Biology subjects

Gevaert, J. J.

Publications and source records attributed to Gevaert, J. J..

5 recordsLinked to original sources

bioRxiv2023

Multichannel joint image reconstruction allows for artifact-free focused small field of view magnetic particle imaging

Tumour Associated Macrophages (TAMs) play a crucial role in breast cancer progression and have the potential to be used as a biomarker for patient prognosis. Magnetic particle imaging (MPI) is an emerging modality which can detect cells labelled with superparamagnetic iron oxide (SPIO) nanoparticles and can be used for non-invasive TAM assessment. However, MPI TAM detection is limited by its effective dynamic range. This limitation occurs when SPIO nanoparticles injected intravenously accumulate in the liver resulting in a large MPI signal which shadows regions of interest with lower signals (i.e the tumour) preventing their isolation and quantification. In this study we test an advanced reconstruction algorithm which allows us to prescribe a small focused field of view (FOV) on lower signals of interest. We then demonstrate the success of this method with an in vivo tumour model and show enhanced image quality and successful quantification of TAMs in mouse mammary tumours with different metastatic potentials (4T1 and E0771). Utilizing in vivo MPI, we did not see significant differences in the MPI signal for 4T1 tumours compared to E0771. These findings highlight the potential of MPI for in vivo TAM quantification offering a promising avenue for broader applications in cancer research and potentially overcoming constraints of MPI in other in vivo imaging contexts.

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↗

bioRxiv2023

In vivo tracking of adenoviral-transduced iron oxide-labeled bone marrow-derived dendritic cells using magnetic particle imaging

BackgroundDespite widespread study of dendritic cell (DC)-based cancer immunotherapies, the in vivo post-injection fate of DC remains largely unknown. Due in part to a lack of quantifiable imaging modalities, this is troubling as the amount of DC migration to secondary lymphoid organs correlates with therapeutic efficacy. Preliminary studies have identified magnetic particle imaging (MPI) as a suitable modality to quantify in vivo migration of superparamagnetic iron oxide-(SPIO)-labeled DC. Herein, we describe a lymph node- (LN)-focused MPI scan to quantify DC in vivo migration accurately and consistently. MethodsBoth adenovirus (Ad)-transduced SPIO+ (Ad SPIO+) and SPIO+ C57BL/6 bone marrow-derived DC were generated and assessed for viability and phenotype using flow cytometry. Ad SPIO+ and SPIO+ DC were fluorescently-labeled and injected into C57BL/6 mouse hind footpads (n=6). Two days later, in vivo DC migration was quantified using whole animal, popliteal LN- (pLN)-focused, and ex vivo pLN MPI scans. ResultsNo significant differences in viability, phenotype and in vivo pLN migration were noted for Ad SPIO+ and SPIO+ DC. Day 2 pLN-focused MPI successfully quantified DC migration in all instances while whole animal MPI only quantified pLN migration in 75% of cases. Ex vivo MPI and fluorescence microscopy confirmed MPI signal was pLN-localized and due to originally-injected Ad SPIO+ and SPIO+ DC. ConclusionsWe overcame a reported limitation of MPI by using a pLN-focused MPI scan to quantify pLN-migrated Ad SPIO+ and SPIO+ DC in 100% of cases. With this improved method, we detected as few as 1000 DC (4.4 ng Fe) in vivo. MPI is a suitable pre-clinical imaging modality to assess DC-based cancer immunotherapeutic efficacy.

immunology↗

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

Magnetic Particle Imaging is a sensitive in vivo imaging modality for the quantification of dendritic cell migration

Immunotherapies, such as dendritic cell- (DC-)based therapies, are useful for treating cancer as an alternative to or in combination with traditional therapies. Cells must migrate to lymphoid organs to be effective and the magnitude of the ensuing T cell response is proportional to the number of lymph node-migrated DC. With less than 10% of cells expected to reach their destination, there is a need for an imaging modality capable of sensitively and quantitatively detecting cells. MRI has been used to track DC using iron and 19F methods, with limitations. Quantification of iron-induced signal loss is indirect and challenging; 19F signal is directly quantifiable but lacks sensitivity. Magnetic Particle Imaging (MPI) directly detects superparamagnetic iron oxide nanoparticles (SPIO) and enables quantitation of low numbers of SPIO-labeled cells. Here we describe the first study using MPI to track and quantify the migration of DC, injected into the footpads of C57BL/6 mice, to the popliteal lymph nodes (pLNs). As DC migrate from the site of injection to the lymph nodes, we measured a decrease in signal in the footpads and an increase in signal at the pLNs. The presence of SPIO-labeled DC in nodes was validated by ex vivo MPI and histology. By measuring the iron mass per cell in samples of labeled cells, we were able to provide an estimate of cell number for each source of signal and we report a sensitivity of approximately 4000 cells in vivo and 2000 cells ex vivo. For some mice, MPI was compared to cellular MRI. We also bring attention to the issue of resolving unequal signals within close proximity, a challenge for many pre-clinical studies using a highly concentrated tracer bolus that over shadows nearby lower signals. This study demonstrates the clear advantage of MPI to detect and quantify cells in vivo, bridging the gap left by cellular MRI, and all other in vivo imaging modalities, and opening the door for quantitative imaging of cellular immunotherapies.

biophysics↗