CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved. METHODS: We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics. RESULTS: Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats. CONCLUSIONS: Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.

Transient intracranial pressure elevations (B waves) are associated with sleep apnea.

BACKGROUND: Repetitive transient intracranial pressure waveform elevations up to 50 mmHg (ICP B-waves) are often used to define pathological conditions and determine indications for ICP-reducing treatment. We recently showed that nocturnal transient ICP elevations are present in patients without structural brain lesions or hydrocephalus in whom they are associated with sleep apnea. However, whether this signifies a general association between ICP macropatterns and sleep apnea remains unknown. METHODS: We included 34 patients with hydrocephalus, or idiopathic intracranial hypertension (IIH), who were referred to the Neurosurgical Department, Copenhagen, Denmark, from 2017 to 2021. Every patient underwent diagnostic overnight ICP monitoring for clinical indications, with simultaneous polysomnography (PSG) sleep studies. All transient ICP elevations were objectively quantified in all patients. Three patients were monitored with continuous positive airway pressure (CPAP) treatment for an additional night. RESULTS: All patients had transient ICP elevations associated with sleep apnea. The mean temporal delay from sleep apnea to transient ICP elevations for all patients was 3.6 s (SEM 0.2 s). Ramp-type transient ICP elevations with a large increase in ICP were associated with rapid eye movement (REM) sleep and sinusoidal-type elevations with non-REM (NREM) sleep. In three patients treated with CPAP, the treatment reduced the number of transient ICP elevations with a mean of 37%. CPAP treatment resulted in insignificant changes in the average ICP in two patients but elevated the average ICP during sleep in one patient by 5.6 mmHg. CONCLUSION: The findings suggest that sleep apnea causes a significant proportion of transient ICP elevations, such as B-waves, and sleep apnea should be considered in ICP evaluation. Treatment of sleep apnea with CPAP can reduce the occurrence of transient ICP elevations. More research is needed on the impact of slow oscillating mechanisms on transient ICP elevations during high ICP and REM sleep.

Modelling idiopathic intracranial hypertension in rats: contributions of high fat diet and testosterone to intracranial pressure and cerebrospinal fluid production.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure (ICP), impaired vision, and headache. Most cases of IIH occur in obese women of childbearing age, though age, BMI, and female sex do not encompass all aspects of IIH pathophysiology. Systemic metabolic dysregulation has been identified in IIH with a profile of androgen excess. However, the mechanistic coupling between obesity/hormonal perturbations and cerebrospinal fluid dynamics remains unresolved. METHODS: Female Wistar rats were either fed a high fat diet (HFD) for 21 weeks or exposed to adjuvant testosterone treatment for 28 days to recapitulate IIH causal drivers. Cerebrospinal fluid (CSF) and blood testosterone levels were determined with mass spectrometry, ICP and CSF dynamics with in vivo experimentation, and the choroid plexus function revealed with transcriptomics and ex vivo isotope-based flux assays. RESULTS: HFD-fed rats presented with increased ICP (65%), which was accompanied by increased CSF outflow resistance (50%) without altered CSF secretion rate or choroid plexus gene expression. Chronic adjuvant testosterone treatment of lean rats caused elevated ICP (55%) and CSF secretion rate (85%), in association with increased activity of the choroid plexus Na+,K+,2Cl- cotransporter, NKCC1. CONCLUSIONS: HFD-induced ICP elevation in experimental rats occurred with decreased CSF drainage capacity. Adjuvant testosterone, mimicking the androgen excess observed in female IIH patients, elevated the CSF secretion rate and thus ICP. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH.

k-Shape clustering for extracting macro-patterns in intracranial pressure signals.

