Publications

Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the "prefrontal" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.

PURPOSE: Compressed sensing methods with motion estimation and compensation techniques have been proposed for the reconstruction of accelerated dynamic MRI. However, artifacts that naturally arise in compressed sensing reconstruction procedures hinder the estimation of motion from reconstructed images, especially at high acceleration factors. This work introduces a robust groupwise nonrigid motion estimation technique applied to the compressed sensing reconstruction of dynamic cardiac cine MRI sequences. THEORY AND METHODS: A spatio-temporal regularized, groupwise, nonrigid registration method based on a B-splines deformation model and a least squares metric is used to estimate and to compensate the movement of the heart in breath-hold cine acquisitions and to obtain a quasistatic sequence with highly sparse representation in temporally transformed domains. RESULTS: Short axis in vivo datasets are used for validation, both original multicoil as well as DICOM data. Fully sampled data were retrospectively undersampled with various acceleration factors and reconstructions were compared with the two well-known methods k-t FOCUSS and MASTeR. The proposed method achieves higher signal to error ratio and structure similarity index for medium to high acceleration factors. CONCLUSIONS: Reconstruction methods based on groupwise registration show higher quality reconstructions for cardiac cine images than the pairwise counterparts tested.

PURPOSE: The delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) method can be used to assess the content of glycosaminoglycan in cartilage. In in vitro and model studies, the content of glycosaminoglycan is often expressed in terms of a fixed charge density (FCD). Values of the fixed charge density obtained using the dGEMRIC method differs from values obtained using other methods. The purpose of this work was to further clarify the origin of this discrepancy. METHODS: dGEMRIC experiments were performed in a μMRI setup on a custom-designed, well-defined model system capturing the relevant ionic features of cartilage. The model system allows for good control over and systematic variation of relevant parameters. The experimental data was compared with results from Monte Carlo simulations on a coarse-grained model. RESULTS: Application of ideal Donnan theory on data obtained from experiments as well as simulations lead to underestimation of the fixed charge density, in agreement with previous studies. CONCLUSION: To obtain more accurate estimates of the fixed charge density using the dGEMRIC method, interionic interactions need to be taken into account in the Donnan analysis. Furthermore, the results suggest that the combination of μMRI dGEMRIC experiments and Monte Carlo simulations are useful tools for an improved understanding of these effects. Magn Reson Med 76:500-509, 2016. © 2015 Wiley Periodicals, Inc.

Registration of multiple 3D ultrasound sectors in order to provide an extended field of view is important for the appreciation of larger anatomical structures at high spatial and temporal resolution. In this paper, we present a method for fully automatic spatio-temporal registration between two partially overlapping 3D ultrasound sequences. The temporal alignment is solved by aligning the normalized cross correlation-over-time curves of the sequences. For the spatial alignment, corresponding 3D Scale Invariant Feature Transform (SIFT) features are extracted from all frames of both sequences independently of the temporal alignment. A rigid transform is then calculated by least squares minimization in combination with random sample consensus. The method is applied to 16 echocardiographic sequences of the left and right ventricles and evaluated against manually annotated temporal events and spatial anatomical landmarks. The mean distances between manually identified landmarks in the left and right ventricles after automatic registration were (mean ± SD) 4.3 ± 1.2 mm compared to a reference error of 2.8 ± 0.6 mm with manual registration. For the temporal alignment, the absolute errors in valvular event times were 14.4 ± 11.6 ms for Aortic Valve (AV) opening, 18.6 ± 16.0 ms for AV closing, and 34.6 ± 26.4 ms for mitral valve opening, compared to a mean inter-frame time of 29 ms.

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system. In this paper, we present data indicating that the routine interaction with computer keyboards can be used to detect motor signs in the early stages of PD. We explore a solution that measures the key hold times (the time required to press and release a key) during the normal use of a computer without any change in hardware and converts it to a PD motor index. This is achieved by the automatic discovery of patterns in the time series of key hold times using an ensemble regression algorithm. This new approach discriminated early PD groups from controls with an AUC = 0.81 (n = 42/43; mean age = 59.0/60.1; women = 43%/60%;PD/controls). The performance was comparable or better than two other quantitative motor performance tests used clinically: alternating finger tapping (AUC = 0.75) and single key tapping (AUC = 0.61).

