue. We integrated organic electrochemical transistors used as sensors with organic photovoltaic power sources on a one-micrometre-thick ultra-flexible substrate. A high-throughput room-temperature moulding process was used to form nano-grating morphologies (with a periodicity of 760 nanometres) on the charge transporting layers. This substantially increased the efficiency of the organophotovoltaics, giving a high power-conversion efficiency that reached 10.5 per cent and resulted in a high power-per-weight value of 11.46 watts per gram. The organic electrochemical transistors exhibited a transconductance of 0.8 millisiemens and fast responsivity above one kilohertz under physiological conditions, which resulted in a maximum signal-to-noise ratio of 40.02 decibels for cardiac signal detection. Our findings offer a general platform for next-generation self-powered electronics.

Efficacy of wearable vibration dressings on full-thickness wound healing in a hyperglycemic rat model.

Local low-frequency vibration promotes blood flow and wound healing in hard-to-heal diabetic foot ulcers (DFUs). However, vibration treatment is challenging in patients with DFUs due to wound management difficulties and low adherence. Consequently, developing wearable self-care devices becomes imperative for effective wound healing. This study introduces a wearable vibration dressing and assesses its impact on wound healing in hyperglycemic rats. Low-frequency vibration at 52 Hz was applied to the wound for 40 min/day in awake rats. Relative wound areas on post-wounding days (PWDs) 4-7 were significantly smaller and the wound closure rate was significantly higher in the vibration group than in the control group (p < 0.05, respectively). The total haemoglobin at baseline and after vibration on post-wounding day 7 was significantly larger in the vibration group than in the control group (p < 0.05). On PWD 7, the thickness of the granulation tissue was significantly higher in the vibration group than in the control group (p < 0.05). Moreover, the number of blood vessels at the wound site and vascular endothelial growth factor A protein expression were significantly higher in the vibration group than in the control group (p < 0.05, respectively). The ratio of (CD68+ /iNOS+ )/(CD163+ ) macrophages in the vibration group was significantly lower than that in the control group (p < 0.05). These results indicate the potential of wearable vibration dressings as new self-care devices that can promote angiogenesis and blood flow, improve inflammation, and enhance wound healing in DFUs.

Ultraflexible organic light-emitting diodes for optogenetic nerve stimulation.

Organic electronic devices implemented on flexible thin films are attracting increased attention for biomedical applications because they possess extraordinary conformity to curved surfaces. A neuronal device equipped with an organic light-emitting diode (OLED), used in combination with animals that are genetically engineered to include a light-gated ion channel, would enable cell type-specific stimulation to neurons as well as conformal contact to brain tissue and peripheral soft tissue. This potential application of the OLEDs requires strong luminescence, well over the neuronal excitation threshold in addition to flexibility. Compatibility with neuroimaging techniques such as MRI provides a method to investigate the evoked activities in the whole brain. Here, we developed an ultrathin, flexible, MRI-compatible OLED device and demonstrated the activation of channelrhodopsin-2-expressing neurons in animals. Optical stimulation from the OLED attached to nerve fibers induced contractions in the innervated muscles. Mechanical damage to the tissues was significantly reduced because of the flexibility. Owing to the MRI compatibility, neuronal activities induced by direct optical stimulation of the brain were visualized using MRI. The OLED provides an optical interface for modulating the activity of soft neuronal tissues.

Flexible Light Sources.

Various light sources have been developed for the application of optical stimulation in the optogenetics field. Light transmission inside living tissue is limited to a distance of a few millimeters; hence, it is necessary to insert the light source near the nerve tissue to be stimulated. If a device is rigid, it causes mechanical stimulation to act on the nerve tissue. The application of mechanical stimulation may induce inflammation, obstructing neural activity. Fabricating such a device out of a soft material can prevent mechanical stimulation of cells and mitigate biological reactions such as inflammation or encapsulation. Minimizing the sizes of LED and other light sources as much as possible and mounting them on a flexible substrate can provide the entire device with flexibility. Micro-LEDs can be reduced to a size almost comparable to that of a cell and it has even been reported that some have been mounted on the tip of needle-shaped devices inserted into living tissue. A device using organic semiconductors is sufficiently soft to be bent, which is a characteristic not observed in inorganic semiconductors. Using organic LEDs can realize wide-area flexible light-emitting surfaces and they are widely anticipated to be the next generation of light sources. This chapter introduces technologies used to manufacture these soft light sources and examples of optical stimulation devices that incorporate them.

