Mapping fine-scale anatomy of gray matter,white matter,and trigeminal-root region applying spherical deconvolution to high-resolution 7-T diffusion MRI

Objectives

We assessed the use of high-resolution ultra-high-field diffusion magnetic resonance imaging (dMRI) to determine neuronal fiber orientation density functions (fODFs) throughout the human brain, including gray matter (GM), white matter (WM), and small intertwined structures in the cerebellopontine region.

Materials and methods

We acquired 7-T whole-brain dMRI data of 23 volunteers with 1.4-mm isotropic resolution; fODFs were estimated using constrained spherical deconvolution.

Results

High-resolution fODFs enabled a detailed view of the intravoxel distributions of fiber populations in the whole brain. In the brainstem region, the fODF of the extra- and intrapontine parts of the trigeminus could be resolved. Intrapontine trigeminal fiber populations were crossed in a network-like fashion by fiber populations of the surrounding cerebellopontine tracts. In cortical GM, additional evidence was found that in parts of primary somatosensory cortex, fODFs seem to be oriented less perpendicular to the cortical surface than in GM of motor, premotor, and secondary somatosensory cortices.

Conclusion

With 7-T MRI being introduced into clinical routine, high-resolution dMRI and derived measures such as fODFs can serve to characterize fine-scale anatomic structures as a prerequisite to detecting pathologies in GM and small or intertwined WM tracts.

     

Diffusion simulation-based fiber tracking using time-of-arrival maps: a comparison with standard methods

Object

We propose a new tracking method based on time-of-arrival (TOA) maps derived from simulated diffusion processes.

Materials and methods

The proposed diffusion simulation-based tracking consists of three steps that are successively evaluated on small overlapping sub-regions in a diffusion tensor field. First, the diffusion process is simulated for several time steps. Second, a TOA map is created to store simulation results for the individual time steps that are required for the tract reconstruction. Third, the fiber pathway is reconstructed on the TOA map and concatenated between neighboring sub-regions. This new approach is compared with probabilistic and streamline tracking. All methods are applied to synthetic phantom data for an easier evaluation of their fiber reconstruction quality.

Results

The comparison of the tracking results did show severe problems for the streamline approach in the reconstruction of crossing fibers, for example. The probabilistic method was able to resolve the crossing, but could not handle strong curvature. The new diffusion simulation-based tracking could reconstruct all problematic fiber constellations.

Conclusion

The proposed diffusion simulation-based tracking method used the whole tensor information of a neighborhood of voxels and is, therefore, able to handle problematic tracking situations better than established methods.     

The effect of diffusion gradient direction number on corticospinal tractography in the human brain: an along-tract analysis

Objectives

We evaluated diffusion imaging measures of the corticospinal tract obtained with a probabilistic tractography algorithm applied to data of two acquisition protocols based on different numbers of diffusion gradient directions (NDGDs).

Materials and methods

The corticospinal tracts (CST) of 18 healthy subjects were delineated using 22 and 66-NDGD data. An along-tract analysis of diffusion metrics was performed to detect possible local differences due to NDGD.

Results

FA values at 22-NDGD showed an increase along the central portion of the CST. The mean of partial volume fraction of the orientation of the second fiber (f2) was higher at 66-NDGD bilaterally, because for 66-NDGD data the algorithm more readily detects dominant fiber directions beyond the first, thus the increase in FA at 22-NDGD is due to a substantially reduced detection of crossing fiber volume. However, the good spatial correlation between the tracts drawn at 22 and 66 NDGD shows that the extent of the tract can be successfully defined even at lower NDGD.

Conclusions

Given the spatial tract localization obtained even at 22-NDGD, local analysis of CST can be performed using a NDGD compatible with clinical protocols. The probabilistic approach was particularly powerful in evaluating crossing fibers when present.

     

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.     

Morphologic and functional changes in the unilateral 6-hydroxydopamine lesion rat model for Parkinson’s disease discerned with μSPECT and quantitative MRI

Object

In the present study, we aimed to evaluate the impact of neurodegeneration of the nigrostriatal tract in a rodent model of Parkinson’s disease on the different MR contrasts (T₂, T₁, CBF and CBV) measured in the striatum.

