ABSTRACT
Neurofibromatosis type-1 (NF1) is a common neurogenetic disorder and an important cause of intellectual disability. Brain-behaviour associations can be examined in vivo using morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to study brain structure. Here, we studied structural and behavioural phenotypes in heterozygous Nf1 mice (Nf1(+/-) ) using T2-weighted imaging MRI and DTI, with a focus on social recognition deficits. We found that Nf1(+/-) mice have larger volumes than wild-type (WT) mice in regions of interest involved in social cognition, the prefrontal cortex (PFC) and the caudate-putamen (CPu). Higher diffusivity was found across a distributed network of cortical and subcortical brain regions, within and beyond these regions. Significant differences were observed for the social recognition test. Most importantly, significant structure-function correlations were identified concerning social recognition performance and PFC volumes in Nf1(+/-) mice. Analyses of spatial learning corroborated the previously known deficits in the mutant mice, as corroborated by platform crossings, training quadrant time and average proximity measures. Moreover, linear discriminant analysis of spatial performance identified 2 separate sub-groups in Nf1(+/-) mice. A significant correlation between quadrant time and CPu volumes was found specifically for the sub-group of Nf1(+/-) mice with lower spatial learning performance, suggesting additional evidence for reorganization of this region. We found strong evidence that social and spatial cognition deficits can be associated with PFC/CPu structural changes and reorganization in NF1.
Subject(s)
Brain/physiopathology , Neurofibromatosis 1/physiopathology , Animals , Behavior, Animal/physiology , Brain/diagnostic imaging , Cognition/physiology , Cognition Disorders/diagnostic imaging , Cognition Disorders/physiopathology , Diffusion Tensor Imaging , Disease Models, Animal , Female , Magnetic Resonance Imaging , Male , Mice , Mice, Inbred C57BL , Neurofibromatosis 1/diagnostic imaging , Phenotype , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Social Behavior , Social Behavior Disorders/physiopathology , Structure-Activity RelationshipABSTRACT
BACKGROUND: The ultrasound biomicroscopy (UBM) technique generates high-resolution echographic images using acoustic frequencies between 20 and 200 MHz. In dermatology, it enables non-invasive visualization of cutaneous structures. In this sense, several studies are being conducted for the measurement of cutaneous tumor sizes and for the evaluation of their response to therapeutic procedures. The present work was conducted to analyze the ability of UBM to identify diverse histological structures associated with cutaneous carcinomas ex vivo regarding the evaluation of the technique as a diagnostic tool that could, eventually, improve the patient's healthcare protocol. METHODS: Ex vivo human tissue samples, corresponding to basal cell carcinoma and squamous cell carcinoma cases, were studied. The ultrasonic system operated with a center frequency of 45MHz and the histological structures were identified by comparison with the light microscopy images. RESULTS: The histological components present in the tumors were identified by variations in the echogenicity level for several of the studied cases and particular characteristics were observed for the different tumor types. CONCLUSION: The possibility of differentiating the histological components associated with cutaneous carcinomas indicates the potential use of UBM for diagnostic applications. However, a larger number of specimens must be studied.
