Imaging Center

Abstract Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves 1 and in the first imaging of a black hole 2 . Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1 and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest."

The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorodeoxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquired at multiple time points. All data will be cross-linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications that guided protocol development. A major effort was devoted to evaluating 3D T(1)-weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced-scale clinical trial. The protocol selected for the ADNI study includes: back-to-back 3D magnetization prepared rapid gradient echo (MP-RAGE) scans; B(1)-calibration scans when applicable; and an axial proton density-T(2) dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials.

An automated coordinate-based system to retrieve brain labels from the 1988 Talairach Atlas, called the Talairach Daemon (TD), was previously introduced [Lancaster et al., 1997]. In the present study, the TD system and its 3-D database of labels for the 1988 Talairach atlas were tested for labeling of functional activation foci. TD system labels were compared with author-designated labels of activation coordinates from over 250 published functional brain-mapping studies and with manual atlas-derived labels from an expert group using a subset of these activation coordinates. Automated labeling by the TD system compared well with authors' labels, with a 70% or greater label match averaged over all locations. Author-label matching improved to greater than 90% within a search range of +/-5 mm for most sites. An adaptive grey matter (GM) range-search utility was evaluated using individual activations from the M1 mouth region (30 subjects, 52 sites). It provided an 87% label match to Brodmann area labels (BA 4 & BA 6) within a search range of +/-5 mm. Using the adaptive GM range search, the TD system's overall match with authors' labels (90%) was better than that of the expert group (80%). When used in concert with authors' deeper knowledge of an experiment, the TD system provides consistent and comprehensive labels for brain activation foci. Additional suggested applications of the TD system include interactive labeling, anatomical grouping of activation foci, lesion-deficit analysis, and neuroanatomy education.

Brain aging research relies mostly on cross-sectional studies, which infer true changes from age differences. We present longitudinal measures of five-year change in the regional brain volumes in healthy adults. Average and individual differences in volume changes and the effects of age, sex and hypertension were assessed with latent difference score modeling. The caudate, the cerebellum, the hippocampus and the association cortices shrunk substantially. There was minimal change in the entorhinal and none in the primary visual cortex. Longitudinal measures of shrinkage exceeded cross-sectional estimates. All regions except the inferior parietal lobule showed individual differences in change. Shrinkage of the cerebellum decreased from young to middle adulthood, and increased from middle adulthood to old age. Shrinkage of the hippocampus, the entorhinal cortices, the inferior temporal cortex and the prefrontal white matter increased with age. Moreover, shrinkage in the hippocampus and the cerebellum accelerated with age. In the hippocampus, both linear and quadratic trends in incremental age-related shrinkage were limited to the hypertensive participants. Individual differences in shrinkage correlated across some regions, suggesting common causes. No sex differences in age trends except for the caudate were observed. We found no evidence of neuroprotective effects of larger brain size or educational attainment.

New evidence on breast Magnetic Resonance Imaging (MRI) screening has become available since the American Cancer Society (ACS) last issued guidelines for the early detection of breast cancer in 2003. A guideline panel has reviewed this evidence and developed new recommendations for women at different defined levels of risk. Screening MRI is recommended for women with an approximately 20-25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease. There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography. Diagnostic uses of MRI were not considered to be within the scope of this review.

Mitochondrial morphology is determined by a dynamic equilibrium between organelle fusion and fission, but the significance of these processes in vertebrates is unknown. The mitofusins, Mfn1 and Mfn2, have been shown to affect mitochondrial morphology when overexpressed. We find that mice deficient in either Mfn1 or Mfn2 die in midgestation. However, whereas Mfn2 mutant embryos have a specific and severe disruption of the placental trophoblast giant cell layer, Mfn1-deficient giant cells are normal. Embryonic fibroblasts lacking Mfn1 or Mfn2 display distinct types of fragmented mitochondria, a phenotype we determine to be due to a severe reduction in mitochondrial fusion. Moreover, we find that Mfn1 and Mfn2 form homotypic and heterotypic complexes and show, by rescue of mutant cells, that the homotypic complexes are functional for fusion. We conclude that Mfn1 and Mfn2 have both redundant and distinct functions and act in three separate molecular complexes to promote mitochondrial fusion. Strikingly, a subset of mitochondria in mutant cells lose membrane potential. Therefore, mitochondrial fusion is essential for embryonic development, and by enabling cooperation between mitochondria, has protective effects on the mitochondrial population.

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this problem, we have developed the Brain Imaging Data Structure (BIDS), a standard for organizing and describing MRI datasets. The BIDS standard uses file formats compatible with existing software, unifies the majority of practices already common in the field, and captures the metadata necessary for most common data processing operations.

Human learning is a complex phenomenon requiring flexibility to adapt existing brain function and precision in selecting new neurophysiological activities to drive desired behavior. These two attributes--flexibility and selection--must operate over multiple temporal scales as performance of a skill changes from being slow and challenging to being fast and automatic. Such selective adaptability is naturally provided by modular structure, which plays a critical role in evolution, development, and optimal network function. Using functional connectivity measurements of brain activity acquired from initial training through mastery of a simple motor skill, we investigate the role of modularity in human learning by identifying dynamic changes of modular organization spanning multiple temporal scales. Our results indicate that flexibility, which we measure by the allegiance of nodes to modules, in one experimental session predicts the relative amount of learning in a future session. We also develop a general statistical framework for the identification of modular architectures in evolving systems, which is broadly applicable to disciplines where network adaptability is crucial to the understanding of system performance.

