Jared G. Cobb

Contributions of chemical exchange to T1ρ dispersion in a tissue model.

Variations in T1ρ with locking‐field strength (T1ρ dispersion) may be used to estimate proton exchange rates. We developed a novel approach utilizing the second derivative of the dispersion curve to measure exchange in a model system of cross‐linked polyacrylamide gels. These gels were varied in relative composition of comonomers, increasing stiffness, and in pH, modifying exchange rates. Magnetic resonance images were recorded with a spin‐locking sequence as described by Sepponen et al. These measurements were fit to a mono‐exponential decay function yielding values for T1ρ at each locking‐field measured. These values were then fit to a model by Chopra et al. for estimating exchange rates. For low stiffness gels, the calculated exchange values increased by a factor of 4 as pH increased, consistent with chemical exchange being the dominant contributor to T1ρ dispersion. Interestingly, calculated chemical exchange rates also increased with stiffness, likely due to modified side‐chain exchange kinetics as the composition varied. This article demonstrates a new method to assess the structural and chemical effects on T1ρ relaxation dispersion with a suitable model. These phenomena may be exploited in an imaging context to emphasize the presence of nuclei of specific exchange rates, rather than chemical shifts. Magn Reson Med, 2011.

Magnetic nanoparticles for imaging dendritic cells.

We report the development of superparamagnetic iron oxide (SPIOs) nanoparticles and investigate the migration of SPIO‐labeled dendritic cells (DCs) in a syngeneic mouse model using magnetic resonance (MR) imaging. The size of the dextran‐coated SPIO is roughly 30 nm, and the DCs are capable of independent uptake of these particles, although not at levels comparable to particle uptake in the presence of a transfecting reagent. On average, with the assistance of polylysine, the particles were efficiently delivered inside DCs within one hour of incubation. The SPIO particles occupy approximately 0.35% of cell surface and are equivalent to 34.6 pg of iron per cell. In vivo imaging demonstrated that the labeled cells migrated from the injection site in the footpad to the corresponding popliteal lymph node. The homing of labeled cells in the lymph nodes resulted in a signal drop of up to 79%. Furthermore, labeling DCs with SPIO particles did not compromise cell function, we demonstrated that SPIO‐enhanced MR imaging can be used to track the migration of DCs effectively in vivo. Magn Reson Med 63:1383–1390, 2010.

Multimodal imaging of dendritic cells using a novel hybrid magneto-optical nanoprobe

UNLABELLED A transfecting agent-coated hybrid imaging nanoprobe (HINP) composed of visible and near-infrared (NIR) light emitting quantum dots (QDs) tethered to superparamagnetic iron oxide (SPIO) nanoparticles was developed. The surface modification of QDs and SPIO particles and incorporation of dual QDs within the SPIO were characterized by dynamic light scattering (DLS), quartz crystal microbalance (QCM) analysis and atomic force microscopy (AFM). The optical contrasting properties of HINP were characterized by absorption and photoluminescence spectroscopy and fluorescence imaging. Multicolor HINP was used in imaging the migration of dendritic cells (DCs) by optical, two-photon and magnetic resonance imaging techniques. FROM THE CLINICAL EDITOR The development of a transfecting agent-coated hybrid imaging nanoprobe (HINP) composed of visible and near-infrared light emitting quantum dots (QDs) tethered to superparamagnetic iron oxide nanoparticles is reported in this paper. Multicolor HINP was used in imaging the migration of dendritic cells by optical, two-photon and magnetic resonance imaging techniques.

Contributions of chemical and diffusive exchange to T1ρ dispersion.

Variations in local magnetic susceptibility may induce magnetic field gradients that affect the signals acquired for MR imaging. Under appropriate diffusion conditions, such fields produce effects similar to slow chemical exchange. These effects may also be found in combination with other chemical exchange processes at multiple time scales. We investigate these effects with simulations and measurements to determine their contributions to rotating frame (R1ρ) relaxation in model systems. Simulations of diffusive and chemical exchange effects on R1ρ dispersion were performed using the Bloch equations. Additionally, R1ρ dispersion was measured in suspensions of Sephadex and latex beads with varying spin locking fields at 9.4 T. A novel analysis method was used to iteratively fit for apparent chemical and diffusive exchange rates with a model by Chopra et al. Single‐ and double‐inflection points in R1ρ dispersion profiles were observed, respectively, in simulations of slow diffusive exchange alone and when combined with rapid chemical exchange. These simulations were consistent with measurements of R1ρ in latex bead suspensions and small‐diameter Sephadex beads that showed single‐ and double‐inflection points, respectively. These observations, along with measurements following changes in temperature and pH, are consistent with the combined effects of slow diffusion and rapid −OH exchange processes. Magn Reson Med, 2013.

Exchange-mediated contrast in CEST and spin-lock imaging.

