Introduction: from image to inference

1 Introduction: Traumatic Brain Injury Chris Rorden Deficits associated with focal injury Typical scanning modalities 2 Describing cortex location Brodmann Areas (BAs, 1909) Appearance of cortex under microscope Not necessarily function Arbitrary numbers are hard to remember

3 Squirrels vs humans squirrel brain Surface of human brain is grooved. Surface of brain from many animals is flat. If we completely flattened a squirrel brain, it would be the size of a stamp. 4

Cortical folding Cortical folding increases surface area. Ridges are called Gyri (singular = Gyrus) Greek gyros = circle, hence a coil of brain cortex Valleys are called Sulci (singular = Sulcus). Latin = a groove. Gyri Sulci 5 Anatomy Surface of human cortex and cerebellum is very folded

Flattened, each hemisphere 1100cm2 Cerebellum is also 1100cm2 Crumpled shape hides size of cortex Compare Folded/Unfolded (from Marty Sereno) Human Chimpanzee Monkey 6 Frontal Cortex (ch12) Prefrontal cortex Dorsolateral) (DLPFC): Executive control,

perseveration Oribitofrontal (OFC): Inhibition, personality, OCD Anterior Cingulate: Abulia, Apathy 7 Hemispheres Right Hemisphere Injury Associated with Neglect Dominant Left Hemisphere Associated with Speech and Language

8 Language Production Brocas Area (1861) Difficulty in speech production Loss of ability to repeat speech Comprehension intact Foot of 3rd frontal convolution (BA 44) Left hemisphere (1865) Except left handers 9

Language Comprehension Wernickes Area (1874) Normal production (speech sounds and fluent nonsense) Sounds okay if you do not know the patients language (e.g. Chinese Wernickes aphasic would sound fine to me) Unaware of deficit Impaired comprehension Left hemisphere Superior temporal gyrus (BA 42, 22) 10

Wernickes prediction Predicted two language centers: Brocas Area: speech articulation. Wernickes Area: language comprehension. Predicted 3rd Syndrome: Disconnection syndrome Conduction aphasia Damage to arcuate fasciculus 11 Conduction aphasia

Can comprehend speech Articulation is intact Difficulty in repeating speech Lesions in Temporal Parietal Junction that knock out underlying white matter Patients with damage ONLY to the arcuate fasciculus can still generate speech. Why? Other pathways 12 Wernicke-Lichtheim (1885) Schema From auditory input (a) to motoric articulation of speech (m) Concepts

(Distributed) Brocas Aphasia Wernickes Aphasia Conduction aphasia 13 Memory Severe memory deficits seen with damage to Papez circuit. Fornix (Squires

Patient) Mammillary body (Korsakoff Patients) Hippocampal formation - HM 14 HMs lesion Corkin et al. (1997) bilaterally symmetrical

medial temporal pole most of the amygdaloid complex most or all of the entorhinal cortex anterior half of hippocampal formation (dentate gyrus, hippocampus, and subicular complex) 15 HM severe anterograde amnesia Anterograde amnesia since lesion Suggests encoding deficit Retrograde amnesia prior to lesion anterograde

1/9/1953 Memory retrograde 1945 1950 1955 16

Limbic system Memory and emotions tightly coupled. Fear and reward 17 Anatomy of t Patients who spontaneously confabulate tend to have orbitofrontal damage (aka damage to the ventromedial PFC).

18 Frontal lobe injury Personality Executive function, organization, problem solving Set switching - Perseveration 19 The homonculus Clear spatial mapping in gray and white matter. M1: movement

S1: sensation 20 Somatosensory Cortex Woolsey and Wann (1976) examined plasticity of somatosensory cortex in mice. Normally, cortical barrels topographic map of space. If whiskers removed, mapping of remaining whiskers grows 21

Phantom Limbs MEG offers evidence of reorganization. Patient lost one arm When face is brushed, he experiences his old arm is touched. Consistent spatial mapping of face to lost limb. MEG reveals that arm and face encroach hand area Figure below: arm hand and face regions in normal locations contralateral to intact arm, but arm and face representation have grown together contralateral to lost limb.

For review Ramachandran and Hirstein (2000), Brain, 121, 1603-1630 Arm Hand Face 22 Is plasticity reversible? Sirigu et al. (Nature Neuroscience, 4, 691-692). CD lost both hands in 1996 Bilateral hand transplantation in 2000 Both M1 and S1 show elbow activity had taken over hand area before graft.

After graft: hand area enlarges and elbow representation shrinks. 23 Thought experiment What brain injury leads to visual field injury? 24 Mapping Lesions With MRIcron it is easy to trace injured area. We can create an overlay plot of damaged region.

For example: here are the lesion maps for 36 people with visual field defects: 25 The problem with overlay plots Overlay plots are misleading: Highlight areas involved with task (good) Highlight areas commonly damaged (bad) Brain damage is not random: some brain areas more vulnerable. Overlay plots highlight these areas of common damage. Solution: collect data from patients with similar injury but without target deficit.

