Possibilities and limitations for high resolution small animal MRI on a clinical whole-body 3T scanner

Object

To investigate the potential of a clinical 3 T scanner to perform MRI of small rodents.

Materials and methods

Different dedicated small animal coils and several imaging sequences were evaluated to optimize image quality with respect to SNR, contrast and spatial resolution. As an application, optimal grey-white-matter contrast and resolution were investigated for rats. Furthermore, manganese-enhanced MRI was applied in mice with unilateral crush injury of the optic nerve to investigate coil performance on topographic mapping of the visual projection.

Results

Differences in SNR and CNR up to factor 3 and more were observed between the investigated coils. The best grey-white matter contrast was achieved with a high resolution 3D T ₂-weighted TSE (SPACE) sequence. Delineation of the retino-tectal projection and detection of defined visual pathway damage on the level of the optic nerve could be achieved by using a T ₁-weighted, 3D gradient echo sequence with isotropic resolution of (0.2?mm)³.

Conclusions

Experimental studies in small rodents requiring high spatial resolution can be performed by using a clinical 3 T scanner with appropriate dedicated coils.     

Two eyes see more than one: double echo stereoscopic MRA for rapid 3D visualization of vascular structures

Object

A three-dimensional (3D) visualization of the target region during intravascular interventions in real-time is challenging since the acquisition of a time-consuming 3D dataset is required. In this work, a novel stereoscopic double echo sequence for achieving 3D depth perception by sampling only two oblique projection images is presented.

Materials and methods

A double echo (DE) FLASH pulse sequence was developed to acquire continuously stereoscopic image pairs of the vascular target anatomy. Stereo image data were displayed on a stereoscopic 3D LCD monitor in real time after image reconstruction. Phantom experiments followed by a depth perception test were performed to assess the usability of the stereo image pairs for 3D visualization. In an animal experiment the sequence was tested in vivo and was compared with a slower interleaved (IL) sequence variant.

Results

In the phantom experiments an SNR difference of 6?% between left and right image was found which did not influence the depth perception. The DE acquisition was superior to the IL sequence (SNR_DE?=?10.3, 2.3 images/s over SNR_IL?=?7.1, 1.7 images/s), and during contrast enhancement the abdominal arterial vasculature was clearly perceived as a 3D structure.

Conclusion

A novel stereoscopic DE pulse sequence can be utilized for the fast 3D stereoscopic visualization of vascular structures in real-time.     

Spatial phase encoding exploiting the Bloch–Siegert shift effect

Objective

The present work introduces an alternative to the conventional \(B_{0}\) -gradient spatial phase encoding technique. By applying far off-resonant radiofrequency (RF) pulses, a spatially dependent phase shift is introduced to the on-resonant transverse magnetization. This so-called Bloch–Siegert (BS) phase shift has been recently used for \(B_{1}^{ + }\) -mapping. The current work presents the theoretical background for the BS spatial encoding technique (BS-SET) using RF-gradients.

Materials and methods

Since the BS-gradient leads to nonlinear encoding, an adapted reconstruction method was developed to obtain undistorted images. To replace conventional phase encoding gradients, BS-SET was implemented in a two-dimensional (2D) spin echo sequence on a 0.5 T portable MR scanner.

Results

A 2D spin echo (SE) measurement imaged along a single dimension using the BS-SET was compared to a conventional SE 2D measurement. The proposed reconstruction method yielded undistorted images.

Conclusions

BS-gradients were demonstrated as a feasible option for spatial phase encoding. Furthermore, undistorted BS-SET images could be obtained using the proposed reconstruction method.     

Fully refocused multi-shot spatiotemporally encoded MRI: robust imaging in the presence of metallic implants

Object

An approach has been recently introduced for acquiring arbitrary 2D NMR spectra or images in a single scan, based on the use of frequency-swept RF pulses for the sequential excitation and acquisition of the spins response. This spatiotemporal-encoding (SPEN) approach enables a unique, voxel-by-voxel refocusing of all frequency shifts in the sample, for all instants throughout the data acquisition. The present study investigates the use of this full-refocusing aspect of SPEN-based imaging in the multi-shot MRI of objects, subject to sizable field inhomogeneities that complicate conventional imaging approaches.

Materials and methods

2D MRI experiments were performed at 7 T on phantoms and on mice in vivo, focusing on imaging in proximity to metallic objects. Fully refocused SPEN-based spin echo imaging sequences were implemented, using both Cartesian and back-projection trajectories, and compared with k-space encoded spin echo imaging schemes collected on identical samples under equal bandwidths and acquisition timing conditions.

