BM402: Engineering in Medicine - Course Outline PDF

BM402: ENGINEERING IN MEDICINE 10th October 2024 M 2170 – South Campus TENTATIVE COURSE OUTLINE 􀀀 Introduction to Engineering in Medicine 􀀀 Human Anatomy and Physiology 􀀀 Biomedical Instrumentation and Signal Processing: E.g., Sensors, medical devices (e.g., E...

BM402: ENGINEERING IN MEDICINE 10th October 2024 M 2170 – South Campus TENTATIVE COURSE OUTLINE 􀀀 Introduction to Engineering in Medicine 􀀀 Human Anatomy and Physiology 􀀀 Biomedical Instrumentation and Signal Processing: E.g., Sensors, medical devices (e.g., EEG, ECG, pulse oximeters) 􀀀 Medical Imaging I – Introduction to Imaging Modalities (e.g., Xray, CT, PET) 􀀀 Medical Imaging II – MRI and Multimodal Imaging (e.g., EEG-fMRI, PET-MRI) 􀀀 Rehabilitation Technologies and Neurofeedback 􀀀 Midterm TODAY’S SCHEDULE Classification of animals/brains Anatomy of the brain Brain function and physiology Measures of physiology CLASSIFICATION OF ANIMALS (BRAINS) Invertebrates & vertebrates (without and with backbone) Invertebrates All animals have to respond to changes in their internal and external environment in order to survive. To do this, they have evolved cells that are sensitive to stimuli such as light and sound. The sensory cells are, in turn, connected to other cells that can move the organism or change its state in response to the stimulus. In invertebrates, such as worms, the nervous system is distributed throughout the creature’s body, as a loose network of reactive fibers. Some of these networks contain small masses of nerves, known as ganglia. INVERTEBRATE BRAIN PRIMITIVE NERVOUS SYSTEM The simplest system, as seen in this hydra (a tiny aquatic invertebrate), consists of a loose network of sensory cells with clumps of interconnected cells called ganglia. Ganglia INVERTEBRATE BRAIN PRIMITIVE NERVOUS SYSTEM EARTHWORM BRAIN The simplest system, as seen in this hydra (a The earthworm has a crude brain, the tiny aquatic invertebrate), consists of a loose cerebral ganglion, which is connected network of sensory cells with clumps of to a cord of nervous tissue (the ventral interconnected cells called ganglia. nerve cord) that runs the length of its body. Nerve fibers from the cord extend into each segment, so muscle contraction along the body can be coordinated to produce movement Ganglia in response to stimuli. VERTEBRATE BRAIN Through the course of evolution, the brain has undergone considerable changes. Compared to the primitive nervous systems of invertebrates, the brain of vertebrates is a well-developed, highly interconnected organ. The central nervous system is connected to the rest of the body by a peripheral nervous system that includes the fibers running to and from the sensory organs. The basic vertebrate brain—also sometimes referred to as the “reptilian brain”— consists of the cluster of nuclei that lies just above the brainstem in humans. They include the The cerebellum, which means “little modules that produce arousal, sensation, and reaction to brain,” is a part of the brain involved in stimuli. coordinating movement and balance. This basic vertebrate brain does not include more advanced Regulates growth, metabolism, and features, such as the limbic system or cerebral cortex, which reproduction through the hormones that it produces. exist only in the brains of mammals. Sense of smell VERTEBRATE BRAIN MAMMAL BRAINS The mammalian brain comprises a cluster of structures that evolved on top of the basic vertebrate brain, known as the limbic system, and a wrinkled covering called the cortex, which interconnects with the limbic structures beneath. The limbic system is the part of the brain that produces emotions. - goes beyond the basic “grab” or “avoid” reactions in the vertebrate brain. The limbic system also contains structures that encode experiences as memories, to be recalled for use in guiding future actions. The emotional and memory faculties greatly increase the range and complexity of behavior that a mammal displays, because it is not governed purely by instinct. MAMMAL BRAINS BRAIN SIZE AND SHAPE One striking aspect of mammalian brain evolution is the development of the cortex. This outer layer has evolved to serve the particular needs of each species, and therefore varies dramatically between one animal and another. A few mammals, such as humans, elephants, and dolphins, have a disproportionately large cortex compared to most mammals. MAMMAL BRAINS BRAIN SIZE AND SHAPE One striking aspect of mammalian brain evolution is the development of the cortex. This outer layer has evolved to serve the particular needs of each species, and therefore varies dramatically between one animal and another. A few mammals, such as humans, elephants, and dolphins, have a disproportionately large cortex compared to most mammals. HOMINID BRAINS The brains of hominids (modern humans and their ancestors) underwent a surge of evolutionary changes that left them, in some ways, distinctly different even from their near relatives, such as chimpanzees and gorillas. The main distinction between human and other mammalian brains is the size and density of the cortex, and particularly of the frontal lobe, which is responsible for complex thought, conscious judgement, and self-reflection. MAMMAL BRAINS The cerebellum, which means “little brain,” is a part of the brain involved in coordinating movement and balance. Regulates growth, metabolism, and reproduction through the hormones that it produces. Sense of smell HUMAN BRAIN True or False ? 1. The average brain weighs about 1.4 kg. ? 2. The brain is attached to the skull. ? 3. There are six lobes in each hemisphere. ? 4. The brain floats in cerebrospinal fluid. ? 5. Neurons are the basic brain cells. ? 6. The brain communicates via chemicals. ? 7. Each lobe of the brain has specific functions. HUMAN BRAIN True or False T 1. The average brain weighs about 1.4 kg. F 2. The brain is attached to the skull. F 3. There are six lobes in each hemisphere. T 4. The brain floats in cerebrospinal fluid. T 5. Neurons are the basic brain cells. T 6. The brain communicates via chemicals. T 7. Each lobe of the brain has specific functions. HUMAN BRAIN Brain anatomy is hidden, secret, and more complex than any other part of the body. Controls thought, memory, emotion, touch, motor skills, vision, breathing, temperature, hunger and every process that regulates our body. Together, the brain and spinal cord that extends from it make up the central nervous system, or CNS. Gray and white matter are two different regions of the central nervous system. In the brain, gray matter refers to the darker, outer portion, while white matter describes the lighter, inner section underneath. HUMAN BRAIN Gray and white matter are two different regions of the central nervous system. In the brain, gray matter refers to the darker, outer portion, while white matter describes the lighter, inner section underneath. The central nervous system of the brain is made up of two kinds of tissue: gray matter and white matter. The gray matter contains the cell bodies, dendrites and the axon terminals, where all synapses are. The white matter is made up of axons, which connect different parts of grey matter to each other. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS The brain can be divided into three basic units: the forebrain, the midbrain, and the hindbrain. The hindbrain includes the upper part of the spinal cord, the brain stem, and a wrinkled ball of tissue called the cerebellum. The hindbrain controls the body’s vital functions such as respiration and heart rate. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS The brain can be divided into three basic units: the forebrain, the midbrain, and the hindbrain. The uppermost part of the brainstem is the midbrain. This small but important structure plays a crucial role in reflex actions, and processing visual and auditory signals. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS The brain can be divided into three basic units: the forebrain, the midbrain, and the hindbrain. The forebrain is the largest and most highly developed part of the human brain: - contains the entire cerebrum and several structures directly nestled within it - the thalamus, hypothalamus, the pineal gland and the limbic system. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS At a higher level, the brain can be divided into the cerebrum, brainstem and cerebellum. Cerebrum The cerebrum (front of brain) comprises gray matter (the cerebral cortex) and white matter at its center. - speech, judgment, thinking and reasoning, problem-solving, emotions and learning; other functions related to vision, hearing, touch etc. