Neural correlates of lower limbs proprioception: An fMRI study of foot position matching.

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.

Brain intra- and extracellular sodium concentration in multiple sclerosis: a 7 T MRI study.

Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered (23)Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P < 0.05 and P < 0.01), and intracellular sodium concentration (both P < 0.001) were higher while grey matter and white matter intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) were lower (respectively P = 0.62 and P < 0.001) in patients compared with healthy controls. At a brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P < 0.05 family-wise error corrected for total sodium concentration, P < 0.05 uncorrected for multiple comparisons for intracellular sodium concentration and intracellular sodium volume fraction). Measures of total sodium concentration and intracellular sodium volume fraction, but not measures of intracellular sodium concentration were correlated with T2-weighted and T1-weighted lesion volumes (0.05 < P < 0.01) and with Expanded Disability Status Scale (P < 0.05). Thus, suggesting that while intracellular sodium volume fraction decrease could reflect expansion of extracellular space due to tissue loss, intracellular sodium concentration increase could reflect neuro-axonal metabolic dysfunction.

Sodium MRI of multiple sclerosis.

Multiple sclerosis (MS) is the most common cause of non-traumatic disability in young adults. The mechanisms underlying neurodegeneration and disease progression are poorly understood, in part as a result of the lack of non-invasive methods to measure and monitor neurodegeneration in vivo. Sodium MRI is a topic of increasing interest in MS research as it allows the metabolic characterization of brain tissue in vivo, and integration with the structural information provided by (1)H MRI, helping in the exploration of pathogenetic mechanisms and possibly offering insights into disease progression and monitoring of treatment outcomes. We present an up-to-date review of the sodium MRI application in MS organized into four main sections: (i) biological and pathogenetic role of sodium; (ii) brief overview of sodium imaging techniques; (iii) results of sodium MRI application in clinical studies; and (iv) future perspectives.

Feasibility and reproducibility of BOLD and TOLD measurements in the liver with oxygen and carbogen gas challenge in healthy volunteers and patients with hepatocellular carcinoma.

PURPOSE: To quantify baseline relaxation rates R2* and R1 in the abdomen, their changes after respiratory challenges, and their reproducibility in healthy volunteers and patients with hepatocellular carcinoma (HCC) at 1.5T and 3.0T. MATERIALS AND METHODS: R2* measurements were acquired in the liver in 8 volunteers and 27 patients with 34 HCCs using multiecho T2* at baseline and after respiratory challenges with 100% oxygen (O2 ) and carbogen (CB = 95%O2 /5%CO2 ). R1 was measured at 1.5T in one volunteer and 21 patients with 23 HCCs. Test-retest coefficient of variation (CV) was assessed in 10 subjects. Intra- and interobserver variability of R2* and R1 measurements was assessed in 12 and 10 patients, respectively. Parameters for HCC, liver, and muscle were compared between baseline and after gas challenges. RESULTS: We observed that R2* and R1 imaging of HCCs with O2 and CB is feasible and reproducible (test-retest CV R2*<15%/R1 <5%; intra- and interobserver intraclass correlation coefficient R2*>0.88/R1 >0.7 and CV R2*<7%/R1 <3% at 1.5T). R2* measurements were observed to be less reproducible at 3.0T (CV<35%). There was a statistically significant decrease in R2* values in HCC before and after O2 (P = 0.02) and increase in R1 after O2 (P = 0.004). CB had no significant effect (P R2* = 0.47/R1 = 0.278). CONCLUSION: R2* measurements in HCC and liver parenchyma are more reproducible at 1.5T than at 3.0T, and with O2 than with CB challenge. We observed a decrease in R2* and an increase in R1 of HCCs from baseline in response to O2 challenge, as expected with increased tissue and blood oxygenation.

Noninvasive quantification of intracellular sodium in human brain using ultrahigh-field MRI.

