Cardiac pulsations in the human brain have received recent interest due to their possible role in the pathogenesis of neurodegenerative diseases. Further interest stems from their possible application as an endogenous signal source that can be utilized for brain imaging in general. The (pulse-)wave describing the blood flow velocity along an intracranial artery consists of a forward (anterograde) and a backward (retrograde, reflected) part, but measurements of this wave usually consist of a superposition of these components. In this paper, we provide a mathematical framework for the inverse problem of estimating the pulse wave velocity, as well as the forward and backward component of the pulse wave separately from MRI measurements on the middle cerebral artery. After a mathematical analysis of this problem, we consider possible reconstruction approaches, and derive an alternate direction approach for its solution. The resulting methods provide estimates for anterograde/retrograde wave forms and the pulse wave velocity under specified assumptions on a cerebrovascular model system.

Purpose: To provide a tool for the automatic segmentation of an arteriogram of the brain from MRA images and the estimation of arterial tortuosity as a summary marker. Methods: A deep learning model was trained and validated on a previously published set of semi-automatically segmented brain arteriograms. We tested whether arterial tortuosity estimated from a large number of age-representative subjects (N = 478) would reproduce previously published statistics of increasing tortuosity with age. Results: The tool provides a segmentation of the arteriograms from MRA images of varying resolution and quality. The arterial tortuosity estimated from the automatically segmented brain arteriograms approximately matched their previously published statistics. Further, a highly significant increase of tortuosity with age was observed in the large dataset with 478 subjects (p = 9 x 10-8). Discussion and conclusion: The proposed ASN (Angiogram Segmentation Network) algorithm can provide the radiologist with a clean arteriogram of the brain, without the need for manual segmentation by the MR operator. Moreover, it offers arterial tortuosity as an instant quantitative metric that can augment the qualitative visual reading of the MRA. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data that were originally located at: https://github.com/iMED-Lab/COSTA https://brain-development.org/ixi-dataset/ http://cng.gmu.edu/brava I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The ASN model for generating a brain arteriogram from data is available on GitHub

There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion-weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts-including association, projection, commissural, brainstem, olfactory, and cerebellar tracts-were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings.

Purpose:To evaluate the phenomenological significance of cerebral blood pulsatility imaging in aging research. Methods:N = 38 subjects from 20 to 72 years of age (24 females) were imaged with ultrafast MRI with a sampling rate of 100 ms and simultaneous acquisition of pulse oximetry data. Of these, 28 subjects had acceptable MRI and pulse data, with 16 subjects between 20 and 28 years of age, and 12 subjects between 61 and 72 years of age. Pulse amplitude in the circle of Willis was assessed with the recently developed method of analytic phase projection to extract blood volume waveforms. Results:Arteries in the circle of Willis showed pulsatility in the MRI for both the young and old age groups. Pulse amplitude in the circle of Willis significantly increased with age (p = 0.01) but was independent of gender, heart rate, and head motion during MRI. Discussion and conclusion:Increased pulse wave amplitude in the circle of Willis in the elderly suggests a phenomenological significance of cerebral blood pulsatility imaging in aging research. The physiologic origin of increased pulse amplitude (increased pulse pressure vs. change in arterial morphology vs. re-shaping of pulse waveforms caused by the heart, and possible interaction with cerebrospinal fluid pulsatility) requires further investigation.

BACKGROUND:Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS:In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS:Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS:Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

