Intra- and Inter-visit Repeatability of 129 Xenon Multiple-Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease.

BACKGROUND: Multiple-breath washout (MBW) 129 Xe MRI (MBW Xe-MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies. PURPOSE: To assess intravisit and intervisit repeatability of MBW Xe-MRI in healthy and CF children. STUDY TYPE: Prospective, longitudinal cohort study. SUBJECTS: A total of 18 pediatric subjects (7 healthy, 11 CF). FIELD STRENGTH/SEQUENCE: A 3 T/2D coronal hyperpolarized (HP) 129 Xe images using GRE sequence. ASSESSMENT: All subjects completed MBW Xe-MRI, pulmonary function tests (PFTs) (spirometry, nitrogen [N2 ] MBW for lung clearance index [LCI]) and ventilation defect percent (VDP) at baseline (visit 1) and 1-month after. Fractional ventilation (FV), coefficient of variation (CoVFV ) maps were calculated from MBW Xe-MRI data acquired between intervening air washout breaths performed after an initial xenon breath-hold. Skewness of FV and CoVFV map distributions was also assessed. STATISTICAL TESTS: Repeatability: intraclass correlation coefficients (ICC), within-subject coefficient of variation (CV%), repeatability coefficient (CR). Agreement: Bland-Altman. For correlations between MBW Xe-MRI, VDP and PFTs: Spearman's correlation. Significance threshold: P < 0.05. RESULTS: For FV, intravisit median [IQR] ICC was high in both healthy (0.94 [0.48, 0.99]) and CF (0.83 [0.04, 0.97]) subjects. CoVFV also had good intravisit ICC in healthy (0.92 [0.42, 0.99]) and CF (0.79 [0.02, 0.96]) subjects. Similarly, for FV, intervisit ICC was high in health (0.94 [0.68, 0.99]) and CF (0.89 [0.61, 0.97]). CoVFV also had good intervisit ICC in health (0.92 [0.42, 0.99]) and CF (0.78 [0.26, 0.94]). FV had better intervisit repeatability than VDP. CoVFV correlated significantly with LCI (R = 0.56). Skewness of FV distributions significantly distinguished between cohorts at baseline. DATA CONCLUSION: MBW Xe-MRI had high intravisit and intervisit repeatability in healthy and stable CF subjects. CoVFV correlated with LCI, suggesting the importance of ventilation heterogeneity to early CF. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

PURPOSE: The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests. METHODS: Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross-correlation maps were determined from the free-breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent ), regional flow volume loop cross-correlation maps (VDPCC ), VDPRVent ∪ VDPCC , and multi-slice Xe-MRI. Repeatability was evaluated using Bland-Altman analysis, coefficient of repeatability (CR), and intraclass correlation. RESULTS: Minimal bias and no significant differences were reported for all PREFUL MRI and Xe-MRI VDP parameters between intra- and intervisits (all P > 0.05). Repeatability of VDPRVent , VDPCC , VDPRVent ∪ VDPCC , and multi-slice Xe-MRI were lower between the two-visit scans (CR = 14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same-day scans (CR = 3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe-MRI. CONCLUSION: PREFUL MRI, similar to Xe-MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.

A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer.

BACKGROUND: Women who receive adjuvant chemotherapy for breast cancer develop fatigue, and a subset reports cognitive impairment. Methylphenidate is reported to improve fatigue and to decrease cognitive impairment in other populations. MATERIALS AND METHODS: Women were randomised early during their chemotherapy to receive d-methylphenidate (d-MPH), a form of methylphenidate, or an identical appearing placebo. All participants took placebo for one cycle to ensure compliance and then study medication until completion of chemotherapy. Subjects were assessed at baseline, end of chemotherapy and at approximately 6 months follow-up with the High Sensitivity Cognitive Screen (HSCS) and the Hopkins Verbal Learning Test-Revised (HVLT-R). They also completed the self-report Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-F (F = fatigue) questionnaires, evaluating quality of life and fatigue. RESULTS: A total of 57 evaluable women were randomised: 29 to d-MPH and 28 to placebo; the study did not meet its accrual goal of 170 patients, mainly because women were reluctant to take additional medication in general and methylphenidate in particular. Groups were well matched for age (median, 50 years) and education. d-MPH and placebo were well tolerated. There were no significant differences between the randomised groups in classification of cognitive function by HSCS or in summed FACT-F fatigue scores (the primary endpoints of the study) at any of the assessments. There were also no differences in HLTV-R scores or quality of life. CONCLUSIONS: This study is underpowered, but there are no trends to suggest that d-MPH, taken concurrently with adjuvant chemotherapy, improves quality of life or fatigue.