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1.

Objective

Partial volume (PV) correction is an important step in arterial spin labeling (ASL) MRI that is used to separate perfusion from structural effects when computing the mean gray matter (GM) perfusion. There are three main methods for performing this correction: (1) GM-threshold, which includes only voxels with GM volume above a preset threshold; (2) GM-weighted, which uses voxel-wise GM contribution combined with thresholding; and (3) PVC, which applies a spatial linear regression algorithm to estimate the flow contribution of each tissue at a given voxel. In all cases, GM volume is obtained using PV maps extracted from the segmentation of the T1-weighted (T1w) image. As such, PV maps contain errors due to the difference in readout type and spatial resolution between ASL and T1w images. Here, we estimated these errors and evaluated their effect on the performance of each PV correction method in computing GM cerebral blood flow (CBF).

Materials and methods

Twenty-two volunteers underwent scanning using 2D echo planar imaging (EPI) and 3D spiral ASL. For each PV correction method, GM CBF was computed using PV maps simulated to contain estimated errors due to spatial resolution mismatch and geometric distortions which are caused by the mismatch in readout between ASL and T1w images. Results were analyzed to assess the effect of each error on the estimation of GM CBF from ASL data.

Results

Geometric distortion had the largest effect on the 2D EPI data, whereas the 3D spiral was most affected by the resolution mismatch. The PVC method outperformed the GM-threshold even in the presence of combined errors from resolution mismatch and geometric distortions. The quantitative advantage of PVC was 16% without and 10% with the combined errors for both 2D and 3D ASL. Consistent with theoretical expectations, for error-free PV maps, the PVC method extracted the true GM CBF. In contrast, GM-weighted overestimated GM CBF by 5%, while GM-threshold underestimated it by 16%. The presence of PV map errors decreased the calculated GM CBF for all methods.

Conclusion

The quality of PV maps presents no argument for the preferential use of the GM-threshold method over PVC in the clinical application of ASL.
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2.

Objective

Here we develop a three-dimensional analytic model for MR image contrast of collagen lamellae in the annulus fibrosus of the intervertebral disc of the spine, based on the dependence of the MRI signal on collagen fiber orientation.

Materials and methods

High-resolution MRI scans were performed at 1.5 and 7 T on intact whole disc specimens from ovine, bovine, and human spines. An analytic model that approximates the three-dimensional curvature of the disc lamellae was developed to explain inter-lamellar contrast and intensity variations in the annulus. The model is based on the known anisotropic dipolar relaxation of water in tissues with ordered collagen.

Results

Simulated MRI data were generated that reproduced many features of the actual MRI data. The calculated inter-lamellar image contrast demonstrated a strong dependence on the collagen fiber angle and on the circumferential location within the annulus.

Conclusion

This analytic model may be useful for interpreting MR images of the disc and for predicting experimental conditions that will optimize MR image contrast in the annulus fibrosus.
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3.

Objectives

We present a method based on a proposed statistical definition of white matter hyperintensities (WMH), which can work with any combination of conventional magnetic resonance (MR) sequences without depending on manually delineated samples.

Materials and methods

T1-weighted, T2-weighted, FLAIR, and PD sequences acquired at 1.5 Tesla from 119 subjects from the Kings Health Partners-Dementia Case Register (healthy controls, mild cognitive impairment, Alzheimer’s disease) were used. The segmentation was performed using a proposed definition for WMH based on the one-tailed Kolmogorov–Smirnov test.

Results

The presented method was verified, given all possible combinations of input sequences, against manual segmentations and a high similarity (Dice 0.85–0.91) was observed. Comparing segmentations with different input sequences to one another also yielded a high similarity (Dice 0.83–0.94) that exceeded intra-rater similarity (Dice 0.75–0.91). We compared the results with those of other available methods and showed that the segmentation based on the proposed definition has better accuracy and reproducibility in the test dataset used.

