Free-Breathing Functional Pulmonary Proton MRI: A Novel Approach Using Voxel-Wise Lung Ventilation (VOLVE) Assessment in Healthy Volunteers and Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: In respiratory medicine, there is a need for sensitive measures of regional lung function that can be performed using standard imaging technology, without the need for inhaled or intravenous contrast agents. PURPOSE: To describe VOxel-wise Lung VEntilation (VOLVE), a new method for quantifying regional lung ventilation (V) and perfusion (Q) using free-breathing proton MRI, and to evaluate VOLVE in healthy never-smokers, healthy people with smoking history, and people with chronic obstructive pulmonary disease (COPD). STUDY TYPE: Prospective pilot. POPULATION: Twelve healthy never-smoker participants (age 30.3 ± 12.5 years, five male), four healthy participants with smoking history (>10 pack-years) (age 42.5 ± 18.3 years, one male), and 12 participants with COPD (age 62.8 ± 11.1 years, seven male). FIELD STRENGTH/SEQUENCE: Single-slice free-breathing two-dimensional fast field echo sequence at 3 T. ASSESSMENT: A novel postprocessing was developed to evaluate the MR signal changes in the lung parenchyma using a linear regression-based approach, which makes use of all the data in the time series for maximum sensitivity. V/Q-weighted maps were produced by computing the cross-correlation, lag and gradient between the respiratory/cardiac phase time course and lung parenchyma signal time courses. A comparison of histogram median and skewness values and spirometry was performed. STATISTICAL TESTS: Kruskal-Wallis tests with Dunn's multiple comparison tests to compare VOLVE metrics between groups; Spearman correlation to assess the correlation between MRI and spirometry-derived parameters; and Bland-Altman analysis and coefficient of variation to evaluate repeatability were used. A P-value <0.05 was considered significant. RESULTS: Significant differences between the groups were found for ventilation between healthy never-smoker and COPD groups (median XCCV, LagV, and GradV) and perfusion (median XCCQ, LagQ, and GradQ). Minimal bias and no significant differences between intravisit scans were found (P range = 0.12-0.97). DATA CONCLUSION: This preliminary study showed that VOLVE has potential to provide metrics of function quantification. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Light Cannabis Use and the Adolescent Brain: An 8-years Longitudinal Assessment of Mental Health, Cognition, and Reward Processing.

RATIONALE: For decades, cannabis has been the most widely used illicit substance in the world, particularly among youth. Research suggests that mental health problems associated with cannabis use may result from its effect on reward brain circuit, emotional processes, and cognition. However, findings are mostly derived from correlational studies and inconsistent, particularly in adolescents. OBJECTIVES AND METHODS: Using data from the IMAGEN study, participants (non-users, persistent users, abstinent users) were classified according to their cannabis use at 19 and 22 years-old. All participants were cannabis-naïve at baseline (14 years-old). Psychopathological symptoms, cognitive performance, and brain activity while performing a Monetary Incentive Delay task were used as predictors of substance use and to analyze group differences over time. RESULTS: Higher scores on conduct problems and lower on peer problems at 14 years-old (n = 318) predicted a greater likelihood of transitioning to cannabis use within 5 years. At 19 years of age, individuals who consistently engaged in low-frequency (i.e., light) cannabis use (n = 57) exhibited greater conduct problems and hyperactivity/inattention symptoms compared to non-users (n = 52) but did not differ in emotional symptoms, cognitive functioning, or brain activity during the MID task. At 22 years, those who used cannabis at both 19 and 22 years-old n = 17), but not individuals that had been abstinent for ≥ 1 month (n = 19), reported higher conduct problems than non-users (n = 17). CONCLUSIONS: Impairments in reward-related brain activity and cognitive functioning do not appear to precede or succeed cannabis use (i.e., weekly, or monthly use). Cannabis-naïve adolescents with conduct problems and more socially engaged with their peers may be at a greater risk for lighter yet persistent cannabis use in the future.

Test-retest assessment of non-contrast MRI sequences to characterise and quantify the small bowel wall in healthy participants.

