Longitudinal Magnetic Resonance Imaging Study Research Articles

Functional changes during visuo-spatial working memory in autism spectrum disorder: 2-year longitudinal functional magnetic resonance imaging study.

This study examined functional changes longitudinally over 2 years in neural correlates associated with working memory in youth with and without autism spectrum disorder, and the impact of increasing cognitive load. We used functional magnetic resonance imaging and a visuo-spatial 1-back task with four levels of difficulty. A total of 14 children with autism spectrum disorder and 15 typically developing children (ages 7-13) were included at baseline and followed up approximately 2 years later. Despite similar task performance between groups, differences were evident in the developmental trajectories of neural responses. Typically developing children showed greater load-dependent activation which intensified over time in the frontal, parietal and occipital lobes and the right fusiform gyrus, compared to those with autism spectrum disorder. Children with autism spectrum disorder showed minimal age-related changes in load-dependent activation, but greater longitudinal load-dependent deactivation in default mode network compared to typically developing children. Results suggest inadequate modulation of neural activity with increasing cognitive demands in children with autism spectrum disorder, which does not mature into adolescence, unlike their typically developing peers. Diminished ability for children with autism spectrum disorder to modulate neural activity during this period of maturation suggests that they may be more vulnerable to the increasing complexity of social and academic demands as they progress through adolescence than their peers.

Current methods and limitations for longitudinal fMRI analysis across development

The human brain is remarkably plastic. The brain changes dramatically across development, with ongoing functional development continuing well into the third decade of life and substantial changes occurring again in older age. Dynamic changes in brain function are thought to underlie the innumerable changes in cognition, emotion, and behavior that occur across development. The brain also changes in response to experience, which raises important questions about how the environment influences the developing brain. Longitudinal functional magnetic resonance imaging (fMRI) studies are an essential means of understanding these developmental changes and their cognitive, emotional, and behavioral correlates. This paper provides an overview of common statistical models of longitudinal change applicable to developmental cognitive neuroscience, and a review of the functionality provided by major software packages for longitudinal fMRI analysis. We demonstrate that there are important developmental questions that cannot be answered using available software. We propose alternative approaches for addressing problems that are commonly faced in modeling developmental change with fMRI data.

A longitudinal functional magnetic resonance imaging study of task control circuits and bulimic symptoms over adolescence

Previous cross-sectional findings from adolescents and adults with Bulimia Nervosa (BN) suggest disturbances in fronto-striatal and cingulo-opercular task control circuits that support self-regulatory processes, including the resolution of cognitive conflict. Herein, we used longitudinal data to examine the developmental trajectories of such disturbances and how the functioning of these circuits relates to changes in BN symptoms over adolescence. Thirty-two adolescent females with BN symptoms and 28 healthy control (HC) adolescents participated in the study. Functional magnetic resonance images (fMRI) during performance of a Simon task were acquired at three time points within 2-year intervals over adolescence. From the initial sample, 70% and 30% of the participants completed the second and third time points, respectively. Participants who completed all study time points did not differ from those lost to attrition on baseline demographic characteristics or any outcome measures. Using a region-of-interest approach, growth curve models tested group differences in the trajectory of conflict-related activation in task control circuits over time. Cross-lagged panel models examined transactional relationships between conflict-related activation in the same regions and BN symptoms over time. Growth curve models revealed different trajectories of conflict-related activation in right task control regions across BN and HC adolescents, such that HC but not BN adolescents showed activation decreases over time. These group differences were greatest when including only the BN adolescents whose symptoms remitted over time. Cross-lagged panel models revealed that less frequent bulimic episodes at first follow-up predicted later increases in conflict-related activation in bilateral task control regions. These longitudinal findings suggest overengagement of task control circuits in BN adolescents, especially those most resilient to persistent illness. Such overengagement may compensate for regulatory disturbances, allowing them to regulate eating behaviors over development. Thus, task control circuits may constitute targets for early interventions that enhance self-regulatory control.

Effect of Adjuvant Chemotherapy on Left Ventricular Remodeling in Women with Newly Diagnosed Primary Breast Cancer: A Pilot Prospective Longitudinal Cardiac Magnetic Resonance Imaging Study.

