Tracking and predicting cognitive development using magnetic resonance imaging

Neuroimaging of the developing brain has helped describing and quantifying many of the biological processes underlying cognitive development. The protracted development of higher order cognitive functions has allowed detailed description of their neural correlates. While primary sensory and motor functions have been found to be relatively localized, higher order cognitive functions including Working Memory (WM) have been found to be distributed over many brain regions. A growing amount of literature is describing a complex interaction of anatomically separate nodes making up networks sub-serving WM. The development of these networks is dependent on both predetermined maturation and environmental stimulation. The current thesis aims to expand the current knowledge by exploring if WM development can be predicted by using Magnetic Resonance Imaging (MRI) data explaining future development rather than correlating to current capacity. We further apply this principle on a sample of premature born children to predict future cognitive outcome using MRI at birth. Finally we address the question if individual variability in developmental timing affects cognitive abilities in childhood and adolescence. Study I: In this study we show that WM development to some degree can be predicted using structural and functional MRI. The prediction was based on a multivariate model of MRI data and could significantly predict WM two years after the scans. This significance was retained after controlling for three concurrent WM tests. Analysis to localize the predictive effect of MRI suggests basal ganglia and thalamic structures as important for future development while classical cortical WM areas correlate to concurrent WM capacity. Study II: We apply a similar analysis strategy as in Study I on a longitudinal sample of preterm born children. T2 and Diffusion Tensor Imaging (DTI) sequences were collected in the perinatal period and used to predict WM and Numerical Ability (NA) at five and seven years of age. We show that multivariate models can predict NA and WM capacity at five years of age. This was the strongest predictor when compared with previously known important clinical features. T2 based volumetric analysis points towards reductions in insula and basal ganglia volume in the perinatal period among children with low cognitive function at five years of age. Study III: The study explores weather the individual time course of development affects WM abilities when children start school. We trained a multivariate model of brain development using DTI from a sample of normally developing children. We then apply the model on a sample of seven year old children to show that brain maturation correlates strongly with WM abilities while age does not. In summary the articles add to the developmental neuroscience literature by showing the ability of MRI to predict cognitive development. Prediction of development is an area discussed as a promising target for clinical implementation of cognitive neuroimaging. We show the feasibility and clinically relevant effects of prediction in a clinical sample. Finally the measuring of variability in developmental timing in Study III highlight the view of WM development as result of multiple processes

Flow-directed micro-catheterisation technique over a detachable coil

Embolisation of neonatal arteriovenous shunts poses several challenges: tortuous and fragile vessels, limited contrast volume and few specialised paediatric endovascular devices. In a 9-day-old patient with a choroidal type vein of Galen malformation we encountered an extremely tortuous posterior choroidal artery pedicle during endovascular treatment. After attempted selection using a traditional over-the-wire technique, we advanced a platinum coil through the micro-catheter. High flow within the feeder directed the soft and malleable coil anterograde. We then advanced the catheter over the coil's pusher wire in a facile manner to an ideal position for embolisation. This approach may be especially useful in cases requiring coil/vinyl-based liquid embolics, given that the only flow-directed micro-catheter available to most operators is compatible with n-Butyl cyanoacrylate alone. Moreover, the soft distal portion of coil may impart a safety benefit over traditional guidewires in easily perforated neonatal vasculature

Focused Ultrasound Ablation of an Arteriovenous Malformation Model

Brain AVMs are rare but serious vascular lesions that often pose a management dilemma between the risk of various treatment modalities and uncertain natural history during observation. We describe preliminary data on the use of focused ultrasound as a novel therapeutic strategy. In an AVM model, one session of ultrasound gradually reduced flow through the lesion without inducing rupture. Due to its non-invasive yet immediate ablative effects, focused ultrasound may allow safer treatment of AVMs. However, further studies are needed to clarify its efficacy and side effect profile

Similar outcome of femoral neck fractures treated with Pinloc or Hansson Pins : 1-year data from a multicenter randomized clinical study on 439 patients

Background and purpose - There are few reports on the efficiency of the Hansson Pinloc System (Pinloc) for fixation of femoral neck fractures. We compare Pinloc with the commonly used Hansson Pin System in a randomized clinical trial. The primary outcome measure is non-union or avascular necrosis within 2 years. We now report fracture failures and reoperations within the first year. Patients and methods - Between May 2014 and February 2017, 439 patients were included in the study. They were above 50 years of age and treated for a femoral neck fracture at 9 orthopedic departments in Sweden. They were randomized to either Pinloc or Hansson pins. The fractures were grouped as (a) non-displaced regardless of age, (b) displaced in patients < 70 years, or (c) >= 70 years old, but deemed unfit to undergo arthroplasty. Follow-up with radiographs and outpatient visits were at 3 and 12 months. Failure was defined as early displacement/non-union, symptomatic segmental collapse, or deep infection. Results - 1-year mortality was 11%. Of the 325 undisplaced fractures, 12% (21/169) Pinloc and 13% (20/156) Hansson pin patients had a failure during the first year. The reoperation frequencies were 10% (16/169) and 8% (13/156) respectively. For the 75 patients 50-69 years old with displaced fractures, 11/39 failures occurred in the Pinloc group and 11/36 in the Hansson group, and 8/39 versus 9/36 patients were reoperated. Among those 39 patients >= 70 years old, 7/21 failures occurred in the Pinloc group and 4/18 in the Hansson group. Reoperation frequencies were 4/21 for Pinloc and 3/18 for the Hansson pin patients. No statistically significant differences were found in any of the outcomes between the Pinloc and Hansson groups. Interpretation - We found no advantages with Pinloc regarding failure or reoperation frequencies in this 1-year follow-up

Investigation of the viral and bacterial microbiota in intestinal samples from mink (Neovison vison) with pre-weaning diarrhea syndrome using next generation sequencing.

Pre-weaning diarrhea (PWD) in mink kits is a common multifactorial syndrome on commercial mink farms. Several potential pathogens such as astroviruses, caliciviruses, Escherichia coli and Staphylococcus delphini have been studied, but the etiology of the syndrome seems complex. In pooled samples from 38 diarrheic and 42 non-diarrheic litters, each comprising of intestinal contents from 2-3 mink kits from the same litter, the bacterial populations were studied using Illumina Next Generation Sequencing technology and targeted 16S amplicon sequencing. In addition, we used deep sequencing to determine and compare the viral intestinal content in 31 healthy non-diarrheic and 30 diarrheic pooled samples (2-3 mink kits from the same litter per pool). The results showed high variations in composition of the bacterial species between the pools. Enterococci, staphylococci and streptococci dominated in both diarrheic and non-diarrheic pools. However, enterococci accounted for 70% of the reads in the diarrheic group compared to 50% in the non-diarrheic group and this increase was at the expense of staphylococci and streptococci which together accounted for 45% and 17% of the reads in the non-diarrheic and diarrheic group, respectively. Moreover, in the diarrheic pools there were more reads assigned to Clostridia, Escherichia-Shigella and Enterobacter compared to the non-diarrheic pools. The taxonomically categorized sequences from the virome showed that the most prevalent viruses in all pools were caliciviruses and mamastroviruses (almost exclusively type 10). However, the numbers of reads assigned to caliciviruses were almost 3 times higher in the diarrheic pools compared the non-diarrheic pools and Sapporo-like caliciviruses were more abundant than the Norwalk-like caliciviruses. The results from this study have contributed to the insight into the changes in the intestinal microbiota associated with the PWD syndrome of mink