Material and methods

Animals were injected with 6-hydroxydopamine (6OHDA) in the substantia nigra resulting in massive loss of nigrostriatal neurons and hence dopamine depletion in the ipsilateral striatum. Using 7T MRI imaging, we have quantified T₂, T₁, CBF and CBV in the striata of 6OHDA and control rats. To validate the lesion size, behavioral testing, dopamine transporter μSPECT and tyrosine hydroxylase staining were performed.

Results

No significant differences were demonstrated in the absolute MRI values between 6OHDA animals and controls; however, 6OHDA animals showed significant striatal asymmetry for all MRI parameters in contrast to controls.

Conclusions

These PD-related asymmetry ratios might be the result of counteracting changes in both intact and affected striatum and allowed us to diagnose PD lesions. As lateralization is known to occur also in PD patients and might be expected in transgenic PD models as well, we propose that MR-derived asymmetry ratios in the striatum might be a useful tool for in vivo phenotyping of animal models of PD.     

Distribution and fibre field similarity mapping of the human anterior commissure fibres by diffusion tensor imaging

Object

The anterior commissure is a critical interhemispheric pathway in animals, yet its connections in humans are not clearly understood. Its distribution has shown to vary greatly between species, and it is thought that in humans it may convey axons from a larger territory than previously thought. The aim was to use an anatomical mapping tool to look at the anterior commissure fibres and to compare the distribution findings with published anatomical understanding.

Materials and methods

Two different diffusion-weighted imaging data sets were acquired from eight healthy subjects using a 3 Tesla MR scanner with 32 gradient directions. Diffusion tensor imaging tractography was performed, and the anterior commissure fibres were selected using three-dimensional regions of interest. Distribution of the fibres was observed by means of registration with T2-weighted images. The fibre field similarity maps were produced for five of the eight subjects by comparing each subject’s fibres to the combined map of the five data sets.

Results

Fibres were shown to lead into the temporal lobe and towards the orbitofrontal cortex in the majority of subjects. Fibres were also distributed to the parietal or occipital lobes in all five subjects in whom the anterior commissure was large enough for interhemispheric fibres to be tracked through. The fibre field similarity maps highlighted areas where the local distances of fibre tracts were displayed for each subject compared to the combined bundle map.

Conclusion

The anterior commissure may play a more important role in interhemispheric communication than currently presumed by conveying axons from a wider territory, and the fibre field similarity maps give a novel approach to quantifying and visualising characteristics of fibre tracts.     

Topography of brain sodium accumulation in progressive multiple sclerosis

Object

Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury.

Materials and methods

3D-²³Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed.

Results

Progressive MS patients presented higher GM–TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T₂lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability.

Conclusion

Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.     

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.     

Magnetic resonance imaging in patients with granulomatosis with polyangiitis (Wegener’s) and subglottic stenosis

Objective

To evaluate the ability of MRI to detect subglottic stenosis and to differentiate between active and inactive subglottic inflammation in patients with granulomatosis with polyangiitis (GPA).

Materials and methods

MRI studies of the larynx of 18 GPA patients with suspected SGS were included. The MRI protocol included T1- and T2-weighted and STIR-sequences, dynamic contrast enhancement (DCE) and diffusion weighted imaging (DWI). Two independent observers reviewed the MR images. SGS were identified and quantified, inflammatory activity was assessed using edema imaging, DCE and DWI. Final MRI diagnoses were compared to the clinical, laryngoscopic and histopathologic results.

Results

MRI confirmed SGS in all GPA patients with significant narrowing of the airway lumen and thickening of subglottic wall. Assessing the subglottic inflammatory activity, MRI showed a sensitivity of 87.5 % and a specificity of 60.0 %. Interrater agreement was κ = 0.769. Of the different MR technical approaches tested, edema imaging was most sensitive and specific. DWI led to significant differences in the apparent diffusion coefficient between active and inactive subglottic inflammation. No significant differences were found with DCE imaging.