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS The cerebral cortex is divided into two halves, or hemispheres. It is covered with ridges (gyri) and folds (sulci). - consists of four lobes: frontal, parietal, temporal and occipital. Each of these lobes is responsible for processing different types of information. - responsible for the higher-level processes of the human brain, including language, memory, reasoning, thought, learning, decision-making, emotion, intelligence and personality. FRONTAL LOBE The largest lobe of the brain, located in the front of the head. Some functions of the frontal lobe: Speech and language production: Broca’s area, a region in the frontal lobe, helps put thoughts into words. Damage to this area can lead to difficulty with fluent speech. Some motor skills: The frontal lobe houses the primary motor cortex, which helps control voluntary movements, including walking and running. And more.. Decision-making, problem-solving. Conscious thought. Attention. Emotional and behavioral control. Personality. OCCIPITAL, PARIETAL AND TEMPORAL LOBES Occipital lobes: These lobes in the back of your brain allow you to notice and interpret visual information. Your occipital lobes control how you process shapes, colors and movement. OCCIPITAL, PARIETAL AND TEMPORAL LOBES Occipital lobes: These lobes in the back of your brain allow you to notice and interpret visual information. Your occipital lobes control how you process shapes, colors and movement. Parietal lobe: The middle part of the brain, the parietal lobe helps a person identify objects, integrates many sensory inputs so that you can understand your environment and the state of your body. The parietal lobe is also involved in interpreting pain and touch in the body. Temporal lobes: These parts of the brain are near your ears on each side of your brain. The temporal lobes are involved in short-term memory and processing auditory information. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS At a higher level, the brain can be divided into the cerebrum, brainstem and cerebellum. Brainstem - connects the cerebrum of the brain to the spinal cord and cerebellum. - responsible for many vital functions of life. - regulates many automatic body functions. You don’t consciously control these functions, like your heart rate, breathing, sleep and wake cycles, and swallowing. - connects the rest of your brain to your spinal cord. MAIN PARTS OF THE BRAIN AND THEIR FUNCTIONS At a higher level, the brain can be divided into the cerebrum, brainstem and cerebellum. Cerebellum - maintains your balance, posture, coordination and fine motor skills. It's located in the back of your brain. - While it's very small compared to your brain overall, it holds more than half of the neurons (cells that make up your nervous system) in your whole body. CEREBROSPINAL FLUID (CSF) Cerebrospinal fluid is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. Main functions: - Protection - Nourishment - Waste removal OVERVIEW (10 MINUTES) ? 1. Breathing ? 2. Sensory Integration 1. Brainstem ? 3. Vision 2. Cerebellum ? 4. Judgment 3. Occipital Lobes ? 5. Swallowing 4. Parietal Lobes ? 6. Language 5. Temporal Lobes ? 7. Recognition of Printed Words 6. Frontal Lobes ? 8. Balance ? 9. Control of Emotional Response ? 10. Attention ? 11. Hearing Ability ? 12. Touch Perception ? 13. Coordination ? 14. Memory Acquisition ? 15. Categorization of Objects Brainstem BREAK (10 MINUTES) TENTATIVE COURSE OUTLINE 􀀀 Introduction to Engineering in Medicine 􀀀 Human Anatomy and Physiology 􀀀 Biomedical Instrumentation and Signal Processing: E.g., Sensors, medical devices (e.g., EEG, ECG, pulse oximeters) 􀀀 Medical Imaging I – Introduction to Imaging Modalities (e.g., Xray, CT, PET) 􀀀 Medical Imaging II – MRI and Multimodal Imaging (e.g., EEG-fMRI, PET-MRI) 􀀀 Rehabilitation Technologies and Neurofeedback 􀀀 Midterm Overview on CNS and PNS Central nervous system Central nervous system Brain Cerebrum: higher-level thinking Cerebellum: balance and coordination Brainstem: heart rate and breathing Central nervous system Brain Corpus callosum: large white matter nerve tract, movement control, cognitive functions, and vision. Central nervous system Brain Corpus callosum: large white matter nerve tract, movement control, cognitive functions, and vision. Grey and white matter mostly neuron cell bodies, as well as dendrites, which are the short, branching projections that receive signals from other neurons. Central nervous system Brain Corpus callosum: large white matter nerve tract, movement control, cognitive functions, and vision. Grey and white matter mostly axons that are coated with myelin, a fatty substance that insulates and speeds up the transmission of electrical signals between neurons. Central nervous system Brain Thalamus: mostly grey matter, acts as a relay station between brain and body. Except for olfaction very sensory system has a thalamic nucleus that receives, processes, and sends information to an associated cortical area. Hypothalamus: Central nervous system Brain Thalamus: mostly grey matter, acts as a relay station between brain and body. Except for olfaction very sensory system has a thalamic nucleus that receives, processes, and sends information to an associated cortical area. Hypothalamus: main link between your endocrine system and your nervous system. - produces certain hormones that are stored elsewhere (e.g., Helps manage your: Body temperature, the posterior pituitary). blood pressure, hunger and thirst, mood, - sends signals (hormones) to the pituitary gland, which then sleep etc. releases hormones that directly affect specific body parts. Central nervous system Brain Pituitary gland: Structure: Located at the base of the brain Divided into two main parts: the anterior pituitary and the posterior pituitary - Anterior pituitary produces and secretes hormones. - Posterior pituitary stores and releases hormones produced by the hypothalamus. Central nervous system Brain Pituitary gland: Function: - Regulates growth, development, and metabolism - Produces and secretes hormones: e.g., growth hormone, and thyroid- stimulating hormone. - Stores and releases hormones produced by the hypothalamus: e.g., oxytocin and vasopressin. Central nervous system Spinal Cord - long, thin, tubular structure that runs from the brainstem to the lower back. It is a vital part of the CNS and plays several important functions, including: - Sensory processing - Motor function - Reflexes - Autonomic functions - Rapid responses to stimuli Central nervous system Spinal Cord - long, thin, tubular structure that runs from the brainstem to the lower back. It is a vital part of the CNS and plays several important functions, including: - Sensory processing - Motor function - Reflexes - Autonomic functions - Rapid responses to stimuli Peripheral nervous system Peripheral nervous system Somatic nervous system Autonomic nervous system sympathetic nervous system parasympathetic nervous system Peripheral nervous system Somatic nervous system - responsible for carrying sensory information from the body to the CNS and for transmitting motor commands from the CNS to the muscles that control voluntary movements. - includes the sensory neurons that detect stimuli such as touch, pain, and temperature, as well as the motor neurons that control skeletal muscles. Peripheral nervous system Autonomic nervous system "fight or flight" response. When activated, it increases heart rate, constricts blood vessels, and dilates the airways in order to prepare the body for action. Peripheral nervous system Autonomic nervous system "fight or flight" response. When activated, it causes the release of adrenaline and other stress hormones, which increase heart rate and blood pressure, dilate the pupils. Peripheral nervous system Autonomic nervous system "rest and digest" response. When activated, it slows heart rate, stimulates digestion, and promotes relaxation. Peripheral nervous system Autonomic nervous system "rest and digest" response. When activated, it slows heart rate, stimulates digestion, and promotes relaxation. Nervous system, brain and physiology The brain and nervous system work together to regulate and coordinate physiological processes throughout the body. For example, the hypothalamus in the brain is responsible for regulating body temperature, hunger, thirst, and the release of hormones from the pituitary gland. Nervous system, brain and physiology The brain and nervous system work together to regulate and coordinate physiological processes throughout the body. For example, the Overall, the nervous hypothalamus in the brain is system, physiology, and responsible for regulating brain are intricately body temperature, hunger, interconnected, with the thirst, and the release of brain playing a crucial role hormones from the pituitary in controlling and gland. coordinating physiological processes throughout the body. Measures of physiology in the concept of engineering in medicine Measures of physiology & devices Data Acquisition Systems Amplifiers and Modules Transducers and Sensors Software Measures of physiology & devices Measures of physiology & devices Measures of physiology & devices Let’s spend 10 minutes on the webpage Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt transducer Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt amplifier transducer Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt Measurement of Respiratory Parameters: respiration rate (breaths per minute) and tidal volume (the amount of air inhaled or exhaled with each breath) Strain Gauge Technology: - The device typically uses strain gauge technology to measure the expansion and contraction of the thorax or abdomen during breathing. - As the chest or abdominal area expands and contracts, the strain gauge detects these changes and converts them into electrical signals. - Non-invasive - Real-time monitoring - Data output and analysis - Can be MR-compatible Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt Normal data – relaxed sitting subject Normal data – talking Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt Normal data – relaxed sitting subject What do you think? Normal data – talking Measures of physiology and devices 2. Pulse Oximetry & Photoplethysmography: - Device: Pulse