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Edward A Neuwelt - One of the best experts on this subject based on the ideXlab platform.

  • cerebral blood volume mapping with Ferumoxytol in dynamic susceptibility contrast perfusion mri comparison to standard of care
    Journal of Magnetic Resonance Imaging, 2018
    Co-Authors: Csanad Varallyay, Seymur Gahramanov, Leslie L Muldoon, William D Rooney, Eric Nesbit, Andrea Horvath, Peter Varallyay, Edward A Neuwelt
    Abstract:

    BACKGROUND Cerebral blood volume (CBV) mapping with a dynamic susceptibility contrast (DSC) perfusion technique has become a clinical tool in diagnosing and follow-up of brain tumors. Ferumoxytol, a long-circulating iron oxide nanoparticle, has been tested for CBV mapping, but the optimal dose has not been established. PURPOSE To compare Ferumoxytol DSC of two different doses to standard of care gadoteridol by analyzing time-intensity curves and CBV maps in normal-appearing brain regions. STUDY TYPE Retrospective. SUBJECTS Fifty-four patients with various brain disorders. FIELD STRENGTH/SEQUENCE 3T MRI. DSC-MRI was performed with 0.1 mmol/kg gadoteridol and 1 day later with Ferumoxytol in doses of 1 or 2 mg/kg. ASSESSMENT Signal changes during first pass, relative CBV (rCBV) in normal-appearing thalamus, putamen, and globus pallidus, and contrast-to-noise ratio (CNR) of the CBV maps were compared between gadoteridol and various doses of Ferumoxytol using an automated method. To subjectively assess the quality of the CBV maps, two blinded readers also assessed visual conspicuity of the putamen. STATISTICAL TESTS Linear mixed effect model was used for statistical comparison. RESULTS Compared to gadoteridol, 1 mg/kg Ferumoxytol showed no difference in CNR (P = 0.6505), peak ΔR2*, and rCBV in the putamen (P = 0.2669, 0.0871) or in the thalamus (P = 0.517, 0.9787); 2 mg/kg Ferumoxytol increased peak ΔR2* as well as the CNR (P < 0.0001), but also mildly increased rCBV in putamen and globus pallidus (P = 0.0005, 0.0012). Signal intensities during first pass remained highly above the noise level, with overlapping of 95% confidence intervals with noise only in 3 out of 162 tested regions. Compared to gadoteridol, the visual image quality showed mild improvement with 1 mg/kg (P = 0.02) and marked improvement with 2 mg/kg Ferumoxytol (P < 0.0001). DATA CONCLUSION 1 mg/kg Ferumoxytol provides similar imaging results to standard gadoteridol for DSC-MRI, and 2 mg/kg has a benefit of increased CNR, but may also result in mildly increased rCBV values. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:441-448.

  • what does the boxed warning tell us safe practice of using Ferumoxytol as an mri contrast agent
    American Journal of Neuroradiology, 2017
    Co-Authors: Csanad Varallyay, Gerda B Toth, Joao Prola Netto, Jenny Firkins, Prakash Ambady, Edward A Neuwelt
    Abstract:

    BACKGROUND AND PURPOSE: Despite the label change and the FDA9s boxed warning added to the Feraheme (Ferumoxytol) label in March 2015, radiologists have shown increasing interest in using Ferumoxytol as an MR imaging contrast agent as a supplement or alternative to gadolinium. The goals of this study were to provide information regarding Ferumoxytol safety as an imaging agent in a single center and to assess how the Feraheme label change may affect this potential, currently off-label indication. MATERIALS AND METHODS: This retrospective study evaluated the overall frequency of Ferumoxytol-related adverse events when used for CNS MR imaging. Patients with various CNS pathologies were enrolled in institutional review board–approved imaging studies. Ferumoxytol was administered as multiple rapid bolus injections. The risk of adverse events was correlated with demographic data/medical history. RESULTS: The safety of 671 Ferumoxytol-enhanced MR studies in 331 patients was analyzed. No anaphylactic, life-threatening, or fatal (grade 4 or 5) adverse events were recorded. The overall proportion of Ferumoxytol-related grade 1–3 adverse events was 10.6% (8.6% occurring within 48 hours), including hypertension (2.38%), nausea (1.64%), diarrhea (1.04%), and headache (1.04%). History of 1 or 2 allergies was associated with an increased risk of adverse events (14.61% versus 7.51% [no history]; P = .007). CONCLUSIONS: The frequency of mild Ferumoxytol-related adverse events was comparable with literature results, and no serious adverse event was recorded. Although the recommendations in the boxed warning should be followed, serious adverse events appear to be rare, and with proper precautions, Ferumoxytol may be a valuable MR imaging agent.