PURPOSE Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. METHODS Simulations and experimental measurements at 9.4 T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. RESULTS The simulations and experimental measurements confirm that both CEST and R1ρ measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. >2 ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (<2 ppm) and exchange is in the intermediate-to-fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CONCLUSION CEST and R1ρ measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1ρ-dependent acquisitions can be employed to selectively portray protons of specific exchange rates.

Exchange-mediated contrast agents for spin-lock imaging

Measurements of relaxation rates in the rotating frame with spin‐locking techniques are sensitive to substances with exchanging protons with appropriate chemical shifts. The authors develop a novel approach to exchange‐rate selective imaging based on measured T1ρ dispersion with applied locking field strength, and demonstrate the method on samples containing the X‐ray contrast agent Iohexol with and without cross‐linked bovine serum albumin. T1ρ dispersion of water in the phantoms was measured with a Varian 9.4‐T magnet by an on‐resonance spin‐locking pulse with fast spin‐echo readout, and the results used to estimate exchange rates. The Iohexol phantom alone gave a fitted exchange rate of ∼1 kHz, bovine serum albumin alone was ∼11 kHz, and in combination gave rates in between. By using these estimated rates, we demonstrate how a novel spin‐locking imaging method may be used to enhance contrast due to the presence of a contrast agent whose protons have specific exchange rates. Magn Reson Med, 2012.

T1ρ mapping of pediatric epiphyseal and articular cartilage in the knee

To evaluate the feasibility of measuring T1ρ values in epiphyseal cartilage in children, we have conducted a novel study of spin locking techniques. Adult articular cartilage has been widely studied with spin locking techniques by magnetic resonance imaging. However, no results are available for in vivo T1ρ imaging of developing cartilage.

Improved in vivo measurement of myocardial transverse relaxation with 3 Tesla magnetic resonance imaging

To develop practical methods at 3 Tesla (T) for measuring myocardial transverse relaxation in normal human myocardium.

Implementation of a Semi-automated Post-processing System for Parametric MRI Mapping of Human Breast Cancer

Magnetic resonance imaging (MRI) investigations of breast cancer incorporate computationally intense techniques to develop parametric maps of pathophysiological tissue characteristics. Common approaches employ, for example, quantitative measurements of T1, the apparent diffusion coefficient, and kinetic modeling based on dynamic contrast-enhanced MRI (DCE-MRI). In this paper, an integrated medical image post-processing and archive system (MIPAS) is presented. MIPAS demonstrates how image post-processing and user interface programs, written in the interactive data language (IDL) programming language with data storage provided by a Microsoft Access database, and the file system can reduce turnaround time for creating MRI parametric maps and provide additional organization for clinical trials. The results of developing the MIPAS are discussed including potential limitations of the use of IDL for the application framework and how the MIPAS design supports extension to other programming languages and imaging modalities. We also show that network storage of images and metadata has a significant (p < 0.05) increase in data retrieval time compared to collocated storage. The system shows promise for becoming both a robust research picture archival and communications system working with the standard hospital PACS and an image post-processing environment that extends to other medical image modalities.

Amyloid burden measured by T1-rho–weighted MRI in Down syndrome

Background: Individuals with Down syndrome (DS; trisomy 21) are at increased risk for Alzheimer’s disease (AD) and they develop amyloid beta plaques (Ab) by 30 years because they have 3 copies of the gene encoding amyloid precursor protein (APP). Therefore, they are an ideal population in which to validate Ab biomarkers. Currently, brain levels of Ab are measured invasively via lumbar puncture or radioactive ligand-based positron emission tomography. Non-invasive biomarkers are necessary for early screening and repeatability. Non-invasive T1-rho-weighted magnetic resonance imaging (T1r MRI) detects Ab in transgenic mouse models of AD and shows decreases at plaque deposition; we are investigating its use as an early biomarker of Ab in DS subjects. Methods: The current sample includes 9 DS subjects (ages 36-54) compared to 9 subjects (ages 54-89) with normal cognition (NC). T1r dispersion curves were quantified in AD-related regions of interest (ROIs) delineated using FreeSurfer. The dispersion curves include quantified T1, T2, and two T1r values (at FSL1⁄4275 and 550 Hz). Curve features between DS and NC were compared and APOE status and family history of AD will be incorporated into analyses. Results: DS subjects showed a lower slope between the two T1rho data points compared to NC subjects in a priori ROIs, including the left amygdala (p1⁄4.005), left temporal pole (p1⁄4.013), right isthmus of the cingulate gyrus (p1⁄4.029), and right parahippocampal gyrus (p1⁄4.012). The contralateral temporal pole and isthmus of the cingulate trended in the same direction but did not reach significance. Preliminary analysis suggests APOE status and family history modulate the relationship between diagnostic category and T1r. Conclusions: Quantitative T1r and its dispersion curve followed the expected between-group trend for detecting Ab (DS < NC). Recruitment is ongoing to obtain 20 subjects per group. If further validated in larger samples and in ex vivo studies, T1r could be used as a non-invasive alternative to PET imaging of Ab for early identification of patients at highest risk for AD, allowing for earlier disease treatment and monitoring of progression.