Conclusion

MR imaging has shown the ability to detect and grade SGS in patients with GPA. It non-invasively assesses the status of inflammatory activity utilizing edema sensitive sequences and DWI.     

Ultra-high field diffusion tensor imaging of articular cartilage correlated with histology and scanning electron microscopy

Object

To investigate the relationship of the different diffusion tensor imaging (DTI) parameters (ADC, FA, and first eigenvector (EV)) to the constituents (proteoglycans and collagen), the zonal arrangement of the collagen network, and mechanical loading of articular cartilage.

Material and methods

DTI of eight cartilage-on-bone samples of healthy human patellar cartilage was performed at 17.6 T. Three samples were additionally imaged under indentation loading. After DTI, samples underwent biomechanical testing, safranin-O staining for semiquantitative proteoglycan estimation, and scanning electron microscopy (SEM) for depicting collagen architecture.

Results

From the articular surface to the bone–cartilage interface, ADC continuously decreased and FA increased. Cartilage zonal heights calculated from EVs strongly correlated with SEM-derived zonal heights (P r ²=0.87). Compression reduced ADC in the superficial 30% of cartilage and increased FA in the superficial 5% of cartilage. Reorientation of the EVs indicative of collagen fiber reorientation under the indenter was observed. No significant correlation was found between ADC, FA, and compressive stiffness.

Conclusions

Correlating ADC and FA with proteoglycan and collagen content suggests that diffusion is dominated by different depth-dependent mechanisms within cartilage. Knowledge of the spatial distribution of the DTI parameters and their variation contributes to form a database for future analysis of defective cartilage.     

Diffusion time dependence of magnetic resonance diffusion signal decays: an investigation of water exchange in human brain in vivo

Object

To understand the behavior of diffusion signal decays of water in white matter of human brain in vivo and to estimate tissue microstructure parameters such as exchange time of diffusing water molecules in human brain.

Materials and methods

Diffusion decays were measured over an extended range of diffusion weightings (b-values) up to a maximum of 12,500?s/mm² and diffusion times between 19.9 and 53.8?ms in eight healthy human subjects using MRI scans. The diffusion signal decays were all Rician noise corrected and then analyzed using multi-component non-negative least squares (NNLS) data analysis.

Results

Three diffusion coefficients including one at (0.930?±?0.003)?×?10^?3 (80?±?1%)?mm²/s, another at (0.067?±?0.002)?×?10^?3 (19?±?1%)?mm²/s and a small contribution at (1.20?±?0.02)?×?10^?2 (1.00?±?0.01%)?mm²/s were observed in the diffusion decay using the highest b-value. The diffusion decays show diffusion time dependence for the slow diffusion coefficient which has not previously been reported.

Conclusion

This study presents the accurate diffusion parameters by the use of very large b-values along with Rician noise correction and multi-component data analysis. The experimental results are consistent with the theoretical predictions used to estimate the exchange time of diffusing water molecules for a model of human brain tissue.     

Diffusion property differences of the lower leg musculature between athletes and non-athletes using 1.5T MRI

Object

To compare the differences in diffusion properties—namely fractional anisotropy (FA), three eigenvalues of the diffusion tensor (λ1, λ2, and λ3), and apparent diffusion coefficient (ADC)—between athletically-trained and untrained lower leg musculature.

Materials and methods

Twelve athletes (Group A) and 11 non-athletes (Group B) were recruited. All were females in their 20s. We scanned diffusion tensor images of both calves and compared FA, the three eigenvalues, and ADC in the gastrocnemius medialis, gastrocnemius lateralis, soleus (SOL), and anterior tibialis muscles between Groups A and B, and between the right and left sides, using two-factor fractional ANOVA.

