Neurite orientation dispersion and density imaging can detect presymptomatic axonal degeneration in the spinal cord of ALS mice.

Neurite orientation dispersion and density imaging (NODDI), a MRI multi-shell diffusion technique, has offered new insights for the study of microstructural changes in neurodegenerative diseases. Mainly, the present study aimed to determine the connection between NODDI-derived parameters and changes in white matter (WM) abnormalities at early stages of amyotrophic lateral sclerosis (ALS). Spinal cords from ALS mice (G93A-SOD1 mice) were scanned in a Bruker Avance III HD 17.6T magnet. Fluorescent axonal-tagged mice (YFP, G93A-SOD1 mice) were used for quantitative histological analysis. NODDI showed a decrease in intra-cellular volume fraction (-24%) and increases in orientation dispersion index (+35%) and isotropic volume fraction (+33%). In addition, histoathological results demonstrated a reductions in axonal area (-11%) and myelin content (-29%). A histological decrease in WM intra-axonal space (-71%) and an increase in the extra-axonal compartment (+22%) were also detected. Our studies demonstrate that NODDI may be a suitable technique for detecting presymptomatic spinal cord WM microstructural degeneration in ALS.

Imaging of current flow in the human head during transcranial electrical therapy.

BACKGROUND: It has been assumed that effects caused by tDCS or tACS neuromodulation are due to electric current flow within brain structures. However, to date, direct current density distributions in the brains of human subjects have not been measured. Instead computational models of tDCS or tACS have been used to predict electric current and field distributions for dosimetry and mechanism analysis purposes. OBJECTIVE/HYPOTHESIS: We present the first in vivo images of electric current density distributions within the brain in four subjects undergoing transcranial electrical stimulation. METHODS: Magnetic resonance electrical impedance tomography (MREIT) techniques encode current flow in phase images. In four human subjects, we used MREIT to measure magnetic flux density distributions caused by tACS currents, and then calculated current density distributions from these data. Computational models of magnetic flux and current distribution, constructed using contemporaneously collected T1-weighted structural MRI images, were co-registered to compare predicted and experimental results. RESULTS: We found consistency between experimental and simulated magnetic flux and current density distributions using transtemporal (T7-T8) and anterior-posterior (Fpz-Oz) electrode montages, and also differences that may indicate a need to improve models to better interpret experimental results. While human subject data agreed with computational model predictions in overall scale, differences may result from factors such as effective electrode surface area and conductivities assumed in models. CONCLUSIONS: We believe this method may be useful in improving reproducibility, assessing safety, and ultimately aiding understanding of mechanisms of action in electrical and magnetic neuromodulation modalities.

A majority rule approach for region-of-interest-guided streamline fiber tractography.

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.

Test-retest reliability of high angular resolution diffusion imaging acquisition within medial temporal lobe connections assessed via tract based spatial statistics, probabilistic tractography and a novel graph theory metric.

This study examined the reliability of high angular resolution diffusion tensor imaging (HARDI) data collected on a single individual across several sessions using the same scanner. HARDI data was acquired for one healthy adult male at the same time of day on ten separate days across a one-month period. Environmental factors (e.g. temperature) were controlled across scanning sessions. Tract Based Spatial Statistics (TBSS) was used to assess session-to-session variability in measures of diffusion, fractional anisotropy (FA) and mean diffusivity (MD). To address reliability within specific structures of the medial temporal lobe (MTL; the focus of an ongoing investigation), probabilistic tractography segmented the Entorhinal cortex (ERc) based on connections with Hippocampus (HC), Perirhinal (PRc) and Parahippocampal (PHc) cortices. Streamline tractography generated edge weight (EW) metrics for the aforementioned ERc connections and, as comparison regions, connections between left and right rostral and caudal anterior cingulate cortex (ACC). Coefficients of variation (CoV) were derived for the surface area and volumes of these ERc connectivity-defined regions (CDR) and for EW across all ten scans, expecting that scan-to-scan reliability would yield low CoVs. TBSS revealed no significant variation in FA or MD across scanning sessions. Probabilistic tractography successfully reproduced histologically-verified adjacent medial temporal lobe circuits. Tractography-derived metrics displayed larger ranges of scanner-to-scanner variability. Connections involving HC displayed greater variability than metrics of connection between other investigated regions. By confirming the test retest reliability of HARDI data acquisition, support for the validity of significant results derived from diffusion data can be obtained.

Progress in high field MRI at the University of Florida.

In this article we report on progress in high magnetic field MRI at the University of Florida in support of our new 750MHz wide bore and 11.7T/40cm MR instruments. The primary emphasis is on the associated rf technology required, particularly high frequency volume and phased array coils. Preliminary imaging results at 750MHz are presented. Our results imply that the pursuit of even higher fields seems warranted.