  • safety report of Ferumoxytol for magnetic resonance imaging in children and young adults
    Investigative Radiology, 2016
    Co-Authors: Anne M Muehe, Edward A Neuwelt, Dan Feng, Rie Von Eyben, Sandra Lunafineman, Michael P Link, Travis Muthig, Amy Huddleston, Heike E Daldruplink
    Abstract:

    ObjectiveThe aim of this study was to assess the safety profile of Ferumoxytol as an intravenous magnetic resonance imaging contrast agent in children.Materials and MethodsWe prospectively evaluated the safety of Ferumoxytol administrations as an “off-label” contrast agent for magnetic resonance ima

  • high resolution steady state cerebral blood volume maps in patients with central nervous system neoplasms using Ferumoxytol a superparamagnetic iron oxide nanoparticle
    Journal of Cerebral Blood Flow and Metabolism, 2013
    Co-Authors: Csanad Varallyay, Seymur Gahramanov, Leslie L Muldoon, William D Rooney, Eric Nesbit, Brendan Moloney, Eric Earl, Edward A Neuwelt
    Abstract:

    Cerebral blood volume (CBV) measurement complements conventional magnetic resonance imaging (MRI) to indicate pathologies in the central nervous system (CNS). Dynamic susceptibility contrast (DSC) perfusion imaging is limited by low resolution and distortion. Steady-state (SS) imaging may provide higher resolution CBV maps but was not previously possible in patients. We tested the feasibility of clinical SS-CBV measurement using Ferumoxytol, a nanoparticle blood pool contrast agent. SS-CBV measurement was analyzed at various Ferumoxytol doses and compared with DSC-CBV using gadoteridol. Ninety nine two-day MRI studies were acquired in 65 patients with CNS pathologies. The SS-CBV maps showed improved contrast to noise ratios, decreased motion artifacts at increasing Ferumoxytol doses. Relative CBV (rCBV) values obtained in the thalamus and tumor regions indicated good consistency between the DSC and SS techniques when the higher dose (510 mg) Ferumoxytol was used. The SS-CBV maps are feasible using ferumox...

  • Ferumoxytol-Enhanced MRI to Image Inflammation Within Human Brain Arteriovenous Malformations: a Pilot Investigation
    Translational Stroke Research, 2012
    Co-Authors: David M. Hasan, Edward A Neuwelt, Michael T Lawton, Alastair J Martin, Matthew Amans, Tarik Tihan, Christopher Hess, Yi Guo, Soonmee Cha, David A. Saloner
    Abstract:

    Inflammation cell infiltration and cytokine expression are seen in the vascular walls and intervening stroma of resected brain arteriovenous malformation (bAVM) specimens, even in unruptured and previously untreated lesions. Macrophages may play a critical role in bAVM progression to rupture and could serve as a marker for rupture risk. We assessed feasibility of imaging macrophages within the bAVM nidus using Ferumoxytol-enhanced magnetic resonance imaging (MRI) in four patients with already diagnosed bAVMs using iron-sensitive imaging (ISI; T2* GE MRI sequence). Patients were imaged at baseline and at either 1 day ( n  = 2) or 5 days ( n  = 2) after infusion of 5 mg/kg of Ferumoxytol. Residual intravascular Ferumoxytol obscured evaluation for uptake in bAVM vascular walls and stroma at the 1-day time point. The two cases imaged at 5 days showed less intravascular tracer but had signal loss in the nidal region consistent with Ferumoxytol localization. One case underwent surgical resection; there was prominent vascular wall CD68 staining. Ferumoxytol-enhanced MRI for assessing bAVM inflammatory cell burden appears feasible and has the potential to be developed as a biomarker to study lesional inflammatory events.

Scott B Reeder - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of a motion robust 2d chemical shift encoded technique for r2 and field map quantification in Ferumoxytol enhanced mri of the placenta in pregnant rhesus macaques
    Journal of Magnetic Resonance Imaging, 2020
    Co-Authors: Ante Zhu, Sydney M Nguyen, Scott B Reeder, Kevin M Johnson, Ian M Bird, Thaddeus G Golos, Ann Shimakawa, Matthias R Muehler, Christopher J Francois, Sean B Fain
    Abstract:

    Background 3D chemical shift-encoded (CSE)-MRI techniques enable assessment of Ferumoxytol concentration but are unreliable in the presence of motion. Purpose To evaluate a motion-robust 2D-sequential CSE-MRI for R2* and B0 mapping in Ferumoxytol-enhanced MRI of the placenta. Study type Prospective. Animal model Pregnant rhesus macaques. Field strength/sequence 3.0T/CSE-MRI. Assessment 2D-sequential CSE-MRI was compared with 3D respiratory-gated CSE-MRI in placental imaging of 11 anesthetized animals at multiple timepoints before and after Ferumoxytol administration, and in Ferumoxytol phantoms (0 μg/mL-440 μg/mL). Motion artifacts of CSE-MRI in 10 pregnant women without Ferumoxytol administration were assessed retrospectively by three blinded readers (4-point Likert scale). The repeatability of CSE-MRI in seven pregnant women was also prospectively studied. Statistical tests Placental R2* and boundary B0 field measurements (ΔB0) were compared between 2D-sequential and 3D respiratory-gated CSE-MRI using linear regression and Bland-Altman analysis. Results In phantoms, a slope of 0.94 (r2 = 0.99, concordance correlation coefficient ρ = 0.99), and bias of -4.8 s-1 (limit of agreement [LOA], -41.4 s-1 , +31.8 s-1 ) in R2*, and a slope of 1.07 (r2 = 1.00, ρ = 0.99) and bias of 11.4 Hz (LOA -12.0 Hz, +34.8 Hz) in ΔB0 were obtained in 2D CSE-MRI compared with 3D CSE-MRI for reference R2* ≤390 s-1 . In animals, a slope of 0.92 (r2 = 0.97, ρ = 0.98) and bias of -2.2 s-1 (LOA -55.6 s-1 , +51.3 s-1 ) in R2*, and a slope of 1.05 (r2 = 0.95, ρ = 0.97) and bias of 0.4 Hz (LOA -9.0 Hz, +9.7 Hz) in ΔB0 were obtained. In humans, motion-impaired R2* maps in 3D CSE-MRI (Reader 1: 1.8 ± 0.6, Reader 2: 1.3 ± 0.7, Reader 3: 1.9 ± 0.6), while 2D CSE-MRI was motion-free (Reader 1: 2.9 ± 0.3, Reader 2: 3.0 ± 0, Reader 3: 3.0 ± 0). A mean difference of 0.66 s-1 and coefficient of repeatability of 9.48 s-1 for placental R2* were observed in the repeated 2D CSE-MRI. Data conclusion 2D-sequential CSE-MRI provides accurate R2* and B0 measurements in Ferumoxytol-enhanced placental MRI of animals in the presence of respiratory motion, and motion-robustness in human placental imaging. Level of evidence 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:580-592.

