A PCA3 gene-based transcriptional amplification system targeting primary prostate cancer.

Targeting specifically primary prostate cancer (PCa) cells for immune therapy, gene therapy or molecular imaging is of high importance. The PCA3 long non-coding RNA is a unique PCa biomarker and oncogene that has been widely studied. This gene has been mainly exploited as an accurate diagnostic urine biomarker for PCa detection. In this study, the PCA3 promoter was introduced into a new transcriptional amplification system named the 3-Step Transcriptional Amplification System (PCA3-3STA) and cloned into type 5 adenovirus. PCA3-3STA activity was highly specific for PCa cells, ranging between 98.7- and 108.0-fold higher than that for benign primary prostate epithelial or non-PCa cells, respectively. In human PCa xenografts, PCA3-3STA displayed robust bioluminescent signals at levels that are sufficient to translate to positron emission tomography (PET)-based reporter imaging. Remarkably, when freshly isolated benign or cancerous prostate biopsies were infected with PCA3-3STA, the optical signal produced from primary PCa biopsies was significantly higher than from benign prostate biopsies (4.4-fold, p < 0.0001). PCA3-3STA therefore represents a PCa-specific expression system with the potential to target, with high accuracy, primary or metastatic PCa epithelial cells for imaging, vaccines, or gene therapy

Spatio-temporal changes in littoral fish community structure along the St. Lawrence River (Québec, Canada) following round goby (Neogobius melanostomus) invasion

The round goby (Neogobius melanostomus), a small Ponto-Caspian bottom-dwelling fish species, was first observed in the St. Lawrence River in 1997. After twenty years, it is now considered as one of the most successful invaders of the St. Lawrence River. Despite the elevated abundances observed throughout the river, little is known about its impacts on the littoral/mid-shore fish community. In this study, we used a large dataset obtained from an annual standardized fish survey held in the St. Lawrence River to analyze the impacts of round goby on littoral native fish community and native predator assemblages within five distinct segments of the river characterized by different round goby abundances. Throughout the system, the round goby negatively impacted the abundances of tessellated darter (Etheostoma olmstedi) likely as a consequence of competitive exclusion. In contrast, the small pelagic/demersal brook silverside (Labidesthes sicculus) and emerald shiner (Notropis atherinoides) increased in abundance. Indirect food web effects, such as predation pressure relaxation, are suspected. Native predator abundances exhibited contrasting trends in the different sectors analyzed, with the exception of smallmouth bass (Micropterus dolomieu) abundances that increased in all fluvial lakes. We hypothesize that trophic relationships between littoral fish and native predators are influencing the outcomes of the round goby invasion of the St. Lawrence River

Measurement of Local Partial Pressure of Oxygen in the Brain Tissue under Normoxia and Epilepsy with Phosphorescence Lifetime Microscopy

In this work a method for measuring brain oxygen partial pressure with confocal phosphorescence lifetime microscopy system is reported. When used in conjunction with a dendritic phosphorescent probe, Oxyphor G4, this system enabled minimally invasive measurements of oxygen partial pressure (pO2) in cerebral tissue with high spatial and temporal resolution during 4-AP induced epileptic seizures. Investigating epileptic events, we characterized the spatio-temporal distribution of the "initial dip" in pO2 near the probe injection site and along nearby arterioles. Our results reveal a correlation between the percent change in the pO2 signal during the "initial dip" and the duration of seizure-like activity, which can help localize the epileptic focus and predict the length of seizure

