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

2021 ◽  
Author(s):  
Julia J Gevaert ◽  
Corby Fink ◽  
Jimmy D. Dikeakos ◽  
Gregory A. Dekaban ◽  
Paula J Foster
Keyword(s):  
Dendritic Cell ◽  
Lymph Nodes ◽  
In Vivo Imaging ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Cellular Mri ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

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.

scholarly journals Development of Magnetic Particle Imaging (MPI) for Cell Tracking and Detection

2020 ◽  
Author(s):  
Kierstin P Melo ◽  
Ashley V Makela ◽  
Natasha N Knier ◽  
Amanda M Hamilton ◽  
Paula J Foster
Keyword(s):  
Iron Content ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Superparamagnetic Iron Oxide ◽  
Cell Injection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractIntroductionMagnetic particle imaging (MPI) is a new imaging modality that sensitively and specifically detects superparamagnetic iron oxide nanoparticles (SPIONs) within a sample. SPION-based MRI cell tracking has very high sensitivity, but low specificity and quantification of iron labeled cells is difficult. MPI cell tracking could overcome these challenges.MethodsMDM-AB-231BR cells labeled with MPIO, mice were intracardially injected with either 2.5 × 105 or 5.0 × 105 cells. MRI was performed in vivo the same day at 3T using a bSSFP sequence. After mice were imaged ex vivo with MPI. In a second experiment Mice received an intracardiac injection of either 2.5 × 10 5 or 5 × 10 4 MPIO-labeled 231BR cells. In a third experiment, mice were injected with 5 × 10 4 4T1BR cells, labelled with either MPIO or the SPION Vivotrax. MRI and MPI was performed in vivo.ResultsSignal from MPI and signal voids from MRI both showed more iron content in mice receiving an injection of 5.0 × 105 cells than the 2.5 × 105 injection. In the second experiment, Day 0 MRI showed signal voids and MPI signal was detected in all mouse brains. The MPI signal and iron content measured in the brains of mice that were injected with 2.5 × 10 5 cells were approximately four times greater than in brains injected with 5 × 10 4 cells. In the third experiment, in vivo MRI was able to detect signal voids in the brains of mice injected with Vivotrax and MPIO, although voids were fainter in Vivotrax labeled cells. In vivo MPI signal was only detectable in mice injected with MPIO-labeled cells.ConclusionThis is the first example of the use of MPIO for cell tracking with MPI. With an intracardiac cell injection, approximately 15% of the injected cells are expected to arrest in the brain vasculature. For our lowest cell injection of 5.0 × 104 cells this is ∼10000 cells.

scholarly journals Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging

2020 ◽  
Author(s):  
Angelie Rivera-Rodriguez ◽  
Lan B. Hoang-Minh ◽  
Andreina Chiu-Lam ◽  
Nicole Sarna ◽  
Leyda Marrero-Morales ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Intraventricular Administration ◽  
Magnetic Particle Imaging ◽  
Particle Imaging ◽  
The Brain

ABSTRACTAdoptive cellular therapy (ACT) is a potent strategy to boost the immune response against cancer. ACT is an effective treatment for blood cancers, such as leukemias and lymphomas, but faces challenges treating solid tumors and cancers in locations like the brain. A critical step for success of ACT immunotherapy is achieving efficient trafficking of T cells to solid tumors, and the non-invasive and quantitative tracking of adoptively transferred T cell biodistribution would accelerate its development. Here, we demonstrate the use of Magnetic Particle Imaging (MPI) to non-invasively track ACT T cells in vivo. Labeling T cells with the superparamagnetic iron oxide nanoparticle tracer ferucarbotran did not affect T cell viability, phenotype, or cytotoxic function in vitro. Following ACT, ferucarbotran-labeled T cells were detected and quantified using MPI ex vivo and in vivo, in a mouse model of invasive brain cancer. Proof-of-principle in vivo MPI demonstrated its capacity to detect labeled T cells in lungs and liver after intravenous administration and to monitor T cell localization in the brain after intraventricular administration. Ex vivo imaging using MPI and optical imaging suggests accumulation of systemically administered ferucarbotran-labeled T cells in the brain, where MPI signal from ferucarbotran tracers and fluorescently tagged T cells were observed. Ex vivo imaging also suggest differential accumulation of nanoparticles and viable T cells in other organs like the spleen and liver. These results support the use of MPI to track adoptively transferred T cells and accelerate the development of ACT treatments for brain tumors and other cancers.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Olivia C. Sehl ◽  
Paula J. Foster
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Cell Detection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractMagnetic 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. Cells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. Using 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 × 1016 19F atoms) were detected with 19F MRI, with SNR > 5. MPI has the potential to be more sensitive than 19F MRI for cell tracking. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.

