Brain Imaging Core: MRI of Structure,

Microstructure, Metabolites, and Animals

Andrew L. Alexander, Ph.D.alalexander2@wisc.edu

Departments of Medical Physics & Psychiatry

Waisman Laboratory for Brain Imaging and Behavior

University of Wisconsin - Madison

Magnetic Resonance Imaging (MRI)

• 3 Tesla!

• 10,000 times Earth’s magnetic field

• Superconducting (magnet is always on)

• Cooled with liquid helium (-265 °C)

• 11,000 kg.

• ~200km of wire

Large magnet

Send radio waves into body(no X-rays)

Ras

mus

M. B

irn

T1-weighted T2-weighted

Structural MRI of the Brain

Morphometry – Size and Shape of Brain Structures

Moo Chung

AJNR 2001

Cortical Thickness - Freesurfer

Greg Kirk

Diffusion Tensor Imaging Non-invasive imaging technique for estimating the diffusion properties of

water in biological tissues Highly sensitive to differences in white matter microstructure White matter connectivity properties influence microstructure and diffusion

Orientationof WhiteMatter

T2WStructure

Total Diffusion

(1/Density)

Anisotropy(‘White

Matter’)

Axonal DensityDiffusion

Myelin Diffusion

More barriers Fewer barriersMore barriers Fewer barriers

ADC low ADC highADC low ADC high

Diffusion probes tissue microstructureDiffusion probes tissue microstructure

ADC = ADC = ApparentApparent Diffusion Coefficient Diffusion Coefficient

x

y

z

1, 12, 2

3, 3

x

y

z

The Diffusion Tensor is a Matrix

Diffusion Tensors

x

y

z

x

y

z

xy

z

Rhesus NH Primate Template Human Template

Study Specific DTI Templates

N=270; Adluru et al. submitted

Rhesus Tractography

Human Tractography

Nagesh Adluru, Do Tromp

TRACULA

Tracula• Automated Global Tractography Method - Freesurfer

Greg Kirk;From A. Yendiki 2011

Framework of modeling human connectome using dMRI

[Zalesky et. al., 2010]

Structural Network Connectivity Mapping

Chung 2009

Degree of Connectivity

Control AutismChung 2009

MR Spectroscopy

MR spectroscopy provides chemical information.Measurement can be localized to a specific brain region.Like other MR imaging, MR spectroscopy is non-invasive.Can do (coarse) spectroscopic imaging

1H MR spectroscopy can be added as one or more additional scans in an MR imaging protocol.Data is collected from a single voxel (typically 8mL voxel, 7 minute acquisition). Offline data processing with LC Model determines the concentrations of about 16 metabolites.

Lisa Angelos

Fitting and MetabolitesNAA mI

Cho Cre

Lisa Angelos

Amygdala Spectroscopy

Protocol to collect data from the amygdalaOblique localizer scans to visualize anatomySaturation bands help isolate amygdala signal7-minute acquisition, LC Model processingCorrections for tissue content and voxel edge location

Reproducibility studyFive major metabolites (NAA, Cre, Cho, mI, Glx) measured with better than 20% accuracyIn a healthy adult sample, NAA and Cre individual differences detected with ICC = 0.6.

Lisa Angelos

Difference shows GABA refocusing (Cre cancels).

Every other acquisition has freq range suppressed

GABA refocusing

Every other acquisition is “normal”

GABA minimized (TE=68)

TE=35 spectrumRed line: GABA + baseline

Spectral Editing (MEGA-PRESS)

Lisa Angelos

Small phe peak overlaps large tryptophan peak

“upfield” from water“downfield” from water

water peak removed

Lisa Angelos

Phenylalanine in PKU

Other Details

Image Processing / Statistics Canned Software Packages

Custom Software Tools

Advice and Interpretation

Atlasing

Studies in humans, NHP, dogs, cats

Ex vivo possible

Other Methods

Myelin Characterization: Magnetization Transfer,

Myelin Water Fraction Mapping (Relaxometry)

Iron Mapping (T2, T2*)

High b-value diffusion imaging / complex white

matter characterization

Image guided surgery / drug delivery

Contrast agents

Scanning in Children – Infants to Adults

Pre-Clinical MRI LabVarian 4.7T imaging system -scan small animals up to 600 grams - in-plane resolution on the order of 50 microns.

