What contributes to disability in progressive MS? A brain and cervical cord-matched quantitative MRI study.

BACKGROUND: We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability. METHODS: A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord-matched protocol with brain-and-cord-unified imaging readouts. Lesion and NA-tissue volumes and qMRI metrics reflecting demyelination and axonal loss were obtained. Random forest analyses identified the most relevant volumetric/qMRI measures to clinical outcomes. Confounder-adjusted linear regression estimated the actual MRI-clinical associations. RESULTS: Several qMRI/volumetric differences between patients and controls were observed (p < 0.01). Higher NA-deep grey matter quantitative-T1 (EDSS: beta = 7.96, p = 0.006; 9HPT: beta = -0.09, p = 0.004), higher NA-white matter orientation dispersion index (TWT: beta = -3.21, p = 0.005; SDMT: beta = -847.10, p < 0.001), lower whole-cord bound pool fraction (9HPT: beta = 0.79, p = 0.001) and higher NA-cortical grey matter quantitative-T1 (SDMT = -94.31, p < 0.001) emerged as particularly relevant predictors of greater disability. CONCLUSION: Fast brain-and-cord-matched qMRI protocols are feasible and identify demyelination - combined with other mechanisms - as key for disability accumulation in PMS.

Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments.

BACKGROUND: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). PURPOSE: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. STUDY-TYPE: Longitudinal. POPULATION: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. FIELD STRENGTH/SEQUENCE: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. ASSESSMENT: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. STATISTICAL TESTS: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. RESULTS: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (ß = -0.21); in the riluzole arm, GM Glx (ß = -0.25) and Glx/tCr (ß = -0.29) were reduced. Baseline tNAA(ß = 0.22) and tNAA/tCr (ß = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. DATA CONCLUSION: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Generalized low-rank nonrigid motion-corrected reconstruction for MR fingerprinting.

PURPOSE: Develop a novel low-rank motion-corrected (LRMC) reconstruction for nonrigid motion-corrected MR fingerprinting (MRF). METHODS: Generalized motion-corrected (MC) reconstructions have been developed for steady-state imaging. Here we extend this framework to enable nonrigid MC for transient imaging applications with varying contrast, such as MRF. This is achieved by integrating low-rank dictionary-based compression into the generalized MC model to reconstruct MC singular images, reducing motion artifacts in the resulting parametric maps. The proposed LRMC reconstruction was applied for cardiac motion correction in 2D myocardial MRF (T1 and T2 ) with extended cardiac acquisition window (~450 ms) and for respiratory MC in free-breathing 3D myocardial and 3D liver MRF. Experiments were performed in phantom and 22 healthy subjects. The proposed approach was compared with reference spin echo (phantom) and with 2D electrocardiogram-triggered/breath-hold MOLLI and T2 gradient-and-spin echo conventional maps (in vivo 2D and 3D myocardial MRF). RESULTS: Phantom results were in general agreement with reference spin-echo measurements, presenting relative errors of approximately 5.4% and 5.5% for T1 and short T2 (<100 ms), respectively. The proposed LRMC MRF reduced residual blurring artifacts with respect to no MC for cardiac or respiratory motion in all cases (2D and 3D myocardial, 3D abdominal). In 2D myocardial MRF, left-ventricle T1 values were 1150 ± 41 ms for LRMC MRF and 1010 ± 56 ms for MOLLI; T2 values were 43.8 ± 2.3 ms for LRMC MRF and 49.5 ± 4.5 ms for T2 gradient and spin echo. Corresponding measurements for 3D myocardial MRF were 1085 ± 30 ms and 1062 ± 29 ms for T1 , and 43.5 ± 1.9 ms and 51.7 ± 1.7 ms for T2 . For 3D liver, LRMC MRF measured liver T1 at 565 ± 44 ms and liver T2 at 35.4 ± 2.4 ms. CONCLUSION: The proposed LRMC reconstruction enabled generalized (nonrigid) MC for 2D and 3D MRF, both for cardiac and respiratory motion. The proposed approach reduced motion artifacts in the MRF maps with respect to no motion compensation and achieved good agreement with reference measurements.