In vivo sodium magnetic resonance imaging (MRI) measures tissue sodium content in living human brain but current methods do not allow noninvasive quantitative assessment of intracellular sodium concentration (ISC) - the most useful marker of tissue viability. In this study, we report the first noninvasive quantitative in vivo measurement of ISC and intracellular sodium volume fraction (ISVF) in healthy human brain, made possible by measuring tissue sodium concentration (TSC) and intracellular sodium molar fraction (ISMF) at ultra-high field MRI. The method uses single-quantum (SQ) and triple-quantum filtered (TQF) imaging at 7 Tesla to separate intra- and extracellular sodium signals and provide quantification of ISMF, ISC and ISVF. This novel method allows noninvasive quantitative measurement of ISC and ISVF, opening many possibilities for structural and functional metabolic studies in healthy and diseased brains.

Exploiting sparsity to accelerate noncontrast MR angiography in the context of parallel imaging.

Noncontrast techniques for peripheral MR angiography are receiving renewed interest because of safety concerns about the use of gadolinium in patients with renal insufficiency. One class of techniques involves subtraction of dark-blood images acquired during fast systolic flow from bright-blood images obtained during slow diastolic flow. The goal of this work was to determine whether the inherent sparsity of the difference images could be exploited to achieve greater acceleration without loss of image quality in the context of generalized autocalibrating partially parallel acquisition (GRAPPA). It is shown that noise amplification at high acceleration factors can be reduced by performing subtraction on the raw data, before calculation of the GRAPPA weights, rather than on the final magnitude images. Use of the difference data to calculate the GRAPPA weights decreases the geometry factor (g-factor), because the difference data represent a sparse image set. This demonstrates an inherent property of GRAPPA and does not require the use of compressed sensing. Application of this approach to highly accelerated data from healthy volunteers resulted in similar depiction of large arteries to that obtained with low acceleration and standard reconstruction. However, visualization of very small vessels and arterial branches was compromised.

MAGNIMS recommendations for harmonization of MRI data in MS multicenter studies.

There is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. However, differences in MRI acquisition parameters, image analysis and data storage across sites, with their potential bias, represent a substantial constraint. This review focuses on the state of the art, recent technical advances, and desirable future developments of the harmonization of acquisition, analysis and storage of large-scale multicentre MRI data of MS cohorts. Huge efforts are currently being made to achieve all the requirements needed to provide harmonized MRI datasets in the MS field, as proper management of large imaging datasets is one of our greatest opportunities and challenges in the coming years. Recommendations based on these achievements will be provided here. Despite the advances that have been made, the complexity of these tasks requires further research by specialized academical centres, with dedicated technical and human resources. Such collective efforts involving different professional figures are of crucial importance to offer to MS patients a personalised management while minimizing consumption of resources.

B0 inhomogeneity-insensitive triple-quantum-filtered sodium imaging using a 12-step phase-cycling scheme.

Triple-quantum-filtered (TQF) sodium MRI can be used to separate sodium NMR signals from different physiological compartments. Although three-pulse triple-quantum filtering has been demonstrated to be better suited for in vivo imaging, the absence of the refocusing pulse in the filter increases its sensitivity to magnetic field inhomogeneities. Therefore, several TQF cycles have been developed previously to correct image distortions caused by B(0) inhomogeneities. In this paper, we present a new 12-step phase-cycling TQF scheme based on three radiofrequency pulses which allows the compensation of B(0) variations both with and without ancillary B(0) map information. The method offers 40% higher signal-to-noise-ratio efficiency compared with the previously developed B(0)-correcting phase-cycling schemes.

The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions.

UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.

Hybrid adiabatic-rectangular pulse train for effective saturation of magnetization within the whole heart at 3 T.

Uniform T(1)-weighting is a major challenge for first-pass cardiac perfusion MRI at 3 T. Previously proposed adiabatic amplitude of radiofrequency field (B(1))-insensitive rotation (BIR-4) pulse and standard and tailored pulse trains of three nonselective pulses have been important developments but each pulse has limitations at 3 T. As an extension of the tailored pulse train, we developed a hybrid pulse train by synergistically combining two nonselective rectangular radiofrequency pulses and an adiabatic half-passage pulse, in order to achieve effective saturation of magnetization within the heart, while remaining within clinically acceptable specific absorption rate limits. The standard pulse train, tailored pulse train, hybrid pulse train, and BIR-4 pulse train were evaluated through numerical, phantom, and in vivo experiments. Among the four saturation pulses, only the hybrid pulse train yielded residual magnetization <2% of equilibrium magnetization in the heart while remaining within clinically acceptable specific absorption rate limits for multislice first-pass cardiac perfusion MRI at 3 T.

