MRI Evidence of Altered Callosal Sodium in Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Mild traumatic brain injury is a leading cause of death and disability worldwide with 42 million cases reported annually, increasing the need to understand the underlying pathophysiology because this could help guide the development of targeted therapy. White matter, particularly the corpus callosum, is susceptible to injury. Animal models suggest stretch-induced mechanoporation of the axonal membrane resulting in ionic shifts and altered sodium ion distribution. The purpose of this study was to compare the distribution of total sodium concentration in the corpus callosum between patients with mild traumatic brain injury and controls using sodium (23Na) MR imaging. MATERIALS AND METHODS: Eleven patients with a history of mild traumatic brain injury and 10 age- and sex-matched controls underwent sodium (23Na) MR imaging using a 3T scanner. Total sodium concentration was measured in the genu, body, and splenium of the corpus callosum with 5-mm ROIs; total sodium concentration of the genu-to-splenium ratio was calculated and compared between patients and controls. RESULTS: Higher total sodium concentration in the genu (49.28 versus 43.29 mmol/L, P = .01) and lower total sodium concentration in the splenium (which was not statistically significant; 38.35 versus 44.06 mmol/L, P = .08) was seen in patients with mild traumatic brain injury compared with controls. The ratio of genu total sodium concentration to splenium total sodium concentration was also higher in patients with mild traumatic brain injury (1.3 versus 1.01, P = .001). CONCLUSIONS: Complex differences are seen in callosal total sodium concentration in symptomatic patients with mild traumatic brain injury, supporting the notion of ionic dysfunction in the pathogenesis of mild traumatic brain injury. The total sodium concentration appears to be altered beyond the immediate postinjury phase, and further work is needed to understand the relationship to persistent symptoms and outcome.

Serial triple quantum sodium MRI during non-human primate focal brain ischemia.

Triple quantum (TQ) sodium MRI techniques with clinically acceptable 18-min data acquisition times were demonstrated in vivo in a nonhuman primate model of focal brain ischemia. Focal brain ischemia was induced in four animals using embolization coils to occlude the posterior cerebral artery, and a balloon catheter to occlude the middle cerebral artery. A statistically significant increase (P < 0.001) in the TQ sodium MRI signal intensity in the ischemic hemisphere relative to the contralateral hemisphere was seen at all time points in all four animals. This increased TQ sodium MRI signal intensity was demonstrated as early as 0.6 hr after the onset of ischemia. The TQ sodium MRI hyperintensity corresponded to the anatomical location of the ischemic cortex, as indicated by the registration of the TQ imaging data with anatomical proton MRI data. The results demonstrate that early after the onset of ischemia, there was an increase in the TQ signal intensity in the ischemic hemisphere, and a negligible change in the single quantum (SQ) signal intensity.

Non-invasive assessment of tumor proliferation using triple quantum filtered 23/Na MRI: technical challenges and solutions.

We address the development of triple-quantum-filtered sodium MRI as a non-invasive surrogate measure for cell proliferation in brain tumors. We demonstrate that through careful consideration of the theoretical description of the signal, triple-quantum-filtered sodium images of adequate signal-to-noise ratio (SNR) can be acquired in clinically acceptable imaging times.

Noninvasive quantification of total sodium concentrations in acute reperfused myocardial infarction using 23Na MRI.

The transport of sodium and potassium between the intra- and extracellular pools and the maintenance of the transmembrane concentration gradients are important to cell function and integrity. The early disruption of the sodium pump in myocardial infarction in response to the exhaustion of energy reserves following ischemia and reperfusion results in increased intracellular (and thus total) sodium levels. In this study a method for noninvasively quantifying myocardial sodium levels directly from sodium (23Na) MRI is presented. It was used to measure total myocardial sodium on a clinical 1.5T system in six normal dogs and five dogs with experimentally-induced myocardial infarction (MI). The technique was validated by comparing total sodium content measured by 23Na MRI with that measured by atomic absorption spectrophotometry (AAS) in biopsied tissue. Total sodium measured by 23Na MRI was significantly elevated in regions of infarction (81.3 +/- 14.3 mmol/kg wet wt, mean +/- SD) compared to noninfarcted myocardial tissue from both infarcted dogs (36.2 +/- 1.1, P < 0.001) and from normal controls (34.4 +/- 2.8, P < 0.0001). Myocardial tissue sodium content as measured by 23Na MRI did not vary regionally in the lateral, anterior, or inferior regions in normal hearts (ANOVA, P = NS). Sodium content measured by 23Na MRI agreed with the mean AAS estimates of 31.3 +/- 5.6 mmol/kg wet wt (P = NS) in normal hearts, and did not differ significantly from AAS measurements in MI (P = NS). Thus, local tissue sodium levels can be accurately quantified noninvasively using 23Na MRI in normal and acutely reperfused MI. The detection of regional myocardial sodium elevations may help differentiate viable from nonviable, infarcted tissue.

