Statistical estimation with Kronecker products in positron emission tomography

AbstractA method for linear statistical analysis of multidimensional imaging data is presented. It is applicable for a class of design and covariance matrices which involve Kronecker products. An efficient algorithm which allows for application of the method to large multidimensional data volumes is given. This has direct application to neuroimaging, and here the technique is applied to positron emission tomography (PET) data. PET is an in vivo functional imaging technique that measures biological processes such as blood flow and receptor concentrations. Here, the algorithm is used to correct for resolution degradation in these images. This process is typically referred to as PET partial volume correction. Examples involving both measured phantom and human data are given. This rapid algorithm leads to advances in the types of quantitative brain imaging studies that can be performed

GAN Augmentation: Augmenting Training Data using Generative Adversarial Networks

One of the biggest issues facing the use of machine learning in medical imaging is the lack of availability of large, labelled datasets. The annotation of medical images is not only expensive and time consuming but also highly dependent on the availability of expert observers. The limited amount of training data can inhibit the performance of supervised machine learning algorithms which often need very large quantities of data on which to train to avoid overfitting. So far, much effort has been directed at extracting as much information as possible from what data is available. Generative Adversarial Networks (GANs) offer a novel way to unlock additional information from a dataset by generating synthetic samples with the appearance of real images. This paper demonstrates the feasibility of introducing GAN derived synthetic data to the training datasets in two brain segmentation tasks, leading to improvements in Dice Similarity Coefficient (DSC) of between 1 and 5 percentage points under different conditions, with the strongest effects seen fewer than ten training image stacks are available

CCD Readout Electronics for the Subaru Prime Focus Spectrograph

We present details of the design for the CCD readout electronics for the Subaru Telescope Prime Focus Spectrograph (PFS). The spectrograph is comprised of four identical spectrograph modules, each collecting roughly 600 spectra. The spectrograph modules provide simultaneous wavelength coverage over the entire band from 380 nm to 1260 nm through the use of three separate optical channels: blue, red, and near infrared (NIR). A camera in each channel images the multi-object spectra onto a 4k x 4k, 15 um pixel, detector format. The two visible cameras use a pair of Hamamatsu 2k x 4k CCDs with readout provided by custom electronics, while the NIR camera uses a single Teledyne HgCdTe 4k x 4k detector and ASIC Sidecar to read the device. The CCD readout system is a custom design comprised of three electrical subsystems: the Back End Electronics (BEE), the Front End Electronics (FEE), and a Pre-amplifier. The BEE is an off-the-shelf PC104 computer, with an auxiliary Xilinx FPGA module. The computer serves as the main interface to the Subaru messaging hub and controls other peripheral devices associated with the camera, while the FPGA is used to generate the necessary clocks and transfer image data from the CCDs. The FEE board sets clock biases, substrate bias, and CDS offsets. It also monitors bias voltages, offset voltages, power rail voltage, substrate voltage and CCD temperature. The board translates LVDS clock signals to biased clocks and returns digitized analog data via LVDS. Monitoring and control messages are sent from the BEE to the FEE using a standard serial interface. The Pre-amplifier board resides behind the detectors and acts as an interface to the two Hamamatsu CCDs. The Pre-amplifier passes clocks and biases to the CCDs, and analog CCD data is buffered and amplified prior to being returned to the FEE.Comment: 14 pages, 15 figures, SPIE ATI 2014, Montrea

The ExoMars Spectral Tool (ExoSpec):an image analysis tool for ExoMars 2020 PanCam imagery

The upcoming launch of the European Space Agency (ESA) ExoMars 2020 rover signals a need for an analysis tool to be created which can exploit the multi- and hyperspectral data that will be returned by its Panoramic Camera (PanCam), Infrared Spectrometer for Mars (ISEM), and Close-UP Imager (CLUPI) instruments. Data processed by this analysis tool will be invaluable in (i) characterising the geology local to the ExoMars rover, (ii) relating ground-based observations to orbital Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) data, (iii) detecting evidence of past habitability on Mars, and (iv) identifying drilling locations. PanCam, ISEM, and CLUPI offer spectral analysis capabilities in both spatial (140-1310 microns/pixel at 2 m working distance) and spectral (440-3300 nm) dimensions. We have developed the ExoMars Spectral Tool (ExoSpec) which functions as a GUI-based extension to ENVI + IDL and performs steps from image import and compilation into ENVI.dat format, flat-fielding, radiometric correction, radiance-toreflectance (R∗) corrections using the in-scene Gretag MacBeth ColorCheckerTM, and calculation of spectral parameters. We demonstrate the functionality of ExoSpec at its current stage of development and illustrate its utility with results from field expeditions to Mars analogue terrains in: (i) geothermally altered basalts in Ńamafjall, Iceland, and (ii) layered alluvial plains deposits in Hanksville, USA, using ExoMars PanCam, ISEM, and CLUPI emulator instruments