Oximeter A photoplethysmogram (PPG) is an optically obtained plethysmogram that can be used to detect blood volume changes from the fingertip. transducer A PPG is often obtained by using a pulse oximeter which illuminates the skin and measures changes in light absorption. Measures of physiology and devices 2. Pulse Oximetry & Photoplethysmography: - Device: Pulse Oximeter - The light passing through the tissue (finger, ear, or toe) is partially absorbed by the blood's hemoglobin. The photodetector in the oximeter transducer captures the remaining light, producing an electrical signal. - Since the signals generated by the light absorption are often very weak, the amplifier boosts these signals to a level that can be processed by the device. Measures of physiology and devices 2. Pulse Oximetry & Photoplethysmography: - Device: Pulse Oximeter transducer Measures of physiology and devices 1. Respiration Rate and Volume (RVT) - Device: Respiratory Inductive Plethysmography (RIP) Belt 2. Pulse Oximetry & Photoplethysmography: - Device: Pulse Oximeter 3. Blood Pressure: - Device: Sphygmomanometer 4. Galvanic Skin Response (GSR) / Skin Conductance: - Device: GSR Sensor 5. Pupillometry: - Device: Pupillometer, eye camera 6. Temperature - Device: Thermometer, skin temperature sensor And more.. Electrocardiography (ECG), Electroencephalography (EEG), Electromyography (EMG)  PPG and respiratory signal variations Raw respiratory signal Respiratory volume per time Raw PPG signal 0 10 20 30 40 50 60 time (sec) What could be the task? A photoplethysmogram (PPG) is an optically obtained plethysmogram that can be used to detect blood Before DB After DB volume changes from the fingertip. A PPG is often obtained by using a pulse oximeter which illuminates the skin and measures changes in light absorption. BM402: ENGINEERING IN MEDICINE 17th October 2024 M 2170 – South Campus MRI Functional MRI Applications of MRI and fMRI EEG Applications of EEG Multimodal Imaging MRI: ANATOMICAL SCAN Acıbadem Altunizade Hospital Siemens 3 T MR Scanner Sagittal view Axial view Healthy volunteer FMRI: FUNCTIONAL SCAN Functional networks Veer et al. 2010 MAGNETIC RESONANCE IMAGING: MRI The MRI scanner is essentially a giant magnet. The strength of the magnet is measured in a unit called Tesla (T). The earth’s magnetic field is around 0.00006 T. A 3 T MRI scanner is around 50,000 times stronger than the earth’s magnetic field! Most (clinical) MRI scanners used in hospitals and medical research clinics are 1.5 or 3 T, while some research scanners are at fields of 7 T, 10.4 T and 11.7 T. INSTALLATION OF 11.7 T Giant Magnet 11.7 T, NeuroSpin 16.03.2019, NIH, Bethesda, MD, USA 5 meters long, 5 meters in diameter, and It will require about 35,000 liters of helium to cool the weighs over 130 metric tons superconductive coils that create the magnetic field. ~380 tons of steel were needed to prevent the magnet’s field from interfering with other equipment in the building. Unboxing - World's Most Powerful Brain Scanner - YouTube HOW MRI WORKS HOW MRI WORKS HOW MRI WORKS HOW MRI WORKS HOW MRI WORKS Some Glossary B0: ↑ The MRI scanner’s main magnetic field. Precessional Frequency: ↑ The rate at which protons spin in a magnetic field. RF: ↑ Radio frequency pulse (also referred as B1) used to tip on resonance protons away from the B0 field. On Resonance: ↑ Have the same frequency. Fourier Transform: ↑ A mathematical calculation that is used to change the electrical current in a coil into an image. HOW MRI WORKS Some Glossary B0: ↑ The MRI scanner’s main magnetic field. Precessional Frequency: ↑ The rate at which protons spin in a magnetic field. RF: ↑ Radio frequency pulse (also referred as B1) used to tip on resonance protons away from the B0 field. On Resonance: ↑ Have the same frequency. Fourier Transform: ↑ A mathematical calculation that is used to change the electrical current in a coil into an image. The natural precession frequency of a spin system is also known as the Larmor frequency. HOW MRI WORKS: PRECESSION The natural precession frequency of a spin system is also known as the Larmor frequency. ω = γB where ω is the Larmor frequency in MHz, γ is the gyromagnetic ratio in MHz/tesla and γ is a constant specific to each specific nucleus or particle (e.g., H-1=42.58); and B is the strength of the static magnetic field in tesla. Larmor, 1857 – 1942 HOW MRI WORKS: FOCUSING OUR IMAGING Head coil HOW MRI WORKS: FOCUSING OUR IMAGING Head coil HOW MRI WORKS: IMAGE FORMATION Ridgway, 2010 FOURIER TRANSFORM Converting from k-space to image space In image space, the basic sampling unit is distance; in k-space, the basic sampling unit is spatial frequency (1/distance). Qualitatively speaking, a wider range of coverage in k-space results in higherspatial resolution in image space (i.e., smaller voxels). Dr. Seiji Ogawa Converting from k-space to image space Different parts of the k-space data correspond to different spatial-frequency components of the image. The center of k-space (B) provides low-spatial frequency information, retaining most of the signal but not fine details. The periphery of k-space (C) provides high spatial-frequency information, and thus more image detail, but it contributes relatively little signal to the image. Dr. Seiji Ogawa Converting from k-space to image space Different parts of the k-space data correspond to different spatial-frequency components of the image. The center of k-space (B) provides low-spatial frequency information, retaining most of the signal but not fine details. The periphery of k-space (C) provides high spatial-frequency information, and thus more image detail, but it contributes relatively little signal to the image. Dr. Seiji Ogawa FIRST MR IMAGE 2003 Nobel Prize in Physiology or Medicine was not awarded for the discovery of the medical applications of MR, but for the development of techniques for image formation. FIRST MR IMAGE 2003 Nobel Prize in Physiology or Medicine was not awarded for the discovery of the medical applications of MR, but for the development of techniques for image formation. On October 12, 2003, the Nobel Committee on Physiology and Medicine awarded the Nobel Prize to Paul Lauterbur and Sir Peter Mansfield for MRI. MRI BASICS As Rabi used a strong magnetic field to measure spin properties of nuclei, today’s MRI scanners use a strong magnetic field to induce changes in proton spin. Just as Bloch detected nuclear induction using transmitter and receiver coils, scanners now use similar coil systems to obtain MR signals. Configuration of the gradient coils used for spatial encoding in all three dimensions. Transceiver indicates And, just as Lauterbur manipulated the the RF system comprising a transmitter, coil and magnetic field strength using changing receiver (Coyne 2012). gradient fields to create an image, almost every current MRI study relies on magnetic gradients for image acquisition. 1.5 T 3T 7T MRI HARDWARE Static magnetic field Gradient coils Gradients are loops of wire or thin conductive sheets on a cylindrical shell Configuration of the gradient coils used for spatial lying just inside the bore of an MR scanner. encoding in all three dimensions (Coyne 2012). When current is passed through these coils a secondary magnetic field is created. This gradient field slightly distorts the main magnetic field in a predictable pattern, causing the resonance frequency of protons to vary in as a function of position. The primary function of gradients, therefore, is to allow spatial encoding of the MR signal. MRI HARDWARE Static magnetic field Gradient coils RF coils RF coils are the antennas of the MRI system and have two functions: first, to excite the magnetization by broadcasting the RF power (Tx‐Coil) and second to receive the signal from the excited spins (Rx‐Coil). MRI HARDWARE Static magnetic field Gradient coils RF coils Shimming coils Other necessary parts are the shimming coils that ensure the homogeneity of the static magnetic field; specialized computer systems for controlling the scanner; and the experimental task, and physiological monitoring equipment. BASICS OF MR IMAGE CONTRAST (T1, T2, T2*) T1 and T2 are inherent properties of tissues and are thus fixed for a specific tissue (at a given magnetic field strength). The parameter T2*, however, also depends on inhomogeneities in the main magnetic field, but again is fixed for a specific tissue within a given external magnetic environment. BASICS OF MR IMAGE CONTRAST (T1, T2, T2*) T1 and T2 are inherent properties of tissues and are thus fixed for a specific tissue (at a given magnetic field strength). The parameter T2*, however, also depends on inhomogeneities in the main magnetic field, but again is fixed for a specific tissue within a given external magnetic environment. RF OFF: The spins will go back to the lowest energy state. The spins will get out of phase with each other. Once the RF is turned off, the transverse magnetization vector begins to decay while the longitudinal component begins to recover. BASICS OF MR IMAGE CONTRAST (T1, T2, T2*) BASICS OF MR IMAGE CONTRAST (T1, T2, T2*) T1-weighted images are produced by using short acquisiton times; conversely, T2-weighted images are produced by using longer times. BASICS OF MR IMAGE CONTRAST (T1, T2, T2*) WM CSF CSF GM T1-weighted images are produced by using short acquisiton times; conversely, T2-weighted images are produced by using longer times. BASICS OF MR IMAGE CONTRAST (T1, T2, T2*) Time to Echo (TE) is the time between the delivery of the T2* image showing low signal area due RF pulse and the receipt of the echo signal. to old blood products.  