Image reconstruction is essential for imaging applications across the physical and life sciences, including optical and radar systems, magnetic resonance imaging, X-ray computed tomography, positron ...emission tomography, ultrasound imaging and radio astronomy. During image acquisition, the sensor encodes an intermediate representation of an object in the sensor domain, which is subsequently reconstructed into an image by an inversion of the encoding function. Image reconstruction is challenging because analytic knowledge of the exact inverse transform may not exist a priori, especially in the presence of sensor non-idealities and noise. Thus, the standard reconstruction approach involves approximating the inverse function with multiple ad hoc stages in a signal processing chain, the composition of which depends on the details of each acquisition strategy, and often requires expert parameter tuning to optimize reconstruction performance. Here we present a unified framework for image reconstruction-automated transform by manifold approximation (AUTOMAP)-which recasts image reconstruction as a data-driven supervised learning task that allows a mapping between the sensor and the image domain to emerge from an appropriate corpus of training data. We implement AUTOMAP with a deep neural network and exhibit its flexibility in learning reconstruction transforms for various magnetic resonance imaging acquisition strategies, using the same network architecture and hyperparameters. We further demonstrate that manifold learning during training results in sparse representations of domain transforms along low-dimensional data manifolds, and observe superior immunity to noise and a reduction in reconstruction artefacts compared with conventional handcrafted reconstruction methods. In addition to improving the reconstruction performance of existing acquisition methodologies, we anticipate that AUTOMAP and other learned reconstruction approaches will accelerate the development of new acquisition strategies across imaging modalities.
Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic ...waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non-rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.
Optogenetics is currently the state-of-the-art method for causal-oriented brain research. Despite an increasingly large number of invertebrate and rodent studies showing profound electrophysiological ...and behavioral effects induced by optogenetics 1, 2, only two primate studies have reported modulation of local single-cell activity but with no behavioral effects 3, 4. Here, we show that optogenetic stimulation of cortical neurons within rhesus monkey arcuate sulcus, during the execution of a visually guided saccade task, evoked significant and reproducible changes in saccade latencies as a function of target position. Moreover, using concurrent optogenetic stimulation and opto-fMRI 5, 6), we observed optogenetically induced changes in fMRI activity in specific functional cortical networks throughout the monkey brain. This is critical information for the advancement of optogenetic primate research models and for initiating the development of optogenetically based cell-specific therapies with which to treat neurological diseases in humans.
► Optogenetics induces behavioral changes in monkeys ► Optogenetics evokes fMRI signal changes in functional networks of macaques ► Saccade latencies decrease by optogenetic stimulation of the arcuate sulcus
As of the end of 2020, the State of Israel, with a population of 9.3 million, had administered more COVID-19 vaccine doses than all countries aside from China, the US, and the UK. Moreover, Israel ...had administered almost 11.0 doses per 100 population, while the next highest rates were 3.5 (in Bahrain) and 1.4 (in the United Kingdom). All other countries had administered less than 1 dose per 100 population.While Israel's rollout of COVID-19 vaccinations was not problem-free, its initial phase had clearly been rapid and effective. A large number of factors contributed to this early success, and they can be divided into three major groups.The first group of factors consists of long-standing characteristics of Israel which are extrinsic to health care. They include: Israel's small size (in terms of both area and population), a relatively young population, relatively warm weather in December 2020, a centralized national system of government, and well-developed infrastructure for implementing prompt responses to large-scale national emergencies.The second group of factors are also long-standing, but they are health-system specific. They include: the organizational, IT and logistical capacities of Israel's community-based health care providers, the availability of a cadre of well-trained, salaried, community-based nurses who are directly employed by those providers, a tradition of effective cooperation between government, health plans, hospitals, and emergency care providers - particularly during national emergencies; and support tools and decisionmaking frameworks to support vaccination campaigns.The third group consists of factors that are more recent and are specific to the COVID-19 vaccination effort. They include: the mobilization of special government funding for vaccine purchase and distribution, timely contracting for a large amount of vaccines relative to Israel's population, the use of simple, clear and easily implementable criteria for determining who had priority for receiving vaccines in the early phases of the distribution process, a creative technical response that addressed the demanding cold storage requirements of the Pfizer-BioNTech COVID-19 vaccine, and well-tailored outreach efforts to encourage Israelis to sign up for vaccinations and then show up to get vaccinated.While many of these facilitating factors are not unique to Israel, part of what made the Israeli rollout successful was its combination of facilitating factors (as opposed to each factor being unique separately) and the synergies it created among them. Moreover, some high-income countries (including the US, the UK, and Canada) are lacking several of these facilitating factors, apparently contributing to the slower pace of the rollout in those countries.
