How to accurately quantify brain magnetic susceptibility in the context of Parkinson's disease: Validation on phantoms and healthy volunteers at 1.5 and 3 T.

Currently, brain iron content represents a new neuromarker for understanding the physiopathological mechanisms leading to Parkinson's disease (PD). In vivo quantification of biological iron is possible by reconstructing magnetic susceptibility maps obtained using quantitative susceptibility mapping (QSM). Applying QSM is challenging, as up to now, no standardization of acquisition protocols and phase image processing has emerged from referenced studies. Our objectives were to compare the accuracy and the sensitivity of 10 QSM pipelines built from algorithms from the literature, applied on phantoms data and on brain data. Two phantoms, with known magnetic susceptibility ranges, were created from several solutions of gadolinium chelate. Twenty healthy volunteers from two age groups were included. Phantoms and brain data were acquired at 1.5 and 3 T, respectively. Susceptibility-weighted images were obtained using a 3D multigradient-recalled-echo sequence. For brain data, 3D anatomical T1- and T2-weighted images were also acquired to segment the deep gray nuclei of interest. Concerning in vitro data, the linear dependence of magnetic susceptibility versus gadolinium concentration and deviations from the theoretically expected values were calculated. For brain data, the accuracy and sensitivity of the QSM pipelines were evaluated in comparison with results from the literature and regarding the expected magnetic susceptibility increase with age, respectively. A nonparametric Mann-Whitney U-test was used to compare the magnetic susceptibility quantification in deep gray nuclei between the two age groups. Our methodology enabled quantifying magnetic susceptibility in human brain and the results were consistent with those from the literature. Statistically significant differences were obtained between the two age groups in all cerebral regions of interest. Our results show the importance of optimizing QSM pipelines according to the application and the targeted magnetic susceptibility range, to achieve accurate quantification. We were able to define the optimal QSM pipeline for future applications on patients with PD.

Impact of Sonic Hedgehog-dependent sphenoid bone defect on craniofacial growth.

OBJECTIVES: The main objective of this study was to evaluate how an apparently minor anomaly of the sphenoid bone, observed in a haploinsufficient mouse model for Sonic Hedgehog (Shh), affects the growth of the adult craniofacial region. This study aims to provide valuable information to orthodontists when making decisions regarding individuals carrying SHH mutation. MATERIALS AND METHODS: The skulls of embryonic, juvenile and adult mice of two genotypes (Shh heterozygous and wild type) were examined and measured using landmark-based linear dimensions. Additionally, we analysed the clinical characteristics of a group of patients and their relatives with SHH gene mutations. RESULTS: In the viable Shh+/ - mouse model, bred on a C57BL/6J background, we noted the presence of a persistent foramen at the midline of the basisphenoid bone. This particular anomaly was attributed to the existence of an ectopic pituitary gland. We discovered that this anomaly led to premature closure of the intrasphenoidal synchondrosis and contributed to craniofacial deformities in adult mice, including a longitudinally shortened skull base. This developmental anomaly is reminiscent of that commonly observed in human holoprosencephaly, a disorder resulting from a deficiency in SHH activity. However, sphenoid morphogenesis is not currently monitored in individuals carrying SHH mutations. CONCLUSION: Haploinsufficiency of Shh leads to isolated craniofacial skeletal hypoplasia in adult mouse. This finding highlights the importance of radiographic monitoring of the skull base in all individuals with SHH gene mutations.

PBPK model of methotrexate in cerebrospinal fluid ventricles using a combined microdialysis and MRI acquisition.

The objective of the study was to evaluate the distribution of methotrexate (MTX) in cerebrospinal fluid (CSF) lateral ventricles and in cisterna magna after 3rd intraventricular CSF administration in a rabbit model. MTX or gadolinium chelate (Gd-DOTA) was administered in the 3rd ventricle with a local microdialysis to study the pharmacokinetics at the site of administration and with a simultaneous magnetic resonance imaging (MRI) acquisition in the 3rd ventricle, the lateral ventricles and in the cisterna magna. A specific CSF Physiologically Based Pharmacokinetic (PBPK) model was then extrapolated for MTX from Gd-DOTA data. The relative contribution of elimination and distribution processes to the overall disposition of MTX and Gd-DOTA in the 3rd ventricle was similar (i.e., around 60% for CLE and 40% for CLI) suggesting that Gd-DOTA was a suitable surrogate marker for MTX disposition in ventricular CSF. The PBPK predictions for MTX both in CSF of the 3rd ventricle and in plasma were in accordance with the in vivo results. The present study showed that the combination of local CSF microdialysis with MRI acquisition of the brain ventricles and a PBPK model could be a useful methodology to estimate the drug diffusion within CSF ventricles after direct brain CSF administration. Such a methodology would be of interest to clinicians for a rationale determination and optimization of drug dosing parameters in the treatment of leptomeningeal metastases.

