Comparative study of MRI biomarkers in the substantia nigra to discriminate idiopathic Parkinson disease

BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice

Longitudinal changes in functional connectivity of cortico-basal ganglia networks in manifests and premanifest huntington's disease

Huntington's disease (HD) is a genetic neurological disorder resulting in cognitive and motor impairments. We evaluated the longitudinal changes of functional connectivity in sensorimotor, associative and limbic cortico-basal ganglia networks. We acquired structural MRI and resting-state fMRI in three visits one year apart, in 18 adult HD patients, 24 asymptomatic mutation carriers (preHD) and 18 gender- and age-matched healthy volunteers from the TRACK-HD study. We inferred topological changes in functional connectivity between 182 regions within cortico-basal ganglia networks using graph theory measures. We found significant differences for global graph theory measures in HD but not in preHD. The average shortest path length (L) decreased, which indicated a change toward the random network topology. HD patients also demonstrated increases in degree k, reduced betweeness centrality bc and reduced clustering C. Changes predominated in the sensorimotor network for bc and C and were observed in all circuits for k. Hubs were reduced in preHD and no longer detectable in HD in the sensorimotor and associative networks. Changes in graph theory metrics (L, k, C and bc) correlated with four clinical and cognitive measures (symbol digit modalities test, Stroop, Burden and UHDRS). There were no changes in graph theory metrics across sessions, which suggests that these measures are not reliable biomarkers of longitudinal changes in HD. preHD is characterized by progressive decreasing hub organization, and these changes aggravate in HD patients with changes in local metrics. HD is characterized by progressive changes in global network interconnectivity, whose network topology becomes more random over time. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc

Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease

This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson’s disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson’s disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson’s disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson’s disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra’s morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson’s disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification

Second T = 3/2 state in 9^9B and the isobaric multiplet mass equation

Recent high-precision mass measurements and shell model calculations~[Phys. Rev. Lett. {\bf 108}, 212501 (2012)] have challenged a longstanding explanation for the requirement of a cubic isobaric multiplet mass equation for the lowest $A = 9$ isospin quartet. The conclusions relied upon the choice of the excitation energy for the second $T = 3/2$ state in $^9$B, which had two conflicting measurements prior to this work. We remeasured the energy of the state using the $^9{\rm Be}(^3{\rm He},t)$ reaction and significantly disagree with the most recent measurement. Our result supports the contention that continuum coupling in the most proton-rich member of the quartet is not the predominant reason for the large cubic term required for $A = 9$ nuclei

Euclid preparation: VII. Forecast validation for Euclid cosmological probes

Aims: The Euclid space telescope will measure the shapes and redshifts of galaxies to reconstruct the expansion history of the Universe and the growth of cosmic structures. The estimation of the expected performance of the experiment, in terms of predicted constraints on cosmological parameters, has so far relied on various individual methodologies and numerical implementations, which were developed for different observational probes and for the combination thereof. In this paper we present validated forecasts, which combine both theoretical and observational ingredients for different cosmological probes. This work is presented to provide the community with reliable numerical codes and methods for Euclid cosmological forecasts. / Methods: We describe in detail the methods adopted for Fisher matrix forecasts, which were applied to galaxy clustering, weak lensing, and the combination thereof. We estimated the required accuracy for Euclid forecasts and outline a methodology for their development. We then compare and improve different numerical implementations, reaching uncertainties on the errors of cosmological parameters that are less than the required precision in all cases. Furthermore, we provide details on the validated implementations, some of which are made publicly available, in different programming languages, together with a reference training-set of input and output matrices for a set of specific models. These can be used by the reader to validate their own implementations if required. / Results: We present new cosmological forecasts for Euclid. We find that results depend on the specific cosmological model and remaining freedom in each setting, for example flat or non-flat spatial cosmologies, or different cuts at non-linear scales. The numerical implementations are now reliable for these settings. We present the results for an optimistic and a pessimistic choice for these types of settings. We demonstrate that the impact of cross-correlations is particularly relevant for models beyond a cosmological constant and may allow us to increase the dark energy figure of merit by at least a factor of three

Euclid: The importance of galaxy clustering and weak lensing cross-correlations within the photometric Euclid survey

Context. The data from the Euclid mission will enable the measurement of the angular positions and weak lensing shapes of over a billion galaxies, with their photometric redshifts obtained together with ground-based observations. This large dataset, with well-controlled systematic effects, will allow for cosmological analyses using the angular clustering of galaxies (GCph) and cosmic shear (WL). For Euclid, these two cosmological probes will not be independent because they will probe the same volume of the Universe. The cross-correlation (XC) between these probes can tighten constraints and is therefore important to quantify their impact for Euclid. Aims. In this study, we therefore extend the recently published Euclid forecasts by carefully quantifying the impact of XC not only on the final parameter constraints for different cosmological models, but also on the nuisance parameters. In particular, we aim to decipher the amount of additional information that XC can provide for parameters encoding systematic effects, such as galaxy bias, intrinsic alignments (IAs), and knowledge of the redshift distributions. Methods. We follow the Fisher matrix formalism and make use of previously validated codes. We also investigate a different galaxy bias model, which was obtained from the Flagship simulation, and additional photometric-redshift uncertainties; we also elucidate the impact of including the XC terms on constraining these latter. Results. Starting with a baseline model, we show that the XC terms reduce the uncertainties on galaxy bias by ∼17% and the uncertainties on IA by a factor of about four. The XC terms also help in constraining the γ parameter for minimal modified gravity models. Concerning galaxy bias, we observe that the role of the XC terms on the final parameter constraints is qualitatively the same irrespective of the specific galaxy-bias model used. For IA, we show that the XC terms can help in distinguishing between different models, and that if IA terms are neglected then this can lead to significant biases on the cosmological parameters. Finally, we show that the XC terms can lead to a better determination of the mean of the photometric galaxy distributions. Conclusions. We find that the XC between GCph and WL within the Euclid survey is necessary to extract the full information content from the data in future analyses. These terms help in better constraining the cosmological model, and also lead to a better understanding of the systematic effects that contaminate these probes. Furthermore, we find that XC significantly helps in constraining the mean of the photometric-redshift distributions, but, at the same time, it requires more precise knowledge of this mean with respect to single probes in order not to degrade the final “figure of merit”