Conclusion

Overall, the presented definition is shown to produce accurate results with higher reproducibility than manual delineation. This approach can be an alternative to other manual or automatic methods not only because of its accuracy, but also due to its good reproducibility.
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4.

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.
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5.

Objective

We demonstrate the potential clinical utility of a 4D non-gadolinium dynamic angiography technique based on arterial spin-labeling called contrast inherent inflow enhanced multi-phase angiography (CINEMA) in pediatric patients.

Materials and Methods

CINEMA was qualitatively compared to conventional time-of-flight (TOF) angiography in a cohort of 31 pediatric patients at 3 Tesla.

Results

CINEMA data were successfully acquired and reconstructed in all patients with no image artifacts. There were no cases where CINEMA was rated inferior to TOF in depicting intracranial vessel conspicuity. In 19 cases, CINEMA was rated equivalent to TOF and in the 12 remaining cases CINEMA was rated superior to TOF.

Conclusion

There is a steadily rising concern in adults and children over the potential effects of intracranial deposition of gadolinium. CINEMA is therefore a viable alternative in dynamic neurovascular imaging.
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6.

Objectives

Contrast agent (CA) relaxivities are generally not well established in vivo, and the relationship between frequency/phase shift and magnetic susceptibility might be a useful alternative for CA quantification.

Materials and methods

Twenty volunteers (25–84 years old) were investigated using test–retest pre-bolus dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI). The pre-bolus phase-based venous output function (VOF) time integral was used for arterial input function (AIF) rescaling. Resulting cerebral blood flow (CBF) data for grey matter (GM) were compared with pseudo-continuous arterial spin labelling (ASL). During the main bolus CA passage, the apparent spatial shift (pixel shift) of the superior sagittal sinus (seen in single-shot echo-planar imaging (EPI)) was converted to CA concentration and compared with conventional ΔR2*-based data and with a predicted phase-based VOF from the pre-bolus experiment.

Results

The phase-based pre-bolus VOF resulted in a reasonable inter-individual GM CBF variability (coefficient of variation 28 %). Comparison with ASL CBF values implied a tissue R2*-relaxivity of 32 mM?1 s?1. Pixel-shift data at low concentrations (data not available at peak concentrations) were in reasonable agreement with the predicted phase-based VOF.

Conclusion

Susceptibility-induced phase shifts and pixel shifts are potentially useful for large-vein CA quantification. Previous predictions of a higher R2*-relaxivity in tissue than in blood were supported.
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7.

Purpose

Real-time monitoring is important for the safety and effectiveness of high-intensity focused ultrasound (HIFU) therapy. Magnetic resonance imaging is the preferred imaging modality for HIFU monitoring, with its unique capability of temperature imaging. For real-time temperature imaging, higher temporal resolution and larger spatial coverage are needed. In this study, a sequence based on the echo-shifted RF-spoiled gradient echo (GRE) with simultaneous multi-slice (SMS) imaging was designed for fast temperature imaging.

Methods

A phantom experiment was conducted to evaluate the accuracy of the echo-shifted sequence using a fluorescent fiber thermometer as reference. The temperature uncertainty of the echo-shifted sequence was compared with the traditional GRE sequence at room temperature through the ex vivo porcine muscle. Finally, the ex vivo porcine liver tissue experiment using HIFU heating was performed to demonstrate that the spatial coverage was increased without decreasing temporal resolution.

Results

The echo-shifted sequence had a better temperature uncertainty performance compared with the traditional GRE sequence with the same temporal resolution. The ex vivo heating experiment confirmed that by combining the SMS technique and echo-shifted sequence, the spatial coverage was increased without decreasing the temporal resolution while maintaining high temperature measurement precision.

Conclusion

The proposed technique was validated as an effective real-time method for monitoring HIFU therapy.
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8.

