Realistic 3D Phantoms for Validation of Microwave Sensing in Health Monitoring Applications.

The development of new medical-monitoring applications requires precise modeling of effects on the human body as well as the simulation and the emulation of realistic scenarios and conditions. The first aim of this paper is to develop realistic and adjustable 3D human-body emulation platforms that could be used for evaluating emerging microwave-based medical monitoring/sensing applications such as the detection of brain tumors, strokes, and breast cancers, as well as for capsule endoscopy studies. New phantom recipes are developed for microwave ranges for phantom molds with realistic shapes. The second aim is to validate the feasibility and reliability of using the phantoms for practical scenarios with electromagnetic simulations using tissue-layer models and biomedical antennas. The third aim is to investigate the impact of the water temperature in the phantom-cooking phase on the dielectric properties of the stabilized phantom. The evaluations show that the dielectric properties of the developed phantoms correspond closely to those of real human tissue. The error in dielectric properties varies between 0.5-8%. In the practical-scenario simulations, the differences obtained with phantoms-based simulations in S21 parameters are 0.1-13 dB. However, the differences are smaller in the frequency ranges used for medical applications.

Real-Time Tissue Classification Using a Novel Optical Needle Probe for Biopsy.

Core needle biopsy is a part of the histopathological process, which is required for cancerous tissue examination. The most common method to guide the needle inside of the body is ultrasound screening, which in greater part is also the only guidance method. Ultrasound screening requires user experience. Furthermore, patient involuntary movements such as breathing might introduce artifacts and blur the screen. Optically enhanced core needle biopsy probe could potentially aid interventional radiologists during this procedure, providing real-time information on tissue properties close to the needle tip, while it is advancing inside of the body. In this study, we used diffuse optical spectroscopy in a custom-made core needle probe for real-time tissue classification. Our aim was to provide initial characteristics of the smart needle probe in the differentiation of tissues and validate the basic purpose of the probe of informing about breaking into a desired organ. We collected optical spectra from rat blood, fat, heart, kidney, liver, lungs, and muscle tissues. Gathered data were analyzed for feature extraction and evaluation of two machine learning-based classifiers: support vector machine and k-nearest neighbors. Their performances on training data were compared using subject-independent k-fold cross-validation. The best classifier model was chosen and its feasibility for real-time automated tissue recognition and classification was then evaluated. The final model reached nearly 80% of correct real-time classification of rat organs when using the needle probe during real-time classification.

Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature.

BACKGROUND: Inside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation. METHODS: Blood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg-1 min-1) or the Ca2+-channel blocker (nicardipine hydrochloride, 0.5 µg kg-1 min-1) for 10, and 15 to 40 min, respectively. The effect of blood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy. RESULTS: Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (- 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes. CONCLUSIONS: This is the first study showing that cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid  flow.

Altered cerebrovascular-CSF coupling in Alzheimer's Disease measured by functional near-infrared spectroscopy.

In-vivo microscopical studies indicate that brain cerebrospinal fluid (CSF) transport driven by blood vessel pulsations is reduced in the early stages of Alzheimer's disease (AD). We hypothesized that the coupling pattern between cerebrovascular pulsations and CSF is altered in AD, and this can be measured using multi-wavelength functional near-infrared spectroscopy (fNIRS). To study this, we quantified simultaneously cerebral hemo- and CSF hydrodynamics in early AD patients and age-matched healthy controls. Physiological pulsations were analysed in the vasomotor very low frequency (VLF 0.008-0.1 Hz), respiratory (Resp. 0.1-0.6 Hz), and cardiac (Card. 0.6-5 Hz) bands. A sliding time window cross-correlation approach was used to estimate the temporal stability of the cerebrovascular-CSF coupling. We investigated how the lag time series variation of the coupling differs between AD patients and control. The couplings involving deoxyhemoglobin (HbR) and CSF water, along with their first derivative, in the cardiac band demonstrated significant difference between AD patients and controls. Furthermore, the lag time series variation of HbR-CSF in the cardiac band provided a significant relationship, p-value = 0.04 and r2 = 0.16, with the mini-mental state exam (MMSE) score. In conclusion, the coupling pattern between hemodynamics and CSF is reduced in AD and it correlates with MMSE score.

Acousto-Optics: Recent Studies and Medical Applications.

