Why do we keep missing left circumflex artery myocardial infarctions?

BACKGROUND: Diagnosis of left circumflex artery (LCx) myocardial infarctions via 12­lead electrocardiogram (ECG) has posed a challenge to healthcare professionals for many years. METHODS AND RESULTS: A retrospective observational study was performed to analyze patients admitted with myocardial infarction. The study used electronic medical records and specific ICD-10 codes to identify eligible patients, resulting in 2032 encounters. After independent adjudication of cardiac biomarkers, coronary angiography, and electrocardiographic changes, a final patient population of 58 encounters with acute occlusion myocardial infarction (OMI) with a culprit LCx lesion was established. OMI was defined as a lesion with either thrombolysis in myocardial infarction flow (TIMI) 0-2 or TIMI 3 with Troponin I > 1 ng/mL (Reference range 0.00-0.03 ng/mL). ECGs of these patients were then independently evaluated and grouped into 8 different classifications based on the presence or absence of ST elevation and/or depression in corresponding leads. ECG patterns and anatomical characteristics (proximal or distal to the first obtuse marginal artery) of the LCx lesions were then correlated. The appropriateness of triage and delay in reperfusion therapy were also assessed. Those with a left dominant or codominant circulation, and with LCx lesions proximal to the first obtuse marginal artery, were more likely to present with no or subtle ST-segment changes that led to delays in reperfusion therapy. CONCLUSIONS: Patients with left or codominant coronary artery circulation, with OMI proximal to the first obtuse marginal artery, may be less likely to have "classic" findings of ST-segment elevation on ECG due to cancellation forces in the limb leads.

Critical Care of Patients With Cardiopulmonary Complications of Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease defined by the presence of aberrant granulomas affecting various organs. Due to its multisystem involvement, care of patients with established sarcoidosis becomes challenging, especially in the intensive care setting. While the lungs are typically involved, extrapulmonary manifestations also occur either concurrently or exclusively within a significant proportion of patients, complicating diagnostic and management decisions. The scope of this review is to focus on what considerations are necessary in the evaluation and management of patients with known sarcoidosis and their associated complications within a cardiopulmonary and critical care perspective.

Frequency drift in MR spectroscopy at 3T.

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

Sensorimotor Cortical Oscillations during Movement Preparation in 16p11.2 Deletion Carriers.

Sensorimotor deficits are prevalent in many neurodevelopmental disorders like autism, including one of its common genetic etiologies, a 600 kb reciprocal deletion/duplication at 16p11.2. We have previously shown that copy number variations of 16p11.2 impact regional brain volume, white matter integrity, and early sensory responses in auditory cortex. Here, we test the hypothesis that abnormal cortical neurophysiology is present when genes in the 16p11.2 region are haploinsufficient, and in humans that this in turn may account for behavioral deficits specific to deletion carriers. We examine sensorimotor cortical network activity in males and females with 16p11.2 deletions compared with both typically developing individuals, and those with duplications of 16p11.2, using magnetoencephalographic imaging during preparation of overt speech or hand movements in tasks designed to be easy for all participants. In deletion carriers, modulation of beta oscillations (12-30 Hz) were increased during both movement types over effector-specific regions of motor cortices compared with typically developing individuals or duplication carriers, with no task-related performance differences between cohorts, even when corrected for their own cognitive and sensorimotor deficits. Reduced left hemispheric language specialization was observed in deletion carriers but not in duplication carriers. Neural activity over sensorimotor cortices in deletion carriers was linearly related to clinical measures of speech and motor impairment. These findings link insufficient copy number repeats at 16p11.2 to excessive neural activity (e.g., increased beta oscillations) in motor cortical networks for speech and hand motor control. These results have significant implications for understanding the neural basis of autism and related neurodevelopmental disorders.SIGNIFICANCE STATEMENT The recurrent ∼600 kb deletion at 16p11.2 (BP4-BP5) is one of the most common genetic etiologies of ASD and, more generally, of neurodevelopmental disorders. Here, we use high-resolution magnetoencephalographic imaging (MEG-I) to define with millisecond precision the underlying neurophysiological signature of motor impairments for individuals with 16p11.2 deletions. We identify significant increases in beta (12-30 Hz) suppression in sensorimotor cortices related to performance during speech and hand movement tasks. These findings not only provide a neurophysiological phenotype for the clinical presentation of this genetic deletion, but also guide our understanding of how genetic variation encodes for neural oscillatory dynamics.