SENSE EPI reconstruction with 2D phase error correction and channel-wise noise removal.

PURPOSE: To develop a robust reconstruction pipeline for EPI data that enables 2D Nyquist phase error correction using sensitivity encoding without incurring major noise artifacts in low SNR data. METHODS: SENSE with 2D phase error correction (PEC-SENSE) was combined with channel-wise noise removal using Marcenko-Pastur principal component analysis (MPPCA) to simultaneously eliminate Nyquist ghost artifacts in EPI data and mitigate the noise amplification associated with phase correction using parallel imaging. The proposed pipeline (coined SPECTRE) was validated in phantom DW-EPI data using the accuracy and precision of diffusion metrics; ground truth values were obtained from data acquired with a spin echo readout. Results from the SPECTRE pipeline were compared against PEC-SENSE reconstructions with three alternate denoising strategies: (i) no denoising; (ii) denoising of magnitude data after image formation; (iii) denoising of complex data after image formation. SPECTRE was then tested using high b $$ b $$ -value (i.e., low SNR) diffusion data (up to b = 3000 $$ b=3000 $$ s/mm 2 $$ {}^2 $$ ) in four healthy subjects. RESULTS: Noise amplification associated with phase error correction incurred a 23% bias in phantom mean diffusivity (MD) measurements. Phantom MD estimates using the SPECTRE pipeline were within 8% of the ground truth value. In healthy volunteers, the SPECTRE pipeline visibly corrected Nyquist ghost artifacts and reduced associated noise amplification in high b $$ b $$ -value data. CONCLUSION: The proposed reconstruction pipeline is effective in correcting low SNR data, and improves the accuracy and precision of derived diffusion metrics.

An MR fingerprinting approach for quantitative inhomogeneous magnetization transfer imaging.

PURPOSE: Magnetization transfer (MT) and inhomogeneous MT (ihMT) contrasts are used in MRI to provide information about macromolecular tissue content. In particular, MT is sensitive to macromolecules, and ihMT appears to be specific to myelinated tissue. This study proposes a technique to characterize MT and ihMT properties from a single acquisition, producing both semiquantitative contrast ratios and quantitative parameter maps. THEORY AND METHODS: Building on previous work that uses multiband RF pulses to efficiently generate ihMT contrast, we propose a cyclic steady-state approach that cycles between multiband and single-band pulses to boost the achieved contrast. Resultant time-variable signals are reminiscent of an MR fingerprinting acquisition, except that the signal fluctuations are entirely mediated by MT effects. A dictionary-based low-rank inversion method is used to reconstruct the resulting images and to produce both semiquantitative MT ratio and ihMT ratio maps, as well as quantitative parameter estimates corresponding to an ihMT tissue model. RESULTS: Phantom and in vivo brain data acquired at 1.5 Tesla demonstrate the expected contrast trends, with ihMT ratio maps showing contrast more specific to white matter, as has been reported by others. Quantitative estimation of semisolid fraction and dipolar T1 was also possible and yielded measurements consistent with literature values in the brain. CONCLUSION: By cycling between multiband and single-band pulses, an entirely MT-mediated fingerprinting method was demonstrated. This proof-of-concept approach can be used to generate semiquantitative maps and quantitatively estimate some macromolecular-specific tissue parameters.

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter.

PURPOSE: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. METHODS: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open-access multicenter data set of the spinal cord MRI (N = 267 participants). RESULTS: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial-volume effects. CONCLUSION: We propose quality assessment criteria and metrics for gray-matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open-source code can serve as a benchmark for future optimization of spinal cord gray-matter imaging protocols.

Estimating central blood pressure from aortic flow: development and assessment of algorithms.

