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Purpose In vivo immune cell tracking using MRI is a valuable tool for studying the mechanisms underlying successful cancer therapies. Current cell labeling methods using superparamagnetic iron oxide (SPIO) lack the specificity and persistence needed to track the fate and location of transplanted cells long-term. Magnetospirillium magneticum is a commercially available, iron-producing bacterium that can be taken up by, and live harmoniously within, mammalian cells as magneto-endosymbionts (MEs). MEs have shown promise as labeling agents for in vivo stem and cancer cell tracking but have yet to be evaluated in immune cells. This pilot study examined ME labeling in myeloid-derived suppressor cells (MDSCs), cytotoxic T lymphocytes (CTLs) and dendritic cells (DCs) and its effects on cell purity, function and MRI contrast. Procedures: MDSCs, CTLs and DCs were incubated with MEs at various ME labelling ratios (MLR) and various biological metrics and iron uptake were assessed. For in vivo imaging, MDSCs were labeled overnight with either MEs or SPIO (Molday ION Rhodamine B) and injected into C3 tumor-bearing mice via tail vein injection 24 days post-implant and scanned daily with MRI for one week to assess cellular quantification. Results Following incubations MDSCs contained 0.62 and 2.22 pg Fe/ cell. CTLs achieved Fe loading of In vivo data demonstrated that the MDSCs labeled with MEs generated sufficient contrast to be detectable using TurboSPI, similar to SPIO-labeled cells. Conclusions Cells can be labeled with pre-clinically relevant amounts of MEs without compromising cell viability. Care must be taken at higher concentrations of MEs, which may affect the functional activity and/or morphology of some cell types. Immune cells with minimal phagocytic behaviour have much lower iron content per cells after incubation with MEs vs SPIO; however, MEs can successfully be used as a contrast agent for phagocytic immune cells.

Purpose Develop a magnetic resonance fingerprinting (MRF) methodology with R2∗ quantification, intended for use with simultaneous contrast agent concentration mapping, particularly gadolinium (Gd) and iron labelled CD8+ T cells. Methods Variable-density spiral SSFP MRF was used, modified to allow variable TE, and with an exp.(−TE·R2∗) dictionary modulation. In vitro phantoms containing SPIO labelled cells and/or gadolinium were used to validate parameter maps, probe undersampling capacity, and verify dual quantification capabilities. A C57BL/6 mouse was imaged using MRF to demonstrate acceptable in vivo resolution and signal at 8× undersampling necessary for a 25-min scan. Results Strong agreement was found between conventional and MRF-derived values for R1, R2, and R2∗. Expanded MRF allowed quantification of iron-loaded CD8+ T cells. Results were robust to 8× undersampling and enabled recreation of relaxation profiles for both a Gd agent and iron labelled cells simultaneously. In vivo data demonstrated sufficient SNR in undersampled data for parameter mapping to visualise key features. Conclusion MRF can be expanded to include R1, R2, and R2∗ mapping required for simultaneous quantification of gadolinium and SPIO in vitro, allowing for potential implementation of a variety of future in vivo studies using dual MR contrast agents, including molecular imaging of labelled cells.

Image quality metrics (IQMs) such as root mean square error (RMSE) and structural similarity index (SSIM) are commonly used in the evaluation and optimization of accelerated magnetic resonance imaging (MRI) acquisition and reconstruction strategies. However, it is unknown how well these indices relate to a radiologist's perception of diagnostic image quality. In this study, we compare the image quality scores of five radiologists with the RMSE, SSIM, and other potentially useful IQMs: peak signal to noise ratio (PSNR) multi-scale SSIM (MSSSIM), information-weighted SSIM (IWSSIM), gradient magnitude similarity deviation (GMSD), feature similarity index (FSIM), high dynamic range visible difference predictor (HDRVDP), noise quality metric (NQM), and visual information fidelity (VIF). The comparison uses a database of MR images of the brain and abdomen that have been retrospectively degraded by noise, blurring, undersampling, motion, and wavelet compression for a total of 414 degraded images. A total of 1017 subjective scores were assigned by five radiologists. IQM performance was measured via the Spearman rank order correlation coefficient (SROCC) and statistically significant differences in the residuals of the IQM scores and radiologists' scores were tested. When considering SROCC calculated from combining scores from all radiologists across all image types, RMSE and SSIM had lower SROCC than six of the other IQMs included in the study (VIF, FSIM, NQM, GMSD, IWSSIM, and HDRVDP). In no case did SSIM have a higher SROCC or significantly smaller residuals than RMSE. These results should be considered when choosing an IQM in future imaging studies.

