Noise suppression of proton magnetic resonance spectroscopy improves paediatric brain tumour classification.

Proton magnetic resonance spectroscopy (1H-MRS) is increasingly used for clinical brain tumour diagnosis, but suffers from limited spectral quality. This retrospective and comparative study aims at improving paediatric brain tumour classification by performing noise suppression on clinical 1H-MRS. Eighty-three/forty-two children with either an ependymoma (ages 4.6 ± 5.3/9.3 ± 5.4), a medulloblastoma (ages 6.9 ± 3.5/6.5 ± 4.4), or a pilocytic astrocytoma (8.0 ± 3.6/6.3 ± 5.0), recruited from four centres across England, were scanned with 1.5T/3T short-echo-time point-resolved spectroscopy. The acquired raw 1H-MRS was quantified by using Totally Automatic Robust Quantitation in NMR (TARQUIN), assessed by experienced spectroscopists, and processed with adaptive wavelet noise suppression (AWNS). Metabolite concentrations were extracted as features, selected based on multiclass receiver operating characteristics, and finally used for identifying brain tumour types with supervised machine learning. The minority class was oversampled through the synthetic minority oversampling technique for comparison purposes. Post-noise-suppression 1H-MRS showed significantly elevated signal-to-noise ratios (P < .05, Wilcoxon signed-rank test), stable full width at half-maximum (P > .05, Wilcoxon signed-rank test), and significantly higher classification accuracy (P < .05, Wilcoxon signed-rank test). Specifically, the cross-validated overall and balanced classification accuracies can be improved from 81% to 88% overall and 76% to 86% balanced for the 1.5T cohort, whilst for the 3T cohort they can be improved from 62% to 76% overall and 46% to 56%, by applying Naïve Bayes on the oversampled 1H-MRS. The study shows that fitting-based signal-to-noise ratios of clinical 1H-MRS can be significantly improved by using AWNS with insignificantly altered line width, and the post-noise-suppression 1H-MRS may have better diagnostic performance for paediatric brain tumours.

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.

Exploring the acute effects of running on cerebral blood flow and food cue reactivity in healthy young men using functional magnetic resonance imaging.

Acute exercise suppresses appetite and alters food-cue reactivity, but the extent exercise-induced changes in cerebral blood flow (CBF) influences the blood-oxygen-level-dependent (BOLD) signal during appetite-related paradigms is not known. This study examined the impact of acute running on visual food-cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2 ) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five-minute pseudo-continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD-fMRI was acquired during a food-cue reactivity task before and 28 min after exercise/rest. Food-cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤ .018). No time-by-trial interactions for CBF were identified (p ≥ .087). Exercise induced moderate-to-large reductions in subjective appetite ratings (Cohen's d = 0.53-0.84; p ≤ .024) and increased food-cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise-induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food-cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.

MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial.

