Dominique Finas

Is Endometriosis Associated with Systemic Subclinical Inflammation

Endometriosis is a pelvic inflammatory process with altered function of immune-related cells and increased number of activated macrophages in the peritoneal environment that secrete various local products, such as growth factors and cytokines. The elevation of cytokines and other factors in the peritoneal fluid is accompanied by the elevation of similar factors, such as CRP, SAA, TNF-α, MCP-1, IL-6, IL-8 and CCR1, in the peripheral blood of patients with endometriosis. CD44+ and CD14+ monocytes are significantly increased, while CD3+ T lymphocytes and CD20+ B lymphocytes show modest, but significant decrease in peripheral blood of women with endometriosis. This indicates that endometriosis could be viewed as a local disease with systemic subclinical manifestations. This review provides an overview of data on the changes of various factors in peripheral blood and their potential use as diagnostic tools in patients with endometriosis.

Cetrorelix in the treatment of female infertility and endometriosis

The use of cetrorelix within ovarian-stimulation protocols demonstrates several advantages compared with gonadotropin-releasing hormone (GnRH) agonist-containing protocols, which include, for example, significantly less time for analogue treatment and a reduction in the amount of gonadotropins needed. Furthermore, fewer side effects can be expected. There is no difference regarding endometrium quality and hormone profiles, and the results of assisted reproduction cycles are comparable. Cetrorelix also seems to be useful in the treatment of endometriosis which, in most cases, is an estrogen-dependent disease. Furthermore, fewer side effects occur with this agent (e.g., postmenopausal symptoms) and no estradiol add-back is needed. In the future, new nonpeptic GnRH antagonists are expected to be available for oral administration. Although they are still under investigation, these agents have the potential to improve patients’ comfort and compliance.

Magnetic-Particle-Imaging for Sentinel Lymph Node Biopsy in Breast Cancer

Magnetic Particle Imaging (MPI) is a very recent medical imaging technique providing tomographic data avoiding use of ionizing radiation. The first MPI scanner presented by Gleich and Weizenecker has a closed geometry which has to fit the object of interest [1]. In order to be able to examine larger objects, Sattel et al. developed a new coil configuration, the single-sided MPI scanner geometry [2]. The detection of axillary sentinel lymph nodes is one medical application scenario. MPI improves the surgical procedure by real-time 3D image guidance and may contribute towards reducing cost and the time needs per patient. This contribution presents improvements of various coil topologies. Furthermore, the cooling system is optimized and the send and receive chain will be improved.

L1 cell adhesion molecule as a potential therapeutic target in murine models of endometriosis using a monoclonal antibody approach.

Background/Aims The neural cell adhesion molecule L1CAM is a transmembrane glycoprotein abnormally expressed in tumors and previously associated with cell proliferation, adhesion and invasion, as well as neurite outgrowth in endometriosis. Being an attractive target molecule for antibody-based therapy, the present study assessed the ability of the monoclonal anti-L1 antibody (anti-L1 mAb) to impair the development of endometriotic lesions in vivo and endometriosis-associated nerve fiber growth. Methods and Results Endometriosis was experimentally induced in sexually mature B6C3F1 (n=34) and CD-1 nude (n=21) mice by autologous and heterologous transplantation, respectively, of endometrial fragments into the peritoneal cavity. Transplantation was confirmed four weeks post-surgery by in vivo magnetic resonance imaging and laparotomy, respectively. Mice were then intraperitoneally injected with anti-L1 mAb or an IgG isotype control antibody twice weekly, over a period of four weeks. Upon treatment completion, mice were sacrificed and endometrial implants were excised, measured and fixed. Endometriosis was histologically confirmed and L1CAM was detected by immunohistochemistry. Endometriotic lesion size was significantly reduced in anti-L1-treated B6C3F1 and CD-1 nude mice compared to mice treated with control antibody (P<0.05). Accordingly, a decreased number of PCNA positive epithelial and stromal cells was detected in autologously and heterologously induced endometriotic lesions exposed to anti-L1 mAb treatment. Anti-L1-treated mice also presented a diminished number of intraperitoneal adhesions at implantation sites compared with controls. Furthermore, a double-blind counting of anti-neurofilament L stained nerves revealed significantly reduced nerve density within peritoneal lesions in anti-L1 treated B6C3F1 mice (P=0.0039). Conclusions Local anti-L1 mAb treatment suppressed endometriosis growth in B6C3F1 and CD-1 nude mice and exerted a potent anti-neurogenic effect on induced endometriotic lesions in vivo. The findings of this preliminary study in mice provide a strong basis for further testing in in vivo models.