PURPOSE: To determine whether sonography could help accurately distinguish benign solid breast nodules from indeterminate or malignant nodules and whether this distinction could be definite enough to obviate biopsy. MATERIALS AND METHODS: Seven hundred fifty sonographically solid breast nodules were prospectively classified as benign, indeterminate, or malignant. Benign nodules had no malignant characteristics and had either intense homogeneous hyperechogenicity or a thin echogenic pseudocapsule with an ellipsoid shape or fewer than four gentle lobulations. Sonographic classifications were compared with biopsy results. The sensitivity, specificity, and negative and positive predictive values of the classifications were calculated. RESULTS: Benign histologic features were found in 625 (83%) lesions; malignant histologic features, in 125 (17%). Of benign lesions, 424 had been prospectively classified as benign. Two lesions classified as benign were found to be malignant at biopsy. Thus, the classification scheme had a negative predictive value of 99.5%. Of 125 malignant lesions, 123 were correctly classified as indeterminate or malignant (98.4% sensitivity). CONCLUSION: Sonography can be used to accurately classify some solid lesions as benign, allowing imaging follow-up rather than biopsy.

With mounting data on its accuracy and prognostic value, cardiovascular magnetic resonance (CMR) is becoming an increasingly important diagnostic tool with growing utility in clinical routine. Given its versatility and wide range of quantitative parameters, however, agreement on specific standards for the interpretation and post-processing of CMR studies is required to ensure consistent quality and reproducibility of CMR reports. This document addresses this need by providing consensus recommendations developed by the Task Force for Post-Processing of the Society for Cardiovascular Magnetic Resonance (SCMR). The aim of the Task Force is to recommend requirements and standards for image interpretation and post-processing enabling qualitative and quantitative evaluation of CMR images. Furthermore, pitfalls of CMR image analysis are discussed where appropriate. It is an update of the original recommendations published 2013.

MNI coordinates determined using SPM2 and FSL/FLIRT with the ICBM-152 template were compared to Talairach coordinates determined using a landmark-based Talairach registration method (TAL). Analysis revealed a clear-cut bias in reference frames (origin, orientation) and scaling (brain size). Accordingly, ICBM-152 fitted brains were consistently larger, oriented more nose down, and translated slightly down relative to TAL fitted brains. Whole brain analysis of MNI/Talairach coordinate disparity revealed an ellipsoidal pattern with disparity ranging from zero at a point deep within the left hemisphere to greater than 1-cm for some anterior brain areas. MNI/Talairach coordinate disparity was generally less for brains fitted using FSL. The mni2tal transform generally reduced MNI/Talairach coordinate disparity for inferior brain areas but increased disparity for anterior, posterior, and superior areas. Coordinate disparity patterns differed for brain templates (MNI-305, ICBM-152) using the same fitting method (FSL/FLIRT) and for different fitting methods (SPM2, FSL/FLIRT) using the same template (ICBM-152). An MNI-to-Talairach (MTT) transform to correct for bias between MNI and Talairach coordinates was formulated using a best-fit analysis in one hundred high-resolution 3-D MR brain images. MTT transforms optimized for SPM2 and FSL were shown to reduced group mean MNI/Talairach coordinate disparity from a 5-13 mm to 1-2 mm for both deep and superficial brain sites. MTT transforms provide a validated means to convert MNI coordinates to Talairach compatible coordinates for studies using either SPM2 or FSL/FLIRT with the ICBM-152 template.

BACKGROUND: The differential diagnosis of disorders of consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing, particularly if the patient's capacity to show behavioral signs of awareness is diminished. METHODS: At two major referral centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study involving 54 patients with disorders of consciousness. We used functional magnetic resonance imaging (MRI) to assess each patient's ability to generate willful, neuroanatomically specific, blood-oxygenation-level-dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions. RESULTS: Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside. CONCLUSIONS: These results show that a small proportion of patients in a vegetative or minimally conscious state have brain activation reflecting some awareness and cognition. Careful clinical examination will result in reclassification of the state of consciousness in some of these patients. This technique may be useful in establishing basic communication with patients who appear to be unresponsive.

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. METHODS AND RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS: This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.

English and Russian color terms divide the color spectrum differently. Unlike English, Russian makes an obligatory distinction between lighter blues ("goluboy") and darker blues ("siniy"). We investigated whether this linguistic difference leads to differences in color discrimination. We tested English and Russian speakers in a speeded color discrimination task using blue stimuli that spanned the siniy/goluboy border. We found that Russian speakers were faster to discriminate two colors when they fell into different linguistic categories in Russian (one siniy and the other goluboy) than when they were from the same linguistic category (both siniy or both goluboy). Moreover, this category advantage was eliminated by a verbal, but not a spatial, dual task. These effects were stronger for difficult discriminations (i.e., when the colors were perceptually close) than for easy discriminations (i.e., when the colors were further apart). English speakers tested on the identical stimuli did not show a category advantage in any of the conditions. These results demonstrate that (i) categories in language affect performance on simple perceptual color tasks and (ii) the effect of language is online (and can be disrupted by verbal interference).

Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce mitochondrial outer membrane permeabilization, leading to cytochrome c release and activation of apoptotic caspases. In the absence of active caspases, mitochondrial DNA (mtDNA) triggers the innate immune cGAS/STING pathway, causing dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains unclear. We used live-cell lattice light-sheet microscopy to examine the mitochondrial network in mouse embryonic fibroblasts. We found that after BAK/BAX activation and cytochrome c loss, the mitochondrial network broke down and large BAK/BAX pores appeared in the outer membrane. These BAK/BAX macropores allowed the inner mitochondrial membrane to herniate into the cytosol, carrying with it mitochondrial matrix components, including the mitochondrial genome. Apoptotic caspases did not prevent herniation but dismantled the dying cell to suppress mtDNA-induced innate immune signaling.