The design, calibration and usage of a solid scattering and absorbing phantom for near infra red spectroscopy.

Following a review of methods for measuring the optical properties of tissue, the majority of this thesis is concerned with the design, construction, calibration and use of a solid, tissue equivalent phantom. The phantom material is a clear polyester plastic. This is obtained in unpolymerised form, scattering particles and absorbing dyes are added to it, and it is then polymerised to form a stable solid. Purely scattering and absorbing phantoms were made separately, and their optical properties were measured using a specially built system. This has a co-linear collimated light source and detector, and measures the unscattered light transmitted through a sample as a function of its thickness. Other methods of measuring the optical coefficients of tissue were tested with this phantom. One of these uses integrating spheres to measure the transmitted and reflected light from a sample. A model of light transport (in this case a Monte Carlo model) is used to convert these measurements into scattering and absorption coefficients. It was found that the measurement of scattering coefficient was reasonably accurate, but that the absorption coefficient was overestimated at the low values typical of tissue. A measurement of the optical properties of bone was made with this system. The other system investigated uses the diffusion theory to calculate optical properties from measurements made through a thick slab. The material was also employed to create a test phantom for near infrared spectroscopy machines. This provides a diffusing medium with an attenuation that is variable in discrete steps over three orders of magnitude. The relative attenuation between steps is totally wavelength independent. This phantom was adopted by the EC concerted action on near infrared spectroscopy and imaging. Finally, the phantom was used to create test objects with which to investigate the potential of imaging with infrared light

Lewy body compared with Alzheimer dementia is associated with decreased functional connectivity in resting state networks.

Resting state functional magnetic resonance imaging (fMRI) was used to measure whole brain functional connectivity within specific networks hypothesised to be more affected in dementia with Lewy bodies (DLB) (a disease characterised by prominent attentional deficits, spontaneous motor features of parkinsonism and depression) than in Alzheimer׳s disease (AD) and controls. This study involved 68 subjects (15 DLB, 13 AD and 40 controls) who were scanned using resting state BOLD (blood-oxygen-level-dependent) fMRI on a 3T MRI scanner. Functional connectivity was measured using a model-free independent component analysis approach that consisted of temporally concatenating the resting state fMRI data of all study subjects and investigating group differences using a back-reconstruction procedure. Resting state functional connectivity was affected in the default mode, salience, executive and basal ganglia networks in DLB subjects compared with AD and controls. Functional connectivity was lower in DLB compared with AD and controls in these networks, except for the basal ganglia network, where connectivity was greater in DLB. No resting state networks showed less connectivity in AD compared with DLB or controls. Our results suggest that functional connectivity of resting state networks can identify differences between DLB and AD subjects that may help to explain why DLB subjects have more frequent attentional deficits, parkinsonian symptoms, and depression than those with AD.North East Dementia and Neurodegenerative Diseases Research Network (DeNDRoN)This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.pscychresns.2014.06.00

Time-Resolved Diffusing Wave Spectroscopy for selected photon paths beyond 300 transport mean free paths

This paper is devoted to the theoretical and experimental demonstration of the possibility to perform time-resolved diffusing wave spectroscopy: we successfully registered field fluctuations for selected photon path lengths that can overpass 300 transport mean free paths. Such a performance opens new possibilities for biomedical optics applications.Comment: 12 pages, 3 figure

The benefits of organic farming for biodiversity

Previous studies suggest widespread positive responses of biodiversity to organic farming. Many of these studies, however, have been small-scale. This project tested the generality of habitat and biodiversity differences between matched pairs of organic and non-organic farms containing cereal crops in lowland England on a large-scale across a range of taxa including plants, insects, birds and bats. The extent of both cropped and un-cropped habitats together with their composition and management on a range of scales were also compared. Organic farms was likely to favour higher levels of biodiversity and indeed organic farms tended to support higher numbers of species and overall abundance across most taxa. However, the magnitude of the response differed strikingly; plants showed stronger and more consistent responses than other taxa. Some, but not all, differences in biodiversity between systems appear to be a consequence of differences in habitat quantity

Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies.

BACKGROUND & OBJECTIVE: Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. METHODS: 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. RESULTS: AD had significantly greater atrophy over 1 year (1.8%) compared to DLB (1.0%; p = 0.01) and HC (0.9%; p < 0.01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0.95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0.49, p < 0.01). CONCLUSIONS: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.This work was supported by the Sir Jules Thorn Charitable Trust (grant number 05/JTA), the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge, PhD studentship.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S2213158215000182#

Progressive cortical thinning and subcortical atrophy in dementia with Lewy bodies and Alzheimer's disease.