Results

In all cases assayed, the fully refocused spatiotemporally encoded experiments evidenced a ca. 50?% reduction in signal dephasing in the proximity of the metal, as compared to analogous results stemming from the k-space encoded spin echo counterparts.

Conclusion

The results in this study suggest that SPEN-based acquisition schemes carry the potential to overcome strong field inhomogeneities, of the kind that currently preclude high-field, high-resolution tissue characterizations in the neighborhood of metallic implants.     

Alleviating artifacts in 1H MRI thermometry by single scan spatiotemporal encoding

Objective

Recent years have seen an increased interest in combining MRI thermometry with devices capable of destroying malignancies by heat ablation. Expected from the MR protocols are accurate and fast thermal characterizations, providing real time feedback on restricted tissue volumes and/or rapidly moving organs like liver. This article explores the potential advantages of relying on spatiotemporally encoded (SPEN) sequences for retrieving real-time thermometric images based on the water’s proton resonance frequency (PRF) shifts.

Materials and methods

Hybrid spatiotemporal/k-space encoding single-scan MRI experiments were implemented on animal and human scanners, and their abilities to deliver single- and multi-slice real-time thermometric measurements based on PRF-derived phase maps in phantoms and in vivo, were compared against echo planar imaging (EPI) and gradient-echo counterparts.

Results

Under comparable acquisition conditions, SPEN exhibited advantages vis-à-vis EPI in terms of dealing with inhomogeneous magnetic field distortions, with shifts arising due to changes in the central frequency offsets, with PRF distributions, and for zooming into restricted fields-of-view without special pulse sequence provisions.

Conclusion

This work confirms the ability of SPEN sequences, particularly when implemented under fully-refocused conditions, to exploit their built-in robustness to shift- and field-derived inhomogeneities for monitoring thermal changes in real-time under in vitro and in vivo conditions.     

Exploring and enhancing relaxation-based sodium MRI contrast

Object

Sodium MRI is typically concerned with measuring tissue sodium concentration. This requires the minimization of relaxation weighting. However, ²³Na relaxation may itself be interesting to explore, given an underlying mechanism (i.e. the electric-quadrupole-moment–electric-field-gradient interaction) that differs from ¹H. A new sodium sequence was developed to enhance ²³Na relaxation contrast without decreasing signal-to-noise ratio.

Materials and Methods

The new sequence, labeled Projection Acquisition in the steady-state with Coherent MAgNetization (PACMAN), uses gradient refocusing of transverse magnetization following readout, a short repetition time, and a long radiofrequency excitation pulse. It was developed using simulation, verified in model environments (saline and agar), and evaluated in the brain of three healthy adult volunteers.

Results

Projection Acquisition in the steady-state with Coherent MAgNetization generates a large positive contrast-to-noise ratio (CNR) between saline and agar, matching simulation-based design. In addition to enhanced CNR between cerebral spinal fluid and brain tissue in vivo, PACMAN develops substantial contrast between gray and white matter. Further simulation shows that PACMAN has a ln(T _2f/T ₁) contrast dependence (where T _2f is the fast component of ²³Na T ₂), as well as residual quadrupole interaction dependence.

Conclusion

The relaxation dependence of PACMAN sodium MRI may provide contrast related to macromolecular tissue structure.     

Initial clinical application of modified Dixon with flexible echo times: hepatic and pancreatic fat assessments in comparison with 1H MRS

Objects

Hepatic and pancreatic fat content become increasingly important for phenotyping of individuals with metabolic diseases. This study aimed to (1) evaluate hepatic fat fractions (HFF) and pancreatic fat fractions (PFF) using ¹H magnetic resonance spectroscopy (MRS) and the recently introduced fast mDixon method, and to examine body fat effects on HFF and PFF, (2) investigate regional differences in HFF and PFF by mDixon.

Materials and methods

HFF and PFF were quantified by mDixon with two flexible echo times and by single voxel ¹H MRS in 24 healthy subjects. The regional differences of PFF within the pancreas were assessed with mDixon. Abdominal visceral and subcutaneous fat was assessed by T1-weighted MRI at 3T.

Results

Both methods correlated well for quantification of HFF (r = 0.98, p < 0.0001) and PFF (r = 0.80, p < 0.0001). However, mDixon showed a higher low limit in HFF and PFF. PFF showed no regional differences using mDixon. In addition, both visceral and subcutaneous fat correlated with pancreatic fat, while only visceral fat correlated with liver fat, employing both ¹H MRS and mDixon.