  • quantitative Ferumoxytol enhanced mri in pregnancy a feasibility study in the nonhuman primate
    Magnetic Resonance Imaging, 2020
    Co-Authors: Ante Zhu, Sydney M Nguyen, Scott B Reeder, Kevin M Johnson, Sean B Fain, Ian M Bird, Thaddeus G Golos, Oliver Wieben, Dinesh Shah, Diego Hernando
    Abstract:

    Abstract Objectives To assess the feasibility of Ferumoxytol-enhanced MRI in pregnancy with a nonhuman primate model. Materials and methods In this prospective study, eleven pregnant rhesus macaques at day 98 ± 5 of gestation were divided into three groups, untreated control (UC) (n = 3), saline control (SC) (n = 4) and interleukin 1 beta (IL-1β) treated (IT) (n = 4), which were administered with either saline or IL-1β into the amniotic fluid. All animals were imaged at multiple time points before and after Ferumoxytol administration (4 mg/kg). Longitudinal R2* and susceptibility of tissues were obtained using region-of-interest analysis and the longitudinal changes were assessed using linear mixed models and Student's t-test. Results In fetuses, a slope of 0.3 s−1/day (P = 0.008), 0.00 ppm/day (P = 0.699) and − 0.2 s−1/day (P = 0.023) was observed in liver R2*, liver susceptibility, and lung R2*, respectively. In placentas, R2* and susceptibility increased immediately after Ferumoxytol administration (P  Conclusions This work demonstrates the feasibility of quantitative Ferumoxytol-enhanced MRI to measure dynamics of Ferumoxytol delivery and washout in the placenta. Stable MRI measurements indicated no evidence of iron deposition in fetal tissues of nonhuman primates after maternal Ferumoxytol exposure.

  • impact of Ferumoxytol magnetic resonance imaging on the rhesus macaque maternal fetal interface
    Biology of Reproduction, 2019
    Co-Authors: Sydney M Nguyen, Gregory J Wiepz, Michele L Schotzko, Heather A Simmons, Andres Mejia, Kai D Ludwig, Ante Zhu, Kevin Brunner, Diego Hernando, Scott B Reeder
    Abstract:

    Ferumoxytol is a superparamagnetic iron oxide nanoparticle used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, Ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through Ferumoxytol-induced image contrast changes. Therefore, Ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after Ferumoxytol administration. In initial developmental studies, seven pregnant rhesus macaques were imaged with or without Ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of Ferumoxytol on the maternal–fetal interface (MFI), fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ∼100 gestational day underwent MRI before and after Ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 2–3 days following Ferumoxytol administration. A control group that did not receive Ferumoxytol or MRI was used for comparison. Iron levels in fetal and MFI tissues did not differ between groups, and there was no significant difference in tissue histopathology with or without exposure to Ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of Ferumoxytol and MRI in pregnant rhesus macaques does not negatively impact the MFI and can be a valuable experimental tool in research with this important animal model.Summary SentenceFerumoxytol magnetic resonance imaging for non-invasive pregnancy monitoring of the rhesus macaque does not impact histopathology or iron content of the maternal–fetal interface.

  • impact of Ferumoxytol magnetic resonance imaging on the rhesus macaque maternal fetal interface
    bioRxiv, 2019
    Co-Authors: Sydney M Nguyen, Gregory J Wiepz, Michele L Schotzko, Heather A Simmons, Andres Mejia, Kai D Ludwig, Ante Zhu, Kevin Brunner, Diego Hernando, Scott B Reeder
    Abstract:

    Abstract Ferumoxytol is a superparamagnetic iron oxide nanoparticle (SPION) used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent. Additionally, Ferumoxytol-uptake by macrophages facilitates detection of inflammatory sites by MRI through Ferumoxytol-induced image contrast changes. Therefore, Ferumoxytol-enhanced MRI holds great potential for assessing vascular function and inflammatory response, critical to determine placental health in pregnancy. This study sought to assess the fetoplacental unit and selected maternal tissues, pregnancy outcomes, and fetal well-being after Ferumoxytol administration. In initial developmental studies, pregnant rhesus macaques were imaged with and without Ferumoxytol administration. Pregnancies went to term with vaginal delivery and infants showed normal growth rates compared to control animals born the same year that did not undergo MRI. To determine the impact of Ferumoxytol on the maternal-fetal interface, fetal well-being, and pregnancy outcome, four pregnant rhesus macaques at ∼100 gd (gestational day) underwent MRI before and after Ferumoxytol administration. Collection of the fetoplacental unit and selected maternal tissues was performed 3-4 days following Ferumoxytol administration. A control group that did not receive Ferumoxytol or MRI was used for comparison. Iron levels in fetal and maternal-fetal interface tissues did not vary between groups. There was no significant difference in tissue histopathology with or without exposure to Ferumoxytol, and no effect on placental hormone secretion. Together, these results suggest that the use of Ferumoxytol and MRI in pregnant rhesus macaques will not introduce a detectable risk to the mother or fetus at the time of imaging or up to one year following normal vaginal delivery. Summary Sentence Ferumoxytol magnetic resonance imaging for non-invasive pregnancy monitoring of the rhesus macaque does not impact histopathology or iron content of the maternal-fetal interface.