Tracking the migration of superparamagnetic iron oxide (SPIO)-labeled immune cells in vivo is valuable for understanding the immunogenic response to cancer and therapies. Quantitative cell tracking using TurboSPI-based R2* mapping is a promising development to improve accuracy in longitudinal studies on immune recruitment. However, off-resonance fat signal isochromats lead to modulations in the signal time-course that can be erroneously fit as R2* signal decay, overestimating the density of labeled cells, while excluding voxels with fat-typical modulations results in underestimation of cell density in voxels with mixed content. Approaches capable of accurate R2* estimation in the presence of fat are needed. We propose a dual-decay (separate R2f* and R2w* for fat and water) Dixon-based signal model that accounts for the presence of fat in a voxel to provide better estimates of SPIO-induced dephasing. This model was tested in silico, in phantoms with varying quantities of fat and SPIO-labeled cells, and in 5 mice injected with SPIO-labeled CD8+ T cells. In silico single voxel simulations illustrate how the proposed dual-decay model provides stable R2w* estimates that are invariant to fat content. The proposed model outperforms previous methods when applied to in vitro samples of SPIO-labeled cells and oil prepared with oil content ≥ 15%. Preliminary in vivo results show that, compared to previous methods, the dual-decay model improves the balance of R2* mapping in fat-dense areas, which will yield more reliable analysis in future cell tracking studies. The proposed model is a promising tool for quantitative TurboSPI R2* cell tracking, with further refinements offering the possibility of better specificity and sensitivity.

We aim to extend the use of image quality metrics (IQMs) from static magnetic resonance imaging (MRI) applications to dynamic MRI studies. We assessed the use of 2 IQMs, the root mean square error and structural similarity index, in evaluating the reconstruction of quantitative dynamic contrast-enhanced (DCE) MRI data acquired using golden-angle sampling and compressed sensing (CS). To address the difficulty of obtaining ground-truth knowledge of parameters describing dynamics in real patient data, we developed a Matlab simulation framework to assess quantitative CS-DCE-MRI. We began by validating the response of each IQM to the CS-MRI reconstruction process using static data and the performance of our simulation framework with simple dynamic data. We then extended the simulations to the more realistic extended Tofts model. When assessing the Tofts model, we tested 4 different methods of selecting a reference image for the IQMs. Results from the retrospective static CS-MRI reconstructions showed that each IQM is responsive to the CS-MRI reconstruction process. Simulations of a simple contrast evolution model validated the performance of our framework. Despite the complexity of the Tofts model, both IQM scores correlated well with the recovery accuracy of a central model parameter for all reference cases studied. This finding may form the basis of algorithms for automated selection of image reconstruction aspects, such as temporal resolution, in golden-angle-sampled CS-DCE-MRI. These further suggest that objective measures of image quality may find use in general dynamic MRI applications.

