Magnetic Resonance Microimaging Research Articles

In VivoMagnetic Resonance Microimaging of Individual Amyloid Plaques in Alzheimer's Transgenic Mice

The ability to detect individual Alzheimer's amyloid plaques in vivo by magnetic resonance microimaging (MRI) should improve diagnosis and also accelerate discovery of effective therapeutic agents for Alzheimer's disease (AD). Here, we perform in vivo and ex vivo MRI on double transgenic AD mice as well as wild-type mice at varying ages and correlate these with thioflavin-S and iron staining histology. Quantitative counts of individual plaques on MRI increase with age and correlate with histologically determined plaque burden. Plaques 20 microm in diameter can be detected in AD mice as young as 3 months of age with ex vivo MRI. Plaques 35 microm in diameter can be detected by 9 months of age with in vivo MRI. In vivo MRI of individual Alzheimer's amyloid plaques provides a noninvasive estimate of plaque burden in transgenic AD mice that might be useful in assessing the efficacy of amyloid reduction therapies.

Effect of Testosterone Replacement on Trabecular Architecture in Hypogonadal Men

We evaluated the effect of testosterone treatment on trabecular architecture by microMRI in 10 untreated severely hypogonadal men. After 2 years, microMRI parameters of trabecular connectivity improved significantly, suggesting the possibility that testosterone improves trabecular architecture. Osteoporosis, characterized by low BMD and diminished bone quality, is a significant public health problem in men. Hypogonadal men have decreased BMD and deteriorated trabecular architecture compared with eugonadal men, and testosterone treatment improves their BMD. We tested the hypothesis that testosterone replacement in hypogonadal men would also improve their trabecular architecture. We selected 10 untreated severely hypogonadal men and treated them with a testosterone gel for 24 months to maintain their serum testosterone concentrations within the normal range. Each subject was assessed before and after 6, 12, and 24 months of testosterone treatment by magnetic resonance microimaging (microMRI) of the distal tibia and by DXA of the spine and hip. The microMRI parameters reflect the integrity of the trabecular network and include the ratio of all surface voxels (representing plates) to curve voxels (representing rods) and the topological erosion index, a ratio of topological parameters expected to increase on trabecular deterioration to those expected to decrease. The higher the surface-to-curve ratio and the lower the topological erosion index, the more intact the trabecular network. Serum testosterone concentrations increased to midnormal after 3 months of treatment and remained normal thereafter. After 24 months of testosterone treatment, BMD of the spine increased 7.4% (p<0.001), and of the total hip increased 3.8% (p=0.008). Architectural parameters assessed by microMRI also changed: the surface-to-curve ratio increased 11% (p=0.004) and the topological erosion index decreased 7.5% (p=0.004). These results suggest the possibility that testosterone replacement of hypogonadal men improves trabecular architecture.

Water uptake and distribution in germinating tobacco seeds investigated in vivo by nuclear magnetic resonance imaging.

The regulation of water uptake of germinating tobacco (Nicotiana tabacum) seeds was studied spatially and temporally by in vivo (1)H-nuclear magnetic resonance (NMR) microimaging and (1)H-magic angle spinning NMR spectroscopy. These nondestructive state-of-the-art methods showed that water distribution in the water uptake phases II and III is inhomogeneous. The micropylar seed end is the major entry point of water. The micropylar endosperm and the radicle show the highest hydration. Germination of tobacco follows a distinct pattern of events: rupture of the testa is followed by rupture of the endosperm. Abscisic acid (ABA) specifically inhibits endosperm rupture and phase III water uptake, but does not alter the spatial and temporal pattern of phase I and II water uptake. Testa rupture was associated with an increase in water uptake due to initial embryo elongation, which was not inhibited by ABA. Overexpression of beta-1,3-glucanase in the seed-covering layers of transgenic tobacco seeds did not alter the moisture sorption isotherms or the spatial pattern of water uptake during imbibition, but partially reverted the ABA inhibition of phase III water uptake and of endosperm rupture. In vivo (13)C-magic angle spinning NMR spectroscopy showed that seed oil mobilization is not inhibited by ABA. ABA therefore does not inhibit germination by preventing oil mobilization or by decreasing the water-holding capacity of the micropylar endosperm and the radicle. Our results support the proposal that different seed tissues and organs hydrate at different extents and that the micropylar endosperm region of tobacco acts as a water reservoir for the embryo.