Euclid preparation: VII. Forecast validation for Euclid cosmological probes

Aims. The Euclid space telescope will measure the shapes and redshifts of galaxies to reconstruct the expansion history of the Universe and the growth of cosmic structures. The estimation of the expected performance of the experiment, in terms of predicted constraints on cosmological parameters, has so far relied on various individual methodologies and numerical implementations, which were developed for different observational probes and for the combination thereof. In this paper we present validated forecasts, which combine both theoretical and observational ingredients for different cosmological probes. This work is presented to provide the community with reliable numerical codes and methods for Euclid cosmological forecasts. Methods. We describe in detail the methods adopted for Fisher matrix forecasts, which were applied to galaxy clustering, weak lensing, and the combination thereof. We estimated the required accuracy for Euclid forecasts and outline a methodology for their development. We then compare and improve different numerical implementations, reaching uncertainties on the errors of cosmological parameters that are less than the required precision in all cases. Furthermore, we provide details on the validated implementations, some of which are made publicly available, in different programming languages, together with a reference training-set of input and output matrices for a set of specific models. These can be used by the reader to validate their own implementations if required. Results. We present new cosmological forecasts for Euclid. We find that results depend on the specific cosmological model and remaining freedom in each setting, for example flat or non-flat spatial cosmologies, or different cuts at non-linear scales. The numerical implementations are now reliable for these settings. We present the results for an optimistic and a pessimistic choice for these types of settings. We demonstrate that the impact of cross-correlations is particularly relevant for models beyond a cosmological constant and may allow us to increase the dark energy figure of merit by at least a factor of three

Euclid preparation - VII. Forecast validation for Euclid cosmological probes

Aims. The Euclid space telescope will measure the shapes and redshifts of galaxies to reconstruct the expansion history of the Universe and the growth of cosmic structures. The estimation of the expected performance of the experiment, in terms of predicted constraints on cosmological parameters, has so far relied on various individual methodologies and numerical implementations, which were developed for different observational probes and for the combination thereof. In this paper we present validated forecasts, which combine both theoretical and observational ingredients for different cosmological probes. This work is presented to provide the community with reliable numerical codes and methods for Euclid cosmological forecasts. Methods. We describe in detail the methods adopted for Fisher matrix forecasts, which were applied to galaxy clustering, weak lensing, and the combination thereof. We estimated the required accuracy for Euclid forecasts and outline a methodology for their development. We then compare and improve different numerical implementations, reaching uncertainties on the errors of cosmological parameters that are less than the required precision in all cases. Furthermore, we provide details on the validated implementations, some of which are made publicly available, in different programming languages, together with a reference training-set of input and output matrices for a set of specific models. These can be used by the reader to validate their own implementations if required. Results. We present new cosmological forecasts for Euclid. We find that results depend on the specific cosmological model and remaining freedom in each setting, for example flat or non-flat spatial cosmologies, or different cuts at non-linear scales. The numerical implementations are now reliable for these settings. We present the results for an optimistic and a pessimistic choice for these types of settings. We demonstrate that the impact of cross-correlations is particularly relevant for models beyond a cosmological constant and may allow us to increase the dark energy figure of merit by at least a factor of three

Measurement and analysis of nuclear γ-ray production cross sections in proton interactions with Mg, Si, and Fe nuclei abundant in astrophysical sites over the incident energy range E = 30–66 MeV

The modeling of nuclear γ -ray line emission induced by highly accelerated particles in astrophysical sites (e.g., solar flares, the gas and dust in the inner galaxy) and the comparison with observed emissions from these sites needs a comprehensive database of related production cross sections. The most important reactions of protons and α particles are those with abundant target elements like C, O, N, Ne, Mg, Si, and Fe at projectile energies extending from the reaction threshold to a few hundred MeV per nucleon. In this work, we have measured γ -ray production cross section excitation functions for 30, 42, 54, and 66 MeV proton beams accelerated onto nat C , C + O (Mylar), nat Mg , nat Si , and 56 Fe targets of astrophysical interest at the Separated Sector Cyclotron (SSC) of iThemba LABS (near Cape Town, South Africa). The AFRODITE array equipped with eight Compton suppressed high-purity (HPGe) clover detectors was used to record γ -ray line energy spectra. For known, intense lines previously reported experimental data measured up to E p ≃ 25 MeV at the Washington and Orsay tandem accelerators were thus extended to higher proton energies. Our experimental data for the last three targets are reported here and discussed with respect to previous data and to the Murphy et al. compilation [Astrophys. J. Suppl. Ser. 183, 142 (2009)]