Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.

Background and Purpose: Recent studies using automated perfusion imaging software have identified adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral tissue is poorly characterized in childhood arterial ischemic stroke (AIS). We explore the feasibility of using automated perfusion-diffusion imaging software to characterize penumbra in childhood AIS. Methods: An observational cohort study of children with acute unilateral AIS presenting to our institution. Diffusion-weighted imaging and dynamic susceptibility contrast perfusion magnetic resonance imaging performed within 72 hours of symptom onset were necessary for inclusion. Perfusion-diffusion mismatch was estimated using RAPID software. Ischemic core was defined as apparent diffusion coefficient <620×10−6 mm2/s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume <70 mL, mismatch volume ≥15 mL, and a mismatch ratio ≥1.8. Results: Twenty-nine children (median 8 years old, interquartile range, 4.4­14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3­11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5­25.3). RAPID detected an ischemic core in 19 (66%) patients. In the remaining cases, the mean apparent diffusion coefficient values were mostly higher than the threshold as the majority of these presentations were delayed (median >21 hours) and infarct volumes were small (<3.5 mL). Overall, 3 children, imaged at 3.75, 11, and 23.5 hours had favorable mismatch profiles. Conclusions: This study demonstrates it is feasible to rapidly assess perfusion-diffusion mismatch in childhood AIS using automated software. Favorable mismatch profiles, using adult-based parameters, persisted beyond the standard 4.5 hours window for thrombolysis, suggesting potential therapeutic benefit of RAPID use. Further work is required to determine the utility of perfusion-based imaging to guide clinical decision making, whether adult thresholds require modification in childhood AIS, and to investigate the effect of time-delay and cause on mismatch characteristics.

Altered resting-state functional connectivity within the developing social brain after pediatric traumatic brain injury.

Traumatic brain injury (TBI) in childhood and adolescence can interrupt expected development, compromise the integrity of the social brain network (SBN) and impact social skills. Yet, no study has investigated functional alterations of the SBN following pediatric TBI. This study explored functional connectivity within the SBN following TBI in two independent adolescent samples. First, 14 adolescents with mild complex, moderate or severe TBI and 16 typically developing controls (TDC) underwent resting-state functional magnetic resonance imaging 12-24 months post-injury. Region of interest analyses were conducted to compare the groups' functional connectivity using selected SBN seeds. Then, replicative analysis was performed in an independent sample of adolescents with similar characteristics (9 TBI, 9 TDC). Results were adjusted for age, sex, socioeconomic status and total gray matter volume, and corrected for multiple comparisons. Significant between-group differences were detected for functional connectivity in the dorsomedial prefrontal cortex and left fusiform gyrus, and between the left fusiform gyrus and left superior frontal gyrus, indicating positive functional connectivity for the TBI group (negative for TDC). The replication study revealed group differences in the same direction between the left superior frontal gyrus and right fusiform gyrus. This study indicates that pediatric TBI may alter functional connectivity of the social brain. Frontal-fusiform connectivity has previously been shown to support affect recognition and changes in the function of this network could relate to more effortful processing and broad social impairments.

Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery.

Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery-related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI-based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530-3543, 2016. © 2016 Wiley Periodicals, Inc.

Developmental brain trajectories in children with ADHD and controls: a longitudinal neuroimaging study.

BACKGROUND: The symptom profile and neuropsychological functioning of individuals with Attention Deficit/Hyperactivity Disorder (ADHD), change as they enter adolescence. It is unclear whether variation in brain structure and function parallels these changes, and also whether deviations from typical brain development trajectories are associated with differential outcomes. This paper describes the Neuroimaging of the Children's Attention Project (NICAP), a comprehensive longitudinal multimodal neuroimaging study. Primary aims are to determine how brain structure and function change with age in ADHD, and whether different trajectories of brain development are associated with variations in outcomes including diagnostic persistence, and academic, cognitive, social and mental health outcomes. METHODS/DESIGN: NICAP is a multimodal neuroimaging study in a community-based cohort of children with and without ADHD. Approximately 100 children with ADHD and 100 typically developing controls will be scanned at a mean age of 10 years (range; 9-11years) and will be re-scanned at two 18-month intervals (ages 11.5 and 13 years respectively). Assessments include a structured diagnostic interview, parent and teacher questionnaires, direct child cognitive/executive functioning assessment and magnetic resonance imaging (MRI). MRI acquisition techniques, collected at a single site, have been selected to provide optimized information concerning structural and functional brain development. DISCUSSION: This study will allow us to address the primary aims by describing the neurobiological development of ADHD and elucidating brain features associated with differential clinical/behavioral outcomes. NICAP data will also be explored to assess the impact of sex, ADHD presentation, ADHD severity, comorbidities and medication use on brain development trajectories. Establishing which brain regions are associated with differential clinical outcomes, may allow us to improve predictions about the course of ADHD.

