Quantitative iron-neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification.

Background: Neuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case-control PD cohort, we evaluated the diagnostic accuracy of quantitative iron-neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association. Methods: PD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin-iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity. Results: In total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p < 0.0001) and smaller sizes after thresholding for low susceptibility (p < 0.0001) on QSM and (b) lower contrast range (p < 0.0001) and smaller sizes after thresholding for high-signal voxels (p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r | <0.6, p < 0.0001), respectively. A composite quantitative neuromelanin-iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI. Conclusion: Quantitative neuromelanin-iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.

Bone Marrow Fat Distribution in Patients With ß-Thalassemia: A Study Using Chemical Shift-Based Water-Fat MRI.

RATIONALE AND OBJECTIVES: Molecular studies have shown the changes in bone marrow fat in relation to altered hematopoiesis. This study aims to investigate the changes in the bone marrow fat in patients affected by ß-thalassemia by using chemical shift-encoded (CSE)-MRI. MATERIALS AND METHODS: Twenty-three subjects, comprising of six healthy (17-31 years old) and 17 ß-thalassemia subjects (19-39 years old), were scanned using a multiecho fast low angle shot sequence (0.94 × 0.94 × 3.00 mm3) and a stimulated echo acquisition mode sequence using 3T MRI. Bone marrow proton density fat fraction (PDFF) was quantified in the left femur of each subject. Regression and Bland-Altman analysis were used to analyze agreement between CSE-MRI and 1H-MRS. PDFF distribution was analyzed using Hartigan's dip test and the computed Wasserstein distances. Jonckheere-Terpstra trend analysis was performed to evaluate the effect of disease severity on PDFF distribution. RESULTS: An excellent agreement was found between PDFF measured using CSE-MRI with 1H-MRS (R2 = 0.91; bias =-1.41%). Healthy subjects showed left-skewed or bimodal PDFF distribution while ß-thalassemia subjects showed bimodal, normal or right-skewed distribution. Jonckheere-Terpstra test shows that PDFF distribution was increasingly different from the norm as disease severity increased (TJT = 166.0, z = 3.806, p < 0.05). Increase in variability of PDFF distribution within each subject group was also seen with increasing disease severity (TJT = 169.0, z = 3.971, p < 0.05). CONCLUSION: CSE-MRI is a promising tool to demonstrate spatial changes and variability in marrow fat distribution, resulting from ineffective erythropoiesis.

Brown Adipose Tissue, Adiposity, and Metabolic Profile in Preschool Children.

CONTEXT: An inverse relationship between brown adipose tissue (BAT) and obesity has previously been reported in older children and adults but is unknown in young children. OBJECTIVE: We investigated the influence of BAT in thermoneutral condition on adiposity and metabolic profile in Asian preschool children. DESIGN, SETTING, AND PARTICIPANTS: A total of 198 children aged 4.5 years from a prospective birth cohort study, Growing Up in Singapore Towards Healthy Outcomes (GUSTO) were successfully studied with water-fat magnetic resonance imaging of the supraclavicular and axillary fat depot (FDSA). Regions within FDSA with fat-signal-fraction between 20% and 80% were considered BAT, and percentage BAT (%BAT; 100*BAT volume/ FDSA volume) was calculated. MAIN OUTCOME MEASURES: Abdominal adipose tissue compartment volumes, ectopic fat in the soleus muscle and liver, fatty liver index, metabolic syndrome scores, and markers of insulin sensitivity. RESULTS: A 1% unit increase in %BAT was associated with lower body mass index, difference (95% CI), -0.08 (-0.10, -0.06) kg/m2 and smaller abdominal adipose tissue compartment volumes. Ethnicity and sex modified these associations. In addition, each unit increase in %BAT was associated with lower ectopic fat at 4.5 years in the liver, -0.008% (-0.013%, -0.003%); soleus muscle, -0.003% (-0.006%, -0.001%) of water content and lower fatty liver index at 6 years. CONCLUSIONS: Higher %BAT is associated with a more favorable metabolic profile. BAT may thus play a role in the pathophysiology of obesity and related metabolic disorders. The observed ethnic and sex differences imply that the protective effect of BAT may vary among different groups.

