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      Handheld magnetic probe with permanent magnet and Hall sensor for identifying sentinel lymph nodes in breast cancer patients

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          Abstract

          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.

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          Tomographic imaging using the nonlinear response of magnetic particles.

          The use of contrast agents and tracers in medical imaging has a long history. They provide important information for diagnosis and therapy, but for some desired applications, a higher resolution is required than can be obtained using the currently available medical imaging techniques. Consider, for example, the use of magnetic tracers in magnetic resonance imaging: detection thresholds for in vitro and in vivo imaging are such that the background signal from the host tissue is a crucial limiting factor. A sensitive method for detecting the magnetic particles directly is to measure their magnetic fields using relaxometry; but this approach has the drawback that the inverse problem (associated with transforming the data into a spatial image) is ill posed and therefore yields low spatial resolution. Here we present a method for obtaining a high-resolution image of such tracers that takes advantage of the nonlinear magnetization curve of small magnetic particles. Initial 'phantom' experiments are reported that demonstrate the feasibility of the imaging method. The resolution that we achieve is already well below 1 mm. We evaluate the prospects for further improvement, and show that the method has the potential to be developed into an imaging method characterized by both high spatial resolution as well as high sensitivity.
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            Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe.

            We have recently reported on a technique of gamma probe localization of radiolabelled lymph nodes to identify the sentinel node in malignant melanoma. In order to determine whether this technique is applicable to assist in staging breast cancer, a pilot study was begun to address two questions: (i) can the sentinel lymph node draining a breast cancer be identified for selective resection; and (ii) is the sentinel lymph node predictive of the status of the entire axillary lymph nodes? One to four hours prior to axillary lymph node dissection, 22 consecutive patients had approximately 0.4 mCi of technetium sulfur colloid in 0.5 ml saline injected around the perimeter of the breast lesion. A hand-held gamma counter was used at surgery to locate the lymph node(s) receiving drainage from the breast. A sentinel lymph node was identified in 18 of 22 patients. Of these 18 patients, the sentinel lymph node was positive in seven of seven patients, with pathologically verified metastatic breast cancer to at least one lymph node. In three out of seven patients, the sentinel lymph node was the only lymph node with metastatic cancer. In this pilot study of breast cancer patients, we conclude that: (i) radiolocalization and selective resection of sentinel lymph nodes is possible; and (ii) the sentinel lymph node appears to predict correctly the status of the remaining axilla. These data justify a larger clinical trial to verify the value of this technique.
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              Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications.

              Ferucarbotran (Resovist) is the second clinically approved superparamagnetic iron oxide developed for contrast-enhanced MRI of the liver. The purpose of this review is to provide an overview on the properties, clinical development, and application of ferucarbotran. Safety data obtained during clinical phases I-III revealed a total of 162 adverse events within 1053 patients, of which 75 were classified as possibly, probably, or definitely drug related. The majority of events occurred within the first 3 h (73 of 75) and was of mild intensity. The agent significantly improves the detection of hypovascular focal liver lesions with a comparable sensitivity in lesion detection to CTAP but without a relevant loss in specificity. Furthermore, ferucarbotran leads to a significant improvement of the sensitivity for lesion classification and characterization of the most frequent liver lesions. Contrast-enhanced MRA is not feasible and the angiographic effect is not sufficient to allow for postprocessing of data into maximum intensity projections. Intraindividual studies at low-field (0.2 T) and high-field (1.5 T) showed similar rates for lesion detection. The time window for contrast-enhanced MRI of the liver is at least 1 day up to 4 days. The compound can be regarded as safe and well tolerated. Even bolus injections caused no cardiovascular side effects, lumbar back pain, or clinically relevant laboratory changes. The examination time can be kept short with T1- and T2-weighted pre-contrast sequences, dynamic MRI over 10 min, and finally accumulation phase T2-weighted MRI. Patients who may benefit in particular are surgical candidates for resection, transplantation, or interventional therapies, and patients with liver cirrhosis and/or suspected hepatocellular carcinoma to either exclude malignancy or to define the extent of disease, the location of lesions, and the type of newly detected lesions.
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                Author and article information

                Contributors
                sekino@bee.t.u-tokyo.ac.jp
                kuwahata@bee.t.u-tokyo.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                19 January 2018
                19 January 2018
                2018
                : 8
                : 1195
                Affiliations
                [1 ]ISNI 0000 0001 2151 536X, GRID grid.26999.3d, Graduate School of Engineering, , The University of Tokyo, ; Tokyo, 113-0032 Japan
                [2 ]GRID grid.417054.3, Tochigi-Medical-Center-Shimotsuga, ; Tochigi, 329-4498 Japan
                [3 ]iMed Japan Inc, Chiba, 275-0001 Japan
                [4 ]ISNI 0000 0001 2248 6943, GRID grid.69566.3a, Institute of Development, Aging and Cancer, , Tohoku University, ; Miyagi, 980-8575 Japan
                [5 ]ISNI 0000 0001 2151 536X, GRID grid.26999.3d, Graduate School of Frontier Sciences, , The University of Tokyo, ; Kashiwa, 277-8561 Japan
                [6 ]ISNI 0000 0004 0616 2203, GRID grid.416279.f, Department of Breast Oncology, , Nippon Medical School Hospital, ; Tokyo, 113-8603 Japan
                [7 ]ISNI 0000 0001 2151 536X, GRID grid.26999.3d, Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, , The University of Tokyo, ; Tokyo, 113-8657 Japan
                [8 ]Matrix Cell Research Institute Inc, Ibaraki, 300-1232 Japan
                Article
                19480
                10.1038/s41598-018-19480-1
                5775278
                29352214
                d643be1c-747d-46b2-86d8-ce16893c7f8b
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 August 2017
                : 12 December 2017
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