Self-Oscillation Liquid Front inside a Partially Wetted Catalyst Pellet under α-Methylstyrene Hydrogenation: Experiment and Theory

Self-oscillations on a partially wetted cylindrical catalyst pellet 1% Pd/γ-Al2O3 in α-methylstyrene (AMS) hydrogenation accompanied by liquid evaporation are studied. By NMR tomography (magnetic resonance microimaging), images of the liquid-phase distribution within the porous pellet are obtained and the liquid-phase redistribution is monitored immediately during the process. The physical mechanism and simplified one-dimensional model are suggested to explain the observed phenomenon. The model predicts well the experimental period (2−3 min) and the amplitudes of the temperature oscillations at the lower (dry) part of the pellet and also the liquid front oscillations at the upper part. The instability mechanism (negative feedback with time lag) is based on complex interaction among the processes of imbibition, evaporation, and gas-phase hydrogenation.

Comparison of Macromolecular Contrast Agents for Dynamic Micromagnetic Resonance Lymphangiography

Few methods are currently available to visualize the entire lymphatic system. We recently developed a method of micromagnetic resonance (MR) lymphangiography (MRL) in mice that uses a dendrimer-based MR imaging (MRI) contrast agent (PAMAM-G8) and a clinical-grade 1.5-Tesla MRI instrument. In the present study, four dendrimer-based MRI contrast agents with different pharmacokinetic characteristics were compared in an attempt to optimize the choice of reagent for specific visualization of the lymphatic system compared with established macromolecular MRI contrast agents, Magnevist (Schering, Berlin, Germany) and Gadomer-17 (Schering), in both normal and disease model mice.

Magnetic resonance microimaging and numerical simulations of velocity fields inside enlarged flow cells used for coupled NMR microseparations.

The coupling of various chemical microseparation methods with small-scale NMR detection is a growing area in analytical chemistry. The formation of enlarged flow cells within the active volume of the NMR detector can significantly increase the coil filling factor and hence the signal-to-noise ratio of the NMR spectra. However, flow cells can also lead to deterioration of the separation efficiency due to the development of complex flow patterns, the form of which depend on the particular geometry of the flow cell and the flow rate used. In this study, we investigated the flow characteristics in different flow cell geometries relevant to the coupling of capillary liquid chromatography and NMR. Computational fluid dynamics was used to simulate fluid flow inside flow cells with a volume of approximately 1 microL. Magnetic resonance microimaging was used to measure experimentally the velocity fields inside these flow cells. The results showed good agreement between experiment and simulation and demonstrated that a relatively gradual expansion and contraction is necessary to avoid areas of weak recirculation and strong radial velocities, both of which can potentially compromise separation efficiency.

The future of radioimmunotherapy: A PET perspective

The future success of radioimmunotherapy (RIT) lies in building relationships between oncologists and nuclear medicine physicians. Communication between these specialists is key to the progress of radioimmunotherapy, and a team approach is required among all those involved in the process, not only for the benefit of the patient, but also for the success of research endeavors. Identification of the key questions regarding diagnosis and management of cancer must be formulated to design appropriate clinical trials incorporating radioimmunotherapy. The use of imaging modalities to conduct radiotracer studies may provide valuable information with regard to drug delivery and target specificity. One such approach is positron emission tomography (PET), a functional imaging modality with high sensitivity and specificity for tumor detection. The recent addition of hybrid PET/computed tomography, enabling biologic and anatomic whole-body imaging to be performed in one examination, has further facilitated the assignment of biologic abnormalities to anatomic structures. The most widely used radiotracer for PET is 18 F-fluorodeoxyglucose; however, fluorodeoxyglucose is a relatively nonspecific tracer. Novel, more specific tracers are being designed to assess cell proliferation. Radiolabeled non-catabolized derivatives of thymidine that are incorporated into cellular DNA are undergoing clinical trials for diagnostic efficacy using PET. In vivo anatomic micro-imaging technologies, such as microPET, microcomputed tomography, and micro-magnetic resonance imaging, enable the assessment of metabolism, cell communication, and gene expression in animal models. Fast-tracking imaging methods through translational research to human use is critical if imaging is to aid in the delivery of optimal cancer treatments. This article presents an overview of the way in which imaging may facilitate the evaluation of new treatment modalities to advance patient treatment and care.

Self-oscillations on a partially wetted catalyst pellet in ?-methylstyrene hydrogenation: Experiment and mathematical modeling

Self-oscillation modes on an irrigated porous catalyst pellet in exothermic hydrogenation accompanied by liquid evaporation is studied. By NMR tomography (magnetic resonance microimaging), images of the liquid-phase distribution within the porous object are obtained and the liquid-phase redistribution is monitored immediately during the process without destroying the object and without introducing any probes or molecular labels.