The aim of this study was to assess the left ventricular (LV) remodeling response to chemotherapy in low-cardiac-risk women with newly diagnosed nonmetastatic breast cancer. Cardiotoxic effects of chemotherapy are an increasing concern. To effectively interpret cardiac imaging studies performed for screening purposes in patients undergoing cancer therapy it is necessary to understand the normal changes in structure and function that may occur. Twenty women without preexisting cardiovascular disease, of a mean age of 50 years, newly diagnosed with nonmetastatic breast cancer and treated with anthracycline or trastuzumab, were prospectively enrolled and evaluated at four time points (at baseline, during chemotherapy, 2 weeks after chemotherapy, and 6 months after chemotherapy) using cardiac magnetic resonance imaging, blood samples, and a clinical questionnaire. Over a 6-month period, the left ventricular ejection fraction (%) decreased (64.15±5.30 to 60.41±5.77, P<0.002) and the LV end-diastolic (mm) and end-systolic (mm) volumes increased (124.73±20.25 to 132.21±19.33, P<0.04 and 45.16±11.88 to 52.57±11.65, P<0.00, respectively). The LV mass (g) did not change (73.06±11.51 to 69.21±15.3, P=0.08), but the LV mass to LVEDV ratio (g/mm) decreased (0.594±0.098 to 0.530±0.124, P<0.04). In low-cardiac-risk women with nonmetastatic breast cancer, the increased LV volume and a mildly decreased left ventricular ejection fraction during and after chemotherapy do not seem to be associated with laboratory or clinical evidence of increased risk for heart failure.

The Default Mode Network as a Biomarker of Persistent Complaints after Mild Traumatic Brain Injury: A Longitudinal Functional Magnetic Resonance Imaging Study.

The objective of this study was to examine longitudinal functional connectivity of resting-state networks in patients with and without complaints after uncomplicated mild traumatic brain injury (mTBI). Second, we aimed to determine the value of network connectivity in predicting persistent complaints, anxiety, depression and long-term outcome. Thirty mTBI patients with three or more post-traumatic complaints at 2 weeks post-injury, 19 without complaints, and 20 matched healthy controls were selected for this study. Resting-state functional MRI (fMRI) was performed in patients at 1 month and 3 months post-injury, and once in healthy controls. Independent component analysis (ICA) was used to investigate the default mode, executive and salience networks. Persistent post-traumatic complaints, anxiety, and depression were measured at 3 months post-injury, and outcome was determined at 1 year post-injury. Within the group with complaints, higher functional connectivity between the anterior and posterior components of the default mode network at 1 month post-injury was associated with a greater number of complaints at 3 months post-injury (ρ = 0.59, p = 0.001). Minor longitudinal changes in functional connectivity were found for patients with and without complaints after mTBI, which were limited to connectivity within the precuneus component of the default mode network. No significant results were found for the executive and salience networks. Current results suggest that the default mode network may serve as a biomarker of persistent complaints in patients with uncomplicated mTBI.

Effects of antidepressant therapy on neural components of verbal working memory in depression.

Impairments in verbal working memory are evident in major depression. Verbal working memory is comprised of the components of encoding, maintenance and retrieval. Whether the neural impairments are expressed in specific components, and how pharmacological therapy could modify the neural correlates are not well understood. We investigated the neural correlates of verbal working memory components in depression using the Sternberg task in a longitudinal magnetic resonance imaging study. Serial scans were acquired in 23 patients (mean age 39.8 years) during an acute depressive episode and following 12 weeks of pharmacological therapy with duloxetine and in 22 matched healthy controls (mean age 39.1 years) at the same time points. A significant group by time interaction was evident during the long maintenance phase, extending from the left middle frontal to the middle temporal and caudate regions, in which there was reduced activation in healthy participants at the follow -up scan but there were no changes in patients. Persistent neural engagement during the maintenance phase following treatment was revealed in major depression. The findings emphasize that impairments in verbal working memory may be initiated in the maintenance phase in major depression in order to sustain performance. Further research with larger sample size and using randomized, placebo-controlled double-blind studies are required to confirm our results.

Longitudinal increases of brain metabolite levels in 5-10 year old children.