T2*-sensitive sequences also form the basis for functional MRI (fMRI) using the BOLD (Blood Oxygen Level Dependent) technique ∙ Arteries, veins, capillaries: 2% brain 20% energy (oxygen supply)  T2*-sensitive sequences also form the basis for functional MRI (fMRI) using the BOLD (Blood Oxygen Level Dependent) technique ∙ Arteries, veins, capillaries: 2% brain 20% energy (oxygen supply)  T2*-sensitive sequences also form the basis for functional MRI (fMRI) using the BOLD (Blood Oxygen Level Dependent) technique Source: Jorge Jovicich, fMRIB Brief Introduction to fMRI Background: the birth of functional brain imaging Apparatus used by Mosso to record Increases in temperature in the cat visual Increase in CBF produced by hand changes in brain volume in patients cortex by shining light into the eye movement in the contralateral sensory with skull defects (Mosso, 1880). (Schmidt and Hendrix, 1938). motor cortex (Lassen et al., 1978) Recordings of brain expansion in response Increase in cerebral blood flow (CBF) to intracarotid infusion of a brain extract produced in the calcarine cortex and (Roy and Sherrington, 1890). superior colliculus by visual stimulation (Freygang and Sokoloff, 1958). Iadecola et al., 2017 FMRI TERMINOLOGY FMRI TERMINOLOGY RESTING STATE EXPERIMENT FUNCTIONAL MRI – TASK DESIGN  FUNCTIONAL MRI – TASK DESIGN Simplest task: eyes open & eyes closed Subtraction of the eyes-closed condition from the eyes-open condition identifies a BOLD signal intensity difference in the primary visual cortex (shown on the right).  FUNCTIONAL CONNECTIVITY A term that appears frequently in the literature when discussing correlations in spontaneous blood oxygen level dependent (BOLD) fluctuations is ‘functional connectivity’ which may refer to any study examining inter-regional correlations in neuronal variability. Reading assignment (10 min break) @moodle Cognitive Impairment Cognitive impairment refers to a spectrum of difficulties in various cognitive domains, including memory, attention, language, executive function, and visuospatial skills. Cognitive Impairment Cognitive impairment is prevalent across different age groups and can occur as a result of various factors, including aging, neurodegenerative diseases (e.g., Alzheimer's disease), traumatic brain injury, psychiatric disorders, and other medical conditions. Cognitive Impairment & Neurological Cases Alzheimer's Disease (AD) Memory loss (especially recent ones) Difficulty with language (e.g., trouble finding words or understanding speech) Challenges with problem-solving and decision-making Changes in mood or behavior. Changes in the brain Amyloid Plaques Neurofibrillary Tangles Neuronal Loss Shrinkage of Brain Tissue Impaired Neurotransmission Cognitive Impairment & Neurological Cases Alzheimer's Disease (AD) Memory loss (especially recent ones) Difficulty with language (e.g., trouble finding words or understanding speech) Challenges with problem-solving and decision-making Changes in mood or behavior. Changes in the brain The hippocampus is a critical structure in the brain, primarily Amyloid Plaques involved in memory processes. Neurofibrillary Tangles Neuronal Loss Shrinkage of Brain Tissue Impaired Neurotransmission Cognitive Impairment & Neurological Cases Mild Cognitive Impairment (MCI) MCI represents an intermediate stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer's disease (AD) or other types of dementia. Memory Impairment Risk of Progression to Dementia (not all cases of MCI progress to Alzheimer's disease) Underlying Pathology: The underlying causes of MCI can vary and may include age-related changes, vascular issues, medication side effects, or early stages of neurodegenerative diseases such as Alzheimer's disease. Cognitive Impairment & Neurological Cases Working memory, visuospatial ability, attention, semantic understanding, and motor performance are areas where fMRI findings in AD have been discovered. The at-risk patients performed the fMRI tasks pretty well, which was a common aspect of the studies revealing evidence of elevated fMRI activity. Hyperactivity was seen primarily during successful memory trials in event-related fMRI experiments, suggesting that hyperactivity could be a compensatory strategy in the early stages of AD. Cognitive Impairment & Neurological Cases Cognitive Impairment & Neurological Cases Cognitive Impairment & Neurological Cases Face Recognition Visual Object Recognition Cognitive Impairment & Neurological Cases Parkinson's disease Parkinson's disease is associated with a range of motor and non-motor symptoms. Neurodegenerative disorder that primarily affects movement. It is characterized by a progressive loss of dopaminergic neurons in a region of the brain called the substantia nigra, leading to a shortage of dopamine, a neurotransmitter involved in regulating movement. The iron overload has been associated with the loss of dopamine-producing neurons. Cognitive Impairment & Neurological Cases Parkinson's disease T2-weighted Imaging: MRI sequences known as T2- weighted imaging are particularly sensitive to the presence of iron. Iron-rich structures in the brain, such as the basal ganglia and substantia nigra, appear hypointense (dark) on T2-weighted images due to the paramagnetic properties of iron. This dark signal intensity indicates the presence of iron deposits in these regions. The iron overload has been associated with the loss of dopamine-producing neurons. Jetlag Salivary cortisol levels in cabin crew after repeated exposure to jet lag were significantly higher than after short distance flights. Cho, K. et al. (2000) Jetlag One hypothesis suggests that significant high cortisol elevations induce hippocampal atrophy and deficits in hippocampus- dependent learning and memory. Therefore, the long-term effect of repeated jet lag on both the volume of the temporal lobe and hippocampus- dependent memory performance were tested in 20 healthy women employed by international airline companies. Compared the volume of the temporal lobe in two flight attendant groups with different jet lag recovery periods (n = 10 subjects in each group). Jetlag Subjects were assigned to groups based on their individual flight records: The short-recovery group had recovery intervals of less than 5 days between outward transmeridian flights across at least 7 times zones, whereas the long-recovery group had intervals of more than 14 days between outward transmeridian flights. Compared the volume of the temporal lobe in two flight attendant groups with different jet lag recovery periods (n = 10 subjects in each group). Jetlag Compared the volume of the temporal lobe in two flight attendant groups with different jet lag recovery periods (n = 10 subjects in each group). EEG basics Electro-encephalo-gram Brain Electrical Picture/Record sleeping EEG is the measurement of electrical patterns at the surface of the scalp which reflect cortical activity - commonly referred as “brainwaves”. EEG basics Electro-encephalo-gram Brain Electrical Picture/Record sleeping EEG is the measurement of electrical patterns at the surface of the scalp which reflect cortical activity - commonly referred as “brainwaves”. International 10-20 system 21 channel EEG Electrocorticography ECoG, iEEG Grid and stick electrodes Dr Kareem Zaghloul - Neural signatures of memory and information in the human brain EEG History Analysis – next week(s) EEG History EEG - brain rhythms BM402: ENGINEERING IN MEDICINE 24th October 2024 M 2170 – South Campus MRI Functional MRI Applications of MRI and fMRI EEG Applications of EEG Multimodal Imaging EEG basics Electro-encephalo-gram Brain Electrical Picture/Record sleeping EEG is the measurement of electrical patterns at the surface of the scalp which reflect cortical activity - commonly referred as “brainwaves”. EEG basics Electro-encephalo-gram Brain Electrical Picture/Record sleeping EEG is the measurement of electrical patterns at the surface of the scalp which reflect cortical activity - commonly referred as “brainwaves”. International 10-20 system 21 channel EEG Electrocorticography ECoG, iEEG Grid and stick electrodes Dr Kareem Zaghloul - Neural signatures of memory and information in the human brain EEG History Analysis – next week(s) EEG History EEG - brain rhythms EEG - brain rhythms & frequency bands EEG - brain rhythms & frequency bands EEG - brain rhythms & frequency bands Light sleep Deep sleep REM sleep – rapid eye movement Recording the electrical activity of the brain Definition: An action potential is a rapid, large change in membrane potential that travels along the axon of a neuron, allowing for long-distance communication. Typically lasts about 1 milliseconds, with high- amplitude (~100 mV) pulses. Postsynaptic potentials To be clear, EEG does not measure action potentials, but rather postsynaptic potentials. An action potential is a rapid sequence of changes in the voltage across a membrane, ,i.e., a temporary shift (from negative to positive) in the neuron's membrane potential caused by ions suddenly flowing in and out of the neuron. Postsynaptic potentials (PSP) A temporary change in the electric polarization of the membrane of a nerve cell (neuron). The result of chemical transmission of a nerve impulse at the synapse (neuronal junction), the postsynaptic potential can lead to the firing of a new impulse. A postsynaptic potential is