Background Diffuse midline gliomas (DMG) are characterized by a high incidence of H3 K27 mutations and poorer outcome. The HERBY trial has provided one of the largest cohorts of pediatric DMGs with available radiologic, histologic-genotypic, and survival data. Purpose To define MRI and molecular characteristics of DMG. Materials and Methods This study is a secondary analysis of a prospective trial (HERBY; ClinicalTrials.gov identifier, NCT01390948) undertaken between October 2011 and February 2016. Among 121 HERBY participants, 50 had midline nonpontine-based tumors. Midline high-grade gliomas were reclassified into DMG H3 K27 mutant, H3 wild type with enhancer of zest homologs inhibitory protein overexpression, epidermal growth factor receptormutant, or not otherwise stated. The epicenter of each tumor and other radiologic characteristics were ascertained from MRI and correlated with the new subtype classification, histopathologic characteristics, surgical extent, and outcome parameters. Kaplan-Meier curves and log-rank tests were applied to determine and describe survival differences between groups. Results There were 42 participants (mean age, 12 years ± 4 [SD]; 23 girls) with radiologically evaluable thalamic-based DMG. Eighteen had partial thalamic involvement (12 thalamopulvinar, six anteromedial), 10 involved a whole thalamus, nine had unithalamic tumors with diffuse contiguous extension, and five had bithalamic tumors (two symmetric, three partial). Twenty-eight participants had DMG H3 K27 mutant tumors; there were no differences in outcome compared with other DMGs (n = 4). Participants who underwent major debulking or total or near-total resection had longer overall survival (OS): 18.5 months vs 11.4 months (P = .02). Enrolled participants who developed leptomeningeal metastatic dissemination before starting treatment had worse outcomes (event-free survival, 2.9 months vs 8.0 months [P = .02]; OS, 11.4 months vs 18.5 months [P = .004]). Conclusion Thalamic involvement of diffuse midline gliomas ranged from localized partial thalamic to holo- or bithalamic with diffuse contiguous spread and had poor outcomes, irrespective of H3 K27 subtype alterations. Leptomeningeal dissemination and less than 50% surgical resection were adverse risk factors for survival. Clinical trial registration no. NCT01390948 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Widjaja in this issue.

Metabolite selection for machine learning in childhood brain tumour classification.

MRS can provide high accuracy in the diagnosis of childhood brain tumours when combined with machine learning. A feature selection method such as principal component analysis is commonly used to reduce the dimensionality of metabolite profiles prior to classification. However, an alternative approach of identifying the optimal set of metabolites has not been fully evaluated, possibly due to the challenges of defining this for a multi-class problem. This study aims to investigate metabolite selection from in vivo MRS for childhood brain tumour classification. Multi-site 1.5 T and 3 T cohorts of patients with a brain tumour and histological diagnosis of ependymoma, medulloblastoma and pilocytic astrocytoma were retrospectively evaluated. Dimensionality reduction was undertaken by selecting metabolite concentrations through multi-class receiver operating characteristics and compared with principal component analysis. Classification accuracy was determined through leave-one-out and k-fold cross-validation. Metabolites identified as crucial in tumour classification include myo-inositol (P < 0.05, AUC=0.81±0.01 ), total lipids and macromolecules at 0.9 ppm (P < 0.05, AUC=0.78±0.01 ) and total creatine (P < 0.05, AUC=0.77±0.01 ) for the 1.5 T cohort, and glycine (P < 0.05, AUC=0.79±0.01 ), total N-acetylaspartate (P < 0.05, AUC=0.79±0.01 ) and total choline (P < 0.05, AUC=0.75±0.01 ) for the 3 T cohort. Compared with the principal components, the selected metabolites were able to provide significantly improved discrimination between the tumours through most classifiers (P < 0.05). The highest balanced classification accuracy determined through leave-one-out cross-validation was 85% for 1.5 T 1 H-MRS through support vector machine and 75% for 3 T 1 H-MRS through linear discriminant analysis after oversampling the minority. The study suggests that a group of crucial metabolites helps to achieve better discrimination between childhood brain tumours.

Dynamic susceptibility-contrast magnetic resonance imaging with contrast agent leakage correction aids in predicting grade in pediatric brain tumours: a multicenter study.

