Purpose:To determine whether the combination of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI provides higher diagnostic sensitivity for prostate cancer than each technique alone. Materials and Methods:Fourteen patients with a clinical suspicion of prostate cancer underwent endorectal MRI on a 1.5T scanner prior to transrectal ultrasound (TRUS)-guided biopsies. The average values of the apparent diffusion coefficient (ADC, calculated from b-values of 0 and 600), K trans , v e , maximum gadolinium (Gd) concentration, onset time, mean gradient, and maximum enhancement were determined. Correlation with histology was based on biopsy (six patients) and prostatectomy specimen (eight patients) results. The Tukey-Kramer test was used for statistical analysis. Results:The average values of all MRI parameters, except v e and maximum Gd concentration, showed significant differences between tumor and normal prostate. The sensitivity and specificity values were respectively 54% (35-72%) and 100% (95-100%) for the ADC data, and 59% (39 -77%) and 74% (63-83%) for the DCE data. When both ADC and DCE results were combined, the sensitivity increased to 87% (68 -95%) and specificity decreased to 74% (62-83%). Conclusion:All but two DW-and DCE-MRI parameters showed significant differences between tumor and normal prostate. Combining both techniques provides better sensitivity, with a small decrease in specificity.
Copy number variants (CNVs) are genomic rearrangements resulting from gains or losses of DNA segments. Typically, the term refers to rearrangements of sequences larger than 1 kb. This type of polymorphism has recently been shown to be a key contributor to intra-species genetic variation, along with single-nucleotide polymorphisms and short insertion-deletion polymorphisms. Over the last decade, a growing number of studies have highlighted the importance of copy number variation (CNV) as a factor affecting human phenotype and individual CNVs have been linked to risks for severe diseases. In plants, the exploration of the extent and role of CNV is still just beginning. Initial genomic analyses indicate that CNVs are prevalent in plants and have greatly affected plant genome evolution. Many CNV events have been observed in outcrossing and autogamous species. CNVs are usually found on all chromosomes, with CNV hotspots interspersed with regions of very low genetic variation. Although CNV is mainly associated with intergenic regions, many CNVs encompass protein-coding genes. The collected data suggest that CNV mainly affects the members of large families of functionally redundant genes. Thus, the effects of individual CNV events on phenotype are usually modest. Nevertheless, there are many cases in which CNVs for specific genes have been linked to important traits such as flowering time, plant height and resistance to biotic and abiotic stress. Recent reports suggest that CNVs may form rapidly in response to stress.
Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy in which brainstem spreading depolarization may play a pivotal role, as suggested by animal studies. However, patiotemporal details of spreading depolarization occurring in relation to fatal seizures have not been investigated. In addition, little is known about behavioural and neurophysiological features that may discriminate spontaneous fatal from non-fatal seizures. Transgenic mice carrying the missense mutation S218L in the a 1A subunit of Ca v 2.1 (P/Q-type) Ca 2+ channels exhibit enhanced excitatory neurotransmission and increased susceptibility to spreading depolarization. Homozygous Cacna1a S218L mice show spontaneous non-fatal and fatal seizures, occurring throughout life, resulting in reduced life expectancy. To identify characteristics of fatal and non-fatal spontaneous seizures, we compared behavioural and electrophysiological seizure dynamics in freely-behaving homozygous Cacna1a S218L mice. To gain insight on the role of brainstem spreading depolarization in SUDEP, we studied the spatiotemporal distribution of spreading depolarization in the context of seizure-related death. Spontaneous and electrically-induced seizures were investigated by video monitoring and electrophysiological recordings in freely-behaving Cacna1a S218L and wild-type mice. Homozygous Cacna1a S218L mice showed multiple spontaneous tonic-clonic seizures and died from SUDEP in adulthood. Death was preceded by a tonic-clonic seizure terminating with hindlimb clonus, with suppression of cortical neuronal activity during and after the seizure. Induced seizures in freely-behaving homozygous Cacna1a S218L mice were followed by multiple spreading depolarizations and death. In wild-type or heterozygous Cacna1a S218L mice, induced seizures and spreading depolarization were never followed by death. To identify temporal and regional features of seizure-induced spreading depolarization related to fatal outcome, diffusion-weighted MRI was performed in anaesthetized homozygous Cacna1a S218L and wild-type mice. In homozygous Cacna1a S218L mice, appearance of seizure-related spreading depolarization in the brainstem correlated with respiratory arrest that was followed by cardiac arrest and death. Recordings in freely-behaving homozygous Cacna1a S218L mice confirmed brainstem spreading depolarization during spontaneous fatal seizures. These data underscore the value of the homozygous Cacna1a S218L mouse model for identifying discriminative features of fatal compared to non-fatal seizures, and support a key role for cortical neuronal suppression and brainstem spreading depolarization in SUDEP pathophysiology.
Purpose-To assess the feasibility of luminal water imaging (LWI), a quantitative T 2 -based MRI technique, for the detection and grading of prostatic cancer (PCa).Material and Methods-18 patients with biopsy proven PCa provided informed consent to be included in this institutional human ethics board approved prospective study between January 2015, and January 2016. Patients underwent 3T MRI shortly before radical prostatectomy. T 2 distributions were generated with regularized Non-Negative Least Squares (NNLS)algorithm from multi-echo spin echo MRI data. From T 2 distributions, maps of seven MR parameters: N comp , T 2-short , T 2-long , geometric mean T 2 (gmT 2 ), Luminal Water Fraction (LWF), A short , and A long were generated and compared with digitized images of Hematoxylin and Eosin (H&E) stained whole-mount histology sections. Paired-t-test determined significant differences between MR parameters in malignant and non-malignant tissue. Correlation with Gleason score (GS) was evaluated with Spearman's rank correlation test. Diagnostic accuracy was evaluated using logistic generalized linear mixed effect models (GLMMs) and receiver operating characteristic (ROC) analysis. Results-The average values of four MR parameters: gmT 2 , A short , A long , and LWF were significantly different between malignant and non-malignant tissue. All MR parameters except for T 2-long showed significant correlation (P<0.05) with GS in peripheral zone (PZ). The highest correlation with GS was obtained for LWF (−0.78 ± 0.11, p < 0.001
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