UNLABELLED: Cognitive neuroscience of aging studies traditionally target participants age 65 and older. However, epidemiological surveys show that many women report increased forgetfulness earlier in the aging process, as they transition to menopause. In this population-based fMRI study, we stepped back by over a decade to characterize the changes in memory circuitry that occur in early midlife, as a function of sex and women’s reproductive stage. Participants (N = 200; age range, 45-55) performed a verbal encoding task during fMRI scanning. Reproductive histories and serologic evaluations were used to determine menopausal status. Results revealed a pronounced impact of reproductive stage on task-evoked hippocampal responses, despite minimal difference in chronological age. Next, we examined the impact of sex and reproductive stage on functional connectivity across task-related brain regions. Postmenopausal women showed enhanced bilateral hippocampal connectivity relative to premenopausal and perimenopausal women. Across women, lower 17β-estradiol concentrations were related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task, strongly implicating sex steroids in the regulation of this circuitry. Finally, subgroup analyses revealed that high-performing postmenopausal women (relative to low and middle performers) exhibited a pattern of brain activity akin to premenopausal women. Together, these findings underscore the importance of considering reproductive stage, not simply chronological age, to identify neuronal and cognitive changes that unfold in the middle decades of life. In keeping with preclinical studies, these human findings suggest that the decline in ovarian estradiol production during menopause plays a significant role in shaping memory circuitry. SIGNIFICANCE STATEMENT: Maintaining intact memory function with age is one of the greatest public health challenges of our time, and women have an increased risk for memory disorders relative to men later in life. We studied adults early in the aging process, as women transition into menopause, to identify neuronal and cognitive changes that unfold in the middle decades of life. Results demonstrate regional and network-level differences in memory encoding-related activity as a function of women’s reproductive stage, independent of chronological age. Analyzing data without regard to sex or menopausal status obscured group differences in circuit-level neural strategies associated with successful memory retrieval. These findings suggest that early changes in memory circuitry are evident decades before the age range traditionally targeted by cognitive neuroscience of aging studies.

INTRODUCTION: Diffusion weighted MRI (dMRI) is a method sensitive to pathological changes affecting tissue microstructure. Most dMRI studies in schizophrenia, however, have focused solely on white matter. There is a possibility, however, that subtle changes in diffusivity exist in gray matter (GM). Accordingly, we investigated diffusivity in GM in patients with recent onset schizophrenia. METHODS: We enrolled 45 patients and 21 age and sex-matched healthy controls. All subjects were evaluated using the short form of the Wechsler Adult Intelligence Scale, the Positive and Negative Syndrome Scale (PANSS), and the video based social cognition scale. DMRI and T1W images were acquired on a 3 Tesla magnet, and mean Fractional Anisotropy (FA), Trace (TR) and volume were calculated for each of the 68 cortical GM Regions of Interest parcellated using FreeSurfer. RESULTS: There was no significant difference of FA and GM volume between groups after Bonferroni correction. For the dMRI measures, however, patients evinced increased TR in the left bank of the superior temporal sulcus, the right inferior parietal, the right inferior temporal, and the right middle temporal gyri. In addition, higher TR in the right middle temporal gyrus and the right inferior temporal gyrus, respectively, was associated with decreased social function and higher PANSS score in patients with schizophrenia. CONCLUSION: This study demonstrates high sensitivity of dMRI to subtle pathology in GM in recent onset schizophrenia, as well as an association between increased diffusivity in temporal GM regions and abnormalities in social cognition and exacerbation of psychiatric symptoms.

OBJECTIVE: Prior work has described the relationship between pulmonary vascular pruning on computed tomography (CT) scans and metrics of right-sided heart dysfunction in smokers. In this analysis, we sought to look at pruning on a lobar level, as well as examine the effect of the arterial and venous circulation on this association. METHODS: Automated vessel segmentation applied to noncontrast CT scans from the COPDGene Study in 24 subjects with cardiac magnetic resonance imaging scans was used to create a blood volume distribution profile. These vessels were then manually tracked to their origin and characterized as artery or vein. RESULTS: Assessment of pruning on a lobar level revealed associations between pruning and right ventricular function previously not observed on a global level. The right ventricular mass index, the right ventricular end-systolic volume index, and pulmonary arterial-to-aorta ratio were associated with both arterial and venous pruning, whereas right ventricular ejection fraction was associated with only arterial pruning. CONCLUSIONS: Lobar assessment and segmentation of the parenchymal vasculature into arterial and venous components provide additional information about the relationship between loss of vasculature on CT scans and right ventricular dysfunction.

Hydrophobic resin acids (RAs) are synthesized by conifer trees as part of their defense mechanisms. One of the functions of RAs in plant defense is suggested to be the perturbation of the cellular membrane. However, there is a vast diversity of chemical structures within this class of molecules, and there are no clear correlations to the molecular mechanisms behind the RA’s toxicity. In this study we unravel the molecular interactions of the three closely related RAs dehydroabietic acid, neoabietic acid, and the synthetic analogue dichlorodehydroabietic acid with dipalmitoylphosphatidylcholine (DPPC) model membranes and the polar lipid extract of soybeans. The complementarity of the biophysical techniques used (NMR, DLS, NR, DSC, Cryo-TEM) allowed correlating changes at the vesicle level with changes at the molecular level and the co-localization of RAs within DPPC monolayer. Effects on DPPC membranes are correlated with the physical chemical properties of the RA and their toxicity.

The title compound, C12H10Br2N2O2, represents an example of a planar π-con-jugated 2-aza-butadiene mol-ecule, which is both an inter-esting starting material for further organic transformations and a potential ligand in organometallic coordination chemistry. Its metric mol-ecular parameters are typical for the family of 2-aza-buta-1,3-dienes not substituted at the (CH) 3-position. In the crystal, the almost planar (r.m.s. deviation = 0.0658 Å) aza-diene mol-ecules form one-dimensional double-wide ribbons through inter-molecular halogen bonds (C-Br...O and C-Br...Br-C), which then stack in a slipped manner through weak C-H...Br and π-π inter-actions to generate a three-dimensional network.