In vivo 1H magnetic resonance imaging and spectroscopy of the rat spinal cord using an inductively-coupled chronically implanted RF coil.

An inductively coupled, chronically implanted short-solenoid coil was used to obtain in vivo localized 1H NMR spectra and diffusion-weighted images from a rat spinal cord. A 5 x 8 mm two-turn elliptically shaped solenoid coil was implanted in rats at the site of a T-12 vertebral-level laminectomy. Excitation was achieved solely by a 3 x 3 cm external surface coil, and signal detection was achieved by inductively coupling the external coil to the implanted coil. The image signal-to-noise ratio (SNR) obtained with the inductively-coupled implanted coil was compared with that obtained using a linear or a quadrature external surface coil. The implanted coil provided a gain by over a factor of 3 in SNR. The implanted coil was used to measure localized 1H spectra in vivo at the T13/L1 spinal-cord level within a 1.85 x 1.85 x 4.82 mm (16.5 microL) volume. With 256 averages, a approximately 3-s repetition delay and respiratory gating, a high-quality spectrum was acquired in 13 min. In addition, water translational diffusion was measured in three orthogonal directions using a stimulated-echo imaging sequence, with a short echo time (TE), to produce a quantitative map of diffusion in a rat spinal cord in vivo.

Visualization of neural tissue water compartments using biexponential diffusion tensor MRI.

The apparent diffusion tensor (ADT) imaging method was extended to account for multiple diffusion components. A biexponential ADT imaging experiment was used to obtain separate images of rapidly and slowly diffusing water fractions in excised rat spinal cord. The fast and slow component tensors were compared and found to exhibit similar gross features, such as fractional anisotropy, in both white and gray matter. However, there were also some important differences, which are consistent with the different structures occupying intracellular and extracellular spaces. Evidence supporting the assignment of the two tensor components to extracellular and intracellular water fractions is provided by an NMR spectroscopic investigation of homogeneous samples of brain tissue. Magn Reson Med 45:580-587, 2001.

NMR spectroscopy of single neurons.

The first spatially localized NMR spectra of osmolytes and metabolites from single isolated neurons have been obtained using a combination of high magnetic field strengths and NMR radio frequency (RF) microcoils. The proton spectra display peaks at high concentrations (100-300 mM) assigned to betaine and choline, and other metabolite resonances including lactate at lower concentrations in the order of 10s of millimoles. The volumes examined were approximately 10 nl, over two orders of magnitude less than previously possible. In these initial experiments; the cells were unperfused and the signal intensities of the osmolytes decrease with time, a phenomenon consistent with cell swelling. This work demonstrates the technical feasibility of NMR spectroscopy of single cells, further broadening the scope of NMR spectroscopy of living tissues from application to entire living organisms (man and animal models) and isolated tissues (perfused organs and cultured assemblies of cells) and now to single cells. Magn Reson Med 44:19-22, 2000.

Diffusion tensor MR imaging and comparative histology of glioma engrafted in the rat spinal cord.

MR imaging using contrast material derived from the diffusion of tissue water was tested for its ability to provide a nondestructive histologic analysis of tumor morphology. An apparent diffusion tensor MR image of a glioma engrafted within a rat spinal cord was generated in which fiber orientation in three dimensions was displayed in color. This imaging method clearly separated tumor from host white and gray matter and corresponded well with conventional histologic microscopy.

In vivo dynamics and distribution of intracerebroventricularly administered gadodiamide, visualized by magnetic resonance imaging.

Direct injections into the cerebroventricles have been extensively utilized in neurophysiological studies. Mapping the distribution of injectate after intracerebroventricular injection has been made only by post mortem analysis, and the dynamic distribution of injectate within the brain has not been well characterized. In this report, we apply contrast-enhanced magnetic resonance imaging to study the pharmacokinetics and extent of non-ionic gadodiamide transport into brain tissue in vivo after intracerebroventricular administration. The results indicate that intracerebroventricular injectate travels quickly throughout the ventricular system from the lateral ventricular site of injection to the fourth ventricle and foramina of Luschka and Magendie within 2 min. After this, the signal intensity begins to increase in the periventricular and paraventricular brain parenchyma. Contrast enhancement is visible 2 mm into the brain tissue from the ventricles. Quantitative analysis of the data shows that the transport of gadodiamide across the ependymal layer that lines the cerebrospinal fluid space characterized a rate constant of 0.066+/-0.017 min(-1). These results provide a better understanding of chemical transport and diffusion following direct injection into the cerebroventricles. They provide information on the in vivo dynamics of injectate after intracerebroventricular administration, and show that contrast enhanced magnetic resonance imaging may be used to more precisely define the target sites of chemicals after intracerebroventricular administration into the brain.