Results

In all muscles of bilateral calves, all three eigenvalues and ADC were lower in Group A than in Group B, with statistically significant differences in all muscles for λ1, λ2, and λ3 and ADC, with a P value of <0.01. Moreover, statistical differences were also found between right and left for λ1, λ2, and λ3 (P?P?Conclusions Our results indicate that training causes a decrease of the three eigenvalues and ADC, which we hypothesize is due to an increase of density of myofilaments in the intracellular space, and deformation of the cell induced by enlargement of extracellular components.     

T 2 relaxometry measurements in low spatial frequency brain regions differ between fast spin-echo and multiple-echo spin-echo sequences

Object

Dual-echo fast spin-echo (FSE) sequences are used in T ₂ relaxometry studies of neurological disorders because of shorter clinical scanning times and protocol simplicity. However, FSE sequences have possible spatial frequency-dependent effects, and derived T ₂ values may include errors that depend on the spatial frequency characteristics of the brain region of interest.

Materials and methods

Dual-echo FSE and multi-echo spin-echo (MESE) sequences were acquired in nine subjects. The T ₂ decay curves for FSE and MESE sequences were estimated and percent error maps were generated. T ₂ error values were obtained along each patient’s corticospinal tract (CST). Whole-brain white matter (WM) and gray matter (GM) T ₂ error values were also obtained. The paired t test was performed to evaluate differences in T ₂ values in the CST between FSE and MESE sequences.

Results

Histograms of error values in CST and in whole-brain WM and GM structures revealed systematic errors in FSE sequences. Significant differences (P < 0.001) in CST T ₂ values were also observed between FSE and MESE sequences.

Conclusion

Our findings indicate that T ₂ values derived from FSE sequences are prone to large errors, even in low spatial frequency regions such as the CST, when compared to MESE sequences. Future studies should be aware of this limitation of FSE sequences.     

Iterative separation of transmit and receive phase contributions and B 1 + -based estimation of the specific absorption rate for transmit arrays

Object

The specific absorption rate (SAR) can be determined from radiofrequency transmit fields measured via magnetic resonance imaging.

Materials and methods

The proposed method estimates the SAR solely from the complex transmit field (B ₁ ⁺ ) by taking into account the particular properties of the electromagnetic field generated by an 8-channel transmit array. It is further based on an iterative consistency check between the measured B ₁ ⁺ magnitude and an appropriate field estimate fulfilling Maxwell’s equations. For testing the method, simulations and phantom experiments were performed for a multi-transmit array at 3T using a cylindrical phantom.

Results

The method’s robustness with respect to the assumptions made about electric tissue properties as well as its stability under different initial conditions regarding the signal phase was shown. A high sensitivity to signal noise was found. Robust reconstruction results were achieved including information from more than two transmit elements. The validity of the experimental results was confirmed by a qualitative comparison to simulated electromagnetic fields.

Conclusions

The method allows the determination of the SAR as well as the transmit phase of the individual channels of a multi-transmit array. With additional B₀ inhomogeneity measurements, a reconstruction of the receive phase is feasible independent of the receive coil type in use.     

Quantitative breast MRI: 2D histogram analysis of diffusion tensor parameters in normal tissue

Object

Diffusion tensor imaging (DTI) of the breast may provide a powerful new approach for the detection of intraductal processes. The aim of this investigation was to characterize the relation between diffusion tensor parameters [fractional anisotropy (FA), mean diffusivity (MD)] in normal breast tissue to obtain information on the microenvironment of the diffusing water molecules and to provide a systematic approach for DTI analysis.

Materials and methods

Seven female, healthy volunteers underwent prospective double-spin-echo prepared echo-planar diffusion-weighted sequence (TR/TE 8,250 ms/74 ms, b values 0 and 500 s/mm (2), six encoding directions, 12 averages, 35 slices) in 4 consecutive weeks (3.0 T). Quantitative maps of diffusion tensor parameters were computed offline with custom routines. The interdependence of MD and FA in different voxels was analysed by linear and exponential regression.

Results

All MD and FA maps were of excellent quality. A consistent pattern was observed in that lower fractional anisotropy values were more likely associated with higher mean diffusivity values. The dependence exhibited an exponential behavior with a correlation coefficient R = 0.60 (R linear = 0.57).