BACKGROUND: Relative cerebral blood volume (rCBV) measured using dynamic susceptibility-contrast MRI can differentiate between low- and high-grade pediatric brain tumors. Multicenter studies are required for translation into clinical practice. OBJECTIVE: We compared leakage-corrected dynamic susceptibility-contrast MRI perfusion parameters acquired at multiple centers in low- and high-grade pediatric brain tumors. MATERIALS AND METHODS: Eighty-five pediatric patients underwent pre-treatment dynamic susceptibility-contrast MRI scans at four centers. MRI protocols were variable. We analyzed data using the Boxerman leakage-correction method producing pixel-by-pixel estimates of leakage-uncorrected (rCBVuncorr) and corrected (rCBVcorr) relative cerebral blood volume, and the leakage parameter, K2. Histological diagnoses were obtained. Tumors were classified by high-grade tumor. We compared whole-tumor median perfusion parameters between low- and high-grade tumors and across tumor types. RESULTS: Forty tumors were classified as low grade, 45 as high grade. Mean whole-tumor median rCBVuncorr was higher in high-grade tumors than low-grade tumors (mean ± standard deviation [SD] = 2.37±2.61 vs. -0.14±5.55; P<0.01). Average median rCBV increased following leakage correction (2.54±1.63 vs. 1.68±1.36; P=0.010), remaining higher in high-grade tumors than low grade-tumors. Low-grade tumors, particularly pilocytic astrocytomas, showed T1-dominant leakage effects; high-grade tumors showed T2*-dominance (mean K2=0.017±0.049 vs. 0.002±0.017). Parameters varied with tumor type but not center. Median rCBVuncorr was higher (mean = 1.49 vs. 0.49; P=0.015) and K2 lower (mean = 0.005 vs. 0.016; P=0.013) in children who received a pre-bolus of contrast agent compared to those who did not. Leakage correction removed the difference. CONCLUSION: Dynamic susceptibility-contrast MRI acquired at multiple centers helped distinguish between children's brain tumors. Relative cerebral blood volume was significantly higher in high-grade compared to low-grade tumors and differed among common tumor types. Vessel leakage correction is required to provide accurate rCBV, particularly in low-grade enhancing tumors.

Dorsolateral prefrontal circuit effective connectivity mediates the relationship between white matter structure and PASAT-3 performance in multiple sclerosis.

Three decades ago a series of parallel circuits were described involving the frontal cortex and deep grey matter structures, with putative roles in control of motor and oculomotor function, cognition, behaviour and emotion. The circuit comprising the dorsolateral prefrontal cortex, caudate, globus pallidus and thalamus has a putative role in regulating executive functions. The aim of this study is to investigate effective connectivity (EC) of the dorsolateral-prefrontal circuit and its association with PASAT-3 performance in people with multiple sclerosis(MS). We use Granger causality analysis of resting-state functional MRI from 52 people with MS and 36 healthy people to infer that reduced EC in the afferent limb of the dorsolateral prefrontal circuit occurs in the people with MS with cognitive dysfunction (left: p = .006; right: p = .029), with bilateral EC reductions in this circuit resulting in more severe cognitive dysfunction than unilateral reductions alone (p = .002). We show that reduced EC in the afferent limb of the dorsolateral prefrontal circuit mediates the relationship between cognitive performance and macrostrucutral and microstructural alterations of white matter tracts in components of the circuit. Specificity is shown by the absence of any relationship between cognition and EC in the analogous and anatomically proximal motor circuit. We demonstrate good stability of the EC measures in people with MS over an interval averaging 8-months. Key positive and negative results are replicated in an independent cohort of people with MS. Our findings identify the dorsolateral prefrontal circuit as a potential target for therapeutic strategies aimed at improving cognition in people with MS.

Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Response criteria for paediatric high-grade glioma vary historically and across different cooperative groups. The Response Assessment in Neuro-Oncology working group developed response criteria for adult high-grade glioma, but these were not created to meet the unique challenges in children with the disease. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric high-grade glioma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric high-grade gliomas to various treatments. For areas in which scientific investigation was scarce, consensus was reached through an iterative process. RAPNO response assessment recommendations include the use of MRI of the brain and the spine, assessment of clinical status, and the use of corticosteroids or antiangiogenics. Imaging standards for brain and spine are defined. Compared with the recommendations for the management of adult high-grade glioma, for paediatrics there is inclusion of diffusion-weighted imaging and a higher reliance on T2-weighted fluid-attenuated inversion recovery. Consensus recommendations and response definitions have been established and, similar to other RAPNO recommendations, prospective validation in clinical trials is warranted.

