Brain Imaging Core: MRI of Structure,
Microstructure, Metabolites, and Animals
Andrew L. Alexander, [email protected]
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 [email protected]
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 [email protected] 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 [email protected] or 608-
263-1109.
www.medphysics.wisc.edu/preclinmri.html