Beyond Hepatocellular Carcinoma and Colorectal Metastasis: The Expanding Applications of Radioembolization

As a relatively safe outpatient procedure, radioembolization can potentially be used to treat any type of tumor within the liver, primary or metastatic. The safety and effectiveness of radioembolization in the treatment of hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC) has led many groups to explore its application in other malignancies. Moreover, other organs, such as the lungs and kidneys, have been explored as targets for therapy. Although the most data for radioembolization is related to HCC and mCRC, there is increasing experience and data regarding metastatic disease to the liver for other primary tumors. We review the current state of liver-directed therapy with radioembolization outside of HCC and mCRC, including metastatic neuroendocrine, breast, and melanoma, as well as limited experiences with other primary malignancies. Applications of radioembolization related to these other cancers and new trends and future directions will be discussed. With increasing use and availability of radioembolization, it promises to serve an expanding role in the repertoire of tools available for treating and managing oncologic disease

Magnetic Resonance Molecular Imaging Using Iron Oxide Nanoparticles

Magnetic resonance imaging (MRI) is regularly used to obtain anatomical images, greatly advancing biomedical research and clinical health care today, but its full potential in providing functional, physiological, and molecular information is only beginning to emerge. The goal of magnetic resonance molecular imaging is to utilize MRI to acquire information on the molecular level. This dissertation is focused on ways to increase the use of MRI for molecular imaging using superparamagnetic iron oxide (SPIO) nanoparticle induced MRI contrast. This work is divided into three main sections: 1) Elucidation of the contribution of size and coating properties to magnetic nanoparticle induced proton relaxation. To maximize contrast generated without increasing particle size, new methods to increase effects on relaxivity must be developed. Experimental data obtained on a new class of biocompatible particles are presented, along with simulated data. The effects of coating size, proton exchange, and altered diffusion are examined. Simulations are presented confirming the effect of particle coatings on clustering-induced relaxivity changes, and an experimental system demonstrating the clustering effect is presented. 2) Development of a diffusion-dependent, off-resonance imaging protocol for magnetic nanoparticles. This work demonstrates an alternative approach, off-resonance saturation (ORS), for generating contrast sensitive to SPIO nanoparticles. This method leads to a calculated contrast that increases with SPIO concentration. Experimental data and a mathematical model demonstrate and characterize this diffusion-dependent, off-resonance effect. Dependence on off-resonance frequency and power are also investigated. 3) Development of a genetic MRI marker via in vivo magnetic nanoparticle synthesis. This work seeks to provide a gene expression marker for MRI based on bacterial magnetosomes, tiny magnets produced by naturally occurring magnetotactic bacteria. Here, magA is expressed in a commonly used human cell line, 293FT, resulting in the production of magnetic, iron oxide nanoparticles by these cells. MRI shows these particles can be formed in vivo utilizing endogenous iron and can be used to visualize cells positive for magA. These results demonstrate magA alone is sufficient to produce magnetic nanoparticles and that it is an appropriate candidate for an MRI reporter gene.Ph.D.Committee Chair: Hu, Xiaoping; Committee Member: Bao, Gang; Committee Member: Martin, Diego; Committee Member: Murthy, Niren; Committee Member: Oshinski, Joh

MagA is sufficient for producing magnetic nanoparticles in mammalian cells, making it an MRI reporter