Switching from linear to macrocyclic gadolinium-based contrast agents halts the relative T1 -Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study.

BACKGROUND: Studies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium-based contrast agent (GBCA). HYPOTHESIS: The trajectory of changes in relative dentate nucleus (DN) and globus pallidus (GP) SI in children receiving multiple doses of GBCA will alter when switched from linear to macrocyclic agents. STUDY TYPE: Retrospective longitudinal. POPULATION: Thirty-five children, age range 0.5-17.0 years, undergoing brain tumor follow-up between 2006 and 2017. FIELD STRENGTH/SEQUENCE: Unenhanced T1 WI, serial scans at both 1.5T and 3T. ASSESSMENT: Regions of interest were drawn on DN, GP, and SIs normalized to middle cerebellar peduncle (DN/MCP) and cerebral white matter (GP/CWM), respectively. A change in SI ratios as a function of dose (slope gradient) calculated according to the type of contrast agent received: linear only, macrocyclic only, or switchover from linear to macrocyclic. For the latter, gradients were compared before and after switchover. The effect of anticancer treatment on slope gradient was tested. STATISTICAL TESTS: One-sample t-test or Mann-Whitney U-test for slope gradients differing from zero. Independent samples t-tests to compare slope gradient groups. Paired sample t-tests to compare slope gradients before and after switchover. RESULTS: A significant (P < 0.05) increase in SI ratio was observed following multiple doses of linear but not macrocyclic agents: mean percentage increase per dose in SI was 0.063% vs. -0.034% for DN/MCP, and 0.078% vs. 0.004% for GP/CWM ratios. A significant (P < 0.05) change of SI trajectory in the DN/MCP ratio was demonstrated when switching from a linear to macrocyclic agent. There was no difference in SI trajectory between patients who had anticancer therapies and those who did not, DN/MCP P = 0.740; GP/BWM P = 0.694. DATA CONCLUSION: Switching from linear to macrocyclic gadolinium-based contrast agents seems to halt the relative T1 signal increase in deep gray matter in children. Anticancer treatments appeared to have no impact on the trajectory of T1 SI. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:288-295.

Single Test to ARrive at Multiple Sclerosis (STAR-MS) diagnosis: A prospective pilot study assessing the accuracy of the central vein sign in predicting multiple sclerosis in cases of diagnostic uncertainty.

BACKGROUND: Misdiagnosis is common in multiple sclerosis (MS) as a proportion of patients present with atypical clinical/magnetic resonance imaging (MRI) findings. The central vein sign has the potential to be a non-invasive, MS-specific biomarker. OBJECTIVE: To test the accuracy of the central vein sign in predicting a diagnosis of MS in patients with diagnostic uncertainty at disease presentation using T2*-weighted, 3 T MRI. METHODS: In this prospective pilot study, we recruited individuals with symptoms unusual for MS but with brain MRI consistent with the disease, and those with a typical clinical presentation of MS whose MRI did not suggest MS. We calculated the proportion of lesions with central veins for each patient and compared the results to the eventual clinical diagnoses. The optimal central vein threshold for diagnosis was established. RESULTS: Thirty-eight patients were scanned, 35 of whom have received a clinical diagnosis. Median percentage of lesions with central veins was 51% in MS and 28% in non-MS. A threshold of 40.7% lesions with central veins resulted in 100% sensitivity and 73.9% specificity. CONCLUSION: The central vein sign assessed with a clinically available T2* scan can successfully diagnose MS in cases of diagnostic uncertainty. The central vein sign should be considered as a diagnostic biomarker in MS.

Aberrant visual pathway development in albinism: From retina to cortex.