Diffusion anisotropy in excised normal rat spinal cord measured by NMR microscopy.

A conventional spin-echo NMR imaging pulse sequence was used to obtain high-resolution images of excised normal rat spinal cord at 7 and 14 T. It was observed that the large pulsed-field gradients necessary for high-resolution imaging caused a diffusion weighting that dominated the image contrast and that could be used to infer microscopic structural organization beyond that defined by the resolution of the image matrix (i.e., fiber orientation could be assigned based on diffusion anisotropy). Anisotropic diffusion coefficients were therefore measured using apparent diffusion tensor (ADT) imaging to assess more accurately fiber orientations in the spinal cord; structural anisotropy information is portrayed in the six unique images of the complete ADT. To reduce the dimensionality of the data, a trace image was generated using a separate color scale for each of the three diagonal element images of the ADT. This new image retains much of the invariance of the trace to the relative orientations of laboratory and sample axes (inherent to a greyscale trace image) but provides, by the use of color, contrast reflecting diffusion anisotropy. The colored trace image yields a pseudo-three-dimensional view of the rat spinal cord, from which it is possible to deduce fiber orientations.

A field-gradient coil using concentric return paths.

An approach to transverse field-gradient coil design is presented which locates all current elements in planes perpendicular to the main magnetic field. The linear volume of the resulting coil structure can be made to extend nearly to both ends of the coil. This design is based on forming a concentric return path in the same plane as the field-producing arcs. The coil structure consists of stacked planar units which give a desired field-gradient configuration. The size of the linear-field region is optimized by varying the current in each plane, by varying the location of a plane relative to the others in the stack, or by varying both current and location. Coils with linear regions having a wide range of length-to-diameter ratios can be designed, as illustrated by two examples. The construction of a prototype coil is presented and its performance in imaging confirms the analysis. This type of design is suited to magnetic resonance of the human head without obstruction from the shoulders.

Dynamic assessment of intraspinal neural graft survival using magnetic resonance imaging.

Although previous work has demonstrated the usefulness of magnetic resonance imaging (MRI) for visualizing intraspinal transplants in vivo, the degree to which MRI can differentiate viable fetal neural tissue from evolving spinal cord pathology has not been investigated. Thus, the present study assessed whether MRI performed at earlier postgrafting intervals (0-20 weeks) could document the survival of fetal neural transplants in the injured cat spinal cord. Twelve adult female cats received a hemisection injury at the L1 level, followed immediately by implantation of either embryonic cat spinal cord or neocortex into the cavity. The spinal cords of three control animals were hemisected but received no transplant. Each animal was subsequently imaged at 4 and 8 weeks postoperative. Selected animals from each group were also studied at additional time points ranging from immediately postoperative to 20 weeks. Multislice T2-weighted and intermediate T1-weighted spin-echo images of the lesion or graft site were obtained. Correlative postmortem histological analyses revealed viable donor tissue in 6 of 12 transplant recipients. Spinal cords from the remaining hosts and the control animals all contained cysts at the surgical site that were devoid of donor neural tissue. The graft sites with viable tissue tended to exhibit a slightly hyperintense signal on both intermediate T1-weighted (T1WI) and T2-weighted images (T2WI) throughout the entire experiment. Control cats and cats with failed transplants also were slightly bright on T1WI, but were very hyperintense on T2WI.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of an inductively coupled implanted coil with optimized surface coils for in vivo NMR imaging of the spinal cord.

A study was performed to determine whether an implanted, inductively coupled nuclear magnetic resonance (NMR) imaging spine coil could provide a significant gain in signal-to-noise ratio (SNR) on images of the spinal cord relative to the SNR of optimized surface coils. Implanted coils were surgically affixed to the upper lumbar spine (first lumbar through third lumbar vertebrae) in a total of four adult cats. The implanted coil was inductively coupled to an external 12 x 12 cm square surface coil that was mounted on a 14-cm diameter Plexiglas cradle (Townsend Industries, Des Moines, IA). Two similar cradles were prepared with transmit-only 12 x 12 cm surface coils and either a receive-only 6 x 6 cm square surface coil or a receive-only quadrature coil pair (two 4 x 6 cm coils overlapped slightly to minimize their mutual inductance) with the same surface area (6 x 6 cm). A total of five single-slice, T1-weighted spin-echo images (TR = 500 ms, TE = 30 ms, 4-mm slice thickness) were acquired from a 1-liter saline phantom and from the second lumbar spinal level in an adult cat with a normal, uninjured spinal cord. On the spinal cord images, the quadrature coil exhibited a factor of 1.65 increase in SNR relative to the single-turn surface coil, whereas the implanted coil achieved a factor of 2.19 increase in SNR. The improved SNR for the quadrature and implanted coils was observed as a dramatic improvement in the clarity of the images.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo magnetic resonance imaging of fetal cat neural tissue transplants in the adult cat spinal cord.