Single-sided magnetic particle imaging device for the sentinel lymph node biopsy scenario

Beside the original scanner geometry for Magnetic Particle Imaging (MPI) introduced by Gleich et. al. in 2005,1 alternative scanner geometries have been introduced.2-4 In excess of the opportunities in medical application offered by MPI itself, these new scanner geometries permit additional medical application scenarios. Here, the single-sided scanner geometry is implemented as imaging device for supporting the sentinel lymph node biopsy concept. In this contribution, the medical application is outlined, and the geometry of the scanner device is presented together with first simulation results providing information about the achievable image quality.

Detection and distribution of superparamagnetic nanoparticles in lymphatic tissue in a breast cancer model for magnetic particle imaging

Introduction The axillary lymph node extraction (ALNE) is part of the surgical staging in breast cancer. Radical ALNE was associated with high morbidity and significant loss of QoL. The adverse effects decreased since the introduction of the sentinel lymph node biopsy (SNLB), with dyes and radio nuclides as tracer substances. They could be replaced by super paramagnetic iron oxide nano particles (SPIOs). Through the magnetic particle imaging (MPI), a 3D-imaging and distinct localization of SPIOs can be achieved in SNLB. Qualitative and quantitative enrichment of SPIOs in the axillary lymphatic tissue is unexplored until now. Methods We aim to prove the principle of SNLB by MPI within a healthy mouse model and than in a tumor bearing mouse model with metastatic axillary lymph nodes. Axillary and environmental tissues are analyzed with different techniques: histology, Prussian blue staining, electron microscopy, atomic absorption spectrometry and MPI spectrometry. Results The SPIOs are moving from the injection site through the lymph-fat tissue to the axillary region and finally into the axillary lymph nodes. They are following the traces of lymphatic vessels, respecting the borders and spaces between different tissues e.g. muscle fibers. SPIOs were found in the neighborhood of collagen fibers. They accumulate in the cortex region of lymph nodes. We present first results of the approach of SNLB by MPI. Conclusion The use of SPIOs and the MPI technique as SNLB tracer and finder as a new SNLB technique will be less complex and incriminating for patient and staff and makes it more precise. A MPI hand probe for use in the operating theatre is under construction. Therewith the SNL detection can be easily performed and by the avoidance of intensive surgical exploration the morbidity is dramatically reduced. The tracer for MPI is easy to obtain. This makes the method accessible to all patients. The concept of SNLB by MPI can be applied in principle in all solid tumors.

An Application Scenario for Single-Sided Magnetic Particle Imaging

K. Grafe, Institute of Medical Engineering, University of Luebeck, Lubeck, Germany, grafe@imt.uni-luebeck.de T. F. Sattel, Institute of Medical Engineering, University of Luebeck, Lubeck, Germany K. Ludtke-Buzug, Institute of Medical Engineering, University of Luebeck, Lubeck, Germany D. Finas, Department of Obstetrics and Gynaecology, University of Luebeck, Lubeck, Germany J. Borgert, Phillips Technology GmbH, Innovative Technologies, Research Laboratories, Hamburg, Germany T. M. Buzug, Institute of Medical Engineering, University of Luebeck, Lubeck, Germany, buzug@imt.uni-luebeck.de