  • safety and technique of Ferumoxytol administration for mri
    Magnetic Resonance in Medicine, 2016
    Co-Authors: Shreyas S Vasanawala, Michael D Hope, Scott B Reeder, Kimlien Nguyen, Thomas A Hope, Mellena D Bridges, Mustafa R Bashir
    Abstract:

    Ferumoxytol is an ultrasmall superparamagnetic iron oxide agent marketed for the treatment of anemia. There has been increasing interest in its properties as an MRI contrast agent as well as greater awareness of its adverse event profile. This mini-review summarizes the current state of knowledge of the risks of Ferumoxytol and methods of administration.

Olga Lenkov - One of the best experts on this subject based on the ideXlab platform.

  • Ferumoxytol can be used for quantitative magnetic particle imaging of transplanted stem cells
    Molecular Imaging and Biology, 2019
    Co-Authors: Hossein Nejadnik, Ketan Yerneni, Olga Lenkov, Prachi Pandit, Arian Pourmehdi Lahiji, Heike E Daldruplink
    Abstract:

    To evaluate, if clinically translatable Ferumoxytol nanoparticles can be used for in vivo detection and quantification of stem cell transplants with magnetic particle imaging (MPI). Mesenchymal stem cells (MSCs) were labeled with Ferumoxytol or ferucarbotran and underwent MPI, magnetic resonance imaging (MRI), Prussian blue staining, and inductively coupled plasma (ICP) spectrometry. Unlabeled, Ferumoxytol, and ferucarbotran-labeled MSCs were implanted in calvarial defects of eight mice and underwent MPI, MRI, and histopathology. The iron concentration calculated according to the MPI signal intensity and T2 relaxation times of the three different groups were compared using an analysis of variance (ANOVA) with Bonferroni correction, and a p < 0.05. Compared to unlabeled controls, Ferumoxytol- and ferucarbotran-labeled MSC showed significantly increased iron content, MPI signal and MRI signal. The Ferumoxytol MPI signal was approximately 4× weaker compared to ferucarbotran at equimolar concentrations (p = 0.0003) and approximately 1.5× weaker for labeled cells when using optimized labeling protocols (p = 0.002). In vivo, the MPI signal of Ferumoxytol-labeled MSC decreased significantly between day 1 and day 14 (p = 0.0124). This was confirmed by histopathology where we observed a decrease in Prussian blue stain of MSCs at the transplant site. The MRI signal of the same transplants did not change significantly during this observation period (p = 0.93). Ferumoxytol nanoparticles can be used for in vivo detection of stem cell transplants with MPI and provide quantitative information not attainable with MRI.

  • nanoparticle enhanced mri can monitor macrophage response to cd47 mab immunotherapy in osteosarcoma
    Cell Death and Disease, 2019
    Co-Authors: Suchismita Mohanty, Ketan Yerneni, Johanna Theruvath, Claus Moritz Graef, Hossein Nejadnik, Olga Lenkov, Laura Pisani, Jarrett Rosenberg, Siddhartha Mitra
    Abstract:

    CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though CD47 mAbs have entered clinical trials, diagnostic tests for monitoring therapy response in vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used “off label” as a contrast agent: the nanoparticle-based drug is phagocytosed by TAM and can be detected with magnetic resonance imaging (MRI). We evaluated if Ferumoxytol-enhanced MRI can monitor TAM response to CD47 mAb therapy in osteosarcomas. Forty-eight osteosarcoma-bearing mice were treated with CD47 mAb or control IgG and underwent pre- and post-treatment Ferumoxytol-MRI scans. Tumor enhancement, quantified as T2 relaxation times, was compared with the quantity of TAMs as determined by immunofluorescence microscopy and flow cytometry. Quantitative data were compared between experimental groups using exact two-sided Wilcoxon rank-sum tests. Compared to IgG-treated controls, CD47 mAb-treated tumors demonstrated significantly shortened T2 relaxation times on Ferumoxytol-MRI scans (p < 0.01) and significantly increased F4/80+CD80+ M1 macrophages on histopathology (p < 0.01). CD47 mAb-treated F4/80+ macrophages demonstrated significantly augmented phagocytosis of Ferumoxytol nanoparticles (p < 0.01). Thus, we conclude that Ferumoxytol-MRI can detect TAM response to CD47 mAb in mouse models of osteosarcoma. The Ferumoxytol-MRI imaging test could be immediately applied to monitor CD47 mAb therapies in clinical trials.