Conclusion

The likelihood with which FA and MD values are observed in a voxel within normal breast tissue is characterized by a specific pattern, which can be described by an exponential model. Moreover, we could show that the proposed technique does not depend on the menstrual cycle.     

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.     

The impact of fibre orientation on <Emphasis Type="Italic">T</Emphasis><Subscript>1</Subscript>-relaxation and apparent tissue water content in white matter

Objective

Recent MRI studies have shown that the orientation of nerve fibres relative to the main magnetic field affects the R₂*(= 1/T₂*) relaxation rate in white matter (WM) structures. The underlying physical causes have been discussed in several studies but are still not completely understood. However, understanding these effects in detail is of great importance since this might serve as a basis for the development of new diagnostic tools and/or improve quantitative susceptibility mapping techniques. Therefore, in addition to the known angular dependence of R₂*, the current study investigates the relationship between fibre orientation and the longitudinal relaxation rate, R₁ (= 1/T₁), as well as the apparent water content.

Materials and methods

For a group of 16 healthy subjects, a series of gradient echo, echo-planar and diffusion weighted images were acquired at 3T from which the decay rates, the apparent water content and the diffusion direction were reconstructed. The diffusion weighted data were used to determine the angle between the principle fibre direction and the main magnetic field to examine the angular dependence of R₁ and apparent water content.

Results

The obtained results demonstrate that both parameters depend on the fibre orientation and exhibit a positive correlation with the angle between fibre direction and main magnetic field.

Conclusion

These observations could be helpful to improve and/or constrain existing biophysical models of brain microstructure by imposing additional constraints resulting from the observed angular dependence R₁ and apparent water content in white matter.

     

Highly accelerated PSF-mapping for EPI distortion correction with improved fidelity

Objective

This study presents an improved point-spread-function (PSF) mapping-based distortion correction method and accelerated PSF acquisition for distortion correction in EPI without loss of quality or reliability compared to full encoding.

Materials and methods

To correct geometric distortions accurately, the PSF in the EPI phase-encoding coordinates (EPI-PSF) was measured and used as a kernel for distortion correction. FOV reduction was applied in the PSF mapping dimension for highly accelerated PSF acquisition. A novel approach for fold-over artifact correction in this reduced dimension is introduced. Conventional gradient-echo EPI and corresponding full PSF reference data were acquired in phantoms and in human brain at 7 T. The distortion corrected EPI data with the proposed acceleration were compared to result with full encoding. Previously published interpolation methods based on shift maps, non-uniform Fourier transformation and a b-spline interpolation were compared with the proposed method.

Results

The results demonstrate that the proposed method corrects geometric distortions in EPI with high accuracy and quality despite the high acceleration. In contrast to partial parallel imaging acceleration, no noise enhancement is introduced.

Conclusion

The proposed EPI-PSF-based distortion correction improves correction of EPI and accelerates PSF reference data acquisition and computation.     

In vivo visualization of cells labeled with superparamagnetic iron oxides by a sub-millisecond gradient echo sequence

Object

In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic islets (PIs) transplanted into the liver is still challenging in humans. The aim of this study was to develop and evaluate a double contrast method for the detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles.

Materials and methods

A double-echo three-dimensional (3D) spoiled gradient echo sequence was adapted to yield a sub-millisecond first echo time using variable echo times and highly asymmetric Cartesian readout. Positive contrast was achieved by conventional and relative image subtraction. Experiments for cell detection efficiency were performed in vitro on gelatin phantoms, in vivo on a Lewis rat and on a patient 6 months after PI transplantation.

Results

It was demonstrated that the proposed method can be used for the detection of transplanted PIs with positive contrast in vitro and in vivo. For all experiments, relative subtraction yielded comparable and in some cases better contrast than conventional subtraction. For the first time, positive contrast imaging of transplanted human PIs was performed in vivo in patients.

Conclusion

The proposed method allows 3D data acquisition within a single breath-hold and yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic islets relative to negative contrast images, therefore providing improved identification.     

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.