BACKGROUND: Intracranial pressure (ICP) monitoring is a core component of neurosurgical diagnostics. With the introduction of telemetric monitoring devices in the last years, ICP monitoring has become feasible in a broader clinical setting including monitoring during full mobilization and at home, where a greater diversity of ICP waveforms are present. The need for identification of these variations, the so-called macro-patterns lasting seconds to minutes-emerges as a potential tool for better understanding the physiological underpinnings of patient symptoms. METHODS: We introduce a new methodology that serves as a foundation for future automatic macro-pattern identification in the ICP signal to comprehensively understand the appearance and distribution of these macro-patterns in the ICP signal and their clinical significance. Specifically, we describe an algorithm based on k-Shape clustering to build a standard library of such macro-patterns. RESULTS: In total, seven macro-patterns were extracted from the ICP signals. This macro-pattern library may be used as a basis for the classification of new ICP variation distributions based on clinical disease entities. CONCLUSIONS: We provide the starting point for future researchers to use a computational approach to characterize ICP recordings from a wide cohort of disorders.

Echogenic Surface Enhancements for Improving Needle Visualization in Ultrasound: A PRISMA Systematic Review.

Optimal visualization of needles in clinical ultrasound imaging is important and challenging, especially at steep angles. Improvement of visualization has been attempted with various techniques, for example, coatings and dimples. This systematic review summarizes enhancement techniques and identifies superior echogenic surface enhancements. Twenty-four papers were identified providing visibility measures for 33 different echogenic needles. These were grouped according to surface characteristics and ranked. Echogenic needles ranked higher than standard needles especially at steeper angles. Among the echogenic needles, coated needles were seemingly better visualized "in vivo" than noncoated needles, despite heterogeneity in study conditions. No unambiguous comparison revealed which needle was best visualized.

Empirical Mode Decomposition-Based Method for Artefact Removal in Raw Intracranial Pressure Signals.

Intracranial pressure (ICP) signals are often contaminated by artefacts and segments of missing values. Some of these artefacts can be observed as very high and short spikes with a physiologically impossible high slope. The presence of these spikes reduces the accuracy of pattern recognition techniques. Thus, we propose a modified empirical mode decomposition (EMD) method for spike removal in raw ICP signals. The EMD breaks down the signal into 16 intrinsic mode functions (IMFs), combines the first 4 to localize spikes using adaptive thresholding, and then either removes or imputes the identified ICP spikes.

Physical Model for Investigating Intracranial Pressure with Clinical Pressure Sensors and Diagnostic Ultrasound: Preliminary Results.

INTRODUCTION: Intracranial pressure (ICP) is a commonly collected neurocritical parameter, but accurate signal modelling remains challenging. The goal of this project was to mimic clinical ICP waveforms using a physical model. MATERIALS AND METHODS: A physical head model was developed. The skull was segmented from a head computed tomography (CT) scan, remodelled, 3D-printed, and filled with a brain tissue mimicking material and a pressure generator. Pressure measurements and tissue displacement around an attached pressure sensor were explored. RESULTS: Analysis of the measured pressure demonstrated that the waveform did not perfectly resemble that of the clinical ICP. Through iterative improvements and using a revised second pressure generator, subpeaks could be seen in the waveform. A speckle image recorded using ultrasound during pressure application enabled visualization of tissue displacement around the pressure sensor. Comparison with measured ICP signals revealed that minuscule patterns were not distinct in the displacement images. DISCUSSION: We present the first steps towards mimicking clinical ICP using a physical head phantom model. The physical model enabled pressure tests and visualization of tissue displacement and will be foundational for further improvements.

Preliminary study on the separation of specular reflection and backscattering components using synthetic aperture beamforming.

PURPOSE: In the early stages of atherosclerosis, the luminal surface of the arterial wall becomes rough due to injury and detachment of endothelial cells. This roughening can potentially be estimated with ultrasound since the electrical echo signal from the transducer is sensitive to both the angle of incidence to an extended surface as well as the roughness of the surface. Specifically, as the roughness of an interface increases, specular reflection is substituted by scattering. We propose a method that attempts separation of reflection and backscattering components in the received echo signals. METHOD: Assuming the predominant propagation directions of the reflected and scattered waves can be somewhat controlled by the emitted sound field, separation of those components was attempted using synthetic aperture imaging with a transmit beam, focused at a point more distant than the imaging depth. Specifically, two dedicated beamforming processes were used for generation of reflection-emphasized and backscattering-emphasized images. RESULT: Experimental verifications on a phantom using an ultrasound system with a limited number of active transmit-receive channels yielded a difference between these two images of 8 dB. The results further showed a similar (slightly improved) lateral spatial resolution size of 0.41 mm for the backscattering-emphasized image compared with conventional B-mode imaging (0.47 mm). CONCLUSION: A new technique for separation of the reflection and backscattering components using synthetic aperture beamforming with a transmit beam featuring a large focal distance was proposed. The technique demonstrated a partial separation of the reflection and backscattering components, which potentially may be used to estimate surface roughness.