Albinism refers to a group of genetic abnormalities in melanogenesis that are associated neuronal misrouting through the optic chiasm. We perform quantitative assessment of visual pathway structure and function in 23 persons with albinism (PWA) and 20 matched controls using optical coherence tomography (OCT), volumetric magnetic resonance imaging (MRI), diffusion tensor imaging and visual evoked potentials (VEP). PWA had a higher streamline decussation index (percentage of total tractography streamlines decussating at the chiasm) compared with controls (Z = -2.24, p = .025), and streamline decussation index correlated weakly with inter-hemispheric asymmetry measured using VEP (r = .484, p = .042). For PWA, a significant correlation was found between foveal development index and total number of streamlines (r = .662, p < .001). Significant positive correlations were found between peri-papillary retinal nerve fibre layer thickness and optic nerve (r = .642, p < .001) and tract (r = .663, p < .001) width. Occipital pole cortical thickness was 6.88% higher (Z = -4.10, p < .001) in PWA and was related to anterior visual pathway structures including foveal retinal pigment epithelium complex thickness (r = -.579, p = .005), optic disc (r = .478, p = .021) and rim areas (r = .597, p = .003). We were unable to demonstrate a significant relationship between OCT-derived foveal or optic nerve measures and MRI-derived chiasm size or streamline decussation index. Our novel tractographic demonstration of altered chiasmatic decussation in PWA corresponds to VEP measured cortical asymmetry and is consistent with chiasmatic misrouting in albinism. We also demonstrate a significant relationship between retinal pigment epithelium and visual cortex thickness indicating that retinal pigmentation defects in albinism lead to downstream structural reorganisation of the visual cortex.

Application of pattern recognition techniques for classification of pediatric brain tumors by in vivo 3T 1 H-MR spectroscopy-A multi-center study.

PURPOSE: 3T magnetic resonance scanners have boosted clinical application of 1 H-MR spectroscopy (MRS) by offering an improved signal-to-noise ratio and increased spectral resolution, thereby identifying more metabolites and extending the range of metabolic information. Spectroscopic data from clinical 1.5T MR scanners has been shown to discriminate between pediatric brain tumors by applying machine learning techniques to further aid diagnosis. The purpose of this multi-center study was to investigate the discriminative potential of metabolite profiles obtained from 3T scanners in classifying pediatric brain tumors. METHODS: A total of 41 pediatric patients with brain tumors (17 medulloblastomas, 20 pilocytic astrocytomas, and 4 ependymomas) were scanned across four different hospitals. Raw spectroscopy data were processed using TARQUIN. Borderline synthetic minority oversampling technique was used to correct for the data skewness. Different classifiers were trained using linear discriminative analysis, support vector machine, and random forest techniques. RESULTS: Support vector machine had the highest balanced accuracy for discriminating the three tumor types. The balanced accuracy achieved was higher than the balanced accuracy previously reported for similar multi-center dataset from 1.5T magnets with echo time 20 to 32 ms alone. CONCLUSION: This study showed that 3T MRS can detect key differences in metabolite profiles for the main types of childhood tumors. Magn Reson Med 79:2359-2366, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Prospective multicentre evaluation and refinement of an analysis tool for magnetic resonance spectroscopy of childhood cerebellar tumours.

BACKGROUND: A tool for diagnosing childhood cerebellar tumours using magnetic resonance (MR) spectroscopy peak height measurement has been developed based on retrospective analysis of single-centre data. OBJECTIVE: To determine the diagnostic accuracy of the peak height measurement tool in a multicentre prospective study, and optimise it by adding new prospective data to the original dataset. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) and single-voxel MR spectroscopy were performed on children with cerebellar tumours at three centres. Spectra were processed using standard scanner software and peak heights for N-acetyl aspartate, creatine, total choline and myo-inositol were measured. The original diagnostic tool was used to classify 26 new tumours as pilocytic astrocytoma, medulloblastoma or ependymoma. These spectra were subsequently combined with the original dataset to develop an optimised scheme from 53 tumours in total. RESULTS: Of the pilocytic astrocytomas, medulloblastomas and ependymomas, 65.4% were correctly assigned using the original tool. An optimized scheme was produced from the combined dataset correctly assigning 90.6%. Rare tumour types showed distinctive MR spectroscopy features. CONCLUSION: The original diagnostic tool gave modest accuracy when tested prospectively on multicentre data. Increasing the dataset provided a diagnostic tool based on MR spectroscopy peak height measurement with high levels of accuracy for multicentre data.

