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author:("Xu, jungian")
1.  Evaluation of slice accelerations using multiband echo planar imaging at 3 Tesla 
NeuroImage  2013;83:10.1016/j.neuroimage.2013.07.055.
We evaluate residual aliasing among simultaneously excited and acquired slices in slice accelerated multiband (MB) echo planar imaging (EPI). No in-plane accelerations were used in order to maximize and evaluate achievable slice acceleration factors at 3 Tesla. We propose a novel leakage (L-) factor to quantify the effects of signal leakage between simultaneously acquired slices. With a standard 32-channel receiver coil at 3 Tesla, we demonstrate that slice acceleration factors of up to eight (MB = 8) with blipped controlled aliasing in parallel imaging (CAIPI), in the absence of in-plane accelerations, can be used routinely with acceptable image quality and integrity for whole brain imaging. Spectral analyses of single-shot fMRI time series demonstrate that temporal fluctuations due to both neuronal and physiological sources were distinguishable and comparable up to slice-acceleration factors of nine (MB = 9). The increased temporal efficiency could be employed to achieve, within a given acquisition period, higher spatial resolution, increased fMRI statistical power, multiple TEs, faster sampling of temporal events in a resting state fMRI time series, increased sampling of q-space in diffusion imaging, or more quiet time during a scan.
doi:10.1016/j.neuroimage.2013.07.055
PMCID: PMC3815955  PMID: 23899722
lipped CAIPI; leakage (L-) factor; g-factor; residual aliasing; spectral analysis; single-shot fMRI time series
2.  Advances in diffusion MRI acquisition and processing in the Human Connectome Project 
NeuroImage  2013;80:125-143.
The Human Connectome Project (HCP) is a collaborative 5-year effort to map human brain connections and their variability in healthy adults. A consortium of HCP investigators will study a population of 1200 healthy adults using multiple imaging modalities, along with extensive behavioral and genetic data. In this overview, we focus on diffusion MRI (dMRI) and the structural connectivity aspect of the project. We present recent advances in acquisition and processing that allow us to obtain very high-quality in-vivo MRI data, while enabling scanning of a very large number of subjects. These advances result from 2 years of intensive efforts in optimising many aspects of data acquisition and processing during the piloting phase of the project. The data quality and methods described here are representative of the datasets and processing pipelines that will be made freely available to the community at quarterly intervals, beginning in 2013.
doi:10.1016/j.neuroimage.2013.05.057
PMCID: PMC3720790  PMID: 23702418
3.  The Minimal Preprocessing Pipelines for the Human Connectome Project 
NeuroImage  2013;80:105-124.
The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinates spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCP’s acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements for the pipelines.
doi:10.1016/j.neuroimage.2013.04.127
PMCID: PMC3720813  PMID: 23668970
Human Connectome Project; Image Analysis Pipeline; Surface-based Analysis; CIFTI; Grayordinates; Multi-modal Data Integration
4.  Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project 
NeuroImage  2013;80:80-104.
The human connectome project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the temporal fluctuations in an fMRI time series to deduce ‘functional connectivity’; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3 Tesla, leading to whole brain coverage with 2 mm isotropic resolution in 0.7 second for fMRI, and 1.25 mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7 Tesla magnetic field are also presented, targeting higher resolution, specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields and power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure.
doi:10.1016/j.neuroimage.2013.05.012
PMCID: PMC3740184  PMID: 23702417
5.  Resting-state fMRI in the Human Connectome Project 
NeuroImage  2013;80:144-168.
Resting-state functional magnetic resonance imaging (rfMRI) allows one to study functional connectivity in the brain by acquiring fMRI data while subjects lie inactive in the MRI scanner, and taking advantage of the fact that functionally related brain regions spontaneously co-activate. rfMRI is one of the two primary data modalities being acquired for the Human Connectome Project (the other being diffusion MRI). A key objective is to generate a detailed in vivo mapping of functional connectivity in a large cohort of healthy adults (over 1,000 subjects), and to make these datasets freely available for use by the neuroimaging community. In each subject we acquire a total of one hour of whole-brain rfMRI data at 3 Tesla, with a spatial resolution of 2×2×2mm and a temporal resolution of 0.7s, capitalizing on recent developments in slice-accelerated echo-planar imaging. We will also scan a subset of the cohort at higher field strength and resolution. In this paper we outline the work behind, and rationale for, decisions taken regarding the rfMRI data acquisition protocol and pre-processing pipelines, and present some initial results showing data quality and example functional connectivity analyses.
doi:10.1016/j.neuroimage.2013.05.039
PMCID: PMC3720828  PMID: 23702415
6.  Spinal cord tract diffusion tensor imaging reveals disability substrate in demyelinating disease 
Neurology  2013;80(24):2201-2209.