It has broadband capability allowing us to scan a variety of nuclei including H1, P31, F19 and C13.

This system has the ability to perform a wide array of MRI sequences including T1 and T2 weighting, T1, T2 and T2*

mapping, functional MRI (EPI), diffusion and diffusion tensor imaging, localized spectroscopy (STEAM and PRESS) as well

as chemical-shift imaging, and perfusion imaging with Gadolinium based contrast agents. This allows for visualization and

quantification of a variety of moieties and processes including metabolites, anatomical structures, tumor morphology, blood

flow/vessels, fiber pathways, drug effects, brain activity, and heart motion. Our system is equipped with a variety of

surface coils and dual tune volume coils.

In addition, our lab system includes a Carbon-13 Hyperpolarizer. High signal to noise and high resolution are two essential

factors for successful molecular imaging. Normally, MR provides poor signal to noise especially when attempting to image

molecules containing low natural abundance nuclei, such as carbon-13. Recently, a new commercially available dynamic

nuclear polarizer (DNP), the Hypersense system by Oxford instruments, has been acquired that is able to increase the

signal to noise available for carbon-13 by over 10 000 times. This enables the rapid acquisition of images from injected

substrates such as carbon-13 labeled pyruvate and any compounds that may be produced via its in vivo metabolism. The

system works by freezing a solution of a carbon-13 enriched substance mixed with a paramagnetic compound to just above

1 kelvin inside a 3 tesla magnet. The mixture is microwaved (to transfer polarization from electrons to the carbon-13 nuclei)

and, after a period of time, heated quickly using super-heated water to enable the hyperpolarized material to be extracted

for injection. This system provides many opportunities to study perfusion, angiography and metabolism in a variety of in

vivo models.

CONTACT INFORMATION: if you are interested in our services, wish to tour our facility, or arrange a meeting discuss how

we can assist your research, please contact Beth Rauch at 608-265-1109 or brauch@wisc.edu

Pre-Clinical MRI LabThe Carbone Cancer Research Imaging Center at the University of Wisconsin features a Varian 4.7T horizontal

bore imaging/spectroscopy system. This system provides the capability to scan samples up to 600 grams in size,

or with a diameter of 72 mm or less, with an in-plane resolution in the order of 50 microns. It is also equipped with

an anesthesia system and physiologic monitoring that allows for image gating. MRI is totally non-invasive (there is

no ionizing radiation) and scans can be repeated multiple times to track disease progression or treatment

effectiveness. This system is a shared resource for the UW system and is the only one of it’s kind on campus.

Potential Uses of the System:•Ex-vivo and In-vivo Imaging

•Molecular imaging

•Track stem cells in vivo

•Macrophage infiltration

•Pin-point brain ischemia

•Tracking neural pathways

•Image Anatomy

•Transgenic Animals

•Oncology

•Phenotyping

•Atherosclerosis

•Neuological disorders

Scheduling and Fee Information:All users must first schedule a planning session to discuss how

our services can best meet your needs. Please contact Beth

Rauch at brauch@wisc.edu or 608-263-1109 to do so.

Fee Structure:

*the preliminary scans for start-up for new projects are free of

charge.

UWCCC Members: $220/hour

Non UWCCC Members: $375/hour

Commercial Users (non UW): $556/hour

Anesthesia & Supply Charge: $5/scan

Data Analysis: $30/hour

Technical Development Time: $40/hour

Contact us for a free consultation at brauch@wisc.edu or 608-

263-1109.

www.medphysics.wisc.edu/preclinmri.html