Beyond Crossing Fibers: Bootstrap Probabilistic Tractography Using Complex Subvoxel Fiber Geometries

Diffusion magnetic resonance imaging fiber tractography is a powerful tool for investigating human white matter connectivity in vivo. However, it is prone to false positive and false negative results, making interpretation of the tractography result difficult. Optimal tractography must begin with an accurate description of the subvoxel white matter fiber structure, includes quantification of the uncertainty in the fiber directions obtained, and quantifies the confidence in each reconstructed fiber tract. This paper presents a novel and comprehensive pipeline for fiber tractography that meets the above requirements. The subvoxel fiber geometry is described in detail using a technique that allows not only for straight crossing fibers but for fibers that curve and splay. This technique is repeatedly performed within a residual bootstrap statistical process in order to efficiently quantify the uncertainty in the subvoxel geometries obtained. A robust connectivity index is defined to quantify the confidence in the reconstructed connections. The tractography pipeline is demonstrated in the human brain

Optimization of acquisition parameters for cortical inhomogeneous magnetization transfer (ihMT) imaging using a rapid gradient echo readout

Purpose: Imaging biomarkers with increased myelin specificity are needed to better understand the complex progression of neurological disorders. Inhomogeneous magnetization transfer (ihMT) imaging is an emergent technique that has a high degree of specificity for myelin content but suffers from low signal-to-noise ratio (SNR). This study used simulations to determine optimal sequence parameters for ihMT imaging for use in high-resolution cortical mapping. Methods: MT-weighted cortical image intensity and ihMT SNR were simulated using modified Bloch equations for a range of sequence parameters. The acquisition time was limited to 4.5 min/volume. A custom MT-weighted RAGE sequence with center-out k-space encoding was used to enhance SNR at 3 Tesla. Pulsed MT imaging was studied over a range of saturation parameters and the impact of the turbo-factor on effective ihMT was investigated. 1 mm isotropic ihMTsat maps were generated in 25 healthy adults using an optimized protocol. Results: Greater SNR was observed for larger number of bursts consisting of 6-8 saturation pulses each, combined with a high readout turbo-factor. However, that protocol suffered from a point spread function that was more than twice the nominal resolution. For high-resolution cortical imaging, we selected a protocol with a higher effective resolution at the cost of a lower SNR. We present the first group-average ihMTsat whole-brain map at 1 mm isotropic resolution. Conclusion: This study presents the impact of saturation and excitation parameters on ihMTsat SNR and resolution. We demonstrate the feasibility of high-resolution cortical myelin imaging using ihMTsat in less than 20 minutes

Correcting for T1 bias in Magnetization Transfer Saturation (MTsat) Maps Using Sparse-MP2RAGE

Purpose: Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed sensing (cs)MP2RAGE T1 mapping for accelerating MTsat imaging. Methods: VFA, MP2RAGE and csMP2RAGE were compared against inversion recovery (IR) T1 in a phantom at 3 Tesla. The same 1 mm VFA, MP2RAGE and csMP2RAGE protocols were acquired in four healthy subjects to compare the resulting T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Finally, ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. Results: The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. All approaches provided accurate T1 values (<5% difference) in the phantom, but the accuracy of the T1 times was more impacted by differences in T2 for VFA than for MP2RAGE. In vivo, VFA generated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the bias in the T1 values between VFA and IR-based approaches (MP2RAGE and IR) could be explained by the MT-effects from the inversion pulse. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 3% for T1 mapping and 7.9% for MTsat imaging. Conclusions: We demonstrated that csMP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.Comment: 23 pages, 7 figures, 2 table

Dual-encoded magnetization transfer and diffusion imaging and its application to tract-specific microstructure mapping

We present a novel dual-encoded magnetization transfer (MT) and diffusion-weighted sequence and demonstrate its potential to resolve distinct properties of white matter fiber tracts at the sub-voxel level. The sequence was designed and optimized for maximal MT contrast efficiency. The resulting whole brain 2.6 mm isotropic protocol to measure tract-specific MT ratio (MTR) has a scan time under 7 minutes. Ten healthy subjects were scanned twice to assess repeatability. Two different analysis methods were contrasted: a technique to extract tract-specific MTR using Convex Optimization Modeling for Microstructure Informed Tractography (COMMIT), a global optimization technique; and conventional MTR tractometry. The results demonstrate that the tract-specific method can reliably resolve the MT ratios of major white matter fiber pathways and is less affected by partial volume effects than conventional multi-modal tractometry. Dual-encoded MT and diffusion is expected to both increase the sensitivity to microstructure alterations of specific tracts due to disease, ageing or learning, as well as lead to weighted structural connectomes with more anatomical specificity.Comment: 26 pages, 7 figure