Activation induced changes in GABA: Functional MRS at 7T with MEGA-sLASER.

Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence was developed at 7T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (-12±5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10min of hand-clenching, compared to an initial baseline level (GABA/tCr =0.11±0.02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA-sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7T.

Can functional magnetic resonance imaging studies help with the optimization of health messaging for lifestyle behavior change? A systematic review.

Unhealthy behaviors, including smoking, poor nutrition, excessive alcohol consumption, physical inactivity and sedentary lifestyles, are global risk factors for non-communicable diseases and premature death. Functional magnetic resonance imaging (fMRI) offers a unique approach to optimize health messages by examining how the brain responds to information relating to health. Our aim was to systematically review fMRI studies that have investigated variations in brain activation in response to health messages relating to (i) smoking; (ii) alcohol consumption; (iii) physical activity; (iv) diet; and (v) sedentary behavior. The electronic databases used were Medline/PubMed, Web of Science (Core Collection), PsychINFO, SPORTDiscuss, Cochrane Library and Open Grey. Studies were included if they investigated subjects aged ≥10years and were published before January 2017. Of the 13,836 studies identified in the database search, 18 studies (smoking k=15; diet k=2; physical activity/sedentary behavior k=1) were included in the review. The prefrontal cortex was activated in seven (47%) of the smoking-related studies and the physical activity study. Results suggest that activation of the ventromedial, dorsolateral and medial prefrontal cortex regions were predictive of subsequent behavior change following exposure to aversive anti-smoking stimuli. Studies investigating the neurological responses to anti-smoking material were most abundant. Of note, the prefrontal cortex and amygdala were most commonly activated in response to health messages across lifestyle behaviors. The review highlights an important disparity between research focusing on different lifestyle behaviors. Insights from smoking literature suggest fMRI may help to optimize health messaging in relation to other lifestyle behaviors.

Brain Activation in Response to Personalized Behavioral and Physiological Feedback From Self-Monitoring Technology: Pilot Study.

BACKGROUND: The recent surge in commercially available wearable technology has allowed real-time self-monitoring of behavior (eg, physical activity) and physiology (eg, glucose levels). However, there is limited neuroimaging work (ie, functional magnetic resonance imaging [fMRI]) to identify how people's brains respond to receiving this personalized health feedback and how this impacts subsequent behavior. OBJECTIVE: Identify regions of the brain activated and examine associations between activation and behavior. METHODS: This was a pilot study to assess physical activity, sedentary time, and glucose levels over 14 days in 33 adults (aged 30 to 60 years). Extracted accelerometry, inclinometry, and interstitial glucose data informed the construction of personalized feedback messages (eg, average number of steps per day). These messages were subsequently presented visually to participants during fMRI. Participant physical activity levels and sedentary time were assessed again for 8 days following exposure to this personalized feedback. RESULTS: Independent tests identified significant activations within the prefrontal cortex in response to glucose feedback compared with behavioral feedback (P<.001). Reductions in mean sedentary time (589.0 vs 560.0 minutes per day, P=.014) were observed. Activation in the subgyral area had a moderate correlation with minutes of moderate-to-vigorous physical activity (r=0.392, P=.043). CONCLUSION: Presenting personalized glucose feedback resulted in significantly more brain activation when compared with behavior. Participants reduced time spent sedentary at follow-up. Research on deploying behavioral and physiological feedback warrants further investigation.

Metadata Correction: Brain Activation in Response to Personalized Behavioral and Physiological Feedback From Self-Monitoring Technology: Pilot Study.