Moving a neodymium magnet promotes the migration of a magnetic tracer and increases the monitoring counts on the skin surface of sentinel lymph nodes in breast cancer.

BACKGROUND: We suspected that moving a small neodymium magnet would promote migration of the magnetic tracer to the sentinel lymph node (SLN). Higher monitoring counts on the skin surface before making an incision help us detect SLNs easily and successfully. The present study evaluated the enhancement of the monitoring count on the skin surface in SLN detection based on the magnet movement in a sentinel lymph node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles. METHODS: After induction of general anesthesia, superparamagnetic iron oxide nanoparticles were injected sub-dermally into the subareolar area or peritumorally. The neodymium magnet was moved over the skin from the injection site to the axilla to promote migration of the magnetic tracer without massage. A total of 62 patients were enrolled from February 2018 to November 2018: 13 cases were subjected to magnet movement 20 times (Group A), 8 were subjected to 1-min magnet movement (Group B), 26 were given a short (about 5 min) interval from injection to 1-min magnet movement (Group C), and 15 were given a long (about 25 min) interval before 1-min magnet movement using the magnetometer's head (Group D). In all cases, an SNB was conducted using both the radioisotope (RI) and SPIO methods. The monitoring counts on the skin surface were measured by a handheld magnetometer and compared among the four groups. Changes in the monitoring count by the interval and magnet movement were evaluated. RESULTS: The identification rates of the SPIO and RI methods were 100 and 95.2%, respectively. The mean monitoring counts of Group A, B, C, and D were 2.39 µT, 2.73 µT, 3.15 µT, and 3.92 µT, respectively (p < 0.0001; Kruskal-Wallis test). The monitoring counts were higher with longer magnet movement and with the insertion of an interval. Although there were no relationships between the monitoring count on the skin surface and clinicopathologic factors, magnet movement strongly influenced the monitoring count on the skin surface. CONCLUSION: Moving a small neodymium magnet is effective for promoting migration of a magnetic tracer and increasing monitoring counts on the skin surface. TRIAL REGISTRATION: UMIN, UMIN000029475. Registered 9 October 2017.

Transparent, conformable, active multielectrode array using organic electrochemical transistors.

Mechanically flexible active multielectrode arrays (MEA) have been developed for local signal amplification and high spatial resolution. However, their opaqueness limited optical observation and light stimulation during use. Here, we show a transparent, ultraflexible, and active MEA, which consists of transparent organic electrochemical transistors (OECTs) and transparent Au grid wirings. The transparent OECT is made of Au grid electrodes and has shown comparable performance with OECTs with nontransparent electrodes/wirings. The transparent active MEA realizes the spatial mapping of electrocorticogram electrical signals from an optogenetic rat with 1-mm spacing and shows lower light artifacts than noise level. Our active MEA would open up the possibility of precise investigation of a neural network system with direct light stimulation.

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.

Effects of 7 T static magnetic fields on the expression of biological markers and the formation of bone in rats.

In this study, we aimed to evaluate the effects of 7 T static magnetic fields (SMFs) on rat mesenchymal stem cells (MSCs) in order to determine whether strong SMFs affected the osteogenesis of MSCs. MSCs were prepared from bone marrow cells obtained from the femurs of 7-week-old male Fischer 344 rats. MSCs were then combined with ß-tricalcium phosphate (ß-TCP), yielding two types of TCP/MSC constructs (TCP/P-1 and P-2) on day 0. Exposure was performed for 3 h/day for 6 days, and the experiments were performed twice using different exposure apparatus (cryovials or 4-well chambers) for each experiment. The results from gene expression, protein expression, and histological analyses showed no reproducible effects on both TCP/P-1 and TCP/P-2 MSC constructs, although osteocalcin levels for TCP/P-1 MSC constructs increased significantly once after 7 T exposure in two experiments. These findings contribute to understanding the effects of strong SMFs on MSC and osteoblasts. Bioelectromagnetics. 40:16-26, 2019. © 2018 Wiley Periodicals, Inc.