Moisture movement and thickness swelling in oriented strandboard, part 1. Analysis using nuclear magnetic resonance microimaging

A procedure was developed to observe the water absorption characteristics of small specimens of oriented strandboard (OSB) and solid wood in a nuclear magnetic resonance (NMR) microimaging facility. The procedure allowed a specimen to be surrounded in water while remaining in a fixed position within the imaging coil, after which the water could be removed and the specimen immediately imaged. This technique permitted images of the specimen to be taken after a number of different periods of water soak without having to remove and replace the specimen, thus easily maintaining the same image location. Both the distribution of free water and its movement as a function of time were observed using this technique. Inter-strand voids within OSB were shown to be the main route for moisture movement through a specimen of this type. The influence of the inherent anisotropy of OSB on moisture movement was investigated by sealing selected surfaces of a specimen with silicone to observe moisture absorption in predetermined directions.

Methane and Carbon Dioxide Hydrate Formation in Water Droplets: Spatially Resolved Measurements from Magnetic Resonance Microimaging

We have used 1H magnetic resonance microimaging to probe both methane and carbon dioxide hydrate formation processes inside dispersed water droplets. When bulk techniques such as gas uptake measurements are used for determining the kinetics of hydrate formation, these show a gradual conversion to hydrate, suggesting a relatively homogeneous process that might be modeled using a set of intrinsic kinetic parameters. The spatially resolved microimaging measurements show that in fact the conversion to hydrate is quite inhomogeneous, some drops converting quickly, others requiring hours or days. This indicates that the observation of gradual conversion in bulk samples only arises as a result of averaging over many local environments. Quantitative measurements of kinetic processes in subvolumes of a larger sample suggests that the smaller the volume observed, the more inhomogeneous the process appears to be. When hydrate-coated water droplets in 3,5,5-trimethylpentane are converted to hydrate, there is evidence...

Patterns of gene expression reveal a temporally orchestrated wound healing response in the injured spinal cord.

Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.

Simultaneous NMR microimaging of multiple single‐cell samples

AbstractNuclear magnetic resonance (NMR) microimaging experiments performed on small samples such as single cells typically require long data acquisition times and are usually carried out on high‐field systems with limited access time. When using small probe coils on millimetre (or smaller) size scale to study single cells, it is desirable to take advantage of the comparatively large volume of homogeneous static magnetic field within the magnet to increase the efficiency of NMR data acquisition. Here we describe the development of a four‐channel probehead that consists of four individual solenoid coils (length 2.8 mm, outer diameter 2 mm) stacked along the z axis. The probehead was designed for a 17.6 Tesla (750 MHz) wide‐bore magnet, and operates within a 40 mm inner diameter gradient set with maximum strength 1 Tesla per metre. We performed simulations to estimate the impact of shielding between the coils on the B1 field distribution. Results showed that for coil‐shield separations on the order of a coil radius, no significant change in B1 homogeneity is expected, and therefore coils were spaced accordingly. Coil isolation of greater than 35 dB was achieved for all coils, and the Q values were ∼160 unloaded and ∼60 loaded with 100 mM NaCl solution. Practical use of the probehead was demonstrated by obtaining simultaneously four three‐dimensional T1 maps of chemically fixed Xenopus laevis oocytes at a spatial resolution of 30 × 60 × 60 μm. The T1 values for the nucleus were ∼2.7 seconds, and the animal pole ∼1.2 seconds. © 2004 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 22B: 7–14, 2004.

Epicuticular wax of large and small white butterflies, Pieris brassicae and P. rapae crucivora: qualitative and quantitative comparison between diapause and non-diapause pupae.

We compared the quantity and quality of the epicuticular wax of diapause and non-diapause pupae in two closely related Pieris species, P. brassicae and P. rapae crucivora. Main components of their epicuticular wax were identified as hydrocarbons. In P. brassicae, more than 95% of hydrocarbons were saturated regardless of whether the pupae were in diapause or not. In P. rapae crucivora, 93% of hydrocarbons were saturated in non-diapause pupae whereas in diapause pupae 41% were saturated and 59% unsaturated. From measurements of body surface area by nuclear magnetic resonance microimaging, we calculated the average thickness of the wax layer. The thickness in diapause and non-diapause pupae of P. brassicae was 800 and 160 nm, respectively. In P. rapae crucivora, the thickness was 195 nm in diapause and 11 nm in non-diapause. This is the first report to clarify the compositional difference in epicuticular wax between diapause and non-diapause pupae.