a change in the membrane potential of a postsynaptic neuron that occurs in response to neurotransmitter binding at synapses. PSPs are longer in duration than action potentials, lasting up to tens or even hundreds of milliseconds. Postsynaptic potentials Postsynaptic potentials International 10-20 system 21 channel EEG Electrocorticography ECoG, iEEG Grid and stick electrodes Dr Kareem Zaghloul - Neural signatures of memory and information in the human brain EEG History Analysis EEG History Simultaneous EEG-fMRI Simultaneous EEG-fMRI: how to make it compatible Simultaneous EEG-fMRI: how to make it compatible Simultaneous EEG-fMRI: how to make it compatible Parallel vs. concurrent Simultaneous EEG-fMRI: how to make it compatible - the presence of static and time-varying magnetic fields and - their associated EEG artefacts; - the need to limit radiofrequency (RF) emissions to preserve image quality; - and finally the obvious requirement to avoid the introduction of ferrous materials into the scanner environment. (A) electrode cap, (B) connector box containing current-limiting resistors, (C) battery power pack and (D) 32 channel EEG amplifier/digitizer. Simultaneous EEG-fMRI: how to make it compatible - MR bore: a “hostile” environment for the recording of EEG. - There are several reasons for this, mostly related to the homogeneous and gradient- switching magnetic environment of the MR bore. - In addition to the strong homogeneous static magnetic field of the scanner and also, more importantly, to the rapidly changing variable magnetic fields generated by gradient switching, the cap, electrodes, and electrode leads are also exposed to the profound radio frequency (RF) energy emitted during the scan sequence. Simultaneous EEG-fMRI: how to make it compatible Back view of a commonly used MR-compatible EEG cap system (BrainCap MR, Brain Products GmbH, Gilching, Germany). Safety features on this cap are: (1) plastic electrode holders to avoid direct contact of Ag/AgCl element with the scalp, (2) RF shielding resistor on electrode (e.g., black “dot”), Simultaneous EEG-fMRI: how to make it compatible Magnetic Properties Relevant to MRI: Ferromagnetism: Importance: Ferromagnetic materials are strongly attracted to magnetic fields. In the context of MRI, any ferromagnetic material (like iron) can pose safety risks, as it may be pulled into the magnet, potentially causing injury or equipment damage. MRI Design: MRI systems are designed to minimize the presence of ferromagnetic materials to ensure patient safety and equipment integrity. Paramagnetism: Importance: Paramagnetic substances, such as gadolinium, are Diamagnetism: used as contrast agents in MRI. These agents enhance the contrast of images by altering the relaxation times of nearby protons. Importance: Diamagnetic materials are slightly repelled by magnetic - Aluminum, Platinum fields and do not pose a safety risk in MRI. Most biological tissues are Deoxyhemoglobin (the form of hemoglobin without bound oxygen) weakly diamagnetic. has unpaired electrons and exhibits paramagnetic properties. This - Copper, Carbon, Silicon makes it attracted to magnetic fields. Behavior in MRI: While they do not enhance images, understanding their When hemoglobin binds oxygen, it undergoes a conformational properties is essential for interpreting the effects of magnetic fields on change that reduces its paramagnetic characteristics (it becomes body tissues. diamagnetic when fully oxygenated). Simultaneous EEG-fMRI: how to make it compatible Magnetic Properties Relevant to MRI: Ferromagnetism: Importance: Ferromagnetic materials are strongly attracted to magnetic fields. In the context of MRI, any ferromagnetic material (like iron) can pose safety risks, as it may be pulled into the magnet, potentially causing injury or equipment damage. MRI Design: MRI systems are designed to minimize the presence of ferromagnetic materials to ensure patient safety and equipment integrity. Paramagnetism: Importance: Paramagnetic substances, such as gadolinium, are Diamagnetism: used as contrast agents in MRI. These agents enhance the contrast of images by altering the relaxation times of nearby protons. Importance: Diamagnetic materials are slightly repelled by magnetic - Aluminum, Platinum fields and do not pose a safety risk in MRI. Most biological tissues are Deoxyhemoglobin (the form of hemoglobin without bound oxygen) weakly diamagnetic. has unpaired electrons and exhibits paramagnetic properties. This - Copper, Carbon, Silicon makes it attracted to magnetic fields. Behavior in MRI: While they do not enhance images, understanding their When hemoglobin binds oxygen, it undergoes a conformational properties is essential for interpreting the effects of magnetic fields on change that reduces its paramagnetic characteristics (it becomes body tissues. diamagnetic when fully oxygenated). Simultaneous EEG-fMRI: how to make it compatible Magnetic Properties Relevant to MRI: Ferromagnetism: Importance: Ferromagnetic materials are strongly attracted to magnetic fields. In the context of MRI, any ferromagnetic material (like iron) can pose safety risks, as it may be pulled into the magnet, potentially causing injury or equipment damage. MRI Design: MRI systems are designed to minimize the presence of ferromagnetic materials to ensure patient safety and equipment integrity. Paramagnetism: Importance: Paramagnetic substances, such as gadolinium, are Diamagnetism: used as contrast agents in MRI. These agents enhance the contrast of images by altering the relaxation times of nearby protons. Importance: Diamagnetic materials are slightly repelled by magnetic - Aluminum, Platinum fields and do not pose a safety risk in MRI. Most biological tissues are Deoxyhemoglobin (the form of hemoglobin without bound oxygen) weakly diamagnetic. has unpaired electrons and exhibits paramagnetic properties. This - Copper, Carbon, Silicon makes it attracted to magnetic fields. Behavior in MRI: While they do not enhance images, understanding their When hemoglobin binds oxygen, it undergoes a conformational properties is essential for interpreting the effects of magnetic fields on change that reduces its paramagnetic characteristics (it becomes body tissues. diamagnetic when fully oxygenated). Simultaneous EEG-fMRI: how to make it compatible Back view of a commonly used MR-compatible EEG cap system (BrainCap MR, Brain Products GmbH, Gilching, Germany). Safety features on this cap are: (1) plastic electrode holders to avoid direct contact of Ag/AgCl element with the scalp, (2) RF shielding resistor on electrode (e.g., black “dot”), (3) fixation of electrode cables with nylon, and (4) routing of electrode cables together in bundles of increasing numbers of electrodes. Simultaneous EEG-fMRI: how to make it compatible Back view of a commonly used MR-compatible EEG cap system (BrainCap MR, Brain Products GmbH, Gilching, Germany). Safety features on this cap are: (1) plastic electrode holders to avoid direct contact of Ag/AgCl element with the scalp, (2) RF shielding resistor on electrode (e.g., black “dot”), (3) fixation of electrode cables with nylon, and (4) routing of electrode cables together in bundles of increasing numbers of electrodes. Simultaneous EEG-fMRI: how to make it compatible The arrangement shown consists of two EEG amplifiers at the top and bottom with a rechargeable power pack positioned in the middle. Cap connections are made with standard flat ribbon cables at the front of the amplifiers. *Sandbags used to fix the electrode cables in place to avoid cable movement induced by mechanical resonances caused by gradient switching and by the action of the Helium pump. Simultaneous EEG-fMRI: main artifacts Correction of gradient and cardioballistic artifacts is valuable for ensuring data quality A much less commonly seen cardiac artifact is cardioballistic artifact, in which the EEG electrode is placed just above an artery, and each pulsation of the artery is picked up as motion artifact on the EEG. Simultaneous EEG-fMRI: main artifacts Gradient artifact (GA) is the largest source of noise in EEG-fMRI, and is used for fMRI acquisition due to the magnetic field gradients, which induce current in EEG electrodes up to 400 times larger than neural activity, therefore obscuring the EEG information of interest. Ballistocardiogram (BCG) artifact occurs due to the subject's cardio-respiratory patterns, specifically scalp pulse and cardiac-related motion. Simultaneous EEG-fMRI: main artifacts Gradient artifact (GA) is the largest source of noise in EEG-fMRI, and is used for fMRI acquisition due to the magnetic field gradients, which induce current in EEG electrodes up to 400 times larger than neural activity, therefore obscuring the EEG information of interest. Ballistocardiogram (BCG) artifact occurs due to the subject's cardio-respiratory patterns, specifically scalp pulse and cardiac-related motion. Motion artifact occurs when movement of the subject's head within the scanner creates artifacts on the EEG due to induced current at electrodes. Environmental artifact occurring on the EEG recording is mostly due to interference from power line noise, ventilation, and lights in the MR room, as well as the vibration arising from the helium cooling pump. Simultaneous EEG-fMRI: main artifacts – how bad? Correction of gradient and cardioballistic artifacts is valuable for ensuring data quality Ikemoto et al. 2022 Simultaneous EEG-fMRI: main artifacts – how bad? Correction of gradient and