Temporal trends of transport-related injuries on New Zealand roads.

AIM: This observational study aimed to investigate temporal trends in transport-related injuries in New Zealand by mode of transport and explore whether specific population groups and localities have a relatively higher incidence of injury. These trends provide insight into changes in injury patterns from road trauma. METHODS: A retrospective study of hospitalised road trauma in New Zealand was conducted between 1 July 2017 to 30 June 2021. Data were obtained from the National Minimum Dataset of hospital admissions, and the New Zealand Trauma Registry (NZTR). Road trauma was identified using ICD-10 coding, and major trauma using Abbreviated Injury Scale (AIS) coding. Analysis included road trauma by mode, ethnicity, rurality and population rates. Statistical analysis included Interrupted Time Series (ITS) analysis to account for the impact of COVID-19 on road trauma. RESULTS: Over the 4-year period there were 20,607 incidents of transport-related injury that resulted in admission to a New Zealand hospital. Of these, 14.5% (2,992) involved injuries that were classified as major trauma. Car occupants accounted for 62% of hospitalisations, followed by motorcyclists (23%), pedestrians (9%) and pedal cyclists (4%). Temporal trends showed no reduction in injuries from cars, pedal cyclists and pedestrian injuries, but an increase in motorcycling injuries. Maori had an age-standardised incidence rate almost 3.5 times higher than the rate for Asian peoples. CONCLUSION: The increases in motorcycling injuries and no changes in pedestrian and cycling injuries, as well as demographic variation, highlight the need to focus on vulnerable road users. Effective and targeted initiatives on vulnerable road users will support objectives to reduce deaths and serious injury on New Zealand roads. Enhanced exposure data is needed for vulnerable road users to account for mobility changes over time. Linked data across population-based datasets is an important asset that enhances our understanding of road traffic injuries and allows evidence-based countermeasures to be developed.

A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.

BACKGROUND: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment. METHODS: This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline. RESULTS: Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period. CONCLUSION: ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD. TRIAL REGISTRATION: Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246.

Correlation between whole body muscle MRI and functional measures in paediatric patients with facioscapulohumeral muscular dystrophy.

Symptoms and severity of facioscapulohumeral muscular dystrophy (FSHD) can vary greatly, even within the same family. Clinical trial readiness requires accurate and reliable methods of assessing disease stage and progression. MRI has not previously been assessed as a disease biomarker in paediatric FSHD. Eleven patients with FSHD1 underwent whole body muscle MRI. Pre-selected muscles were analysed by a paediatric radiologist using the semi-quantitative Mercuri/Kim method. Within each domain (oedema, fat replacement, atrophy) scores for each muscle were then summated to give each participant three cumulative domain scores. The same participants had functional measures scored: FSHD-CSS (Ricci), FSHD-CS (Lamperti), FSHD-COM, PUL2.0, MFM-32, 6MWT, myometry and manual muscle testing. Pearson coefficient was calculated to determine strength of correlation. The scores for atrophy and fat replacement showed strong correlation with functional outcome measures, particularly FSHD-CSS, FSHD-CS and FSHD-COM. In contrast, muscle oedema correlated poorly with all functional outcome measures, with no relationship seen to the 6MWT. This study of eleven children suggests that semi-quantitative visual Mercuri score utilising fat replacement or atrophy on whole body muscle MRI correlates strongly with disease-specific functional measures and may be a useful measure of disease severity in paediatric FSHD.

Karawun: a software package for assisting evaluation of advances in multimodal imaging for neurosurgical planning and intraoperative neuronavigation.

