Comparison of Myocardial Blood Flow Quantification Models for Double ECG Gating Arterial Spin Labeling MRI: Reproducibility Assessment.

BACKGROUND: Arterial spin labeling (ASL) allows non-invasive quantification of myocardial blood flow (MBF). Double-ECG gating (DG) ASL is more robust to heart rate variability than single-ECG gating (SG), but its reproducibility requires further investigation. Moreover, the existence of multiple quantification models hinders its application. Frequency-offset-corrected-inversion (FOCI) pulses provide sharper edge profiles than hyperbolic-secant (HS), which could benefit myocardial ASL. PURPOSE: To assess the performance of MBF quantification models for DG compared to SG ASL, to evaluate their reproducibility and to compare the effects of HS and FOCI pulses. STUDY TYPE: Prospective. SUBJECTS: Sixteen subjects (27 ± 8 years). FIELD STRENGTH/SEQUENCE: 1.5 T/DG and SG flow-sensitive alternating inversion recovery ASL. ASSESSMENT: Three models for DG MBF quantification were compared using Monte Carlo simulations and in vivo experiments. Two models used a fitting approach (one using only a single label and control image pair per fit, the other using all available image pairs), while the third model used a T1 correction approach. Slice profile simulations were conducted for HS and FOCI pulses with varying B0 and B1. Temporal signal-to-noise ratio (tSNR) was computed for different acquisition/quantification strategies and inversion pulses. The number of images that minimized MBF error was investigated in the model with highest tSNR. Intra and intersession reproducibility were assessed in 10 subjects. STATISTICAL TESTS: Within-subject coefficient of variation, analysis of variance. P-value <0.05 was considered significant. RESULTS: MBF was not different across acquisition/quantification strategies (P = 0.27) nor pulses (P = 0.9). DG MBF quantification models exhibited significantly higher tSNR and superior reproducibility, particularly for the fitting model using multiple images (tSNR was 3.46 ± 2.18 in vivo and 3.32 ± 1.16 in simulations, respectively; wsCV = 16%). Reducing the number of ASL pairs to 13/15 did not increase MBF error (minimum = 0.22 mL/g/min). DATA CONCLUSION: Reproducibility of MBF was better for DG than SG acquisitions, especially when employing a fitting model. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Diagnostic and Prognostic Potential of Multiparametric Renal MRI in Kidney Transplant Patients.

BACKGROUND: Multiparametric MRI provides assessment of functional and structural parameters in kidney allografts. It offers a non-invasive alternative to the current reference standard of kidney biopsy. PURPOSE: To evaluate the diagnostic and prognostic utility of MRI parameters in the assessment of allograft function in the first 3-months post-transplantation. STUDY TYPE: Prospective. SUBJECTS: 32 transplant recipients (54 ± 17 years, 20 females), divided into two groups according to estimated glomerular filtration rate (eGFR) at 3-months post-transplantation: inferior graft function (IGF; eGFR<45 mL/min/1.73 m2 , n = 10) and superior graft function (SGF; eGFR ≥ 45 mL/min/1.73 m2 , n = 22). Further categorization was based on the need for hemodialysis (C1) and decrease in s-creatinine (C2) at 1-week post-transplantation: delayed-graft-function (DGF: n = 4 C1, n = 10 C2) and early graft-function (EGF: n = 28 C1, n = 22 C2). FIELD STRENGTH/SEQUENCE: 3-T, pseudo-continuous arterial spin labeling, T1-mapping, and diffusion-weighted imaging. ASSESSMENT: Multiparametric MRI was evaluated at 1-week in all patients and 3-months after transplantation in 28 patients. Renal blood flow (RBF), diffusion coefficients (ADC, ΔADC, D, ∆ $$ \Delta $$ D, D*, flowing fraction f), T1 and ∆ $$ \Delta $$ T1 were calculated in cortex and medulla. The diagnostic and prognostic value of these parameters, obtained at 3-months and 1-week post-transplantation, respectively, was evaluated in the cortex to discriminate between DGF and EGF, and between SGF and IGF. STATISTICAL TESTS: Logistic regression, receiver-operating-characteristics, area-under-the-curve (AUC), confidence intervals (CIs), analysis-of-variance, t-test, Wilcoxon-Mann-Whitney test, Fisher's exact test, Pearson's correlation. P-value<0.05 was considered significant. RESULTS: DGF patients exhibited significantly lower cortical RBF and f and higher D*. The diagnostic value of MRI for detecting DGF was excellent (AUC = 100%). Significant differences between patients with IGF and SGF were found in RBF, ∆T1 , and ∆D. Multiparametric MRI showed higher diagnostic (AUC = 95.32%; CI: 88%-100%) and prognostic (AUC = 97.47%, CI: 92%-100%) values for detecting IGF than eGFR (AUC = 89.50%, CI: 79%-100%). DATA CONCLUSION: Multiparametric MRI may show high diagnostic and prognostic value in transplanted patients, yielding better results compared to eGFR measurements. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Multiparametric renal magnetic resonance imaging: A reproducibility study in renal allografts with stable function.