Ultraflexible, large-area, physiological temperature sensors for multipoint measurements.

We report a fabrication method for flexible and printable thermal sensors based on composites of semicrystalline acrylate polymers and graphite with a high sensitivity of 20 mK and a high-speed response time of less than 100 ms. These devices exhibit large resistance changes near body temperature under physiological conditions with high repeatability (1,800 times). Device performance is largely unaffected by bending to radii below 700 µm, which allows for conformal application to the surface of living tissue. The sensing temperature can be tuned between 25 °C and 50 °C, which covers all relevant physiological temperatures. Furthermore, we demonstrate flexible active-matrix thermal sensors which can resolve spatial temperature gradients over a large area. With this flexible ultrasensitive temperature sensor we succeeded in the in vivo measurement of cyclic temperatures changes of 0.1 °C in a rat lung during breathing, without interference from constant tissue motion. This result conclusively shows that the lung of a warm-blooded animal maintains surprising temperature stability despite the large difference between core temperature and inhaled air temperature.

Magnetic sentinel lymph node biopsy in a murine tumour model.

The magnetic technique for sentinel node biopsy provides a radioisotope-free alternative for staging breast cancer. It requires refinement to reduce "residual iron content" at injection sites by maximising lymphatic uptake to prevent "void artefacts" on magnetic resonance imaging (MRI), which could adversely affect clinical use. The site and timing of injection of magnetic tracer was evaluated in a murine tumour model (right hind limb) in 24 wild type mice. Right-sided intratumoural and left sided subcutaneous injection of magnetic tracer and assessment of nodal iron uptake on MRI, surgical excision and histopathological grading at time frames up to 24 hours were performed. Rapid iron uptake on MRI, smaller "void artefacts"(P<0.001) and a significant increase in iron content with time were identified in the subcutaneous injection group (r=0.937; P<0.001).Subcutaneous injection and increasing delay between tracer injection and surgery is beneficial for lymphatic iron uptake. FROM THE CLINICAL EDITOR: Sentinel lymph node biopsy (SLNB) has been the standard of care in breast cancer management for some time. Recent development has seen the introduction of magnetic tracer for SLNB. In this article, the authors investigated the refined use of magnetic tracer in determining the optimal timing of administration and the location of injection. The findings should provide more data on the future use of this new technique.

Effectiveness of magnetically aligned collagen for neural regeneration in vitro and in vivo.

We investigated the effectiveness of using magnetically aligned collagen (after exposure to a maximum 8-T magnetic field) for nerve regeneration in both an in vitro and in vivo model. Neurite outgrowth from embryonic chick dorsal root ganglion (DRG) neurons was significantly greater on magnetically aligned collagen gel than on control gel, and was dependent on magnetic field strength. Silicone tubes (15 mm length) filled with collagen gel formed bridges between severed rat sciatic nerves. We prepared tubes for four groups: collagen gel only (COL), magnetically aligned collagen gel (M-COL), collagen gel mixed with Schwann cells (S-COL), and magnetically aligned collagen gel mixed with Schwann cells (M-S-COL). The ratio of infiltrating regenerated nerves was higher in the M-COL group compared to the COL group at 8 weeks post-operation. There were no significant differences between the two groups with and without Schwann cells. Compound action potentials showed higher amplitude and shorter latency in the M-COL than COL group at 12 weeks post-operation. The number and diameter of regenerated axons increased significantly in the M-COL compared with the COL group at 12 weeks post-operation. Here we demonstrated that magnetically orientated collagen promoted nerve regeneration using both an in vitro and in vivo model.

Eccentric figure-eight coils for transcranial magnetic stimulation.

Previously we proposed an eccentric figure-eight coil that can cause threshold stimulation in the brain at lower driving currents. In this study, we performed numerical simulations and magnetic stimulations to healthy subjects for evaluating the advantages of the eccentric coil. The simulations were performed using a simplified spherical brain model and a realistic human brain model. We found that the eccentric coil required a driving current intensity of approximately 18% less than that required by the concentric coil to cause comparable eddy current densities within the brain. The eddy current localization of the eccentric coil was slightly higher than that of the concentric coil. A prototype eccentric coil was designed and fabricated. Instead of winding a wire around a bobbin, we cut eccentric-spiral slits on the insulator cases, and a wire was woven through the slits. The coils were used to deliver magnetic stimulation to healthy subjects; among our results, we found that the current slew rate corresponding to motor threshold values for the concentric and eccentric coils were 86 and 78 A/µs, respectively. The results indicate that the eccentric coil consistently requires a lower driving current to reach the motor threshold than the concentric coil. Future development of compact magnetic stimulators will enable the treatment of some intractable neurological diseases at home.