Relationship between neuromelanin and dopamine terminals within the Parkinson's nigrostriatal system.

Parkinson's disease is characterized by the progressive loss of pigmented dopaminergic neurons in the substantia nigra and associated striatal deafferentation. Neuromelanin content is thought to reflect the loss of pigmented neurons, but available data characterizing its relationship with striatal dopaminergic integrity are not comprehensive or consistent, and predominantly involve heterogeneous samples. In this cross-sectional study, we used neuromelanin-sensitive MRI and the highly specific dopamine transporter PET radioligand, 11C-PE2I, to assess the association between neuromelanin-containing cell levels in the substantia nigra pars compacta and nigrostriatal terminal density in vivo, in 30 patients with bilateral Parkinson's disease. Fifteen healthy control subjects also underwent neuromelanin-sensitive imaging. We used a novel approach taking into account the anatomical and functional subdivision of substantia nigra into dorsal and ventral tiers and striatal nuclei into pre- and post-commissural subregions, in accordance with previous animal and post-mortem studies, and consider the clinically asymmetric disease presentation. In vivo, Parkinson's disease subjects displayed reduced neuromelanin levels in the ventral (-30 ± 28%) and dorsal tiers (-21 ± 24%) as compared to the control group [F(1,43) = 11.95, P = 0.001]. Within the Parkinson's disease group, nigral pigmentation was lower in the ventral tier as compared to the dorsal tier [F(1,29) = 36.19, P < 0.001] and lower in the clinically-defined most affected side [F(1,29) = 4.85, P = 0.036]. Similarly, lower dopamine transporter density was observed in the ventral tier [F(1,29) = 76.39, P < 0.001] and clinically-defined most affected side [F(1,29) = 4.21, P = 0.049]. Despite similar patterns, regression analysis showed no significant association between nigral pigmentation and nigral dopamine transporter density. However, for the clinically-defined most affected side, significant relationships were observed between pigmentation of the ventral nigral tier with striatal dopamine transporter binding in pre-commissural and post-commissural striatal subregions known to receive nigrostriatal projections from this tier, while the dorsal tier correlated with striatal projection sites in the pre-commissural striatum (P < 0.05, Benjamini-Hochberg corrected). In contrast, there were no statistically significant relationships between these two measures in the clinically-defined least affected side. These findings provide important insights into the topography of nigrostriatal neurodegeneration in Parkinson's disease, indicating that the characteristics of disease progression may fundamentally differ across hemispheres and support post-mortem data showing asynchrony in the loss of neuromelanin-containing versus tyrosine hydroxylase positive nigral cells.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) [FP7-242003], from the Medical Research Council (MRC) [MR/P025870/1] and from Parkinson’s UK [J-1204]. Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC) and NIHR Imperial CRF at Imperial College healthcare NHS trust. The views expressed are those of the authors and not necessarily those of the funder, the NHS, the NIHR, or the Department of Health. This work was also supported financially by a PhD studentship awarded to N.P.L-K from Parkinson’s UK

DREADD activation of pedunculopontine cholinergic neurons reverses motor deficits and restores striatal dopamine signaling in parkinsonian rats