Neural correlates of retrieval-based enhancement of autobiographical memory in older adults.

Lifelog photo review is considered to enhance the recall of personal events. While a sizable body of research has explored the neural basis of autobiographical memory (AM), there is limited neural evidence on the retrieval-based enhancement effect on event memory among older adults in the real-world environment. This study examined the neural processes of AM as was modulated by retrieval practice through lifelog photo review in older adults. In the experiment, blood-oxygen-level dependent response during subjects' recall of recent events was recorded, where events were cued by photos that may or may not have been exposed to a priori retrieval practice (training). Subjects remembered more episodic details under the trained relative to non-trained condition. Importantly, the neural correlates of AM was exhibited by (1) dissociable cortical areas related to recollection and familiarity, and (2) a positive correlation between the amount of recollected episodic details and cortical activation within several lateral temporal and parietal regions. Further analysis of the brain activation pattern at a few regions of interest within the core remember network showed a training_condition × event_detail interaction effect, suggesting that the boosting effect of retrieval practice depended on the level of recollected event details.

Determinants of intramyocellular lipid accumulation in early childhood.

BACKGROUND/OBJECTIVES: Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. SUBJECTS/METHODS: This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. RESULTS: The mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. CONCLUSION: This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

Association Between Early Life Weight Gain and Abdominal Fat Partitioning at 4.5 Years is Sex, Ethnicity, and Age Dependent.

OBJECTIVE: The aim of this study was to investigate the independent associations between age-specific annual weight gain from birth to age 4 years and fat deposition in metabolically distinct compartments at age 4.5 years in a South Asian longitudinal birth cohort. METHODS: Volumetric abdominal magnetic resonance imaging with comprehensive segmentation of deep and superficial subcutaneous adipose tissue (SAT) and visceral adipose tissues (VAT) was performed in 316 children (150 boys and 166 girls in three ethnic groups; 158 Chinese, 94 Malay, and 64 Indian) aged 4.5 years. Associations between fat volumes and annual relative weight gain conditional on past growth were assessed overall and stratified by sex and ethnicity. RESULTS: Conditional relative weight gain had stronger associations with greater SAT and VAT at age 4.5 years in girls than boys and in Indians compared with Malay and Chinese. Overall, the magnitude of association was the largest during 2 to 3 years for SAT and 1 to 2 years for VAT. Despite similar body weight, Indian children and girls had the highest deep and superficial SAT volumes at age 4.5 years (all interactions P < 0.05). No significant sex or ethnic differences were observed in VAT. With increasing BMI, Indian children had the highest tendency to accumulate VAT, and girls accumulated more fat than boys in all depots (all interactions P < 0.001). CONCLUSIONS: Indian ethnicity and female sex predisposed children to accumulate more fat in the VAT depot with increasing conditional relative weight gain in the second year of life. Thus, 1 to 2 years of age may be a critical window for interventions to reduce visceral fat accumulation.

Fast undersampled functional magnetic resonance imaging using nonlinear regularized parallel image reconstruction.

In this article we aim at improving the performance of whole brain functional imaging at very high temporal resolution (100 ms or less). This is achieved by utilizing a nonlinear regularized parallel image reconstruction scheme, where the penalty term of the cost function is set to the L(1)-norm measured in some transform domain. This type of image reconstruction has gained much attention recently due to its application in compressed sensing and has proven to yield superior spatial resolution and image quality over e.g. Tikhonov regularized image reconstruction. We demonstrate that by using nonlinear regularization it is possible to more accurately localize brain activation from highly undersampled k-space data at the expense of an increase in computation time.