Involvement of glial P2Y1 receptors in cognitive deficit after focal cerebral stroke in a rodent model.

BACKGROUND: Neuroinflammation is associated with many conditions that lead to dementia, such as cerebrovascular disorders or Alzheimer's disease. However, the specific role of neuroinflammation in the progression of cognitive deficits remains unclear. To understand the molecular mechanisms underlying these events we used a rodent model of focal cerebral stroke, which causes deficits in hippocampus-dependent cognitive function. METHODS: Cerebral stroke was induced by middle cerebral artery occlusion (MCAO). Hippocampus-dependent cognitive function was evaluated by a contextual fear conditioning test. The glial neuroinflammatory responses were investigated by immunohistochemical evaluation and diffusion tensor MRI (DTI). We used knockout mice for P2Y1 (P2Y1KO), a glial ADP/ATP receptor that induces the release of proinflammatory cytokines, to examine the links among P2Y1-mediated signaling, the neuroinflammatory response, and cognitive function. RESULTS: Declines in cognitive function and glial neuroinflammatory response were observed after MCAO in both rats and mice. Changes in the hippocampal tissue were detected by DTI as the mean diffusivity (MD) value, which corresponded with the cognitive decline at 4 days, 1 week, 3 weeks, and 2 months after MCAO. Interestingly, the P2Y1KO mice with MCAO showed a decline in sensory-motor function, but not in cognition. Furthermore, the P2Y1KO mice showed neither a hippocampal glial neuroinflammatory response (as assessed by immunohistochemistry) nor a change in hippocampal MD value after MCAO. In addition, wild-type mice treated with a P2Y1-specific antagonist immediately after reperfusion did not show cognitive decline. CONCLUSION: Our findings indicate that glial P2Y1 receptors are involved in the hippocampal inflammatory response. The findings from this study may contribute to the development of a therapeutic strategy for brain infarction, targeting the P2Y1 receptor.

Accuracy of equilibrium magnetization mapping in sliced two-dimensional spoiled gradient-recalled echo pulse sequence with variable flip angle.

PURPOSE: To evaluate the accuracy of an equilibrium magnetization (M0 ) map obtained using a two-dimensional (2D) spoiled gradient-recalled echo (SPGR) pulse sequence with variable flip angle (VFA). MATERIALS AND METHODS: Single-slice 2D SPGR images of 4% agar gel phantoms with different gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) concentrations (0-1 mM) were obtained with a VFA (2-30°). The 2D SPGR-VFA data were acquired with different repetition times (TRs; 7.8-117.2 ms), Gaussian and sinc RF pulses, and different field strengths (4.7, 7, and 9.4 Tesla). M0 and T1 maps were calculated from the 2D SPGR-VFA data. M0 and T1 values were compared with those calculated from free-relaxed 2D gradient-recalled echo (GRE) images and inversion recovery-prepared 2D SPGR images. The M0 and T1 slice profiles were also investigated. RESULTS: Consistent M0 values were obtained, regardless of the different Gd concentrations, TRs, and pulse sequences. The M0 slice profiles calculated from the sliced SPGR-VFA data quantitatively reproduced those calculated from the free-relaxed sliced GRE. In contrast, the T1 values calculated from the 2D SPGR-VFA data were underestimated at a high Gd concentration, short TR, and Gaussian RF pulse. CONCLUSION: M0 values calculated from 2D SPGR-VFA images are highly quantitative.

Investigating the technical feasibility of magnetoencephalography during transcranial direct current stimulation.