Conclusion

The novel and fast two-point mDixon exhibits a good correlation with the gold-standard ¹H MRS for assessment of HFF and PFF, with limited sensitivity for assessing lower fat content.     

Contrast agent derived determination of the total circulating blood volume using magnetic resonance

Object

Knowledge of the total circulating blood volume (TCBV) is essential for the treatment of a variety of medical conditions and blood disorders. To date, blood volume analysis is rarely carried out due to the disadvantages of available methods. Our aim was to develop a widely available, simple, fast, yet accurate method for the determination of the total circulating blood volume.

Materials and methods

Magnetic resonance (MR) is a well-established, non-invasive technique. In this article, we present a method that uses MR contrast agents for the determination of the blood volume. The dependence of MR relaxation times on the concentration of MR contrast agents allows the calculation of the volume the contrast agent has been diluted in.

Results

In phantom and in vivo experiments we could demonstrate that TCBV can be determined with high accuracy and precision.

Conclusion

This work introduces a novel method for the determination of the total circulating blood volume using magnetic resonance contrast agents as tracers.     

Effect of motion on the ADC quantification accuracy of whole-body DWIBS

Background and methods

Diffusion-weighted whole-body imaging with background body signal subtraction was introduced as a qualitative approach to detecting metastases in the body. A liver-mimicking phantom with embedded tumours that could be moved to replicate respiratory motion was developed to assess its ability to accurately quantify ADC values.

Results

Mean tumour ADC values were unaltered by the motion; however, a significant (p?Conclusions These findings may be of significance in cancer therapy monitoring where subtle changes in ADC histograms may reveal changes in tumour heterogeneity.     

Proton CSI without solvent suppression with strongly reduced field gradient related sideband artifacts

Object

Non-water-suppressed MRSI (magnetic resonance spectroscopy imaging) offers a number of advantages; however, spectra are hampered by the sideband artifacts. The origin of those is associated with the vibration of the gradient coils, and most of the sidebands are assumed to be related to the crusher gradients. The aim was to examine the dependency between the physical direction of the crushers and the sidebands. Additionally, the possibilities of optimization of the point resolved spectroscopy sequence (PRESS) were investigated.

Materials and methods

For the assessment of the sidebands, spectra at short echo time (TE) were collected at 3 T from standard water phantom. A homemade agar phantom was used to test the optimal strength of the crusher gradients. Optimized PRESS sequence was tested in vivo.

Results

The greatest sidebands were found to be associated with the crusher gradient in x-direction. Agar phantom and in vivo measurements revealed that reduction of the crusher’s strength to 5 mT/m could provide a significant minimization of the sidebands without raising the unwanted signals produced by volume selection.

Conclusion

This study demonstrates that crusher gradients in different directions produce a unique pattern of the sidebands. Moreover, optimization of the strength of crushers has been found to decrease sidebands so, the remaining part could be reduced in postprocessing.     

Comparison between different implementations of the 3D FLASH sequence for knee cartilage quantification

Objective

To compare several sequence implementations of the 3D FLASH sequence in the context of quantitative cartilage imaging.

Materials and methods

Test–retest coronal fast low angle shot (FLASH) sequences with water excitation were acquired in knees of 12 healthy participants, using two 1.5?T scanners from the same manufacturer. On one of the scanners, the FLASH was additionally compared with a FLASH VIBE, 75% with 100% slice resolution, a non-selective with a conventional spatial pulse, and “asymmetric echo allowed” with “not allowed”.

Results

Implementations of the FLASH showed systematic differences of up to 3.3%, but these were not statistically significant. Precision errors were similar between protocols, but tended to be smallest for the FLASH VIBE with 100% slice resolution (0.6–6.7%). In the medial tibia cartilage volume and thickness differed significantly (P?Conclusion Using a validated FLASH sequence, one can reduce slice resolution to 75% and allow asymmetric echo without sacrificing precision, in order to reduce the total acquisition time. However, in longitudinal studies, the scanner and the specific sequence implementation should be kept constant between baseline and follow-up, in order to avoid systematic off-sets in the measurements.     

Eddy current compensation for delta relaxation enhanced MR by dynamic reference phase modulation

Object

Eddy current compensation by dynamic reference phase modulation (eDREAM) is a compensation method for eddy current fields induced by B ₀ field-cycling which occur in delta relaxation enhanced MR (dreMR) imaging. The presented method is based on a dynamic frequency adjustment and prevents eddy current related artifacts. It is easy to implement and can be completely realized in software for any imaging sequence.