Magnetic resonance imaging (MRI) has emerged as a promising technique for non-invasive medical imaging. The primary challenge in MRI is the trade-off between image visual quality and acquisition time. Current MRI image denoising algorithms employ global thresholding to denoise the whole image, which leads to inadequate denoising or image distortion. This study introduces a novel pixel-wise (localized) thresholding approach of singular vectors, obtained from singular value decomposition, to denoise magnetic resonance (MR) images. The pixel-wise thresholding of singular vectors is performed using separate singular values as thresholds at each pixel, which is advantageous given the spatial noise variation throughout the image. The method presented is validated on MR images of a standard phantom approved by the magnetic resonance accreditation program (MRAP). The denoised images display superior visual quality and recover minute structural information otherwise suppressed in the noisy image. The increase in peak-signal-to-noise-ratio (PSNR) and contrast-to-noise-ratio (CNR) values of ≥ 18% and ≥ 200% of the denoised images, respectively, imply efficient noise removal and visual quality enhancement. The structural similarity index (SSIM) of ≥ 0.95 for denoised images indicates that the crucial structural information is recovered through the presented method. A comparison with the standard filtering methods widely used for MRI denoising establishes the superior performance of the presented method. The presented pixel-wise denoising technique reduces the scan time by 2-3 times and has the potential to be integrated into any MRI system to obtain faster and better quality images.

Assessing cognitive function-especially language processing-in severely brain-injured patients is critical for prognostication, care, and development of communication devices (e.g. brain-computer interfaces). In patients with diminished motor function, language processing has been probed using EEG measures of command-following in motor imagery tasks. While such tests eliminate the need for motor response, they require sustained attention. However, passive listening tasks, with an EEG response measure can reduce both motor and attentional demands. These considerations motivated the development of two assays of low-level language processing-identification of differential phoneme-class responses and tracking of the natural speech envelope. This cross-sectional study looks at a cohort of 26 severely brain-injured patient subjects and 10 healthy controls. Patients' level of function was assessed via the coma recovery scale-revised at the bedside. Patients were also tested for command-following via EEG and/or MRI assays of motor imagery. For the present investigation, EEG was recorded while presenting a 148 s audio clip of Alice in Wonderland. Time-locked EEG responses to phoneme classes were extracted and compared to determine a differential phoneme-class response. Tracking of the natural speech envelope was assessed from the same recordings by cross-correlating the EEG response with the speech envelope. In healthy controls, the dynamics of the two measures were temporally similar but spatially different: a central parieto-occipital component of differential phoneme-class response was absent in the natural speech envelope response. The differential phoneme-class response was present in all patient subjects, including the six classified as vegetative state/unresponsive wakefulness syndrome by behavioural assessment. However, patient subjects with evidence of language processing either by behavioural assessment or motor imagery tests had an early bilateral response in the first 50 ms that was lacking in patient subjects without any evidence of language processing. The natural speech envelope tracking response was also present in all patient subjects and responses in the first 100 ms distinguished patient subjects with evidence of language processing. Specifically, patient subjects with evidence of language processing had a more global response in the first 100 ms whereas those without evidence of language processing had a frontopolar response in that period. In summary, we developed two passive EEG-based methods to probe low-level language processing in severely brain-injured patients. In our cohort, both assays showed a difference between patient subjects with evidence of command-following and those with no evidence of command-following: a more prominent early bilateral response component.

Southern giant pouched rats ( Cricetomys ansorgei ) are a small muroid species native to the sub-Saharan Africa. Their exceptionally developed olfactory system, trainability, and relatively small size makes them useful working animals for various applications in humanitarian work. At our institution, a breeding colony of Southern giant pouched rats is maintained to study their physiology and utility as scent detectors. This case report describes the occurrence of spontaneous pituitary neoplasms with distinct clinical presentations in 2 geriatric (approximately 7.5 y old) wild-caught female Southern giant pouched rats. The first pouched rat displayed vestibular deficits, including left-sided head tilt, ataxia, disorientation, and circling. MRI revealed a large, focal heterogeneous mass arising from the pituitary fossa. The second pouched rat presented with polyuria, polydipsia, and hyperglycemia but no neurologic signs. Examination after euthanasia revealed a prolactin (PRL)-expressing pituitary carcinoma and adenoma in the first and second pouched rat, respectively, associated with mammary hyperplasia in both animals. This is the first report of spontaneous PRL-producing pituitary tumors in Southern giant pouched rats.

