Fully Automated Segmentation of the Pons and Midbrain Using Human T1 MR Brain Images

Purpose

This paper describes a novel method to automatically segment the human brainstem into midbrain and pons, called LABS: Landmark-based Automated Brainstem Segmentation. LABS processes high-resolution structural magnetic resonance images (MRIs) according to a revised landmark-based approach integrated with a thresholding method, without manual interaction.

Methods

This method was first tested on morphological T1-weighted MRIs of 30 healthy subjects. Its reliability was further confirmed by including neurological patients (with Alzheimer''s Disease) from the ADNI repository, in whom the presence of volumetric loss within the brainstem had been previously described. Segmentation accuracies were evaluated against expert-drawn manual delineation. To evaluate the quality of LABS segmentation we used volumetric, spatial overlap and distance-based metrics.

Results

The comparison between the quantitative measurements provided by LABS against manual segmentations revealed excellent results in healthy controls when considering either the midbrain (DICE measures higher that 0.9; Volume ratio around 1 and Hausdorff distance around 3) or the pons (DICE measures around 0.93; Volume ratio ranging 1.024–1.05 and Hausdorff distance around 2). Similar performances were detected for AD patients considering segmentation of the pons (DICE measures higher that 0.93; Volume ratio ranging from 0.97–0.98 and Hausdorff distance ranging 1.07–1.33), while LABS performed lower for the midbrain (DICE measures ranging 0.86–0.88; Volume ratio around 0.95 and Hausdorff distance ranging 1.71–2.15).

Conclusions

Our study represents the first attempt to validate a new fully automated method for in vivo segmentation of two anatomically complex brainstem subregions. We retain that our method might represent a useful tool for future applications in clinical practice.     

Brief Parenteral Nutrition Accelerates Weight Gain,Head Growth Even in Healthy VLBWs

IntroductionWhether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate.MethodsWe studied 4005 hospitalized VLBW, very preterm (23–32 weeks'' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003–2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement <10^th percentile for postmenstrual age) at discharge.Results40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates.DiscussionEven in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants.     

Postoperative Hypoxia and Length of Intensive Care Unit Stay after Cardiac Surgery: The Underweight Paradox?

Objective

Cardiac operations with cardiopulmonary bypass can be associated with postoperative lung dysfunction. The present study investigates the incidence of postoperative hypoxia after cardiac surgery, its relationship with the length of intensive care unit stay, and the role of body mass index in determining postoperative hypoxia and intensive care unit length of stay.

Design

Single-center, retrospective study.

Setting

University Hospital. Patients. Adult patients (N = 5,023) who underwent cardiac surgery with CPB.

Interventions

None.

Measurements and main results

According to the body mass index, patients were attributed to six classes, and obesity was defined as a body mass index >30. POH was defined as a PaO2/FiO2 ratio <200 at the arrival in the intensive care unit. Postoperative hypoxia was detected in 1,536 patients (30.6%). Obesity was an independent risk factor for postoperative hypoxia (odds ratio 2.4, 95% confidence interval 2.05–2.78, P = 0.001) and postoperative hypoxia was a determinant of intensive care unit length of stay. There is a significant inverse correlation between body mass index and PaO2/FiO2 ratio, with the risk of postoperative hypoxia increasing by 1.7 folds per each incremental body mass index class. The relationship between body mass index and intensive care unit length of stay is U-shaped, with longer intensive care unit stay in underweight patients and moderate-morbid obese patients.

Conclusions

Obese patients are at higher risk for postoperative hypoxia, but this leads to a prolonged intensive care unit stay only for moderate-morbid obese patients. Obese patients are partially protected against the deleterious effects of hemodilution and transfusions. Underweight patients present the “paradox” of a better lung gas exchange but a longer intensive care unit stay. This is probably due to a higher severity of their cardiac disease.     

Allergen-Specific IL-5 Responses in Early Childhood Predict Asthma at Age Eight

Background

The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life.

Methods

Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640), had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), 5 years (n = 370) and 8 years (n = 275). We measured interleukin (IL-) 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ), at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression.

Results

HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years.

Conclusion

HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.     

Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

Background

Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients.

Methods and Findings

Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons.

Conclusions

Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally.

Trial Registration

ClinicalTrials.gov Identifiers: FLU 002- {"type":"clinical-trial","attrs":{"text":"NCT01056354","term_id":"NCT01056354"}}NCT01056354, FLU 003- {"type":"clinical-trial","attrs":{"text":"NCT01056185","term_id":"NCT01056185"}}NCT01056185.     

Effects of Multidisciplinary Rehabilitation on Chronic Fatigue in Multiple Sclerosis: A Randomized Controlled Trial

Background

Several rehabilitation programmes aim at reducing the impact of fatigue in MS patients. Acute and chronic fatigue should require different management.

Objectives

To assess the effects of individually tailored, multidisciplinary outpatient rehabilitation (MDR) on chronic fatigue.

Methods

Forty-eight ambulatory MS patients with chronic fatigue were randomized to MDR or to MS–nurse consultation. Fatigue was assessed by the Checklist Individual Strength (CIS-20R). Secondary outcomes included the Modified Fatigue Impact Scale, Fatigue Severity Scale, Functional Independence Measure, Disability and Impact Profile (DIP), Multiple Sclerosis Impact Scale and the Impact on Participation and Autonomy (IPA).

Results

The primary outcome measure CIS-20R overall score showed no significant differences between groups at 12 weeks (P = 0.39) and 24 weeks follow-up (P = 0.14), nor for subscales (t = 12 and t = 24, 0.19≤P≤0.88). No significant within-group effects were found for both groups with respect to the primary (0.57≤p≤0.97) and secondary (0.11≤p≤0.92) outcome measures from baseline to 12 or 24 weeks.

Conclusion

Multidisciplinary rehabilitation was not more effective in terms of reducing self-reported fatigue in MS patients compared to MS-nurse consultation. Our results suggest that chronic fatigue in patients with MS may be highly invariant over time, irrespective of interventions.

Trial Registration

controlled-trials.com ISRCTN05017507     

Right Anterior Insula: Core Region of Hallucinations in Cognitive Neurodegenerative Diseases

Objectives

We investigated the neural basis of hallucinations Alzheimer''s disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.

Methods

AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. “Core regions” (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.

Results

Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).

Conclusion

Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.     

Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

Objective

Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth.

Methods

A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy.

Results

Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001).

Conclusions

Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb.     

Taenia solium Infection in Peru: A Collaboration between Peace Corps Volunteers and Researchers in a Community Based Study

Background

Neurocysticercosis is a leading cause of seizures and epilepsy in most of the world, and it occurs when Taenia solium larval cysts infect the central nervous system. T. solium tapeworm infection is endemic in much of Peru, but there are scarce data on the prevalence in many rural highland communities where it is likely to be hyper-endemic. Peace Corps Volunteers live and work in these communities; however, to our knowledge, they have not been used to facilitate public health research.

Materials and Methods

We utilized Peace Corps Volunteers to estimate the prevalence of T. solium tapeworm infection in seven rural communities in northern Peru. A convenience non-random sampling frame was used. Peace Corps Volunteers facilitated the collection of stool samples (N = 2,328), which were analyzed by sedimentation and microscopy. Niclosamide treatment and purgation preceded species identification, which was done by PCR-REA.

Results

Taenia sp. egg-positive stool samples were found in three of the seven communities we surveyed. The overall prevalence of Taenia sp. egg positivity was 2.1% (49/2,328) (95% CI = 1.6–2.8%) with prevalence up to 4.3% (42/977) (95% CI = 3.1–5.8%) by community. All 34 of the specimens tested by PCR-REA were T. solium. The overall prevalence of T. solium tapeworm infection was 1.5% (34/2,328) (95% CI = 1.0–2.0%). Prevalence up to 2.9% (28/977) (95% CI = 1.9–4.1%) by community was observed.

Conclusion/Significance

This study recorded high T. solium tapeworm prevalence, and identified hyper-endemic rural communities. It demonstrates that synergy between researchers and Peace Corps Volunteers can be an effective means to conducting large-scale, community-based studies in remote areas of Peru.