Magneto-endosymbionts (MEs) show promise as living magnetic resonance imaging (MRI) contrast agents for in vivo cell tracking. Here we characterize the biomedical imaging properties of ME contrast agents, in vitro and in vivo. By adapting and engineering magnetotactic bacteria to the intracellular niche, we are creating magneto-endosymbionts (MEs) that offer advantages relative to passive iron-based contrast agents (superparamagnetic iron oxides, SPIOs) for cell tracking. This work presents a biomedical imaging characterization of MEs including: MRI transverse relaxivity (r 2) for MEs and ME-labeled cells (compared to a commercially available iron oxide nanoparticle); microscopic validation of labeling efficiency and subcellular locations; and in vivo imaging of a MDA-MB-231BR (231BR) human breast cancer cells in a mouse brain. At 7T, r 2 relaxivity of bare MEs was higher (250 s−1 mM−1) than that of conventional SPIO (178 s−1 mM−1). Optimized in vitro loading of MEs into 231BR cells yielded 1–4 pg iron/cell (compared to 5–10 pg iron/cell for conventional SPIO). r 2 relaxivity dropped by a factor of ~3 upon loading into cells, and was on the same order of magnitude for ME-loaded cells compared to SPIO-loaded cells. In vivo, ME-labeled cells exhibited strong MR contrast, allowing as few as 100 cells to be detected in mice using an optimized 3D SPGR gradient-echo sequence. Our results demonstrate the potential of magneto-endosymbionts as living MR contrast agents. They have r 2 relaxivity values comparable to traditional iron oxide nanoparticle contrast agents, and provide strong MR contrast when loaded into cells and implanted in tissue.

Nonalcoholic fatty liver disease (NAFLD) is a growing health problem, and a major challenge in NAFLD management is identifying which patients are at risk of progression to more serious disease. Simple measurements of liver fat content are not strong predictors of clinical outcome, but biomarkers related to fatty acid composition (ie, saturated vs. unsaturated fat) may be more effective. MR spectroscopic imaging (MRSI) methods allow spatially resolved, whole‐liver measurements of chemical composition but are traditionally limited by slow acquisition times. In this work we present an accelerated MRSI acquisition based on spin echo single point imaging (SE‐SPI), which, using appropriate sampling and compressed sensing reconstruction, allows free‐breathing acquisition in a mouse model of fatty liver disease. After validating the technique's performance in oil/water phantoms, we imaged mice that had received a normal diet or a methionine and choline deficient (MCD) diet, some of which also received supplemental injections of iron to mimic hepatic iron overload. SE‐SPI was more resistant to the line‐broadening effects of iron than single‐voxel spectroscopy measurements, and was consistently able to measure the amplitudes of low‐intensity spectral peaks that are important to characterizing fatty acid composition. In particular, in the mice receiving the MCD diet, SE‐SPI showed a significant decrease in a metric associated with unsaturated fat, which is consistent with the literature. This or other related metrics may therefore offer more a specific biomarker of liver health than fat content alone. This preclinical study is an important precursor to clinical testing of the proposed method. MR‐based quantification of fatty acid composition may allow for improved characterization of non‐alcoholic fatty liver disease. A spectroscopic imaging method with appropriate sampling strategy allows whole‐liver mapping of fat composition metrics in a free‐breathing mouse model. Changes in metrics like the surrogate unsaturation index (UIs) are visible in mice receiving a diet which induces fat accumulation in the liver, as compared to a normal diet; such metrics may prove useful in future clinical studies of liver disease., MR‐based quantification of fatty acid composition may allow for improved characterization of non‐alcoholic fatty liver disease. A spectroscopic imaging method with appropriate sampling strategy allows whole‐liver mapping of fat composition metrics in a free‐breathing mouse model. Changes in metrics like the surrogate unsaturation index (UIs) are visible in mice receiving a diet which induces fat accumulation in the liver, as compared withto a normal diet; such metrics may prove useful in future clinical studies of liver disease.