Introduction: Magnetoencephalography (MEG) can measure weak magnetic fields produced by electrical brain activity. Transcranial direct current stimulation (tDCS) can affect such brain activities. The concurrent application of both, however, is challenging because tDCS presents artifacts on the MEG signal. If brain activity during tDCS can be elucidated by MEG, mechanisms of plasticity-inducing and other effects of tDCS would be more comprehensively understood. We tested the technical feasibility of MEG during tDCS using a phantom that produces an artificial current dipole simulating focal brain activity. An earlier study investigated estimation of a single oscillating phantom dipole during tDCS, and we systematically tested multiple dipole locations with a different MEG device. Methods: A phantom provided by the manufacturer was used to produce current dipoles from 32 locations. For the 32 dipoles, MEG was recorded with and without tDCS. Temporally extended signal space separation (tSSS) was applied for artifact rejection. Current dipole sources were estimated as equivalent current dipoles (ECDs). The ECD modeling quality was assessed using localization error, amplitude error, and goodness of fit (GOF). The ECD modeling performance with and without tDCS, and with and without tSSS was assessed. Results: Mean localization errors of the 32 dipoles were 1.70 ± 0.72 mm (tDCS off, tSSS off, mean ± standard deviation), 6.13 ± 3.32 mm (tDCS on, tSSS off), 1.78 ± 0.83 mm (tDCS off, tSSS on), and 5.73 ± 1.60 mm (tDCS on, tSSS on). Mean GOF findings were, respectively, 92.3, 87.4, 97.5, and 96.7%. Modeling was affected by tDCS and restored by tSSS, but improvement of the localization error was marginal, even with tSSS. Also, the quality was dependent on the dipole location. Discussion: Concurrent tDCS-MEG recording is feasible, especially when tSSS is applied for artifact rejection and when the assumed location of the source of activity is favorable for modeling. More technical studies must be conducted to confirm its feasibility with different source modeling methods and stimulation protocols. Recovery of single-trial activity under tDCS warrants further research.

Brain Response to Interferential Current Compared with Alternating Current Stimulation.

Temporal interference (TI) stimulation, which utilizes multiple external electric fields with amplitude modulation for neural modulation, has emerged as a potential noninvasive brain stimulation methodology. However, the clinical application of TI stimulation is inhibited by its uncertain fundamental mechanisms, and research has previously been restricted to numerical simulations and immunohistology without considering the acute in vivo response of the neural circuit. To address the characterization and understanding of the mechanisms underlying the approach, we investigated instantaneous brainwide activation patterns in response to invasive interferential current (IFC) stimulation compared with low-frequency alternative current stimulation (ACS). Results demonstrated that IFC stimulation is capable of inducing regional neural responses and modulating brain networks; however, the activation threshold for significantly recruiting a neural response using IFC was higher (at least twofold) than stimulation via alternating current, and the spatial distribution of the activation signal was restricted. A distinct blood oxygenation level-dependent (BOLD) response pattern was observed, which could be accounted for by the activation of distinct types of cells, such as inhibitory cells, by IFC. These results suggest that IFC stimulation might not be as efficient as conventional brain modulation methods, especially when considering TI stimulation as a potential alternative for stimulating subcortical brain areas. Therefore, we argue that a future transcranial application of TI on human subjects should take these implications into account and consider other stimulation effects using this technique.

Depression induced by low-frequency repetitive transcranial magnetic stimulation to ventral medial frontal cortex in monkeys.

The medial frontal cortex (MFC), especially its ventral part, has long been of great interest with respect to the pathology of mood disorders. A number of human brain imaging studies have demonstrated the abnormalities of this brain region in patients with mood disorders, however, whether it is critically and causally involved in the pathogenesis of such disorders remains to be fully elucidated. In this study, we examined how the suppression of neural activity in the ventral region of the MFC (vMFC) affects the behavioral and physiological states of monkeys by using repetitive transcranial magnetic stimulation (rTMS). By using low-frequency rTMS (LF-rTMS) as an inhibitory intervention, we found that LF-rTMS targeting the vMFC temporarily induced a depression-like state in monkeys, which was characterized by a reduced movement activity level, impaired sociability, and decreased motivation level, as well as increased plasma cortisol level. On the other hand, no such significant changes in behavioral and physiological states were observed when targeting the other MFC regions, dorsal or posterior. We further found that the administration of an antidepressant agent, ketamine, ameliorated the abnormal behavioral and physiological states induced by the LF-rTMS intervention. These findings causally indicate the involvement of the vMFC in the regulation of mood and the validity of the LF-rTMS-induced dysfunction of the vMFC as a nonhuman primate model of depression.