Quantitative high-resolution magnetic resonance imaging reveals structural implications of renal osteodystrophy on trabecular and cortical bone.

To explore the potential role of micro-magnetic resonance imaging (micro-MRI) for quantifying trabecular and cortical bone structural parameters in renal osteodystrophy (ROD), a multifactorial disorder of bone metabolism, traditionally evaluated by bone biopsy. Seventeen hemodialysis patients (average PTH level = 502 +/- 415 microg/liter) were compared with 17 age-, gender-, and body mass index (BMI)-matched control subjects. The average dialysis duration for the patients was 5.5 years (range = 0.96-18.2 years). Three-dimensional (3D) fast large-angle spin-echo (FLASE) MR images of the distal tibia (voxel size = 137 x 137 x 410 microm(3)) were processed to yield bone volume fraction (BV/TV). From a skeletonized representation of the trabecular bone network, the topology of each bone voxel was determined providing surface and curve voxel densities (SURF and CURV) and the topological erosion index (EI). Further, high-resolution two-dimensional (2D) spin-echo images were collected at the tibial midshaft for measurement of cortical bone cross-sectional area (CCA), relative CCA expressed as a percentage of total bone area (RCA), and mean cortical thickness (MCT). The data show both RCA and MCT to be lower in the patients (61.2 vs. 69.1%, P = 0.008, and 4.53 vs. 5.19 mm, P = 0.01). BV/TV and SURF were lower, while EI was increased in the patients, although these differences were not quite significant (P = 0.06-0.09). All of the cortical and trabecular findings are consistent with increased bone fragility. The data suggest that micro-MRI may have potential to characterize the structural implications of metabolic bone disease, potentially providing a noninvasive tool for the evaluation of therapies for ROD.

Reproducibility and error sources of μ-MRI-based trabecular bone structural parameters of the distal radius and tibia

The mechanical competence of trabecular bone is significantly determined, next to material density, by its three-dimensional (3D) structure. Recent advances in micromagnetic resonance imaging (μ-MRI) acquisition and processing techniques allow the 3D trabecular structure to be analyzed in vivo at peripheral sites such as the distal radius and tibia. The practicality of μ-MRI-based noninvasive virtual bone biopsy (VBB) for longitudinal studies of patients hinges on the reproducibility of the derived structural parameters, which largely determine the size of the effect that can be detected at a given power and significance level. In this paper, the reproducibility of μ-MRI-derived trabecular bone structure measures was examined by performing repeat studies in six healthy subjects in whom the distal aspects of the radius and tibia were scanned with a 3D spin-echo sequence at 137 × 137 × 410 μm 3 voxel size. Bone volume fraction (BV/TV) and digital topological analysis (DTA) structural parameters including the topological bone surface-to-curve ratio (SCR) and topological erosion index (TEI) were evaluated after subjecting the raw images to a cascade of processing steps. The average coefficient of variation was 4–7% and was comparable for the two anatomic sites and for all parameters measured. The reliability expressed in terms of the intraclass correlation coefficient ranged from 0.95 to 0.97 in the radius and 0.68 to 0.92 in the tibia. Error analysis based on simulations suggests involuntary patient motion, primarily rotation, to be the chief source of imprecision, followed by failure to accurately match the analysis volumes in repeat studies.

Regional cerebral blood volume reduction in transgenic mutant APP (V717F, K670N/M671L) mice

Recent advance in nuclear magnetic resonance (NMR) microimaging has enabled in vivo cerebral blood volume (CBV) mapping with high spatial resolution. Using an intravascular susceptibility contrast agent and T 2-weighted magnetic resonance imaging (MRI) on a 9.4 T NMR microimager, the regional CBV was measured in mice as the transverse relaxation increase induced by the contrast agent. CBV maps in an Alzheimer’s disease mouse model at resting state were obtained and examined. Four-month-old male transgenic mutant APP (V717F, K670N/M671L) mice ( N = 10) and littermate wild-type controls ( N = 12) were used. Regional analysis of the multi-slice CBV maps revealed statistically significant CBV reductions among the APP mice in cerebral cortex (−9.29%, P = 0.0002), hippocampus (−4.22%, P = 0.02), and thalamus (−5.21%, P = 0.03), indicating an early change of microvasculature in these selected regions. No significant difference was found in olfactory bulb, pons, midbrain, superior colliculus, medulla, and cerebellum.

