# Presentation: 450618

## Neuroimaging with MRI:Some of the Things We Can See

- Robert W Cox, PhD
- Scientific and Statistical Computing Core
- DIRP / NIMH / NIH / DHHS / USA / Earth

- 06 Dec 2007

## Preview of Coming Attractions

- Quick overview of MRI physics (all on one slide!)
- Some images and their applications
- T1-weighted = gray/white/CSF delineation
- T2-weighted = detection of tissue abnormalities
- T2*-weighted = venography
- Contrast agents
- Enhancement of signals from various tissue types/conditions
- DCEMRI & tumor quantification
- Diffusion weighted imaging = white matter quantification
- Imaging brain function with MRI
- Brain atlases and statistical neuroanatomy

## Synopsis of MRI

**1**) Put subject in big magnetic field [and leave him there]
- 		 Magnetizes the H nuclei in water (**H**2O)
**2**) Transmit radio waves into subject  [about 3 ms]
- 		  Perturbs the magnetization of the water
**3**) Turn off radio wave transmitter
**4**) Receive radio waves re-transmitted by subject’s H nuclei
-  		  Manipulate re-transmission by playing with H magnetization with extra time-varying magnetic fields during this readout interval  [10-100 ms]
-  		  Radio waves transmitted by H nuclei are sensitive to magnetic fields — those imposed from outside and those generated inside the body:
-  		  Magnetic fields generated by tissue components change the data and so will change the computed image
**5**) Store measured radio wave data vs time
-  		  Now go back to **2**) to get some more data [many times]
**6**) Process raw (“*k*-space”) radio wave data to reconstruct images

## T1-Weighted Images

- Images whose design (timing of radio pulses and data readout) is to produce ***contrast***  between gray matter, white matter, and CSF

- Three axial (AKA transaxial or horizontal) slices:
- Spatial resolution is about 1 mm3
- Acquisition time for whole head is 5-10 minutes

## Zooming In

- Can follow GM cortex fairly well
- Can measure thickness of cortex and try to quantify vs age and/or disease and/or genes
- Bright spots and lines: arterial inflow artifact
- Leads to idea of MRA = Magnetic Resonance Angiography = acquire images to make arteries stand out even more
- Higher spatial resolution is possible
- At the cost of scan time

## Three Slices from a Volume

- A single acquisition is somewhat noisy
- Previous T1-weighted image was actually average of 4 separate acquisitions (to average out noise)
- MRI can be a 2D or a 3D acquisition technique

## Some Bad MR Images

- Subject moved head during acquisition
- Ghosting and ringing artifacts
- Might be OK for some clinical purposes, but not much use for most quantitative brain research

## MRI vs CT in the Brain

- Skull gets in the way of X-ray imaging:
- Bone scatters X-rays much more than soft tissue
- MRI radio waves pass unimpeded through bone

- Images have been “skull stripped”

- Same patient

## Brain Slice Animations

- Fun to watch (brain soup)
- More useful if movement through slices is under your direct interactive control

## 3D Visualization

- MR images are 3D, but screens and retinas are 2D
- Understanding 3D structures requires looking at them in different ways

- Volume rendering of T1-weighted image showing how corpus callosum spreads into hemisphere

## T2-Weighted Images

- Often better than T1-weighting in detecting tumors and infarcts (usually radiologists look at both types of scans)

- Same subject

## T2*-Weighted Images

- Designed to make venous blood (with lots of deoxy-hemoglobin) darker than normal tissue = *venography*

- Output image

- minIP 1 slice

- minIP  2 slices

- Images post-processed to enhance small effects

## MRI Contrast Agents

- Chemicals injected into blood, designed to alter MRI signal by affecting magnetic environment of H nuclei
- Developed starting in late 1980s (and still continuing)
- Used millions of times per year in USA
- Designed to be biologically inert (only “active” magnetically)
- About 1 person in 100,000 has allergic reaction
- Purpose is to increase ***contrast****** ***of some tissue type
- Most commonly used is Gd-DTPA (Magnevist)
- Gadolinium ion (highly magnetizable) chelated to a molecule that won’t pass an intact blood-brain barrier
- Makes T1-weighted images brighter where it accumulates and makes T2- and T2*-weighted images darker
- Deoxy-hemoglobin is an *endogenous* T2* agent