Magnetic resonance imaging (MRI) is routinely used to obtain anatomical images that have greatly advanced biomedical research and clinical health care today, but the full potential of MRI in providing functional, physiological, and molecular information is only beginning to emerge. In this work, we sought to provide a gene expression marker for MRI based on bacterial magnetosomes, tiny magnets produced by naturally occurring magnetotactic bacteria. Specifically, magA, a gene in magnetotactic bacteria known to be involved with iron transport, is expressed in a commonly used human cell line, 293FT, resulting in the production of magnetic, iron-oxide nanoparticles by these cells and leading to increased transverse relaxivity. MRI shows that these particles can be formed in vivo utilizing endogenous iron and can be used to visualize cells positive for magA. Synthetic superparamagnetic iron-oxide (SPIO) nanoparticles have been widely used for targeted molecular imaging applications (1-5). One major application is in vivo tracking of stem cells (6,7) and tumor progression (5). Labeling nonphagocytic cells in culture using modified particles, followed by transplantation or transfusion into living organisms, has made it possible to monitor cellular distribution in vivo, including cell migration and trafficking. A limitation of using synthetic SPIO is the need to label cells in vitro with presynthesized nanoparticles prior to cell transplant. As a result, particle concentration within cells decreases over time as the cells grow and divide, and particles cannot be readily linked directly to in vivo gene expression. One way to overcome this is to utilize a genetic approach. Green fluorescent protein (GFP) is perhaps the most well-known genetic marker for optical imaging. Magnetic resonance spectroscopy (MRS) has been used to detect creatine kinase (8) and chemical shift imaging (CSI) to observe betagalactosidase (9) activity. MRI gene expression strategies thus far include detection of beta-galactosidase activity (10,11), frequency-selective targeting of amide protons of expressed proteins (12), and expression of natural iron homeostasis proteins such as the transferrin receptor (13) and ferritin (14,15). For the transferrin receptor approach, administration of exogenous transferrin coupled to magnetic particles is required. Thus far, only ferritin exists as a purely in vivo superparamagnetic MRI marker. Although the relaxivity of ferritin is dependent on factors such as iron loading, data obtained on solutions of iron-containing materials suggest iron-oxide particles could provide higher relaxivity (16). In the present work, we report the gene-mediated cellular production of magnetic iron-oxide nanoparticles of the same composition as synthetic SPIO preparations using a gene present in magnetotactic bacteria, making it a possible MRI gene reporter. Magnetotactic bacteria, a diverse set of Gram-negative bacteria that exhibit motility thought to be directed by the earth's magnetic field (17), produce magnetosomes which are naturally synthesized intracellular magnetic structures (18). Each species of magnetotactic bacteria has a different, but specific, type and shape of magnetosome that can affect the MRI signal in the same way as synthetic SPIO nanoparticles (19). It is likely that natural magnetosome production requires multiple genes. Recent work has identified a 98-kb genomic island (20), among other regions, in the Magnetospirillum magneticum AMB-1 strain related to magnetosome regulation, and iron response studies have revealed 464 upregulated and 263 downregulated genes (21). Our efforts here focus on magA, a gene known to be involved in production of magnetosomes in M. magneticum (18,22,23). Nakamura et al. (22, In this work, magA was expressed in mammalian cells and its effect was evaluated in vitro and in vivo. It was shown that: 1) its expression leads to the formation of magnetic nanoparticles that strongly affect MRI signal; and 2) its expression in vivo generates readily detectable MR contrast

Provocative mesenteric angiography for occult gastrointestinal bleeding: a systematic review

Abstract Occult gastrointestinal bleeding (GIB) is a challenge for physicians to diagnose and treat. A systematic literature search of the PubMed and Embase databases was conducted up to January 1, 2023. Eligible studies included primary research studies with patients undergoing provocative mesenteric angiography (PMA) for diagnosis or localization of occult GIB. Twenty-seven articles (230 patients) were included in the review. Most patients (64.8%) presented with lower GIB. The average positivity rate for provocative angiography was 48.7% (58% with heparin and 46.7% in thrombolytics). Embolization was performed in 46.4% of patients, and surgical management was performed in 37.5%. Complications were rare. PMA can be an important diagnostic and treatment tool but studies with high-level evidence and standardized protocols are needed to establish its safety and optimal use

Treatment of multiple system atrophy using intravenous immunoglobulin

<p>Abstract</p> <p>Background</p> <p>Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA.</p> <p>Methods</p> <p>This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment.</p> <p>Results</p> <p>Nine subjects were enrolled, and seven (2 women and 5 men, age range 55–64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment.</p> <p>Conclusions</p> <p>Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.</p

Additional file 1 of Provocative mesenteric angiography for occult gastrointestinal bleeding: a systematic review

Additional file 1: Table S1. Quality assessment. Table S2. Treatment details and outcomes- heparin provocation. Table S3. Treatment details for studies that used thrombolytics/other agents. Table S4. Drug dose details