Analysis of image formation in optical coherence elastography using a multiphysics approach

Image formation in optical coherence elastography (OCE) results from a combination of two processes: the mechanical deformation imparted to the sample and the detection of the resulting displacement using optical coherence tomography (OCT). We present a multiphysics model of these processes, validated by simulating strain elastograms acquired using phase-sensitive compression OCE, and demonstrating close correspondence with experimental results. Using the model, we present evidence that the approximation commonly used to infer sample displacement in phase-sensitive OCE is invalidated for smaller deformations than has been previously considered, significantly affecting the measurement precision, as quantified by the displacement sensitivity and the elastogram signal-to-noise ratio. We show how the precision of OCE is affected not only by OCT shot-noise, as is usually considered, but additionally by phase decorrelation due to the sample deformation. This multiphysics model provides a general framework that could be used to compare and contrast different OCE techniques.OCIS codes: (000.3860) Mathematical methods in physics, (000.4430) Numerical approximation and analysis, (030.6140) Speckle, (110.2990) Image formation theory, (110.4500) Optical coherence tomography     

Motor cortical inhibition in ADHD: modulation of the transcranial magnetic stimulation-evoked N100 in a response control task

The N100 component, evoked by transcranial magnetic stimulation (TMS) and electroencephalography is associated with the activation of inhibitory cortical circuits and has recently been suggested as a potential marker of inhibition in attention-deficit/hyperactivity disorder (ADHD). The aim of the present ADHD study was to investigate the modulation of the TMS-N100 in go and nogo trials of a response control task considering stages of response preparation, activation, execution and inhibition. Eighteen children with ADHD and 19 typically developing children, aged 10–14 years, were assessed. TMS was delivered over the left motor cortex, the TMS-N100 was measured at electrode P3. The TMS-N100 was determined at rest and at different time points (50 ms before S2; 150, 300 and 500 ms after S2) in a cued go/nogo task (S1–S2 paradigm). Correlations between the TMS-N100 measures, MEP-related TMS measures (e.g., short-interval intracortical inhibition) and performance measures were calculated. At rest, the amplitude of TMS-N100 was not found to be significantly reduced in the ADHD group. During the go/nogo task, children with ADHD showed a smaller increase of TMS-N100 amplitude in go trials and a smaller decrease after inhibiting a response. In go trials, a lower TMS-N100 was associated with a smaller variability of reaction times. A smaller TMS-N100 modulation extends the picture of cortical inhibition deficits in ADHD. Findings suggest a functional involvement of the mechanisms underlying the TMS-N100 at the motor output stage.     

Molecular characterization of the human common fragile site FRA1H

The molecular basis of the fragility of common fragile sites (CFS) and their role in chromosome instability and in altered expression of associated genes in cancer cells have not yet been clarified. In the present work we analyzed the human CFS FRA1H. FRA1H is the first characterized CFS the expression of which is not induced by aphidicolin but instead by DAPI. 5-azaC, 5-azadC, and Ad12 induce a CFS with the same cytogenetic location. By using FISH analysis with BAC clones, we determined that this CFS extends for approximately 10 Mb, and is therefore one of the largest characterized CFSs. FRA1H maps to the chromosome bands 1q41 and 1q42.1 thus spanning an R-band/G-band boundary, a region considered difficult to duplicate. The FRA1H DNA sequence was analyzed to identify coding sequences, the AT content, the type and quantity of the DNA repeats, the CpG islands, the matrix attachment regions, and the number and distribution of high-flexibility regions. A 120 kb long sequence was identified that is very AT-rich (64.6%), has a very large number of flexibility peaks and that may be involved in inducing fragility in the surrounding regions. Among the other genes, two very large genes (USH2A, ESRRG) and two microRNA genes (MIRN194-1, MIRN215) map within the fragile region.     

Transcriptional profiling of genes at the human common fragile site FRA1H in tumor-derived cell lines

Common fragile sites (CFSs) are chromosome regions that exhibit gaps and breaks when the cells are exposed to replication stress and to some DNA-binding compounds. In cancer cells, the CFSs are frequently involved in recurrent chromosome rearrangements. Furthermore, altered expression of associated genes, known or potential oncogenes, and tumor-suppressor genes has often been observed. Seventeen of the 88 listed CFSs have been analyzed at the molecular level, but the basis of their fragility has not been clarified. In the present work, the nine genes TGFB2, IARS2, MARK1, TAF1A, TP53BP2, ADPRT, including a very large gene ESRRG and two microRNA genes, MIRN194-1 and MIRN215, localized in the fragile site FRA1H, were investigated by polymerase chain reaction (PCR) for homozygous deletions and by real-time PCR for modification or loss of gene expression in a panel of 19 cancer cell lines. The expression level of five (ESRRG, TGFB2, MIRN194-1, MIRN215, and MARK1) of the nine genes studied presented significant modifications in some of the 19 examined tumor-derived cell lines compared to their normal control tissues. Because of their function, these genes could have a role in neoplastic transformation.