Gram-negative bacteria are notoriously more resistant to antibiotics than Gram-positive bacteria, primarily due to the presence of the outer membrane and a plethora of active efflux pumps. However, the potency of antibiotics also varies dramatically between different Gram-negative pathogens, suggesting major mechanistic differences in how antibiotics penetrate permeability barriers.

This study utilized sub-millimeter 3T gradient echo MRI of the brainstem ex vivo to obtain a magnetic susceptibility map (QSM). ROIs of both deep brain nuclei and myelinated fiber tracts were chosen and quantified from QSM obtained from MRI field. The ex vivo specimens were then stained with Luxol Fast Blue and the resultant absorbance of the ROIs were compared to QSM. A strong linear correlation was observed (R 2 = 0.897, p = 0.0041).

Magnetic resonance guided focused ultrasound (MRgFUS) is a non-invasive therapeutic modality for neurodegenerative diseases that employs real-time imaging and thermometry monitoring of targeted regions. MRI is used in guidance of ultrasound treatment; however, the MR image quality in current clinical applications is poor when using the vendor built-in body coil. We present an 8-channel, ultra-thin, flexible, and acoustically transparent receive-only head coil design (FUS-Flex) to improve the signal-to-noise ratio (SNR) and thus the quality of MR images during MRgFUS procedures. Acoustic simulations/experiments exhibit transparency of the FUS-Flex coil as high as 97% at 650 kHz. Electromagnetic simulations show a SNR increase of $13\times $ over the body coil. In vivo results show an increase of the SNR over the body coil by a factor of 7.3 with $2\times $ acceleration (equivalent to $11\times $ without acceleration) in the brain of a healthy volunteer, which agrees well with simulation. These preliminary results show that the use of a FUS-Flex coil in MRgFUS surgery can increase MR image quality, which could yield improved focal precision, real-time intraprocedural anatomical imaging, and real-time 3D thermometry mapping.

— The periodically driven harmonic oscillator with damping is one of the most elementary and trusted models in physics and normally applied in its steady state, disregarding specific initial conditions and associated transients. For example, steady state solutions are already sufficient to describe resonance. In some applications transient solutions might play a role though, and a review of these might be useful. In order to characterize the transients of the harmonic oscillator, its winding number is graphed in dependence of initial conditions. These visualizations show a complexity of the transients of the harmonic oscillator that are not readily evident from the inspection of the model alone.

Background and Objectives Following severe brain injury, up to 16% of adults showing no clinical signs of cognitive function nonetheless have preserved cognitive capacities detectable via neuroimaging and neurophysiology; this has been designated cognitive-motor dissociation (CMD). Pediatric medicine lacks both practice guidelines for identifying covert cognition and epidemiologic data regarding CMD prevalence. Methods We applied a diverse battery of neuroimaging and neurophysiologic tests to evaluate 2 adolescents (aged 15 and 18 years) who had shown no clinical evidence of preserved cognitive function following brain injury at age 9 and 13 years, respectively. Clinical evaluations were consistent with minimally conscious state (minus) and vegetative state, respectively. Results Both participants' EEG, and 1 participant's fMRI, provided evidence that they could understand commands and make consistent voluntary decisions to follow them. Both participants' EEG demonstrated larger-than-expected responses to auditory stimuli and intact semantic processing of words in context. Discussion These converging lines of evidence lead us to conclude that both participants had preserved cognitive function dissociated from their motor output. Throughout the 5+ years since injury, communication attempts and therapy had remained uninformed by such objective evidence of their cognitive abilities. Proper diagnosis of CMD is an ethical imperative. Children with covert cognition reflect a vulnerable and isolated population; the methods outlined here provide a first step in identifying such persons to advance efforts to alleviate their condition.

We propose a 2-dimensional cylindrical high-pass ladder (2D c-HPL) coil and exploit the added second dimension in a longitudinal direction to create a body-sized volume coil with a length of 91 cm for use in ultra-high-field (UHF) magnetic resonance imaging (MRI). Theory, circuit model, and in-silico results show that this architecture exhibits improved transmit field inhomogeneity (6.44%), decreased specific absorption rate (0.014 W/kg), and improved specific absorption rate (SAR) efficiency (0.59 μT/√W/kg). This could prove particularly useful for whole-body and spinal-cord imaging, among others, and could open up new pathways for clinical diagnostics in UHF MRI.

