Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping.

BACKGROUND AND PURPOSE: Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination. MATERIALS AND METHODS: This prospective study included 41 pregnant women (gestational age range, 18-38 weeks) without abnormal findings on fetal brain MR imaging performed for clinical indications. A fast fetal brain macromolecular proton fraction mapping protocol was implemented on a clinical 1.5T MR imaging scanner without software modifications and was performed after a clinical examination with an additional scan time of <5 minutes. 3D macromolecular proton fraction maps were reconstructed from magnetization transfer-weighted, T1-weighted, and proton density-weighted images by the single-point method. Mean macromolecular proton fraction in the brain stem, cerebellum, and thalamus and frontal, temporal, and occipital WM was compared between structures and pregnancy trimesters using analysis of variance. Gestational age dependence of the macromolecular proton fraction was assessed using the Pearson correlation coefficient (r). RESULTS: The mean macromolecular proton fraction in the fetal brain structures varied between 2.3% and 4.3%, being 5-fold lower than macromolecular proton fraction in adult WM. The macromolecular proton fraction in the third trimester was higher compared with the second trimester in the brain stem, cerebellum, and thalamus. The highest macromolecular proton fraction was observed in the brain stem, followed by the thalamus, cerebellum, and cerebral WM. The macromolecular proton fraction in the brain stem, cerebellum, and thalamus strongly correlated with gestational age (r = 0.88, 0.80, and 0.73; P < .001). No significant correlations were found for cerebral WM regions. CONCLUSIONS: Myelin is the main factor determining macromolecular proton fraction in brain tissues. Macromolecular proton fraction mapping is sensitive to the earliest stages of the fetal brain myelination and can be implemented in a clinical setting.

Iron-Insensitive Quantitative Assessment of Subcortical Gray Matter Demyelination in Multiple Sclerosis Using the Macromolecular Proton Fraction.

BACKGROUND AND PURPOSE: Fast macromolecular proton fraction mapping is a recent quantitative MR imaging method for myelin assessment. The objectives of this study were to evaluate the macromolecular proton fraction as a measure of demyelination in subcortical GM structures in multiple sclerosis and assess a potential relationship between demyelination and excess iron deposition using the macromolecular proton fraction and T2* mapping. MATERIALS AND METHODS: Macromolecular proton fraction and T2* maps were obtained from 12 healthy controls, 18 patients with relapsing-remitting MS, and 12 patients with secondary-progressive MS using 3T MR imaging. Parameter values in the caudate nucleus, globus pallidus, putamen, substantia nigra, and thalamus were compared between groups and correlated to clinical data. RESULTS: The macromolecular proton fraction in all subcortical structures and T2* in the globus pallidus, putamen, and caudate nucleus demonstrated a significant monotonic decrease from controls to patients with relapsing-remitting MS and from those with relapsing-remitting MS to patients with secondary-progressive MS. The macromolecular proton fraction in all subcortical structures significantly correlated with the Expanded Disability Status Scale and MS Functional Composite scores with absolute Pearson correlation coefficient (r) values in a range of 0.4-0.6. Significant correlations (r = -0.4 to -0.6) were also identified between the macromolecular proton fraction and the 9-Hole Peg Test, indicating a potential relationship with nigrostriatal pathway damage. Among T2* values, weak significant correlations with clinical variables were found only in the putamen. The macromolecular proton fraction did not correlate with T2* in any of the studied anatomic structures. CONCLUSIONS: The macromolecular proton fraction provides an iron-insensitive measure of demyelination. Myelin loss in subcortical GM structures in MS is unrelated to excess iron deposition. Subcortical GM demyelination is more closely associated with the disease phenotype and disability than iron overload.

MR carotid plaque imaging and contrast-enhanced MR angiography identifies lesions associated with recent ipsilateral thromboembolic symptoms: an in vivo study at 3T.

BACKGROUND AND PURPOSE: Recent research has suggested the importance of plaque composition to identify patients at risk for stroke. This study aims to identify specific plaque features on 3T carotid MR imaging and CE-MRA associated with recent carotid thromboembolic symptoms in patients with mild/moderate versus severe stenosis. MATERIALS AND METHODS: Ninety-seven consecutive patients (symptomatic, 13; asymptomatic, 84) with 50%-99% stenosis by sonography or CT angiography underwent carotid plaque imaging combined with MRA at 3T. The symptomatic carotid artery or the most stenotic asymptomatic carotid artery was chosen as the index vessel to be analyzed. Plaque features were compared by symptomatic status in patients with mild/moderate (30%-70%) versus severe (70%-99%) stenosis on MRA. RESULTS: Ninety (92.8%) patients had sufficient image quality for interpretation. In 50 patients with mild/moderate stenosis, there were significant associations between the presence of the following plaque characteristics and symptoms: thin/ruptured fibrous cap (100% versus 36%, P = .006) and lipid-rich necrotic core (100% versus 39%, P = .022), with marginal association with hemorrhage (86% versus 33%, P = .055). In 40 patients with severe stenosis, only the angiographic presence of ulceration (86% versus 36%, P = .039) was associated with symptoms. CONCLUSIONS: Several plaque components identified on 3T MR imaging are correlated with recent ipsilateral carotid thromboembolic symptoms. These preliminary results also suggest that associations between plaque characteristics and symptom history may vary by degree of stenosis. If confirmed in larger studies, carotid MR imaging may distinguish stable from unstable lesions, particularly in individuals with mild/moderate stenosis in whom the role of surgical intervention is currently unclear.