  • Nanoparticle enhanced MRI can monitor macrophage response to CD47 mAb immunotherapy in osteosarcoma
    Cell Death & Disease, 2019
    Co-Authors: Suchismita Mohanty, Ketan Yerneni, Johanna Theruvath, Claus Moritz Graef, Hossein Nejadnik, Olga Lenkov, Laura Pisani, Jarrett Rosenberg, Siddhartha Mitra, Alejandro Sweet Cordero
    Abstract:

    CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though CD47 mAbs have entered clinical trials, diagnostic tests for monitoring therapy response in vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used “off label” as a contrast agent: the nanoparticle-based drug is phagocytosed by TAM and can be detected with magnetic resonance imaging (MRI). We evaluated if Ferumoxytol-enhanced MRI can monitor TAM response to CD47 mAb therapy in osteosarcomas. Forty-eight osteosarcoma-bearing mice were treated with CD47 mAb or control IgG and underwent pre- and post-treatment Ferumoxytol-MRI scans. Tumor enhancement, quantified as T2 relaxation times, was compared with the quantity of TAMs as determined by immunofluorescence microscopy and flow cytometry. Quantitative data were compared between experimental groups using exact two-sided Wilcoxon rank-sum tests. Compared to IgG-treated controls, CD47 mAb-treated tumors demonstrated significantly shortened T2 relaxation times on Ferumoxytol-MRI scans ( p  

  • detection of stem cell transplant rejection with Ferumoxytol mr imaging correlation of mr imaging findings with those at intravital microscopy
    Radiology, 2017
    Co-Authors: Heike E Daldruplink, Hossein Nejadnik, Olga Lenkov, Aman Khurana, Fanny Chapelin, Carmel T Chan, Seyedmeghdad Taghavigarmestani, Toktam Nazekati, Xinming Tong, Fan Yang
    Abstract:

    Purpose To determine whether endogenous labeling of macrophages with clinically applicable nanoparticles enables noninvasive detection of innate immune responses to stem cell transplants with magnetic resonance (MR) imaging. Materials and Methods Work with human stem cells was approved by the institutional review board and the stem cell research oversight committee, and animal experiments were approved by the administrative panel on laboratory animal care. Nine immunocompetent Sprague-Dawley rats received intravenous injection of Ferumoxytol, and 18 Jax C57BL/6-Tg (Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6) 2Bck/J mice received rhodamine-conjugated Ferumoxytol. Then, 48 hours later, immune-matched or mismatched stem cells were implanted into osteochondral defects of the knee joints of experimental rats and calvarial defects of Jax mice. All animals underwent serial MR imaging and intravital microscopy (IVM) up to 4 weeks after surgery. Macrophages of Jax C57BL/6-Tg (Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6) 2Bck/J mice express enhanced green fluorescent protein (GFP), which enables in vivo correlation of Ferumoxytol enhancement at MR imaging with macrophage quantities at IVM. All quantitative data were compared between experimental groups by using a mixed linear model and t tests. Results Immune-mismatched stem cell implants demonstrated stronger Ferumoxytol enhancement than did matched stem cell implants. At 4 weeks, T2 values of mismatched implants were significantly lower than those of matched implants in osteochondral defects of female rats (mean, 10.72 msec for human stem cells and 11.55 msec for male rat stem cells vs 15.45 msec for sex-matched rat stem cells; P = .02 and P = .04, respectively) and calvarial defects of recipient mice (mean, 21.7 msec vs 27.1 msec, respectively; P = .0444). This corresponded to increased recruitment of enhanced GFP- and rhodamine-Ferumoxytol-positive macrophages into stem cell transplants, as visualized with IVM and histopathologic examination. Conclusion Endogenous labeling of macrophages with Ferumoxytol enables noninvasive detection of innate immune responses to stem cell transplants with MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

  • iron oxide nanoparticles inhibit tumour growth by inducing pro inflammatory macrophage polarization in tumour tissues
    Nature Nanotechnology, 2016
    Co-Authors: Saeid Zanganeh, Hossein Nejadnik, Olga Lenkov, Gregor Hutter, Ryan Spitler, Morteza Mahmoudi, Aubie Shaw, Jukka Pajarinen, Stuart B Goodman, Michael E Moseley
    Abstract:

    Until now, the Food and Drug Administration (FDA)-approved iron supplement Ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of Ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with Ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to Ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, Ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous Ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that Ferumoxytol could be applied ‘off label’ to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies. The Food and Drug Administration (FDA)-approved iron supplement Ferumoxytol, which contains iron oxide nanoparticles, can suppress growth of early mammary cancers and lung cancer metastasis by inducing pro-inflammatory M1 type macrophage polarization in the tumour tissue, offering a new ‘off label’ application for an approved drug.

Hossein Nejadnik - One of the best experts on this subject based on the ideXlab platform.

  • brain iron deposition after Ferumoxytol enhanced mri a study of porcine brains
    Nanotheranostics, 2020
    Co-Authors: Hossein Nejadnik, Laura Pisani, Ashok J. Theruvath, Maryam Aghighi, Jonathan Lavezo, Heike E Daldruplink
    Abstract:

