Biology subjects

Sehl, O. C.

Publications and source records attributed to Sehl, O. C..

6 recordsLinked to original sources

bioRxiv2025

Magnetic Particle Imaging Lymphography (MPIL): A novel technique for lymph node mapping

During metastasis, tumour cells drain to nearby lymph nodes, the first of which are named the sentinel lymph node(s) (SLN). SLN biopsy (SLNB) determines if metastasis has occurred. Traditionally, SLNB involves injecting a Technetium-labeled tracer peritumourally, pre-operative imaging with SPECT to locate the SLN, and surgery guided by a gamma probe to remove them. Limitations include short tracer half-life which can make scheduling the SLNB difficult, and radiation dose to patients and healthcare workers. Alternatively, magnetic localization, with superparamagnetic iron oxide nanoparticles (SPIONs) as the tracer and a magnetometer to detect SPIONs in the SLN during surgery can be used, however, this lacks pre-operative imaging. Magnetic Particle Imaging (MPI) is a new imaging modality that directly detects SPIONs, holding potential for pre-operative imaging in magnetic SLNB. SPIONs for SLNB should have rapid drainage, high SLN accumulation, and high specificity to the SLN. For MPI Lymphography (MPIL), high particle sensitivity is also important. This study assesses the in vivo pharmacokinetics for SLN mapping with MPIL in a murine model, using five commercially available SPIONs of varying iron core sizes and surface coatings. We show that some SPIONs provide higher MPI signal at the SLN and show the potential to detect higher echelon nodes (HENs). PEGylation of SPIONs and mannose targeted SPIONs increase clearance from the injection site and the mannose targeted SPION reduces flow to HENs.

biophysics↗

bioRxiv2024

Labeling Natural Killer cells with superparamagnetic iron oxide nanoparticles for detection by preclinical and clinical-scale magnetic particle imaging

IntroductionClinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) for the detection, localization, and quantification of VivoTrax-labeled NK cells. MethodsHuman-derived NK-92 cells were labeled by co-incubation with VivoTrax for 24 hours then the excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled vs. unlabeled NK-92 cells was assessed after 4 hours of co- incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17) using bioluminescent or GFP counts. Labeled NK-92 cells at two different doses (0.5 or 1 x 106) were administered to excised mouse brains (cerebellum), tibias, and lungs then imaged by 3D preclinical MPI (MOMENTUM imager) and localized relative to fiducial markers. NK-92 cells were imaged by clinical-scale MPI under development at Magnetic Insight Inc. ResultsNK-92 cells were labeled with an average of 3.17 pg Fe/cell with no measured effects on cell viability or cytolytic activity against 3 tumor cell lines. MPI signal was directly quantitative with the number of VivoTrax-labeled NK-92 cells, with preclinical limit of detection of 3.1 x 104 cells on MOMENTUM imager. Labeled NK-92 cells could be accurately localized in mouse brains, tibias, and lungs within < 1 mm of stereotactic injection coordinates with preclinical scanner. Feasibility for detection of a clinically relevant dose of 4 x 107 labeled NK-92 cells was demonstrated on clinical-scale MPI. ConclusionMPI can provide sensitive, quantitative, and accurate spatial information on NK cell delivery, showing its potential to resolve a significant unmet clinical need to track NK cell treatments in patients.

biophysics↗

bioRxiv2023

Inter-user comparison for quantification of superparamagnetic iron oxides with magnetic particle imaging across two institutions highlights a need for standardized approaches

PurposeMagnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions. ProceduresSix users (3 from each institute) imaged a known amount of Vivotrax+ (10 g Fe), diluted in a small (10 L) or large (500 L) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users x triplicate samples x 2 sample volumes x 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax+ quantification, and ROI selection was compared across users, within and across institutions. ResultsMPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax+. Overall quantification yielded measurements that were within {+/-} 20% from ground truth, however SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples. ConclusionsThis study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental set up, image acquisition parameters, and ROI selection analysis.

biophysics↗

bioRxiv2022

MPI region of interest (ROI) analysis and quantification of iron in different volumes

MPI directly detects superparamagnetic iron oxides (SPIONs), which should enable precise, accurate, and linear quantification. However, selecting a region of interest (ROI) has strong effects on MPI quantification results. Ideally, ROI selection should be simple, user-independent, and widely applicable. In this work, we describe and compare four MPI ROI selection methods and assess their performance in vitro and in vivo. To explore the effect of ROI selection, ten ferucarbotran phantoms were imaged, each contained the same amount of iron but varied in volume. Three users tested the accuracy of the ROI methods for quantification of these samples. Lastly, the four ROI methods were applied to quantify ferucarbotran in vivo after intravenous, intramuscular, and subcutaneous injections in mice. We demonstrate that each ROI method has strengths. We conclude there is an important trade-off between ROI size and the accuracy of iron quantification, therefore the choice of ROI selection method for each study must be carefully informed.

biophysics↗

bioRxiv2021

Tracking the fates of iron-labeled tumor cells in vivo using Magnetic Particle Imaging

The use of imaging to detect and monitor the movement and accumulation of cells in living subjects can provide significant insights that can improve our understanding of metastasis and guide therapeutic development. For cell tracking using Magnetic Resonance Imaging (MRI), cells are labeled with iron oxides and the effects of the iron on water provides contrast. However, due to low specificity and difficulties in quantification with MRI, other modalities and approaches need to be developed. Magnetic Particle Imaging (MPI) is an emerging imaging technique which directly detects magnetic iron, allowing for a specific, quantitative and sensitive readout. Here, we use MPI to image iron-labeled tumor cells longitudinally, from implantation and growth at a primary site to movement to distant anatomic sites. In vivo bioluminescent imaging (BLI) was used to localize tumor metastases and computed tomography (CT) allowed for correlation of these signals to anatomic locations. These three imaging modalities provide information on immune escape and metastasis of iron-labeled, and unlabeled, tumor cells, and the accumulation of cell-free iron contrast over time. We identified iron signals by MPI and tumor cells via BLI, and correlated these positive contrast images with CT scans to reveal the anatomic sites with cancer cells; histologic analysis confirmed the presence of iron-labeled tumor cells in the tissues, suggesting that the metastatic cells retained enough iron for MPI detection. The use of multi-modality cell tracking reveals the movement, accumulation and fates of labeled cells that will be helpful understanding cancer progression and guiding the development of targeted therapies.

biophysics↗

bioRxiv2021

The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking

PurposeMagnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells. MethodsCells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes. ResultsUsing the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 x 1016 19F atoms) were detected with 19F MRI, with SNR > 5. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number. ConclusionMPI has the potential to be more sensitive than 19F MRI for cell tracking. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.

biophysics↗