B waves: a systematic review of terminology, characteristics, and analysis methods.

BACKGROUND: Although B waves were introduced as a concept in the analysis of intracranial pressure (ICP) recordings nearly 60 years ago, there is still a lack consensus on precise definitions, terminology, amplitude, frequency or origin. Several competing terms exist, addressing either their probable physiological origin or their physical characteristics. To better understand B wave characteristics and ease their detection, a literature review was carried out. METHODS: A systematic review protocol including search strategy and eligibility criteria was prepared in advance. A literature search was carried out using PubMed/MEDLINE, with the following search terms: B waves + review filter, slow waves + review filter, ICP B waves, slow ICP waves, slow vasogenic waves, Lundberg B waves, MOCAIP. RESULTS: In total, 19 different terms were found, B waves being the most common. These terminologies appear to be interchangeable and seem to be used indiscriminately, with some papers using more than five different terms. Definitions and etiologies are still unclear, which makes systematic and standardized detection difficult. CONCLUSIONS: Two future lines of action are available for automating macro-pattern identification in ICP signals: achieving strict agreement on morphological characteristics of "traditional" B waveforms, or starting a new with a fresh computerized approach for recognition of new clinically relevant patterns.

Investigations on the viscoelastic behaviour of a human healthy heel pad: in vivo compression tests and numerical analysis.

The aim of this study was to investigate the viscoelastic behaviour of the human heel pad by comparing the stress-relaxation curves obtained from a compression device used on an in vivo heel pad with those obtained from a three-dimensional computer-based subject-specific heel pad model subjected to external compression. The three-dimensional model was based on the anatomy revealed by magnetic resonance imaging of a 31-year-old healthy female. The calcaneal fat pad tissue was described with a viscohyperelastic model, while a fibre-reinforced hyperelastic model was formulated for the skin. All numerical analyses were performed to interpret the mechanical response of heel tissues, with loading conditions and displacement rate in agreement with experimental tests. The heel tissues showed a non-linear, viscoelastic behaviour described by characteristic hysteretic curves, stress-relaxation and viscous recovery phenomena. The reliability of the investigations was validated by the interpretation of the mechanical response of heel tissues under the application of three pistons with diameter of 15, 20 and 40 mm, at the same displacement rate of about 1.7 mm/s. The maximum and minimum relative errors were found to be less than 0.95 and 0.064, respectively.

Internal strain estimation for quantification of human heel pad elastic modulus: A phantom study.

Shock absorption is the most important function of the human heel pad. However, changes in heel pad elasticity, as seen in e.g. long-distance runners, diabetes patients, and victims of Falanga torture are affecting this function, often in a painful manner. Assessment of heel pad elasticity is usually based on one or a few strain measurements obtained by an external load-deformation system. The aim of this study was to develop a technique for quantitative measurements of heel pad elastic modulus based on several internal strain measures from within the heel pad by use of ultrasound images. Nine heel phantoms were manufactured featuring a combination of three heel pad stiffnesses and three heel pad thicknesses to model the normal human variation. Each phantom was tested in an indentation system comprising a 7MHz linear array ultrasound transducer, working as the indentor, and a connected load cell. Load-compression data and ultrasound B-mode images were simultaneously acquired in 19 compression steps of 0.1mm each. The internal tissue displacement was for each step calculated by a phase-based cross-correlation technique and internal strain maps were derived from these displacement maps. Elastic moduli were found from the resulting stress-strain curves. The elastic moduli made it possible to distinguish eight of nine phantoms from each other according to the manufactured stiffness and showed very little dependence of the thickness. Mean elastic moduli for the three soft, the three medium, and the three hard phantoms were 89kPa, 153kPa, and 168kPa, respectively. The combination of ultrasound images and force measurements provided an effective way of assessing the elastic properties of the heel pad due to the internal strain estimation.