Are psychotherapies with more dropouts less effective?

Psychotherapy dropout is often regarded as an indicator of treatment failure; however, evidence of a relationship between dropout and outcome has not been well established. The current research consisted of three meta-analytic studies, the results of which found (a) individuals who dropped out began treatment more distressed than those who completed therapy, (b) individuals who dropped out of therapy were more distressed at posttreatment than individuals who completed therapy, and (c) treatments with higher rates of dropout were also less effective for the treatment completers. Dropout may particularly signal poor outcomes for shorter treatments. The continued ambiguity in the meaning of dropout is discussed as well as the promising potential for future research in the area of dropout as it relates to outcome.

Does involving patients in treatment decisions affect perceptions of treatments and therapists?

Psychotherapists may offer patients more or less involvement when deciding on a treatment. The aim of the present research was to examine whether perceptions of the treatment and therapist differ when a therapist uses a paternalistic style in making treatment decisions or a more collaborative approach, in which the patient helps in selecting treatment. In the study, 172 participants, recruited from a university setting and a national sample, listened to a simulated conversation representing either a paternalism or informed-choice model of a therapist-patient interaction. The participants then rated their expectation the treatment would help the patient, their perception of the therapist's trustworthiness, and their own preference for relying on clinicians for knowledge and decisions. Analysis indicated that among participants preferring to rely on clinicians, perceptions did not differ reliably based on the type of interaction they heard. However, participants wanting more involvement in treatment choices perceived greater treatment effectiveness and clinician trustworthiness for the interaction in which the patient was offered treatment choices. These results suggest that if therapists adopt a collaborative approach, it has the potential to enhance perceptions of individuals preferring the collaborative style without negatively affecting those who prefer less involvement in treatment decisions.

Abnormal maturation of the resting-state peak alpha frequency in children with autism spectrum disorder.

Age-related changes in resting-state (RS) neural rhythms in typically developing children (TDC) but not children with autism spectrum disorder (ASD) suggest that RS measures may be of clinical use in ASD only for certain ages. The study examined this issue via assessing RS peak alpha frequency (PAF), a measure previous studies, have indicated as abnormal in ASD. RS magnetoencephalographic (MEG) data were obtained from 141 TDC (6.13-17.70 years) and 204 ASD (6.07-17.93 years). A source model with 15 regional sources projected the raw MEG surface data into brain source space. PAF was identified in each participant from the source showing the largest amplitude alpha activity (7-13 Hz). Given sex differences in PAF in TDC (females > males) and relatively few females in both groups, group comparisons were conducted examining only male TDC (N = 121) and ASD (N = 183). Regressions showed significant group slope differences, with an age-related increase in PAF in TDC (R2 = 0.32) but not ASD (R2 = 0.01). Analyses examining male children below or above 10-years-old (median split) indicated group effects only in the younger TDC (8.90 Hz) and ASD (9.84 Hz; Cohen's d = 1.05). In the older ASD, a higher nonverbal IQ was associated with a higher PAF. In the younger TDC, a faster speed of processing was associated with a higher PAF. PAF as a marker for ASD depends on age, with a RS alpha marker of more interest in younger versus older children with ASD. Associations between PAF and cognitive ability were also found to be age and group specific.

Delayed Auditory Evoked Responses in Autism Spectrum Disorder across the Life Span.