The brainstem-based pedunculopontine nucleus (PPN) traditionally associates with motor function, but undergoes extensive degeneration during Parkinson’s disease (PD), which correlates with axial motor deficits. PPN-Deep Brain Stimulation (DBS) can alleviate certain symptoms, but its mecha-nism(s) of action remains unknown. We previously characterized rats hemi-intranigrally injected with the proteasomal inhibitor lactacystin, as an accurate preclinical model of PD. Here we used a combination of chemogenetics with Positron Emission Tomography (PET) imaging for in vivo in-terrogation of discrete neural networks in this rat model of PD. Stimulation of excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) expressed within PPN cholinergic neurons activated residual nigrostriatal dopaminergic neurons to produce pro-found motor recovery, which correlated with striatal dopamine efflux as well as restored dopamine receptor (DR) 1- and DR2-based medium spiny neuron (MSN) activity, as was ascertained with c-Fos-based immunohistochemistry and stereological cell counts. By revealing that the improved axi-al-related motor functions seen in PD patients receiving PPN-DBS may be due to stimulation of remaining PPN cholinergic neurons interacting with dopaminergic ones in both the Substantia Nigra pars compacta (SNpc) and the striatum, our data strongly favor the PPN cholinergic-midbrain dopaminergic connectome as mechanism for PPN-DBS’s therapeutic effects. These findings have implications for refining PPD-DBS as a promising treatment modality available to PD patients

More Than a Moggy; A Population Genetics Analysis of the United Kingdom’s Non-Pedigree Cats

The domestic cat is one of the most popular pets in the world. It is estimated that 89–92% of domestic cats in the UK are non-pedigree Domestic shorthair (DSH), Domestic longhair (DLH), or Domestic semi-longhair cats (DSLH). Despite their popularity, little is known of the UK non-pedigree cats’ population structure and breeding dynamics. Using a custom designed single nucleotide variant (SNV) array, this study investigated the population genetics of 1344 UK cats. Principal components analysis (PCA) and fastSTRUCTURE analysis verified that the UK’s DSH, DLH, and DSLH cats are random-bred, rather than admixed, mix breed, or crossbred. In contrast to pedigree cats, the linkage disequilibrium of these random-bred cats was least extensive and decayed rapidly. Homozygosity by descent (HBD) analysis showed the majority of non-pedigree cats had proportionally less of their genome in HBD segments compared to pedigree cats, and that these segments were older. Together, these findings suggest that the DSH, DLH, and DSLH cats should be considered as a population of random-bred cats rather than a crossbred or pedigree-admixed cat. Unexpectedly, 19% of random-bred cat genomes displayed a higher proportion of HBD segments associated with more recent inbreeding events. Therefore, while non-pedigree cats as a whole are genetically diverse, they are not impervious to inbreeding and its health risks

Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson's disease

BACKGROUND: Recent work has shown loss of phosphodiesterase 10A levels in middle-stage and advanced treated patients with PD, which was associated with motor symptom severity. OBJECTIVES: To assess phosphodiesterase 10A levels in early PD and compare with loss of dopamine transporter as markers of disease burden. METHODS: Seventy-eight subjects were included in this study (17 early de novo, 15 early l-dopa-treated, 24 moderate-advanced l-dopa-treated patients with PD, and 22 healthy controls). All participants underwent [11 C]IMA107 PET, [11 C]PE2I PET, and 3-Tesla MRI scan. RESULTS: Early de novo PD patients showed loss of [11 C]IMA107 and of [11 C]PE2I binding in caudate and putamen (P < 0.001); early l-dopa-treated PD patients showed additional loss of [11 C]IMA107 in the caudate (P < 0.001; annual decline 3.6%) and putamen (P < 0.001; annual decline 2.8%), but loss of [11 C]PE2I only in the putamen (P < 0.001; annual decline 6.8%). Lower [11 C]IMA107 correlated with lower [11 C]PE2I in the caudate (rho = 0.51; P < 0.01) and putamen (rho = 0.53; P < 0.01). Longer disease duration correlated with lower [11 C]IMA107 in the caudate (rho = -0.72; P < 0.001) and putamen (rho = -0.48; P < 0.01), and with lower [11 C]PE2I only in the putamen (rho = -0.65; P < 0.001). Higher burden of motor symptoms correlated with lower [11 C]IMA107 in the caudate (rho = -0.42; P < 0.05) and putamen (rho = -0.41; P < 0.05), and with lower [11 C]PE2I only in the putamen (rho = -0.69; P < 0.001). CONCLUSION: Our findings demonstrate loss of phosphodiesterase 10A levels very early in the course of PD and is associated with the gradual and progressive increase of motor symptoms. Phosphodiesterase 10A imaging shows similar potential with dopamine transporter imaging to follow disease progression. © 2019 International Parkinson and Movement Disorder Society