OBJECTIVE: Quantitative Magnetic Resonance Imaging sequences have been investigated as objective imaging biomarkers of fibrosis and inflammation in Crohn's disease. AIM: To determine the repeatability and inter- and intra-observer agreement of these measures in the prepared small bowel wall. METHODS: Ten healthy participants were scanned at 3 T on 2 separate occasions using T1 and T2 relaxometry, IVIM-DWI and MT sequences. Test-retest repeatability was assessed using the coefficient of variation (CoV) and intra-class correlation coefficients (ICCs) were used to evaluate the intra- and inter-observer agreement RESULTS: Test-retest repeatability in the bowel wall was excellent for apparent diffusion coefficient (ADC), magnetisation transfer ratio (MTR), T1, and diffusion coefficient D (CoV 5%, 7%, 8%, and 10%, respectively), good for perfusion fraction (PF) (CoV 20%) and acceptable for T2 (CoV 21%). Inter-observer agreement was good for the T2, D and ADC (ICC = 0.89, 0.86, 0.76, respectively) and moderate for T1 (ICC = 0.55). Intra-observer agreement was similar to inter-observer agreement. DISCUSSION: This study showed variable results between the different parameters measured. Test-retest repeatability was at least acceptable for all parameters except pseudo-diffusion coefficient D*. Good inter- and intra-observer agreement was obtained for T2, ADC and D, with these parameters performing best in this technical validation study.

Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment.

Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.

Ultra-high-field arterial spin labelling MRI for non-contrast assessment of cortical lesion perfusion in multiple sclerosis.

OBJECTIVES: To assess the feasibility of using an optimised ultra-high-field high-spatial-resolution low-distortion arterial spin labelling (ASL) MRI acquisition to measure focal haemodynamic pathology in cortical lesions (CLs) in multiple sclerosis (MS). METHODS: Twelve MS patients (eight female, mean age 50 years; range 35-64 years) gave informed consent and were scanned on a 7 Tesla Philips Achieva scanner. Perfusion data were collected at multiple post-labelling delay times using a single-slice flow-sensitive alternating inversion recovery ASL protocol with a balanced steady-state free precession readout scheme. CLs were identified using a high-resolution Phase-Sensitive Inversion Recovery (PSIR) scan. Significant differences in perfusion within CLs compared to immediately surrounding normal appearing grey matter (NAGMlocal) and total cortical normal appearing grey matter (NAGMcortical) were assessed using paired t-tests. RESULTS: Forty CLs were identified in PSIR scans that overlapped with the ASL acquisition coverage. After excluding lesions due to small size or intravascular contamination, 27 lesions were eligible for analysis. Mean perfusion was 40 ± 25 ml/100 g/min in CLs, 53 ± 12 ml/100 g/min in NAGMlocal, and 53 ± 8 ml/100 g/min in NAGMcortical. CL perfusion was significantly reduced by 23 ± 9% (mean ± SE, p = 0.013) and 26 ± 9% (p = 0.006) relative to NAGMlocal and NAGMcortical perfusion, respectively. CONCLUSION: This is the first ASL MRI study quantifying CL perfusion in MS at 7 Tesla, demonstrating that an optimised ASL acquisition is sensitive to focal haemodynamic pathology previously observed using dynamic susceptibility contrast MRI. ASL requires no exogenous contrast agent, making it a more appropriate tool to monitor longitudinal perfusion changes in MS, providing a new window to study lesion development. KEY POINTS: • Perfusion can be quantified within cortical lesions in multiple sclerosis using an optimised high spatial resolution arterial spin Labelling MRI acquisition at ultra-high-field. • The majority of cortical lesions assessed using arterial spin labelling are hypo-perfused compared to normal appearing grey matter, in agreement with dynamic susceptibility contrast MRI literature. • Arterial spin labelling MRI, which does not involve the injection of a contrast agent, is a safe and appropriate technique for repeat scanning of an individual patient.

Cine MRI assessment of motility in the unprepared small bowel in the fasting and fed state: Beyond the breath-hold.