The M50 and M100 auditory evoked responses reflect early auditory processes in the primary/secondary auditory cortex. Although previous M50 and M100 studies have been conducted on individuals with autism spectrum disorder (ASD) and indicate disruption of encoding simple sensory information, analogous investigations of the neural correlates of auditory processing through development from children into adults are very limited. Magnetoencephalography was used to record signals arising from the left and right superior temporal gyrus during auditory presentation of tones to children/adolescents and adults with ASD as well as typically developing (TD) controls. One hundred and thirty-two participants (aged 6-42 years) were included into the final analyses (children/adolescents: TD, n = 36, 9.21 ± 1.6 years; ASD, n = 58, 10.07 ± 2.38 years; adults: TD, n = 19, 26.97 ± 1.29 years; ASD, n = 19, 23.80 ± 6.26 years). There were main effects of group on M50 and M100 latency (p < 0.001) over hemisphere and frequency. Delayed M50 and M100 latencies were found in participants with ASD compared to the TD group, and earlier M50 and M100 latencies were associated with increased age. Furthermore, there was a statistically significant association between language ability and both M50 and M100 latencies. Importantly, differences in M50 and M100 latencies between TD and ASD cohorts, often reported in children, persisted into adulthood, with no evidence supporting latency convergence.

Pilot study on renal magnetic resonance diffusion tensor imaging: are quantitative diffusion tensor imaging values useful in the evaluation of children with ureteropelvic junction obstruction?

BACKGROUND: Ureteropelvic junction (UPJ) obstruction is a common cause of renal injury in children. Indications for surgery are still controversial. Currently, there is no threshold to differentiate patients with suspected UPJ obstruction requiring surgery from the ones that do not, or to predict renal outcome after surgery. Several studies have demonstrated that diffusion tensor imaging (DTI) results may correlate with microstructural changes in the kidneys. OBJECTIVE: To evaluate the feasibility of using DTI to identify UPJ obstruction kidneys. MATERIALS AND METHODS: We analyzed functional MR urography (fMRU) with renal DTI (b=0 and b=400, 20 directions, 1.5 Tesla, no respiratory triggering) in 26 kidneys of 19 children (mean age: 6.15 years) by comparing 13 kidneys with UPJ obstruction configuration that underwent pyeloplasty following the fMRU, and 13 anatomically normal age- and gender-matched kidneys. DTI tractography was reconstructed using a fractional anisotropy threshold of 0.10 and an angle threshold of 55°. User-defined regions of interest (ROIs) of the renal parenchyma (excluding collecting system) were drawn to quantify DTI parameters: fractional anisotropy, apparent diffusion coefficient (ADC), track length and track volume. The failure rate was evaluated. RESULTS: All DTI parameters changed with age; fractional anisotropy decreased (P<0.032). Track volume and track length increased (P<0.05). ADC increased with age in normal kidneys (P<0.001) but not in UPJ obstruction kidneys (P=0.11). After controlling for age, the fractional anisotropy (UPJ obstruction mean: 0.18, normal kidney mean: 0.21; P=0.001) and track length (UPJ obstruction mean: 11.9 mm, normal kidney mean: 15.4 mm; P<0.001) were lower in UPJ obstruction vs. normal kidneys. There was a trend toward a higher ADC in UPJ obstruction kidneys vs. normal kidneys (P=0.062). The failure rate in UPJ obstruction kidneys due to technical limitations of DTI was 13/26 (50%). CONCLUSION: We demonstrated that fractional anisotropy is lower in UPJ obstruction than in normal kidneys. It is necessary to improve this technique to increase the success rate and to perform more studies to evaluate if a decrease in fractional anisotropy can differentiate UPJ obstruction kidneys from hydronephrotic kidneys without UPJ obstruction.

Correlation between diffusion tensor imaging parameters of the distal femoral physis and adjacent metaphysis, and subsequent adolescent growth.