cardioballistic artifacts is valuable for ensuring data quality Ikemoto et al. 2022 Main gradient artifact (GA) correction methods A. Template methods B. Blind source separation C. Filtering Main gradient artifact (GA) correction methods A. Template methods B. Blind source separation C. Filtering Template methods are techniques that create an estimate of the artifact, which is removed from the noisy data, to obtain clean EEG. GA is assumed to be repetitive and time-locked to each repetition time (TR). Template methods average the signal over many TRs, leveraging the fact that the neuronal EEG signal, which is not time locked to the TR, will average out toward zero. Main gradient artifact (GA) correction methods A. Template methods B. Blind source separation C. Filtering Bullock et al. 2021  (A) The raw EEG during periodic fMRI flat (B) The averaged imaging artifact. (C): (A) – (B) (D) The averaged pulse artifact. (E): (C) – (D) - > alpha power visible EEG recorded outside the scanner Illustrative example of 10 seconds of EEG data Marino et al. 2018 Break – 15 minutes Frequency based analysis EEG & SLEEP  Markers of deep sleep Markers of N2 –light- sleep EEG & SLEEP Frequency based analysis Frequency based analysis In Berger’s first EEG recordings from the human scalp in the late 1920s, he noticed a prominent sinusoidal wave of around 10 cycles/s that he later named the alpha rhythm (8-12Hz). The alpha rhythm is highest in amplitude when a subject is awake and relaxed with eyes closed, and is attenuated by opening the eyes and by mental effort, as well as by drowsiness or sleep. Frequency based analysis fMRI & EEG alpha Alpha rhythm as an index of cortical inactivity that may be generated in part by the thalamus. Reading time: 15 minutes Event related potentials (ERPs) What is an ERP? An event-related potential (ERP) is the neural response associated with a specific sensory, e.g., cognitive, or motor event. An ERP can be recorded using scalp EEG and looks at the average change in voltage over time starting at the onset of the stimulus over multiple trials. Event related potentials (ERPs) What is an ERP? An event-related potential (ERP) is the neural response associated with a specific sensory, e.g., cognitive, or motor event. An ERP can be recorded using scalp EEG and looks at the average change in voltage over time starting at the onset of the stimulus over multiple trials. How to record? ERPs are evoked by stimuli and measured at the scalp with EEG. They are recorded in response to an isolated, discrete event. Usually, this stimulus is presented multiple times, which allows the EEG to be averaged after discarding low-quality trials. Event related potentials (ERPs) ERPs are positive and negative voltage fluctuations (or components) in the ongoing EEG that are time-locked to the onset of a sensory, motor, or cognitive event. ERPs reflect brain activity that is specifically related to some stimulus or other event. This activity cannot be directly observed in the EEG, as the "signal" (the brain response to some event) is swamped by the "noise" (the brain activity that is unrelated to that event). The solution to this problem is to present not just one instance of the event of interest, but many instances: Epochs Event related potentials (ERPs) The "random" activity washes out during averaging, whereas the brain activity of interest -- namely, what is constant over presentations of the event of interest -- stays in the signal. Through this signal-averaging procedure, it is possible to isolate the brain response that is specifically elicited in response to some event of interest. ERP components are usually named in terms of their polarity (N/P: negative/positive) and peak latency (in milliseconds). Event related potentials (ERPs) The majority of ERP studies investigated responses that occur in the first 100–500 ms following a stimulus. Early components (P100, N100, P200) relate to sensory properties of stimuli and to selective attention. Later ERP waves are used to index endogenous cognitive activity. Event related potentials (ERPs) Later ERP waves are used to index endogenous cognitive activity. The positive going ERP component at 300 ms (P300) is related to processes that involve classifying or updating memory representations of stimuli. The amplitude of the P300 increases as the demand for cognitive resources increases and as the significance of the event and its relevance to the subject increases. Latency and amplitude Shorter latencies indicate superior mental performance relative to longer latencies. P3 amplitude seems to reflect stimulus information such that greater attention produces larger P3 waves. Reduced P300 amplitude is an indicator of the broad neurobiological vulnerability that underlies disorders within the externalizing spectrum {alcohol dependence, drug dependence, nicotine dependence, conduct disorder and adult antisocial behavior} (Patrick et al., 2006). Event-related potential changes in psychiatric disorders – P300 One of the most robust neurophysiological findings in schizophrenia is decrease in P300 amplitude. P300 latency was found to be increased in schizophrenic patients but not in their first-degree relatives (Simlai & Nizamie, 1998). Salisbury et al. (1999) have recently noted P300 reduction in manic psychosis. Latency prolongation and amplitude reduction were seen both in schizophrenia and chronic bipolar patients (O’Donell et al., 2004). Event-related potential changes in psychiatric disorders – P300 Latency prolongation and amplitude reduction were seen both in schizophrenia and chronic bipolar patients (O’Donell et al., 2004). Event-related potential changes in psychiatric disorders – P300 Latency prolongation and amplitude reduction were seen both in schizophrenia and chronic bipolar patients (O’Donell et al., 2004). Event-related potential changes in psychiatric disorders – P300 Results suggest that while both bipolar patients and patients with schizophrenia have reduced P300 amplitude and prolonged latency, patients with schizophrenia additionally have disturbances of earlier stages of auditory processing. P300 latency prolongation is suggestive of deficits in attentional or working memory systems. Caffeine effect on P300 Caffeine effect on P300 Caffeine effect on P300 Caffeine yields quicker mental processing and less overall demand on attention resources required for task performance. Caffeine may modulate the mental processing for repeated stimulus by reducing the overall demand on attention and producing a net increase in allocating attention resources for task performance. Tiredness, getting bored with the task. Reading – 15 minutes Simultaneous EEG-fMRI: an overnight sleep study 3T EEG fMRI 12 successful subjects, ~ 10% of total participants 3T, GE-EPI, TR = 3s, TE = 36ms Physiology Respiratory bellow & pulse oximeter EEG 64 channel Manual sleep scoring (based on 30-s epochs) Moehlman et al., J. Neur. Methods 2019 Simultaneous EEG-fMRI: an overnight sleep study 0.5 - Sleep stages Wake NREM1 NREM2 - 20 NREM3 NREM2 NREM3 1000 LF-EEG 3T Frequency (µV2) (Hz) 100 - EEG PPG-AMP 0 (a.u.) 0.52 - % fMRIGM 0 signal change -2 Sleep stages hypnogram fMRI Wake NREM1 Rotation Degree 3T, GE-EPI, TR = 3s, TE = 36ms NREM2 1 NREM30 Physiology LF-EEG 1000 1 300 600 900 1200 1500 1800 2100 2400 2676 Respiratory bellow & pulse oximeter (µV2) time (sec) 0 EEG 64 channel PPG-AMP 0 (a.u.) Manual sleep scoring (based on 30-s epochs) 2 % fMRIGM 0 signal change -2 Özbay et al., Commun. Biol. 2019 Reminder for upcoming classes: Xray, CT, PET, PET-MRI Neurofeedback Midterm Biomechanichs Biomaterials Trends, e.g., Big data, open science, AI Ethics Presentations Lab visits BM402: ENGINEERING IN MEDICINE 14th Nov 2024 M 2170 – South Campus Neurofeedback Rehab Engineering Case Study Physiology, emotions and brain Emotions can have a significant impact on our physiological responses, including our heart rate and respiratory rate. Fear, anger, anxiety - release of adrenaline and other stress hormones - increase in heart rate - rapid breathing. Happiness - releases endorphins - decrease in heart rate Brain structures involved in dealing with stress and fear. - shallower breathing Happiness and fMRI - The studies found that recalling happy events activates various areas including the anterior cingulate cortex, prefrontal cortex, and insula. - These areas are also associated with other basic emotions such as sadness and anger. Suardi et al. 2016 Happiness and fMRI fMRI - Neurofeedback Real-time fMRI (rtfMRI): - fMRI data processing and display are performed at a speed that makes them consequent with image acquisition. - enabled real-time neurofeedback - allows a person to watch and regulate the fMRI signal from his or her own brain. fMRI - Neurofeedback - provides real-time feedback about brain activity to a person, with the goal of helping them learn to regulate their brain function. - a person undergoing neurofeedback training may be monitored with fMRI to identify which brain regions are involved in the process of learning to regulate brain activity. Reading – 15 minutes Neurofeedback - A type of biofeedback that teaches self-regulation of brain activity. - Focused on enhancing cognitive functions or managing conditions (e.g., ADHD, anxiety). - Provides real-time brain activity data to help users adjust their mental state. Brain-Computer Interface (BCI) - A system that enables direct communication between the brain and external devices. - Allows users to