Four-dimensional ultrasound imaging of complex biological systems such as the brain is technically challenging because of the spatiotemporal sampling requirements. We present computational ultrasound imaging (cUSi), an imaging method that uses complex ultrasound fields that can be generated with simple hardware and a physical wave prediction model to alleviate the sampling constraints. cUSi allows for high-resolution four-dimensional imaging of brain hemodynamics in awake and anesthetized mice.

Functional ultrasound (fUS) using a 1-D-array transducer normally is insufficient to capture volumetric functional activity due to being restricted to imaging a single brain slice at a time. Typically, for volumetric fUS, functional recordings are repeated many times as the transducer is moved to a new location after each recording, resulting in a nonunique average mapping of the brain response and long scan times. Our objective was to perform volumetric 3-D fUS in an efficient and cost-effective manner. This was achieved by mounting a 1-D-array transducer to a high-precision motorized linear stage and continuously translating over the mouse brain in a sweeping manner. We show how the speed at which the 1-D-array is translated over the brain affects the sampling of the hemodynamic response (HR) during visual stimulation as well as the quality of the resulting power Doppler image (PDI). Functional activation maps were compared between stationary recordings, where only one functional slice is obtained for every recording, and our swept-3-D method, where volumetric fUS was achieved in a single functional recording. The results show that the activation maps obtained with our method closely resemble those obtained during a stationary recording for that same location, while our method is not restricted to functional imaging of a single slice. Lastly, a mouse brain subvolume of 6 mm is scanned at a volume rate of 1.5 s per volume, with a functional PDI reconstructed every 200\mu \text{m} , highlighting swept-3-D's potential for volumetric fUS. Our method provides an affordable alternative to volumetric fUS using 2-D-matrix transducers, with a high SNR due to using a fully sampled 1-D-array transducer, and without the need to repeat functional measurements for every 2-D slice, as is most often the case when using a 1-D-array. This places our swept-3-D method as a potentially valuable addition to conventional 2-D fUS, especially when investigating whole-brain functional connectivity, or when shorter recording durations are desired.

Volumetric 3-D Doppler ultrasound imaging can be used to investigate large scale blood dynamics outside of the limited view that conventional 2-D power Doppler images (PDIs) provide. To create 3-D PDIs, 2-D-matrix array transducers can be used to insonify a large volume for every transmission; however, these matrices suffer from low sensitivity, high complexity, and high cost. More typically, a 1-D-Array transducer is used to scan a series of stationary 2-D PDIs, after which a 3-D volume is created by concatenating the 2-D PDIs in postprocessing, which results in long scan times due to repeated measurements. Our objective was to achieve volumetric 3-D Doppler ultrasound imaging with a high Doppler sensitivity, similar to that of a typical stationary recording using a 1-D-Array transducer, while being more affordable than using 2-D-matrix arrays. We achieved this by mounting a 1-D-Array transducer to a high-precision motorized linear stage and continuously translating over the mouse brain in a sweeping manner. For Part I of this article, we focused on creating the best vascular images by investigating how to best combine filtered beamformed ultrasound frames, which were not acquired at the same spatial locations, into PDIs. Part II focuses on the implications of sampling transient brain hemodynamics through functional ultrasound (fUS) while continuously translating over the mouse brain. In Part I, we show how the speed at which we sweep our 1-D-Array transducer affects the Doppler spectrum in a flow phantom. In vivo recordings were performed on the mouse brain while varying the sweeping speed, showing how higher sweeping speeds negatively affect the PDI quality. A weighting vector is found to combine frames while continuously moving over the mouse brain, allowing us to create swept PDIs of similar sensitivity when compared with those obtained using a stationary 1-D-Array while allowing a significantly higher 3-D Doppler volume rate and maintaining the benefits of having a low computational and monetary cost. We show that a vascular subvolume of 6 mm can be scanned in 2.5 s, with a PDI reconstructed every $200 \mu \text{m}$ , outperforming classical staged recording methods.