Materials and methods

In this paper, the theory of eDREAM is derived and two applications are demonstrated. The theory describes how to model the behavior of the eddy currents and how to implement the compensation. Phantom and in vivo measurements are carried out and demonstrate the benefits of eDREAM.

Results

A comparison of images acquired with and without eDREAM shows a significant improvement in dreMR image quality. Images without eDREAM suffer from severe artifacts and do not allow proper interpretation while images with eDREAM are artifact free. In vivo experiments demonstrate that dreMR imaging without eDREAM is not feasible as artifacts completely change the image contrast.

Conclusion

eDREAM is a flexible eddy current compensation for dreMR. It is capable of completely removing the influence of eddy currents such that the dreMR images do not suffer from artifacts.     

Measurement of anesthetic uptake kinetics in the brain using 19F MRI and cross-correlation analysis after pulsed application

Object

We present a pilot study based on ¹⁹F-MRI to measure fast and slow wash-in and wash-out kinetics of volatile anesthetics in pig brain.

Method

The periodic administration of anesthetics in pulsed mode is used to enhance the sensitivity of the anesthetic concentration detection by ¹⁹F-MRI signal. Temporal correlation analysis allows mapping the kinetics time constants.

Results

The clear correlation response to anesthetics concentration changes was found in the brain region in comparison with fatty tissues.

Conclusion

The methodology may yield important pharmacological findings on regional effect of the anesthetics in brain and be a step towards human studies.     

DQF-MT MRI of connective tissues: application to tendon and muscle

Object

The sequence combining DQF (double quantum filtering) with magnetisation transfer (DQF-MT) was tested as an alternative to the DQF sequence for characterising tendon and muscle by MR imaging.

Materials and methods

DQF-MT images of tendon–muscle phantoms were obtained at 4.7 T using ultra-short time to echo (UTE) methods in order to alleviate the loss of SNR due to the short T₂ of the tissues. Two different sampling schemes of the k-space, Cartesian or radial, were employed. In vivo images of the human ankle on a clinical 1.5 T scanner are also presented. Parameters providing optimal tendon signal as well as optimal contrast between this tissue and muscle were determined.

Results

Two sets of parameters resulting in different contrasts between the tissues were found. For the first set (short creation time τ = 10 μs and magnetisation exchange time t _LM = 100 ms), DQF-MT signals in muscle and tendon were detected, with that of the tendon being the larger one. For the second set (long creation time τ = 750 μs and magnetisation exchange time 10 μs < t _LM < 100 ms), the DQF-MT signal was detected only in the tendon, and the decay of the double quantum coherence was slower than that observed for the first one, which allowed us to acquire DQF-MT MR images on a clinical 1.5 T MR scanner with minimal software interventions. In favourable conditions, the DQF-MT signal in the tendon could represent up to 10 % of the single-quantum signal.

Conclusion

Dipolar interaction within macromolecules such as collagen and myosin is at the origin of the DQF-MT signal observed in the first parameter set. This should enable the detection of muscle fibrosis.     

A correction method for streak artifacts in gradient-echo EPI using spin-echo EPI reference data

Objective

To analyze the streak artifacts in a gradient-echo echo planar imaging (GE-EPI) sequence and to propose a correction method for the Nyquist ghost artifacts that does not cause streak artifacts in the GE-EPI imaging.

Materials and methods

Several GE-EPI imaging experiments with various reference scans, using both GE-EPI and SE-EPI scan data, were performed to analyze the streak artifacts and to investigate the spin dephasing phenomena of the GE-EPI reference scan. In addition, the analysis based on the spin dephasing was undertaken in order to demonstrate that the SE-EPI reference data can be used for the correction of the GE-EPI main scan data.

Results

The experimental results confirmed that the improvement of the reference data using either signal averaging or a large flip angle cannot guarantee perfect correction of the streak artifact if the noise is not completely removed. Due to the main field inhomogeneity, the spins of the GE-EPI reference data were dephased in multiple echo signals. The proposed correction method, which uses a SE-EPI reference scan for the GE-EPI images, eliminates the N/2 ghost artifacts without producing streak artifacts.

Conclusion

It is believed that the proposed phase error correction scheme can improve the EPI performance in high field MRIs with higher magnetic field inhomogeneities.     

Visualization of immune cell infiltration in experimental viral myocarditis by 19F MRI in vivo

Objective

This paper introduces a new approach permitting for the first time a specific, non-invasive diagnosis of myocarditis by visualizing the infiltration of immune cells into the myocardium.