control devices (e.g., prosthetics, computers) using thought. - Translates brain signals into commands for devices, without a primary focus on self-regulation. Common Tools: Both use EEG and signal processing techniques. Relationship: Neurofeedback is a specialized application of BCI technology, but their intents and interactions differ. Neurofeedback (NFB) NFB is an operant conditioning technique for learning how to control one’s brain activity to improve cognitive performance, regulate stress levels, emotional functioning and behavior. Neurofeedback (NFB) NFB is an operant conditioning technique for learning how to control one’s brain activity to improve cognitive performance, regulate stress levels, emotional functioning and behavior. Neurofeedback (NFB) NFB is an operant conditioning technique for learning how to control one’s brain activity to improve cognitive performance, regulate stress levels, emotional functioning and behavior. Happiness and fMRI fMRI - Neurofeedback & Happiness Happy Memories condition: - the word ‘‘Happy’’, two color bars, and a number indicating the neurofeedback fMRI signal level were displayed on the screen. - participants were instructed to evoke happy autobiographical memories to make themselves feel happy while trying to increase the level of the red bar to a given target level (indicated by the fixed height blue bar). Happiness and fMRI Fronto-temporo-limbic network - Important for the regulation of emotions, decision-making, and social cognition. - The fronto-temporo-limbic network is a functional network of brain regions that are involved in emotional processing, memory, and attention. - It includes the prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, insula. - Dysregulation of this network has been Activation Network for Happy Memories and Count Conditions. The implicated in various psychiatric group activation analysis for Happy>Count contrast revealed disorders, such as depression, anxiety, significant BOLD signal changes in a fronto-temporo-limbic network, and post-traumatic stress disorder. while the Count>Happy contrast revealed activations in a parietal network. EEG & Neurofeedback (NFB) EEG & Neurofeedback Neurofeedback as a Rehabilitation Tool Neurofeedback, e.g., EEG biofeedback, is a technique that uses real-time monitoring of brain activity (usually through EEG - Electroencephalography) to help individuals learn to self-regulate their brain function. This process can be valuable in rehabilitation, particularly for patients recovering from neurological conditions, injuries, or disorders that affect brain function. - - a non-invasive method of promoting neural plasticity - - important for people recovering from neurological injuries (e.g., stroke, traumatic brain injury, spinal cord injury) or neurological conditions (e.g., ADHD, anxiety, depression, epilepsy). Neurofeedback as a Rehabilitation Tool Neurofeedback as a Rehabilitation Tool - Stroke Rehabilitation - Traumatic Brain Injury (TBI) Recovery - Cognitive Rehabilitation (memory, attention) - Pain Management and Stress Reduction - - Integration with VR, Robotics Neurofeedback as a Rehabilitation Tool - Memory Training: Specific neurofeedback protocols can be designed to improve working memory or long-term memory. For example, theta/beta ratio training has been shown to be effective in conditions like ADHD, which often coexists with cognitive dysfunction. - Attention and Focus: In conditions like ADHD or after brain injuries (where attention and focus are often impaired), neurofeedback can train the brain to increase focus and attention by increasing the power of specific brainwave frequencies (like beta waves). Reading – 15 mins Rehabilitation Engineering  Case Study: Engineering Solutions for Traumatic Brain Injury (TBI) Rehabilitation – Focus on Brainstem Damage Recovery Traumatic Brain Injury (TBI) is a major cause of long-term Patient Profile: disability, particularly when damage occurs to the brainstem. Age: 35 Cause of Injury: Motor vehicle accident We know that brainstem is responsible for regulating Symptoms: Severe motor impairment, respiratory essential life functions such as breathing, heart rate, and difficulties, and swallowing problems. Initially, the patient consciousness. was in a coma and then progressed to a minimally conscious state. The patient suffered significant Injuries to this critical area can lead to profound impairments, brainstem damage, resulting in partial paralysis (locked-in including motor dysfunction, respiratory problems, and syndrome) and difficulty with vital functions like difficulty swallowing. breathing and swallowing.  Case Study: Engineering Solutions for Traumatic Brain Injury (TBI) Rehabilitation – Focus on Brainstem Damage Recovery Rehabilitation Strategies and Engineering Treatment Timeline: Solutions: Acute Phase (0-6 weeks): Immediate medical In class assignment based on 3 rehabs (1 given) intervention to stabilize the brain injury. The patient patient needs: was placed on a ventilator to assist with breathing, - Brainstorm on challenge, solution, outcome and a feeding tube was used for nutrition. - Work in groups (2-3 p.) Rehabilitation Phase (6 weeks - 6 months): - 30 minutes Introduction of physical, occupational, and speech therapy to address motor, respiratory, and swallowing 1. Speech and Swallowing Rehabilitation difficulties. Use of engineering solutions to promote 2. XX Rehabilitation neuroplasticity and recovery of lost functions. 3. YY Rehabilitation - Group presentations X-ray An X-ray, also called a radiograph, sends radiation through the body. Areas with high levels of calcium (bones and teeth) block the radiation, causing them to appear white on the image. Soft tissues allow the radiation to pass through. They appear gray or black on the image. Fractures Dislocations Misalignments Narrowed joint spaces X-ray An X-ray won’t show subtle bone injuries, soft tissue injuries or inflammation. Portrait of Wilhelm Conrad Röntgen. The electromagnetic spectrum. X-rays have higher energy than visible light. What injuries require an X-ray? An X-ray won’t show soft tissue injuries or inflammation. Broken arm The electromagnetic spectrum. X-rays have higher energy than visible light. What injuries require an X-ray? An X-ray won’t show soft tissue injuries or inflammation. Broken arm Detects bone fractures, certain tumors and other abnormal masses, pneumonia, some types of injuries, calcifications, foreign objects, or dental problems. The electromagnetic spectrum. X-rays have higher energy than visible light. What injuries require an X-ray? An X-ray won’t show soft tissue injuries or inflammation. Broken arm For example, our bones contain calcium, which has a higher atomic number than most other tissues. Because of this property, bones readily absorb x-rays and therefore produce high contrast on the x-ray detector. As a result, bony structures appear whiter than other tissues against the black background of a radiograph. Detects bone fractures, certain tumors and other abnormal masses, pneumonia, some types of injuries, Conversely, x-rays travel more easily through less radiologically dense calcifications, foreign objects, or dental problems. tissues, such as air-filled cavities such as the lungs. These structures are displayed in shades of gray on a radiograph When are medical x-rays used? Detects bone fractures, certain tumors and other abnormal masses, Broken arm X-ray radiography pneumonia, some types of injuries, calcifications, foreign objects, or dental problems. A mammogram is a radiograph of the breast Mammography used to detect and diagnose breast cancer. Tumors typically appear as masses, either regular or irregular in shape, and are brighter than the surrounding tissue on the image (whiter on a black background or blacker on a white background). Mammograms can also identify small calcium deposits, called microcalcifications, which appear as bright specks on the image When are medical x-rays used? Computed tomography (CT): Combines traditional x-ray technology with computer processing to generate a series of cross-sectional images of the body that can later be combined to form a three- dimensional x-ray image. CT images are more detailed than plain radiographs and give doctors the ability to view structures within the body from different angles. When are medical x-rays used? Here are the steps for CT image formation: 1. X-ray Source and Detector Rotation: The X-ray tube and detectors rotate around the patient. 2. X-ray Attenuation: Different tissues absorb X-rays at varying degrees. 3.Data Collection Detectors capture X-rays passing through the body from multiple angles. 4. Reconstruction: The computer processes the data and reconstructs cross-sectional slices using algorithms, such as filtered back projection, and iterative recon. 5. Image Display: The reconstructed images are displayed on a monitor, with contrast and brightness adjusted. When are medical x-rays used? Basal ganglia calcification Here are the steps for CT image formation: 1. X-ray Source and Detector Rotation: The X-ray tube and detectors rotate around the patient. 2. X-ray Attenuation: Different tissues absorb X-rays at varying degrees. 3.Data Collection Detectors capture X-rays passing through the body from multiple angles. 