Objective:
This study assessed the tissue integrity of major cervical cord tracts by using diffusion tensor imaging (DTI) to determine the relationship with specific clinical functions carried by those tracts.
Methods:
This was a cross-sectional study of 37 patients with multiple sclerosis or neuromyelitis optica with remote cervical cord disease. Finger vibratory thresholds, 25-foot timed walk (25FTW), 9-hole peg test (9HPT), and Expanded Disability Status Scale were determined. DTI covered cervical regions C1 through C6 with 17 5-mm slices (0.9 × 0.9 mm in-plane resolution). Regions of interest included posterior columns (PCs) and lateral corticospinal tracts (CSTs). Hierarchical linear mixed-effect modeling included covariates of disease subtype (multiple sclerosis vs neuromyelitis optica), disease duration, and sex.
Results:
Vibration thresholds were associated with radial diffusivity (RD) and fractional anisotropy (FA) in the PCs (both p < 0.01), but not CSTs (RD, p = 0.29; FA, p = 0.14). RD and FA in PCs, and RD in CSTs were related to 9HPT (each p < 0.0001). 25FTW was associated with RD and FA in PCs (p < 0.0001) and RD in CSTs (p = 0.008). Expanded Disability Status Scale was related to RD and FA in PCs and CSTs (p < 0.0001). Moderate/severe impairments in 9HPT (p = 0.006) and 25FTW (p = 0.017) were more likely to show combined moderate/severe tissue injury within both PCs and CSTs by DTI.
Conclusions:
DTI can serve as an imaging biomarker of spinal cord tissue injury at the tract level. RD and FA demonstrate strong and consistent relationships with clinical outcomes, specific to the clinical modality.
doi:10.1212/WNL.0b013e318296e8f1
PMCID: PMC3721096  PMID: 23667060
7.  Study protocol: the Whitehall II imaging sub-study 
BMC Psychiatry  2014;14:159.
Background
The Whitehall II (WHII) study of British civil servants provides a unique source of longitudinal data to investigate key factors hypothesized to affect brain health and cognitive ageing. This paper introduces the multi-modal magnetic resonance imaging (MRI) protocol and cognitive assessment designed to investigate brain health in a random sample of 800 members of the WHII study.
Methods/design
A total of 6035 civil servants participated in the WHII Phase 11 clinical examination in 2012–2013. A random sample of these participants was included in a sub-study comprising an MRI brain scan, a detailed clinical and cognitive assessment, and collection of blood and buccal mucosal samples for the characterisation of immune function and associated measures. Data collection for this sub-study started in 2012 and will be completed by 2016. The participants, for whom social and health records have been collected since 1985, were between 60–85 years of age at the time the MRI study started. Here, we describe the pre-specified clinical and cognitive assessment protocols, the state-of-the-art MRI sequences and latest pipelines for analyses of this sub-study.
Discussion
The integration of cutting-edge MRI techniques, clinical and cognitive tests in combination with retrospective data on social, behavioural and biological variables during the preceding 25 years from a well-established longitudinal epidemiological study (WHII cohort) will provide a unique opportunity to examine brain structure and function in relation to age-related diseases and the modifiable and non-modifiable factors affecting resilience against and vulnerability to adverse brain changes.
doi:10.1186/1471-244X-14-159
PMCID: PMC4048583  PMID: 24885374
Epidemiology; Magnetic resonance imaging; Diffusion tensor imaging; White matter; Functional MRI; Connectome; Resting state brain networks; Neuropsychology; Dementia; Affective disorders
8.  Multi-band accelerated spin-echo echo planar imaging with reduced peak RF power using time-shifted RF pulses 
Purpose
To evaluate an alternative method for generating multi-banded RF pulses for use in multiband slice-accelerated imaging with slice-GRAPPA unaliasing, substantially reducing the required peak power without bandwidth compromises. This allows much higher accelerations for spin-echo methods such as SE-fMRI and diffusion-weighted MRI where multi-banded slice acceleration has been limited by available peak power.
Theory and Methods
Multi-banded “time-shifted” RF pulses were generated by inserting temporal shifts between the applications of RF energy for individual bands, avoiding worst-case constructive interferences. Slice profiles and images in phantoms and human subjects were acquired at 3T.