Objective

Ultrahigh field MRI provides great opportunities for medical diagnostics and research. However, ultrahigh field MRI also brings challenges, such as larger magnetic susceptibility induced field changes. Parallel-transmit radio-frequency pulses can ameliorate these complications while performing advanced tasks in routine applications. To address one class of such pulses, we propose an optimal-control algorithm as a tool for designing advanced multi-dimensional, large flip-angle, radio-frequency pulses. We contrast initial conditions, constraints, and field correction abilities against increasing pulse trajectory acceleration factors.

Materials and methods

On an 8-channel 7T system, we demonstrate the quasi-Newton algorithm with pulse designs for reduced field-of-view imaging with an oil phantom and in vivo with scans of the human brain stem. We used echo-planar imaging with 2D spatial-selective pulses. Pulses are computed sufficiently rapid for routine applications.

Results

Our dataset was quantitatively analyzed with the conventional mean-square-error metric and the structural-similarity index from image processing. Analysis of both full and reduced field-of-view scans benefit from utilizing both complementary measures.

Conclusion

We obtained excellent outer-volume suppression with our proposed method, thus enabling reduced field-of-view imaging using pulse trajectory acceleration factors up to 4.
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9.

Objective

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data.

Materials and methods

We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s).

Results

The delineated Pearson’s correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work.

Conclusion

Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson’s disease, and other motor disorders.
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10.

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.
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11.

Objective

This study evaluates the inter-site and intra-site reproducibility of 7 Tesla brain imaging and compares it to literature values for other field strengths.

Materials and methods

The same two subjects were imaged at eight different 7 T sites. MP2RAGE, TSE, TOF, SWI, EPI as well as B1 and B0 field maps were analyzed quantitatively to assess inter-site reproducibility. Intra-site reproducibility was measured with rescans at three sites.

Results

Quantitative measures of MP2RAGE scans showed high agreement. Inter-site and intra-site reproducibility errors were comparable to 1.5 and 3 T. Other sequences also showed high reproducibility between the sites, but differences were also revealed. The different RF coils used were the main source for systematic differences between the sites.

Conclusion

Our results show for the first time that multi-center brain imaging studies of the supratentorial brain can be performed at 7 T with high reproducibility and similar reliability as at 3T. This study develops the basis for future large-scale 7 T multi-site studies.
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12.

Objectives

The purpose of this study was to assess the reproducibility of substantia nigra pars compacta (SNpc) and locus coeruleus (LC) delineation and measurement with neuromelanin-sensitive MRI.

Materials and methods

Eleven subjects underwent two neuromelanin-sensitive MRI scans. SNpc and LC volumes were extracted for each scan. Reproducibility of volume and magnetization transfer contrast measurements in SNpc and LC was assessed using intraclass correlation coefficients (ICC) and dice similarity coefficients (DSC).

Results

SNpc and LC volume measurements showed excellent reproducibility (SNpc-ICC: 0.94, p < 0.001; LC-ICC: 0.96, p < 0.001). SNpc and LC were accurately delineated between scans (SNpc-DSC: 0.80 ± 0.03; LC-DSC: 0.63 ± 0.07).

Conclusion

Neuromelanin-sensitive MRI can consistently delineate SNpc and LC.
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13.

Objectives

In the present study, we have tested whether MRI T1 relaxation time is a sensitive marker to detect early stages of amyloidosis and gliosis in the young 5xFAD transgenic mouse, a well-established animal model for Alzheimer’s disease.

Materials and methods

5xFAD and wild-type mice were imaged in a 4.7 T Varian horizontal bore MRI system to generate T1 quantitative maps using the spin-echo multi-slice sequence. Following immunostaining for glial fibrillary acidic protein, Iba-1, and amyloid-β, T1 and area fraction of staining were quantified in the posterior parietal and primary somatosensory cortex and corpus callosum.