## Tumor: T2 and T1+contrast

- T2-weighted

- T1-weighted post-contrast

## T2* MRV on a Seizure Patient

- Gd-enhanced T1-weighted

- Gd-enhanced T2*-weighted

- Bad

## DCE-MRI and Brain Tumors

- DCE = Dynamic Contrast Enhancement
- Inject contrast agent rapidly (“bolus”) and take rapid images of brain repeatedly to observe its influx
- Cost of taking such rapid images: coarser spatial resolution *and* limited spatial coverage *and* more noise
- Below: rapid T1-weighted images (20 s per volume)
- 12 slices at 5 mm thickness (0.9 mm in-slice resolution)

## Time Series of Images

- Time Point #7:
- Before Gd hits
- (bright spot =
- sagittal sinus)

- Time Point #9:
- Gd into vessels

- Time Point #23:
- Gd leaks into tumor
- (now mostly gone from vessels)

- From John Butman’s group in NIH/CC

## Time Courses of Voxel Intensities

-  _Voxel in tumor_
-  Can fit math model of Gd infiltration to quantify “leakiness”
-  Tumor grade?
-  Necrosis?
-  Treatment effects?

-  _Voxel in vessel_
-  This data is used as “arterial input function” for math model below

## Diffusion Weighted Imaging

- Water molecules diffuse around during the imaging readout window of 10-100 ms
- Scale of motion is 1-10 microns  size of cells
- Imaging can be made sensitive to this random diffusive motion (images are darkened where motion is larger)
- Can quantify diffusivity by taking an image without diffusion weighting and taking a separate image with diffusion weighting, then dividing the two:
-      Image(no DWI)  Image(with DW) = *e** **b****D*
-  where *b* is a known factor and *D* is a coefficient that measures (apparent) diffusivity
- Can thus compute images of ADC from multiple (2+) scans

## DWI in Stroke

- ADC decreases in infarcted brain tissue within *minutes* of the vessel blockage
- Causes thought to include cell swelling shutting down water pores that allow easy H20 exchange between intra- and extra-cellular spaces
- Cell swelling also causes reduction in extra-cellular space which has a higher ADC than intra-cellular space
- Stroke damage doesn’t show up on T1- or T2-weighted images for 2-3 *days* post-blockage
- DWI is now commonly used to assess region of damage in stroke emergencies
- And whether to administer TPA (clot dissolving agent with many bad side-effects)

## From Mike Mosely (Stanford Radiology)

## Diffusion Tensor Imaging

- Diffusive movement of water in brain is not necessarily the same in all directions — not isotropic
- In WM, diffusion transverse to axonal fiber orientation is much slower (3-5 times) than diffusion along fibers
- This anisotropic diffusion is described mathematically by a *tensor*  33 symmetric matrix  3 perpendicular directions with 3 separate diffusion coefficients *D* along each one
- Diffusion weighted MR images can be designed to give more weight to diffusion in some directions than in others
- By acquiring a collection (7+) of images with different directional encodings, can compute the diffusion tensor in each voxel  _WM fiber orientation_

## DTI Results

- Unweighted (baseline b=0) image

- Fractional Anisotropy (FA):
- Measures how much ADC depends on direction

- FA Color-coded for fiber directionality:
*x** *=* *Red *y** *=* *Green
*z** *=* *Blue

## Other Types of MR Images

- MR Angiography = designed to enhance arterial blood (moving H20) — sometimes with Gd contrast
- Much more commonly used than MRV
- Useful in diagnosing blood supply problems
- Magnetization Transfer = designed to indirectly image H in proteins (not normally visible in MRI) via their magnetic effects on magnetized H in water
- Useful in diagnosing MS and ALS abnormalities in WM
- Especially when used with Gd contrast agent
- Possibly useful in detecting Alzheimer’s plaques
- Perfusion weighted images = designed to image blood flow into capillaries only
- MRI methodology R&D continues to advance ....

