Using Near-Infrared Light to Image how the Brain Rewires after Injury and Rehabilitation George Alexandrakis Department of Bioengineering University of Texas at Arlington Functional Near-Infrared Spectroscopy (fNIRS) Near infrared (NIR) light (750-900 nm) can penetrate the human scalp/skull, reach the brain, and its absorbed by the oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) in the tissue. fNIRS can be thought of as the optical analogue of fMRI for imaging the cerebral cortex. Physiological Basis of the fNIRS Signal: Changes in Brain Oxygenation • The neuronal firing occurring when the brain does work results into an oversupply of oxygen in areas that doe the work – this is known as neurovascular coupling • The increase in cerebral blood oxygenation during functional activation is mostly due to an increase in blood flow velocity, and occurs without a significant swelling of the blood vessels. Functional Near-Infrared Spectroscopy (fNIRS) Imaging as an alternate technology for imaging brain function Main body of the CW-5 system Geometry of CW-5 probe on the motor cortex (circle: light source; square: detector). What does an fNIRS measurement look like? Tapping ∆HbO Full time-series 100 Average time-series 200 seconds 300 400 Source-detector geometry on head ∆HbO fNIRS Image 0 10 20 30 seconds 40 What do fNIRS images look like? Time series (5sec/frame) Patient with Right Hemiparesis Right Finger Tapping Block average (30 sec) Don’t people usually lie inside fMRIa tube to map their brains? Functional Magnetic Resonance Imaging (fMRI) An example of the information one gets from fMRI: A map of change in deoxygenated blood during a specified activity Brain activity is superimposed onto an anatomical map of the brain in 3D Vandermeeren, et al 2003 Limitations of fMRI • Extremely rigid stabilization of the head • High magnetic fields and rapid RF gradients • High intensity acoustic environment • Highly propensity for movement artifacts • 50% of normal 5 yr-old can have a successful fMRI Wilke, et al 2003 Validation of fNIRS Imaging with fMRI (a) HbO 0 o1 o9 o8 o7 o6 o5 o4 o3 o2 HbR o10 o11 o12 o13 o14 -2 0 o1 o9 o8 o7 o6 o5 o4 o3 o2 HbT o10 o11 o12 o13 o14 -2 x1 x2 x3 x4 x5 0 o1 o9 o8 o7 o6 o5 o4 o3 o2 o10 o11 o12 o13 o14 -2 x1 x2 x3 x4 x5 x1 x2 x3 x4 x5 -4 -4 -4 -6 o15 o16 o17 o18 o19 o20 0 5 10 -6 o15 o16 o17 o18 o19 o20 0 5 10 -6 o15 o16 o17 o18 o19 o20 0 5 10 X3 X2 (b) X4 X2 O16 O16 O17 O18 -1 0 1 2O19 -5 -1 0 1 2 -1 -5 0 1 2 -5 x 10 x 10 x 10 (a) fNIR and (b) fMRI images, showing good spatial correlation during a 15-second finger tapping task. The data were averaged over 10 blocks. Specifically, (a) shows HbO, HbR, and HbT activation maps that are reconstructed from fNIR measurement: x represents sources and o represents detectors; (b) shows axial (left panel), coronal (middle), and sagittal (right) views of fMRI images during finger tapping. Limitations: • Can only see the cortical surface of the brain but not deeper • Lower spatial resolution (~1 cm) In what clinical applications could using fNIRS have an advantage over fMRI? “…So far, fNIRS has been promoted in a number of fields in which fMRI is limited due to the constraints induced by the scanning environment and the experimental measurements take place in a more comfortable and natural environment… Only these devices can be utilized for example in infant and children developmental studies, in neuro-rehabilitation assessment, and in simultaneous brain activation studies on multiple subjects.” M. Ferrari, V. Quaresima / NeuroImage 63 (2012) 921–935 FNIRS applications that I have pursued so far: • Monitoring brain plasticity during rehabilitation in children with cerebral palsy (CP) • Monitoring brain activation while playing Wii games • Continuous bedside monitoring of brain health in traumatic brain injury (TBI) • Real-time guidance for treatment optimization (electrical stimulation) in stroke Cerebral Palsy (CP) • What is Cerebral Palsy? – Lesion or stroke in the cortex or in the subcortex caused before or during birth. – Results in damage to the motor control areas of the brain which leads to restricted movements. – Affects 1 in 500 children • Currently Used Functional Assessments – Physical Assessments • Measures refined motion • Measures ability to perform daily activities – EEG measures neuronal activity – fMRI measures hemodynamic activity fNIRS for Cerebral Palsy (b) (a) Left Hemiparesis (c) Cortical Subject 1 R L (d) (e) Right Hemiparesis (f) Subcortical R Subject 2 L (g) (h) Right Hemiparesis (i) Subcortical R Healthy, Control L Subject 3 Subject with CP (note lesion) recruits secondary cortical regions for finger tapping Texas Scottish Rite Hospital for Children Pirate Camps 2012-2013 Constraint Induced Movement Therapy (CIMT) Group Activity, Outside Activities, Craft, Fine Motor Stations, Gross Motor Stations, Large Group Game, Personal Goals (tying laces, holding a fork, buttoning a shirt) 2 weeks, 6 hours per day Correlation between improved hand use and cortical activation laterality R2 = 0.94 P < 0.01 - Increased contralateral cortical activity after CIMT (Laterality index improves) - Improvement in uni-manual hand use after CIMT (Melbourne test benefit) - Increase laterality and hand use significantly correlate (p < 0.01) fNIRS detected a relapse at six moths post-therapy Healthy Children n=6 Before Rehabilitation Immediately after Rehabilitation Children with CP n=6 Six months after Rehabilitation • Less impaired subjects did not benefit as much from CIMT, as proven by the non-significant changes in their clinical scores post-therapy. • There were no children with CP in this study that significantly improved both their unimanual and bimanual abilities after CIMT while also normalizing their sensorimotor activation patterns, as measured by fNIRS. • The laterality index and the resting-state functional connectivity appeared to be normalized, compared to the corresponding patterns seen in the controls group, immediately post-CIMT but then relapsed at the six-month time point. On the other hand, the blood flow metric remained at near-normal values even at the six-month time point. • ‘Booster’ treatments would be needed to maintain long term benefits. Measuring Brain Activity While Playing Nintendo Wii and I-Pad Probe Configuration L Right Handed Movements R PMC PMC M1 M1 S1 SMA S1 PMC M1 PPC PPC PPC SMA S1 M1 S1 PPC Activation Pattern Changes Time Signals Baseball (Wii) Boxing (Wii) Guitar Hero (I-pad) Activation Maps PMC M1 S1 SMA PPC PMC M1 S1 PPC SMA PPC PMC M1 S1 PPC PMC M1 S1 PMC M1 S1 PPC SMA PMC M1 S1 PPC Transcranial Direct Current Stimulation (tDCS) • tDCS is a form of neurostimulation which delivers a constant, low current to the brain by two 5 x 5 cm2 electrodes (anode and cathode) • tDCS is potentially helpful in treating a wide range of physiological disorders – – – – – – Depression Stroke Alzheimer’s Chronic Pain Epilepsy Parkinson’s Disease How Does tDCS Work? • tDCS stimulation modulates brain function by changing the neuron membrane polarization. • A change in the membrane polarization leads to changes in neuron, synaptic, and network activity. • The membrane polarization will either increase or decrease depending on the current