Results

In comparison with age-matched wild-type mice, we observed first signs of amyloidosis in 2.5-month-old 5xFAD mice, and development of gliosis in 5-month-old 5xFAD mice. In contrast, MRI T1 relaxation times of young, i.e., 2.5- and 5-month-old, 5xFAD mice were not significantly different to those of age-matched wild-type controls. Furthermore, although disease progression was detectable by increased amyloid-β load in the brain of 5-month-old 5xFAD mice compared with 2.5-month-old 5xFAD mice, MRI T1 relaxation time did not change.

Conclusions

In summary, our data suggest that MRI T1 relaxation time is neither a sensitive measure of disease onset nor progression at early stages in the 5xFAD mouse transgenic mouse model.
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14.

Object

The objective of this study is to propose a modified VARiable PROjection (VARPRO) algorithm specifically tailored for fitting the intravoxel incoherent motion (IVIM) model to diffusion-weighted magnetic resonance imaging (DW-MRI) data from locally advanced rectal cancer (LARC).

Materials and methods

The proposed algorithm is compared with classical non-linear least squares (NLLS) analysis using the Levenberg-Marquardt (LM) algorithm and with two recently proposed algorithms for ‘segmented’ analysis. These latter two comprise two consecutive steps: first, a subset of parameters is estimated using a portion of data; second, the remaining parameters are estimated using the whole data and the previous estimates. The comparison between the algorithms was based on the \(R^2\) goodness-of-fit measure: performance analysis was carried out on real data obtained by DW-MRI on 40 LARC patients.

Results

The performance of the proposed algorithm was higher than that of LM in 64 % of cases; ‘segmented’ methods were poorer than our algorithm in 100 % of cases.

Conclusion

The proposed modified VARPRO algorithm can lead to better fit of the IVIM model to LARC DW-MRI data compared to other techniques.
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15.

Objectives

The objective of the current work was to evaluate flow and turbulent kinetic energy in different transcatheter aortic valve implants using highly undersampled time-resolved multi-point 3-directional phase-contrast measurements (4D Flow MRI) in an in vitro setup.

Materials and methods

A pulsatile flow setup was used with a compliant tubing mimicking a stiff left ventricular outflow tract and ascending aorta. Five different implants were measured using a highly undersampled multi-point 4D Flow MRI sequence. Velocities and turbulent kinetic energy values were analysed and compared.

Results

Strong variations of turbulent kinetic energy distributions between the valves were observed. Maximum turbulent kinetic energy values ranged from 100 to over 500 J/m3 while through-plane velocities were similar between all valves.

Conclusion

Highly accelerated 4D Flow MRI for the measurement of velocities and turbulent kinetic energy values allowed for the assessment of hemodynamic parameters in five different implant models. The presented setup, measurement protocol and analysis methods provides an efficient approach to compare different valve implants and could aid future novel valve designs.
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16.

Objective

We assess inter- and intra-subject variability of magnetic resonance (MR)-based attenuation maps (MRμMaps) of human subjects for state-of-the-art positron emission tomography (PET)/MR imaging systems.

Materials and methods

Four healthy male subjects underwent repeated MR imaging with a Siemens Biograph mMR, Philips Ingenuity TF and GE SIGNA PET/MR system using product-specific MR sequences and image processing algorithms for generating MRμMaps. Total lung volumes and mean attenuation values in nine thoracic reference regions were calculated. Linear regression was used for comparing lung volumes on MRμMaps. Intra- and inter-system variability was investigated using a mixed effects model.

Results

Intra-system variability was seen for the lung volume of some subjects, (p = 0.29). Mean attenuation values across subjects were significantly different (p < 0.001) due to different segmentations of the trachea. Differences in the attenuation values caused noticeable intra-individual and inter-system differences that translated into a subsequent bias of the corrected PET activity values, as verified by independent simulations.

Conclusion

Significant differences of MRμMaps generated for the same subjects but different PET/MR systems resulted in differences in attenuation correction factors, particularly in the thorax. These differences currently limit the quantitative use of PET/MR in multi-center imaging studies.
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17.