Subject–Motion Correction in HARDI Acquisitions: Choices and Consequences

Diffusion-weighted imaging (DWI) is known to be prone to artifacts related to motion originating from subject movement, cardiac pulsation, and breathing, but also to mechanical issues such as table vibrations. Given the necessity for rigorous quality control and motion correction, users are often left to use simple heuristics to select correction schemes, which involves simple qualitative viewing of the set of DWI data, or the selection of transformation parameter thresholds for detection of motion outliers. The scientific community offers strong theoretical and experimental work on noise reduction and orientation distribution function (ODF) reconstruction techniques for HARDI data, where post-acquisition motion correction is widely performed, e.g., using the open-source DTIprep software (1), FSL (the FMRIB Software Library) (2), or TORTOISE (3). Nonetheless, effects and consequences of the selection of motion correction schemes on the final analysis, and the eventual risk of introducing confounding factors when comparing populations, are much less known and far beyond simple intuitive guessing. Hence, standard users lack clear guidelines and recommendations in practical settings. This paper reports a comprehensive evaluation framework to systematically assess the outcome of different motion correction choices commonly used by the scientific community on different DWI-derived measures. We make use of human brain HARDI data from a well-controlled motion experiment to simulate various degrees of motion corruption and noise contamination. Choices for correction include exclusion/scrubbing or registration of motion corrupted directions with different choices of interpolation, as well as the option of interpolation of all directions. The comparative evaluation is based on a study of the impact of motion correction using four metrics that quantify (1) similarity of fiber orientation distribution functions (fODFs), (2) deviation of local fiber orientations, (3) global brain connectivity via graph diffusion distance (GDD), and (4) the reproducibility of prominent and anatomically defined fiber tracts. Effects of various motion correction choices are systematically explored and illustrated, leading to a general conclusion of discouraging users from setting ad hoc thresholds on the estimated motion parameters beyond which volumes are claimed to be corrupted

Magnetic resonance imaging relaxometry of normal pediatric brain development

This thesis establishes normal age-related changes in the magnetic resonance (MR) T1 and T2 relaxation time constants using data collected as part of the National Institutes of Health (NIH) MRI Study of Normal Brain Development. This ongoing multi-centre study of normal brain and behaviour development provides both longitudinal and cross-sectional data and has enabled us to investigate the relaxation time constant evolution in several brain regions for children within the range of 0-4.5 years. Due to the multi-centre nature of the study and the extended period of data collection, periodically scanned inanimate and human phantoms were used to assess intra and inter-site variability. The main finding of this thesis is the parametrization of the mono-exponential behaviour of both the T1 and T2 relaxation time constants from birth until 4.5 years of age. This behaviour is believed to reflect the rapid changes in water content as well as myelination processes observable during neonatal brain development. These results, comprising over 200 subject scans, represents a subset of a publicly available normative pediatric MRI database, providing a basis for comparison for studies assessing normal brain development and deviation due to various neurological disorders

Subject–Motion Correction in HARDI Acquisitions: Choices and Consequences

Diffusion-weighted imaging (DWI) is known to be prone to artifacts related to motion originating from subject movement, cardiac pulsation, and breathing, but also to mechanical issues such as table vibrations. Given the necessity for rigorous quality control and motion correction, users are often left to use simple heuristics to select correction schemes, which involves simple qualitative viewing of the set of DWI data, or the selection of transformation parameter thresholds for detection of motion outliers. The scientific community offers strong theoretical and experimental work on noise reduction and orientation distribution function (ODF) reconstruction techniques for HARDI data, where post-acquisition motion correction is widely performed, e.g., using the open-source DTIprep software (1), FSL (the FMRIB Software Library) (2), or TORTOISE (3). Nonetheless, effects and consequences of the selection of motion correction schemes on the final analysis, and the eventual risk of introducing confounding factors when comparing populations, are much less known and far beyond simple intuitive guessing. Hence, standard users lack clear guidelines and recommendations in practical settings. This paper reports a comprehensive evaluation framework to systematically assess the outcome of different motion correction choices commonly used by the scientific community on different DWI-derived measures. We make use of human brain HARDI data from a well-controlled motion experiment to simulate various degrees of motion corruption and noise contamination. Choices for correction include exclusion/scrubbing or registration of motion corrupted directions with different choices of interpolation, as well as the option of interpolation of all directions. The comparative evaluation is based on a study of the impact of motion correction using four metrics that quantify (1) similarity of fiber orientation distribution functions (fODFs), (2) deviation of local fiber orientations, (3) global brain connectivity via graph diffusion distance (GDD), and (4) the reproducibility of prominent and anatomically defined fiber tracts. Effects of various motion correction choices are systematically explored and illustrated, leading to a general conclusion of discouraging users from setting ad hoc thresholds on the estimated motion parameters beyond which volumes are claimed to be corrupted

Permanent tissue damage in multiple sclerosis lesions is associated with reduced pre-lesion myelin and axon volume fractions

BACKGROUND: The use of advanced magnetic resonance imaging (MRI) techniques in MS research has led to new insights in lesion evolution and disease outcomes. It has not yet been determined if, or how, pre-lesional abnormalities in normal-appearing white matter (NAWM) relate to the long-term evolution of new lesions. OBJECTIVE: To investigate the relationship between abnormalities in MRI measures of axonal and myelin volume fractions (AVF and MVF) in NAWM preceding development of black-hole (BH) and non-BH lesions in people with MS. METHODS: We obtained magnetization transfer and diffusion MRI at 6-month intervals in patients with MS to estimate MVF and AVF during lesion evolution. Lesions were classified as either BH or non-BH on the final imaging visit using T(1) maps. RESULTS: Longitudinal data from 97 new T(2) lesions from 9 participants were analyzed; 25 lesions in 8 participants were classified as BH 6–12 months after initial appearance. Pre-lesion MVF, AVF, and MVF/AVF were significantly lower, and T(1) was significantly higher, in the lesions that later became BHs (p  0.05). CONCLUSION: The present work demonstrated that pre-lesion abnormalities are associated with worse long-term lesion-level outcome