Purely phase-encoded techniques such as single point imaging (SPI) are generally unsuitable for in vivo imaging due to lengthy acquisition times. Reconstruction of highly undersampled data using compressed sensing allows SPI data to be quickly obtained from animal models, enabling applications in preclinical cellular and molecular imaging. TurboSPI is a multi-echo single point technique that acquires hundreds of images with microsecond spacing, enabling high temporal resolution relaxometry of large-R 2* systems such as iron-loaded cells. TurboSPI acquisitions can be pseudo-randomly undersampled in all three dimensions to increase artifact incoherence, and can provide prior information to improve reconstruction. We evaluated the performance of CS-TurboSPI in phantoms, a rat ex vivo, and a mouse in vivo. An algorithm for iterative reconstruction of TurboSPI relaxometry time courses does not affect image quality or R 2* mapping in vitro at acceleration factors up to 10. Imaging ex vivo is possible at similar acceleration factors, and in vivo imaging is demonstrated at an acceleration factor of 8, such that acquisition time is under 1 h. Accelerated TurboSPI enables preclinical R 2* mapping without loss of data quality, and may show increased specificity to iron oxide compared to other sequences.

Purpose Magnetization transfer in white matter (WM) causes biexponential relaxation, but most quantitative T1 measurements fit data assuming monoexponential relaxation. The resulting monoexponential T1 estimate varies based on scan parameters and represents a source of variation between studies, especially at high fields. In this study, we characterized WM T1 relaxation and performed simulations to determine how to minimize this deviation. Methods To characterize biexponential relaxation, four volunteers were scanned at 3T and 7T using inversion recovery fast spin echo (IR-FSE) with 13 inversion times (TIs). Three volunteers were scanned with IR-FSE using TIs chosen by simulations to reduce T1 deviation, and with MP2RAGE. Results At 3T, the biexponential relaxation has a short component of T1 = 48 ms (9%) and a long component of T1 = 939 ms. At 7T the short component is T1 = 57 ms (11%) and the long component is 1349 ms (89%). For IR-FSE, acquiring four TIs with a minimum of 150 ms (3T) or 200 ms (7T) yielded monoexponential T1 estimates that match the long component to within 10 ms. For MP2RAGE, significant differences (90 ms at 3T, 125 ms at 7T) remain at all parameter values. Conclusion Many T1 mapping sequences yield robust estimates of the long T1 component with suitable choice of TIs, allowing reproducible, sequence-independent T1 values to be measured. However, this is not true of MP2RAGE in its current implementation. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Recently, several methods have been proposed for measuring the magnetic fields produced by weak electric currents using magnetic resonance imaging (MRI), including a theoretically described technique for source localization of current dipoles using signal phase. We have investigated whether these results can be replicated experimentally using 4.0 Tesla (T) MRI with a dipole phantom. While the use of high magnetic fields is advantageous in conventional functional MRI, it is unclear, a priori, whether MR current source localization also benefits. This study presents the technical challenges in MRI current source imaging and quantifies sensitivity using a phantom containing a current dipole.

The weldline strength of injection-molded thermoplastic elastomers (TPEs) were determined in terms of crack growth resistance. The specimens were injection molded under identical processing conditions except the cavity surface temperature; one cavity has a cold mold surface of 20°C and the other has a hot mold surface equal to the melt temperature of the TPE, 189°C. These two conditions were investigated simultaneously utilizing a two-cavity mold, where the isothermal cavity is based on low thermal inertia molding (LTIM) using thermoelectric devices for rapidly heating and cooling this cavity. A single-specimen, trouser tear test method was employed in determining the crack growth resistance curves (R curve) from the load-displacement curves. For the LTIM specimens the critical J integral value (Jc ) was 6 kJ/m2 and the conventional specimens had a Jc of 5 kJ/m2. Both types of specimen exhibited a rising crack growth region, with only the LTIM specimens reaching a plateau region equal to the maxi...