The Israel Journal of Health Policy Research (IJHPR) was launched in January 2012. In December 2021 it will be completing 10 years of continuous publication. I have had the privilege of serving as ...the journal's co-editor in chief during this period, and after ten years of service I am now preparing to step down from that role. IJHPR achievements of which I am particularly proud include remaining true to its mission, attracting manuscripts from virtually all the Israeli institutions engaged in health policy research as well as many leading institutions abroad, widening the circle of Israeli professionals who are submitting manuscripts to journals, and helping many established Israeli academics expand their repertoires to include articles with strong policy components. Several people and organizations have helped make editing the IJHPR such a wonderful experience for me. They include IJHPR co-editor Avi Israeli, IJHPR associate editor Steve Schoenbaum, the Israel National Institute for Health Policy Research (which sponsors the journal), BioMed Central (which publishes the journal), the Myers-JDC-Brookdale Institute (my employer), my family (and particularly my wife, Laura Rosen), and the thousands of authors who have chosen to publish with the IJHPR. May the journal's second decade be even better than its first one!
Oscillatory neural dynamics play an important role in the coordination of large-scale brain networks. High-level cognitive processes depend on dynamics evolving over hundreds of milliseconds, so ...measuring neural activity in this frequency range is important for cognitive neuroscience. However, current noninvasive neuroimaging methods are not able to precisely localize oscillatory neural activity above 0.2 Hz. Electroencephalography and magnetoencephalography have limited spatial resolution, whereas fMRI has limited temporal resolution because it measures vascular responses rather than directly recording neural activity. We hypothesized that the recent development of fast fMRI techniques, combined with the extra sensitivity afforded by ultra-high-field systems, could enable precise localization of neural oscillations. We tested whether fMRI can detect neural oscillations using human visual cortex as a model system. We detected small oscillatory fMRI signals in response to stimuli oscillating at up to 0.75 Hz within single scan sessions, and these responses were an order of magnitude larger than predicted by canonical linear models. Simultaneous EEG–fMRI and simulations based on a biophysical model of the hemodynamic response to neuronal activity suggested that the blood oxygen level-dependent response becomes faster for rapidly varying stimuli, enabling the detection of higher frequencies than expected. Accounting for phase delays across voxels further improved detection, demonstrating that identifying vascular delays will be of increasing importance with higher-frequency activity. These results challenge the assumption that the hemodynamic response is slow, and demonstrate that fMRI has the potential to map neural oscillations directly throughout the brain.
Slow changes in systemic brain physiology can elicit large fluctuations in fMRI time series, which manifest as structured spatial patterns of temporal correlations between distant brain regions. ...Here, we investigated whether such “physiological networks”—sets of segregated brain regions that exhibit similar responses following slow changes in systemic physiology—resemble patterns associated with large-scale networks typically attributed to remotely synchronized neuronal activity. By analyzing a large group of subjects from the 3T Human Connectome Project (HCP) database, we demonstrate brain-wide and noticeably heterogenous dynamics tightly coupled to either respiratory variation or heart rate changes. We show, using synthesized data generated from physiological recordings across subjects, that these physiologically-coupled fluctuations alone can produce networks that strongly resemble previously reported resting-state networks, suggesting that, in some cases, the “physiological networks” seem to mimic the neuronal networks. Further, we show that such physiologically-relevant connectivity estimates appear to dominate the overall connectivity observations in multiple HCP subjects, and that this apparent “physiological connectivity” cannot be removed by the use of a single nuisance regressor for the entire brain (such as global signal regression) due to the clear regional heterogeneity of the physiologically-coupled responses. Our results challenge previous notions that physiological confounds are either localized to large veins or globally coherent across the cortex, therefore emphasizing the necessity to consider potential physiological contributions in fMRI-based functional connectivity studies. The rich spatiotemporal patterns carried by such “physiological” dynamics also suggest great potential for clinical biomarkers that are complementary to large-scale neuronal networks.