PURPOSE: The neuroimaging research community-which includes a broad range of scientific, medical, statistical, and engineering disciplines-has developed many tools to advance our knowledge of brain structure, function, development, aging, and disease. Past research efforts have clearly shaped clinical practice. However, translation of new methodologies into clinical practice is challenging. Anything that can reduce these barriers has the potential to improve the rate at which research outcomes can contribute to clinical practice. In this article, we introduce Karawun, a file format conversion tool, that has become a key part of our work in translating advances in diffusion imaging acquisition and analysis into neurosurgical practice at our institution. METHODS: Karawun links analysis workflows created using open-source neuroimaging software, to Brainlab (Brainlab AG, Munich, Germany), a commercially available surgical planning and navigation suite. Karawun achieves this using DICOM standards supporting representation of 3D structures, including tractography streamlines, and thus offers far more than traditional screenshot or color overlay approaches. RESULTS: We show that neurosurgical planning data, created from multimodal imaging data using analysis methods implemented in open-source research software, can be imported into Brainlab. The datasets can be manipulated as if they were created by Brainlab, including 3D visualizations of white matter tracts and other objects. CONCLUSION: Clinicians can explore and interact with the results of research neuroimaging pipelines using familiar tools within their standard clinical workflow, understand the impact of the new methods on their practice and provide feedback to methods developers. This capability has been important to the translation of advanced analysis techniques into practice at our institution.

Prospective Associations of Susceptibility-Weighted Imaging Biomarkers with Fatigue Symptom Severity in Childhood Traumatic Brain Injury.

Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d = 0.44), cognitive fatigue (Cohen d = 0.59), sleep/rest fatigue (Cohen d = 0.37), and total fatigue (Cohen d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.

Assessment of intraoperative diffusion EPI distortion and its impact on estimation of supratentorial white matter tract positions in pediatric epilepsy surgery.

The effectiveness of correcting diffusion Echo Planar Imaging (EPI) distortion and its impact on tractography reconstruction have not been adequately investigated in the intraoperative MRI setting, particularly for High Angular Resolution Diffusion Imaging (HARDI) acquisition. In this study, we evaluated the effectiveness of EPI distortion correction using 27 legacy intraoperative HARDI datasets over two consecutive surgical time points, acquired without reverse phase-encoded data, from 17 children who underwent epilepsy surgery at our institution. The data was processed with EPI distortion correction using the Synb0-Disco technique (Schilling et al., 2019) and without distortion correction. The corrected and uncorrected b0 diffusion-weighted images (DWI) were first compared visually. The mutual information indices between the original T1-weighted images and the fractional anisotropy images derived from corrected and uncorrected DWI were used to quantify the effect of distortion correction. Sixty-four white matter tracts were segmented from each dataset, using a deep-learning based automated tractography algorithm for the purpose of a standardized and unbiased evaluation. Displacement was calculated between tracts generated before and after distortion correction. The tracts were grouped based on their principal morphological orientations to investigate whether the effects of EPI distortion vary with tract orientation. Group differences in tract distortion were investigated both globally, and regionally with respect to proximity to the resecting lesion in the operative hemisphere. Qualitatively, we observed notable improvement in the corrected diffusion images, over the typically affected brain regions near skull-base air sinuses, and correction of additional distortion unique to intraoperative open cranium images, particularly over the resection site. This improvement was supported quantitatively, as mutual information indices between the FA and T1-weighted images were significantly greater after the correction, compared to before the correction. Maximum tract displacement between the corrected and uncorrected data, was in the range of 7.5 to 10.0 mm, a magnitude that would challenge the safety resection margin typically tolerated for tractography-informed surgical guidance. This was particularly relevant for tracts oriented partially or fully in-line with the acquired diffusion phase-encoded direction. Portions of these tracts passing close to the resection site demonstrated significantly greater magnitude of displacement, compared to portions of tracts remote from the resection site in the operative hemisphere. Our findings have direct clinical implication on the accuracy of intraoperative tractography-informed image guidance and emphasize the need to develop a distortion correction technique with feasible intraoperative processing time.

Focal thinning of the posterior corpus callosum: normal variant or post-traumatic?