SPIO Detection and Distribution in Biological Tissue—A Murine MPI-SLNB Breast Cancer Model

Surgical breast cancer related staging with radical axillary lymph node extraction was mandatory in past times. High morbidity and significant loss of quality of life was inevitable. By introduction of the concept of sentinel lymph node biopsy (SLNB), these adverse effects decreased. Detection of sentinel lymph nodes (SNLs) is realized by the use of dyes and radio nuclides as tracer substances. These tracers can be replaced by superparamagnetic iron oxide nanoparticles (SPIOs) in the near future. Magnetic particle imaging (MPI) guided 3-D real-time imaging and a distinct localization of SPIOs can be achieved in SLNB by the use of MPI. However, qualitative and quantitative enrichment of SPIOs in biologic tissue, in particular, the axillary lymphatic tissue is unexplored until now. We aim to prove the principle of SLNB with MPI within a healthy and than in a tumor bearing mouse model with metastatic axillary lymph nodes in breast cancer. Axillary tissue, surrounding tissues, and tissue from the whole body are analyzed with the following techniques: histology, Prussian blue staining, electron microscopy, atomic absorption spectrometry, and magnetic particle spectroscopy. We found that the SPIOs moves from the injection site through the lymph-fat tissue to the axillary region and finally into the axillary lymph nodes. SPIOs follow traces of lymphatic vessels, respecting borders, and spaces between different tissues. They accumulate near collagen fibers and distinct regions. We present our results of the approach of SLNB with MPI. Application of SPIOs and tracer detection in SNLs with MPI as a new SLNB technology could be less complex and incriminating for patient and staff and could make SLNB more accurate. To realize this approach, an MPI hand probe for intraoperative use is under construction. This will simplify SNL detection and helps to reduce axillary exploration morbidity by avoidance of intensive surgical quest. The tracer for MPI is easy to obtain and this makes the method accessible to many patients. The concept of SLNB by MPI may be applied in principle in all solid tumors.

Distribution of Superparamagnetic Nanoparticles in Lymphatic Tissue for Sentinel Lymph Node Detection in Breast Cancer by Magnetic Particle Imaging

Breast cancer diagnostic and treatment consists of surgical tumor removal and axillary lymph node resection. Radical axillary lymph node removemend is associated with high morbidity and significant loss of quality of life. The concept of sentinel lymph node biopsy (SNLB) by the use of dye and radio nuclides strongly reduced those side effects. To further reduce the side effects when axillary lymph nodes are removed, super paramagnetic iron oxide nano particles (SPIOs) could replace these marker substances. The magnetic particle imaging (MPI)-procedure will be used to visualize these SPIOs. Intraoperative three-dimensional MPI imaging and distinct localization probably by the use of a MPI hand probe will facilitate the axillary SNL detection and moreover makes it more precise. A mouse model was applied to prove the mentioned principle of SNLB by MPI. We are presenting first results of this approach and, additionally the qualitative and semi-quantitative distribution of SPIOs in lymph-fat tissue is shown for the first time. SPIOs are moving from the injection site through the lymph-fat tissue to the axillary region and finally into the axillary lymph nodes. This was approved by histology and prussian blue iron staining of the slides, electron transmission microscopy and in vivo magnetic resonance imaging. The concept of SNLB by MPI can be applied in principle in all solid tumors.

Novel hardware developments in magnetic particle imaging

Magnetic Particle Imaging (MPI) has been introduced as a modality that allows for the acquisition of three-dimensional functional images with high sensitivity in real time. Here, alternative coil topologies are presented that differ significantly from the original set-up. Two novel coil topologies will be presented. Beside an asymmetric coil topology, where all field generating coils are arranged on a single side, an effective coil assembly has been accomplished that creates a field-free line for spatial coding. The alternative coil topologies may overcome the problem of a confined measurement field or lead to an increase of the sensitivity of MPI.