Longitudinal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies reveal significant changes in brain structure and structural networks that occur together with cognitive and behavioral maturation in childhood. However, the underlying cellular changes accompanying brain maturation are less understood. Examining regional age-related changes in metabolite levels provides insight into the physiology of neurodevelopment. Magnetic resonance spectroscopy (MRS) measures localize brain metabolism. The majority of neuroimaging studies of healthy development are from the developed world. In a longitudinal MRS study of 64 South African children aged 5 to 10 years old (29 female; 29 HIV exposed, uninfected), we examined the age-related trajectories of creatine (Cr+PCr), N-acetyl-aspartate (NAA), the combined NAA+N-acetyl-aspartyl-glutamate (NAAG), choline (GPC+PCh), glutamate (Glu) and the combined Glu+glutamine (Glu+Gln) in voxels within gray and white matter, as well as subcortically in the basal ganglia (BG). In frontal gray matter, we found age-related increases in Cr+PCr, NAA, NAA+NAAG and Glu+Gln levels pointing to synaptic activity likely related to learning. In the BG we observed increased levels of Glu, Glu+Gln and NAA+NAAG with age that point to subcortical synaptic reorganization. In white matter, we found increased levels of Cr+PCr, NAA, NAA+NAAG, Glu and Glu+Gln with age, implicating these metabolites in ongoing myelination. We observed no sex-age or HIV exposure-age interactions, indicating that physiological changes are independent of sex during this time period. The metabolite trajectories presented, therefore, provide a critical benchmark of normal cellular growth for a low socioeconomic pediatric population in the developing world against which pathology and abnormal development may be compared.

Effects of electroconvulsive therapy on amygdala function in major depression - a longitudinal functional magnetic resonance imaging study.

Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.

Structural brain changes in schizophrenia at different stages of the illness: A selective review of longitudinal magnetic resonance imaging studies.

Schizophrenia is a devastating mental disorder accompanied by aberrant structural brain connectivity. The question whether schizophrenia is a progressive brain disorder is yet to be resolved. Thus, it is not clear when these structural alterations occur and how they develop over time. In our selective review, we summarized recent findings from longitudinal magnetic resonance imaging studies investigating structural brain alterations and its impact on clinical outcome at different stages of the illness: (1) subjects at ultra-high risk of developing psychosis, (2) patients with a first episode psychosis, and (3) chronically ill patients. Moreover, we reviewed studies examining the longitudinal effects of medication on brain structure in patients with schizophrenia. (1) Studies from pre-clinical stages to conversion showed a more pronounced cortical gray matter loss (i.e. superior temporal and inferior frontal regions) in those individuals who later made transition to psychosis. (2) Studies investigating patients with a first episode psychosis revealed a decline in multiple gray matter regions (i.e. frontal regions and thalamus) over time as well as progressive cortical thinning in the superior and inferior frontal cortex. (3) Studies focusing on patients with chronic schizophrenia showed that gray matter decreased to a greater extent (i.e. frontal and temporal areas, thalamus, and cingulate cortices)-especially in poor-outcome patients. Very few studies reported effects on white matter microstructure in the longitudinal course of the illness. There is adequate evidence to suggest that schizophrenia is associated with progressive gray matter abnormalities particularly during the initial stages of illness. However, causal relationships between structural changes and illness course-especially in chronically ill patients-should be interpreted with caution. Findings might be confounded by longer periods of treatment and higher doses of antipsychotics or epiphenomena related to the illness.

Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism

BackgroundWe previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. MethodsA longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. ResultsInfants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen’s d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. ConclusionsThis study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

Compact MRI for the detection of teratoma development following intrathecal human embryonic stem cell injection in NOD-SCID mice

Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the development of methods for detecting teratomas in preclinical safety studies. The aim of the current study is to assess the ability of a compact Magnetic Resonance Imaging (MRI) system to detect teratoma formation in mice. Five NOD-SCID mice were injected intrathecally with human embryonic stem cells (hESCs), with two mice serving as controls. In vivo MRI was performed on days 25 and 48, and ex vivo MRI was performed after scheduled euthanization (day 55). MRI results were compared to histopathology findings. Two animals injected with hESCs developed hind-limb paresis and paralysis, necessitating premature euthanization. MRI examination revealed abnormal pale areas in the spinal cord and brain, which correlated histopathologically with teratomas. This preliminary study shows the efficacy of compact MRI systems in the detection of small teratomas following intrathecal injection of hESCs in a highly sensitive manner. Although these results should be validated in larger studies, they provide further evidence that the use of MRI in longitudinal studies offers a new monitoring strategy for preclinical testing of stem cell applications.

Brain activity for tactile allodynia: a longitudinal awake rat functional magnetic resonance imaging study tracking emergence of neuropathic pain.