Monitoring renal allograft function after transplantation is key for the early detection of allograft impairment, which in turn can contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising noninvasive technique to assess and characterize renal physiopathology; however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period). The purposes of the current study were to evaluate the reproducibility of mpMRI in transplant patients and to characterize normal values of the measured parameters, and to estimate the labeling efficiency of Pseudo-Continuous Arterial Spin Labeling (PCASL) in the infrarenal aorta using numerical simulations considering experimental measurements of aortic blood flow profiles. The subjects were 20 transplant patients with stable kidney function, maintained over 1 year. The MRI protocol consisted of PCASL, intravoxel incoherent motion, and T1 inversion recovery. Phase contrast was used to measure aortic blood flow. Renal blood flow (RBF), diffusion coefficient (D), pseudo-diffusion coefficient (D*), flowing fraction ( f ), and T1 maps were calculated and mean values were measured in the cortex and medulla. The labeling efficiency of PCASL was estimated from simulation of Bloch equations. Reproducibility was assessed with the within-subject coefficient of variation, intraclass correlation coefficient, and Bland-Altman analysis. Correlations were evaluated using the Pearson correlation coefficient. The significance level was p less than 0.05. Cortical reproducibility was very good for T1, D, and RBF, moderate for f , and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r = 0.66), RBF and eGFR (r = 0.64), and D* and eGFR (r = -0.57) were found. Normal values of the measured parameters employing the mpMRI protocol in kidney transplant patients with stable function were characterized and the results showed good reproducibility of the techniques.

Clinical utility of intraoperative arterial spin labeling for resection control in brain tumor surgery at 3 T.

Resection control in brain tumor surgery can be achieved in real time with intraoperative MRI (iMRI). Arterial spin labeling (ASL), a technique that measures cerebral blood flow (CBF) non-invasively without the use of intravenous contrast agents, can be performed intraoperatively, providing morpho-physiological information. This study aimed to evaluate the feasibility, image quality and potential to depict residual tumor of a pseudo-continuous ASL (PCASL) sequence at 3 T. Seventeen patients with brain tumors, primary (16) or metastatic (1), undergoing resection surgery with iMRI monitoring, were prospectively recruited (nine men, age 56 ± 16.6 years). A PCASL sequence with long labeling duration (3000 ms) and postlabeling delay (2000 ms) was added to the conventional protocol, which consisted of pre- and postcontrast 3D T1 -weighted (T1w) images, optional 3D-FLAIR, and diffusion. Three observers independently assessed the image quality (four-point scale) of PCASL-derived CBF maps. In those with diagnostic quality (Scores 2-4) they evaluated the presence of residual tumor using the conventional sequences first, and the CBF maps afterwards (three-point scale). Inter-observer agreement for image quality and the presence of residual tumor was assessed using Fleiss kappa statistics. The intraoperative CBF ratio of the surgical margins (i.e., perilesional CBF values normalized to contralateral gray matter CBF) was compared with preoperative CBF ratio within the tumor (Wilcoxon's test). Diagnostic ASL image quality was observed in 94.1% of patients (interobserver Fleiss κ = 0.76). PCASL showed additional foci suggestive of high-grade residual component in three patients, and a hyperperfused area extending outside the enhancing component in one patient. Interobserver agreement was almost perfect in the evaluation of residual tumor with the conventional sequences (Fleiss κ = 0.92) and substantial for PCASL (Fleiss κ = 0.80). No significant differences were found between pre and intraoperative CBF ratios (p = 0.578) in patients with residual tumor (n = 7). iMRI-PCASL perfusion is feasible at 3 T and is useful for the intraoperative assessment of residual tumor, providing in some cases additional information to the conventional sequences.