Application of Magnetic Nanoparticles for Rapid Detection and In Situ Diagnosis in Clinical Oncology.

Screening, monitoring, and diagnosis are critical in oncology treatment. However, there are limitations with the current clinical methods, notably the time, cost, and special facilities required for radioisotope-based methods. An alternative approach, which uses magnetic beads, offers faster analyses with safer materials over a wide range of oncological applications. Magnetic beads have been used to detect extracellular vesicles (EVs) in the serum of pancreatic cancer patients with statistically different EV levels in preoperative, postoperative, and negative control samples. By incorporating fluorescence, magnetic beads have been used to quantitatively measure prostate-specific antigen (PSA), a prostate cancer biomarker, which is sensitive enough even at levels found in healthy patients. Immunostaining has also been incorporated with magnetic beads and compared with conventional immunohistochemical methods to detect lesions; the results suggest that immunostained magnetic beads could be used for pathological diagnosis during surgery. Furthermore, magnetic nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs), can detect sentinel lymph nodes in breast cancer in a clinical setting, as well as those in gallbladder cancer in animal models, in a surgery-applicable timeframe. Ultimately, recent research into the applications of magnetic beads in oncology suggests that the screening, monitoring, and diagnosis of cancers could be improved and made more accessible through the adoption of this technology.

Sentinel lymph node biopsy with a handheld cordless magnetic probe following preoperative MR lymphography using superparamagnetic iron oxide for clinically N0 early oral cancer: A feasibility study.

PURPOSE: Radioisotope (RI) tracers are generally used for preoperative mapping of sentinel lymph node (SLN) and intraoperative detection with a portable γ probe. However, the use of RI has several limitations. Therefore, a method without RI is required for the widespread application of SLN biopsy. The purpose of this study was to evaluate the feasibility of SLN biopsy with a handheld cordless magnetic probe following magnetic resonance lymphography (MRL) using superparamagnetic iron oxide (SPIO) and for clinically N0 early oral cancer. MATERIALS AND METHODS: MRL using SPIO and SLNB with the handheld cordless magnetic probe were performed for 27 patients with clinically N0 early oral cancer. RESULTS: In all 27 patients (100%), SLNs were detected by MRL, and the total and mean number of SLNs were 73 and 2.7, respectively. All SLNs identified by MRL were detectable using the magnetic probe in all patients. CONCLUSIONS: SLNB with handheld cordless magnetic probe following preoperative SLN mapping by MRL using SPIO is feasible, without RI use, for neck management in cases of clinically N0 early oral cancer.

Exploratory Study of Superparamagnetic Iron Oxide Dose Optimization in Breast Cancer Sentinel Lymph Node Identification Using a Handheld Magnetic Probe and Iron Quantitation.

This exploratory study compared doses of ferucarbotran, a superparamagnetic iron oxide nanoparticle, in sentinel lymph nodes (SLNs) and quantified the SLN iron load by dose and localization. Eighteen females aged ≥20 years scheduled for an SLN biopsy with node-negative breast cancer were divided into two equal groups and administered either 1 mL or 0.5 mL ferucarbotran. Iron content was evaluated with a handheld magnetometer and quantification device. The average iron content was 42.8 µg (range, 1.3-95.0; 0.15% of the injected dose) and 21.9 µg (1.1-71.0; 0.16%) in the 1-mL and 0.5-mL groups, respectively (p = 0.131). The iron content of the closest SLN compared to the second SLN was 53.0 vs. 10.0 µg (19% of the injected dose) and 34.8 vs. 4.1 µg (11.1%) for the 1-mL and 0.5-mL groups, respectively (p = 0.001 for both). The magnetic field was high in both groups (average 7.30 µT and 6.00 µT in the 1-mL and 0.5-mL groups, respectively) but was not statistically significant (p = 0.918). The magnetic field and iron content were correlated (overall SLNs, p = 0.02; 1-mL, p = 0.014; 0.5-mL, p = 0.010). A 0.5-mL dose was sufficient for SLN identification. Primary and secondary SLNs could be differentiated based on iron content. Handheld magnetometers could be used to assess the SLN iron content.