BACKGROUND: Diffusion-tensor imaging (DTI) depicts the movement of water through columns of cartilage and newly formed bone and provides information about velocity of growth and growth potential. OBJECTIVE: To determine the correlation between DTI tractography parameters of the distal femoral physis and metaphysis and the height change after DTI in pubertal and post-pubertal children. MATERIALS AND METHODS: We retrospectively analyzed DTI images of the knee in 47 children with a mean age of 14.1 years in a 2-year period. In sagittal echoplanar DTI studies, regions of interest were placed in the femoral physis. Tractography was performed using a fractional anisotropy threshold of 0.15 and a maximum turning angle of 40°. The sample was divided to assess short-term and long-term growth after DTI. Short-term growth (n=25) was the height change between height at MRI and 1 year later. Long-term growth (n=36) was the height gain between height at MRI and at the growth plateau. RESULTS: For the short-term group, subjects with larger tract volume (R2=0.40) and longer track lengths (R2=0.38) had larger height gains (P<0.01). For the long-term group, subjects with larger tract volume (R2=0.43) and longer track lengths (R2=0.32) had a larger height gain at the growth plateau (P<0.01). Intra- and inter-observer variability were good-excellent. CONCLUSION: Follow-up data of growth 1 year after DTI evaluation and at skeletal maturity confirms that DTI parameters are associated with the amount of post-imaging growth.

Relationship of renal apparent diffusion coefficient and functional MR urography in children with pelvicalyceal dilation.

OBJECTIVE: The aim is to evaluate the age-related changes and relationship of renal apparent diffusion coefficient (ADC) against the morphological and functional changes detected by functional magnetic resonance urography (fMRU) in children with pelvicalyceal dilation, with suspected or known ureteropelvic junction obstruction. MATERIALS AND METHODS: We retrospectively analyzed fMRUs with diffusion-weighted imaging (DWI) of the kidney in 35 subjects (25 males; median age: 7.1 years, range: 0.3-22.7 years) with 70 kidneys (40 with pelvicalyceal dilation and 30 with no pelvicalyceal dilation). Inclusion criteria were pelvicalyceal dilation, the absence of duplex kidneys and no ureteric dilation. DWI was performed with 3 diffusion gradient directions (b values = 0, 200, 500, 800 and 1,000 s/mm2). Metrics for fMRU included calyceal and renal transit times (CTT, RTT), time-to-peak (TTP), differential renal function based on volume (vDRF), Patlak number (pDRF) and combined volume and Patlak number (vpDRF). The grades of pelvicalyceal dilation, cortical thinning and corticomedullary differentiation were evaluated. The relationship between ADC values and the fMRU parameters was analyzed. RESULTS: ADC increases with age in kidneys without pelvicalyceal dilation (R2=0.37, P<0.001). Renal ADC does not correlate with any of the morphological or fMRU parameters (P>0.07). The median ADC of kidneys without pelvicalyceal dilation was 3.73×10-3 mm2/s (range: 2.78-5.37×0-3 mm2/s) and the median ADC of kidneys with pelvicalyceal dilation was 3.82×10-3 mm2/s (range: 2.70-5.70×10-3 mm2/s). There was no correlation between ADC and the absolute differences of vDRF or pDRF (P>0.33). CONCLUSION: Renal ADC does not correlate with morphological and functional results of fMRU changes in children with pelvicalyceal dilation due to suspected or known ureteropelvic junction obstruction.

Brain MR Imaging Findings and Associated Outcomes in Carriers of the Reciprocal Copy Number Variation at 16p11.2.