Magnetic resonance (MR) imaging was evaluated for its possible diagnostic application in determining the survival of fetal central nervous system tissue grafts in the injured spinal cord. Hemisection cavities were made at the T11-L1 level of eight adult female cats. Immediately thereafter, several pieces of tissue, either obtained from the fetal cat brain stem on embryonic Day 37 (E-37), from the fetal neocortex on E-37, or from the fetal spinal cord on E-23, were implanted into the cavities made in seven cats. The eighth cat served as a control for the effect of the lesion only. In another group of four animals, a static-load compression injury was made at the L-2 level. Seven weeks later, the lesion was resected in three cases and fragments of either fetal brain-stem or spinal cord tissue were introduced. A small cyst was observed in a fourth cat in the compression injury group and a suspension of dissociated E-23 brain-stem cells was injected into this region of cavitation without disturbing the surrounding leptomeninges. Five months to 2 years posttransplantation, MR imaging was performed with a 2.0-tesla VIS imaging spectrometer by acquiring multislice spin-echo images (TR 1000 msec, TE 30 msec) in both the transverse and sagittal planes. Collectively, these intermediate-weighted images revealed homogeneous, slightly hyperintense signals at the graft site relative to the neighboring host tissue in seven of the 11 graft recipients. Two of the remaining four cats exhibited signals from the graft site that were approximately isointense with the adjacent host spinal cord, and the final two cats and the lesion-only control presented with very hypointense transplant/resection regions. The hyperintense and isointense images were tentatively interpreted as representing viable graft tissue, whereas the hypointense transplant/resection sites were considered to be indicative of a lack of transplant survival or the absence of tissue in the lesion-only control animal. Postmortem gross inspection of fixed specimens and light microscopy verified the MR findings in the control animal in 10 of the 11 graft recipients by showing either transplants and/or cysts corresponding to the MR images obtained. In one cat in the hemisection group, histological analysis revealed a very small piece of graft tissue that was not detected on the MR images. Therefore, it is suggested that within certain spatial- and contrast-resolution limits, MR imaging can reliably detect the presence of transplanted neural tissue in both the hemisected and compression-injured spinal cord of living animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Selective Fourier transform localization.

We have introduced the selective Fourier transform technique for spectral localization. This technique allows the acquisition of a high-resolution spectrum from a selectable location with control over the shape and size of the spatial response function. The shape and size of the spatial response are defined during data acquisition and the location is selectable through processing after the data acquisition is complete. The technique uses pulsed-field-gradient phase encoding to define the spatial coordinates. In this paper the theoretical basis of the selective Fourier transform technique is developed and experimental results are presented, including comparisons of spectral localization using either the selective Fourier transform method or conventional multidimensional Fourier transform chemical-shift imaging.

Chemical and radiochemical stability of the adrenal-scanning agents, 6beta-iodomethyl-19-norcholest-5(10-en-3beta-ol and 19-iodocholest-5-en-3beta-ol.

The chemical stabilities of the adrenal-scanning agents, 6beta-iodo-methyl-19-norcholest-5(10)-en-3beta-ol (6-iodomethylnorcholesterol) and 19-iodocholest-5-en-3beta-ol (19-iodocholesterol), and several of their derivatives were examined by 13C nuclear magnetic resonance. Neat 6-iodomethylnorcholesterol, sealed in glass under nitrogen and stored at 0 degrees C, remains 98 mole% chemically pure for 3 months. Neat 19-iodocholesterol, stored in the dark at 25 degrees C, remains 98 mole% chemically pure for 3 months. Either 6-iodomethylnorcholesterol-125I or-131I, informulation and stored at 5 degrees C, will remain greater than 97% radiochemically pure for at least 15 days. Labelled 19-iodocholesterol, formulated and stored under the same conditions, shows 20% decomposition after 3 weeks and 40% after 6 weeks.

Synthesis and purification of radioactive 6beta-iodomethyl-19-norcholest-5(10)-en-3beta-ol.

A method for the synthesis and purification of 6beta-iodomethyl-19-norcholest-5(10)-ene-3beta-ol-131I of greater than 98 mole% chemical purity and greater than 99% radiochemical purity is presented. Carbon-13 and proton NMR were used to establish the identity and purity. Discrepancies in the characterization of this compound, previously published by two other research groups, are discussed.