26 Value of control data Solution: collect data from patients with similar injury but without target deficit: 27 Statistical plots We can use statistics to identify areas that reliably predict deficit E.G. Damage that results in visual field cuts 28

Acute brain imaging Structural and perfusion imaging techniques used at admission. Designed to be fast, does not require conscious patient. In contrast, functional measures require participation and typically have long duration (future lectures). 29 CT versus MRI scans CT Clinically crucial:

Detect acute hemorrhage Can be conducted when MRI contraindicated Limited research potential Exposes individual to radiation Difficult to collect control data Typically very thick slices, hard to normalize Little contrast between gray and white matter MRI Different contrasts (T1,T2, DWI) No radiation, so we can collect thin slices

if we have time. 30 Xrays and CT single contrast mechanism: how well does tissue attenuate rays. Air ~transparent, bone ~opaque, soft tissue ~translucent The only way to influence Xray contrast is to change tissue. E.G. injection of radio-opaque Gd into bloodstream

Analogy: overhead projector ~ Xray CT: reconstructed from series of Xrays 31 CT Terms Computerized Axial Tomography (CAT/CT) measured Xray attenuation. Hyperintensity: Bright spot Hypointensity: Dark spot For CT (but not MRI) you can say density instead of intensity W/Window Width describes contrast

setting for display C/L/Window Center/WindowLevel describes brightness setting for display 32 Image Center/Width How do we view an image that has higher resolution than our computer screen? Panning changes the image center. Pan

We will not see some of the image. Zooming changes the image width. We may lose details. Zoom 33 Intensity Center/Width (Brightness/Contrast) Adjust brightness window center

E.G. range -64..124 makes muscles gray, 114..302 shows kidneys C/W 30/188 vs C/W 208/188 Adjust contrast window width E.G. range -64..124 shows muscles, -400..596 shows full range. C/W 30/188 vs C/W 98/996 CT intensity is calibrated (kidneys always ~208 Hounsfield units)

Air -1000 Water 0 White Matter 25 Gray Matter 40 Bone 1000 Pan Zoom 34 CT Perfusion CT can be enhanced with a

contrast agent. For example, Gadolinium (Gd) injected into the blood stream. Gd is radio-opaque. Can show areas of reduced, delayed or slowed flow. Acute mismatch of perfusion and injury shows tissue that can be salvaged. 35 Major Cerebral Arteries de Lucas E M et al. Radiographics

2008;28:1673-1687 Injury not random: common patterns to stroke and TBI. 36 CT Signs of TBI Hematoma: pooled blood Contusion: swelling, bruising.

EDH: epidural hematoma DAI: diffuse axonal injury SDH: subdural hematoma, SAH/IVH: subarachnoid and intraventricular hemorrhage. 37 Magnetic Resonance Imaging (MRI) MRI uses strong magnetic field and radio signals to acquire image. Analogy: Low energy state for compass needle is North, but tap briefly knocks out of alignment.

Likewise, hydrogen atoms align to field. Radio signal knocks them out of alignment, they echo radio signals while they return to alignment. 38 Conventional MRI scans T1 (anatomical): fast to acquire, excellent structural detail (e.g. white and gray matter). T2 (pathological): slower to acquire, therefore usually lower resolution than T1. Excellent for finding lesions. T1

T2 T1 Air CSF T2 Bone Air GM WM

GM WM Fat CSF edema 39 Lesion mapping: T1 vs T2 T1 scans offer good spatial resolution. T2 scans better for identifying extent of injury, but poor spatial resolution.

Solutions: 1. Acquire chronic T1 (>8 weeks) 2. Acquire both T1 and T2, use T2 to guide mapping on T1. 3. Acquire T2, map on normalized iconic brain (requires expert lesion mapper). 4. Aquire high resolution T2 image, use for both mapping and normalization (e.g. 1x1x1mm T2 ~9min). Requires latest generation MRI. Note: Many clinicians like FLAIR as it attenuates CSF. Lesion signal similar to T2. Normalization tricky (thick slices, no standard template). T1

T2 FLAIR 40 Imaging acute stroke T1/T2 MRI and x-rays can not visualize hyperacute ischemic strokes. Acute: Subtle low signal on T1, often difficult to see, and high signal (hyperintense) on spin density and/or T2-weighted and proton densityweighted images starting 8 h after onset. Mass effect maximal at 24 h, sometimes starting 2 h after onset. Subacute (1 wk or older): Low signal on T1, high

signal on T2-weighted images. Follows vascular distribution. Revascularization and blood-brain barrier breakdown may cause enhancement with contrast agents. Old (several weeks to years): Low signal on T1, high signal on T2. Mass effect disappears after 1 mo. Loss of tissue with large infarcts. Parenchymal enhancement fades after several months. www.strokecenter.org/education/ct-mri_criteria/ acute +3days

CT T2 www.med.harvard.edu/AANLIB/ 41 Imaging Hyperacute Stroke T1/T2 scans do not show acute injury. Diffusion and Perfusion weighted scans show acute injury: Diffusion images show permanent injury. Perhaps good predictor of eventual recovery. Perfusion scans show functional injury. Best correlate of acute behavior.

Difference between DWI and PWI is tissue that might survive. Diaschisis: regions connected to damaged areas show acute hypoperfusion and dysfunction. T2 DW 42 Perfusion imaging Allows us to measure perfusion Static images can detect stenosis and

aneurysms (MRA) Dynamic images can measure perfusion (PWI) Measure latency acute latency appears to be strong predictor of functional deficits. Measure volume Perfusion imaging uses either Gadolinium or blood as contrast agent. Gd offers strong signal. However, only a few boluses can be used and requires medical team in case of (very rare) anaphylaxis. Arterial Spin Labelling can be conducted 43

MRI versus CT MRI disadvantages: Expensive Slow to acquire Poor bone contrast MRI advantages: No ionizing radiation Many contrast modalities Some acute modalities 44

T2 vs SWI for micro-hemorrhage Susceptibility weighted imaging shows venous blood useful for microbleeds, DAI 45 Diffuse Axonal Imaging SWI and GRE images of individual with DAI

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