Development of acousto-optic (AO) techniques has made progress in recent years across a range of medical application fields, especially in improving resolution, detection speed, and imaging depth. This paper presents a comprehensive overview of recent advancements in AO-based techniques that have been presented after the previously published review in 2017. The survey covers a description of theoretical modeling strategies and numerical simulation methods as well as recent applications in medical fields. It also provides a comparison between different techniques in terms of complexity, achieved depth in tissue, and resolution. In addition, a comparison between different numerical simulation methods will be outlined. Additionally, a number of challenges faced by AO techniques are considered, particularly in the context of realistic in vivo imaging. Finally, the paper discusses prospects of AO-based medical diagnosis methods.

Cerebral tissue oxygenation response to brain irradiation measured during clinical radiotherapy.

Significance: Cancer therapy treatments produce extensive changes in the physiological and morphological properties of tissues, which are also individual dependent. Currently, a key challenge involves developing more tailored cancer therapy, and consequently, individual biological response measurement during therapy, such as tumor hypoxia, is of high interest. This is the first time human cerebral haemodynamics and cerebral tissue oxygenation index (TOI) changes were measured during the irradiation in clinical radiotherapy and functional near-infrared spectroscopy (fNIRS) technique was demonstrated as a feasible technique for clinical use in radiotherapy, based on 34 online patient measurements. Aim: Our aim is to develop predictive biomarkers and noninvasive real-time methods to establish the effect of radiotherapy during treatment as well as to optimize radiotherapy dose planning for individual patients. In particular, fNIRS-based technique could offer an effective and clinically feasible online technique for continuous monitoring of brain tissue hypoxia and responses to chemo- and radiotherapy, which involves modulating tumor oxygenation to increase or decrease tumor hypoxia. We aim to show that fNIRS is feasible for repeatability measuring in patient radiotherapy, the temporal alterations of tissue oxygenation induced by radiation. Approach: Fiber optics setup using multiwavelength fNIRS was built and combined with a medical linear accelerator to measure cerebral tissue oxygenation changes during the whole-brain radiotherapy treatment, where the radiation dose is given in whole brain area only preventing dosage to eyes. Correlation of temporal alterations in cerebral haemodynamics and TOI response to brain irradiation was quantified. Results: Online fNIRS patient measurement of cerebral haemodynamics during clinical brain radiotherapy is feasible in clinical environment, and results based on 34 patient measurements show strong temporal alterations in cerebral haemodynamics and decrease in TOI during brain irradiation and confirmed the repeatability. Our proof-of-concept study shows evidently that irradiation causes characteristic immediate changes in brain tissue oxygenation. Conclusions: In particular, TOI seems to be a sensitive parameter to observe the tissue effects of radiotherapy. Monitoring the real-time interactions between the subjected radiation dose and corresponding haemodynamic effects may provide important tool for the researchers and clinicians in the field of radiotherapy. Eventually, presented fNIRS technique could be used for improving dose planning and safety control for individual patients.

Photoacoustic Imaging in Biomedicine and Life Sciences.

Photo-acoustic imaging, also known as opto-acoustic imaging, has become a widely popular modality for biomedical applications. This hybrid technique possesses the advantages of high optical contrast and high ultrasonic resolution. Due to the distinct optical absorption properties of tissue compartments and main chromophores, photo-acoustics is able to non-invasively observe structural and functional variations within biological tissues including oxygenation and deoxygenation, blood vessels and spatial melanin distribution. The detection of acoustic waves produced by a pulsed laser source yields a high scaling range, from organ level photo-acoustic tomography to sub-cellular or even molecular imaging. This review discusses significant novel technical solutions utilising photo-acoustics and their applications in the fields of biomedicine and life sciences.

Blood pressure wave propagation-a multisensor setup for cerebral autoregulation studies.