## Functional Brain MRI - 1

- 1991: Discovery that oxygenation fraction of hemoglobin in blood changes *locally* (on the scale of 1-2 mm) about 2 seconds after increased neural activity in the region
- Recall T2*-weighted imaging: sensitive to deoxy-hemoglobin level in veins
- Arterial blood is normally nearly 100% oxygenated
- Resting state venous blood is about 50% oxygenated
- Neural activation *increases* oxygenation state of venous blood (for various complicated reasons)
- Since deoxy-hemoglobin makes T2*-weighted image darker, neural activation will make image brighter (because have less deoxy-hemoglobin) *locally*

## Functional Brain MRI - 2

- FMRI methodology:
- Scan brain with T2*-weighted sequence every 2-3 seconds
- Subject performs task in an on/off fashion, as cued by some sort of stimulus (visual, auditory, tactile, ...)
- Usually gather about 1000 brain
- 	volumes at low spatial resolution
- Images look bad *in **space*, but
- 	are designed to provide useful
- 	information through *time*
- Analyze data time series to look
- 	for up-and-down signals that
- 	match the stimulus time series

- A single fast (100 ms) 2D image

## Functional Brain MRI - 3

-    One fast image   *and*    a 33 grid of voxel time series

## Brain Activation Map

- Time series analysis results overlaid on T1-weighted volume

## Applications of FMRI

- Clinical (in individuals):
- Pre-surgical mapping of eloquent cortex to help the surgeon avoid resecting viable tissue
- Can combine with DTI to help surgeon avoid important white matter bundles (e.g., cortico-spinal tract)
- Measure hemispheric lateralization of language prior to temporal lobe surgery for drug-resistant epilepsy
- Neuroscience (in groups of subjects):
- Segregation of brain into separate functional units
- What *are* the separate functions of the brain pieces-parts?
- Discover differences in activity between patients and normals (e.g., in schizophrenia)
- Map functional (i.e., temporal) connectivity
- vs. anatomical connectivity (e.g., via DTI)

## Other Brain Mapping Tools

- Downsides to FMRI:
- Poor time resolution since we are looking at signal from blood, not directly from neurons
- Physiological connection between neural activity and hemodynamic signal measured by MRI is complex and poorly understood
- EEG and MEG: signal is from neural electrical activity, so time resolution is great
- But spatial resolution is bad (and confusing)
- FDG PET: signal is closer to neural metabolism
- But must give subject radioactive substance — limits repeat studies, etc.
- Time resolution much worse than FMRI, and space resolution somewhat worse
- Through-the-skull IR: new-ish; hits brain surface region

## Digital Brain Atlases

- Attempts to provide *statistical* localization on MRI scans of brain regions determined by post-mortem histology
- Statistical because each person’s brain is different in details
- Major effort by Zilles’ group in Jülich to categorize 10 brains, region by region, using histology
- Also available: Talairach & Tournoux atlas regional boundaries (derived from 1 brain in the 1980s, plus some literature search to clear up ambiguities in the published book) — from Fox’s group at UT San Antonio
- These are the two freely available human brain atlas databases now distributed
- Also are some privately held databases (corporate & academic)

## Cyto-architectonic Atlas

- “Where Am I” Navigation

## Statistical Neuroanatomy

- Attempts to summarize and describe populations (and differences between populations) from MRI scans
- Example: Voxel Based Morphometry (VBM)
- Try to characterize “gray matter density” as a function of location in brain, then map differences between patients and normals, ...
- Can also be applied to other measures (e.g., FA)
- Example: Cortical thickness maps
- Extract gray matter cortical ribbon from images and measure thickness at each location
- Map vs age, disease condition, ...
- Biggest practical issue: ***Spatial*** ***Alignment***

## VBM in Williams Syndrome

- Yellow overlay shows regions with gray matter volume reduction in WS
- (13 WS patients vs 11 normals)
- From Karen Berman’s group in NIMH

- _VBM in Williams Syndrome_

## The End (almost)

- MRI is:
- Widely available (9000+ scanners in USA)
- Harmless to subject ***if *** proper safety precautions are used
- Very flexible: can make image intensity (contrast) sensitive to various sub-voxel structures
- Still advancing in technology and applications
- Still in a growth phase for brain research
- Limitations on spatial resolution and contrast types are frustrating
- e.g., little chemical information is available with even the most sophisticated scanning methods
- Novel contrast agents making some inroads in this direction

## Unfair Pop Quiz

- What are these images of?

- dolphin brain