Myelin biomarkers in the healthy adult brain: Correlation, reproducibility, and the effect of fiber orientation.

PURPOSE: We investigated the correlation, reproducibility, and effect of white matter fiber orientation for three myelin-sensitive MRI techniques: magnetization transfer ratio (MTR), inhomogeneous magnetization transfer ratio (ihMTR), and gradient and spin echo-derived myelin water fraction (MWF). METHODS: We measured the three metrics in 17 white and three deep grey matter regions in 17 healthy adults at 3 T. RESULTS: We found a strong correlation between ihMTR and MTR (r = 0.70, p < 0.001) and ihMTR and MWF (r = 0.79, p < 0.001), and a weaker correlation between MTR and MWF (r = 0.54, p < 0.001). The dynamic range in white matter was greatest for MWF (2.0%-27.5%), followed by MTR (14.4%-23.2%) and then ihMTR (1.2%-5.4%). The average scan-rescan coefficient of variation for white matter regions was 0.6% MTR, 0.3% ihMTR, and 0.7% MWF in metric units; however, when adjusted by the dynamic range, these became 6.3%, 6.1% and 2.8%, respectively. All three metrics varied with fiber direction: MWF and ihMTR were lower in white matter fibers perpendicular to B0 by 6% and 1%, respectively, compared with those parallel, whereas MTR was lower by 0.5% at about 40°, with the highest values at 90°. However, separating the apparent orientation dependence by white matter region revealed large dissimilarities in the trends, suggesting that real differences in myelination between regions are confounding the apparent orientation dependence measured using this method. CONCLUSION: The strong correlation between ihMTR and MWF suggests that these techniques are measuring the same myelination; however, the larger dynamic range of MWF may provide more power to detect small differences in myelin.

Understanding aqueous and non-aqueous proton T1 relaxation in brain.

A full picture of longitudinal relaxation in complex heterogeneous environments like white matter brain tissue remains elusive. In tissue, successive approximations, from the solvation layer model to the two pool model, have highlighted how longitudinal magnetization evolution depends on both inter-compartmental exchange and spin-lattice relaxation. In white matter, however, these models fail to capture the behaviour of the two distinct aqueous pools, myelin water and intra/extra-cellular water. A challenge with testing more comprehensive multi-pool models lies in directly observing all pools, both aqueous and non-aqueous. In this work, we advance these efforts by integrating three main experimental and analytical elements: direct observation of the longitudinal relaxation of both the aqueous and the non-aqueous protons in white matter, a wide range of different initial conditions, and application of an analysis pipeline which includes lineshape, CPMG, and fitting of a four pool model. An eigenvector interpretation of the four pool model highlights how longitudinal relaxation in white matter depends on initial conditions. We find that a single set of model parameters is able to describe the entire range of relaxation behaviour observed in all the separable aqueous and non-aqueous pools in experiments involving six different initial conditions. Understanding of the nature and connectedness of the tissue components is crucial in the design and interpretation of many MRI measurements, especially those based on magnetization transfer and longitudinal relaxation. In particular, the dependency of relaxation behaviour on initial conditions is likely the basis for understanding method-dependent discrepancies in in vivo T1.

The physical mechanism of "inhomogeneous" magnetization transfer MRI.

Inhomogeneous MT (ihMT) is a new magnetic resonance imaging technique that shows promise for myelin selectivity. Materials with a high proportion of lipids, such as white matter tissue, show a reduced intensity in magnetic resonance images acquired with selective prepulses at positive and negative offsets simultaneously compared to images with a single positive or negative offset prepulse of the same power. This effect was initially explained on the basis of hole-burning in inhomogeneously broadened lines of the lipid proton spin system. Our results contradict this explanation. ihMT in lipids can be understood with a simple spin-1 model of a coupled methylene proton pair. More generally, Provotorov theory can be used to consider the evolution of dipolar order in the non-aqueous spins during the prepulses. We show that the flip-angle dependence of the proton spectrum of a model lipid system (Prolipid-161) following dipolar order generation is in quantitative agreement with the model. In addition, we directly observe dipolar order and ihMT signals in the non-aqueous components of Prolipid-161 and homogeneously-broadened systems (hair, wood, and tendon) following ihMT prepulses. The observation of ihMT signals in tendon suggests that the technique may not be as specific to myelin as previously thought. Our work shows that ihMT occurs because of dipolar couplings alone, not from a specific type of spectral line broadening as its name suggests.

NMR of guest-host systems: 8CB in chiral nematic porous glasses.

Liquid crystals confined to porous materials often have different critical phenomena and ordering than in the bulk. Through the selection of pore size, structure and guest liquid crystal, these systems could enable a variety of functional materials for applications such as sensors and displays. A recent example of such a system is chiral nematic mesoporous films infiltrated with liquid crystal 4-cyano-4'-n-octylbiphenyl (8CB), which has reversible thermal switching of its optical bandgap. The optical bandgap is lost when the ordered 8CB guests are heated above ∼50 °C, where the 8CB becomes isotropic. In this study, we have used NMR cryoporometry and pulsed-field gradient diffusion measurements to determine the pore sizes and structures of various chiral nematic mesoporous silica and organosilica films. Temperature and orientation-dependent wideline (15)N NMR spectra of films infiltrated with (15)N-labelled 8CB guests show that the ordering of the 8CB mesogens is consistent with an average orientation parallel to the chiral nematic pore axes. Inclusion of a large, orientation-dependent shift was necessary to fit the spectra, probably due to susceptibility differences between the 8CB guests and the organosilica host.

Thermal switching of the reflection in chiral nematic mesoporous organosilica films infiltrated with liquid crystals.

Materials that undergo stimulus-induced optical changes are important for many new technologies. In this paper, we describe a new free-standing silica-based composite film that exhibits reversible thermochromic reflection, induced by a liquid crystalline guest in the pores of iridescent mesoporous films. We demonstrate that selective reflection from the novel mesoporous organosilica material with chiral nematic organization can be reversibly switched by thermal cycling of the 8CB guest between its isotropic and liquid crystalline states, which was proven by solid-state NMR experiments. The switching of the optical properties of the chiral solid-state host by stimulus-induced transitions of the guest opens the possibility of applications for these novel materials in sensors and displays.

Helium ion microscopy: a new tool for imaging novel mesoporous silica and organosilica materials.

Helium ion microscopy (HIM) has been used to image mesoporous silica and organosilica for the first time. Images of chiral nematic silica, ethylenesilica, and new benzenesilica reveal the structural organization, pore dimensions and connectivity of these materials on the nanometer length scale.

Unsuccessful treatment of a horse with mandibular granulomatous osteomyelitis due to Halicephalobus gingivalis.

An 8-year-old horse was presented with a submandibular swelling. Biopsy of the lesion indicated granulomatous osteomyelitis due to Halicephalobus gingivalis. In the absence of evidence of involvement of the central nervous system at the time of diagnosis, the horse was treated with ivermectin. Unfortunately, the horse did not survive.