9 - What is Biomedical Engineering Biomedical...

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Unformatted text preview: What is Biomedical Engineering? Biomedical engineering (BME) is the application of engineering principles (analysis, design, fabrication, modeling, etc.) to problems in medicine and biology. NAE NAE Grand Challenges • Reverse Engineering of the Brain – Building smarter computers. – Deeper insights about how and why the brain works and fails. – Biotechnology solutions to brain disorders, such as drugs or neural implants. – Technological innovations that allow wiring of new materials into our bodies to do the jobs of lost or materials into our bodies to do the jobs of lost or damaged damaged nerve cells. E.g., implanted electronic devices could help victims of dementia to remember, blind people to see, and crippled people to walk. 1 1 Functional Brain Imaging using MRI Douglas C. Noll Biomedical Engineering University of Michigan Michigan Functional MRI Laboratory 2 2 Outline • Introduction to Magnetic Resonance Imaging – NMR Spins – Localization • Functional MRI – Physiology of Brain Activation – Biophysical Connection to MRI • Topics of Current Interest Bar Magnet Bar Magnets “North” and “South” poles 3 3 A “Spinning” Proton A spinning proton generates a tiny magnetic field Like a little bar magnet Protons in the Human Body • The human body is made up of many individual protons. • Individual protons are found in every hydrogen nucleus. • The body is mostly water, and each water molecule molecule has 2 hydrogen nuclei. protons • 1 gram of your body has ~ 6 x 1022 protons 4 4 Spinning Protons in the Body Spinning protons protons are randomly oriented. On average no net effect. Protons in a Magnetic Field Spinning protons become aligned aligned to the magnetic field. On average body become magnetized. M 5 5 Magnetization of Tissue M Common NMR Active Nuclei Isotope 1H 2H 13C 14N 15N 17O 19F 23Na 31P Spin I % natural abundance MHz/T 1/2 1 1/2 1 1/2 5/2 1/2 3/2 1/2 99.985 0.015 1.108 99.63 0.37 0.037 100 100 100 42.575 6.53 10.71 3.078 4.32 5.77 40.08 11.27 17.25 6 6 Excitation/Reception RF Excitation (Energy into tissue) Magnetic waves are emitted Frequency Encoding • A fundamental property of nuclear spins says that the frequency at which they precess (or emit emit signals) is proportional to the magnetic field strength: = B - The Larmor Relationship • By making the magnetic field vary with spatial position, we can use the frequency information to get location 7 7 Frequency Encoding Low Frequency B Mag. Field Strength Low Frequency Object High Frequency x Position High Frequency x Position Frequency Encoding B x 8 8 Fourier Transforms • The last part of this story is the Fourier transform. • The Fourier transform is the computer program that breaks down each MR signal into its frequency components. • If we plot the strength of each frequency, it will form a representation (or image) of the object in one-dimension. one- Fourier Transforms Low Frequency Object MR Signal Fourier Transform High Frequency time 1D Image x Position 9 9 2D Imaging - 2D Fourier Transform 2D FFT Acquired Data Resultant Image Imaging Breast Cancer 10 10 Imaging Joints Imaging Air Passages 11 11 Tagging Cardiac Motion Functional MRI 12 12 Outline • Introduction to Magnetic Resonance Imaging – NMR Spins – Localization • Functional MRI – Physiology of Brain Activation – Biophysical Connection to MRI • Topics of Current Interest Principles of Functional MRI • MRI can image all of these changes: – – – – Metabolism Blood Flow Blood Volume Blood Oxygenation MR Spectroscopy Arterial Spin Tagging Intravascular contrast agents BOLD Functional MRI • The commonly used of these is BOLD fMRI – Easy to use – High sensitivity (relative to other techniques) – Contrast agents/multinuclear coils not needed 13 13 BOLD fMRI: An Overview Basal state arterioles Stimulated state capillary bed arterioles venules capillary bed venules = HbO2 = Deoxy-Hb Deoxy- - normal flow - basal Deoxy-Hb level Deoxy Hb level - basal CBV - field gradients around vessels resulting from Deoxy-Hb Deoxy- normal T2*-weighted signal T2*- - increased flow - decreased Deoxy-Hb Deoxy - increased CBV - reduced field gradients around vessels due to lower Deoxy-Hb Deoxy- increased T2*-weighted signal T2*- BOLD Activation Imaging • Resting state verses active state – e.g. Finger tapping, memory, reading, etc. • Perform analysis to detect regions which show a signal increase in response to the stimulus. 