Tactile allodynia, a condition in which innocuous mechanical stimuli are perceived as painful, is a common feature of chronic pain. However, how the brain reorganizes in relation to the emergence of tactile allodynia is still largely unknown. This may stem from the fact that experiments in humans are cross-sectional in nature, whereas animal brain imaging studies typically require anaesthesia rendering the brain incapable of consciously sensing or responding to pain. In this longitudinal functional magnetic resonance imaging study in awake rats, we tracked brain activity with the development of tactile allodynia. Before injury, innocuous air-puff stimuli evoked a distributed sensory network of activations, including contralateral somatosensory cortices, thalamus, insula, and cingulate cortex. Moreover, the primary somatosensory cortex displayed a graded response tracking air-puff stimulus intensities. After neuropathic injury, and for stimuli in which the intensity exceeded the paw withdrawal threshold (evoking tactile allodynia), the blood oxygenation level-dependent response in the primary somatosensory cortex was equivalent to that evoked by the identical stimulus before injury. In contrast, nucleus accumbens and prefrontal brain areas displayed abnormal activity to normally innocuous stimuli when such stimuli induced tactile allodynia at 28 days after peripheral nerve injury, which had not been the case at 5 days after injury. Our data indicate that tactile allodynia-related nociceptive inputs are not observable in the primary somatosensory cortex BOLD response. Instead, our data suggest that, in time, tactile allodynia differentially engages neural circuits that regulate the affective and motivational components of pain.

Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study.

It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis.

Imaging the Transformation of Ipsilateral Internal Capsule Following Focal Cerebral Ischemia in Rat by Diffusion Kurtosis Imaging

The purpose of our study is to explore the relationship between recovery of neural function and transformation of the internal capsule (IC) after transient middle cerebral artery occlusion (MCAO) by using diffusion kurtosis imaging (DKI). Six male adult Sprague-Dawley rats implemented with transient MCAO were used in this study. Sensorimotor function was assessed according to repetitive behavioral testing on day 1, 3, 7, 14, and 28 after cerebral ischemia. Metrics of DKI were acquired, and the time course of the region-to-normal ratio was evaluated in IC. After cerebral ischemia, relative fractional anisotropy in IC decreased on day 3 (P < .01). Relative mean diffusivity (rMD) increased on day 28 (P < .05). Relative mean diffusional kurtosis (rMK) increased on day 3 (P < .01) and decreased on day 7 (P < .05). Relative axial diffusional kurtosis (rKa) increased on day 3 (P < .01) and declined on day 7 (P < .05). Relative radial diffusional kurtosis (rKr) was reduced on day 7 (P < .05). Changes in rMK were larger than changes in rMD on day 3 (P < .05). The factor of rKa and rKr revealed marked difference on day 7 (P < .05) and day 14 (P < .05). Neurological function score showed that rats exhibited functional recovery from day 7 (P < .01) post stroke. This longitudinal multiparametric magnetic resonance imaging study suggested that K metrics offers information complimentary to conventional diffusion metrics and revealed the procedure during the structural modification in the ipsilateral IC following focal cerebral ischemia. After transient MCAO, the neural transformation occurred in a time-dependent procedure.

Telmisartan-mediated metabolic profile conferred brain protection in diabetic hypertensive rats as evidenced by magnetic resonance imaging, behavioral studies and histology

Type 2 diabetes and hypertension are associated with cognitive dysfunction that includes pathological changes in brain tissue. It was speculated that the beneficial hypotensive effect of telmisartan, an angiotensin receptor 1 blocker, and its unique hypoglycemic effect due to its PPARγ-activation, could ameliorate the ​ pathological changes in the brain​ that accompany​ these diseases. We examined the effect of telmisartan on brain changes in magnetic resonance imaging (MRI) T2-weighted scans, and behavioral and histological findings in the Cohen-Rosenthal Diabetic Hypertensive (CRDH) rat. Baseline and post-treatment values with telmisartan/vehicle (3 months) of blood pressure, blood glucose levels, behavioral tests, brain MRI scanning and immunohistological staining were obtained. Telmisartan significantly lowered blood pressure and blood glucose levels; induced consistent T2 reduction in specific gray and white regions including hippocampus, corpus callosum, amygdala and cortical regions; and significantly improved performance on behavioral tasks. Immunohistological analysis of the brain revealed significant amelioration of diabetes/hypertension-induced changes in white matter regions and microglia, evidenced by preserved myelin (LBF marker), and improved microglial neuronal markers GFAP, GAP43 and Iba1 expression. In conclusion, the behavioral performance, longitudinal MRI study and histology staining revealed the protective effects of telmisartan on brain microstructure and cognitive function.