Superparamagnetic iron oxide MION as a contrast agent for sodium MRI in myocardial infarction.

An intravascular iron-based contrast agent was used as a sodium (23Na) MRI T2 relaxant in an effort to suppress the blood signal from the ventricular cavities in normal and infarcted canine myocardium in vivo. 23Na MRI signal decreases in blood were attributed to decreases in the fast (T2f) and slow (T2s) transverse relaxation components, which were quantified as a function of dose and MRI echo time (TE). In vivo 23Na MRI signal decreases up to 65% were noted in ventricular blood when imaging under dose and TE conditions of 10 mg/kg body weight and 5 ms, respectively. Contrast injection followed by subsequent 23Na MRI in canine myocardial infarction led to a clear delineation of the location of the injured tissue, as identified by postmortem triphenyltetrazolium chloride staining, and to an improvement in the contrast-to-noise ratio between the blood in the ventricular chamber and the infarcted tissue that was as high as 3.3-fold in the postcontrast images in comparison to the precontrast images.

A model for the dynamics of spins 3/2 in biological media: signal loss during radiofrequency excitation in triple-quantum-filtered sodium MRI.

We have derived the differential equations that describe the dynamics of spin-3/2 nuclei in the presence of radiofrequency (RF) fields and both static and fluctuating quadrupolar interactions. The formalism presented was used to predict the sodium triple-quantum-filtered (TQ-filtered) signal loss in a whole-body scanner, where the widths of the hard 90 degrees RF pulses are on the same order of magnitude as the transverse relaxation times. A small piece of bovine nasal cartilage, known for exhibiting residual quadrupolar splittings, was used to test the theory. The sample was modeled as consisting of small domains, each characterized by a static quadrupolar interaction constant, with an overall Gaussian distribution across the sample. An increase of about 15% in the TQ-filtered signal strength, as the 90 degrees RF pulse width was decreased from 500 to 100 micros, was predicted and demonstrated experimentally for this particular sample.

Three-dimensional tailored RF pulses for the reduction of susceptibility artifacts in T(*)(2)-weighted functional MRI.

A three-dimensional tailored RF pulse method for reducing intravoxel dephasing artifacts in T *(2)-weighted functional MRI is presented. A stack of spirals k-space trajectory is employed to excite a disk of magnetization for small tip angles. Smaller disks with a linear through-plane phase are inserted into the disk to locally refocus regions which are normally dephased due to susceptibility variations. Numerical simulations and imaging experiments which use the tailored RF pulses are presented. Limitations of the method and improvements are also discussed.

Human skeletal muscle: sodium MR imaging and quantification-potential applications in exercise and disease.

PURPOSE: To use sodium 23 magnetic resonance (MR) imaging to quantify noninvasively total sodium in human muscle and to apply the technique in exercise and musculoskeletal disease. MATERIALS AND METHODS: Total [Na] sodium was determined from the ratio of the relaxation-corrected (23)Na signal intensities measured from short echo-time (0.4 msec) (23)Na images to those from an external saline solution reference. The method was validated with the blinded use of saline solutions of varying sodium concentrations. [Na] was measured in the calf muscles in 10 healthy volunteers. (23)Na MR imaging also was performed in two healthy subjects after exercise, two patients with myotonic dystrophy, and two patients with osteoarthritis. RESULTS: (23)Na MR imaging yielded a total [Na] value of 28.4 mmol/kg of wet weight +/- 3.6 (SD) in normal muscle, consistent with prior biopsy data. Spatial resolution was 0.22 mL, with signal-to-noise ratio of 10-15. Mean signal intensity elevations were 16% and 22% after exercise and 47% and 70% in dystrophic muscles compared with those at normal resting levels. In osteoarthritis, mean signal intensity reductions were 36% and 15% compared with those in unaffected knee joints. CONCLUSION: (23)Na MR imaging can be used to quantify total [Na] in human muscle. The technique may facilitate understanding of the role of the sodium-potassium pump and perfusion in normal and diseased muscle.

Multiple channel phased arrays for echo planar imaging.

A new interface combining phased arrays and echo-planar imaging (EPI) technologies was developed for two channel breast MR EPI applications. A detailed design for a dual-channel, EPI-compatible, phased array breast coil is described. EPI digital data multiplexing, signal controlling and sampling schemes are also presented. Results from breast phantoms and patients demonstrate a 55% improvement in signal-to-noise ratio when compared to a conventional two-loop, single channel coil configuration. This method can be easily expanded to a four or more channel, EPI-compatible, phased array system to improve field-of-view coverage and signal-to-noise ratio.