Quantitative pupil analysis in stimulated emission depletion microscopy using phase retrieval.

The resolution attainable with stimulated emission depletion (STED) microscopy greatly depends on the quality of the STED laser focus. So far, visual inspection of a measured STED focus has been the only convenient means of gauging the source of aberrations. Here we describe a method, requiring no instrument modifications, for obtaining an equivalent to the complex pupil function at the back aperture of the objective and show that it provides quantitative information about aberration sources (including aberrations induced by the objective or sample). We show the accuracy of this field representation to be sufficient for reconstructing the STED focus in three dimensions and determining corrective steps.

Clinical performance diagnosing alleged exposure to falanga--a phantom study.

BACKGROUND: Falanga torture involves repetitive blunt trauma to the soles of the feet and typically leaves few detectable changes. Reduced elasticity in the heel pads has been reported as characteristic sequelae and palpatory testing of heel pad elasticity is therefore part of medicolegal assessment of alleged torture victims. OBJECTIVE: The goal was to test the accuracy of two experienced investigators in determining whether a heel pad model was soft, medium or hard. The skin-to-bone distance in the models varied within the human range. METHOD: Two blinded investigators independently palpated nine different heel pad models with three different elasticities combined with three different skin-to-bone distances in five consecutive trials and categorized the models as soft, medium or hard. RESULTS: Two experienced investigators were able to identify three known elasticities correctly in approximately two thirds of the cases. The skin-to-bone distance affected the accuracy. CONCLUSION: The use of clinical examination in documenting alleged exposure to torture warrants a high diagnostic accuracy of the applied tests. The study implies that palpatory testing of the human heel pad may not meet this demand. It is therefore recommended that a device able to perform an accurate measurement of the viscous-elastic properties of the heel pad be developed.

Diagnostic accuracy of heel pad palpation - a phantom study.

UNLABELLED: Falanga torture involves repetitive blunt trauma to the soles of the feet and typically leaves few detectable changes. Reduced elasticity in the heel pads has been reported as characteristic sequelae and palpatory testing of heel pad elasticity is therefore part of medicolegal assessment of alleged torture victims. The goal was to test the accuracy of two experienced investigators in determining whether a heel pad model was soft, medium or hard. The skin-to-bone distance in the models varied within the human range. METHOD: Two blinded investigators independently palpated nine different heel pad models with three different elasticities combined with three different skin-to-bone distances in five consecutive trials and categorized the models as soft, medium or hard. RESULTS: Two experienced investigators were able to identify three known elasticities correctly in approximately two thirds of the cases. The skin-to-bone distance affected the accuracy. CONCLUSION: The use of clinical examination in documenting alleged exposure to torture warrants a high diagnostic accuracy of the applied tests. The study implies that palpatory testing of the human heel pad may not meet this demand. It is therefore recommended that a device able to perform an accurate measurement of the viscous-elastic properties of the heel pad be developed.

An active learning approach to the physics of medical imaging.

This paper describes an experimentally oriented medical imaging course where the students record, process and analyse 3D data of an unknown piece of formalin fixed porcine tissue hidden in agar in order to estimate the tissue types present in a selected 2D slice. The recorded planar X-ray, CT, MRI, ultrasound and SPECT images show the tissue in very different ways. The students can only estimate the tissue type by studying the physical principles of the imaging modalities. The true answer is later revealed by anatomical photographs obtained from physical slicing. The paper describes the phantoms and methods used in the course. Sample images recorded with the different imaging modalities are provided. Challenges faced by the students are outlined. Results of the course show high increase in competencies as judged from graded reports, low course drop-out rate, high pass-rate at the exam, high student participation and large student satisfaction.