Patterns of progressive cortical thinning in dementia with Lewy bodies (DLB) remain poorly understood. We examined spatiotemporal patterns of cortical thinning and subcortical atrophy over 12 months in DLB (n = 13), compared with Alzheimer's disease (AD) (n = 23) and healthy control subjects (HC) (n = 33). Rates of temporal thinning in DLB were relatively preserved compared with AD. Volumetric analyses subcortical changes revealed that the AD group demonstrated significantly increased hippocampal atrophy (-5.8%) relative to the HC (-1.7%; p < 0.001) and DLB groups (-2.5%, p = 0.006). Significant lateral ventricular expansion was also observed in AD (8.9%) compared with HC (4.3%; p < 0.001) and DLB (4.7%; p = 0.008) at trend level. There was no significant difference in subcortical atrophy and ventricular expansion between DLB and HC. In the DLB group, increased rates of cortical thinning in the frontal and parietal regions were significantly correlated with decline in global cognition (Mini-Mental State Examination) and motor deterioration (Unified Parkinson's Disease Rating Scale 3), respectively. Overall, AD and DLB are characterized by different spatiotemporal patterns of cortical thinning over time. Our findings warrant further consideration of longitudinal cortical thinning as a potential imaging marker to differentiate DLB from AD.This work was supported by the Sir Jules Thorn Charitable Trust (Grant number 05/JTA), the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and the Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship. Elijah Mak formulated the research question, performed the statistical analyses, interpreted the results, and wrote the article. Li Su and Guy Williams assisted with the interpretation of the results and provided comments and additional suggestions for revisions of the draft. Rosie Watson recruited and assessed study participants, assisted with the interpretation of the results, and reviewed the article. Michael Firbank designed the imaging protocol, assisted with the interpretation of the results, and reviewed the article. Andrew Blamire obtained funding for the project, designed the imaging protocol, undertook routine quality assurance on the MR system, assisted with the interpretation of the results, and reviewed the article. John O’Brien obtained funding for the project, designed the imaging protocol, assisted with recruitment of study participants, assisted with the interpretation of the results, and reviewed the article. All authors approved the final article.This is the accepted manuscript for a paper published in Neurobiology of Aging Volume 36, Issue 4, April 2015, Pages 1743–1750, DOI: 10.1016/j.neurobiolaging.2014.12.03

Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done. METHODS: We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated. RESULTS: In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls. CONCLUSIONS: In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.parkreldis.2016.01.00

Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors

Greater understanding of the risk factors and mechanisms of incident dementia in stroke survivors is needed for prevention and management. There is limited information on the long-term consequences and forms of incident dementia in older stroke survivors. We recruited 355 patients aged >75 years from hospital-based stroke registers into a longitudinal study 3 months after stroke. At baseline none of the patients had dementia. Patients were genotyped for apolipoprotein E and assessed annually for cognition and development of incident dementia over up to 8 years of follow-up. The effect of baseline vascular risk factors upon incidence of dementia and mortality were estimated by Cox proportional regression analyses adjusted for age and gender. Standard neuropathological examination was performed to diagnose the first 50 cases that came to autopsy. We found that the median survival from the date of the index stroke was 6.72 years (95% confidence intervals: 6.38–7.05). During the follow-up of a mean time of 3.79 years, 23.9% of subjects were known to have developed dementia and 76.1% remained alive without dementia or died without dementia. The incidence of delayed dementia was calculated to be 6.32 cases per 100 person years whereas that for death or dementia was 8.62. Univariate and multivariate regression analyses showed that the most robust predictors of dementia included low (1.5 standard deviations below age-matched control group) baseline Cambridge Cognitive Examination executive function and memory scores, Geriatric Depression Scale score and three or more cardiovascular risk factors. Autopsy findings suggested that remarkably ≥75% of the demented stroke survivors met the current criteria for vascular dementia. Demented subjects tended to exhibit marginally greater neurofibrillary pathology including tauopathy and Lewy bodies and microinfarcts than non-demented survivors. Despite initial improvements in cognition following stroke in older stroke survivors, risk of progression to delayed dementia after stroke is substantial, but is related to the presence of vascular risk factors. Careful monitoring and treatment of modifiable vascular risk factors may be of benefit in preventing post-stroke dementia in the general population