The neurobiological interpretation of developmental BOLD fMRI findings remains difficult due to the confounding issues of potentially varied baseline of brain function and varied strength of neurovascular coupling across age groups. The central theme of the present research is to study the development of brain function and neuronal activity through in vivo assessments of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) both at baseline and during the performance of a working memory task in a cohort of typically developing children aged 7 to 18years. Using a suite of 4 emerging MRI technologies including MR blood oximetry, phase-contrast MRI, pseudo-continuous arterial spin labeling (pCASL) perfusion MRI and concurrent CBF/BOLD fMRI, we found: 1) At baseline, both global CBF and CMRO2 showed an age related decline while global OEF was stable across the age group; 2) During the working memory task, neither BOLD nor CBF responses showed significant variations with age in the activated fronto-parietal brain regions. Nevertheless, detailed voxel-wise analyses revealed sub-regions within the activated fronto-parietal regions that show significant decline of fractional CMRO2 responses with age. These findings suggest that the brain may become more "energy efficient" with age during development.

OBJECTIVE: Our objective was to determine if treatment with cyclophosphamide (CYC) and mycophenolate mofetil (MMF) improves patient-reported outcomes (PROs) among patients with systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: This study examined PROs in patients with SSc-ILD (N = 142) who participated in the Scleroderma Lung Study II, a randomized controlled trial comparing MMF for 2 years with oral CYC for 1 year followed by 1 year of a placebo. Joint models were created to evaluate the course of PROs over 2 years. The difference in PRO scores from baseline to 24 months was measured, and the percentage of patients meeting the minimum clinically important difference (MCID) was calculated. Correlations between PROs and SSc-ILD disease severity measures were also examined. RESULTS: Treatment with CYC and MMF led to improvements in several PROs with no between-treatment differences. Scores for the Transitional Dyspnea Index (TDI) and St. Georges Respiratory Questionnaire (SGRQ) improved significantly over 2 years, and 29%/24% and 28%/25% of participants in the CYC/MMF groups met or exceeded the MCID estimates for TDI and SGRQ, respectively. At baseline, the forced vital capacity (FVC) percentage predicted (FVC%-predicted) did not correlate with the Baseline Dyspnea Index or SGRQ. However, improvements in the FVC%-predicted were weakly associated with improvements in dyspnea (assessed by the TDI) and SGRQ scores. CONCLUSION: Treatment with CYC and MMF improved overall health-related quality of life in patients with SSc-ILD. The relationship between PRO measures and the FVC was relatively weak, suggesting that PROs provide complementary information about treatment efficacy not captured by changes in the FVC alone in this patient population.