Assessment of Splenic Switch-Off With Arterial Spin Labeling in Adenosine Perfusion Cardiac MRI.

BACKGROUND: In patients with suspected coronary artery disease (CAD), myocardial perfusion is assessed under rest and pharmacological stress to identify ischemia. Splenic switch-off, defined as the stress to rest splenic perfusion attenuation in response to adenosine, has been proposed as an indicator of stress adequacy. Its occurrence has been previously assessed in first-pass perfusion images, but the use of noncontrast techniques would be highly beneficial. PURPOSE: To explore the ability of pseudo-continuous arterial spin labeling (PCASL) to identify splenic switch-off in patients with suspected CAD. STUDY TYPE: Prospective. POPULATION: Five healthy volunteers (age 24.8 ± 3.8 years) and 32 patients (age 66.4 ± 8.2 years) with suspected CAD. FIELD STRENGTH/SEQUENCE: A 1.5-T/PCASL (spin-echo) and first-pass imaging (gradient-echo). ASSESSMENT: In healthy subjects, multi-delay PCASL data (500-2000 msec) were acquired to quantify splenic blood flow (SBF) and determine the adequate postlabeling delay (PLD) for single-delay acquisitions (PLD > arterial transit time). In patients, single-delay PCASL (1200 msec) and first-pass perfusion images were acquired under rest and adenosine conditions. PCASL data were used to compute SBF maps and SBF stress-to-rest ratios. Three observers classified patients into "switch-off" and "failed switch-off" groups by visually comparing rest-stress perfusion data acquired with PCASL and first-pass, independently. First-pass categories were used as reference to evaluate the accuracy of quantitative classification. STATISTICAL TESTS: Wilcoxon signed-rank, Pearson correlation, kappa, percentage agreement, Generalized Linear Mixed Model, Mann-Whitney, Pearson Chi-squared, receiver operating characteristic, area-under-the-curve (AUC) and confusion matrix. SIGNIFICANCE: P value < 0.05. RESULTS: A total of 27 patients (84.4%) experienced splenic switch-off according to first-pass categories. Comparison of PCASL-derived SBF maps during stress and rest allowed assessment of splenic switch-off, reflected in a reduction of SBF values during stress. SBF stress-to-rest ratios showed a 97% accuracy (sensitivity = 80%, specificity = 100%, AUC = 85.2%). DATA CONCLUSION: This study could demonstrate the feasibility of PCASL to identify splenic switch-off during adenosine perfusion MRI, both by qualitative and quantitative assessments. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: 2.

Reduction of motion effects in myocardial arterial spin labeling.

PURPOSE: To evaluate the accuracy and reproducibility of myocardial blood flow measurements obtained under different breathing strategies and motion correction techniques with arterial spin labeling. METHODS: A prospective cardiac arterial spin labeling study was performed in 12 volunteers at 3 Tesla. Perfusion images were acquired twice under breath-hold, synchronized-breathing, and free-breathing. Motion detection based on the temporal intensity variation of a myocardial voxel, as well as image registration based on pairwise and groupwise approaches, were applied and evaluated in synthetic and in vivo data. A region of interest was drawn over the mean perfusion-weighted image for quantification. Original breath-hold datasets, analyzed with individual regions of interest for each perfusion-weighted image, were considered as reference values. RESULTS: Perfusion measurements in the reference breath-hold datasets were in line with those reported in literature. In original datasets, prior to motion correction, myocardial blood flow quantification was significantly overestimated due to contamination of the myocardial perfusion with the high intensity signal of blood pool. These effects were minimized with motion detection or registration. Synthetic data showed that accuracy of the perfusion measurements was higher with the use of registration, in particular after the pairwise approach, which probed to be more robust to motion. CONCLUSION: Satisfactory results were obtained for the free-breathing strategy after pairwise registration, with higher accuracy and robustness (in synthetic datasets) and higher intrasession reproducibility together with lower myocardial blood flow variability across subjects (in in vivo datasets). Breath-hold and synchronized-breathing after motion correction provided similar results, but these breathing strategies can be difficult to perform by patients.