Purpose To identify developmental neuroradiologic findings in a large cohort of carriers who have deletion and duplication at 16p11.2 (one of the most common genetic causes of autism spectrum disorder [ASD]) and assess how these features are associated with behavioral and cognitive outcomes. Materials and Methods Seventy-nine carriers of a deletion at 16p11.2 (referred to as deletion carriers; age range, 1-48 years; mean age, 12.3 years; 42 male patients), 79 carriers of a duplication at 16p11.2 (referred to as duplication carriers; age range, 1-63 years; mean age, 24.8 years; 43 male patients), 64 unaffected family members (referred to as familial noncarriers; age range, 1-46 years; mean age, 11.7 years; 31 male participants), and 109 population control participants (age range, 6-64 years; mean age, 25.5 years; 64 male participants) were enrolled in this cross-sectional study. Participants underwent structural magnetic resonance (MR) imaging and completed cognitive and behavioral tests. MR images were reviewed for development-related abnormalities by neuroradiologists. Differences in frequency were assessed with a Fisher exact test corrected for multiple comparisons. Unsupervised machine learning was used to cluster radiologic features and an association between clusters and cognitive and behavioral scores from IQ testing, and parental measures of development were tested by using analysis of covariance. Volumetric analysis with automated segmentation was used to confirm radiologic interpretation. Results For deletion carriers, the most prominent features were dysmorphic and thicker corpora callosa compared with familial noncarriers and population control participants (16%; P < .001 and P < .001, respectively) and a greater likelihood of cerebellar tonsillar ectopia (30.7%; P < .002 and P < .001, respectively) and Chiari I malformations (9.3%; P < .299 and P < .002, respectively). For duplication carriers, the most salient findings compared with familial noncarriers and population control participants were reciprocally thinner corpora callosa (18.6%; P < .003 and P < .001, respectively), decreased white matter volume (22.9%; P < .001, and P < .001, respectively), and increased ventricular volume (24.3%; P < .001 and P < .001, respectively). By comparing cognitive assessments to imaging findings, the presence of any imaging feature associated with deletion carriers indicated worse daily living, communication, and social skills compared with deletion carriers without any radiologic abnormalities (P < .005, P < .002, and P < .004, respectively). For the duplication carriers, presence of decreased white matter, callosal volume, and/or increased ventricle size was associated with decreased full-scale and verbal IQ scores compared with duplication carriers without these findings (P < .007 and P < .004, respectively). Conclusion In two genetically related cohorts at high risk for ASD, reciprocal neuroanatomic abnormalities were found and determined to be associated with cognitive and behavioral impairments. © RSNA, 2017 Online supplemental material is available for this article.

Obesity and sarcoidosis: consequence or contributor?

PURPOSE OF REVIEW: Sarcoidosis is a multisystem disease of unknown cause. Obesity can affect many physiological factors. The relationship between obesity and sarcoidosis is unclear, and can been described as posing a 'chicken and egg' scenario for the patient as it is not always clear whether it is a consequence of, or a risk factor for any disease. The purpose of this review is to examine the dual roles of obesity on sarcoidosis morbidity and the incidence. RECENT FINDINGS: Obesity magnifies the symptoms of sarcoidosis and corticosteroid therapy increases BMI. Prospective epidemiologic studies started to explore the role of obesity as a potential risk factor for sarcoidosis. Three studies in the United States, and one study in Denmark, have demonstrated significantly increased risks of sarcoidosis among obese compared with nonobese patients; risk estimates ranged from 1.42 [95% confidence interval (CI), 1.07-1.89] to 3.59 (95% CI, 2.31-5.57). SUMMARY: Obesity can be both a consequence of sarcoidosis treatment, and a contributor to disease risk likely through the pro-inflammatory environment of obesity. Prospective epidemiologic cohort studies are needed to explore the cause of sarcoidosis and insight into possible avenues of treatment development and prevention.

Event Centrality and Bereavement Symptomatology: The Moderating Role of Meaning Made.

The centrality of a loss to a bereaved individual's identity is associated with greater symptomatology, whereas meaning made of a loss is associated with positive outcomes. This article examines meaning made as a moderator of the relationship between event centrality and symptomatology. Our sample consisted of 204 bereaved undergraduate university students. Centrality was assessed using the Centrality of Events Scale, meaning made was assessed using the Integration of Stressful Life Experiences Scale, and symptomatology was assessed using the posttraumatic stress disorder Checklist-Civilian and Inventory of Complicated Grief-Revised. Meaning made had a significant moderating effect on the relationship between centrality and both measures of symptomatology. At lower levels of meaning made, centrality had a strong and positive association with symptomatology; at higher levels of meaning made, this association became weaker. These results suggest that meaning made is the key to understanding how centrality affects bereavement outcomes.

