Conventional Proton Magnetic Resonance Imaging Research Articles

Subsecond Three-Dimensional Nitrogen-15 Magnetic Resonance Imaging Facilitated by Parahydrogen-Based Hyperpolarization.

Magnetic resonance imaging (MRI) provides unique information about the internal structure and function of living organisms in a non-invasive way. The use of conventional proton MRI for the observation of real-time metabolism is hampered by the dominant signals of water and fat, which are abundant in living organisms. Heteronuclear MRI in conjunction with the hyperpolarization methods does not encounter this issue. In this work, we polarized 15N nuclei of [15N1]fampridine (a drug used for the treatment of multiple sclerosis) to the level of 4% in nuclear magnetic resonance (NMR) experiments and 0.7% in MRI studies using spin-lock-induced crossing combined with signal amplification by reversible exchange. Consequently, three-dimensional 15N MRI of the hyperpolarized 15N-labeled drug was acquired in 0.1 s with a signal-to-noise ratio of 70. In addition, the NMR signal enhancements for 15N-enriched fampridine and fampridine with a natural abundance of 15N nuclei were compared and an explanation for their difference was proposed.

Enabling Clinical Technologies for Hyperpolarized 129Xenon Magnetic Resonance Imaging and Spectroscopy

AbstractHyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4–8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin‐exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as 129Xe. Techniques based on hyperpolarized 129Xe are poised to revolutionize clinical lung imaging, offering a non‐ionizing, high‐contrast alternative to computed tomography (CT) imaging and conventional proton MRI. Moreover, CT and conventional proton MRI report on lung tissue structure but provide little functional information. On the other hand, when a subject breathes hyperpolarized 129Xe gas, functional lung images reporting on lung ventilation, perfusion and diffusion with 3D readout can be obtained in seconds. In this Review, the physics of SEOP is discussed and the different production modalities are explained in the context of their clinical application. We also briefly compare SEOP to other hyperpolarization methods and conclude this paper with the outlook for biomedical applications of hyperpolarized 129Xe to lung imaging and beyond.

Enabling Clinical Technologies for Hyperpolarized 129 Xenon Magnetic Resonance Imaging and Spectroscopy.

Hyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4-8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin-exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as 129 Xe. Techniques based on hyperpolarized 129 Xe are poised to revolutionize clinical lung imaging, offering a non-ionizing, high-contrast alternative to computed tomography (CT) imaging and conventional proton MRI. Moreover, CT and conventional proton MRI report on lung tissue structure but provide little functional information. On the other hand, when a subject breathes hyperpolarized 129 Xe gas, functional lung images reporting on lung ventilation, perfusion and diffusion with 3D readout can be obtained in seconds. In this Review, the physics of SEOP is discussed and the different production modalities are explained in the context of their clinical application. We also briefly compare SEOP to other hyperpolarization methods and conclude this paper with the outlook for biomedical applications of hyperpolarized 129 Xe to lung imaging and beyond.

Sensitive methodologies for tracking Tumor Infiltrating Lymphocyte immunotherapy by MRI

Background & Aim Cancer immunotherapies have made a great progress, have demonstrated encouraging clinical results, and hold much promise in the treatment of cancer. As we target solid tumors with immunotherapies, the hurdle of being able to select a suitable target and achieve successful cellular delivery/homing to the site of disease remains. With this in mind, being able to visualize a rapidly dividing cellular population is another obstacle to consider. Here we demonstrate the application of two clinically applicable perfluorocarbon (PFC) tracers, one commercially available and a next-generation magnetic resonance imaging (MRI) probe called FETRIS. Both of these agents enable the migration and persistence of cellular therapies to be noninvasively imaged by 19F MRI, while the FETRIS reagent enhances detection sensitivity. Methods, Results & Conclusion Here we validate the use of these labels on TIL preparations and donor T cells. We show that adding the cellular label does not alter the viability or release characteristics of cells and generated IND enabling data sets for both reagents. By pairing the PFC signal with conventional proton MRI from the same imaging session, the images are able to be overlaid, allowing cells to be traced to their anatomical location. With nominal exogenous fluorine naturally present in tissue, labeled cells appear with little background. Images of both reagents show the detection and sensitivity of the method and how they can be applied to monitor the distribution of cells over time.

Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema.

