Brain imaging for fun and profit Daniel Marcus, PhD Director, Neuroinformatics Research Group @ Washington University School of Medicine Outline ‣ Brain imaging 101 ‣ Brain imaging & emerging technologies ‣ Brain imaging for hackers 100 billion neurons in the human brain 100 trillion synapses in the human brain Neuron is the basic computational unit in the brain Neurons are organized into circuits in the cerebral cortex Neuron Network Whole brain Brain imaging: single neuron In vivo microscopy Misgeld & Kerschensteiner, 2006 Brain imaging: neuronal networks Transgenics & fluorescence microscopy Livet, et al. Nature (2007) Brain imaging: whole brain ‣ Magnetic Resonance Imaging (MRI) - Structural MRI - Functional MRI - Functional connectivity MRI ‣ Computed tomography (CT) ‣ Positron emission tomography (PET) ‣ EEG, MEG, MRS, SPECT, DTI,… Structural MRI ‣ Essential in clinical care. ‣ Radiologists perform qualitative “lightbox” reads. ‣ Most psychiatric and neurological disorders are invisible to reading radiologists. Aging of the brain 20s 80s aging gracefully 80s with mild Alzheimer’s http://www.oasis-brains.org Brain volume declines with age Marcus et al., 2007 Advanced structural methods Van Essen et al., 2006 Csernansky et al., 2005 fMRI fMRI depends on functional localization The sad tale of Phineas Gage “[P]ossessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent” “fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating...” Harlow, J.M. (1868) Natural History Museum, London Another sad tale “A preexisting strong interest in pornography dating back to adolescence...” “An increasing interest in pornography... acquired an expanding collection of pornographic magazines and increasingly frequented Internet pornography sites.” “Much of this prurient material emphasized children and adolescents and was specifically targeted to purveyors of child pornography. He also solicited prostitution, which he had not previously done.” “Despite his strong desire to avoid prison, he could not restrain himself from soliciting sexual favors from staff at the rehabilitation center. ” Burns and Swerdlow, 2003 Another sad tale Anatomy of an fMRI study Study Test (in scanner) Buckner & Wheeler, 2001 Anatomy of an fMRI study Old New - = Buckner & Wheeler, 2001 Applications of fMRI ‣ Discovery of basic brain function ‣ Discovery of brain dysfunction in disease ‣ Evaluation of treatment efficacy ‣ Sketchy things http://www.noliemri.com “This is your brain on politics”, NY Times, Nov. 11, 2007 1. Voters sense both peril and promise in party brands. 2. Emotions about Hillary Clinton are mixed. 3. The gender gap may be closing. 4. Mitt Romney shows potential. 5. In Rudy Giuliani versus Fred Thompson, the latter evokes more empathy. 6. John Edwards has promise — and a problem. 7. Barack Obama and John McCain have work to do. Where are the language areas? Where are the motor areas? With fMRI, patients must perform an action, which is unreliable in clinic. Functional connectivity MRI (fcMRI) requires NO task. Highly reliable. 2 % BOLD Change 1.5 1 0.5 0 -0.5 0 50 100 150 -1 Time (sec) -1.5 200 250 300 2 % BOLD Change 1.5 1 0.5 0 -0.5 0 50 100 150 200 250 300 200 250 300 -1 Time (sec) -1.5 2 % BOLD Change 1.5 1 0.5 0 -0.5 0 50 100 150 -1 Time (sec) -1.5 Functional connectivity MRI (fcMRI) requires NO task. Emerging technology: quantitative radiology 2. fcMRI 1. Patient visits brain doctor. scan. Doctor orders fcMRI. 3. Quantitative analysis 4. Doctor receives report. 5. Doctor makes dx. and plans treatment. Quantitative report provides diagnostic measures, guides treatment, assesses response. Emerging technology: digital lab on the cloud Input: Raw MRI scans Output: Quantitative reports Emerging technology: Patient-driven care Microsoft HealthVault Emerging technology: Patient-driven care Google Health (prototype) Brain imaging for hackers ‣ Get yourself some brain images ‣ Get yourself some brain analysis tools ‣ Discover something, invent something Get your own brain scanned ‣ Buy a scanner and install it in your basement Get your own brain scanned ‣ Buy a scanner and install it in your basement ‣ Inflict severe brain injury Get your own brain scanned ‣ Buy a scanner and install it in your basement ‣ Inflict severe brain injury ‣ Volunteer for a study - Contact local research centers - Ask for your scans (“I’ve brought a blank CD with me. Will you please copy the DICOM files of my scans onto it?”) Use open access data ‣ Neuron: Neuron Database @ Yale Sense Lab ‣ Gene expression: Allen Brain Atlas ‣ Structural MRI: Open Access Structural Imaging Series (OASIS), mBIRN Data Repository ‣ Functional MRI: fMRI Data Center, fBIRN Data Repository ‣ Functional connectivity MRI: Brainscape oasis-brains.org brainscape.org Get yourself some tools Slicer, Caret, AFNI, Freesurfer, SPM, FSL, ImageJ Neuron Network Whole brain Genesis Neuron Ed Boyden, Thursday 11:50 “Synthetic Neurobiology: Towards Engineering Brain Circuits for Health and Human Augmentation” See also NITRC (http://www.nitrc.org/) Some unsolved problems ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ ‣ Automated brain extraction How many networks are in the brain Methods for distinguishing differences between populations Predicting disease and aptitude Data sharing Individual differences in performance (“gifted”, “savant”) Neuroethics “Deidentifying” images Bridging the spatial divide Security and privacy Data mining Start hacking. Brain imaging: gene expression Lein et al. Nature (2007) Functional Brain Imaging and Brain Blood Flow Veber den Kreislauf des Blutes in Menschlichen Gehirn (Concerning the circulation of the blood in the human brain) Verlag von Viet & Company: Leipzig, 1881 Angelo Mosso Forearm Brain Resting quietly Forearm Brain Arrow: room clock strikes 12 noon and of church bells heard Forearm Brain Arrow: Mosso asked Bertino if the Ave Maria should have been said Brain Forearm Arrow: “What is 8 x 12?” From: Angelo Mosso (1881) ω: response Monday noon, September 23, 1878 fMRI depends on blood oxygenation levels “Rest” “Activation” fMRI BOLD Signal Difference Image ∆ Blood Flow > ∆ Oxygen Consumption