    Recent evidence of gadolinium deposition in the brain has raised safety concerns. Iron oxide nanoparticles are re-emerging as promising alternative MR contrast agents, because the iron core can be metabolized. However, long-term follow up studies of the brain after intravenous iron oxide administration have not been reported thus far. In this study, we investigated, if intravenously administered Ferumoxytol nanoparticles are deposited in porcine brains. Methods: In an animal care and use committee-approved prospective case-control study, ten Gottingen minipigs received either intravenous Ferumoxytol injections at a dose of 5 mg Fe/kg (n=4) or remained untreated (n=6). Nine to twelve months later, pigs were sacrificed and the brains of all pigs underwent ex vivo MRI at 7T with T2 and T2*-weighted sequences. MRI scans were evaluated by measuring R2* values (R2*=1000/T2*) of the bilateral caudate nucleus, lentiform nucleus, thalamus, dentate nucleus, and choroid plexus. Pig brains were sectioned and stained with Prussian blue and evaluated for iron deposition using a semiquantitative scoring system. Data of Ferumoxytol exposed and unexposed groups were compared with an unpaired t-test and a Mann-Whitney U test. Results: T2 and T2* signal of the different brain regions was not visually different between Ferumoxytol exposed and unexposed controls. There were no significant differences in R2* values of the different brain regions in the Ferumoxytol exposed group compared to controls (p>0.05). Prussian blue stains of the same brain regions, scored according to a semiquantitative score, were not significantly different either between the Ferumoxytol exposed group and unexposed controls (p>0.05). Conclusions: Our study shows that intravenous Ferumoxytol doses of 5-10 mg Fe/kg do not lead to iron deposition in the brain of pigs. We suggest iron oxide nanoparticles as a promising alternative for gadolinium-enhanced MRI.

  • magnetic resonance imaging of stem cell macrophage interactions with Ferumoxytol and Ferumoxytol derived nanoparticles
    Wiley Interdisciplinary Reviews-nanomedicine and Nanobiotechnology, 2019
    Co-Authors: Hossein Nejadnik, Jessica Tseng, Heike E Daldruplink
    Abstract:

    "Off the shelf" allogeneic stem cell transplants and stem cell nano-composites are being used for the treatment of degenerative bone diseases. However, major and minor histocompatibility antigens of therapeutic cell transplants can be recognized as foreign and lead to their rejection by the host immune system. If a host immune response is identified within the first week post-transplant, immune modulating therapies could be applied to prevent graft failure and support engraftment. Ferumoxytol (Feraheme™) is an FDA approved iron oxide nanoparticle preparation for the treatment of anemia in patients. Ferumoxytol can be used "off label" as an magnetic resonance (MR) contrast agent, as these nanoparticles provide measurable signal changes on magnetic resonance imaging (MRI). In this focused review article, we will discuss three methods to localize and identify innate immune responses to stem cell transplants using Ferumoxytol-enhanced MRI, which are based on tracking stem cells, tracking macrophages or detecting mediators of cell death: (a) monitor MRI signal changes of Ferumoxytol-labeled stem cells in the presence or absence of innate immune responses, (b) monitor influx of Ferumoxytol-labeled macrophages into stem cell implants, and (c) monitor apoptosis of stem cell implants with caspase-3 activatable nanoparticles. These techniques can detect transplant failure at an early stage, when immune-modulating interventions can potentially preserve the viability of the cell transplants and thereby improve bone and cartilage repair outcomes. Approaches 1 and 2 are immediately translatable to clinical practice. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Cells at the Nanoscale Diagnostic Tools > Biosensing.

  • Ferumoxytol can be used for quantitative magnetic particle imaging of transplanted stem cells
    Molecular Imaging and Biology, 2019
    Co-Authors: Hossein Nejadnik, Ketan Yerneni, Olga Lenkov, Prachi Pandit, Arian Pourmehdi Lahiji, Heike E Daldruplink
    Abstract:

    To evaluate, if clinically translatable Ferumoxytol nanoparticles can be used for in vivo detection and quantification of stem cell transplants with magnetic particle imaging (MPI). Mesenchymal stem cells (MSCs) were labeled with Ferumoxytol or ferucarbotran and underwent MPI, magnetic resonance imaging (MRI), Prussian blue staining, and inductively coupled plasma (ICP) spectrometry. Unlabeled, Ferumoxytol, and ferucarbotran-labeled MSCs were implanted in calvarial defects of eight mice and underwent MPI, MRI, and histopathology. The iron concentration calculated according to the MPI signal intensity and T2 relaxation times of the three different groups were compared using an analysis of variance (ANOVA) with Bonferroni correction, and a p < 0.05. Compared to unlabeled controls, Ferumoxytol- and ferucarbotran-labeled MSC showed significantly increased iron content, MPI signal and MRI signal. The Ferumoxytol MPI signal was approximately 4× weaker compared to ferucarbotran at equimolar concentrations (p = 0.0003) and approximately 1.5× weaker for labeled cells when using optimized labeling protocols (p = 0.002). In vivo, the MPI signal of Ferumoxytol-labeled MSC decreased significantly between day 1 and day 14 (p = 0.0124). This was confirmed by histopathology where we observed a decrease in Prussian blue stain of MSCs at the transplant site. The MRI signal of the same transplants did not change significantly during this observation period (p = 0.93). Ferumoxytol nanoparticles can be used for in vivo detection of stem cell transplants with MPI and provide quantitative information not attainable with MRI.