14 14 Simple Functional MRI Study Hand Clenching T2*Weighted Images Supplementary Motor Area Rest T2*Weighted Images Primary Motor Area Area Statistical Parameter Map Overlay onto Anatomical Image TimeTime-Course Response in Functional MRI • Brief neuronal events can elicit a (positive) blood flo and blood flow and oxygenation oxygenation response. Rise and Start of Event Fall in ~10 s Slower Negative Response • Reponses to events as brief as 50 ms have been recorded. Functional MRI response to a visual stimulus of duration 2s 15 15 Brain Function Neural Activity + Metabolic Function Glucose and Oxygen Metabolism + The BOLD Effect Cerebral Blood Cerebral Blood Flow Flow (CBF) - + Physiological Effects + Cerebral Blood Volume (CBV) Blood Oxygenation Physical Effects Effects + Magnetic Field Uniformity (microscopic) + Other Factors Hematocrit Vessel Diameter Vessel Orientation Blood Volume Fraction Field Strength Decay Time (T2*) + MRI Properties T2*T2*-weighted (BOLD) Image Intensity Hemoglobin • Magnetic properties of hemoglobin: hemoglobin: – Oxygenated hemoglobin is diamagnetic – Deoxy-hemoglobin is Deoxyparamagnetic • The presence of deoxydeoxyhemoglobin distorts the local magnetic field – After contrast development interval, this leads to reduction of signal strength 16 16 Bandettini and Wong. Int. J. Imaging Systems and Technology. 6,133 (1995) Increased Dephasing Vs. 17 17 Signal Changes with Deoxy-Hb DeoxyThe decay rate is proportional to the amount of deoxygenated hemoglobin. activated condition rest condition N-back Working Memory Task 0-Back Condition C P P 2-Back Condition C L X L C P P C L X Target Target 1-Back Condition C P P L 3-Back Condition C Target L X L C P P C L X L Target 18 18 . Working Memory Task The visual system responds similarly for all memory loads consistent with visual decoding Language areas have a complex response that is consistent with verbal rehearsal of memory items verbal rehearsal of memory items Broca’s Area (BA 44) Load: 3-back 0.2 2-back 1-back 0.1 0 0.4 % Signal Change 0.3 0-back h a n g e % Signal Change Visual (BA 18) 0.4 1 2 Scan 3 4 Load: 0.3 3-back 2-back 0.2 1-back 0-back 0.1 0 1 0.4 0.3 Loa d: 3-back 2-back 1-back 0-back 0.2 0.1 Cohen et al, Nature (1997) 0 1 2 3 2 3 4 Scan DLPFC (BA 46/9) % Signal Change . One area in prefrontal cortex exhibits a response consistent with memory storage or control Working memory task: Different areas of the brain respond differently to increasing memory load. 4 Scan Imaging Function in OCD • In this study, patients with OCD are compared to controls during performance controls during performance of of an interference task. • Patients showed significantly more activation in anterior cingulate cortex than controls controls. (From Fitzgerald et al. (2005), Biol Psych, 57:282-294) 19 19 Outline • Introduction (MRI, BOLD fMRI, Motivation) • Some Topics of Current Interest – Physiological noise (respiratory, cardiac) – Background Neural Fluctuations • Summary Physiological Noise B0 • Respiratory movement cause B0 fluctuations • Depends on distance from chest • Cardiac pulsation cause pressure,volume effects • Also has inflow/outflow of unsaturated spins • Both cardiac and respiratory rhythms cause intensity modulation of fMRI timecourse 20 20 Physiological Noise • Respiratory effect is global, cardiac effect is localized • At higher field strengths, physiological noise becomes more dominant Signal Variations Ed at Edge of Head and in CSF Spaces Major Vessels Respiratory Cardiac Physiological noise correction Intensity • Regression method (Hu & Le, MRM 34:201) (Hu • Waveforms used to assign a relative physiological phase for every k-space point k• Relative phase timecourse then used to form secondsecond-order Fourier series to model harmonics; series then fit to data and removed Image Number 21 21 Outline • Introduction (MRI, BOLD fMRI, Motivation) • Some Topics of Current Interest – Physiological noise (respiratory, cardiac) – Background Neural Fluctuations • Summary Neuronal fluctuations • Any neuronal process can lead to BOLD response: – Uncontrolled neuronal events – Different strategies for performing the same task – Subconscious processing • Temporal correlations of low-frequency low-fre fluctuations link functionally related systems in the brain, even at “rest” 22 22 Neuronal fluctuations • Fluctuations may indicate connectivity between functionally related areas • Disruption may indicate pathology Li et al Li, et al MRM 43:45MRM 43:45-51 (2000) Rest Saline Cocaine Neuronal fluctuations Motor activation, smoothed by 8 pts Low-frequency (0.08 Hz cutoff) w(0 cuto 23 23 Self Organizing Maps to Find Functionally Linked Areas Task Correlation Self Organizing Maps Special thanks to the Functional MRI Lab 24 24 ...
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