Materials and methods

The feasibility of this approach is shown in a murine model of viral myocarditis. Our study uses biochemically inert perfluorocarbons (PFCs) known to be taken up by circulating monocytes/macrophages after intravenous injection.

Results

In vivo ¹⁹F MRI at 9.4 T demonstrated that PFC-loaded immune cells infiltrate into inflamed myocardial areas. Because of the lack of any fluorine background in the body, detected ¹⁹F signals of PFCs are highly specific as confirmed ex vivo by flow cytometry and histology.

Conclusion

Since PFCs are a family of compounds previously used clinically as blood substitutes, the technique described in our paper holds the potential as a new imaging modality for the diagnosis of myocarditis in man.     

Using the biophysical CHARMED model to elucidate the underpinnings of contrast in diffusional kurtosis analysis of diffusion-weighted MRI

Object

The aim of this work was to understand biophysical substrate underpinning contrast in diffusional kurtosis imaging (DKI) in white matter, using the composite hindered and restricted model of diffusion (CHARMED).

Materials and methods

A theoretical relationship between the kurtosis function K and the CHARMED parameters, i.e., the restricted volume fraction RF and the axonal longitudinal diffusivity D was derived for the propagator used in the CHARMED model. Evidence for a similar correlation between these measures was then investigated in vivo across different WM regions in five healthy young subjects that underwent a CHARMED protocol at 3T.

Results

Our theoretical treatment shows that K has an increasing trend for both increasing RF values and increasing D. In vivo, a significant positive correlation (P?K _⊥ and RF. A multilinear regression showed that K _⊥ values are better explained by a mixed contribution of both RF and D.

Conclusions

The CHARMED model was used to understand whether and where DKI contrast can be explained in terms of the underlying axonal geometry. This work demonstrates that the information contained in DKI overlaps with the information extracted by CHARMED in areas of higher intra-voxel directional coherence.     

Automated flow quantification for spin labeling MR imaging

Objective

The Time-Spatial Labeling Inversion Pulse (Time-SLIP) technique enables tracing of regional fluid flows without the use of contrast medium. The objective of this study is to quantify automatically slow and complex fluid flows using the Time-SLIP technique.

Materials and methods

Series images were acquired with a 1.5-T MRI scanner using the Time-SLIP technique with half-Fourier fast spin-echo (FSE) and balanced steady-state free precession (bSSFP) sequences. In this method, labeled fluid regions in images were automatically detected based on image processing techniques for a given point. The flow velocity of the labeled fluid region was calculated using regression fitting for the region’s position. To evaluate our method, constant and non-constant laminar flows in a water phantom were studied. In addition, volunteer experiments were conducted to quantify the flow of cerebrospinal fluid.

Results

In the constant flow experiments the correlation factor r ² between the flow velocity calculated from our method and the laminar peak velocity calculated from the volumetric flow rate was 0.9992 for the FSE sequence and 0.9982 for the bSSFP sequence. In the non-constant flow study, the flow velocity was calculated accurately for any period inversion time even when the flow velocity was changed, and the quantification error was negligible. In the volunteer experiments, r ² between the flow velocity calculated by the proposed method and that obtained by manual annotation was 0.9383.

Conclusion

The experimental results showed that our proposed method can quickly and accurately provide information on flow velocities especially for slower and complex flows. Our method is, therefore, expected to be useful in diagnostic support systems.     

k-t BLAST and SENSE accelerated time-resolved three-dimensional phase contrast MRI in an intracranial aneurysm

Objective

The objective of this study was to investigate the performance of k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) accelerated time-resolved 3D PC-MRI compared to SENSE (SENSitivity Encoding) acceleration in an in vitro and in vivo intracranial aneurysm.

Materials and methods

Non-accelerated, SENSE and k-t BLAST accelerated time-resolved 3D PC-MRI measurements were performed in vivo and in vitro. We analysed the consequences of various temporal resolutions in vitro.

Results

Both in vitro and in vivo measurements showed that the main effect of k-t BLAST was underestimation of velocity during systole. In the phantom, temporal blurring decreased with increasing temporal resolution. Quantification of the differences between the non-accelerated and accelerated measurements confirmed that in systole SENSE performed better than k-t BLAST in terms of mean velocity magnitude. In both in vitro and in vivo measurements, k-t BLAST had higher SNR compared to SENSE. Qualitative comparison between measurements showed good similarity.

Conclusion

Comparison with SENSE revealed temporal blurring effects in k-t BLAST accelerated measurements.