Objective.Cerebral autoregulation is critically important to maintain proper brain perfusion and supply the brain with oxygenated blood. Non-invasive measures of blood pressure (BP) are critical in assessing cerebral autoregulation. Wave propagation velocity may be a useful technique to estimate BP but the effect of the location of the sensors on the readings has not been thoroughly examined. In this paper, we were interested in studying whether the propagation velocity of a pressure wave in the direction from the heart to the brain may differ compared with propagation from the heart to the periphery, as well as across different physiological tasks and/or health conditions. Using non-invasive sensors simultaneously placed at different locations of the human body allows for the study of how the propagation velocity of the pressure wave, based on pulse transit time (PTT), varies across different directions.Approach.We present a multi-sensor BP wave propagation measurement setup intended for cerebral autoregulation studies. The presented sensor setup consists of three sensors, one placed on each of the neck, chest and finger, allowing simultaneous measurement of changes in BP propagation velocity towards the brain and to the periphery. We show how commonly tested physiological tasks affect the relative changes of PTT and correlations with BP.Main results.We observed that during maximal blow, valsalva and breath hold breathing tasks, the relative changes of PTT were higher when PTT was measured in the direction from the heart to the brain than from the heart to the peripherals. In contrast, during a deep breathing task, the relative change in PTT from the heart to the brain was lower. In addition, we present a short literature review of the PTT methods used in brain research.Significance.These preliminary data suggest that the physiological task and direction of PTT measurement may affect relative PTT changes. The presented three-sensor setup provides an easy and neuroimaging compatible method for cerebral autoregulation studies by allowing measurement of BP wave propagation velocity towards the brain versus towards the periphery.

Photoplethysmography signal analysis to assess obesity, age group and hypertension.

Photoplethysmography (PPG) provides a simple, convenient and noninvasive method to assess pulse oximetry. Several attempts have been made to use PPG also to estimate blood pressure and arterial stiffness. This paper attempts to assess obesity classes, age group, and hypertension classes using PPG measured from the finger. One set of features was derived from the normalized pulse width of PPG and the other from original PPG. The features were calculated based on the pulse decomposition analysis using five lognormal functions and the up-slope of the PPG pulse. Using kNN and SVM as classifiers, the results were validated using leave-one-out validation. Performances of both features sets have no significant difference, and the kNN outperformed the SVM. The best accuracies are 93%, 88%, and 92% for obesity (5 classes), age group (7 classes), and hypertension (4 classes) respectively. These three assessment targets have a strong relationship with arterial stiffness, therefore it also leads to a study about arterial stiffness using PPG. Width normalization to 1 second might affect some features points based on pulse decomposition analysis. This study also found that the up-slope analysis might give good indices when width normalization was employed. However, these findings still require more experiments to gain conclusions that are more comprehensive.

Breath hold effect on cardiovascular brain pulsations - A multimodal magnetic resonance encephalography study.

Ultra-fast functional magnetic resonance encephalography (MREG) enables separate assessment of cardiovascular, respiratory, and vasomotor waves from brain pulsations without temporal aliasing. We examined effects of breath hold- (BH) related changes on cardiovascular brain pulsations using MREG to study the physiological nature of cerebrovascular reactivity. We used alternating 32 s BH and 88 s resting normoventilation (NV) to change brain pulsations during MREG combined with simultaneously measured respiration, continuous non-invasive blood pressure, and cortical near-infrared spectroscopy (NIRS) in healthy volunteers. Changes in classical resting-state network BOLD-like signal and cortical blood oxygenation were reproduced based on MREG and NIRS signals. Cardiovascular pulsation amplitudes of MREG signal from anterior cerebral artery, oxygenated hemoglobin concentration in frontal cortex, and blood pressure decreased after BH. MREG cardiovascular pulse amplitudes in cortical areas and sagittal sinus increased, while cerebrospinal fluid and white matter remained unchanged. Respiratory centers in the brainstem - hypothalamus - thalamus - amygdala network showed strongest increases in cardiovascular pulsation amplitude. The spatial propagation of averaged cardiovascular impulses altered as a function of successive BH runs. The spread of cardiovascular pulse cycles exhibited a decreasing spatial similarity over time. MREG portrayed spatiotemporally accurate respiratory network activity and cardiovascular pulsation dynamics related to BH challenges at an unpreceded high temporal resolution.

Assessment of the dynamics of human glymphatic system by near-infrared spectroscopy.

