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ObjectiveConventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker.MethodsWe related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion.ResultsWe report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI‐derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.InterpretationNeurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

This paper presents Bingham-NODDI, a clinically-feasible technique for estimating the anisotropic orientation dispersion of neurites. Direct quantification of neurite morphology on clinical scanners was recently realised by a diffusion MRI technique known as neurite orientation dispersion and density imaging (NODDI). However in its current form NODDI cannot estimate anisotropic orientation dispersion, which is widespread in the brain due to common fanning and bending of neurites. This work proposes Bingham-NODDI that extends the NODDI formalism to address this limitation. Bingham-NODDI characterises anisotropic orientation dispersion by utilising the Bingham distribution to model neurite orientation distribution. The new model estimates the extent of dispersion about the dominant orientation, separately along the primary and secondary dispersion orientations. These estimates are subsequently used to estimate the overall dispersion about the dominant orientation and the dispersion anisotropy. We systematically evaluate the ability of the new model to recover these key parameters of anisotropic orientation dispersion with standard NODDI protocol, both in silico and in vivo. The results demonstrate that the parameters of the proposed model can be estimated without additional acquisition requirements over the standard NODDI protocol. Thus anisotropic dispersion can be determined and has the potential to be used as a marker for normal brain development and ageing or in pathology. We additionally find that the original NODDI model is robust to the effects of anisotropic orientation dispersion, when the quantification of anisotropic dispersion is not of interest.

Here we present the application of neurite orientation dispersion and density imaging (NODDI) to the healthy spinal cord in vivo. NODDI provides maps such as the intra-neurite tissue volume fraction (vin), the orientation dispersion index (ODI) and the isotropic volume fraction (viso), and here we investigate their potential for spinal cord imaging. We scanned five healthy volunteers, four of whom twice, on a 3T MRI system with a ZOOM-EPI sequence. In accordance to the published NODDI protocol, multiple b-shells were acquired at cervical level and both NODDI and diffusion tensor imaging (DTI) metrics were obtained and analysed to: i) characterise differences in grey and white matter (GM/WM); ii) assess the scan-rescan reproducibility of NODDI; iii) investigate the relationship between NODDI and DTI; and iv) compare the quality of fit of NODDI and DTI. Our results demonstrated that: i) anatomical features can be identified in NODDI maps, such as clear contrast between GM and WM in ODI; ii) the variabilities of vin and ODI are comparable to that of DTI and are driven by biological differences between subjects for ODI, have similar contribution from measurement errors and biological variation for vin, whereas viso shows higher variability, driven by measurement errors; iii) NODDI identifies potential sources contributing to DTI indices, as in the brain; and iv) NODDI outperforms DTI in terms of quality of fit. In conclusion, this work shows that NODDI is a useful model for in vivo diffusion MRI of the spinal cord, providing metrics closely related to tissue microstructure, in line with findings in the brain.

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.

SummaryDiffusion tensor imaging (DTI) is sensitive to white matter (WM) damage in multiple sclerosis (MS), not only in focal lesions but also in the normal-appearing WM (NAWM). However, DTI indices can also be affected by natural spatial variation in WM, as seen in crossing and dispersing white matter fibers. Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion-weighted imaging technique that provides distinct indices of fiber density and dispersion. We performed NODDI of lesion tissue and NAWM in five MS patients and five controls, comparing the technique with traditional DTI. Both DTI and NODDI identified tissue damage in NAWM and in lesions. NODDI was able to detect additional changes and it provided better contrast in MS-NAWM microstructure, because it distinguished orientation dispersion and fiber density better than DTI. We showed that NODDI is viable in MS patients and that it offers, compared with DTI parameters, improved sensitivity and possibly greater specificity to microstructure features such as neurite orientation.

PurposeDiffusion magnetic resonance imaging (MRI) microstructure imaging provides a unique noninvasive probe into tissue microstructure. The technique relies on biophysically motivated mathematical models, relating microscopic tissue features to the magnetic resonance (MR) signal. This work aims to determine which compartment models of diffusion MRI are best at describing measurements from in vivo human brain white matter.MethodsRecent work shows that three compartment models, designed to capture intra-axonal, extracellular, and isotropically restricted diffusion, best explain multi-b-value data sets from fixed rat corpus callosum. We extend this investigation to in vivo by using a live human subject on a clinical scanner. The analysis compares models of one, two, and three compartments and ranks their ability to explain the measured data. We enhance the original methodology to further evaluate the stability of the ranking.ResultsAs with fixed tissue, three compartment models explain the data best. However, a clearer hierarchical structure and simpler models emerge. We also find that splitting the scanning into shorter sessions has little effect on the ranking of models, and that the results are broadly reproducible across sessions.ConclusionThree compartments are required to explain diffusion MR measurements from in vivo corpus callosum, which informs the choice of model for microstructure imaging applications in the brain. Magn Reson Med 72:1785–1792, 2014. © 2013 The authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.