  • nanoparticle enhanced mri can monitor macrophage response to cd47 mab immunotherapy in osteosarcoma
    Cell Death and Disease, 2019
    Co-Authors: Suchismita Mohanty, Ketan Yerneni, Johanna Theruvath, Claus Moritz Graef, Hossein Nejadnik, Olga Lenkov, Laura Pisani, Jarrett Rosenberg, Siddhartha Mitra
    Abstract:

    CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though CD47 mAbs have entered clinical trials, diagnostic tests for monitoring therapy response in vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used “off label” as a contrast agent: the nanoparticle-based drug is phagocytosed by TAM and can be detected with magnetic resonance imaging (MRI). We evaluated if Ferumoxytol-enhanced MRI can monitor TAM response to CD47 mAb therapy in osteosarcomas. Forty-eight osteosarcoma-bearing mice were treated with CD47 mAb or control IgG and underwent pre- and post-treatment Ferumoxytol-MRI scans. Tumor enhancement, quantified as T2 relaxation times, was compared with the quantity of TAMs as determined by immunofluorescence microscopy and flow cytometry. Quantitative data were compared between experimental groups using exact two-sided Wilcoxon rank-sum tests. Compared to IgG-treated controls, CD47 mAb-treated tumors demonstrated significantly shortened T2 relaxation times on Ferumoxytol-MRI scans (p < 0.01) and significantly increased F4/80+CD80+ M1 macrophages on histopathology (p < 0.01). CD47 mAb-treated F4/80+ macrophages demonstrated significantly augmented phagocytosis of Ferumoxytol nanoparticles (p < 0.01). Thus, we conclude that Ferumoxytol-MRI can detect TAM response to CD47 mAb in mouse models of osteosarcoma. The Ferumoxytol-MRI imaging test could be immediately applied to monitor CD47 mAb therapies in clinical trials.

  • Nanoparticle enhanced MRI can monitor macrophage response to CD47 mAb immunotherapy in osteosarcoma
    Cell Death & Disease, 2019
    Co-Authors: Suchismita Mohanty, Ketan Yerneni, Johanna Theruvath, Claus Moritz Graef, Hossein Nejadnik, Olga Lenkov, Laura Pisani, Jarrett Rosenberg, Siddhartha Mitra, Alejandro Sweet Cordero
    Abstract:

    CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though CD47 mAbs have entered clinical trials, diagnostic tests for monitoring therapy response in vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used “off label” as a contrast agent: the nanoparticle-based drug is phagocytosed by TAM and can be detected with magnetic resonance imaging (MRI). We evaluated if Ferumoxytol-enhanced MRI can monitor TAM response to CD47 mAb therapy in osteosarcomas. Forty-eight osteosarcoma-bearing mice were treated with CD47 mAb or control IgG and underwent pre- and post-treatment Ferumoxytol-MRI scans. Tumor enhancement, quantified as T2 relaxation times, was compared with the quantity of TAMs as determined by immunofluorescence microscopy and flow cytometry. Quantitative data were compared between experimental groups using exact two-sided Wilcoxon rank-sum tests. Compared to IgG-treated controls, CD47 mAb-treated tumors demonstrated significantly shortened T2 relaxation times on Ferumoxytol-MRI scans ( p  

Heike E Daldruplink - One of the best experts on this subject based on the ideXlab platform.

  • Ferumoxytol magnetic resonance imaging detects joint and pleural infiltration of bone sarcomas in pediatric and young adult patients
    Pediatric Radiology, 2021
    Co-Authors: Ashok J. Theruvath, Heike E Daldruplink, Ali Rashidi, Sheri L. Spunt, Raffi S Avedian, Robert J Steffner, Ramya R Nyalakonda
    Abstract:

    The diagnosis of joint infiltration by a malignant bone tumor affects surgical management. The specificity of standard magnetic resonance imaging (MRI) for diagnosing joint infiltration is limited. During our MRI evaluations with Ferumoxytol nanoparticles of pediatric and young adult patients with bone sarcomas, we observed a surprising marked T1 enhancement of joint and pleural effusions in some patients but not in others. To evaluate if nanoparticle extravasation differed between joints and pleura with and without tumor infiltration. We retrospectively identified 15 pediatric and young adult patients (mean age: 16±4 years) with bone sarcomas who underwent 18 MRI scans at 1 h (n=7) or 24 h (n=11) after intravenous Ferumoxytol infusion. Twelve patients also received a gadolinium-enhanced MRI. We determined tumor invasion into the joint or pleural space based on histology (n=11) and imaging findings (n=4). We compared the signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) of the joint or pleural fluid for tumors with and without invasion using a Mann-Whitney U test. MRI scans 24 h after intravenous Ferumoxytol infusion demonstrated a positive T1 enhancement of the effusion in all joints and pleural spaces with tumor infiltration and no joint or pleural space without infiltration. Corresponding SNR (P=0.004) and CNR (P=0.004) values were significantly higher for joints and pleural spaces with tumor infiltration than without. By contrast, unenhanced MRI, gadolinium-enhanced MRI and 1-h post-contrast Ferumoxytol MRI did not show any enhancement of the joint or pleural effusion, with or without tumor infiltration. This pilot study suggests that 24-h post-contrast Ferumoxytol MRI scans can noninvasively differentiate between joints with and without tumor infiltration.