Results
For typical sinc pulses, time-shifted multi-banded RF pulses were generated with little increase in required peak power compared to single-banded pulses. Slice profile quality was improved by allowing for higher pulse bandwidths, and image quality was improved by allowing for optimum flip angles to be achieved.
Conclusion
A simple approach has been demonstrated that significantly alleviates the restrictions imposed on achievable slice acceleration factors in multiband spin-echo imaging due to the power requirements of multi-banded RF pulses. This solution will allow for increased accelerations in diffusion-weighted MRI applications where data acquisition times are normally very long and the ability to accelerate is extremely valuable.
doi:10.1002/mrm.24719
PMCID: PMC3769699  PMID: 23468087
parallel imaging; multiband; simultaneous multislice; diffusion; fMRI
9.  Improved in vivo diffusion tensor imaging of human cervical spinal cord 
NeuroImage  2012;67:64-76.
We describe a cardiac gated high in-plane resolution axial human cervical spinal cord diffusion tensor imaging (DTI) protocol. Multiple steps were taken to optimize both image acquisition and image processing. The former includes slice-by-slice cardiac triggering and individually tiltable slices. The latter includes (i) iterative 2D retrospective motion correction, (ii) image intensity outlier detection to minimize the influence of physiological noise, (iii) a non-linear DTI estimation procedure incorporating non-negative eigenvalue priors, and (iv) tract-specific region-of-interest (ROI) identification based on an objective geometry reference. Using these strategies in combination, radial diffusivity (λ⊥) was reproducibly measured in white matter (WM) tracts (adjusted mean [95% confidence interval]=0.25 [0.22, 0.29]µm2/ms), lower than previously reported λ⊥ values in the in vivo human spinal cord DTI literature. Radial diffusivity and fractional anisotropy (FA) measured in WM varied from rostral to caudal as did mean translational motion, likely reflecting respiratory motion effect. Given the considerable sensitivity of DTI measurements to motion artifact, we believe outlier detection is indispensable in spinal cord diffusion imaging. We also recommend using a mixed-effects model to account for systematic measurement bias depending on cord segment.
doi:10.1016/j.neuroimage.2012.11.014
PMCID: PMC3604900  PMID: 23178538
Directional diffusivity; Outlier rejection; Non-negative eigenvalue priors; Reduced FOV; Cardiac gating; Cervical spinal cord; Lateral corticospinal tract; Posterior column; Diffusion tensor imaging; Reproducibility
10.  Increased Radial Diffusivity in Spinal Cord Lesions in Neuromyelitis Optica Compared to Multiple Sclerosis 
Background
Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology.
Objective
Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions.
Methods
Subjects ≥12 months from a clinical episode of transverse myelitis underwent a novel transaxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS, and 10 healthy controls were included.
Results
Within T2 affected white matter regions, radial diffusivity was increased in both NMO and MS compared to healthy controls (p<0.001, respectively), and to a greater extent in NMO than MS (p<0.001). Axial diffusivity was decreased in T2 lesions in both NMO and MS compared to controls (p<0.001, p=0.001), but did not differ between the two diseases. Radial diffusivity and FA within white matter regions upstream and downstream of T2 lesions were different from controls in each disease.
Conclusions
Higher radial diffusivity, within spinal cord white matter tracts derived from diffusion tensor imaging were appreciated in NMO compared to MS, consistent with the known greater tissue destruction seen in NMO. DTI also detected tissue alterations outside T2 lesions, and may be a surrogate of anterograde and retrograde degeneration.
doi:10.1177/1352458512436593
PMCID: PMC3360125  PMID: 22354742
diffusion tensor imaging; neuromyelitis optica (NMO); multiple sclerosis (MS); spinal cord; MRI
11.  Diffusion Tensor Imaging in Acute Optic Neuropathies 
Archives of neurology  2011;69(1):65-71.
Objective
To evaluate directional diffusivities within the optic nerve in a first event of acute optic neuritis to determine whether decreased axial diffusivity (AD) would predict 6-month visual outcome and optic nerve integrity measures.
Design
Cohort study.
Setting
Academic multiple sclerosis center.
Patients
Referred sample of 25 individuals who presented within 31 days after acute visual symptoms consistent with optic neuritis. Visits were scheduled at baseline, 2 weeks, and 1, 3, 6, and 12 months.
Main Outcome Measures
Visual acuity, contrast sensitivity, visual evoked potentials (VEPs), and thickness of the retinal nerve fiber layer (RNFL).