Optimization of pseudo-continuous arterial spin labeling for renal perfusion imaging.

PURPOSE: To evaluate labeling efficiency of pseudo-continuous arterial spin labeling (PCASL) and to find the gradient parameters that increase PCASL robustness for renal perfusion measurements. METHODS: Aortic blood flow was characterized in 3 groups: young healthy volunteers (YHV1), chronic kidney disease (CKD) patients (CKDP), and healthy controls (HCO). PCASL inversion efficiency was evaluated through numeric simulations considering the measured pulsatile flow velocity profiles and off-resonance effects for a wide range of gradient parameters, and the results were assessed in vivo. The most robust PCASL implementation was used to measure renal blood flow (RBF) in CKDP and HCO. RESULTS: Aortic blood velocities reached peak values of 120 cm/s in YHV1, whereas for elderly subjects values were lower by approximately a factor of 2. Simulations and experiments showed that by reducing the gradient average (Gave ) and the selective to average gradient ratio (Gmax /Gave ), labeling efficiency was maximized and PCASL robustness to off-resonance was improved. The study in CKDP and HCO showed significant differences in RBF between groups. CONCLUSION: An efficient and robust PCASL scheme for renal applications requires a Gmax /Gave ratio of 6-7 and a Gave value that depends on the aortic blood flow velocities (0.5 mT/m being appropriate for CKDP and HCO).

Quantification of Myocardial Perfusion With Vasodilation Using Arterial Spin Labeling at 1.5T.

BACKGROUND: Myocardial perfusion is evaluated in first-pass MRI using a gadolinium-based contrast agent, which limits its repeatability and restricts its use in patients with abnormal kidney function. Arterial spin labeling (ASL) is a promising technique for measuring myocardial perfusion without contrast injection. The ratio of stress to rest perfusion, termed myocardial perfusion reserve (MPR), is an indicator of the severity of stenosis in patients with coronary artery disease (CAD). PURPOSE: To quantify perfusion increases with pharmacological vasodilation, explore MPR differences between segments with and without perfusion defects, and examine the correlations between quantitative ASL and semiquantitative first-pass measurements. STUDY TYPE: Prospective. SUBJECTS: Sixteen patients with suspected CAD: 10 classified as "healthy," having normal perfusion on first-pass and no enhancement on late gadolinium enhancement (LGE), and six as "nonhealthy," having hypoperfused segments including ischemic and infarcted. FIELD STRENGTH/SEQUENCE: Flow-sensitive alternating inversion recovery (FAIR) rest-stress cardiac ASL with balanced steady-state free precession (bSSFP), rest-stress first-pass imaging using gradient-echo and LGE using a phase-sensitive inversion-recovery bSSFP at 1.5T. ASSESSMENT: For healthy subjects, rest-stress perfusion data were compared in global, coronary artery territory, and segment regions of interest (ROIs). A segmental MPR comparison was performed between normal segments from healthy subjects and abnormal segments from nonhealthy subjects. Correlations between ASL and first-pass parameters were explored. STATISTICAL TESTS: Wilcoxon-signed-rank test, nonparametric factorial analysis of variance (ANOVA), and Pearson's/Spearman's correlations. RESULTS: Perfusion increases were significant globally (P = 0.005), per coronary artery territory (P = 0.015), and per segment (P = 0.03 for all segments in ASL and first-pass, except anteroseptal in ASL P = 0.04). MPR differences between normal and abnormal segments were significant (P = 0.0028: ASL, P = 0.033: first-pass). ASL and first-pass measurements were correlated (MPR: r = 0.64, P = 0.008 and perfusion: rho = 0.47, P = 0.007). DATA CONCLUSION: This study demonstrates the feasibility of ASL to detect hyperemia, the potential to differentiate segments with and without perfusion defects, and significant correlations between ASL and semiquantitative first-pass. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Optimal repetition time for free breathing myocardial arterial spin labeling.

The aim of this study was to improve the scan efficiency of ASL in the myocardium. Free breathing FAIR-ASL scans with different TRs were compared, while keeping the acquisition time constant. Scans were named by the trigger pulse that started each acquisition: every two (TP1), four (TP2) and six (TP3) cardiac cycles. TP2 offered the best alternative with a coefficient of variation of 17.15% intrasession and 36.85% intersession. Mean MBF increased by 0.22 ± 0.41 ml/g/min with mild stress.