ObjectiveTo test the hypothesis that tissue sodium and adipose content are elevated in patients with lipedema; if confirmed, this could establish precedence for tissue sodium and adipose content representing a discriminatory biomarker for lipedema.MethodsParticipants with lipedema (n=10) and control (n=11) volunteers matched for biological sex, age, body-mass-index, and calf circumference were scanned noninvasively with 3.0T sodium and conventional proton MRI. Standardized tissue sodium content was quantified in skin, subcutaneous adipose tissue (SAT), and calf muscle. Dixon MRI was employed to quantify tissue fat and water volumes of the calf. Nonparametric statistical tests were applied to compare regional sodium content and fat-to-water volume ratio between groups (significance: two-sided p≤0.05).ResultsSkin (p=0.01) and SAT (p=0.04) sodium content were elevated in lipedema (skin: 14.9±2.9 mmol/L; SAT: 11.9±3.1 mmol/L) relative to control (skin: 11.9±2.0 mmol/L; SAT: 9.4±1.6 mmol/L) participants. Relative fat volume in the calf was elevated in lipedema (1.2±0.48 ratio) relative to control (0.63±0.26 ratio, p<0.001) participants. Skin sodium content was directly correlated with fat-to-water volume ratio (Spearman’s-rho=0.54, p=0.01).ConclusionsInternal metrics of tissue sodium and adipose content are elevated in patients with lipedema potentially providing objective imaging-based biomarkers for differentially diagnosing the under-recognized condition of lipedema from obesity.

Gas Phase UTE MRI of Propane and Propene.

Proton magnetic resonance imaging (1H MRI) of gases can potentially enable functional lung imaging to probe gas ventilation and other functions. Here, 1H MR images of hyperpolarized (HP) and thermally polarized propane gas were obtained using ultrashort echo time (UTE) pulse sequence. A 2-dimensional (2D) image of thermally polarized propane gas with ∼0.9 × 0.9 mm2 spatial resolution was obtained in <2 seconds, showing that even non-HP hydrocarbon gases can be successfully used for conventional proton magnetic resonance imaging. The experiments were also performed with HP propane gas, and high-resolution multislice FLASH 2D images in ∼510 seconds and non-slice-selective 2D UTE MRI images were acquired in ∼2 seconds. The UTE approach adopted in this study can be potentially used for medical lung imaging. Furthermore, the possibility of combining UTE with selective suppression of 1H signals from 1 of the 2 gases in a mixture is shown in this MRI study. The latter can be useful for visualizing industrially important processes where several gases may be present, eg, gas–solid catalytic reactions.

Development of an antibody-based, modular biosensor for129Xe NMR molecular imaging of cells at nanomolar concentrations

Magnetic resonance imaging (MRI) is seriously limited when aiming for visualization of targeted contrast agents. Images are reconstructed from the weak diamagnetic properties of the sample and require an abundant molecule like water as the reporter. Micromolar to millimolar concentrations of conventional contrast agents are needed to generate image contrast, thus excluding many molecular markers as potential targets. To address this limitation, we developed and characterized a functional xenon NMR biosensor that can identify a specific cell surface marker by targeted (129)Xe MRI. Cells expressing the cell surface protein CD14 can be spatially distinguished from control cells with incorporation of as little as 20 nM of the xenon MRI readout unit, cryptophane-A. Cryptophane-A serves as a chemical host for hyperpolarized nuclei and facilitates the sensitivity enhancement achieved by xenon MRI. Although this paper describes the application of a CD14-specific biosensor, the construct has been designed in a versatile, modular fashion. This allows for quick and easy adaptation of the biosensor to any cell surface target for which there is a specific antibody. In addition, the modular design facilitates the creation of a multifunctional probe that incorporates readout modules for different detection methods, such as fluorescence, to complement the primary MRI readout. This modular antibody-based approach not only offers a practical technique with which to screen targets, but one which can be readily applied as the xenon MRI field moves closer to molecular imaging applications in vivo.

Abstract B44: Enabling in vivo visualization of cellular therapies in the clinic: Maturation of αDC1 data sets.

Abstract Cellular therapies are increasingly being used in the clinic to modify a patient's immune function. Human dendritic cells (DC) have great clinical promise as an immunotherapeutic intervention against cancer, but questions concerning the dispersion and persistence of these cells, as well as correlations to therapeutic potency remain. Here we utilize a perfluoropolyether (PFPE) magnetic resonance imaging (MRI) tracer agent that aims to address these questions in the assessment of α-type-1-polarized dendritic cells (αDC1). αDC1 cells, producing high levels of interleukin-12p70 with putative strong lymph node homing capabilities, have been evaluated in support of an IND incorporating post-transfer MR imaging of the therapeutic cells. Important therapeutic functions, such as cytokine production, cellular phenotype, and antigen processing are maintained. Transitioning the protocol from the laboratory into clinical production, taking into account GMP procedural changes, resulted in both maintained cellular properties and detectable signal by 3T MRI. In vivo results demonstrate the capability of MRI to detect and quantify labeled cells with a high degree of specificity. With nominal exogenous fluorine naturally present in tissue, labeled cells appear with little background. Pairing this signal with conventional proton MRI from the same imaging session, cells are able to be traced to their precise anatomical location. The MRI tracking capabilities, safety profiles, and use of 19F labeling in preclinical data sets demonstrate the ability of 19F to be used in clinical applications to strengthen the understanding of cellular therapeutics. Citation Format: Brooke M. Helfer, Anthony Balducci, Julie Urban, Lisa Butterfield, Eric Ahrens, Pawel Kalinski, Amy Wesa. Enabling in vivo visualization of cellular therapies in the clinic: Maturation of αDC1 data sets. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B44.