Background and Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intra-operative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection. Methods: During awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (post-resection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest. Results: A total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial and temporal resolution of 300 μm and 1.5–2.0 ms respectively, revealing real-time tumor-specific, and healthy vascular characteristics. Conclusion: The current study presents the potential of applying fUS during awake brain surgery. We illustrate the relevance of fUS for awake brain surgery based on its ability to capture both task-evoked functional cortical responses as well as differences in vascular characteristics between tumor and healthy tissue. As current neurosurgical practice is still pre-dominantly leaning on inherently limited pre-operative imaging techniques for tumor resection-guidance, fUS enters the scene as a promising alternative that is both anatomically and physiologically informative.

Romano et al. show that cerebellar Purkinje cell activity follows the respiratory rhythm during rest. Triggered by sensory input, Purkinje cells can alter their activity and thereby accelerate the timing of the next inspiration. Concomitantly, they also augment whisker movements, highlighting a coordinating role in aligning autonomic and sensorimotor behaviors.

In heart-beat-based security, a security key is derived from the time difference between consecutive heart beats (the inter-pulse interval, IPI), which may, subsequently, be used to enable secure communication. While heart-beat-based security holds promise in mobile health (mHealth) applications, there currently exists no work that provides a detailed characterization of the delivered security in a real system. In this paper, we evaluate the strength of IPI-based security keys in the context of entity authentication. We investigate several aspects that should be considered in practice, including subjects with reduced heart-rate variability (HRV), different sensor-sampling frequencies, intersensor variability (i.e., how accurate each entity may measure heart beats) as well as average and worst-case-authentication time. Contrary to the current state of the art, our evaluation demonstrates that authentication using multiple, less-entropic keys may actually increase the key strength by reducing the effects of intersensor variability. Moreover, we find that the maximal key strength of a 60-bit key varies between 29.2 bits and only 5.7 bits, depending on the subject's HRV. To improve security, we introduce the inter-multi-pulse interval (ImPI), a novel method of extracting entropy from the heart by considering the time difference between nonconsecutive heart beats. Given the same authentication time, using the ImPI for key generation increases key strength by up to 3.4× (+19.2 bits) for subjects with limited HRV, at the cost of an extended key-generation time of 4.8× (+45 s).

In-vivo and in-vitro experiments are routinely used in neuroscience to unravel brain functionality. Although they are a powerful experimentation tool, they are also time-consuming and, often, restrictive. Computational neuroscience attempts to solve this by using biologically-plausible and biophysically-meaningful neuron models, most prominent among which are the conductance-based models. Their computational complexity calls for accelerator-based computing to mount large-scale or real-time neuroscientific experiments. In this paper, we analyze and draw conclusions on the class of conductance models by using a representative modeling application of the inferior olive (InfOli), an important part of the olivocerebellar brain circuit. We conduct an extensive profiling session to identify the computational and data-transfer requirements of the application under various realistic use cases. The application is, then, ported onto two acceleration nodes, an Intel Xeon Phi and a Maxeler Vectis Data Flow Engine (DFE). We evaluate the performance scalability and resource requirements of the InfOli application on the two target platforms. The analysis of InfOli, which is a real-life neuroscientific application, can serve as a useful guide for porting a wide range of similar workloads on platforms like the Xeon Phi or the Maxeler DFEs. As accelerators are increasingly populating High-Performance Computing (HPC) infrastructure, the current paper provides useful insight on how to optimally use such nodes to run complex and relevant neuron modeling workloads.