BACKGROUND: The symptoms of functional bowel disorders are common in postprandial but investigations are generally undertaken in the fasted state using invasive procedures. MRI provides a noninvasive tool to study the gastrointestinal tract in an unperturbed, fed state. The aim of this study was to develop a technique to assess small bowel motility from cine MRI data in the unprepared bowel in fasting and fed states. METHODS: Fifteen healthy volunteers underwent a baseline MRI scan after which they consumed a 400 g soup. Subjects then underwent a postprandial scan followed by further scans at regular intervals. Small bowel motility was assessed using single-slice bTFE cine MRI. An optimized processing technique was used to generate motility data based on power spectrum analysis of voxel-signal changes with time. Interobserver variability (n = 15) and intra-observer (n = 6) variability were assessed. Changes in the motility index were compared between fasted and immediate postprandial state. KEY RESULTS: Excellent agreement between observers was seen across the range of motility measurements acquired, with intraclass correlation coefficient (ICC) of 0.979 (P < 0.0001) and Bland-Altman limits of agreement 95% CI: -28.9 to 45.9 au. Intra-observer variability was low with ICC of 0.992 and 0.960 (2 observers, P < 0.0001). Changes from the fasted to immediately postprandial state showed an average increase of 122.4% ± 98.7% (n = 15). CONCLUSIONS & INFERENCES: This optimized technique showed excellent inter and intra observer agreement. It was sensitive to changes in motility induced feeding. This technique will be useful to study contractile activity and regional patterns along the gastrointestinal tract under physiological conditions.

31 P magnetization transfer magnetic resonance spectroscopy: Assessing the activation induced change in cerebral ATP metabolic rates at 3 T.

PURPOSE: In vivo 31 P magnetic resonance spectroscopy (MRS) magnetization transfer (MT) provides a direct measure of neuronal activity at the metabolic level. This work aims to use functional 31 P MRS-MT to investigate the change in cerebral adenosine triphosphate (ATP) metabolic rates in healthy adults upon repeated visual stimuli. METHODS: A magnetization saturation transfer sequence with narrowband selective saturation of γ-ATP was developed for 31 P MT experiments at 3 T. RESULTS: Using progressive saturation of γ-ATP, the intrinsic T1 relaxation times of phosphocreatine (PCr) and inorganic phosphate (Pi) at 3 T were measured to be 5.1 ± 0.8 s and 3.0 ± 1.4 s, respectively. Using steady-state saturation of γ-ATP, a significant 24% ± 14% and 11% ± 7% increase in the forward creatine kinase (CK) pseudo-first-order reaction rate constant, k1 , was observed upon visual stimulation in the first and second cycles, respectively, of a paradigm consisting of 10-minute rest followed by 10-minute stimulation, with the measured baseline k1 being 0.35 ± 0.04 s-1 . No significant changes in forward ATP synthase reaction rate, PCr/γ-ATP, Pi/γ-ATP, and nicotinamide adenine dinucleotide/γ-ATP ratios, or intracellular pH were detected upon stimulation. CONCLUSION: This work demonstrates the potential of studying cerebral bioenergetics using functional 31 P MRS-MT to determine the change in the forward CK reaction rate at 3 T. Magn Reson Med 79:22-30, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Gallbladder contraction, gastric emptying and antral motility: single visit assessment of upper GI function in untreated celiac disease using echo-planar MRI.

PURPOSE: To assess gallbladder contraction, gastric emptying, and antral motility in untreated celiac patients and healthy controls using a single MRI examination. MATERIALS AND METHODS: Gallbladder emptying, gastric emptying, and antral motility were measured in 15 celiac patients and 15 age/sex-matched healthy controls following a 323-kcal test meal using EPI techniques. Postprandial dyspepsia scores were recorded on a questionnaire. RESULTS: Fasting gallbladder volume (P=0.01) and the volume of bile ejected postprandially (P=0.014) were increased in celiacs. Gastric emptying tended to be slower in celiacs (P=0.142). Three celiac patients with severe postprandial dyspepsia and total villous atrophy had pathologically delayed gastric emptying and increased fasting gallbladder volume. Antral contractions were absent in five out of 14 patients (36%) five minutes after the meal, but in none of 10 volunteers in whom the antrum could be visualized (P=0.128). CONCLUSION: This study shows that using MRI, multiple parameters related to upper gastrointestinal function in celiac disease can be measured in a single noninvasive study, whereas previously three separate visits would have been required. Celiacs have increased fasting gallbladder volumes and tend to have slower gastric emptying.