Central blood pressure (cBP) is a highly prognostic cardiovascular (CV) risk factor whose accurate, invasive assessment is costly and carries risks to patients. We developed and assessed novel algorithms for estimating cBP from noninvasive aortic hemodynamic data and a peripheral blood pressure measurement. These algorithms were created using three blood flow models: the two- and three-element Windkessel (0-D) models and a one-dimensional (1-D) model of the thoracic aorta. We tested new and existing methods for estimating CV parameters (left ventricular ejection time, outflow BP, arterial resistance and compliance, pulse wave velocity, and characteristic impedance) required for the cBP algorithms, using virtual (simulated) subjects (n = 19,646) for which reference CV parameters were known exactly. We then tested the cBP algorithms using virtual subjects (n = 4,064), for which reference cBP were available free of measurement error, and clinical datasets containing invasive (n = 10) and noninvasive (n = 171) reference cBP waves across a wide range of CV conditions. The 1-D algorithm outperformed the 0-D algorithms when the aortic vascular geometry was available, achieving central systolic blood pressure (cSBP) errors ≤ 2.1 ± 9.7 mmHg and root-mean-square errors (RMSEs) ≤ 6.4 ± 2.8 mmHg against invasive reference cBP waves (n = 10). When the aortic geometry was unavailable, the three-element 0-D algorithm achieved cSBP errors ≤ 6.0 ± 4.7 mmHg and RMSEs ≤ 5.9 ± 2.4 mmHg against noninvasive reference cBP waves (n = 171), outperforming the two-element 0-D algorithm. All CV parameters were estimated with mean percentage errors ≤ 8.2%, except for the aortic characteristic impedance (≤13.4%), which affected the three-element 0-D algorithm's performance. The freely available algorithms developed in this work enable fast and accurate calculation of the cBP wave and CV parameters in datasets containing noninvasive ultrasound or magnetic resonance imaging data.NEW & NOTEWORTHY First, our proposed methods for CV parameter estimation and a comprehensive set of methods from the literature were tested using in silico and clinical datasets. Second, optimized algorithms for estimating cBP from aortic flow were developed and tested for a wide range of cBP morphologies, including catheter cBP data. Third, a dataset of simulated cBP waves was created using a three-element Windkessel model. Fourth, the Windkessel model dataset and optimized algorithms are freely available.

T1, T2, and Fat Fraction Cardiac MR Fingerprinting: Preliminary Clinical Evaluation.

BACKGROUND: Dixon cardiac magnetic resonance fingerprinting (MRF) has been recently introduced to simultaneously provide water T1 , water T2 , and fat fraction (FF) maps. PURPOSE: To assess Dixon cardiac MRF repeatability in healthy subjects and its clinical feasibility in a cohort of patients with cardiovascular disease. POPULATION: T1MES phantom, water-fat phantom, 11 healthy subjects and 19 patients with suspected cardiovascular disease. STUDY TYPE: Prospective. FIELD STRENGTH/SEQUENCE: 1.5T, inversion recovery spin echo (IRSE), multiecho spin echo (MESE), modified Look-Locker inversion recovery (MOLLI), T2 gradient spin echo (T2 -GRASE), 6-echo gradient rewound echo (GRE), and Dixon cardiac MRF. ASSESSMENT: Dixon cardiac MRF precision was assessed through repeated scans against conventional MOLLI, T2 -GRASE, and PDFF in phantom and 11 healthy subjects. Dixon cardiac MRF native T1 , T2 , FF, postcontrast T1 and synthetic extracellular volume (ECV) maps were assessed in 19 patients in comparison to conventional sequences. Measurements in patients were performed in the septum and in late gadolinium enhanced (LGE) areas and assessed using mean value distributions, correlation, and Bland-Altman plots. Image quality and diagnostic confidence were assessed by three experts using 5-point scoring scales. STATISTICAL TESTS: Paired Wilcoxon rank signed test and paired t-tests were applied. Statistical significance was indicated by *(P < 0.05). RESULTS: Dixon cardiac MRF showed good overall precision in phantom and in vivo. Septal average repeatability was ~23 msec for T1 , ~2.2 msec for T2 , and ~1% for FF. Biases in healthy subjects/patients were measured at +37 msec*/+60 msec* and -8.8 msec*/-8 msec* when compared to MOLLI and T2 -GRASE, respectively. No statistically significant differences in postcontrast T1 (P = 0.17) and synthetic ECV (P = 0.19) measurements were observed in patients. DATA CONCLUSION: Dixon cardiac MRF attained good overall precision in phantom and healthy subjects, while providing coregistered T1 , T2 , and fat fraction maps in a single breath-hold scan with similar or better image quality than conventional methods in patients. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis.