The Inter-Pulse-Interval (IPI) of heart beats has previously been suggested for facilitating security in mobile health (mHealth) applications. In heart-beat-based security, a security key is derived from the time difference between consecutive heart beats. As two entities that simultaneously sample the same heart beats may generate the same key (with some inter-key disparity), these keys may be used for various security functions, such as entity authentication or data confidentiality. One of the key limitations in heart-beat-based security is the low randomness intrinsic to the most-significant bits (MSBs) in the digital representation of each IPI. In this paper, we explore the use of a von Neumann entropy extractor on these MSBs in order to increase their randomness. We show that our von Neumann key-generator produces significantly more random bits than a non-extracting key generator with an average bit-extraction rate between 13.4% and 21.9%. Despite this increase in randomness, we also find a substantial increase in inter-key disparity, increasing the mismatch tolerance required for a given true-key pair. Accordingly, the maximum-attainable effective key-strength of our key generator is only slightly higher than that of a non-extracting generator (16.4 bits compared to 15.2 bits of security for a 60-bit key), while the former requires an increase in average key-generation time of 2.5x.

The Inferior-Olivary nucleus (ION) is a well-charted brain region, heavily associated with the sensorimotor control of the body. It comprises neural cells with unique properties which facilitate sensory processing and motor-learning skills. Simulations of such neurons become rapidly intractable when biophysically plausible models and meaningful network sizes (at least in the order of some hundreds of cells) are modeled. To overcome this problem, we accelerate a highly detailed ION network model using a Maxeler Dataflow Computing Machine. The design simulates a 330-cell network at real-time speed and achieves maximum throughputs of 24.7 GFLOPS. The Maxeler machine, integrating a Virtex-6 FPGA, yields speedups of ×92-102, and ×2-8 compared to a reference-C implementation, running on a Intel Xeon 2.66GHz, and a pure Virtex-7 FPGA implementation, respectively.

The Inter-Pulse-Interval (IPI) of heart beats has previously been suggested for security in mobile health (mHealth) applications. In IPI-based security, secure communication is facilitated through a security key derived from the time difference between heart beats. However, there currently exists no work which considers the effect on security of imperfect heart-beat (peak) detection. This is a crucial aspect of IPI-based security and likely to happen in a real system. In this paper, we evaluate the effects of peak misdetection on the security performance of IPI-based security. It is shown that even with a high peak detection rate between 99.9% and 99.0%, a significant drop in security performance may be observed (between -70% and -303%) compared to having perfect peak detection. We show that authenticating using smaller keys yields both stronger keys as well as potentially faster authentication in case of imperfect heart beat detection. Finally, we present an algorithm which tolerates the effect of a single misdetected peak and increases the security performance by up to 155%.

Biologically accurate neuron simulations are increasingly important in research related to brain activity. They are computationally intensive and feature data and task parallelism. In this paper, we present a case study for the mapping of a biologically accurate inferior-olive (InfOli), neural cell simulator on an many-core research platform. The Single-Chip Cloud Computer (SCC) is an experimental processor created by Intel Labs. The target neurons provide a major input to the cerebellum and are involved in motor skills and space perception. We exploit task-and data-partitioning, scaling the simulation over more than 40,000 neurons. The voltage-and frequency-scaling capabilities of the chip are explored, achieving more than 20% energy savings with negligible performance degradation. Four platform configurations are evaluated and a mapping with balanced workload and constant voltage and frequency is formally derived as optimal.

Recent work on wireless Implantable Medical Devices (IMDs) has revealed the need for secure communication in order to prevent data theft and implant abuse by malicious attackers. However, security should not be provided at the cost of patient safety and an IMD should, thus, remain accessible during an emergency regardless of device security. In this paper, we present a novel method of providing IMD emergency access, based on generating Entity Identifiers (EI) using the Inter-Pulse Intervals (IPIs) of heartbeats. We evaluate the current state-of-the-art in EI-generation in terms of security and accessibility for healthy subjects with a wide range of heart rates. Subsequently, we present an adaptive EI-generation algorithm which takes the heart rate into account, maintaining an acceptable emergency-mode activation time (between 5-55.4 s) while improving security by up to 3.4x for high heart rates. Finally, we show that activating emergency mode may consume as little as 0.24μJ from the IMD battery.