  • brain iron deposition after Ferumoxytol enhanced mri a study of porcine brains
    Nanotheranostics, 2020
    Co-Authors: Hossein Nejadnik, Laura Pisani, Ashok J. Theruvath, Maryam Aghighi, Jonathan Lavezo, Heike E Daldruplink
    Abstract:

    Recent evidence of gadolinium deposition in the brain has raised safety concerns. Iron oxide nanoparticles are re-emerging as promising alternative MR contrast agents, because the iron core can be metabolized. However, long-term follow up studies of the brain after intravenous iron oxide administration have not been reported thus far. In this study, we investigated, if intravenously administered Ferumoxytol nanoparticles are deposited in porcine brains. Methods: In an animal care and use committee-approved prospective case-control study, ten Gottingen minipigs received either intravenous Ferumoxytol injections at a dose of 5 mg Fe/kg (n=4) or remained untreated (n=6). Nine to twelve months later, pigs were sacrificed and the brains of all pigs underwent ex vivo MRI at 7T with T2 and T2*-weighted sequences. MRI scans were evaluated by measuring R2* values (R2*=1000/T2*) of the bilateral caudate nucleus, lentiform nucleus, thalamus, dentate nucleus, and choroid plexus. Pig brains were sectioned and stained with Prussian blue and evaluated for iron deposition using a semiquantitative scoring system. Data of Ferumoxytol exposed and unexposed groups were compared with an unpaired t-test and a Mann-Whitney U test. Results: T2 and T2* signal of the different brain regions was not visually different between Ferumoxytol exposed and unexposed controls. There were no significant differences in R2* values of the different brain regions in the Ferumoxytol exposed group compared to controls (p>0.05). Prussian blue stains of the same brain regions, scored according to a semiquantitative score, were not significantly different either between the Ferumoxytol exposed group and unexposed controls (p>0.05). Conclusions: Our study shows that intravenous Ferumoxytol doses of 5-10 mg Fe/kg do not lead to iron deposition in the brain of pigs. We suggest iron oxide nanoparticles as a promising alternative for gadolinium-enhanced MRI.

  • magnetic resonance imaging of stem cell macrophage interactions with Ferumoxytol and Ferumoxytol derived nanoparticles
    Wiley Interdisciplinary Reviews-nanomedicine and Nanobiotechnology, 2019
    Co-Authors: Hossein Nejadnik, Jessica Tseng, Heike E Daldruplink
    Abstract:

    "Off the shelf" allogeneic stem cell transplants and stem cell nano-composites are being used for the treatment of degenerative bone diseases. However, major and minor histocompatibility antigens of therapeutic cell transplants can be recognized as foreign and lead to their rejection by the host immune system. If a host immune response is identified within the first week post-transplant, immune modulating therapies could be applied to prevent graft failure and support engraftment. Ferumoxytol (Feraheme™) is an FDA approved iron oxide nanoparticle preparation for the treatment of anemia in patients. Ferumoxytol can be used "off label" as an magnetic resonance (MR) contrast agent, as these nanoparticles provide measurable signal changes on magnetic resonance imaging (MRI). In this focused review article, we will discuss three methods to localize and identify innate immune responses to stem cell transplants using Ferumoxytol-enhanced MRI, which are based on tracking stem cells, tracking macrophages or detecting mediators of cell death: (a) monitor MRI signal changes of Ferumoxytol-labeled stem cells in the presence or absence of innate immune responses, (b) monitor influx of Ferumoxytol-labeled macrophages into stem cell implants, and (c) monitor apoptosis of stem cell implants with caspase-3 activatable nanoparticles. These techniques can detect transplant failure at an early stage, when immune-modulating interventions can potentially preserve the viability of the cell transplants and thereby improve bone and cartilage repair outcomes. Approaches 1 and 2 are immediately translatable to clinical practice. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Cells at the Nanoscale Diagnostic Tools > Biosensing.

  • Ferumoxytol can be used for quantitative magnetic particle imaging of transplanted stem cells
    Molecular Imaging and Biology, 2019
    Co-Authors: Hossein Nejadnik, Ketan Yerneni, Olga Lenkov, Prachi Pandit, Arian Pourmehdi Lahiji, Heike E Daldruplink
    Abstract:

    To evaluate, if clinically translatable Ferumoxytol nanoparticles can be used for in vivo detection and quantification of stem cell transplants with magnetic particle imaging (MPI). Mesenchymal stem cells (MSCs) were labeled with Ferumoxytol or ferucarbotran and underwent MPI, magnetic resonance imaging (MRI), Prussian blue staining, and inductively coupled plasma (ICP) spectrometry. Unlabeled, Ferumoxytol, and ferucarbotran-labeled MSCs were implanted in calvarial defects of eight mice and underwent MPI, MRI, and histopathology. The iron concentration calculated according to the MPI signal intensity and T2 relaxation times of the three different groups were compared using an analysis of variance (ANOVA) with Bonferroni correction, and a p < 0.05. Compared to unlabeled controls, Ferumoxytol- and ferucarbotran-labeled MSC showed significantly increased iron content, MPI signal and MRI signal. The Ferumoxytol MPI signal was approximately 4× weaker compared to ferucarbotran at equimolar concentrations (p = 0.0003) and approximately 1.5× weaker for labeled cells when using optimized labeling protocols (p = 0.002). In vivo, the MPI signal of Ferumoxytol-labeled MSC decreased significantly between day 1 and day 14 (p = 0.0124). This was confirmed by histopathology where we observed a decrease in Prussian blue stain of MSCs at the transplant site. The MRI signal of the same transplants did not change significantly during this observation period (p = 0.93). Ferumoxytol nanoparticles can be used for in vivo detection of stem cell transplants with MPI and provide quantitative information not attainable with MRI.

  • current and potential imaging applications of Ferumoxytol for magnetic resonance imaging
    Kidney International, 2017
    Co-Authors: Gerda B Toth, Seymur Gahramanov, Csanad Varallyay, Edit Dosa, Andrea Horvath, Mustafa R Bashir, J P Finn, Heike E Daldruplink, Peter L Choyke, Mukesh G Harisinghani
    Abstract:

    Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, Ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. Ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, Ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of Ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of Ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.