[This corrects the article DOI: 10.2196/jmir.8890.].

Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions.

BACKGROUND: White matter lesions are frequently detected using brain magnetic resonance imaging (MRI) performed for various indications. Most are microangiopathic, but demyelination, including multiple sclerosis (MS), is an important cause; conventional MRI cannot always distinguish between these pathologies. The proportion of lesions with a central vein on 7-T T2*-weighted MRI prospectively distinguishes demyelination from microangiopathic lesions. OBJECTIVE: To test whether 3-T T2*-weighted MRI can differentiate MS from microangiopathic brain lesions. METHODS: A total of 40 patients were studied. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent 3-T T2*-weighted brain MRI. Anonymised scans were analysed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients (13 with MS and 7 with microangiopathic lesions) by a blinded observer. RESULTS: Within the test cohort, all patients with MS had central veins visible in >45% of brain lesions, while the rest had central veins visible in <45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorised. CONCLUSION: 3-T T2*-weighted brain MRI distinguishes perivenous MS lesions from microangiopathic lesions. Clinical application of this technique could supplement existing diagnostic algorithms.

Histologic validation of locus coeruleus MRI contrast in post-mortem tissue.

The locus coeruleus (LC) noradrenergic system regulates arousal and modulates attention through its extensive projections across the brain. LC dysfunction has been implicated in a broad range of neurodevelopmental, neurodegenerative and psychiatric disorders, as well as in the cognitive changes observed during normal aging. Magnetic resonance imaging (MRI) has been used to characterize the human LC (elevated contrast relative to surrounding structures), but there is limited understanding of the factors underlying putative LC contrast that are critical to successful biomarker development and confidence in localizing nucleus LC. We used ultra-high-field 7 T magnetic resonance imaging (MRI) to acquire T1-weighted microscopy resolution images (78 µm in-plane resolution) of the LC from post-mortem tissue samples. Histological analyses were performed to characterize the distribution of tyrosine hydroxylase (TH) and neuromelanin in the scanned tissue, which allowed for direct comparison with MR microscopy images. Our results indicate that LC-MRI contrast corresponds to the location of neuromelanin cells in LC; these also correspond to norepinephrine neurons. Thus, neuromelanin appears to serve as a natural contrast agent for nucleus LC that can be used to localize nucleus LC and may have the potential to characterize neurodegenerative disease.

Multi-centre reproducibility of diffusion MRI parameters for clinical sequences in the brain.

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences. An ice-water phantom and nine healthy volunteers were scanned across fives centres on eight scanners (four Siemens 1.5T, four Philips 3T). The mean ADC, IVIM parameters (diffusion coefficient D and perfusion fraction f) and DTI parameters (mean diffusivity MD and fractional anisotropy FA), were measured in grey matter, white matter and specific brain sub-regions. A mixed effect model was used to measure the intra- and inter-scanner coefficient of variation (CV) for each of the five parameters. ADC, D, MD and FA had a good intra- and inter-scanner reproducibility in both grey and white matter, with a CV ranging between 1% and 7.4%; mean 2.6%. Other brain regions also showed high levels of reproducibility except for small structures such as the choroid plexus. The IVIM parameter f had a higher intra-scanner CV of 8.4% and inter-scanner CV of 24.8%. No major difference in the inter-scanner CV for ADC, D, MD and FA was observed when analysing the 1.5T and 3T scanners separately. ADC, D, MD and FA all showed good intra-scanner reproducibility, with the inter-scanner reproducibility being comparable or faring slightly worse, suggesting that using data from multiple scanners does not have an adverse effect compared with using data from the same scanner. The IVIM parameter f had a poorer inter-scanner CV when scanners of different field strengths were combined, and the parameter was also affected by the scan acquisition resolution. This study shows that the majority of diffusion MRI derived parameters are robust across 1.5T and 3T scanners and suitable for use in multi-centre clinical studies and trials.