Sodium long-component T(2)(*) mapping in human brain at 7 Tesla.

Sodium ((23)Na) MRI may provide unique information about the cellular and metabolic integrity of the brain. The quantification of tissue sodium concentration from (23)Na images with nonzero echo time (TE) requires knowledge of tissue-specific parameters that influence the single-quantum sodium signal such as transverse (T(2)) relaxation times. We report the sodium ((23)Na) long component of the effective transverse relaxation time T(2) (*) values obtained at 7 T in several brain regions from six healthy volunteers. A two-point protocol based on a gradient-echo sequence optimized for the least error per given imaging time was used (TE(1) = 12 ms; TE(2) = 37 ms; averaged N(1) = 5; N(2) = 15 times; pulse repetition time = 130 ms). The results reveal that long T(2)(*) component of tissue sodium (mean +/- standard deviation) varied between cerebrospinal fluid (54 +/- 4 ms) and gray (28 +/- 2 ms) and white (29 +/- 2 ms) matter structures. The results also show that the long T(2)(*) component increases as a function of the main static field B(0), indicating that correlation time of sodium ion motion is smaller than the time-scale defined by the Larmor frequency. These results are a prerequisite for the quantification of tissue sodium concentration from (23)Na MRI scans with nonzero echo time, will contribute to the design of future measurements (such as triple-quantum imaging), and themselves may be of clinical utility.

Clinical applications of ultra-high field magnetic resonance imaging in multiple sclerosis.

INTRODUCTION: Magnetic resonance imaging (MRI) is of paramount importance for the early diagnosis of multiple sclerosis (MS) and MRI findings are part of the MS diagnostic criteria. There is a growing interest in the use of ultra-high-field strength -7 Tesla- (7T) MRI to investigate, in vivo, the pathological substrate of the disease. Areas covered: An overview of 7T MRI applications in MS focusing on increased sensitivity for lesion detection, specificity of the central vein sign and better understanding of MS pathophysiology. Implications for disease diagnosis, monitoring and treatment planning are discussed. Expert commentary: 7T MRI provides increased signal-to-noise and contrast-to-noise-ratio that allow higher spatial resolution and better detection of anatomical and pathological features. The high spatial resolution reachable at 7T has been a game changer for neuroimaging applications not only in MS but also in epilepsy, brain tumors, dementia, and neuro-psychiatric disorders. Furthermore, the first 7T device has recently been cleared for clinical use by the food and drug administration.

An MRI evaluation of grey matter damage in African Americans with MS.

OBJECTIVE: Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS. METHODS: In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs). RESULTS: In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs. INTERPRETATION: In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups.

Intraindividual comparison of MR-renal perfusion imaging at 1.5 T and 3.0 T.

PURPOSE: The purpose of this study was to intraindividually compare fast gradient-echo semiquantitative renal perfusion measurements at 1.5 Tesla (T) and 3.0 Tesla. MATERIALS AND METHODS: Fifteen healthy male volunteers underwent renal perfusion measurements at 1.5 T and 3.0 T after the bolus injection of 7 mL of Gd-BOPTA. At both field strengths a Saturation-Recovery-fast gradient echo sequence (SR-TurboFLASH) with a temporal resolution of 4 (1.5 T) and 5 (3.0 T) simultaneously acquired slices per second was used. At 3.0 T, a parallel-imaging factor 2 was applied. For postprocessing, semiquantitative perfusion parameters including mean transit time (MTT), time to peak (TTP), and maximal signal intensity (SMax) were determined. The signal-to-noise ratios (SNR) of kidneys and aorta were determined precontrast and after enhancement. The image quality was rated by 2 radiologists. After Bonferroni correction paired t-tests were performed for statistical analysis. RESULTS: All measurements were successfully performed. At 3.0 T, a significant 63% increase in the baseline SNR (P = 0.00005) of the kidneys was found, the peak SNR was also increased though not statistically significant. Because of the higher SNR, the SMax was also significantly (P = 0.005) increased from 406 A.U. to 522 A.U., whereas MTT and TTP were not significantly changed. The image quality was rated very good to good for the 3.0 T images but only good to moderate at 1.5 T. CONCLUSION: Renal perfusion measurements at 3.0 T are feasible and directly benefit from the inherently higher SNR at 3.0 T. The higher SNR also translates into an increased SMax, whereas MTT and TTP are independent of the field strength.