Arterial spin labeling (ASL) offers a noninvasive and repeatable measurement of tissue blood flow, but its application in the human heart is still challenging. The aim of this study was to improve the scan efficiency of flow-sensitive alternating inversion recovery (FAIR) ASL using a single inversion time. First, by evaluating a free breathing acquisition without navigators. Second, by shortening TR to acquire more ASL pairs. A FAIR ASL with balanced steady state free precession (bSSFP) readout was implemented at 3 T and tested in 14 healthy volunteers. Three cardiac-triggered ASL scans with different TRs were compared while maintaining a constant acquisition time. These scans were named by the trigger pulse (TP) that started each acquisition: every two (TP1), four (TP2) and six (TP3) cardiac cycles. Two studies were performed on different days to assess the reproducibility of TP2 and TP3 scans. Perfusion response during passive leg raising was also evaluated. Student t-test and nonparametric equivalent were computed for perfusion differences. Bland-Altman and coefficient of variation (CV) were calculated for the reproducibility assessment. Mean myocardial blood flow (MBF) values measured at rest were: 1.47 ± 0.91 ml/g/min (TP1), 1.95 ± 0.93 ml/g/min (TP2) and 1.94 ± 1.41 ml/g/min (TP3). Intrasession CV was 17.15% (TP2) and 24.17% (TP3) and intersession CV was 36.86% (TP2) and 18.38% (TP3). Mean MBF was found to increase with passive stress by 0.22 ± 0.41 ml/g/min for TP2 (P = 0.037). Mean MBF values were consistent with the literature, although in the high end of the normal range. The lower MBF values measured in TP1 scans are attributable to saturation of blood outside the slice because of shorter TR. Free breathing FAIR cardiac ASL without navigators is feasible. A TR of approximately four seconds (TP2) offers the best alternative with similar mean ASL and tSNR than longer TR acquisitions.

Assessment of uterine artery geometry and hemodynamics in human pregnancy with 4d flow mri and its correlation with doppler ultrasound.

BACKGROUND: Uterine artery (UtA) hemodynamics might be used to predict risk of hypertensive pregnancy disorders, including preeclampsia and intrauterine growth restriction. PURPOSE OR HYPOTHESIS: To determine the feasibility of 4D flow MRI in pregnant subjects by characterizing UtA anatomy, computing UtA flow, and comparing UtA velocity, and pulsatility and resistivity indices (PI, RI) with transabdominal Doppler ultrasound (US). STUDY TYPE: Prospective cross-sectional study from June 6, 2016, to May 2, 2018. POPULATION OR SUBJECTS OR PHANTOM OR SPECIMEN OR ANIMAL MODEL: Forty-one singleton pregnant subjects (age [range] = 27.0 ± 5.9 [18-41] years) in their second or third trimester. We additionally scanned three subjects who had prepregnancy diabetes or chronic hypertension. FIELD STRENGTH/SEQUENCE: The subjects underwent UtA and placenta MRI using noncontrast angiography and 4D flow at 1.5T. ASSESSMENT: UtA anatomy was described based on 4D flow-derived noncontrast angiography, while UtA flow properties were characterized by net flow, systolic/mean/diastolic velocity, PI and RI through examination of 4D flow data. PI and RI are standard hemodynamic parameters routinely reported on Doppler US. STATISTICAL TESTS: Spearman's rank correlation, Wilcoxon signed rank tests, and Bland-Altman plots were used to preliminarily investigate the relationships between flow parameters, gestational age, and Doppler US. or RESULTS: 4D flow MRI and UtA flow quantification was feasible in all subjects. There was considerable heterogeneity in UtA geometry in each subject between left and right UtAs and between subjects. Mean 4D flow-based parameters were: mean bilateral flow rate = 605.6 ± 220.5 mL/min, PI = 0.72 ± 0.2, and RI = 0.47 ± 0.1. Bilateral flow did not change with gestational age. We found that MRI differed from US in terms of lower PI (mean difference -0.1) and RI (mean difference < -0.1) with Wilcoxon signed rank test P = 0.05 and P = 0.13, respectively. DATA CONCLUSION: 4D flow MRI is a feasible approach for describing UtA anatomy and flow in pregnant subjects. LEVEL OF EVIDENCE: Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:59-68.

Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI.

Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition.

Comparison of PASL, PCASL, and background-suppressed 3D PCASL in mild cognitive impairment.

We compared three implementations of single-shot arterial spin labeled (ASL) perfusion magnetic resonance imaging: two-dimensional (2D) pulsed ASL (PASL), 2D pseudocontinuous ASL (PCASL), and background-suppressed (BS) 3D PCASL obtained in a cohort of patients with mild cognitive impairment (MCI) and elderly controls. Study subjects also underwent 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET). While BS 3D PCASL showed the lowest (P < 0.001) gray matter-white matter cerebral blood flow (CBF) contrast ratio, it provided the highest (P < 0.001) temporal signal-to-noise ratio. Mean relative CBF estimated using the PCASL methods in posterior cingulate cortex (PCC), precuneus, and hippocampus showed hypoperfusion in the MCI cohort compared to the controls consistent with hypometabolism measured by 18 F-FDG PET. BS 3D PCASL demonstrated the highest discrimination between controls and patients with effect size comparable to that seen with 18 F-FDG PET. 2D PASL did not demonstrate group differentiation with relative CBF in any ROI, whereas 2D PCASL demonstrated significant differences only in PCC and hippocampus. Mean global CBF values did not differ across methods and were highly correlated; however, the correlations were significantly higher (P < 0.001) when either the same labeling (PCASL) or the same acquisition strategy (2D) was used as compared to when both the labeling and readout methods differed. In addition, there were differences in regional distribution of CBF between the three modalities, which can be attributed to differences in sequence parameters. These results demonstrate the superiority of ASL with PCASL and BS 3D readout as a biomarker for regional brain function changes in MCI. Hum Brain Mapp 38:5260-5273, 2017. © 2017 Wiley Periodicals, Inc.

3D-accelerated, stack-of-spirals acquisitions and reconstruction of arterial spin labeling MRI.

PURPOSE: The goal of this study was to develop a 3D acceleration and reconstruction method to improve image quality and resolution of background-suppressed arterial spin-labeled perfusion MRI. METHODS: Accelerated acquisition was implemented in all three k-space dimensions in a stack-of-spirals readout using variable density spirals and partition undersampling. A single 3D self-consistent parallel imaging (SPIRiT) kernel was calibrated and iteratively applied to reconstruct each imaging volume. Whole-brain (including cerebellum) perfusion imaging was obtained at 3-mm isotropic resolution (nominal) using single- and 2-shot acquisitions and at 2-mm isotropic resolution (nominal) using four-shot acquisitions, achieving effective acceleration factors between 5.5 and 6.6. The signal-to-noise (SNR) performance of 3D SPIRiT was evaluated. The temporal SNR (tSNR) of the cerebral blood flow (CBF) maps and the gray/white matter CBF ratios were quantified. RESULTS: The readout of the arterial spin labeling (ASL) sequence was significantly shortened with acceleration. The CBF values were consistent between accelerated and fully sampled ASL. With shorter spiral interleaves and shorter echo trains, the accelerated images demonstrated reduced blurring and signal dropout in regions with high susceptibility gradients, resulting in improved image quality and increased gray/white matter CBF ratios. The shortened readout was accompanied by a corresponding decrease in tSNR. CONCLUSION: The 3D acceleration and reconstruction allow a rapid whole-brain readout that improved the quality of ASL perfusion imaging. Magn Reson Med 78:1405-1419, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Improving the robustness of pseudo-continuous arterial spin labeling to off-resonance and pulsatile flow velocity.

PURPOSE: To improve pseudo-continuous arterial spin labeling (PCASL) robustness to off-resonance and pulsatile blood flow velocity. METHODS: Bloch equations were solved to evaluate the effect of labeling parameters in a pulsatile flow model for a range of off-resonance. Experimental confirmation was achieved in volunteers using linear phase increase between labeling pulses to approximate off-resonance errors. We first assessed the location of the labeling plane in four volunteers. Next, we explored a range of parameters-including balanced and unbalanced gradients-in five more volunteers at an optimal labeling plane location. RESULTS: Simulations demonstrated that 1) high velocities are vulnerable to off-resonance, 2) unbalanced PCASL outperforms balanced PCASL, 3) increased B1 and low average gradient improve the labeling efficiency for high-velocity flow, and 4) a low ratio of selective to average gradient improves off-resonance robustness. A good agreement between theory and experiment was observed. CONCLUSION: The robustness of PCASL can be increased by selecting an unbalanced scheme with a low average gradient (0.5 mT/m), a low ratio (7×) of selective to average gradients, and the highest feasible B1 (1.8 µT). Placing the labeling plane above the carotid bifurcation and below the V3 segment, usually between the second and third vertebrae, yielded robust results. Magn Reson Med 78:1342-1351, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Trade-off between frequency and precision during stepping movements: Kinematic and BOLD brain activation patterns.