BACKGROUND: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. OBJECTIVE: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. METHODS: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. RESULTS: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years. CONCLUSION: Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.

Influence of the arterial input sampling location on the diagnostic accuracy of cardiovascular magnetic resonance stress myocardial perfusion quantification.

BACKGROUND: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference. METHODS: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis. RESULTS: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717). CONCLUSIONS: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Multi-parametric quantitative in vivo spinal cord MRI with unified signal readout and image denoising.

Multi-parametric quantitative MRI (qMRI) of the spinal cord is a promising non-invasive tool to probe early microstructural damage in neurological disorders. It is usually performed in vivo by combining acquisitions with multiple signal readouts, which exhibit different thermal noise levels, geometrical distortions and susceptibility to physiological noise. This ultimately hinders joint multi-contrast modelling and makes the geometric correspondence of parametric maps challenging. We propose an approach to overcome these limitations, by implementing state-of-the-art microstructural MRI of the spinal cord with a unified signal readout in vivo (i.e. with matched spatial encoding parameters across a range of imaging contrasts). We base our acquisition on single-shot echo planar imaging with reduced field-of-view, and obtain data from two different vendors (vendor 1: Philips Achieva; vendor 2: Siemens Prisma). Importantly, the unified acquisition allows us to compare signal and noise across contrasts, thus enabling overall quality enhancement via multi-contrast image denoising methods. As a proof-of-concept, here we provide a demonstration with one such method, known as Marchenko-Pastur (MP) Principal Component Analysis (PCA) denoising. MP-PCA is a singular value (SV) decomposition truncation approach that relies on redundant acquisitions, i.e. such that the number of measurements is large compared to the number of components that are maintained in the truncated SV decomposition. Here we used in vivo and synthetic data to test whether a unified readout enables more efficient MP-PCA denoising of less redundant acquisitions, since these can be denoised jointly with more redundant ones. We demonstrate that a unified readout provides robust multi-parametric maps, including diffusion and kurtosis tensors from diffusion MRI, myelin metrics from two-pool magnetisation transfer, and T1 and T2 from relaxometry. Moreover, we show that MP-PCA improves the quality of our multi-contrast acquisitions, since it reduces the coefficient of variation (i.e. variability) by up to 17% for mean kurtosis, 8% for bound pool fraction (myelin-sensitive), and 13% for T1, while enabling more efficient denoising of modalities limited in redundancy (e.g. relaxometry). In conclusion, multi-parametric spinal cord qMRI with unified readout is feasible and provides robust microstructural metrics with matched resolution and distortions, whose quality benefits from multi-contrast denoising methods such as MP-PCA.

Whole-heart T1 mapping using a 2D fat image navigator for respiratory motion compensation.

