We developed a novel magnetometer that employs negatively charged nitrogen-vacancy (NV
) centers in diamond, to detect the magnetic field generated by magnetic nanoparticles (MNPs) for biomedical ...applications. The compact probe system is integrated into a fiber-optics platform allowing for a compact design. To detect signals from the MNPs effectively, we demonstrated, for the first time, the application of an alternating current (AC) magnetic field generated by the excitation coil of several hundred microteslas for the magnetization of MNPs in diamond quantum sensing. In the lock-in detection system, the minimum detectable AC magnetic field (at a frequency of 1.025 kHz) was approximately 57.6 nT for one second measurement time. We were able to detect the micromolar concentration of MNPs at distances of a few millimeters. These results indicate that the magnetometer with the NV
centers can detect the tiny amounts of MNPs, thereby offering potential for future biomedical applications.
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 (99mTc) 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.
New laparoscopic sentinel lymph node navigation using a dedicated magnetic probe and magnetic nanoparticle tracer for gastric cancer patients allows minimally invasive surgeries. By identifying the ...sentinel lymph nodes containing magnetic nanoparticles, patients can avoid excessive lymph node extraction without nuclear facilities and radiation exposure. This paper describes the development of the laparoscopic magnetic probe, ACDC-probe, for laparoscopic sentinel lymph node identification utilizing the nonlinear response of the magnetic nanoparticles magnetized by an alternating magnetic field with a static magnetic field. For highly sensitive detection, the ratio of static to alternating magnetic fields was optimized to approximately 5. The longitudinal detection length was approximately 10 mm for 140 μg of iron, and the detectable amount of iron was approximately 280 ng at a distance of 1 mm. To demonstrate the feasibility of laparoscopic detection using the ACDC-probe and magnetic tracers, an experiment was performed on a wild swine. The gastric sentinel lymph node was clearly identified during laparoscopic navigation. These results suggest that the newly developed ACDC-probe is useful for laparoscopic sentinel lymph node detection and this magnetic technique appears to be a promising method for future sentinel lymph node navigation of gastric cancer patients.
The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld ...magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet. Numerical and experimental results show that the longitudinal detection length is approximately 10 mm, for 140 μg of iron. Clinical tests were performed, for the first time, using magnetic and blue dye tracers-without radioisotopes-in breast cancer patients to demonstrate the performance of the probe. The nodes were identified through transcutaneous and ex-vivo measurements, and the iron accumulation in the nodes was quantitatively revealed. These results show that the handheld magnetic probe is useful in sentinel lymph node biopsy and that magnetic techniques are widely being accepted as future standard methods in medical institutions lacking nuclear medicine facilities.
To minimize the invasiveness and improve the patient's quality of life, sentinel lymph node (SLN) biopsy with magnetic nanoparticles (MNPs) containing superparamagnetic iron oxide is performed on ...breast cancer patients. Identifying the first SLN by quantification of the amount of MNPs can help to investigate the cancer metastasis. We developed the device for performing iron quantification during surgery. The compact desktop-size device can be easily introduced into operation rooms, and simple system of the device enables identification of the first SLN. We investigated the optimum nonlinear magnetic responses that are attributed to magnetic relaxations under moderate small ac and dc magnetic fields (~1 mT) and found that ac magnetic fields with < 5 kHz are effective in the detection of MNPs. In addition, our clinical trials revealed more iron (<inline-formula> <tex-math notation="LaTeX">40~\mu \text{g} </tex-math></inline-formula>) in the first lymph node than in the second lymph node (<inline-formula> <tex-math notation="LaTeX">10~\mu \text{g} </tex-math></inline-formula>), clearly indicating intraoperative quantification in the first node.
Mapping of sentinel lymph nodes (SLNs) can enable less invasive surgery. However, mapping is challenging for cancers of difficult-to-access visceral organs, such as the gallbladder, because the ...standard method using radioisotopes (RIs) requires preoperative tracer injection. Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) have also been used as alternative tracers. In this study, we modified a previously reported magnetic probe for laparoscopic use and evaluated the feasibility of detecting SLNs of the gallbladder using a laparoscopic dual tracer method by injecting ICG and SPIO into five swine and one cancer-bearing swine. The laparoscopic probe identified SPIO nanoparticles in the nodes of 4/5 swine in situ, the magnetic field counts were 2.5-15.9 μT, and fluorescence was detected in SLNs in all five swine. ICG showed a visual lymph flow map, and SPIO more accurately identified each SLN with a measurable magnetic field quite similar to the RI. We then developed an advanced gallbladder cancer model with lymph node metastasis using recombination activating gene 2-knockout swine. We identified an SLN in the laparoscopic investigation, and the magnetic field count was 3.5 μT. The SLN was histologically determined to be one of the two metastatic lymph nodes. In conclusion, detecting the SLNs of gallbladder cancer in situ using a dual tracer laparoscopic technique with ICG and SPIO was feasible in a swine model.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy ...rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.
In the surgical treatment of nonpalpable breast lesions, such as in early-stage cancer, a hook-wire is inserted into the lesion as a marker to enable surgeons to excise the tissue, along with the ...hook-wire, with a good margin. However, a benchmark technique for intraoperatively determining whether the excised tissue has an appropriate margin around the lesion has not yet been established. In this study, a method for locating a ferromagnetic stainless steel hook-wire inside the excised tissue using a magnetometer is proposed. The magnetometer is placed around a phantom along with the hook-wire at varied locations to map the magnetic field distribution. The three-dimensional coordinates of hook-wire are obtained by executing an optimization algorithm. The experimental results indicate that the location of the hook-wire is successfully obtained. Based on the information regarding the margin around the hook-wire, the surgeon can immediately evaluate the risk of whether some cancer cells still remain in the body.
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 (
= 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 (
= 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 (
= 0.918). The magnetic field and iron content were correlated (overall SLNs,
= 0.02; 1-mL,
= 0.014; 0.5-mL,
= 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.
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