In vivo MR spectroscopy of human breast tissue: quantification of fatty acid composition at a clinical field strength (3 T).

OBJECTIVE: To evaluate the feasibility of in vivo measurement of the fatty acid (FA) composition of breast adipose tissue by MRS on a clinical platform. MATERIAL AND METHODS: MRS experiments were performed at 3 T, using a STEAM sequence, on 25 patients diagnosed with breast cancer. MR spectra, acquired on healthy breast tissue, were analysed with the LCModel. RESULTS: The measured values of the saturated fatty acid (SFA), mono-unsaturated fatty acid (MUFA) and poly-unsaturated fatty acid (PUFA) fractions were 23.8 ± 7.1%, 55.4 ± 6.8% and 20.8 ± 4.4%, respectively. The values of SFA, MUFA and PUFA observed in the current study are in the same range as those found in two previous studies performed at 7 T. CONCLUSION: The results of the current study show that it is possible to quantify the fatty acid composition of breast tissue in vivo in a clinical setting (3 T).

The effect of water suppression on the hepatic lipid quantification, as assessed by the LCModel, in a preclinical and clinical scenario.

OBJECTIVE: To investigate the effect of water suppression on the hepatic lipid quantification, using the LCModel. MATERIALS AND METHODS: MR spectra with and without water suppression were acquired in the liver of mice at 4.7 T and patients at 3 T, and processed with the LCModel. The Cramér-Rao Lower Bound (CRLB) values of the seven lipid resonances were determined to assess the impact of water suppression on hepatic lipid quantification. A paired t test was used for comparison between the CRLBs obtained with and without water suppression. RESULTS: For the preclinical data, in the high (low) fat fraction subset an overall impairment in hepatic lipid quantification, i.e. an increase of CRLBs (no significant change of CRLBs) was observed in spectra acquired with water suppression. For the clinical data, there were no substantial changes in the CRLB with water suppression. Because (1) the water suppression does not overall improve the quantification of the lipid resonances and (2) the MR spectrum without water suppression is always acquired for fat fraction calculation, the optimal data-acquisition strategy for liver MRS is to acquire only the MR spectrum without water suppression. CONCLUSION: For quantification of hepatic lipid resonances, it is advantageous to perform MR spectroscopy without water suppression in a clinical and preclinical scenario (at moderate fields).

MRI methodological development of intervertebral disc degeneration: a rabbit in vivo study at 9.4 T.

Intervertebral disc (IVD) degeneration is a complex process characterized by biochemical and structural changes in both the nucleus pulposus and the anulus fibrosus. In this study, we were able to obtain in vivo magnetic resonance (MR) images of the rabbit spine, with several MR imaging (MRI) contrasts (rho, T(1) and T(2)). We quantified several parameters (T(2), apparent diffusion coefficient, disc height and area) to differentiate between healthy and degenerative IVDs and to characterize the degeneration process. To our knowledge, there has not been any previous in vivo study of rabbit IVDs at high-field MRI (9.4 T). A custom radio frequency (RF) coil for 9.4 T was designed to match rabbit IVD morphology, to study the degeneration in vivo on a model of human lumbar disease. Our new probe, a custom half-birdcage-type coil, obtains the necessary exploration depth while meeting the requirements for signal homogeneity and sensitivity of the study. This design addresses some of the difficulties with constructing RF coils at high field strengths.

Perfusional deficit and the dynamics of cerebral edemas in experimental traumatic brain injury using perfusion and diffusion-weighted magnetic resonance imaging.

The aim of this work was to characterize edema dynamics, cerebral blood volume, and flow alterations in an experimental model of brain trauma using quantitative diffusion and perfusion magnetic resonance imaging (MRI). Associated with an influx of water in the intracellular space 1-5 h post-trauma as demonstrated by the 40% reduction in apparent diffusion coefficient, a 70-80% reduction in cerebral blood flow was measured within the lesioned region. Transient hypoperfusion (40-50%) was also observed in the non-traumatized contralateral hemisphere, although there was no evidence of edema formation. After the initial cytotoxic edema, a clear evolution toward extracellular water accumulation was observed, demonstrated by an increase in apparent diffusion coefficient.