PURPOSE: To combine a 3D saturation-recovery-based myocardial T1 mapping (3D SASHA) sequence with a 2D image navigator with fat excitation (fat-iNAV) to allow 3D T1 maps with 100% respiratory scan efficiency and predictable scan time. METHODS: Data from T1 phantom and 10 subjects were acquired at 1.5T. For respiratory motion compensation, a 2D fat-iNAV was acquired before each 3D SASHA k-space segment to correct for 2D translational motion in a beat-to-beat fashion. The effect of the fat-iNAV on the 3D SASHA T1 estimation was evaluated on the T1 phantom. For 3 representative subjects, the proposed free-breathing 3D SASHA with fat-iNAV was compared to the original implementation with the diaphragmatic navigator. The 3D SASHA with fat-iNAV was compared to the breath-hold 2D SASHA sequence in terms of accuracy and precision. RESULTS: In the phantom study, the Bland-Altman plot shows that the 2D fat-iNAVs does not affect the T1 quantification of the 3D SASHA acquisition (0 ± 12.5 ms). For the in vivo study, the 2D fat-iNAV permits to estimate the respiratory motion of the heart, while allowing for 100% scan efficiency, improving the precision of the T1 measurement compared to non-motion-corrected 3D SASHA. However, the image quality achieved with the proposed 3D SASHA with fat-iNAV is lower compared to the original implementation, with reduced delineation of the myocardial borders and papillary muscles. CONCLUSIONS: We demonstrate the feasibility to combine the 3D SASHA T1 mapping imaging sequence with a 2D fat-iNAV for respiratory motion compensation, allowing 100% respiratory scan efficiency and predictable scan time.

Pixel-wise assessment of cardiovascular magnetic resonance first-pass perfusion using a cardiac phantom mimicking transmural myocardial perfusion gradients.

PURPOSE: Cardiovascular magnetic resonance first-pass perfusion for the pixel-wise detection of coronary artery disease is rapidly becoming the clinical standard, yet no widely available method exists for its assessment and validation. This study introduces a novel phantom capable of generating spatially dependent flow values to enable assessment of new perfusion imaging methods at the pixel level. METHODS: A synthetic multicapillary myocardial phantom mimicking transmural myocardial perfusion gradients was designed and manufactured with high-precision 3D printing. The phantom was used in a stationary flow setup providing reference myocardial perfusion rates and was scanned on a 3T system. Repeated first-pass perfusion MRI for physiological perfusion rates between 1 and 4 mL/g/min was performed using a clinical dual-sequence technique. Fermi function-constrained deconvolution was used to estimate pixel-wise perfusion rate maps. Phase contrast (PC)-MRI was used to obtain velocity measurements that were converted to perfusion rates for validation of reference values and cross-method comparison. The accuracy of pixel-wise maps was assessed against simulated reference maps. RESULTS: PC-MRI indicated excellent reproducibility in perfusion rate (coefficient of variation [CoV] 2.4-3.5%) and correlation with reference values (R2 = 0.985) across the full physiological range. Similar results were found for first-pass perfusion MRI (CoV 3.7-6.2%, R2 = 0.987). Pixel-wise maps indicated a transmural perfusion difference of 28.8-33.7% for PC-MRI and 23.8-37.7% for first-pass perfusion, matching the reference values (30.2-31.4%). CONCLUSION: The unique transmural perfusion pattern in the phantom allows effective pixel-wise assessment of first-pass perfusion acquisition protocols and quantification algorithms before their introduction into routine clinical use.

Water-fat Dixon cardiac magnetic resonance fingerprinting.