Objective

To accelerate a passive tracking sequence based on phase-only cross correlation (POCC) using simultaneous slice excitation.

Methods

For magnetic resonance (MR)-guided biopsy procedures, passive markers have been proposed that can be automatically localized online using a POCC-based tracking sequence. To accelerate the sequence, a phase-offset multiplanar (POMP) excitation technique was implemented to acquire tracking images. In a phantom experiment, the POMP–POCC sequence was tested and compared with the sequential non-accelerated version in terms of duration and accuracy. Further, technical feasibility of the POMP–POCC sequence was tested in a patient undergoing a prostate biopsy.

Results

The temporal resolution of the POMP–POCC tracking sequence is accelerated by 33% compared with the sequential approach. In phantom experiments, the POMP–POCC and sequential sequences yielded the same targeting accuracy of 1.6?±?0.7 mm. Technical proof of concept of the new sequence could be demonstrated in a successful in vivo prostate biopsy.

Conclusion

POMP–POCC tracking can substantially reduce the duration of localization of passive markers in MR-guided needle interventions without compromising targeting accuracy.
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18.

Objective

In this paper, we present a new performance measure of a matrix coil (also known as multi-coil) from the perspective of efficient, local, non-linear encoding without explicitly considering target encoding fields.

Materials and methods

An optimization problem based on a joint optimization for the non-linear encoding fields is formulated. Based on the derived objective function, a figure of merit of a matrix coil is defined, which is a generalization of a previously known resistive figure of merit for traditional gradient coils.

Results

A cylindrical matrix coil design with a high number of elements is used to illustrate the proposed performance measure. The results are analyzed to reveal novel features of matrix coil designs, which allowed us to optimize coil parameters, such as number of coil elements. A comparison to a scaled, existing multi-coil is also provided to demonstrate the use of the proposed performance parameter.

Conclusions

The assessment of a matrix gradient coil profits from using a single performance parameter that takes the local encoding performance of the coil into account in relation to the dissipated power.
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19.

Objective

To evaluate the feasibility of in vivo measurement of the fatty acid (FA) composition of breast adipose tissue by MRS on a clinical platform.

Material and methods

MRS experiments were performed at 3 T, using a STEAM sequence, on 25 patients diagnosed with breast cancer. MR spectra, acquired on healthy breast tissue, were analysed with the LCModel.

Results

The measured values of the saturated fatty acid (SFA), mono-unsaturated fatty acid (MUFA) and poly-unsaturated fatty acid (PUFA) fractions were 23.8 ± 7.1 %, 55.4 ± 6.8 % and 20.8 ± 4.4 %, respectively.The values of SFA, MUFA and PUFA observed in the current study are in the same range as those found in two previous studies performed at 7 T.

Conclusion

The results of the current study show that it is possible to quantify the fatty acid composition of breast tissue in vivo in a clinical setting (3 T).
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20.

Object

We aimed to modify our previously published method for arterial input function measurements for evaluation of cerebral perfusion (dynamic susceptibility contrast MRI) such that it can be applied in humans in a clinical setting.

Materials and methods

Similarly to our previous work, a conventional measurement sequence for dynamic susceptibility contrast MRI is extended with an additional measurement slice at the neck. Measurement parameters at this slice were optimized for the blood signal (short echo time, background suppression, magnitude and phase images). Phase-based evaluation of the signal in the carotid arteries is used to obtain quantitative arterial input functions.

Results

In all pilot measurements, quantitative arterial input functions were obtained. The resulting absolute perfusion parameters agree well with literature values (gray and white matter mean values of 46 and 24 mL/100 g/min, respectively, for cerebral blood flow and 3.0% and 1.6%, respectively, for cerebral blood volume).

Conclusions

The proposed method has the potential to quantify arterial input functions in the carotid arteries from a direct measurement without any additional normalization.
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