Tobias C. Wood

Polarization response measurement and simulation of rigid endoscopes

Polarized light can reveal diagnostic information about tissue morphology. To promote easy adoption of polarization imaging techniques in the clinic it would be beneficial if they can be used with standard medical imaging instruments such as rigid endoscopes. We have characterized the polarization properties of two commercial laparoscopes and observed birefringence effects that complicate polarization imaging. Possible solutions are discussed that may be of interest to other tissue polarization imaging researchers.

Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke

Duricki et al. show that intramuscular delivery of human neurotrophin-3 induces corticospinal plasticity and locomotor recovery in adult and elderly rats 24 hours post-stroke. This time-frame would be clinically feasible for most stroke victims, and the safety and tolerability of neurotrophin-3 in humans have been established for other disorders.

Polarized multispectral imaging in a rigid endoscope based on elastic light scattering spectroscopy

Elastic light scattering spectroscopy (LSS) is widely utilized to investigate cellular structures in cultured cells and various tissues. However, few imaging systems, especially endoscopic imaging systems, can implement LSS. It is the aim of this work to create a polarized multispectral imaging system based around a rigid endoscope to detect micrometer sized particles using LSS. The instrument first validated with different sized mono-disperse polystyrene microspheres, then an image is reconstructed based on LSS which shows the differentiation of different sized microspheres. Finally a preliminary experiment is conducted to demonstrate its capability to discriminate different types of cells.

Whole-brain ex-vivo quantitative MRI of the cuprizone mouse model

Myelin is a critical component of the nervous system and a major contributor to contrast in Magnetic Resonance (MR) images. However, the precise contribution of myelination to multiple MR modalities is still under debate. The cuprizone mouse is a well-established model of demyelination that has been used in several MR studies, but these have often imaged only a single slice and analysed a small region of interest in the corpus callosum. We imaged and analyzed the whole brain of the cuprizone mouse ex-vivo using high-resolution quantitative MR methods (multi-component relaxometry, Diffusion Tensor Imaging (DTI) and morphometry) and found changes in multiple regions, including the corpus callosum, cerebellum, thalamus and hippocampus. The presence of inflammation, confirmed with histology, presents difficulties in isolating the sensitivity and specificity of these MR methods to demyelination using this model.

Multi-Excitation Fluorescence Spectroscopy for Analysis of Non-Alcoholic Fatty Liver Disease

The increasing incidence of non‐alcoholic fatty liver diseases (NAFLD) and the consequent progression to cirrhosis is expected to become a major cause of liver transplantation. This will exacerbate the organ donor shortage and mean that ‘marginal’ fatty liver grafts are more frequently used. Autofluorescence spectroscopy is a fast, objective, and non‐destructive method to detect change in the endogenous fluorophores distribution and could prove to be a valuable tool for NAFLD diagnosis and transplant graft assessment.

Improved formulas for the two optimum VFA flip-angles.

The variable flip-angle (VFA) experiment is an efficient way to measure T1 using a spoiled steady-state sequence compared to the gold standard inversion recovery experiment (1–3). The VFA signal curves can be easily linearized and hence only two acquisitions are required (4), although in practice the number of flip-angles used varies (5–8). Deoni et al. showed that the same methods could be used to measure T2 using a balanced steady-state free precession (bSSFP) sequence (9). This method has been less widely used, likely due to off-resonance artifacts at higher field strengths (10–12). If two flip-angles are used, they must be selected carefully. An obvious criterion is that the measurement variance of T1 or T2 should be minimized. Wang et al. derived an expression for the variance in T1 that contains a sum over all flip-angles (13), and found the optimal two by numerical optimization. In contrast, Deoni et al. hypothesized that the optimal flip-angles will generate equal signal intensity but lie either side of the maximum, and derived a formula for the flip-angles in terms of the measured fractional signal f compared to the Ernst signal. Deoni et al. then numerically optimized the product of signal intensity and the distance between points on the regression line and found f1⁄4 0.71 for both T1 and T2 (9). This hypothesis, while intuitive and well grounded, was only checked by comparison to a pair of flip-angles calculated by Wang. Instead, if Wang and Deoni’s formulas are combined f can be found analytically to be 1= ffiffiffi 2 p and this value shown to minimize the experimental variance. The following analysis used the Sympy symbolic algebra package (version 0.7.5, www.sympy.org), provided as part of the Canopy distribution (www.enthought.com). The code used is available as Supporting Information. Equation 10 in (13) gives the variance for T1 only. It can be rewritten in the following form to find the variance in either T1 or T2: s2T1;2 1⁄4 s M 0 N 2 X2 X 2 2 @T1;2 @b 2

Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders

Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation. Genome-wide transcriptional profiling revealed that prenatal immune activation caused a differential expression of 116 and 251 genes in the medial prefrontal cortex and nucleus accumbens, respectively. A large part of genes that were commonly affected in both brain areas were related to myelin functionality and stability. Subsequent epigenetic analyses indicated that altered DNA methylation of promoter regions might contribute to the differential expression of myelin-related genes. Quantitative relaxometry comparing T1, T2, and myelin water fraction revealed sparse increases in T1 relaxation times and consistent reductions in T2 relaxation times. Together, our multi-system approach demonstrates that prenatal viral-like immune activation causes myelin-related transcriptional and epigenetic changes in corticostriatal areas. Even though these abnormalities do not seem to be associated with overt white matter reduction, they may provide a molecular mechanism whereby prenatal infection can impair myelin functionality and stability.

Optimal Feature Selection Applied to Multispectral Fluorescence Imaging

Recent rapid developments in multi-modal optical imaging have created a significant clinical demand for its in vivo--in situ application. This offers the potential for real-time tissue characterization, functional assessment, and intra-operative guidance. One of the key requirements for in vivo consideration is to minimise the acquisition window to avoid tissue motion and deformation, whilst making the best use of the available photons to account for correlation or redundancy between different dimensions. The purpose of this paper is to propose a feature selection framework to identify the best combination of features for discriminating between different tissue classes such that redundant or irrelevant information can be avoided during data acquisition. The method is based on a Bayesian framework for feature selection by using the receiver operating characteristic curves to determine the most pertinent data to capture. This represents a general technique that can be applied to different multi-modal imaging modalities and initial results derived from phantom and ex vivo tissue experiments demonstrate the potential clinical value of the technique.

Visible and near infrared autofluorescence and hyperspectral imaging spectroscopy for the investigation of colorectal lesions and detection of exogenous fluorophores

Colonoscopy is the most widely prescribed method of colonic imaging for the clinical surveillance of colorectal cancer. This white light-based imaging technique is often used for the detection of adenomatous polyps, the dysplastic precursors of cancer, that are subsequently removed to prevent progression to colonic carcinoma. However, some adenomas are diminutive and flat, making them difficult to discriminate from non-neoplastic tissue even for the most experienced of colonoscopists. We report here an optical system for performing excitation resolved visible and near-infrared (NIR) autofluorescence imaging and hyperspectral reflectance imaging for the investigation of differences in the spectral signatures between neoplastic and non-neoplastic mucosa along the gastrointestinal tract. This is demonstrated on ex vivo colorectal tissues using our multimodal laparoscopic imaging system, which consists of a supercontinuum excitation source and a digital multimirror device (DMD) for tuneable wavelength selection. We also demonstrate the discrimination of exogenous fluorophores applied to the tissue using the Isomap dimensionality reduction technique for visualisation of the acquired image data.

Fluorescence excitation spectroscopic imaging with a tunable light source and dimensionality reduction using FR-IsoMap

This paper presents an optical system for performing excitation resolved imaging of fluorescent dyes, tissue phantoms and ex vivo tissues. The excitation source was a supercontinuum generated in a highly nonlinear fibre, spectrally filtered using dispersive optics and a movable slit or digital micromirror device. This allowed excitation with multiple spectra, which may be chosen to optimize the fluorescence yield from a particular fluorophore, or to maximize discrimination between multiple labels. As an initial validation, the analysis of fluorescent dye solutions embedded in collagen gels in the presence of scatterers and absorbers by using fixed reference isomap (FR-IsoMap) is presented, followed by initial evaluation with human lung bronchial tissue. The proposed system has potential applications for in vivo fluorescence endoscopy of cancerous tissues through excitation spectral selection and analysis with FR-IsoMap.