Topological properties of solid states have sparked considerable recent interest due to their importance in the physics of lattices with a non-trivial basis and their potential in the design of novel materials. Here we describe an experimental and an accompanying numerical toolbox to create and analyze topological states in coupled radiofrequency resonator arrays. The arrays are coupled harmonic oscillator systems that are very easily constructed, offer a variety of geometric configurations, and whose eigenfunctions and eigenvalues are amenable to detailed analysis. These systems offer well defined analogs to coupled oscillator systems in general in that they are characterized by resonances whose frequency spectra depend on the individual resonators, the interactions between them, and the geometric and topological symmetries and boundary conditions. In particular, we describe an experimental analog of a small one-dimensional system, with excellent agreement with theory. The numerical part of the toolbox allows for simulations of larger mesoscopic systems with a semi-continuous band structure, in which all resonators still exhibit individual signatures. Systematic parameter variation yields an astonishing richness of band structures in this simple linear system, allowing for further explorations into novel phenomena of topological modes.

The eigenvector-eigenvalue identity relates the eigenvectors of a Hermitian matrix to its eigenvalues and the eigenvalues of its principal submatrices in which the jth row and column have been removed. We show that one-dimensional arrays of coupled resonators, described by square matrices with real eigenvalues, provide simple physical systems where this formula can be applied in practice. The subsystems consist of arrays with the jth resonator removed and, thus, can be realized physically. From their spectra alone, the oscillation modes of the full system can be obtained. This principle of successive single resonator deletions is demonstrated in two experiments of coupled radio-frequency resonator arrays with greater-than-nearest-neighbor couplings in which the spectra are measured with a network analyzer. Both the Hermitian as well as a non-Hermitian case are covered in the experiments. In both cases, the experimental eigenvector estimates agree well with numerical simulations if certain consistency conditions imposed by system symmetries are taken into account. In the Hermitian case, these estimates are obtained from resonance spectra alone without knowledge of the system parameters. It remains an interesting problem of physical relevance to find conditions under which the full non-Hermitian eigenvector set can be obtained from the spectra alone.

We consider the inverse problem of estimating the spatially varying pulse wave velocity in blood vessels in the brain from dynamic MRI data, as it appears in the recently proposed imaging technique of Magnetic Resonance Advection Imaging (MRAI). The problem is formulated as a linear operator equation with a noisy operator and solved using a conjugate gradient-type approach. Numerical examples on experimental data show the usefulness and advantages of the developed algorithm in comparison to previously proposed methods.

Purpose: To quantify CSF transport kinetics and brain glymphatic distribution using MRI following intrathecal injection of gadolinium contrast in healthy adults. Subjects and methods: Eight completely healthy volunteer subjects underwent intrathecal injection of gadolinium via image guided lumbar puncture and serial MRI's at six subsequent time points up to 11 h post-injection. Rate of enhancement and deposition were calculated for various regions and lobes of the brain. Results: Normalized cranial data revealed that gadolinium in the intracranial CSF spaces peaked within 1-3 h and started to decrease at 7 h. In some regions of the brain parenchyma, such as the cerebral cortex and white matter, enhancement was increasing after 11 h. Differential rates of uptake between the parietal and frontal (p = 0.0003), cingulate (p = 0.002) and temporal (p = 0.018) lobes were shown as well as a several fold change between various cortical regions. Lastly, a linear regression comparing laterality between 35 cortical regions yielded (R-2 = 0.90, p < 0.001) with a slope of 1.01 showing symmetry in uptake. Conclusions: Gadolinium enhancement after lumbar intrathecal injection demonstrated differential CSF flow and brain parenchymal penetration, which illustrated the distributory function of the glymphatic system.