AIM: The corpus callosum (CC) can be affected by childhood traumatic brain injury (TBI), through focal lesions, reductions in size and arrested development. Little is known, however, about what constitutes normal CC shape and appearance and how it may be affected in the long-term after early TBI. METHODS: In this study, the appearance of the CC was investigated in individuals with TBI assessed 10 years post-injury (n = 52, mean age = 16.82 years, SD = 3.55 years, 24 male) and compared to age-matched healthy controls (n = 44, mean age = 15.77 years, SD = 1.21 years, 18 male). A simple visual analysis technique was used to code the appearance of the CC according to location of focal thinning and severity of thinning and results between groups were compared using Chi-square analysis. RESULTS: A significantly higher proportion of patients with childhood TBI had focal posterior thinning of the CC than age-matched controls (p = 0.001). CONCLUSIONS: The findings call into question previous conclusions that focal posterior thinning is a normal variant of development. Instead, attenuations of the posterior portion of the CC in the long-term may reflect altered cortical and callosal development as a result of early brain injury, although the functional significance of this remains to be determined.

Airway closure is the predominant physiological mechanism of low ventilation seen on hyperpolarized helium-3 MRI lung scans.

Hyperpolarized helium-3 MRI (3He MRI) provides detailed visualization of low- (hypo- and non-) ventilated lungs. Physiological measures of gas mixing may be assessed by multiple breath nitrogen washout (MBNW) and of airway closure by a forced oscillation technique (FOT). We hypothesize that in patients with asthma, areas of low-ventilated lung on 3He MRI are the result of airway closure. Ten control subjects, ten asthma subjects with normal spirometry (non-obstructed), and ten asthmatic subjects with reduced baseline lung function (obstructed) attended two testing sessions. On visit one, baseline plethysmography was performed followed by spirometry, MBNW, and FOT assessment pre and post methacholine challenge. On visit two, 3He MRI scans were conducted pre and post methacholine challenge. Post methacholine the volume of low-ventilated lung increased from 8.3% to 13.8% in the non-obstructed group (P = 0.012) and from 13.0% to 23.1% in the obstructed group (P = 0.001). For all subjects, the volume of low ventilation from 3He MRI correlated with a marker of airway closure in obstructive subjects, Xrs (6 Hz) and the marker of ventilation heterogeneity Scond with r2 values of 0.61 (P < 0.001) and 0.56 (P < 0.001), respectively. The change in Xrs (6 Hz) correlated well (r2 = 0.45, p < 0.001), whereas the change in Scond was largely independent of the change in low ventilation volume (r2 = 0.13, P < 0.01). The only significant predictor of low ventilation volume from the multi-variate analysis was Xrs (6 Hz). This is consistent with the concept that regions of poor or absent ventilation seen on 3He MRI are primarily the result of airway closure.NEW & NOTEWORTHY This study introduces a novel technique of generating high-resolution 3D ventilation maps from hyperpolarized helium-3 MRI. It is the first study to demonstrate that regions of poor or absent ventilation seen on 3He MRI are primarily the result of airway closure.

One-Stage, Limited-Resection Epilepsy Surgery for Bottom-of-Sulcus Dysplasia.

OBJECTIVE: To determine whether 1-stage, limited corticectomy controls seizures in patients with MRI-positive, bottom-of-sulcus dysplasia (BOSD). METHODS: We reviewed clinical, neuroimaging, electrocorticography (ECoG), operative, and histopathology findings in consecutively operated patients with drug-resistant focal epilepsy and MRI-positive BOSD, all of whom underwent corticectomy guided by MRI and ECoG. RESULTS: Thirty-eight patients with a median age at surgery of 10.2 (interquartile range [IQR] 6.0-14.1) years were included. BOSDs involved eloquent cortex in 15 patients. Eighty-seven percent of patients had rhythmic spiking on preresection ECoG. Rhythmic spiking was present in 22 of 24 patients studied with combined depth and surface electrodes, being limited to the dysplastic sulcus in 7 and involving the dysplastic sulcus and gyral crown in 15. Sixty-eight percent of resections were limited to the dysplastic sulcus, leaving the gyral crown. Histopathology was focal cortical dysplasia (FCD) type IIb in 29 patients and FCDIIa in 9. Dysmorphic neurons were present in the bottom of the sulcus but not the top or the gyral crown in 17 of 22 patients. Six (16%) patients required reoperation for postoperative seizures and residual dysplasia; reoperation was not correlated with ECoG, neuroimaging, or histologic abnormalities in the gyral crown. At a median 6.3 (IQR 4.8-9.9) years of follow-up, 33 (87%) patients are seizure-free, 31 off antiseizure medication. CONCLUSION: BOSD can be safely and effectively resected with MRI and ECoG guidance, corticectomy potentially being limited to the dysplastic sulcus, without need for intracranial EEG monitoring and functional mapping. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that 1-stage, limited corticectomy for BOSD is safe and effective for control of seizures.