PURPOSE: Cardiac magnetic resonance fingerprinting (cMRF) has been recently introduced to simultaneously provide T1 , T2 , and M0 maps. Here, we develop a 3-point Dixon-cMRF approach to enable simultaneous water specific T1 , T2 , and M0 mapping of the heart and fat fraction (FF) estimation in a single breath-hold scan. METHODS: Dixon-cMRF is achieved by combining cMRF with several innovations that were previously introduced for other applications, including a 3-echo GRE acquisition with golden angle radial readout and a high-dimensional low-rank tensor constrained reconstruction to recover the highly undersampled time series images for each echo. Water-fat separation of the Dixon-cMRF time series is performed to allow for water- and fat-specific T1 , T2 , and M0 estimation, whereas FF estimation is extracted from the M0 maps. Dixon-cMRF was evaluated in a standardized T1 -T2 phantom, in a water-fat phantom, and in healthy subjects in comparison to current clinical standards: MOLLI, SASHA, T2 -GRASE, and 6-point Dixon proton density FF (PDFF) mapping. RESULTS: Dixon-cMRF water T1 and T2 maps showed good agreement with reference T1 and T2 mapping techniques (R2 > 0.99 and maximum normalized RMSE ~5%) in a standardized phantom. Good agreement was also observed between Dixon-cMRF FF and reference PDFF (R2 > 0.99) and between Dixon-cMRF water T1 and T2 and water selective T1 and T2 maps (R2 > 0.99) in a water-fat phantom. In vivo Dixon-cMRF water T1 values were in good agreement with MOLLI and water T2 values were slightly underestimated when compared to T2 -GRASE. Average myocardium septal T1 values were 1129 ± 38 ms, 1026 ± 28 ms, and 1045 ± 32 ms for SASHA, MOLLI, and the proposed water Dixon-cMRF. Average T2 values were 51.7 ± 2.2 ms and 42.8 ± 2.6 ms for T2 -GRASE and water Dixon-cMRF, respectively. Dixon-cMRF FF maps showed good agreement with in vivo PDFF measurements (R2 > 0.98) and average FF in the septum was measured at 1.3%. CONCLUSION: The proposed Dixon-cMRF allows to simultaneously quantify myocardial water T1 , water T2 , and FF in a single breath-hold scan, enabling multi-parametric T1 , T2 , and fat characterization. Moreover, reduced T1 and T2 quantification bias caused by water-fat partial volume was demonstrated in phantom experiments.

Multi-parametric liver tissue characterization using MR fingerprinting: Simultaneous T1 , T2 , T2 *, and fat fraction mapping.

PURPOSE: Quantitative T1 , T2 , T2 *, and fat fraction (FF) maps are promising imaging biomarkers for the assessment of liver disease, however these are usually acquired in sequential scans. Here we propose an extended MR fingerprinting (MRF) framework enabling simultaneous liver T1 , T2 , T2 *, and FF mapping from a single ~14 s breath-hold scan. METHODS: A gradient echo (GRE) liver MRF sequence with nine readouts per TR, low flip angles (5-15°), varying magnetisation preparation and golden angle radial trajectory is acquired at 1.5T to encode T1 , T2 , T2 *, and FF simultaneously. The nine-echo time-series are reconstructed using a low-rank tensor constrained reconstruction and used to fit T2 *, B0 and to separate the water and fat signals. Water- and fat-specific T1 , T2, and M0 are obtained through dictionary matching, whereas FF estimation is extracted from the M0 maps. The framework was evaluated in a standardized T1 /T2 phantom, a water-fat phantom, and 12 subjects in comparison to reference methods. Preliminary clinical feasibility is shown in four patients. RESULTS: The proposed water T1 , water T2 , T2 *, and FF maps in phantoms showed high coefficients of determination (r2 > 0.97) relative to reference methods. Measured liver MRF values in vivo (mean ± SD) for T1 , T2 , T2 *, and FF were 671 ± 60 ms, 43.2 ± 6.8 ms, 29 ± 6.6 ms, and 3.2 ± 2.6% with biases of 92 ms, -7.1 ms, -1.4 ms, and 0.63% when compared to conventional methods. CONCLUSION: A nine-echo liver MRF sequence allows for quantitative multi-parametric liver tissue characterization in a single breath-hold scan of ~14 s. Future work will aim to validate the proposed approach in patients with liver disease.

Translating pH-sensitive PROgressive saturation for QUantifying Exchange rates using Saturation Times (PRO-QUEST) MRI to a 3T clinical scanner.