Dynamic magnetic resonance nephrography: is saturation recovery TrueFISP advantageous over saturation recovery TurboFLASH?

PURPOSE: In this volunteer study, 2 navigator-gated strongly T1-weighted saturation-recovery (SR) sequences, a turbo fast low angle shot (TurboFLASH) and a new true fast imaging in steady precession (TrueFISP) readout technique, were compared for suitability in dynamic magnetic resonance nephrography. MATERIALS AND METHODS: Ten healthy volunteers (mean age 26.1 +/- 3.6) were equally divided into 2 subgroups. After bolus-injection of 3.75 mL of gadobutrol (approximately 0.05 mmol/kg body weight), slightly obliqued coronal single-slice images of the kidneys were recorded every 4-5 seconds during free breathing using 1 of the 2 sequences. Time-intensity curves were determined from manually drawn regions-of-interest over the kidney parenchyma. Both sequences were subsequently evaluated with regard to linearity of signal, signal to noise ratio (SNR), and time-dependent behavior of signal intensity curves. RESULTS: : The TurboFLASH readout showed better linearity of the signal behavior as compared with the TrueFISP technique (TurboFLASH: no deviation from linearity down to T1 = 400 milliseconds; TrueFISP at T1 = 700 milliseconds: 12% deviation, at T1 = 400 milliseconds: 19%). The time-intensity curves of the TrueFISP sequence exhibited distinctly lower variability than the TurboFLASH approach. The SNR increased with TrueFISP by 3.4 +/- 0.5-fold for native renal parenchyma and by 3.3 +/- 0.9 for contrast-enhanced renal parenchyma. For split renal function evaluation, the linear regression to the signal increase in the first minutes after the first pass could be performed with higher reliability using the TrueFISP technique (increase of correlation coefficient by 17.1%). CONCLUSION: A SR navigator-gated TrueFISP sequence seems most favorable for dynamic magnetic resonance nephrography due to the high signal yield and low curve variability.

Semiquantitative assessment of first-pass renal perfusion at 1.5 T: comparison of 2D saturation recovery sequences with and without parallel imaging.

OBJECTIVE: The purpose of this study was to assess the feasibility and reliability of measurements performed with true fast imaging with steady-state free precession (FISP) and turbo fast low-angle shot (FLASH) sequences with parallel imaging compared with those obtained with turbo FLASH sequences without parallel imaging in first-pass renal perfusion MRI. SUBJECTS AND METHODS: The subjects in this prospective study were 15 healthy men who volunteered to undergo MRI for acquisition of renal perfusion measurements. Imaging was performed at 1.5 T with the following three techniques after administration of gadobenate dimeglumine at 4 mL/s: saturation recovery (SR) turbo FLASH sequences without parallel imaging, SR turbo FLASH sequences with parallel imaging, and SR true FISP sequences. The spatial resolution was 2.3 x 2.6 x 8 mm with a temporal resolution of four slices per second (turbo FLASH without parallel imaging and true FISP) or six slices per second (turbo FLASH with parallel imaging). The semiquantitative perfusion parameters mean transit time and maximal upslope were determined. Signal-to-noise ratio (SNR), delta ratio, and time to maximal signal intensity also were determined. Image quality was rated in consensus. RESULTS: Image quality was best for turbo FLASH sequences without parallel imaging compared with true FISP and turbo FLASH sequences with parallel imaging. True FISP sequences yielded the highest baseline SNR (26.7) but the lowest delta ratio (3.2). Turbo FLASH sequences without and with parallel imaging had significantly lower SNRs (9.6 and 9.3) and significantly higher delta ratios (5.1 and 5.0). The first-pass perfusion parameters mean transit time and time to maximal signal intensity were independent of the technique used. CONCLUSION: It seems that at 1.5 T, turbo FLASH sequences without parallel imaging are the best approach to renal first-pass perfusion imaging.