Optical imaging of acute epileptic networks in mice

The potential of intrinsic optical imaging and resting-state analysis under anesthetized conditions as a tool to study brain networks associated with epileptic seizures is investigated. Using an acute model of epileptiform activity, the 4-aminopyridine model in live mice, we observe the changes in resting-state networks with the onset of seizure activity and in conditions of spiking activity. Resting-state networks identified before and after the onset of epileptiform activity show both decreased and increased homologous correlations, with a small dependence on seizure intensity. The observed changes are not uniform across the different hemodynamic measures, suggesting a potential decoupling between blood flow and metabolism in the low-frequency networks. This study supports the need for a more extensive investigation of epileptic networks including more than one independent hemodynamic measurement

fNIRS-EEG study of focal interictal epileptiform discharges

Functional near-infrared spectroscopy (fNIRS) acquired with electroencephalography (EEG) is a relatively new non-invasive neuroimaging technique with potential for long term monitoring of the epileptic brain. Simultaneous EEG-fNIRS recording allows the spatio-temporal reconstruction of the hemodynamic response in terms of the concentration changes in oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) associated with recorded epileptic events such as interictal epileptic discharges (IEDs) or seizures. While most previous studies investigating fNIRS in epilepsy had limitations due to restricted spatial coverage and small sample sizes, this work includes a sufficiently large number of channels to provide an extensive bilateral coverage of the surface of the brain for a sample size of 40 patients with focal epilepsies. Topographic maps of significant activations due to each IED type were generated in four different views (dorsal, frontal, left and right) and were compared with the epileptic focus previously identified by an epileptologist. After excluding 5 patients due to the absence of IEDs and 6 more with mesial temporal foci too deep for fNIRS, we report that significant HbR (respectively HbO) concentration changes corresponding to IEDs were observed in 62% (resp. 38%) of patients with neocortical epilepsies. This HbR/HbO response was most significant in the epileptic focus region among all the activations in 28%/21% of patients.CIHR (282447); CIHR-HSF (203422

fNIRS improves seizure detection in multimodal EEG-fNIRS recordings

In the context of epilepsy monitoring, electroencephalography (EEG) remains the modality of choice. Functional near-infrared spectroscopy (fNIRS) is a relatively innovative modality that cannot only characterize hemodynamic profiles of seizures but also allow for long-term recordings. We employ deep learning methods to investigate the benefits of integrating fNIRS measures for seizure detection. We designed a deep recurrent neural network with long short-term memory units and subsequently validated it using the CHBMIT scalp EEG database-a compendium of 896 h of surface EEG seizure recordings. After validating our network using EEG, fNIRS, and multimodal data comprising a corpus of 89 seizures from 40 refractory epileptic patients was used as model input to evaluate the integration of fNIRS measures. Following heuristic hyperparameter optimization, multimodal EEG-fNIRS data provide superior performance metrics (sensitivity and specificity of 89.7% and 95.5%, respectively) in a seizure detection task, with low generalization errors and loss. False detection rates are generally low, with 11.8% and 5.6% for EEG and multimodal data, respectively. Employing multimodal neuroimaging, particularly EEG-fNIRS, in epileptic patients, can enhance seizure detection performance. Furthermore, the neural network model proposed and characterized herein offers a promising framework for future multimodal investigations in seizure detection and prediction

Comparable cerebral oxygenation patterns in younger and older adults during dual-task walking with increasing load