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

2021 ◽  
Author(s):  
Olivia C. Sehl ◽  
Paula J. Foster
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Cell Detection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractPurposeMagnetic 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 × 101619F 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.

scholarly journals Complex Relationship Between Signal Intensity Properties in Magnetic Particle Imaging (MPI) and Iron Oxide Nanoparticle Degradation

2020 ◽  
Author(s):  
Julia Guzy ◽  
Shatadru Chakravarty ◽  
Foster Buchanan ◽  
Haoran Chen ◽  
Jeffrey M. Gaudet ◽  
...  
Keyword(s):  
Magnetic Particle ◽  
Imaging Modality ◽  
Quantitative Imaging ◽  
Superparamagnetic Nanoparticles ◽  
Iron Oxide Nanoparticle ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

Magnetic particle imaging (MPI) is an exciting new biomedical imaging technology that uses superparamagnetic nanoparticles as an imaging tracer. MPI is touted as a quantitative imaging modality but MPI signal properties have never been characterized for nanoparticles undergoing biodegradation. Here we characterize the nature of the MPI signal properties as a function of degradation of various magnetic particle formulations. We show that MPI signal properties can increase or decrease as a function of nanoparticle formulation and chemical environment and that long-term in vitro experiments only roughly approximate long-term in vivo MPI signal properties. Data are supported by electron microscopy of nanoparticle degradation. Knowledge of MPI signal property changes during nanoparticle degradation will be critical in design and interpretation of all MPI experiments. Further, we demonstrate for the first time, an environmentally sensitive MPI contrast mechanism opening the door to smart contrast paradigms in MPI.<br>

scholarly journals Magnetic Particle Imaging: A Novel in Vivo Imaging Platform for Cancer Detection

Nano Letters ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. 1648-1654 ◽  
Author(s):  
Elaine Y. Yu ◽  
Mindy Bishop ◽  
Bo Zheng ◽  
R. Matthew Ferguson ◽  
Amit P. Khandhar ◽  
...  
Keyword(s):  
Cancer Detection ◽  
In Vivo Imaging ◽  
Magnetic Particle ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

scholarly journals Complex Relationship Between Signal Intensity Properties in Magnetic Particle Imaging (MPI) and Iron Oxide Nanoparticle Degradation

2020 ◽  
Author(s):  
Julia Guzy ◽  
Shatadru Chakravarty ◽  
Foster Buchanan ◽  
Haoran Chen ◽  
Jeffrey M. Gaudet ◽  
...  
Keyword(s):  
Magnetic Particle ◽  
Imaging Modality ◽  
Quantitative Imaging ◽  
Superparamagnetic Nanoparticles ◽  
Iron Oxide Nanoparticle ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

Magnetic particle imaging (MPI) is an exciting new biomedical imaging technology that uses superparamagnetic nanoparticles as an imaging tracer. MPI is touted as a quantitative imaging modality but MPI signal properties have never been characterized for nanoparticles undergoing biodegradation. Here we characterize the nature of the MPI signal properties as a function of degradation of various magnetic particle formulations. We show that MPI signal properties can increase or decrease as a function of nanoparticle formulation and chemical environment and that long-term in vitro experiments only roughly approximate long-term in vivo MPI signal properties. Data are supported by electron microscopy of nanoparticle degradation. Knowledge of MPI signal property changes during nanoparticle degradation will be critical in design and interpretation of all MPI experiments. Further, we demonstrate for the first time, an environmentally sensitive MPI contrast mechanism opening the door to smart contrast paradigms in MPI.<br>

scholarly journals Complex Relationship Between Signal Intensity Properties in Magnetic Particle Imaging (MPI) and Iron Oxide Nanoparticle Degradation

2020 ◽  
Author(s):  
Julia Guzy ◽  
Shatadru Chakravarty ◽  
Foster Buchanan ◽  
Haoran Chen ◽  
Jeffrey M. Gaudet ◽  
...  
Keyword(s):  
Magnetic Particle ◽  
Imaging Modality ◽  
Quantitative Imaging ◽  
Superparamagnetic Nanoparticles ◽  
Iron Oxide Nanoparticle ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

Magnetic particle imaging (MPI) is an exciting new biomedical imaging technology that uses superparamagnetic nanoparticles as an imaging tracer. MPI is touted as a quantitative imaging modality but MPI signal properties have never been characterized for nanoparticles undergoing biodegradation. Here we characterize the nature of the MPI signal properties as a function of degradation of various magnetic particle formulations. We show that MPI signal properties can increase or decrease as a function of nanoparticle formulation and chemical environment and that long-term in vitro experiments only roughly approximate long-term in vivo MPI signal properties. Data are supported by electron microscopy of nanoparticle degradation. Knowledge of MPI signal property changes during nanoparticle degradation will be critical in design and interpretation of all MPI experiments. Further, we demonstrate for the first time, an environmentally sensitive MPI contrast mechanism opening the door to smart contrast paradigms in MPI.<br>

scholarly journals Magnetic particle imaging of particle dynamics in complex matrix systems

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sebastian Draack ◽  
Meinhard Schilling ◽  
Thilo Viereck
Keyword(s):  
Magnetic Particle ◽  
Imaging Modality ◽  
Three Dimensional ◽  
Local Environment ◽  
Relaxation Mechanism ◽  
Harmonic Spectrum ◽  
Magnetic Particle Imaging ◽  
Matrix Interactions ◽  
Tracer Distribution ◽  
Particle Imaging

Abstract Magnetic particle imaging (MPI) is a young imaging modality for biomedical applications. It uses magnetic nanoparticles as a tracer material to produce three-dimensional images of the spatial tracer distribution in the field-of-view. Since the tracer magnetization dynamics are tied to the hydrodynamic mobility via the Brownian relaxation mechanism, MPI is also capable of mapping the local environment during the imaging process. Since the influence of viscosity or temperature on the harmonic spectrum is very complicated, we used magnetic particle spectroscopy (MPS) as an integral measurement technique to investigate the relationships. We studied MPS spectra as function of both viscosity and temperature on model particle systems. With multispectral MPS, we also developed an empirical tool for treating more complex scenarios via a calibration approach. We demonstrate that MPS/MPI are powerful methods for studying particle-matrix interactions in complex media.

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