The central nervous system has the ability to adapt our locomotor pattern to produce a wide range of gait modalities and velocities. In reacting to external pacing stimuli, deviations from an individual preferred cadence provoke a concurrent decrease in accuracy that suggests the existence of a trade-off between frequency and precision; a compromise that could result from the specialization within the control centers of locomotion to ensure a stable transition and optimal adaptation to changing environment. Here, we explore the neural correlates of such adaptive mechanisms by visually guiding a group of healthy subjects to follow three comfortable stepping frequencies while simultaneously recording their BOLD responses and lower limb kinematics with the use of a custom-built treadmill device. In following the visual stimuli, subjects adopt a common pattern of symmetric and anti-phase movements across pace conditions. However, when increasing the stimulus frequency, an improvement in motor performance (precision and stability) was found, which suggests a change in the control mode from reactive to predictive schemes. Brain activity patterns showed similar BOLD responses across pace conditions though significant differences were observed in parietal and cerebellar regions. Neural correlates of stepping precision were found in the insula, cerebellum, dorsolateral pons and inferior olivary nucleus, whereas neural correlates of stepping stability were found in a distributed network, suggesting a transition in the control strategy across the stimulated range of frequencies: from unstable/reactive at lower paces (i.e., stepping stability managed by subcortical regions) to stable/predictive at higher paces (i.e., stability managed by cortical regions). Hum Brain Mapp 37:1722-1737, 2016. © 2016 Wiley Periodicals, Inc.

Resting state functional connectivity of the subthalamic nucleus in Parkinson's disease assessed using arterial spin-labeled perfusion fMRI.

Neurophysiological changes within the cortico-basal ganglia-thalamocortical circuits appear to be a characteristic of Parkinson's disease (PD) pathophysiology. The subthalamic nucleus (STN) is one of the basal ganglia components showing pathological neural activity patterns in PD. In this study, perfusion imaging data, acquired noninvasively using arterial spin-labeled (ASL) perfusion MRI, were used to assess the resting state functional connectivity (FC) of the STN in 24 early-to-moderate PD patients and 34 age-matched healthy controls, to determine whether altered FC in the very low frequency range of the perfusion time signal occurs as a result of the disease. Our results showed that the healthy STN was functionally connected with other nuclei of the basal ganglia and the thalamus, as well as with discrete cortical areas including the insular cortex and the hippocampus. In PD patients, connectivity of the STN was increased with two cortical areas involved in motor and cognitive processes. These findings suggest that hyperconnectivity of the STN could underlie some of the motor and cognitive deficits often present even at early stages of the disease. The FC measures provided good discrimination between controls and patients, suggesting that ASL-derived FC metrics could be a putative PD biomarker.

Automated neuromelanin imaging as a diagnostic biomarker for Parkinson's disease.

BACKGROUND: We aimed to analyze the diagnostic accuracy of an automated segmentation and quantification method of the SNc and locus coeruleus (LC) volumes based on neuromelanin (NM)-sensitive MRI (NM-MRI) in patients with idiopathic (iPD) and monogenic (iPD) Parkinson's disease (PD). METHODS: Thirty-six patients (23 idiopathic and 13 monogenic PARKIN or LRRK2 mutations) and 37 age-matched healthy controls underwent 3T-NM-MRI. SNc and LC volumetry were performed using fully automated multi-image atlas segmentation. The diagnostic performance to differentiate PD from controls was measured using the area under the curve (AUC) and likelihood ratios based on receiver operating characteristic (ROC) analyses. RESULTS: We found a significant reduction of SNc and LC volumes in patients, when compared to controls. ROC analysis showed better diagnostic accuracy when using SNc volume than LC volume. Significant differences between ipsilateral and contralateral SNc volumes, in relation to the more clinically affected side, were found in patients with iPD (P = 0.007). Contralateral atrophy in the SNc showed the highest power to discriminate PD subjects from controls (AUC, 0.93-0.94; sensitivity, 91%-92%; specificity, 89%; positive likelihood ratio: 8.4-8.5; negative likelihood ratio: 0.09-0.1 at a single cut-off point). Interval likelihood ratios for contralateral SNc volume improved the diagnostic accuracy of volumetric measurements. CONCLUSION: SNc and LC volumetry based on NM-MRI resulting from the automated segmentation and quantification technique can yield high diagnostic accuracy for differentiating PD from health and might be an unbiased disease biomarker. © 2015 International Parkinson and Movement Disorder Society.

