Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging

The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. This is the second review on the topic of g-ratio mapping using MRI. As such, it summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. Using simulations based on recently published data, this review demonstrates the relevance of the calibration step for three myelin-markers (macromolecular tissue volume, myelin water fraction, and bound pool fraction). It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of many novel techniques yet to be investigated.Comment: Will be published as a review article in Journal of Neuroscience Methods as parf of the Special Issue with Hu Cheng and Vince Calhoun as Guest Editor

Characterizing aging in the human brainstem using quantitative multimodal MRI analysis.

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetization transfer and increase in proton density (PD), accounting for the previously described “midbrain shrinkage.” Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterized, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterized by early, pre-clinical involvement of the brainstem, such as Parkinson’s and Alzheimer’s diseases

Measurement of T1 of the ultrashort T2* components in white matter of the brain at 3T.

Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32 ± 0.09 ms, and a short mean T1 of 226 ± 46 ms were demonstrated for the healthy volunteers at 3T

Deep grey matter volumetry as a function of age using a semi-automatic qMRI algorithm

Quantitative Magnetic Resonance has become more and more accepted for clinical trial in many fields. This technique not only can generate qMRI maps (such as T1/T2/PD) but also can be used for further postprocessing including segmentation of brain and characterization of different brain tissue. Another main application of qMRI is to measure the volume of the brain tissue such as the deep Grey Matter (dGM). The deep grey matter serves as the brain's "relay station" which receives and sends inputs between the cortical brain regions. An abnormal volume of the dGM is associated with certain diseases such as Fetal Alcohol Spectrum Disorders (FASD). The goal of this study is to investigate the effect of age on the volume change of the dGM using qMRI. Thirteen patients (mean age= 26.7 years old and age range from 0.5 to 72.5 years old) underwent imaging at a 1.5T MR scanner. Axial images of the entire brain were acquired with the mixed Turbo Spin-echo (mixed -TSE) pulse sequence. The acquired mixed-TSE images were transferred in DICOM format image for further analysis using the MathCAD 2001i software (Mathsoft, Cambridge, MA). Quantitative T1 and T2-weighted MR images were generated. The image data sets were further segmented using the dual-space clustering segmentation. Then volume of the dGM matter was calculated using a pixel counting algorithm and the spectrum of the T1/T2/PD distribution were also generated. Afterwards, the dGM volume of each patient was calculated and plotted on scatter plot. The mean volume of the dGM, standard deviation, and range were also calculated. The result shows that volume of the dGM is 47.5 ±5.3ml (N=13) which is consistent with former studies. The polynomial tendency line generated based on scatter plot shows that the volume of the dGM gradually increases with age at early age and reaches the maximum volume around the age of 20, and then it starts to decrease gradually in adulthood and drops much faster in elderly age. This result may help scientists to understand more about the aging of the brain and it can also be used to compare with the results from former studies using different techniques