4. Reconstruction: The computer processes the data and reconstructs cross-sectional slices using algorithms, such as filtered back projection, and iterative recon. Normal intracranial calcifications can be defined as all age-related physiologic and neurodegenerative 5. Image Display: The reconstructed images are calcifications that are unaccompanied by any evidence of displayed on a monitor, with contrast and disease and have no demonstrable pathological cause. brightness adjusted. CT recon steps Basal ganglia calcification 1. The Basics of CT Scanning 2. Raw Data Collection 3. Back Projection (The Basic Idea) 4. Filtered Back Projection 5. Iterative Reconstruction (A More Advanced Method) 6. Converting Slices into a 3D Image Normal intracranial calcifications can be defined as all age-related physiologic and neurodegenerative calcifications that are unaccompanied by any evidence of disease and have no demonstrable pathological cause. CT recon steps Basal ganglia calcification Filtered Back Projection (FBP) is based on two main mathematical operations: Fourier transforms and convolution. - A Fourier transform is a mathematical operation that converts data from the spatial domain (like an image) into the frequency domain. In the frequency domain, data is represented as a combination of different frequencies. - For FBP, the Fourier transform is applied to each Normal intracranial calcifications can be defined as all projection to decompose it into its frequency age-related physiologic and neurodegenerative components. This helps us see which frequencies are calcifications that are unaccompanied by any evidence of disease and have no demonstrable pathological cause. present in the data and is useful for filtering out unwanted noise and enhancing edges. BM402: ENGINEERING IN MEDICINE 31st October 2024 M 2170 – South Campus But some good news: You have ca. half an hour to go through the course material. We will start at 1:10 pm, end 1:40 pm. Break - 15 minutes MRI Functional MRI Applications of MRI and fMRI EEG Challenges of EEG-fMRI Literature EEG basics Electro-encephalo-gram Brain Electrical Picture/Record sleeping EEG is the measurement of electrical patterns at the surface of the scalp which reflect cortical activity - commonly referred as “brainwaves”. EEG - brain rhythms & frequency bands Simultaneous EEG-fMRI: how to make it compatible - the presence of static and time-varying magnetic fields and - their associated EEG artefacts; - the need to limit radiofrequency (RF) emissions to preserve image quality; - and finally the obvious requirement to avoid the introduction of ferrous materials into the scanner environment. (A) electrode cap, (B) connector box containing current-limiting resistors, (C) battery power pack and (D) 32 channel EEG amplifier/digitizer. Simultaneous EEG-fMRI: main artifacts – how bad? Correction of gradient and cardioballistic artifacts is valuable for ensuring data quality Ikemoto et al. 2022 Frequency based analysis EEG & SLEEP Frequency based analysis fMRI & EEG alpha Alpha rhythm as an index of cortical inactivity that may be generated in part by the thalamus. Event related potentials (ERPs) What is an ERP? An event-related potential (ERP) is the neural response associated with a specific sensory, e.g., cognitive, or motor event. An ERP can be recorded using scalp EEG and looks at the average change in voltage over time starting at the onset of the stimulus over multiple trials. How to record? ERPs are evoked by stimuli and measured at the scalp with EEG. They are recorded in response to an isolated, discrete event. Usually, this stimulus is presented multiple times, which allows the EEG to be averaged after discarding low-quality trials. Event related potentials (ERPs) Later ERP waves are used to index endogenous cognitive activity. The positive going ERP component at 300 ms (P300) is related to processes that involve classifying or updating memory representations of stimuli. The amplitude of the P300 increases as the demand for cognitive resources increases and as the significance of the event and its relevance to the subject increases. Event-related potential changes in psychiatric disorders – P300 Latency prolongation and amplitude reduction were seen both in schizophrenia and chronic bipolar patients (O’Donell et al., 2004). Caffeine effect on P300 EEG - brain rhythms & frequency bands High frequency EEG One more band we haven’t discussed: EEG ripples, typically defined as oscillations in the frequency range of 80–200 Hz, are fast oscillatory activities that are often associated with various brain processes. Next assignment: explain with its use in clinics, 3-4 references. Physiology, emotions and brain Emotions can have a significant impact on our physiological responses, including our heart rate and respiratory rate. Fear, anger, anxiety - release of adrenaline and other stress hormones - increase in heart rate - rapid breathing. Happiness - releases endorphins - decrease in heart rate Brain structures involved in dealing with stress and fear. - shallower breathing Happiness and fMRI - The studies found that recalling happy events activates various areas including the anterior cingulate cortex, prefrontal cortex, and insula. - These areas are also associated with other basic emotions such as sadness and anger. Suardi et al. 2016 Happiness and fMRI fMRI - Neurofeedback Real-time fMRI (rtfMRI): - fMRI data processing and display are performed at a speed that makes them consequent with image acquisition. - enabled real-time neurofeedback - allows a person to watch and regulate the fMRI signal from his or her own brain. fMRI - Neurofeedback - provides real-time feedback about brain activity to a person, with the goal of helping them learn to regulate their brain function. - a person undergoing neurofeedback training may be monitored with fMRI to identify which brain regions are involved in the process of learning to regulate brain activity. Neurofeedback - A type of biofeedback that teaches self-regulation of brain activity. - Focused on enhancing cognitive functions or managing conditions (e.g., ADHD, anxiety). - Provides real-time brain activity data to help users adjust their mental state. Brain-Computer Interface (BCI) - A system that enables direct communication between the brain and external devices. - Allows users to control devices (e.g., prosthetics, computers) using thought. - Translates brain signals into commands for devices, without a primary focus on self-regulation. Common Tools: Both use EEG and signal processing techniques. Relationship: Neurofeedback is a specialized application of BCI technology, but their intents and interactions differ. Neurofeedback - A type of biofeedback that teaches self-regulation of brain activity. - Focused on enhancing cognitive functions or managing conditions (e.g., ADHD, anxiety). - Provides real-time brain activity data to help users adjust their mental state. Brain-Computer Interface (BCI) - A system that enables direct communication between the brain and external devices. - Allows users to control devices (e.g., prosthetics, computers) using thought. - Translates brain signals into commands for devices, without a primary focus on self-regulation. Common Tools: Both use EEG and signal processing techniques. Relationship: Neurofeedback is a specialized application of BCI technology, but their intents and interactions differ. Reading – 15 minutes Neurofeedback - A type of biofeedback that teaches self-regulation of brain activity. - Focused on enhancing cognitive functions or managing conditions (e.g., ADHD, anxiety). - Provides real-time brain activity data to help users adjust their mental state. Brain-Computer Interface (BCI) - A system that enables direct communication between the brain and external devices. - Allows users to control devices (e.g., prosthetics, computers) using thought. - Translates brain signals into commands for devices, without a primary focus on self-regulation. Common Tools: Both use EEG and signal processing techniques. Relationship: Neurofeedback is a specialized application of BCI technology, but their intents and interactions differ. Neurofeedback (NFB) NFB is an operant conditioning technique for learning how to control one’s brain activity to improve cognitive performance, regulate stress levels, emotional functioning and behavior. Neurofeedback (NFB) NFB is an operant conditioning technique for learning how to control one’s brain activity to improve cognitive performance, regulate stress levels, emotional functioning and behavior. Neurofeedback (NFB) NFB is an operant conditioning technique for learning how to control one’s brain activity to improve cognitive performance, regulate stress levels, emotional functioning and behavior. Happiness and fMRI Read the abstract fMRI - Neurofeedback & Happiness Happy Memories condition: - the word ‘‘Happy’’, two color bars, and a number indicating the neurofeedback fMRI signal level were displayed on the screen. - participants were instructed to evoke happy autobiographical memories to make themselves feel happy while trying to increase the level of the red bar to a given target level (indicated by the fixed height blue bar). Happiness and fMRI Activation Network for Happy Memories and Count Conditions. The group activation analysis for Happy>Count contrast revealed significant BOLD signal changes in a fronto- temporo-limbic network, while the Count>Happy contrast revealed activations in a parietal network. Happiness and fMRI Fronto-temporo-limbic network - Important for the regulation of emotions, decision-making, and social cognition. - The fronto-temporo-limbic network is a functional network of brain regio