PURPOSE: To translate the recently developed PRO-QUEST (Progressive saturation for quantifying exchange rates using saturation times) sequence from preclinical 9.4T to 3T clinical magnetic field strength. METHODS: Numerical simulations were performed to define the optimal saturation flip angles for PRO-QUEST saturation pulses at 3T and demonstrate the effect of a ∆T2 error on the exchange rate (kex ) estimation at various field strengths. Exchange-dependent relaxation rate (Rex ) was measured for glutamate solutions in various pH, healthy volunteers and patients with multiple sclerosis (MS). Additionally, concentration-independent ratiometric Rex maps were produced to evaluate regional signal variations across the brain of human volunteers. RESULTS: The calculated Rex significantly correlates with pH in glutamate samples, however, kex values are underestimated as compared to those previously obtained at 9.4T. In the ratiometric Rex map of healthy volunteers, no significant differences are found between grey matter, white matter, and basal ganglia. In patients with MS, white matter lesions are visible in single saturation power Rex maps whereas only a periventricular lesion is apparent in the ratiometric Rex map. CONCLUSION: We demonstrate that quantification of pH sensitive indices using PRO-QUEST is feasible at 3T within clinically acceptable acquisition times. Our initial findings in patients with MS show that pH sensitive indices varied with the type of lesion examined whereas no significant difference was found in healthy volunteers between tissue types, suggesting that it would be worthwhile to apply PRO-QUEST in a larger cohort of patients to better understand its distinct imaging features relative to conventional techniques.

3D free-breathing cardiac magnetic resonance fingerprinting.

PURPOSE: To develop a novel respiratory motion compensated three-dimensional (3D) cardiac magnetic resonance fingerprinting (cMRF) approach for whole-heart myocardial T1 and T2 mapping from a free-breathing scan. METHODS: Two-dimensional (2D) cMRF has been recently proposed for simultaneous, co-registered T1 and T2 mapping from a breath-hold scan; however, coverage is limited. Here we propose a novel respiratory motion compensated 3D cMRF approach for whole-heart myocardial T1 and T2 tissue characterization from a free-breathing scan. Variable inversion recovery and T2 preparation modules are used for parametric encoding, respiratory bellows driven localized autofocus is proposed for beat-to-beat translation motion correction and a subspace regularized reconstruction is employed to accelerate the scan. The proposed 3D cMRF approach was evaluated in a standardized T1 /T2 phantom in comparison with reference spin echo values and in 10 healthy subjects in comparison with standard 2D MOLLI, SASHA and T2 -GraSE mapping techniques at 1.5 T. RESULTS: 3D cMRF T1 and T2 measurements were generally in good agreement with reference spin echo values in the phantom experiments, with relative errors of 2.9% and 3.8% for T1 and T2 (T2 < 100 ms), respectively. in vivo left ventricle (LV) myocardial T1 values were 1054 ± 19 ms for MOLLI, 1146 ± 20 ms for SASHA and 1093 ± 24 ms for the proposed 3D cMRF; corresponding T2 values were 51.8 ± 1.6 ms for T2-GraSE and 44.6 ± 2.0 ms for 3D cMRF. LV coefficients of variation were 7.6 ± 1.6% for MOLLI, 12.1 ± 2.7% for SASHA and 5.8 ± 0.8% for 3D cMRF T1 , and 10.5 ± 1.4% for T2-GraSE and 11.7 ± 1.6% for 3D cMRF T2 . CONCLUSION: The proposed 3D cMRF can provide whole-heart, simultaneous and co-registered T1 and T2 maps with accuracy and precision comparable to those of clinical standards in a single free-breathing scan of about 7 min.

Reduced neurite density in the brain and cervical spinal cord in relapsing-remitting multiple sclerosis: A NODDI study.