Language lateralization correlates with verbal memory performance in children with focal epilepsy.

PURPOSE: Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy. METHODS: Language fMRI and neuropsychological data (language, visuospatial functions, and memory) of 40 patients (7-18 years of age) with unilateral, refractory focal epilepsy in temporal and/or frontal areas of the left (n = 23) or right hemisphere (n = 17) were analyzed. fMRI data of 18 healthy controls (7-18 years) served as a normative sample. A laterality index was computed to determine the lateralization of activation in three regions of interest (frontal, parietal, and temporal). RESULTS: Atypical language lateralization was demonstrated in 12 (30%) of 40 patients. A correlation between language lateralization and verbal memory performance occurred in patients with left-sided epilepsy over all three regions of interest, with bilateral or right-sided language lateralization being correlated with better verbal memory performance (Word Pairs Recall: frontal r = -0.4, p = 0.016; parietal r = -0.4, p = 0.043; temporal r = -0.4, p = 0.041). Verbal memory performance made the largest contribution to language lateralization, whereas handedness and side of seizures did not contribute to the variance in language lateralization. DISCUSSION: This finding reflects the association between neocortical language and hippocampal memory regions in patients with left-sided epilepsy. Atypical language lateralization is advantageous for verbal memory performance, presumably a result of transfer of verbal memory function. In children with focal epilepsy, verbal memory performance provides a better idea of language lateralization than handedness and side of epilepsy and lesion.

Feasibility of 3-T MRI for the evaluation of Crohn disease in children.

BACKGROUND: Crohn disease (CD) is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract from the oral cavity to the anal canal. It occurs in all ages and is a significant cause for morbidity in children. Interest in MRI evaluation of CD has increased because of the concern regarding cumulative radiation dose from contrast fluoroscopic studies and CT. Several reports have demonstrated MRI to be a useful technique for CD. Most of these studies were performed at 1.5-T field strength. Imaging at a higher field strength, with a greater signal-to-noise ratio, has the potential of reducing scan times and increasing the resolution. However, there is a concurrent increase in artefacts, and these can be pronounced with abdominal imaging at 3 T. OBJECTIVE: To determine the feasibility of 3-T MRI for CD in children and to assess the value of different sequences and the effect of artefacts that could potentially limit the role of bowel MR imaging at higher field strengths. MATERIALS AND METHODS: A retrospective study of 46 children with biopsy-proven CD (ages 8-19 years, 53% boys) was performed. Sixty-eight consecutive MRI studies were performed on a 3-T scanner between 2005 and 2007; 42 of the abdomen (62%) and 26 of the pelvis/perineum (38%). Sorbitol was administered for the abdominal studies; orally for 36/42 (86%) studies and via a naso-jejunal (NJ) tube for 6/42 (14%) studies. For the abdomen, T2-W half-fourier acquisition single-shot turbo spin-echo (T2-W HASTE), true steady-state free precession (true FISP), pre-contrast and contrast-enhanced (CE) T1-volume interpolated gradient-echo (T1-W VIBE) and CE T1-W fast low-angle shot (T1-W FLASH) sequences were performed. For the perianal and pelvic assessment, fat-saturated T2-W turbo spin-echo (TSE), pre-contrast and CE T1-W FLASH or VIBE sequences were performed. The sequences were scored for diagnostic quality by two paediatric radiologists for visualisation of the bowel wall, whether normal or pathological and the visualization of extra intestinal manifestations. The effects of distension, susceptibility artefact and motion were assessed. RESULTS: Six (14%) abdominal MRI studies were normal. Thirty-six (86%) were abnormal with good correlation with endoscopic findings. The pelvic and perianal MRI studies were all abnormal (26/26, 100%) with good correlation with proctoscopy and examination under anaesthesia. All the sequences had high average scores (greater than or close to 3), except true FISP with a score of 2.4. The score was greatest in those who had NJ administration of sorbitol; however, satisfactory distension was also possible with oral administration of contrast. True FISP was the sequence most affected by a combination of suboptimal distension and artefact from colonic contents. With adequate distension, true FISP image quality improved remarkably. The overall score of this sequence was satisfactory in the absence of susceptibility and movement artefact. CONCLUSION: With appropriate attention to technique, with optimal distension and control of movement, high-quality, 3-T assessment of the abdomen, pelvis and perineum is possible. All sequences used at 1.5 T can be used at 3 T, however true FISP was the most prone to artefact.