Results
An incomplete 6-month visual recovery was associated with a lower baseline AD (1.50 μm2/ms [95% confidence interval {CI}, 1.36–1.64 μm2/ms for incomplete recovery vs 1.75 μm2/ms [95% CI, 1.67–1.83 μm2/ms] for complete recovery). Odds of complete recovery decreased by 53% (95% CI, 27%–70%) for every 0.1-unit decrease in baseline AD. A lower baseline AD correlated with worse 6-month visual outcomes in visual acuity (r=0.40, P=.03), contrast sensitivity (r=0.41, P=.02), VEP amplitude (r=0.55, P<.01), VEP latency (r=−0.38, P=.04), and RNFL thickness (r=0.53, P=.02). Radial diffusivity increased between months 1 and 3 to become higher in those with incomplete recovery at 12 months than in those with complete recovery (1.45 μm2/ms [95% CI, 1.31–1.59 μm2/ms] vs 1.19 μm2/ms [95% CI, 1.10–1.28 μm2/ms]).
Conclusions
Decreased AD in acute optic neuritis was associated with a worse 6-month visual outcome and correlated with VEP and RNFL measures of axon and myelin injury. Axial diffusivity may serve as a marker of axon injury in acute white matter injury.
doi:10.1001/archneurol.2011.243
PMCID: PMC3489058  PMID: 21911658
12.  Magnetic Resonance Diffusion Characteristics of Histologically Defined Prostate Cancer in Humans 
The contrast provided by diffusion-sensitive magnetic resonance offers the promise of improved tumor localization in organ-confined human prostate cancer (PCa). Diffusion tensor imaging (DTI) measurements of PCa were performed in vivo, in patients undergoing radical prostatectomy, and later, ex vivo, in the same patients’ prostatectomy specimens. The imaging data were coregistered to histological sections of the prostatectomy specimens, thereby enabling unambiguous characterization of diffusion parameters in cancerous and benign tissues. Increased cellularity, and hence decreased luminal spaces, in peripheral zone PCa led to approximately 40% and 50% apparent diffusion policy (ADC) decrease compared with benign peripheral zone tissues in vivo and ex vivo, respectively. In contrast, no significant diffusion anisotropy differences were observed between the cancerous and noncancerous peripheral zone tissues. However, the dense fibromuscular tissues in prostate, such as stromal tissues in benign prostatic hyperplasia in central gland, exhibited high diffusion anisotropy. A tissue classification method is proposed to combine DTI and T2-weighted image contrasts that may provide improved specificity of PCa detection over T2-weighted imaging alone. PCa identified in volume rendered MR images qualitatively correlates well with histologically determined PCa foci.
doi:10.1002/mrm.21896
PMCID: PMC3080096  PMID: 19215051
prostate carcinoma (PCa); diffusion tensor imaging (DTI); apparent diffusion coefficient (ADC); fractional anisotropy (FA)
13.  Assessing Optic Nerve Pathology with Diffusion MRI: from Mouse to Human 
NMR in biomedicine  2008;21(9):928-940.
Optic nerve is often affected in patients with glaucoma and multiple sclerosis (MS). Conventional MRI can detect nerve damage but it does not accurately assess the underlying pathologies. Mean diffusivity and diffusion anisotropy indices derived from diffusion tensor imaging (DTI) have been shown to be sensitive to a variety of central nervous system (CNS) white matter pathologies. Despite being sensitive, the lack of specificity limits the ability of these measures to differentiate the underlying pathology in CNS white matter tissues. Directional (axial and radial) diffusivities, measuring water diffusion parallel and perpendicular to the axonal tracts, have been shown to be specific to axonal and myelin damages in mouse models of optic nerve injury, including retinal ischemia and experimental autoimmune encephalomyelitis (EAE). The progression of Wallerian degeneration has also been detected using directional diffusivities after retinal ischemia. However, translating these findings to human optic nerve is technically challenging. The current status of human optic nerve diffusion MRI, including the imaging sequences and protocols, are summarized herein. Despite lacking a consensus of the optimal sequence or protocol among different groups, increased mean diffusivity and decreased diffusion anisotropy has been observed in injured optic nerve from chronic optic neuritis patients. Decreased λ∥, correlating with visual function and recovery, was observed recently in acute optic neuritis patients in a pilot study, suggesting the specificity of λ∥ to axonal injury. From different mouse models of optic nerve injuries to the emerging studies on optic neuritis patients, directional diffusivities demonstrate great potential to be specific biomarkers for axonal and myelin injury.
doi:10.1002/nbm.1307
PMCID: PMC2603138  PMID: 18756587

Results 1-13 (13)