Moderating Effect of Cortical Thickness on BOLD Signal Variability Age-Related Changes

The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or “BOLDSD,” is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that these predict functional decline in various cognitive domains. Nevertheless, the interaction between alterations in cortical morphology and BOLDSD changes has not been modeled quantitatively. The objective of the current study was to investigate the influence of cortical morphology metrics [i.e., cortical thickness (CT), gray matter (GM) volume, and cortical area (CA)] on age-related BOLDSD changes by treating these cortical morphology metrics as possible physiological confounds using linear mixed models. We studied these metrics in 28 healthy older subjects scanned twice at approximately 2.5 years interval. Results show that BOLDSD is confounded by cortical morphology metrics. Respectively, changes in CT but not GM volume nor CA, show a significant interaction with BOLDSD alterations. Our study highlights that CT changes should be considered when evaluating BOLDSD alternations in the lifespan

Automated registration and stitching of multiple 3D ultrasound images for monitoring neonatal intraventricular hemorrhage

Dilatation of the cerebral ventricles is a common condition in preterm neonates with intraventricular hemorrhage (IVH). Post Hemorrhagic Ventricular Dilatation (PHVD) can lead to lifelong neurological impairment caused by ischemic injury due to increased intracranial pressure, and without treatment can lead to death. Previously, we have developed and validated a 3D ultrasound (US) system to monitor the progression of ventricle volumes (VV) in IVH patients; however, many patients with severe PHVD have ventricles so large they cannot be imaged within a single 3D US image. This limits the utility of atlas based segmentation algorithms required to measure VV as parts of the ventricles are in separate 3D US images, and thus, an already challenging segmentation becomes increasingly difficult to solve. Without a more automated segmentation, the clinical utility of 3D US ventricle volumes cannot be fully realized due to the large number of images and patients required to validate the technique in a clinical trials. Here, we describe the initial results of an automated ‘stitching’ algorithm used to register and combine multiple 3D US images of the ventricles of patients with PHVD. Our registration results show that we were able to register these images with an average target registration error (TRE) of 4.25±1.95 mm

Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear.

The mammalian inner ear contains two sensory organs, the cochlea and vestibule. Their sensory neuroepithelia are characterized by a mosaic of hair cells and supporting cells. Cochlear hair cells differentiate in four rows: a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs). Recent studies have shown that Math1, a mammalian homolog of Drosophila atonal is a positive regulator of hair cell differentiation. The basic helix-loop-helix (bHLH) genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologs) can influence cell fate determination by acting as negative regulators to inhibit the action of bHLH-positive regulators. We show by using reverse transcription-PCR analysis that Hes1, Hes5, and Math1 are expressed in the developing mouse cochleae. In situ hybridization revealed a widespread expression of Hes1 in the greater epithelial ridge (GER) and in lesser epithelial ridge (LER) regions. Hes5 is predominantly expressed in the LER, in supporting cells, and in a narrow band of cells within the GER. Examination of cochleae from Hes1(-/-) mice showed a significant increase in the number of IHCs, whereas cochleae from Hes5(-/-) mice showed a significant increase in the number of OHCs. In the vestibular system, targeted deletion of Hes1 and to a lesser extent Hes5 lead to formation of supernumerary hair cells in the saccule and utricle. The supernumerary hair cells in the mutant mice showed an upregulation of Math1. These data indicate that Hes1 and Hes5 participate together for the control of inner ear hair cell production, likely through the negative regulation of Math1

Development of a 3D Ultrasound System to Investigate Post-Hemorrhagic Hydrocephalus in Pre-term Neonates

Clinical intracranial ultrasound (US) is performed as a standard of care on neonates at risk of intraventricular hemorrhaging (IVH) and is also used after a diagnosis to monitor for potential ventricular dilation. However, it is difficult to estimate the volume of ventricles with 2D US due to their irregular shape. We developed a 3D US system to be used as an adjunct to a clinical system to investigate volumetric changes in the ventricles of neonates with IVH. Our system has been found have an error of within 1% of actual distance measurements in all three directions and volume measurements of manually segmented volumes from phantoms were not statistically significantly different from the actual values (p\u3e0.3). Inter-observer volume measurements of the lateral ventricles in a patient with grade III IVH found no significant differences between measurements. There is the potential to use this system in IVH patients to monitor the progression of ventriculomegaly over time