The neuroimaging literature on dual-task gait clearly demonstrates increased prefrontal cortex (PFC) involvement when performing a cognitive task while walking. However, findings from direct comparisons of the cerebral oxygenation patterns of younger (YA) and older (OA) adults during dual-task walking are mixed and it is unclear how YA and OA respond to increasing cognitive load (difficulty) while walking. This functional near infra-red (fNIRS) study examined cerebral oxygenation of YA and OA during self-paced dual-task treadmill walking at two different levels of cognitive load (auditory n-back). Changes in accuracy (%) as well as oxygenated (HbO) and deoxygenated (HbR) hemoglobin were examined. For the HbO and HbR measures, eight regions of interest (ROls) were assessed: the anterior and posterior dorsolateral and ventrolateral PFC (aDLPFC, pDLPFC, aVLPFC, pVLPFC) in each hemisphere. Nineteen YA (M = 21.83 years) and 14 OA (M = 66.85 years) walked at a self-selected pace while performing auditory 1-back and 2-back tasks. Walking alone (single motor: SM) and performing the cognitive tasks alone (single cognitive: SC) were compared to dual-task walking (DT = SM + SC). In the behavioural data, participants were more accurate in the lowest level of load (1-back) compared to the highest (2-back; p < 0.001). YA were more accurate than OA overall (p = 0.009), and particularly in the 2-back task (p = 0.048). In the fNIRS data, both younger and older adults had task effects (SM < DT) in specific ROls for A HbO (three YA, one OA) and Delta HbR (seven YA, eight OA). After controlling for walk speed differences, direct comparisons between YA and OA did not reveal significant age differences, but did reveal a difficulty effect in HbO in the left aDLPFC (13 = 0.028) and significant task effects (SM < DT) in HbR for six of the eight ROls. Findings suggest that YA and OA respond similarly to manipulations of cognitive load when walking on a treadmill at a self-selected pace

Fully automated dual-resolution serial optical coherence tomography aimed at diffusion MRI validation in whole mouse brains

An automated dual-resolution serial optical coherence tomography (2R-SOCT) scanner is developed. The serial histology system combines a low-resolution ( 25 mu m / voxel ) 3 x OCT with a high-resolution ( 1.5 mu m / voxel ) 40 x OCT to acquire whole mouse brains at low resolution and to target specific regions of interest (ROIs) at high resolution. The 40 x ROIs positions are selected either manually by the microscope operator or using an automated ROI positioning selection algorithm. Additionally, a multimodal and multiresolution registration pipeline is developed in order to align the 2R-SOCT data onto diffusion MRI (dMRI) data acquired in the same ex vivo mouse brains prior to automated histology. Using this imaging system, 3 whole mouse brains are imaged, and 250 high-resolution 40 x three-dimensional ROIs are acquired. The capability of this system to perform multimodal imaging studies is demonstrated by labeling the ROIs using a mouse brain atlas and by categorizing the ROIs based on their associated dMRI measures. This reveals a good correspondence of the tissue microstructure imaged by the high-resolution OCT with various dMRI measures such as fractional anisotropy, number of fiber orientations, apparent fiber density, orientation dispersion, and intracellular volume fraction

An exploration of the effect of hemodynamic changes due to normal aging on the fNIRS response to semantic processing of words

Like other neuroimaging techniques assessing cerebral blood oxygenation, near-infrared spectroscopy (NIRS) has been applied in many neurocognitive studies. With NIRS, neural activation can be explored indirectly via hemodynamic changes in the imaged region. In studies of aging, changes in baseline physiology and brain anatomy confound NIRS measures seeking to investigate age-related changes in neuronal activity. The field is thus hampered by the complexity of the aging process itself, and statistical inferences from functional data acquired by optical imaging techniques must be interpreted with care. Multimodal integration of NIRS with both structural and baseline physiological assessments is crucial to avoid misinterpreting neuroimaging signals. In this study, a combination of two different optical techniques, anatomical MRI and Arterial Spin Labeling (ASL), was used to investigate age-related changes in activation during a lexical-semantic processing task. Quantitative analysis revealed decreased baseline oxyhemoglobin and cerebral blood flow in the older adults. Using baseline physiology measures as regressors in the investigation of functional concentration changes when doing analyses of variance, we found significant changes in task-induced areas of activity. In the right hemisphere, more significant age-related activity was observed around the junction of the inferior frontal gyrus and inferior precentral sulcus, along with engagement of Wernicke's area. In the left hemisphere, the degree and extent of frontal activation, including the dorsolateral prefrontal cortex and inferior frontal gyrus, differed between age groups. Measuring background physiological differences and using their values as regressors in statistical analyses allowed a more appropriate, age-corrected understanding of the functional differentiations between age groups. Age-corrected baselines are thus essential to investigate which components of the NIRS signal are altered by aging