Evaluation of segmented 3D acquisition schemes for whole-brain high-resolution arterial spin labeling at 3 T.

Recent technical developments have significantly increased the signal-to-noise ratio (SNR) of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole-brain high-resolution perfusion imaging, combining pseudo-continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in-plane k-space trajectories. Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in-plane trajectories were compared: Cartesian (3D GRASE) and spiral (3D RARE Stack-Of-Spirals). High-resolution perfusion images (2 × 2 × 4 mm(3) ) were acquired in 15 young healthy volunteers with the two ASL sequences at 3 T. The quality of the perfusion maps was evaluated in terms of SNR and gray-to-white matter contrast. Point-spread-function simulations were carried out to assess the impact of readout differences on the effective resolution. The combination of pCASL, in-plane segmented 3D readouts and BS provided high-SNR high-resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack-Of-Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through-plane blurring due to its inherent oversampling of the central k-space region, its reduced effective TE and shorter total readout time, at the expense of a slight increase in the effective in-plane voxel size.

Chronic neuropathic pain components in whiplash-associated disorders correlate with metabolite concentrations in the anterior cingulate and dorsolateral prefrontal cortex: a consensus-driven MRS re-examination.

Introduction: Whiplash injury (WHI) is characterised by a forced neck flexion/extension, which frequently occurs after motor vehicle collisions. Previous studies characterising differences in brain metabolite concentrations and correlations with neuropathic pain (NP) components with chronic whiplash-associated disorders (WAD) have been demonstrated in affective pain-processing areas such as the anterior cingulate cortex (ACC). However, the detection of a difference in metabolite concentrations within these cortical areas with chronic WAD pain has been elusive. In this study, single-voxel magnetic resonance spectroscopy (MRS), following the latest MRSinMRS consensus group guidelines, was performed in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and occipital cortex (OCC) to quantify differences in metabolite concentrations in individuals with chronic WAD with or without neuropathic pain (NP) components. Materials and methods: Healthy individuals (n = 29) and participants with chronic WAD (n = 29) were screened with the Douleur Neuropathique 4 Questionnaire (DN4) and divided into groups without (WAD-noNP, n = 15) or with NP components (WAD-NP, n = 14). Metabolites were quantified with LCModel following a single session in a 3 T MRI scanner within the ACC, DLPFC, and OCC. Results: Participants with WAD-NP presented moderate pain intensity and interference compared with the WAD-noNP group. Single-voxel MRS analysis demonstrated a higher glutamate concentration in the ACC and lower total choline (tCho) in the DLPFC in the WAD-NP versus WAD-noNP group, with no intergroup metabolite difference detected in the OCC. Best fit and stepwise multiple regression revealed that the normalised ACC glutamate/total creatine (tCr) (p = 0.01), DLPFC n-acetyl-aspartate (NAA)/tCr (p = 0.001), and DLPFC tCho/tCr levels (p = 0.02) predicted NP components in the WAD-NP group (ACC r 2 = 0.26, α = 0.81; DLPFC r 2 = 0.62, α = 0.98). The normalised Glu/tCr concentration was higher in the healthy than the WAD-noNP group within the ACC (p < 0.05), but not in the DLPFC or OCC. Neither sex nor age affected key normalised metabolite concentrations related to WAD-NP components when compared to the WAD-noNP group. Discussion: This study demonstrates that elevated glutamate concentrations within the ACC are related to chronic WAD-NP components, while higher NAA and lower tCho metabolite levels suggest a role for increased neuronal-glial signalling and cell membrane dysfunction in individuals with chronic WAD-NP components.