Recent developments in fMRI acquisition techniques now enable fast sampling with whole-brain coverage, suggesting fMRI can be used to track changes in neural activity at increasingly rapid ...timescales. When images are acquired at fast rates, the limiting factor for fMRI temporal resolution is the speed of the hemodynamic response. Given that HRFs may vary substantially in subcortical structures, characterizing the speed of subcortical hemodynamic responses, and how the hemodynamic response shape changes with stimulus duration (i.e. the hemodynamic nonlinearity), is needed for designing and interpreting fast fMRI studies of these regions. We studied the temporal properties and nonlinearities of the hemodynamic response function (HRF) across the human subcortical visual system, imaging superior colliculus (SC), lateral geniculate nucleus of the thalamus (LGN) and primary visual cortex (V1) with high spatiotemporal resolution 7 Tesla fMRI. By presenting stimuli of varying durations, we mapped the timing and nonlinearity of hemodynamic responses in these structures at high spatiotemporal resolution. We found that the hemodynamic response is consistently faster and narrower in subcortical structures than in cortex. However, the nonlinearity in LGN is similar to that in cortex, with shorter duration stimuli eliciting larger and faster responses than would have been predicted by a linear model. Using oscillatory visual stimuli, we tested the frequency response in LGN and found that its BOLD response tracked high-frequency (0.5 Hz) oscillations. The LGN response magnitudes were comparable to V1, allowing oscillatory BOLD signals to be detected in LGN despite the small size of this structure. These results suggest that the increase in the speed and amplitude of the hemodynamic response when neural activity is brief may be the key physiological driver of fast fMRI signals, enabling detection of high-frequency oscillations with fMRI. We conclude that subcortical visual structures exhibit fast and nonlinear hemodynamic responses, and that these dynamics enable detection of fast BOLD signals even within small deep brain structures when imaging is performed at ultra-high field.
PET and MR imaging are modalities routinely used for clinical and research applications. Integrated scanners capable of acquiring PET and MR imaging data in the same session, sequentially or ...simultaneously, have recently become available for human use. In this article, we describe some of the technical advances that allowed the development of human PET/MR scanners; briefly discuss methodologic challenges and opportunities provided by this novel technology; and present potential oncologic, cardiac, and neuropsychiatric applications. These examples range from studies that might immediately benefit from PET/MR to more advanced applications on which future development might have an even broader impact.
Abstract
As of March 31, 2021, Israel had administered 116 doses of vaccine for COVID-19 per 100 population (of any age) – far more than any other OECD country. It was also ahead of other OECD ...countries in terms of the share of the population that had received at least one vaccination (61%) and the share that had been fully vaccinated (55%). Among Israelis aged 16 and over, the comparable figures were 81 and 74%, respectively. In light of this, the objectives of this article are:
To describe and analyze the vaccination uptake through the end of March 2021
To identify behavioral and other barriers that likely affected desire or ability to be vaccinated
To describe the efforts undertaken to overcome those barriers
Israel’s vaccination campaign was launched on December 20, and within 2.5 weeks, 20% of Israelis had received their first dose. Afterwards, the pace slowed. It took an additional 4 weeks to increase from 20 to 40% and yet another 6 weeks to increase from 40 to 60%. Initially, uptake was low among young adults, and two religious/cultural minority groups - ultra-Orthodox Jews and Israeli Arabs, but their uptake increased markedly over time.
In the first quarter of 2021, Israel had to enhance access to the vaccine, address a moderate amount of vaccine hesitancy in its general population, and also address more intense pockets of vaccine hesitancy among young adults and religious/cultural minority groups. A continued high rate of infection during the months of February and March, despite broad vaccination coverage at the time, created confusion about vaccine effectiveness, which in turn contributed to vaccine hesitancy. Among Israeli Arabs, some residents of smaller villages encountered difficulties in reaching vaccination sites, and that also slowed the rate of vaccination.
The challenges were addressed via a mix of messaging, incentives, extensions to the initial vaccine delivery system, and other measures. Many of the measures addressed the general population, while others were targeted at subgroups with below-average vaccination rates. Once the early adopters had been vaccinated, it took hard, creative work to increase population coverage from 40 to 60% and beyond.
Significantly, some of the capacities and strategies that helped Israel address vaccine hesitancy and geographic access barriers are different from those that enabled it to procure, distribute and administer the vaccines. Some of these strategies are likely to be relevant to other countries as they progress from the challenges of securing an adequate vaccine supply and streamlining distribution to the challenge of encouraging vaccine uptake.