In vivo triple quantum filtered twisted projection sodium MRI of human articular cartilage.

In this work, we present the first triple quantum filtered (TQF) sodium MR images of the human knee joint in vivo. A 3D TQF data set of 16 slices was obtained in 20 min using a TQF pulse sequence preencoded to a twisted projection imaging readout. Images clearly demarcate patellar cartilage and also demonstrate fluid signal suppressed by the triple quantum filter. Biexponential transverse relaxation times were calculated by fitting the TQF free induction decay to a theoretical signal expression. The average values from three healthy volunteers were T(2fall)(*) = 9.59 +/- 0.35 ms and T(2rise)(*) = 0.84 +/- 0.06 ms. Application of TQF imaging in biological tissues is discussed.

Three-dimensional triple-quantum-filtered (23)Na imaging of in vivo human brain.

A scheme for the generation of three-dimensional, triple-quantum-filtered (TQ) sodium images from normal human brain is presented. In this approach, a three-pulse, six-step, coherence transfer filter was used in conjunction with a fast twisted projection imaging sequence to generate spatial maps of the TQ signal across the entire brain. It is demonstrated, theoretically as well as experimentally, that the use of the three-pulse coherence filter leads to TQ sodium images in which the dependence of the image intensity on the spatial variation of the flip angle is less pronounced than it is in the "standard," four-pulse, TQ filter. Correction for the variation of the TQ signal intensity across the field of view because of radio-frequency (RF) inhomogeneity is straightforward with this approach. This imaging scheme allows the generation of RF inhomogeneity-corrected, TQ, sodium images from human brain at moderate field strength (3.0 T) in times acceptable for routine clinical examinations (20 minutes). Magn Reson Med 42:1146-1154, 1999.

3D spiral cardiac/respiratory ordered fMRI data acquisition at 3 Tesla.

Three-dimensional (3D), multi-shot functional magnetic resonance imaging (fMRI) data acquisitions are desirable because of higher resolution and reduced susceptibility artifacts, due to shorter readouts and thinner slices. However, 3D multi-shot techniques are more susceptible to physiological noise, which can increase inter-image variance and lead to inaccurate assessment of activation. This work presents a 3D spiral fMRI data acquisition method at 3 T in which the acquisition of views was ordered to match the phase of either the respiratory or the cardiac cycle. For the acquisition timing parameters used in this work, cardiac ordering was found to reduce inter-image variance by 19%. Cardiac ordered data acquisitions showed the same reduction in variance as sequentially ordered data with cardiac contributions estimated and removed using an externally acquired reference prior to reconstruction. Respiratory ordering showed no reduction in fluctuation noise due to poor alignment of views to the respiratory phase.

Experimentally verified, theoretical design of dual-tuned, low-pass birdcage radiofrequency resonators for magnetic resonance imaging and magnetic resonance spectroscopy of human brain at 3.0 Tesla.

A new theoretical method is presented for designing frequency responses of double-tuned, low-pass birdcage coils. This method is based on Kirchhoff's equations through a nonsymmetric matrix algorithm and extended through a modification of the corresponding eigenvalue system from a single-tuned mode. Designs from this method are verified for sodium/proton, dual-tuned, double-quadrature, low-pass birdcage coils at 1.5 Tesla and 3.0 Tesla and then are used to design dual-tuned, double-quadrature, lithium/proton and phosphorus/proton birdcage coils for 3.0 Tesla. All frequencies show experimental deviations of less than 3% from theory under unloaded conditions. The frequency shifts caused by loading and radiofrequency shielding are less than 1 MHz and can be compensated readily by adjustment of variable capacitors. Applications to human neuroimaging and spectroscopy are demonstrated.

Partial Fourier reconstruction for three-dimensional gradient echo functional MRI: comparison of phase correction methods.

Partial Fourier (PF) methods take advantage of data symmetry to allow for either faster image acquisition or increased image resolution. Faster acquisition and increased spatial resolution are advantageous for fMRI because of increased temporal resolution and/or reduced partial volume effects, respectively. Standard PF methods, which use a phase reference obtained from a low resolution image, are adequate for the reconstruction of time-stationary images acquired using either spin echoes or short TE gradient echoes. In fMRI, however, multiple images are acquired using long TE gradient echoes, which introduces possible phase drifts in the fMRI data and high spatial frequencies in the phase reference. This work investigates several techniques developed to reconstruct fMRI data obtained with PF acquisitions. PF methods that account for both high-frequency spatial variations and time-dependent drifts in the phase reference are discussed and are quantitatively evaluated using receiver operator characteristic curve analysis.