Diffusion-Tensor Imaging of the Physes: A Possible Biomarker for Skeletal Growth-Experience with 151 Children.

Purpose To determine the changes of diffusion-tensor imaging (DTI) and tractography in the distal femur and proximal tibia related to age, sex, and height. Materials and Methods Following institutional review board approval, with waiver of consent and with HIPAA compliance, the authors retrospectively analyzed DTI images of the knee in 151 children, 73 girls (median age, 14.1 years; range, 6.5-17.8 years) and 78 boys (median age, 16.6 years; range, 6.9-17.9 years), studied from January 2013 to October 2014. At sagittal echo-planar DTI (20 directions, b values of 0 and 600 sec/mm2), regions of interest were placed in the tibial and femoral physes. Using a fractional anisotropy threshold of 0.15 and an angle threshold of 40°, the authors performed tractography and measured apparent diffusion coefficient (ADC) and tract length and volume. Changes related to age, sex, and height were evaluated by using fitted nonlinear polynomial functions on bootstrapped samples. Results Femoral tract volume and length increased and then decreased with age (P < .001); the peaks of femoral tract volume are consistent with the growth spurt, occurring earlier in girls (10.8 years) than in boys (13.0 years) (P < .001). Girls had smaller tract volumes in comparison to boys (P = .013). ADC peaks 2 years earlier than tract volume (girls at 9.3 years, boys at 11.0 years). Girls with greater than 50th percentile of height had longer tracts and greater tract volumes compared with girls with less than 50th percentile (P < .020). DTI parameters of boys do not correlate with percentile of height (P > .300). Conclusion DTI of the physis and metaphysis shows greater tract length and volumes in subjects who are at ages when the growth is fastest. ADC and tract length and volume have an earlier and smaller peak in girls than in boys. Femoral tract length and volume are larger in taller girls. © RSNA, 2017.

The response of FDG uptake to immunosuppressive treatment on FDG PET/CT imaging for cardiac sarcoidosis.

BACKGROUND: Immunosuppression is used to treat cardiac sarcoidosis, despite limited data. FDG PET/CT is used for detecting cardiac inflammation in patients with CS, yet there is variability in interpretation of FDG PET/CT. Our aim was to compare quantitative and qualitative interpretation of FDG PET/CT for CS in defining the FDG response to immunosuppression. METHODS AND RESULTS: Patients with CS (N = 43 total studies from 17 patients) had serial FDG PET/CT studies before/after immunosuppression. FDG uptake was analyzed qualitatively (visually; FDG-positive segments) and quantitatively (SUVmax; cardiac metabolic volume and activity (CMV, CMA); volume above SUV thresholds 2.7 and 4.1 g/mL). Complete resolution of FDG uptake was common using CMA (10/17), CMV (10/17), but a 2.7 g/mL SUV threshold (13/17) and SUVmax (14/17) were more likely to define partial responses. In six patients imaged after a reduction in immunosuppression, 4/6 had a rebound quantitative FDG uptake. CONCLUSIONS: Quantitative interpretation of FDG PET/CT in CS can detect changes in FDG uptake in response to immunosuppression. Further studies are needed to see if quantitative changes in FDG uptake are associated with improved outcomes.

Auditory Evoked M100 Response Latency is Delayed in Children with 16p11.2 Deletion but not 16p11.2 Duplication.