Renal plasma flow (RPF) measured with multiple-inversion-time arterial spin labeling (ASL) and tracer kinetic analysis: Validation against a dynamic contrast-enhancement method.

PURPOSE: To propose and validate a method for accurately quantifying renal plasma flow (RPF) with arterial spin labeling (ASL). MATERIALS AND METHODS: The proposed method employs a tracer-kinetic approach and derives perfusion from the slope of the ASL difference signal sampled at multiple inversion-times (TIs). To validate the method's accuracy, we performed a HIPAA-compliant and IRB-approved study with 15 subjects (9 male, 6 female; age range 24-73) to compare RPF estimates obtained from ASL to those from a more established dynamic contrast-enhanced (DCE) MRI method. We also investigated the impact of TI-sampling density on the accuracy of estimated RPF. RESULTS: Good agreement was found between ASL- and DCE-measured RPF, with a mean difference of 9±30ml/min and a correlation coefficient R=0.92 when ASL signals were acquired at 16 TIs and a mean difference of 9±57ml/min and R=0.81 when ASL signals were acquired at 5 TIs. RPF estimated from ASL signals acquired at only 2 TIs (400 and 1200ms) showed a low correlation with DCE-measured values (R=0.30). CONCLUSION: The proposed ASL method is capable of measuring RPF with an accuracy that is comparable to DCE MRI. At least 5 TIs are recommended for the ASL acquisition to ensure reliability of RPF measurements.

The relationship between cortical lesions and periventricular NAWM abnormalities suggests a shared mechanism of injury in primary-progressive MS.

In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging. To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Lastly, cortical lesions were assessed on phase-sensitive inversion recovery (PSIR) images and cortical thickness was quantified on volumetric T1 images. Our main result was the observation in the PPMS group of a significant correlation between periventricular NAWM MD values and cortical lesion load, with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation between cortical lesion load and deep NAWM MD values or periventricular WM lesions. Our data thus suggest that a common - and relatively selective - factor plays a role in the development of both cortical lesion and periventricular NAWM abnormalities in PPMS.

Attenuation Correction for Magnetic Resonance Coils in Combined PET/MR Imaging: A Review.

With the introduction of clinical PET/magnetic resonance (MR) systems, novel attenuation correction methods are needed, as there are no direct MR methods to measure the attenuation of the objects in the field of view (FOV). A unique challenge for PET/MR attenuation correction is that coils for MR data acquisition are located in the FOV of the PET camera and could induce significant quantitative errors. In this review, current methods and techniques to correct for the attenuation of a variety of coils are summarized and evaluated.

Optimization of yttrium-90 PET for simultaneous PET/MR imaging: A phantom study.

PURPOSE: Positron emission tomography (PET) imaging of yttrium-90 in the liver post radioembolization has been shown useful for personalized dosimetry calculations and evaluation of extrahepatic deposition. The purpose of this study was to quantify the benefits of several MR-based data correction approaches offered by using a combined PET/MR system to improve Y-90 PET imaging. In particular, the feasibility of motion and partial volume corrections were investigated in a controlled phantom study. METHODS: The ACR phantom was filled with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast of 10:1 between the hot cylinders and the background. Y-90 PET motion correction through motion estimates from MR navigators was evaluated by using a custom-built motion stage that simulated realistic amplitudes of respiration-induced liver motion. Finally, the feasibility of an MR-based partial volume correction method was evaluated using a wavelet decomposition approach. RESULTS: Motion resulted in a large (∼40%) loss of contrast recovery for the 8 mm cylinder in the phantom, but was corrected for after MR-based motion correction was applied. Partial volume correction improved contrast recovery by 13% for the 8 mm cylinder. CONCLUSIONS: MR-based data correction improves Y-90 PET imaging on simultaneous PET/MR systems. Assessment of these methods must be studied further in the clinical setting.