Fluctuations in brain water content has attracted increasing interest, particularly as regards studies of the glymphatic system, which is connected with the complex organization of dural lymphatic vessels, responsible for cleaning tissue. Disturbances of glymphatic circulation are associated with several brain disorders, including dementia. This article introduces an approach to noninvasive measurement of water dynamics in the human brain utilizing near-infrared spectroscopy (NIRS). We demonstrate the possibility to sense dynamic variations of water content between the skull and grey matter, for instance, in the subarachnoid space. Measured fluctuations in water content, especially in the cerebrospinal fluid (CSF), are assumed to be correlated with the dynamics of glymphatic circulation. The sampling volume for the NIRS optode was estimated by Monte Carlo modelling for the wavelengths of 660, 740, 830 and 980 nm. In addition, using combinations of these wavelengths, this article presents the calculation models for quantifying water and haemodynamics. The presented NIRS technique allows long-term functional brain monitoring, including sleeping time. Furthermore, it is used in combination with different magnetic neuroimaging techniques, particularly magnetic resonance encephalography. Using the combined setup, we report the preliminary results on the interaction between CSF and blood oxygen level-dependent fluctuations.

Real-time monitoring of human blood-brain barrier disruption.

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 µV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.

Multimodal brain imaging with magnetoencephalography: A method for measuring blood pressure and cardiorespiratory oscillations.

Studies with magnetoencephalography (MEG) are still quite rarely combined simultaneously with methods that can provide a metabolic dimension to MEG investigations. In addition, continuous blood pressure measurements which comply with MEG compatibility requirements are lacking. For instance, by combining methods reflecting neurovascular status one could obtain more information on low frequency fluctuations that have recently gained increasing interest as a mediator of functional connectivity within brain networks. This paper presents a multimodal brain imaging setup, capable to non-invasively and continuously measure cerebral hemodynamic, cardiorespiratory and blood pressure oscillations simultaneously with MEG. In the setup, all methods apart from MEG rely on the use of fibre optics. In particular, we present a method for measuring of blood pressure and cardiorespiratory oscillations continuously with MEG. The potential of this type of multimodal setup for brain research is demonstrated by our preliminary studies on human, showing effects of mild hypercapnia, gathered simultaneously with the presented modalities.

Synchronous multiscale neuroimaging environment for critically sampled physiological analysis of brain function: hepta-scan concept.

Functional connectivity of the resting-state networks of the brain is thought to be mediated by very-low-frequency fluctuations (VLFFs <0.1 Hz) in neuronal activity. However, vasomotor waves and cardiorespiratory pulsations influence indirect measures of brain function, such as the functional magnetic resonance imaging blood-oxygen-level-dependent (BOLD) signal. How strongly physiological oscillations correlate with spontaneous BOLD signals is not known, partially due to differences in the data-sampling rates of different methods. Recent ultrafast inverse imaging sequences, including magnetic resonance encephalography (MREG), enable critical sampling of these signals. In this study, we describe a multimodal concept, referred to as Hepta-scan, which incorporates synchronous MREG with scalp electroencephalography, near-infrared spectroscopy, noninvasive blood pressure, and anesthesia monitoring. Our preliminary results support the idea that, in the absence of aliased cardiorespiratory signals, VLFFs in the BOLD signal are affected by vasomotor and electrophysiological sources. Further, MREG signals showed a high correlation coefficient between the ventromedial default mode network (DMNvmpf) and electrophysiological signals, especially in the VLF range. Also, oxy- and deoxyhemoglobin and vasomotor waves were found to correlate with DMNvmpf. Intriguingly, usage of shorter time windows in these correlation measurements produced significantly (p<0.05) higher positive and negative correlation coefficients, suggesting temporal nonstationary behavior between the measurements. Focus on the VLF range strongly increased correlation strength.

Fibre optic sensor for non-invasive monitoring of blood pressure during MRI scanning.

This report focuses on designing and implementing a non-invasive blood pressure (NIBP) measuring device capable of being used during magnetic resonance imaging (MRI). Based on measuring pulse wave velocity in arterial blood, the device uses the obtained result to estimate diastolic blood pressure. Pulse transit times are measured by two fibre optical accelerometers placed over the chest and carotid artery. The fabricated accelerometer contains two static fibres and a cantilever beam, whose free end is angled at 90 degrees to act as a reflecting surface. Optical fibres are used for both illuminating the surface and receiving the reflected light. When acceleration is applied to the sensor, it causes a deflection in the beam, thereby changing the amount of reflected light. The sensor's output voltage is proportional to the intensity of the reflected light. Tests conducted on the electronics and sensors inside an MRI room during scanning proved that the device is MR- compatible. No artifacts or distortions were detected.