Teemu Myllylä

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 sensors 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.

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.

Light Propagation in NIR Spectroscopy of the Human Brain

In study of the brain, oxygenation changes in the cerebral cortex are of great interest, since the concentrations of oxyhaemoglobin and deoxyhaemoglobin change due to coupling of hemodynamics to cortical neural activity. In order to non-invasively monitor oxygenation in the cerebral cortex by near-infrared spectroscopy (NIRS), light should penetrate into brain tissue to a depth of approximately 1-2 cm. Many studies show that by increasing the source-detector distance, illuminating light penetrates deeper into brain tissue. Using tissue-mimicking phantom measurements, forehead in vivo measurements, and Monte Carlo (MC) simulations, this paper estimates light propagation in the brain and the minimum source-detector distance to allow sensing of the cerebral cortex. We present optical sensing of a pulsating aqueous intralipid suspension in a vessel located at different depths within a multilayered phantom of the human forehead. Experimental results are compared with the MC simulations accounting for the optical properties of the phantom. The thickness and morphology of the different tissue layers were obtained from an anatomical magnetic resonance image of a test subjects head. Results from these three methods correlate with each other and show that the brain cortex can be sensed with optical methods based on NIRS.

Human Heart Pulse Wave Responses Measured Simultaneously at Several Sensor Placements by Two MR-Compatible Fibre Optic Methods

This paper presents experimental measurements conducted using two noninvasive fibre optic methods for detecting heart pulse waves in the human body. Both methods can be used in conjunction with magnetic resonance imaging (MRI). For comparison, the paper also performs an MRI-compatible electrocardiogram (ECG) measurement. By the simultaneous use of different measurement methods, the propagation of pressure waves generated by each heart pulse can be sensed extensively in different areas of the human body and at different depths, for example, on the chest and forehead and at the fingertip. An accurate determination of a pulse wave allows calculating the pulse transit time (PTT) of a particular heart pulse in different parts of the human body. This result can then be used to estimate the pulse wave velocity of blood flow in different places. Both measurement methods are realized using magnetic resonance-compatible fibres, which makes the methods applicable to the MRI environment. One of the developed sensors is an extraordinary accelerometer sensor, while the other one is a more common sensor based on photoplethysmography. All measurements, involving several test patients, were performed both inside and outside an MRI room. Measurements inside the MRI room were conducted using a 3-Tesla strength closed MRI scanner in the Department of Diagnostic Radiology at the Oulu University Hospital.

Optical sensing of a pulsating liquid in a brain-mimicking phantom

In study of the brain, oxygenation changes in the cerebral cortex are increasingly monitored using optical methods based on near-infrared spectroscopy (NIRS). When monitoring blood oxygenation in the cerebral cortex, at depth of approximately 15 mm - 20 mm from the skin surface, separation distance between source and detector becomes significant. Many studies show that by increasing the source-detector distance, illuminating light penetrates deeper into tissue. In this work, we use optical phantoms to determine experimentally the minimum source-detector distance between that allows sensing of the cerebral cortex, particularly the grey matter of the brain. A multilayered forehead phantom was fabricated and a silicon tube was added inside the phantom at depths of 15 mm and 19 mm, measured from the surface of the skin mimicking layer. This depth corresponds to the grey matter layer of the brain. The phantom’s optical properties were specifically designed to mimic the optical properties of tissue layers of the forehead and to facilitate near-infrared sensing. Optical sensing of liquid movement within the tube was measured by varying the distance between the near-infrared light source and the detector. Based on our measurements, we can conclude that it is possible to sense pulsations from a grey matter mimicking layer of the brain using near-infrared spectroscopy at a source-detector distance of 3 - 4 cm.

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

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.

MEMS Technology Sensors as a More Advantageous Technique for Measuring Foot Plantar Pressure and Balance in Humans

Locomotor activities are part and parcel of daily human life. During walking or running, feet are subjected to high plantar pressure, leading sometimes to limb problems, pain, or foot ulceration. A current objective in foot plantar pressure measurements is developing sensors that are small in size, lightweight, and energy efficient, while enabling high mobility, particularly for wearable applications. Moreover, improvements in spatial resolution, accuracy, and sensitivity are of interest. Sensors with improved sensing techniques can be applied to a variety of research problems: diagnosing limb problems, footwear design, or injury prevention. This paper reviews commercially available sensors used in foot plantar pressure measurements and proposes the utilization of pressure sensors based on the MEMS (microelectromechanical systems) technique. Pressure sensors based on this technique have the capacity to measure pressure with high accuracy and linearity up to high pressure levels. Moreover, being small in size, they are highly suitable for this type of measurement. We present two MEMS sensor models and study their suitability for the intended purpose by performing several experiments. Preliminary results indicate that the sensors are indeed suitable for measuring foot plantar pressure. Importantly, by measuring pressure continuously, they can also be utilized for body balance measurements.

Assessment of the dynamics of human glymphatic system by near-infrared spectroscopy (NIRS)

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.

Experimental studies with selected light sources for NIRS of brain tissue: quantifying tissue chromophore concentration

Near-infrared spectroscopy (NIRS) based techniques are utilised in quantifying changes of chromophore concentrations in tissue. Particularly, non-invasive in vivo measurements of tissue oxygenation in the cerebral cortex are of interest. The measurement method is based on illuminating tissue and measuring the back-scattered light at wavelengths of interest. Tissue illumination can be realised using different techniques and various light sources. Commonly, lasers and laser diodes (LD) are utilised, but also high-power light emitting diodes (HPLED) are becoming more common. At the moment, a wide range of available narrow-band light sources exists, covering basically the entire spectrum of interest in brain tissue NIRS measurements. In this paper, in the centre of our interest are LDs and HPLEDs, because of their affordability, efficiency in terms of radiant flux versus size and easiness to adopt in in vivo medical applications. We compare characteristics of LDs and HPLEDs at specific wavelengths and their suitability for in vivo quantifying of different tissue chromophore concentration, particularly in cerebral blood flow (CBF). A special focus is on shape and width of the wavelength bands of interest, generated by the LDs and HPLEDs. Moreover, we experimentally study such effects as, spectroscopy cross talk, separability and signal-to-noise ratio (SNR) when quantifying tissue chromophore concentration. Chromophores of our interest are cytochrome, haemoglobin and water. Various LDs and HPLEDs, producing narrow-band wavelengths in the range from 500 nm to 1000 nm are tested.