BACKGROUND: Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI). OBJECTIVE: The aim of this study was to investigate possible alterations, and their clinical relevance, in neurite morphology along the brain and cervical spinal cord of relapsing-remitting MS (RRMS) patients. METHODS: In total, 28 RRMS patients and 20 healthy controls (HCs) underwent brain and spinal cord NODDI at 3T. Physical and cognitive disability was assessed. Individual maps of orientation dispersion index (ODI) and neurite density index (NDI) in brain and spinal cord were obtained. We examined differences in NODDI measures between groups and the relationships between NODDI metrics and clinical scores using linear regression models adjusted for age, sex and brain tissue volumes or cord cross-sectional area (CSA). RESULTS: Patients showed lower NDI in the brain normal-appearing white matter (WM) and spinal cord WM than HCs. In patients, a lower NDI in the spinal cord WM was associated with higher disability. CONCLUSION: Reduced neurite density occurs in the neuraxis but, especially when affecting the spinal cord, it may represent a mechanism of disability in MS.

Rigid motion-corrected magnetic resonance fingerprinting.

PURPOSE: Develop a method for rigid body motion-corrected magnetic resonance fingerprinting (MRF). METHODS: MRF has shown some robustness to abrupt motion toward the end of the acquisition. Here, we study the effects of different types of rigid body motion during the acquisition on MRF and propose a novel approach to correct for this motion. The proposed method (MC-MRF) follows 4 steps: (1) sliding window reconstruction is performed to produce high-quality auxiliary dynamic images; (2) rotation and translation motion is estimated from the dynamic images by image registration; (3) estimated motion is used to correct acquired k-space data with corresponding rotations and phase shifts; and (4) motion-corrected data are reconstructed with low-rank inversion. MC-MRF was validated in a standard T1 /T2 phantom and 2D in vivo brain acquisitions in 7 healthy subjects. Additionally, the effect of through-plane motion in 2D MC-MRF was investigated. RESULTS: Simulation results show that motion in MRF can introduce artifacts in T1 and T2 maps, depending when it occurs. MC-MRF improved parametric map quality in all phantom and in vivo experiments with in-plane motion, comparable to the no-motion ground truth. Reduced parametric map quality, even after motion correction, was observed for acquisitions with through-plane motion, particularly for smaller structures in T2 maps. CONCLUSION: Here, a novel method for motion correction in MRF (MC-MRF) is proposed, which improves parametric map quality and accuracy in comparison to no-motion correction approaches. Future work will include validation of 3D MC-MRF to enable also through-plane motion correction.

Sparsity and locally low rank regularization for MR fingerprinting.

PURPOSE: Develop a sparse and locally low rank (LLR) regularized reconstruction to accelerate MR fingerprinting (MRF). METHODS: Recent works have introduced low rank reconstructions to MRF, based on temporal compression operators learned from the MRF dictionary. In other MR applications, LLR regularization has been introduced to exploit temporal redundancy in local regions of the image. Here, we propose to include spatial sparsity and LLR regularization terms in the MRF reconstruction. This approach, so called SLLR-MRF, further reduces aliasing in the time-point images and enables higher acceleration factors. The proposed approach was evaluated in simulations, T1 /T2 phantom acquisition, and in vivo brain acquisitions in 5 healthy subjects with different undersampling factors. Acceleration was also used in vivo to enable acquisitions with higher in-plane spatial resolution in comparable scan time. RESULTS: Simulations, phantom, and in vivo results show that low rank MRF reconstructions with high acceleration factors (<875 time-point images, 1 radial spoke per time-point) have residual aliasing artifacts that propagate into the parametric maps. The artifacts are reduced with the proposed SLLR-MRF resulting in considerable improvements in precision, without changes in accuracy. In vivo results show improved parametric maps for the proposed SLLR-MRF, potentially enabling MRF acquisitions with 1 radial spoke per time-point in approximately 2.6 s (~600 time-point images) for 2 × 2 mm and 9.6 s (1750 time-point images) for 1 × 1 mm in-plane resolution. CONCLUSION: The proposed SLLR-MRF reconstruction further improves parametric map quality compared with low rank MRF, enabling shorter scan times and/or increased spatial resolution.