Temporo-parietal connectivity uniquely predicts reading change from childhood to adolescence

Previous research has shown that left posterior middle temporal gyrus (pMTG) is a core node in the semantic network, and cross-sectional studies have shown that activation in this region changes developmentally and is related to skill measured concurrently. However, it is not known how functional connectivity with this region changes developmentally, and whether functional connectivity is related to future gains in reading. We conducted a longitudinal functional magnetic resonance imaging (fMRI) study in 30 typically developing children (aged 8–15) to examine whether initial brain measures, including activation and connectivity, can predict future behavioral improvement in a semantic judgment task. Participants were scanned on entering the study (time 1, T1) and a follow-up period of 2years (time 2, T2). Character pairs were arranged in a continuous variable according to association strength (i.e. strong versus weak), and participants were asked to determine if these visually presented pairs were related in meaning. Our results demonstrated greater developmental changes from time 1 to time 2 for weaker association pairs in the left pMTG for the children (aged 8–11) as compared to the adolescents (aged 12–15). Moreover, the results showed greater developmental changes from time 1 to time 2 for weaker association pairs in connectivity between the pMTG and inferior parietal lobule (IPL) for the children as compared to the adolescents. Furthermore, a hierarchical stepwise regression model revealed that connectivity between the pMTG and IPL in weak association pairs was uniquely predictive of behavioral improvement from time 1 to time 2 for the children, but not the adolescents. Taken together, the activation results suggest relatively rapid development before adolescence of semantic representations in the pMTG. Moreover, the connectivity results of pMTG with IPL tentatively suggest that early development of semantic representations may be facilitated by enhanced engagement of phonological short-term memory.

Trajectories of adolescent conduct problems in relation to cortical thickness development: a longitudinal MRI study

Multiple cross-sectional imaging studies have identified structural abnormalities in prefrontal, temporal and limbic regions related to conduct problems (CPs). However, the relationship between development of such neurobiological deficits and developmental pathways of CPs has remained unclear. The current study investigated distinct trajectories of CP and related trajectories of cortical thickness within a community-based sample of adolescents (n=239), age range 12–19, to address this gap. Three trajectory classes were revealed using latent class growth analyses (LCGAs), comprising a ‘desisting' CP group, an ‘intermediate' CP group and a ‘stable low' CP group. Structural magnetic resonance imaging (MRI) scans were collected with a subgroup of 171 adolescents at three waves throughout adolescence (ages 12, 16 and 19). Generalized estimating equation (GEE) analysis—comparing longitudinal changes in cortical thickness and subcortical volume between CP groups for several regions of interest (ROIs)—showed that these CP groups had differential trajectories of cortical thickness in the dorsolateral prefrontal cortex (dl-PFC), and the anterior cingulate cortex (ACC), and volume of the hippocampus. Adolescents in the desisting CP group showed an attenuation of the typical pattern of cortical thinning as present in the intermediate and stable low CP groups, in addition to an exaggeration of the typical pattern of hippocampal volume increase. These findings suggest that a deviant cortical thickness trajectory was related to a desisting CP pathway across adolescence. Such deviant neurodevelopmental growth trajectories may act as an underlying mechanism for developmental CP pathways, and possibly distinguish desisting antisocial adolescents.

Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation.