3D reconstruction of carotid atherosclerotic plaque: comparison between spatial compound ultrasound models and anatomical models.

This study deals with the creation of 3D models that can work as a tool for discriminating between tissue and background in the development of tissue classification methods. Ten formalin-fixed atherosclerotic carotid plaques removed by endarterectomy were scanned with 3D multi-angle spatial compound ultrasound (US) and subsequently sliced and photographed to produce a 3D anatomical data set. Outlines in the ultrasound data were found by means of active contours and combined into 10 3D ultrasound models. The plaque regions of the anatomical photographs were outlined manually and then combined into 10 3D anatomical models. The volumes of the anatomical models correlated with the volume found by a water displacement method (r = 0.95), except for an offset. The models were compared in three ways. Visual inspection showed quite good agreement between the models. The volumes of the ultrasound models correlated with the volumes of the anatomical models (r = 0.93), again with an offset. Finally, the overlap between the anatomical models and the ultrasound models showed, on average, that the intersection comprised 90%(vol) of the anatomical models and 73%(vol) of the ultrasound models.

PSF dedicated to estimation of displacement vectors for tissue elasticity imaging with ultrasound.

This paper investigates a new approach devoted to displacement vector estimation in ultrasound imaging. The main idea is to adapt the image formation to a given displacement estimation method to increase the precision of the estimation. The displacement is identified as the zero crossing of the phase of the complex cross-correlation between signals extracted from the lateral direction of the ultrasound RF image. For precise displacement estimation, a linearity of the phase slope is needed as well as a high phase slope. Consequently, a particular point spread function (PSF) dedicated to this estimator is designed. This PSF, showing oscillations in the lateral direction, leads to synthesis of lateral RF signals. The estimation is included in a 2-D displacement vector estimation method. The improvement of this approach is evaluated quantitatively by simulation studies. A comparison with a speckle tracking technique is also presented. The lateral oscillations improve both the speckle tracking estimation and our 2-D estimation method. Using our dedicated images, the precision of the estimation is improved by reducing the standard deviation of the lateral displacement error by a factor of 2 for speckle tracking and more than 3 with our method compared to using conventional images. Our method performs 7 times better than speckle tracking. Experimentally, the improvement in the case of a pure lateral translation reaches a factor of 7. Finally, the experimental feasibility of the 2-D displacement vector estimation is demonstrated on data acquired from a Cryogel phantom.

Echolucent, rupture-prone carotid plaques associated with elevated triglyceride-rich lipoproteins, particularly in women.

BACKGROUND: We tested whether fasting and postprandial triglyceride-rich lipoprotein elevations are gender specific (1) in patients with carotid artery stenosis >or=50% vs controls, and (2) in patients with echolucent, rupture-prone plaques compared with controls. METHODS AND RESULTS: We studied 66 controls and 323 patients with carotid artery stenosis >or=50%, of which 160 had echolucent plaques. Participants underwent a fat-tolerance test and carotid artery plaque evaluation with use of high-resolution B-mode ultrasound and computerized image analysis. By comparison, female cases with carotid stenosis >or=50% had higher fasting and postprandial triglyceride levels than did controls; however, this difference was not observed between male cases and controls. Fasting and postprandial very-low-density lipoprotein (VLDL) and intermediate density liprotein (IDL) cholesterol levels were elevated; low density lipoprotein (LDL) cholesterol level was unchanged, and high density lipoprotein (HDL) cholesterol level was reduced in both female and male cases vs controls. Fasting and postprandial triglyceride levels were elevated in women with echolucent plaques vs controls, but not in women with echo-rich plaques, or in men with echolucent or echo-rich plaques. Fasting and postprandial VLDL and IDL cholesterol levels were elevated, LDL cholesterol level was unchanged, and HDL cholesterol level was reduced in both female and male patients with echolucent plaques vs controls. CONCLUSIONS: Fasting and postprandial triglyceride-rich lipoproteins (but not LDLs) are elevated in patients with carotid artery stenosis of >or=50% compared with controls, and particularly identify echolucent, rupture-prone carotid plaques. These observations are more pronounced in women than in men.