Optic nerve diffusion changes and atrophy jointly predict visual dysfunction after optic neuritis.

Recently, there has been strong interest in the development of imaging techniques to quantify axonal and myelin pathology in patients with multiple sclerosis (MS). Optic neuritis, a condition characterised by inflammatory demyelination of the optic nerve, is one of the commonest sites of MS relapse, and exhibits similar pathological alterations to MS lesions elsewhere in the central nervous system (CNS). Unlike other regions of the CNS, however, the function of the optic nerve can be accurately assessed using clinical measures, as well as electrophysiological techniques such as visual evoked potential recordings. Therefore, optic neuritis is useful for investigating the relationship between abnormalities in optic nerve structure, assessed using magnetic resonance imaging (MRI), and visual dysfunction, assessed clinically and electrophysiologically. The aims of the present study were to assess optic nerve structural abnormalities in patients with a history of unilateral optic neuritis using MRI, and then to identify correlations between abnormalities in optic nerve MRI and visual dysfunction. Ten controls and sixteen patients underwent high resolution optic nerve diffusion tensor imaging (DTI), T2- and T1-weighted MRI. In addition, Snellen visual acuity and the latency and amplitude of multifocal visual evoked potentials (mfVEP) were tested in all patients. Diffusion and volumetric MRI indices were correlated to mfVEP functional indices. Significant abnormalities were detected in MRI and mfVEP measures in patients' affected nerves compared to unaffected optic nerves or optic nerves from healthy controls. Reduced mfVEP amplitude in the affected side significantly correlated with both affected optic nerve atrophy (R=0.58, p=0.02) and reduced fractional anisotropy (FA) (R=0.52, p=0.04). However, atrophy and reduced FA did not correlate with each other. To further investigate this disassociation, we used linear regression analysis with optic nerve atrophy and optic nerve FA as independent variables and mfVEP amplitude as the dependent variable. The resulting linear regression model was highly significant (R=0.819, p=0.001). These results show that, 4 years after unilateral optic neuritis, MRI-based measures of optic nerve structural abnormalities (decreased anisotropy and volume) independently predict visual dysfunction.

Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study.

INTRODUCTION: Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD. METHODS AND ANALYSIS: This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3-15 years of age), 70 TD participants (3-15 years) and 35 children with idiopathic ASD (7-15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child's behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria. ETHICS AND DISSEMINATION: This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.

Perinatal risk factors altering regional brain structure in the preterm infant.

Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of preterm infants. In a large prospective longitudinal cohort study of 202 preterm and 36 term infants, MR scans at term equivalent were undertaken for volumetric estimates of cortical and deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF within 8 parcellated regions for each hemisphere of the brain. Perinatal correlates analysed in relation to regional brain structure included gender, gestational age, intrauterine growth restriction, bronchopulmonary dysplasia, white matter injury (WMI) and intraventricular haemorrhage. Results revealed region-specific reductions in brain volumes in preterm infants compared with term controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8--2.3%), sensorimotor (-11.6%; -18.2--5.0%), orbitofrontal (-30.6%; -49.8--11.3%) and premotor (-7.6%; -14.2--0.9%) regions. Within the sensorimotor and orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly within the parieto-occipital and subgenual regions. CSF (ventricular and extracerebral) was doubled in volume within the superior regions in preterm infants compared with term controls. Cerebral WMI and intrauterine growth restriction were both associated with a more posterior reduction in brain volumes, whereas bronchopulmonary dysplasia was associated with a more global reduction across all regions. In contrast degree of immaturity was not related to regional brain structure among preterm infants. In summary, preterm birth is associated with regional cerebral tissue reductions, with the adverse pattern varying between risk factors. These findings add to our understanding of the potential pathways leading to altered brain structure and outcome in the preterm infant.

MRπ: Inside the meat pie.

Meat pies have been adopted as one of Australia's favourite foods, and considered an icon by many. The hand-held convenience of the pie has made them a culinary necessity while watching sport, also beloved in Australia. An enduring question about the meat pie is what exactly is inside. This can be difficult to ascertain by digital, ocular or oral exploration. In this study we use MR imaging to study the contents of some of Australia's best loved pies.