Simultaneous multislice acquisition using rosette trajectories (SMART): a new imaging method for functional MRI.

A new acquisition technique for rapid, whole-brain functional MRI is presented. In this technique, several slices are simultaneously acquired using rosette k-space trajectories and a gradient-induced frequency modulation. This modulation together with the spectral properties of the rosette acquisition allow all slices to be reconstructed individually. In functional MRI studies, acquisition rates of 16.7 to 25 images/s were achieved, a threefold improvement over single-slice acquisitions. The raw images showed some increase in noise. However, because this increase is mostly stationary, the functional activation maps showed only a slight increase in noise (8%).

Correction of B1 inhomogeneities using echo-planar imaging of water.

Reliable interpretation of the MR signal intensity over the FOV of an image must consider the spatial heterogeneity of instrumental sensitivity. A major source of such variation is the nonuniformity of the B1 magnetic field of the radiofrequency coil. This heterogeneity can be minimized by coil design but is exaggerated by surface coils, which are used to maximize the signal-to-noise ratio for some applications. This paper describes a rapid method for mapping the B1 field over the sample of interest, using 1H echo-planar imaging, to correct for B1 distortions. The method applies to 1H imaging and has been extended to non-1H imaging by using dual-frequency coils in which the B1 distributions are matched for the 1H frequency and the frequency of interest. The approach is demonstrated in phantoms, animals, and humans and for sodium imaging.

Spectrally weighted twisted projection imaging: reducing T2 signal attenuation effects in fast three-dimensional sodium imaging.

A scheme for the reduction of T2 signal attenuation effects in three-dimensional twisted projection imaging is presented. By purposely reducing the sample density at the high spatial frequencies, a considerable reduction in readout time is achieved. The reduction in readout time leads to decreased T2 signal attenuation which translates into improved signal-to-noise ratio (SNR). The SNR improvement is achieved without decreasing the image's resolution since the point spread function depends on the sample weighting as well as the T2 attenuation. The results indicate that SNR improvements of up to 40% can be achieved using the proposed scheme.

Dual-frequency, dual-quadrature, birdcage RF coil design with identical B1 pattern for sodium and proton imaging of the human brain at 1.5 T.

Rapid quantification of tissue metabolites in vivo by MRS or MRI can be achieved using dual-frequency RF coils with identical B1 field distributions at the observation frequencies of the metabolites and tissue water protons. Tissue sodium is used as an example for optimizing the dual-frequency, dual-quadrature RF coils for such measurements in humans. In the setting of sodium imaging, the challenge of dual-quadrature birdcage configurations is to decouple the sodium and proton channels because the fourth harmonic of the sodium frequency is very close to the proton frequency. A generalizable method for effectively decoupling these two RF frequencies is presented in this paper. The method is demonstrated with the design of an EPI compatible, dual-quadrature, double-tuned, 23Na/1H birdcage coil. The performance of the RF probe is reported at 1.5 Tesla in terms of signal-to-noise ratio, B1 homogeneity and image quality.

A spectral approach to analyzing slice selection in planar imaging: optimization for through-plane interpolation.

Interpolation between slices is necessary whenever reslicing a volume of data into a different coordinate frame. This may be done to view the data from different perspectives, to align data from different sessions, or to remove the effects of head movement in functional imaging studies. In this paper, issues surrounding slice-selection in two-dimensional imaging are examined in the context of through-plane interpolation and a spectral framework is introduced to describe the sources of error when interpolating between slices. This framework suggests that there is a trade-off between precision in localization, which requires high spatial frequencies, and interpolation, which requires a narrow spectrum of spatial frequencies. An analysis of the sources of error has lead to several approaches to reducing interpolation error including elimination of interslice gaps or making slices overlap, use of a slice profile with a narrower spatial frequency bandwidth such as a Gaussian profile, and use of high-order interpolation. The simulation and experimental data demonstrate significant reductions in interpolation error for these approaches.

Fast three dimensional sodium imaging.

An efficient scheme for fast three dimensional acquisition of sodium MR images is described. This scheme relies on the use of three dimensional k-space trajectories with constant sample density to achieve significant (60-70%) reductions in total data acquisition time over conventional projection imaging schemes. The performance of this data acquisition scheme is demonstrated with acquisition of sodium data sets on phantoms and normal human volunteers at 1.5 and 3.0 Tesla. The experimental results demonstrate that high quality three dimensional sodium images (0.2 cc voxel size, 10:1 signal-to-noise ratio) can be acquired at clinical field strengths (1.5 Tesla) in under 10 min.