direction. Two Types of tDCS Stimulation • Anodal Stimulation Cathode Anode – The anode is placed over the area being excited. • Cathodal Stimulation – The cathode is placed over the area being suppressed. • The direction of the current goes from the Anode to the Cathode. Cathode Anode Detectors Sources Hand Device CW-6 Data Box Instrumentation Setup EMG Box tDCS Box Protocol Move dotted white line into the white box, and keep it there for 1 s. Then rest for ~12 s. Repeat this 20 times. Hand device FNIRS Probe Configuration L R PMC M1 S1 PPC PMC SMA M1 S1 PPC tDCS Electrode fNIRS Source Location fNIRS Detector Location Suppression of critical motor control centers creates transient ‘virtual’ brain lesions Excited Excited Suppressed Before Suppressed During tDCS Anode Electrode tDCS Cathode Electrode fNIRS Source Location fNIRS Detector Location After Indicated ROI Exciting the cortical region in use, increased the activity in that hemisphere Suppressing the cortical region in use, resulted in activity in both hemispheres. Changes in arm muscle excitability and wrist flexion performance after tDCS Suppressed Excited WE Excited Suppressed WE WF WF The perturbation tDCS (ptDCS) concept: A novel, fast method to derive a personalized tDCS electrode arrangement that yields maximal improvements in upper extremity performance ptDCS Protocol Typical tDCS protocol uses a current of 1 – 2mA for a period of 20 minutes. Effects can last up to a week. ptDCS applies current at 0.5 mA for 40 s. This reduced the effects to ~3 minutes. Schematic of the 20 different electrode montages measured during a ptDCS protocol. Red squares indicate anodal (excitation) and black squares cathodal (suppression) stimulation. All were done in a single ~2 hour session. Shortening tDCS Effects tDCS tDCS + Flexion • tDCS applied with current of 0.5 mA for 40 s • ΔHbO returned to pre-tDCS baseline levels within 3 minutes • Allows 20 stimulations to be applied within a 2 hour period. Arm Performance Metrics • Reaction Time (RT): How quickly one responds to the stimulus. • Error: How inaccurate a person puts the cursor into the target. • Error x RT product: Measure of overall performance. Important points found with ptDCS-guided treatment so far: • Current clinical scales are not specific enough in reflecting targeted rehabilitation improvements as they add apples to oranges • General Systems Performance Theory (GSPT) is proposed as a physiology-driven way to derive quantitative performance metrics (Dr. G. Kondraske) GSPT-based resource demand function (RDF) provides quantitative insight into the relationship between EMG and task performance (reaction speed). The RDF defines a minimum level of EMG activation required to achieve a given maximum reaction speed (green curve). Inter-Subject Variability in Healthy Subjects The typically studied tDCS montages (A and M) do not help improve any healthy subjects. Two tDCS montages (C and K) cause 3 healthy subjects to worsen (p < 0.01). A never before used dual PMC montage (O) presented significant (p < 0.01) improvement in all healthy subjects. Identified Optimal tDCS Electrode Arrangement in Stroke Patients is Better than dtDCS Anode Cathode TBI patient population • 5 TBI patients were recruited for this study – Glasgow coma score (GSC) • GCS 6 (1 patient) • GCS 13-14 (4 patients) – Age: 53.8 ± 19.6 years – Gender: • 3 male • 2 female Fluctuation amplitude Healthy Subject (GCS 15) Patient 4 (GCS 6) Amplitude Patient 1 (GCS 14) CT Images L Indicate lesions or subdural/subarachnoid hemorrhages R L R Resting-state connectivity of healthy subjects Component 2 24 % 