Air leakage is generally the most significant factor in small-building energy consumption. This study determined if reducing air leakage in preengineered metal buildings would be cost-effective. The effects of air-retarder treatments on owning and operating costs were examined for two different sizes of buildings that were thermally modeled using a building energy analysis computer program, BLAST. The annual energy consumption and peak loads were then produced by BLAST to find the fuel consumption for each building and the system sizes needed for adequate climate control. A detailed cost estimate was done on the mechanical system based on the required equipment size for each air-retarder treatment used. Life-cycle costs were determined for two types of air retarder and one case without an air retarder at four locations in cold and hot climates, and for five air exchange rates. A payback analysis illustrated the cost-effectiveness of the air-retarder treatments. Both air-retarder treatments proved cost-eff...

Susceptibility field gradients (SFGs) cause problems for functional magnetic resonance imaging (fMRI) in regions like the orbital frontal lobes, leading to signal loss and image artifacts (signal displacement and “pile-up”). Pulse sequences with spiral-in k-space trajectories are often used when acquiring fMRI in SFG regions such as inferior/medial temporal cortex because it is believed that they have improved signal recovery and decreased signal displacement properties. Previously postulated theories explain differing reasons why spiral-in appears to perform better than spiral-out; however it is clear that multiple mechanisms are occurring in parallel. This study explores differences in spiral-in and spiral-out images using human and phantom empirical data, as well as simulations consistent with the phantom model. Using image simulations, the displacement of signal was characterized using point spread functions (PSFs) and target maps, the latter of which are conceptually inverse PSFs describing which spatial locations contribute signal to a particular voxel. The magnitude of both PSFs and target maps was found to be identical for spiral-out and spiral-in acquisitions, with signal in target maps being displaced from distant regions in both cases. However, differences in the phase of the signal displacement patterns that consequently lead to changes in the intervoxel phase coherence were found to be a significant mechanism explaining differences between the spiral sequences. The results demonstrate that spiral-in trajectories do preserve more total signal in SFG regions than spiral-out; however, spiral-in does not in fact exhibit decreased signal displacement. Given that this signal can be displaced by significant distances, its recovery may not be preferable for all fMRI applications.

This work proposes the use of TurboSPI, a multi-echo single point imaging sequence, for the quantification of labeled cells containing moderate to high concentrations of iron oxide contrast agent. At each k-space location, TurboSPI acquires several hundred time points during a spin echo, permitting reliable relaxation rate mapping of large-R(2)(∗) materials. An automatic calibration routine optimizes image quality by promoting coherent alignment of spin and stimulated echoes throughout the multi-echo train, and this calibration is sufficiently robust for in vivo applications. In vitro relaxation rate measurements of SPIO-loaded cervical cancer cells exhibit behavior consistent with theoretical predictions of the static dephasing regime in the spin echo case; the relaxivity measured with TurboSPI was 10.47±2.3 s(-1)/mG, comparable to the theoretical value of 10.78 s(-1)/mG. Similar measurements of micron-sized iron oxide particles (0.96 μm and 1.63 μm diameter) show a reduced relaxivity of 8.06±0.68 s(-1)/mG and 7.13±0.31 s(-1)/mG respectively, indicating that the static dephasing criterion was not met. Nonetheless, accurate quantification of such particles is demonstrated up to R(2)(∗)=900 s(-1), with a potentially higher upper limit for loaded cells having a more favorable R(2)('):R(2) ratio. Based on the cells used in this study, reliable quantification of cells loaded with 10 pg of iron per cell should be possible up to a density of 27 million cells/mL. Such quantification will be of crucial importance to the development of longitudinal monitoring for cellular therapy and other procedures using iron-labeled cells.

We introduce a noninvasive, quantitative magnetic resonance imaging (MRI) wind-tunnel measurement in flowing gas (>10 m s(-1)) at high Reynolds numbers (Re>10(5)). The method pertains to liquids and gases, is inherently three dimensional, and extends the range of Re to which MRI is applicable by orders of magnitude. There is potential for clear time savings over traditional pointwise techniques. The mean velocity and turbulent diffusivity of gas flowing past a bluff obstruction and a wing section at realistic stall speeds were measured. The MRI data are compared with computational fluid dynamics.