Predictors of surface disruption with MR imaging in asymptomatic carotid artery stenosis.

BACKGROUND AND PURPOSE: Surface disruption, either ulceration or fibrous cap rupture, has been identified as a key feature of the unstable atherosclerotic plaque. In this prospective observational study, we sought to determine the characteristics of the carotid lesion that predict the development of new surface disruption. MATERIALS AND METHODS: One hundred eight asymptomatic individuals with 50%-79% carotid stenosis underwent carotid MR imaging at baseline and at 3 years. Multicontrast imaging criteria were used to determine the presence or absence of calcification, LRNC, intraplaque hemorrhage, and surface disruption. Volume measurements of plaque morphology and the LRNC and calcification, when present, were collected. RESULTS: At baseline, 21.3% (23/108) of participants were identified with a surface disruption. After 3 years, 9 (10.6%) of the remaining 85 individuals without disruption at baseline developed a new surface disruption during follow-up. Among all baseline variables associated with new surface disruption during regression analysis, the proportion of wall volume occupied by the LRNC (percentage LRNC volume; OR per 5% increase, 2.6; 95% CI, 1.5-4.6) was the strongest classifier (AUC = 0.95) during ROC analysis. New surface disruption was associated with a significant increase in percentage LRNC volume (1.7 +/- 2.0% per year, P = .035). CONCLUSIONS: This prospective investigation of asymptomatic individuals with 50%-79% stenosis provides compelling evidence that LRNC size may govern the risk of future surface disruption. Identification of carotid plaques in danger of developing new surface disruption may prove clinically valuable for preventing the transition from stable to unstable atherosclerotic disease.

Micro magnetic resonance angiography of the finger in systemic sclerosis.

OBJECTIVE: To characterize vascular lesions in SSc disease with high-resolution magnetic resonance angiography (Micro-MRA) of the finger. METHODS: Eight SSc subjects and eight age- and sex-matched healthy controls were recruited for this study. Among the SSc subjects, the mean +/- s.d. age was 54.5 +/- 4.9 yrs, and the mean +/- s.d. duration of disease was 8.3 +/- 8.4 yrs. The numbers of SSc subjects that had telangiectasia, calcinosis and impaired finger flexion were 3, 2 and 3, respectively. The 2D time-of-flight micro-MRA was performed on a 3T clinical MRI scanner using a custom-designed finger coil with an in-plane resolution of 0.16 x 0.21 mm(2) and slice thickness of 1.2 mm. The data for the proper palmar digital artery lumen area, the number of visible dorsal digital veins and a semi-quantitative vascular score, which evaluates the overall integrity of digital vessels, were independently evaluated by two experienced reviewers who were blinded to the status of the subject. RESULTS: Micro-MRA detected significant differences in the digital vasculature between SSc subjects and healthy volunteers. The SSc subjects had a significantly decreased digital artery lumen area (0.13 +/- 0.06 vs 0.53 +/- 0.26 mm(2), P < 0.001), a reduced number of digital veins (0.63 +/- 1.06 vs 3.13 +/- 0.99, P = 0.001) and a lowered overall vascular score (1.75 +/- 1.04 vs 3.5 +/- 0.53, P = 0.001). The study also found that both the digital artery lumen area (Pearson's; r = -0.72, P = 0.044) and vascular scores (Spearman's; rho = -0.75, P = 0.047) of the SSc subjects were inversely correlated with the duration of the disease. CONCLUSIONS: Micro-MRA can be used to identify and quantitatively characterize the vascular disease in SSc fingers. The parameters derived from micro-MRA could potentially be used as prospective biomarkers for clinical evaluation.

Quantitative evaluation of carotid plaque composition by in vivo MRI.

OBJECTIVE: This study evaluates the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo. METHODS AND RESULTS: Thirty-one subjects scheduled for carotid endarterectomy were imaged with a 1.5T scanner using time-of-flight-, T1-, proton density-, and T2-weighted images. A total of 214 MR imaging locations were matched to corresponding histology sections. For MRI and histology, area measurements of the major plaque components such as lipid-rich/necrotic core (LR/NC), calcification, loose matrix, and dense (fibrous) tissue were recorded as percentages of the total wall area. Intraclass correlation coefficients (ICCs) were computed to determine intrareader and inter-reader reproducibility. MRI measurements of plaque composition were statistically equivalent to those of histology for the LR/NC (23.7 versus 20.3%; P=0.1), loose matrix (5.1 versus 6.3%; P=0.1), and dense (fibrous) tissue (66.3% versus 64%; P=0.4). Calcification differed significantly when measured as a percentage of wall area (9.4 versus 5%; P<0.001). Intrareader and inter-reader reproducibility was good to excellent for all tissue components, with ICCs ranging from 0.73 to 0.95. CONCLUSIONS: MRI-based tissue quantification is accurate and reproducible. This application can be used in therapeutic clinical trials and in prospective longitudinal studies to examine carotid atherosclerotic plaque progression and regression.