BackgroundMagnetic resonance imaging (MRI) has been widely used in studies evaluating the neuropathology of autism spectrum disorder (ASD). Studies are often limited, however, to higher functioning individuals with ASD. MRI studies of individuals with ASD and comorbid intellectual disability (ID) are lacking, due in part to the challenges of acquiring images without the use of sedation.MethodsUtilizing principles of applied behavior analysis (ABA), we developed a protocol for acquiring structural MRI scans in school-aged children with ASD and intellectual impairment. Board certified behavior analysts worked closely with each child and their parent(s), utilizing behavior change techniques such as pairing, shaping, desensitization, and positive reinforcement, through a series of mock scanner visits to prepare the child for the MRI scan. An objective, quantitative assessment of motion artifact in T1- and diffusion-weighted scans was implemented to ensure that high-quality images were acquired.ResultsThe sample consisted of 17 children with ASD who are participants in the UC Davis Autism Phenome Project, a longitudinal MRI study aimed at evaluating brain developmental trajectories from early to middle childhood. At the time of their initial scan (2–3.5 years), all 17 children had a diagnosis of ASD and development quotient (DQ) <70. At the time of the current scan (9–13 years), 13 participants continued to have IQs in the range of ID (mean IQ = 54.1, sd = 12.1), and four participants had IQs in the normal range (mean = 102.2, sd = 7.5). The success rate in acquiring T1-weighted images that met quality assurance for acceptable motion artifact was 100 %. The success rate for acquiring high-quality diffusion-weighted images was 94 %.ConclusionsBy using principles of ABA in a research MRI setting, it is feasible to acquire high-quality images in school-aged children with ASD and intellectual impairment without the use of sedation. This is especially critical to ensure that ongoing longitudinal studies of brain development can extend from infancy and early childhood into middle childhood in children with ASD at all levels of functioning, including those with comorbid ID.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-016-9154-9) contains supplementary material, which is available to authorized users.

The Course of Bone Marrow Edema in Early Undifferentiated Arthritis and Rheumatoid Arthritis: A Longitudinal Magnetic Resonance Imaging Study at Bone Level.

In patients with rheumatoid arthritis (RA), bone marrow edema (BME) scores are associated with development of erosions. However, little is known about the course and outcome of BME at bone level. We undertook this study to determine the association of BME and synovitis with the development of erosions in the same bone longitudinally. Using 1.5T magnetic resonance imaging at baseline and at 4- and 12-month follow-up, we studied 1,947 bones of the metacarpophalangeal, wrist, and metatarsophalangeal joints in 59 patients presenting with RA or undifferentiated arthritis. Scanning and scoring of BME, synovitis, and erosions were performed according to the Outcome Measures in Rheumatology Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system. We evaluated the relationship of the course of BME and synovitis with erosive progression at bone level during 1 year. Of the bones showing BME at baseline (n = 203), BME persisted in 56%, disappeared in 39%, and disappeared and then reappeared in 5%. Stratified analyses at baseline revealed that BME was associated with erosive progression both in the presence and in the absence of local synovitis, with odds ratios (ORs) of 7.5 (95% confidence interval [95% CI] 3.8-14.9) and 6.9 (95% CI 1.9-25.6), respectively. However, local synovitis was not associated with erosive progression in the presence or in the absence of BME (ORs of 2.0 [95% CI 0.6-7.0] and 1.9 [95% CI 0.8-4.1], respectively). In multivariable generalized estimating equation analyses, persistent BME was strongly associated with erosive progression (OR 60.5 [95% CI 16.8-218.1]) in contrast to persistent synovitis (OR 1.3 [95% CI 0.4-4.4]). BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independently of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for comprehending the development of erosions in RA.

Biomimetic phantom for cardiac diffusion MRI

PurposeDiffusion magnetic resonance imaging (MRI) is increasingly used to characterize cardiac tissue microstructure, necessitating the use of physiologically relevant phantoms for methods development. Existing phantoms are generally simplistic and mostly simulate diffusion in the brain. Thus, there is a need for phantoms mimicking diffusion in cardiac tissue.Materials and MethodsA biomimetic phantom composed of hollow microfibers generated using co‐electrospinning was developed to mimic myocardial diffusion properties and fiber and sheet orientations. Diffusion tensor imaging was carried out at monthly intervals over 4 months at 9.4T. 3D fiber tracking was performed using the phantom and compared with fiber tracking in an ex vivo rat heart.ResultsThe mean apparent diffusion coefficient and fractional anisotropy of the phantom remained stable over the 4‐month period, with mean values of 7.53 ± 0.16 × 10‐4 mm2/s and 0.388 ± 0.007, respectively. Fiber tracking of the 1st and 3rd eigenvectors generated analogous results to the fiber and sheet‐normal direction respectively, found in the left ventricular myocardium.ConclusionA biomimetic phantom simulating diffusion in the heart was designed and built. This could aid development and validation of novel diffusion MRI methods for investigating cardiac microstructure, decrease the number of animals and patients needed for methods development, and improve quality control in longitudinal and multicenter cardiac diffusion MRI studies. J. MAGN. RESON. IMAGING 2016;43:594–600.