Semi-automatic segmentation of the fetal brain from magnetic resonance imaging

Background: Volumetric measurements of fetal brain maturation in the third trimester of pregnancy are key predictors of developmental outcomes. Improved understanding of fetal brain development trajectories may aid in identifying and clinically managing at-risk fetuses. Currently, fetal brain structures in magnetic resonance images (MRI) are often manually segmented, which requires both time and expertise. To facilitate the targeting and measurement of brain structures in the fetus, we compared the results of five segmentation methods applied to fetal brain MRI data to gold-standard manual tracings. Methods: Adult women with singleton pregnancies (n = 21), of whom five were scanned twice, approximately 3 weeks apart, were recruited [26 total datasets, median gestational age (GA) = 34.8, IQR = 30.9–36.6]. T2-weighted single-shot fast spin echo images of the fetal brain were acquired on 1.5T and 3T MRI scanners. Images were first combined into a single 3D anatomical volume. Next, a trained tracer manually segmented the thalamus, cerebellum, and total cerebral volumes. The manual segmentations were compared with five automatic methods of segmentation available within Advanced Normalization Tools (ANTs) and FMRIB’s Linear Image Registration Tool (FLIRT) toolboxes. The manual and automatic labels were compared using Dice similarity coefficients (DSCs). The DSC values were compared using Friedman’s test for repeated measures. Results: Comparing cerebellum and thalamus masks against the manually segmented masks, the median DSC values for ANTs and FLIRT were 0.72 [interquartile range (IQR) = 0.6–0.8] and 0.54 (IQR = 0.4–0.6), respectively. A Friedman’s test indicated that the ANTs registration methods, primarily nonlinear methods, performed better than FLIRT (p \u3c 0.001). Conclusion: Deformable registration methods provided the most accurate results relative to manual segmentation. Overall, this semi-automatic subcortical segmentation method provides reliable performance to segment subcortical volumes in fetal MR images. This method reduces the costs of manual segmentation, facilitating the measurement of typical and atypical fetal brain development

Magnetic resonance imaging and histology correlation in the neocortex in temporal lobe epilepsy.

OBJECTIVE: To investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. METHODS: We correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. RESULTS: We found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (rs  = 0.726, pfwe  = 0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. INTERPRETATION: Our results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders

Teaching for the transition: The Canadian PGY-1 neurosurgery \u27rookie camp\u27

Background: Transitioning from medical school to residency is difficult and stressful, necessitating innovation in easing this transition. In response, a Canadian neurosurgical Rookie Camp was designed and implemented to foster acquisition of technical, cognitive and behavioral skills among incoming Canadian post graduate year one (PGY-1) neurosurgery residents. Methods: The inaugural Rookie Camp was held in July 2012 in Halifax. The curriculum was developed based on a national needs-assessment and consisted of a pre-course manual, 7 case-based stations, 4 procedural skills stations and 2 group discussions. The content was clinically focused, used a variety of teaching methods, and addressed multiple CanMEDS competencies. Evaluation included participant and faculty surveys and a pre-course, post-course, and 3-month retention knowledge test. Results: 17 of 23 PGY-1 Canadian neurosurgical residents participated in the Camp. All agreed the course content was relevant for PGY-1 training and the experience prepared them for residency. All participants would recommend the course to future neurosurgical residents. A statistically significant improvement was observed in knowledge related to course content (F(2,32) = 7.572, p\u3c0.002). There were no significant differences between post-test and retention-test scores at three months. Conclusion: The inaugural Canadian Neurosurgery Rookie Camp for PGY-1 residents was successfully delivered, with engagement from participants, training programs, the Canadian Neurosurgical Society, and the Royal College. In addition to providing fundamental knowledge, which was shown to be retained, the course eased junior residents\u27 transition to residency by fostering camaraderie and socialization within the specialty

Cognitive demands of face monitoring: Evidence for visuospatial overload

Young children perform difficult communication tasks better face to face than when they cannot see one another (e.g., Doherty-Sneddon & Kent, 1996). However, in recent studies, it was found that children aged 6 and 10 years, describing abstract shapes, showed evidence of face-to-face interference rather than facilitation. For some communication tasks, access to visual signals (such as facial expression and eye gaze) may hinder rather than help children’s communication. In new research we have pursued this interference effect. Five studies are described with adults and 10- and 6-year-old participants. It was found that looking at a face interfered with children’s abilities to listen to descriptions of abstract shapes. Children also performed visuospatial memory tasks worse when they looked at someone’s face prior to responding than when they looked at a visuospatial pattern or at the floor. It was concluded that performance on certain tasks was hindered by monitoring another person’s face. It is suggested that processing of visual communication signals shares certain processing resources with the processing of other visuospatial information

Investigation of hippocampal substructures in focal temporal lobe epilepsy with and without hippocampal sclerosis at 7T.

PURPOSE: To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes. RESULTS: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P \u3c 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628). CONCLUSION: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370

Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n-back working memory paradigm

{Purpose} Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with 99mTc-HMPAO using low irradiation dose. {Materials and methods} A two-scans protocol was applied to 12 healthy young volunteers using 270 MBq of 99mTc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal {n}-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. {Results} Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and 15O-PET studies. {Conclusion} The results support the use of 99mTc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical populations