19 % Component 4 Healthy 2 (GCS 15) 14 % Component 3 Component 1 Healthy 1 (GCS 15) 17 % Resting-state connectivity of TBI patients GCS 15 (Healthy) GCS 14 GCS 6 18 % 39 % 75 % 17 % 28 % 12 % Indicate lesions or subdural/subarachnoid hemorrhages Resting-state connectivity with respect to injury location CT Images Connectivity Patient 1 (GCS 14) Patient 3 (GCS 14) Patient 2 (GCS 14) Collaborators UT Arlington Dr. Hanli Liu (BME) Dr. Fillia Makedon (CSE) Dr. Fenghua Tian (BME) UT Southwestern Medical Center at Dallas Dr. Timea Hodics (Neurology) Dr. Anne Stowe (Neurology) Current Graduate Students Mr. Bilal Khan (UT Arlington) Mr. Nathan Hervey (UT Arlington) Mrs. Jianwei Cao (UT Arlington) UT Dallas Dr. Duncan MacFarlane (EE) Texas Scottish Rite Hospital for Children Dr. Mauricio Delgado (Pediatric Neurology) Past Graduate Students Ms. Ankita Chainani (UT Arlington) Ms. Laura Shagman (UT Dallas) Industry Dr. Chester Wildey (MRRA Inc) Mr. Robert Francis (Raytheon) Grants Current NIH/NIBIB 1R01EB013313-01 (Alexandrakis), Near Infrared Brain Imaging for Guiding Treatment in Children with Cerebral Palsy UTA – UTD – THR Collaborative Research Program (Alexandrakis), A Near-Infrared Brain Imaging System for the Continual Bedside Monitoring of Hemorrhagic Progression of Contusions after Traumatic Brain Injury Recently Completed UT Arlington – UT Dallas & Texas Health Resource Collaborative Research Program (Alexandrakis), A Near-Infrared Brain Imaging System for the Continuous Bedside Monitoring of Intracranial Pressure Buildup in Patients with Traumatic Brain Injury NSF/CPS 1125441 (Makedon), A Novel Human Centric CPS to Improve Motor/Cognitive Assessment and Enable Adaptive Rehabilitation UT Arlington – UT Dallas & Texas Health Resource Collaborative Research Program (Alexandrakis), A Breakthrough Probe Technology for Translating Near-Infrared Brain Imaging into a Routine Clinical Tool for Assessing Motor Deficits in Children with Cerebral Palsy United Cerebral Palsy Research & Educational Foundation (Delgado), Assessment of Neuroplasticity in Children with CP: A MultiSource-Detector Near Infrared Spectroscopy Imaging Study Recent Publications Hodics T*, Khan B*, Hervey N, Stowe A, Kondraske GV, Alexandrakis G. Functional near-infrared spectroscopy maps cortical plasticity underlying altered motor performance induced by transcranial direct current stimulation. J Biomed Opt. (Accepted October 2, 2013; *equal first authorship). B. Khan, C. Wildey, R. Francis, F. Tian, M.I. Romero, M.R. Delgado, N.J. Clegg, L. Smith, H. Liu, D.L. MacFarlane, G. Alexandrakis, “Improving optical contact for functional near infrared brain imaging with brush optodes,” Biomed. Opt. Express, 3(5):878–898 (2012). B. Khan, P. Chand, G. Alexandrakis, “Spatiotemporal relations of primary sensorimotor and secondary motor activation patterns mapped by fNIR imaging,” Biomed. Opt. Express, 2(12):3367–3386 (2011). F. Tian, M.R. Delgado, S.C. Dhamne, B. Khan, G. Alexandrakis, M.I. Romero, L. Smith, D. Reid, N.J. Clegg, H. Liu, “Quantification of Functional Near Infrared Spectroscopy to Assess Cortical Reorganization in Children with Cerebral Palsy,” Opt. Express 18(25):25973-25986, (2010). B. Khan, F. Tian, K. Behbehani, M.I. Romero-Ortega, M.R. Delgado, N. Clegg, L. Smith, D. Reid, H. Liu, G. Alexandrakis, “Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near infrared spectroscopy,” J. Biomed. Opt. 15(3):036008-1 – 14, (2010). Publicity http://www.sciencecodex.com/the_hair_brush_that_reads_your_mind http://news.cnet.com/8301-27083_3-20020193-247.html (High-tech hair brush improves optical brain scans)