Individuals with the 16p11.2 BP4-BP5 copy number variant (CNV) exhibit a range of behavioral phenotypes that may include mild impairment in cognition and clinical diagnoses of autism spectrum disorder (ASD). To better understand auditory processing impairments in populations with this chromosomal variation, auditory evoked responses were examined in children with the 16p11.2 deletion, 16p11.2 duplication, and age-matched controls. Stimuli consisted of sinusoidal binaural tones presented passively while children underwent recording with magnetoencephalography (MEG). The primary indicator of auditory processing impairment was the latency of the ∼100-ms "M100" auditory response detected by MEG, with the 16p11.2 deletion population exhibiting profoundly delayed M100 latencies relative to controls. This delay remained even after controlling for potential confounds such as age and cognitive ability. No significant difference in M100 latency was observed between 16p11.2 duplication carriers and controls. Additionally, children meeting diagnostic criteria for ASD (16p11.2 deletion carriers) exhibited nonsignificant latency delays when compared with the corresponding CNV carriers not meeting criteria for ASD. Present results indicate that 16p11.2 deletion is associated with auditory processing delays analogous to (but substantially more pronounced than) those previously reported in "idiopathic" ASD.

Reciprocal white matter alterations due to 16p11.2 chromosomal deletions versus duplications.

Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers. We find associations of these white matter alterations with cognitive and behavioral impairments. We further demonstrate the value of imaging metrics for characterizing the copy number variant phenotype by employing linear discriminant analysis to predict the gene dosage status of the study subjects. These results show an effect of 16p11.2 gene dosage on white matter microstructure, and further suggest that opposite changes in diffusion tensor imaging metrics can lead to similar cognitive and behavioral deficits. Given the large effect sizes found in this study, our results support the view that specific genetic variations are more strongly associated with specific brain alterations than are shared neuropsychiatric diagnoses. Hum Brain Mapp 37:2833-2848, 2016. © 2016 Wiley Periodicals, Inc.

Systemic Chemotherapy and White Matter Integrity in Tracts Associated with Cognition Among Children With Neurofibromatosis Type 1.

BACKGROUND: Children with neurofibromatosis type 1 (NF1) are predisposed to both brain tumors and cognitive deficits. While changes in white matter integrity after multimodal therapy are associated with cognitive dysfunction, the effect of isolated chemotherapy in NF1 is unknown. To determine whether chemotherapy is associated with white matter microstructural changes, we examined diffusion tensor imaging (DTI) in NF1 subjects. PROCEDURE: We reviewed DTI measures in tracts associated with cognition but free from tumor in 24 children with NF1-associated optic pathway gliomas unexposed to surgery or radiation. Twelve age-matched pairs were identified based on exposure to chemotherapy. A paired t-test was used to compare fractional anisotropy (FA) in tracts of interest between subjects with and without chemotherapy exposure. RESULTS: On paired t-test, FA was significantly lower in the corpus callosum (P = 0.015) and cerebellothalamic (P = 0.038) tracts of subjects exposed to chemotherapy. There was no effect of age or time from chemotherapy on the difference between groups. In multivariable analysis, FA of these tracts was associated with chemotherapy exposure after adjusting for age, tumor location, and DTI acquisition. In longitudinal measures, FA decreased after chemotherapy exposure while FA increased with age in unexposed subjects. CONCLUSIONS: Exposure to low-intensity chemotherapy in NF1 is associated with changes in white matter microstructure in tracts associated with cognition. Future studies should determine whether these changes are associated with cognitive decline. While chemotherapy may spare cognition relative to radiation and surgery, children with NF1 exposed to chemotherapy may benefit from early cognitive testing to allow for earlier intervention.

Integrity of Bolted Angle Connections Subjected to Simulated Column Removal.

Large-scale tests of steel gravity framing systems (SGFSs) have shown that the connections are critical to the system integrity, when a column suffers damage that compromises its ability to carry gravity loads. When supporting columns were removed, the SGFSs redistributed gravity loads through the development of an alternate load path in a sustained tensile configuration resulting from large vertical deflections. The ability of the system to sustain such an alternate load path depends on the capacity of the gravity connections to remain intact after undergoing large rotation and axial extension demands, for which they were not designed. This study experimentally evaluates the performance of steel bolted angle connections subjected to loading consistent with an interior column removal. The characteristic connection behaviors are described and the performance of multiple connection configurations are compared in terms of their peak resistances and deformation capacities.