High-resolution imaging at 3T and 7T with multiring local volume coils

Magnetic resonance (MR) microimaging of the human is becoming increasingly common for studies of tissue microstructure and microfunction. In this study, we consider the constraints that such experiments place on the design of radio-frequency (rf) coils, and describe the advantages of multiring coils, which offer a locally uniform B(1) field. We show that these coils are particularly suitable for high-field imaging of a restricted region of larger experimental animals or humans, offering the same simplicity and efficient use of rf power as a simple surface coil but without requiring sequence modifications such as adiabatic pulses. Imaging results are shown from human brain and from the abdominal aorta of an experimental animal.

Nuclear magnetic resonance microimaging of mouse spinal cord in vivo

The spinal cord is the site of traumatic injuries, the devastating consequences of which constitute a public health problem in our societies. So far, there is no efficient repair therapeutic approach, and this is mainly due to the great difficulty for elaborating predictive experimental models of this pathology. Up to now, most pathophysiological studies were based on postmortem evaluation of the quantity and extent of the lesions, and their comparison in-between human and rodent specimen. Recent progresses of magnetic resonance imaging provide new tools to examine in vivo rodent central nervous system, and eventually to monitor the progression of lesions. However, up to now, mice spinal cord has been inaccessible to such studies, due to specific physiological characteristics and to the small size of the cord. In this study, the first diffusion-weighted images depicting the mouse thoracic spinal cord in vivo are shown. Motion-related artifacts are significantly reduced by respiratory gating using a dedicated sensor. By changing the direction of diffusion-sensitizing gradients, different contrasts were obtained that are compared with ex vivo MRI and histological preparations. In addition, preliminary results obtained on pathological cords are presented.

Evaluation of 9.4-T MR microimaging in assessing normal and defective fetal bone development: comparison of MR imaging and histological findings

We evaluated 9.4-T magnetic resonance (MR) microimaging in assessing normal and defective bone development in mouse embryos. For this purpose, we performed 9.4-T MR microimaging on developing bones in normal embryos, and also in Runx2/Cbfa1−/− embryos with severely defective bone development. MR images were compared with the histological and histochemical features of these fetal bones. MR microimaging delineate successfully the normal long bone development in embryos. The T1- and T2-weighted MR microimaging demonstrated chondrocyte maturation in different regions of growing cartilage, such as epiphysis, physis, hypertrophic cartilage, and zone of provisional calcification. These developmental changes were detectable in as early as E14.5 embryos. The MR microimaging clearly demonstrated defective bone development in Runx2/Cbfa1−/− embryos. The femur from E18.5 homozygous Runx2/Cbfa1−/− embryos lacked MR signal intensity patterns including the hypertrophic cartilage, which are characteristic of the bone from the age-matched Runx2/Cbfa1+/+ embryos. Interestingly, however, the tibia from the same mutants was associated with MR signal patterns indicative of hypertrophic cartilage but not of the primary spongiosa and ossifying perichondrium, suggesting that bone development is differently regulated in these two long bones. On the other hand, the bones from heterozygous Runx2/Cbfa1+/− embryos exhibited an MR phenotype intermediate between the Runx2/Cbfa1+/+ and Runx2/Cbfa1−/− embryos; the primary spongiosa and ossifying perichondrium formation occurred normally even in the absence of preceding organized maturation of chondrocytes, a phenotype that was not detected by histological examinations. We concluded that MR microimaging is useful in assessing the bone development.

23Na NMR microimaging: a tool for non-invasive monitoring of sodium distribution in living plants.

Detailed knowledge of the sodium (Na) distribution within the tissues of highly salt-tolerant Australian native species could help in understanding the physiological adaptations of salt-tolerance or salt-sensitive plants. 23Na nuclear magnetic resonance (NMR) microimaging is presented as a tool to achieve this goal. Maps of the Na distribution in stem tissue were obtained with an in-plane resolution of approximately125 µm and a slice thickness of 4 mm. Simultaneously recorded high resolution 1H NMR images showing water distribution in the same slice with 31 µm in-plane resolution and 1 mm slice thickness, were used as an anatomical reference together with optical micrographs that were taken immediately after the NMR experiments were completed. To quantify the Na concentration, reference capillaries with known NaCl concentrations were located in the NMR probe together with the plant sample. Average concentration values calculated from signal intensities in the tissue and the capillaries were compared with concentration values obtained from atomic emission photometry and optical microscopy performed on digested stem sections harvested immediately after NMR experiments. Results showed that 23Na NMR microimaging has great potential for physiological studies of salt stress at the macroscopic level, and may become a unique tool for diagnosing salt tolerance and sensitivity.