Lecture 04:

Preprocessing & Registration

BME 234: Neuroimaging Data Analysis, Spring 2016, Course Code 14310

Frithjof Kruggel, M.D.

Department of Biomedical Engineering, University of California, Irvine
Office: REC 204, Phone: 4-3729, Email: fkruggel@uci.edu

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Why process anatomical data?

There are several reasons for analyzing anatomical data:
Morphometry: studying macroscopic properties of structures in groups
of (healthy) subjects,
Structure-function relation: comparing structural properties with other
variables (from physiology, cognitive neuroscience, biochemistry, genetics),
Anatomical Reference: relating functional activation to an anatomical
locus,
Describing pathology: studying macroscopic tissue changes under the
condition of CNS diseases (e.g., focal or diffuse lesions, regional or
global atrophy, developmental disorders),
Visualization: mapping physical, physiological or functional quantities
on structures for displaying results.
Constraining the solution space: restricting the search space in signal
detection to specific sub-compartments.
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Preprocessing: Overview
Very often, anatomical datasets are analyzed in groups or single datasets are
compared against a group. Several analysis steps are required to standardize
image content, collectively called preprocessing:
File conversion: data conversion from scanner format to a format used
by the image analysis software,
Spatial normalization: interpolating data to a standard resolution,
Alignment with a standard coordinate system: the position and orientation of the head is different from scan to scan and must be corrected.
Inhomogeneity correction: the contrast in MR data is not uniform due
to machine imperfection. Data have to be corrected for these intensity
inhomogeneities.
Intensity normalization: because there is no standard intensity scale
(as in X-ray tomography), datasets have to be normalized for intensity
across scans.
Registration: data from different examinations (e.g., different weightings) have to be transformed into the same spatial reference system.
These steps are now discussed in more detail.
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File conversion
MR scanning takes place in k-space (Fourier space). Acquired data are
transformed into an image using an inverse Fourier transform. Most analysis
procedures use images, rarely raw data are required.
Most MR scanners today generate images in DICOM format (Medical Image Format FAQ: http://www.dclunie.com). Advantages of this format are:
standard, contains tags (patient name, acquisition information etc.). Disadvantages: only 2D format defined (i.e., volume data are delivered as a series
of slices).
Most image analysis software uses proprietary data formats for storage.
The most common format is called Analyze format, named
after a SW package developed by the Mayo Clinic (reference:
http://www.mayo.edu/bir/PDF/ANALYZE75.pdf). A revised version is
called NIFTI (reference: http://nifti.nimh.nih.gov/), and an emerging standard among current SW packages. Advantages: 3D format defined. Disadvantages: patient and acquisition information is lost, no tags.
Be aware that some format conversion SW also performs an intensity or
spatial normalization!
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Spatial normalization
Generally, volumetric MRI data are not acquired with an isotropical spatial
resolution, e.g., a voxel corresponds to 0.90.91.5 mm. It is useful to
interpolate data to an isotropic resolution of 1.01.01.0 mm.
All interpolation methods have properties of low-pass filters, i.e., they blur
edges. Multiple interpolation steps should be avoided. The best method is
B-spline filtering.
Thevenaz, Blu, Unser (2000): Interpolation revisited. IEEE TMI 19, 739-758.
Thevenaz, Blu, Unser (2000): Image interpolation and resampling. Handbook of Medical
Imaging, Processing and Analysis.

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Intensity normalization
Because tissue contrast depends on the MR imaging protocol, there is no
tissue-related intensity scale such as in X-ray computed tomography. Rather,
the intensity histogram is described as a sum of Gaussian distributions relating to different tissue classes, and the center and dispersion adjusted across
scans:


K
XX
(vi k )2
uk exp
h=
,
(1)
2k

k=1

where vi corresponds to the voxel-wise intensity in domain , K to the number of classes with mean k and standard deviation k .

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Inhomogeneity correction I
Inhomogeneities of the B1 scanner field lead to contrast differences within
the measurement volume. For some datasets, the contrast ratio of white matter to grey matter varies up to 50 %. Correction is performed by modeling
the histogram as a sum of Gaussian distributions as above, but assuming that
a class-independent but spatially variable gain field g modulated measured
voxel intensities:
h=

K
XX

k=1

((vi gi ) k )2
,
uk exp
2k

(2)

This gain field is estimated by comparing the distribution of the global histogram with those in local histograms. The recovered gain field can be used
to correct the intensities of the original image. Note that intensity inhomogeneities are also found in microscopic images.
Pham, Prince, (1999): An adaptive fuzzy segmentation algorithm of magnetic resonance images. IEEE TMI 18, 737752.
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Inhomogeneity correction II
Top: original MRI dataset. Below: inhomogeneity-corrected image. Note
especially the correction effect in the coronal slice.

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Alignment with a standard coordinate system

For easing a comparison across scans, it is useful to have objects in images
aligned with some reference system. For the human brain, the standard is
the so-called stereotaxic coordinate system. Here, the anterior and posterior
commissure (AC, PC) are selected as reference structures. A recipe for the
aligning with the stereotactical coordinate system is given by:
locate AC and PC in the mid-sagittal plane of the brain,
draw a line touching the caudal margin of AC and the cranial margin of
PC (see Fig. on next slide),
define the positive x-direction along the AC-PC line in sagittal direction
(front-to-back), and
define the positive z-direction to lie perpendicular to x in the mid-sagittal
plane (axial direction, top-to-bottom), thus
the positive y-direction is perpendicular to the mid-sagittal plane (coronal direction, left-to-right).
Note that this procedure involves a translation and rotation, but no scaling,
so the individual space is retained.
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Stereotaxic coordinate system

Enlarged slice of a MR data set in axial (left) and sagittal (right) direction. Axes of the stereotaxic coordinate system are drawn. The numbers correspond to: (1) anterior commissure, (2) posterior commissure,
(3) adhaesio interthalamica, and (4) splenium of the corpus callosum.

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Talairach-Fox coordinate system

A spatial normalization was introduced first by Talairach and Tournoux, and
later refined by Fox et al. This system is commonly refered to as Talairach
coordinates in the neuroscience literature. Introduce a right-handed coordinate system as follows:
The origin of the coordinate system is on the cutpoint AC and the midsagittal plane,
The x-direction runs from the leftmost point of the brain (-64mm) to
right most point (+64mm),
The y-direction extends from the back (-104mm) to the front (+68mm),
The z-direction defines the topmost point as (+72mm).
This definition corresponds to a linear mapping.
Talairach, Tournoux (1957): Atlas danatomie stereotactique des noyaux gris centraux. Masson, Paris.
Fox, Perlmutter, Raichle (1985): A stereotactic method of anatomical localization for positron
emission tomography. Journal of Computer Assisted Tomography 9, 141-153.
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Talairach daemon applet

See http://ric.uthscsa.edu/TDapplet/:

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Registration I
Registration is called a process that aligns two images with the same coordinate space. Examples are:
Two images were taken in spatial continuity (e.g., histological sections)
that shall be aligned as a common map.
Two images of the same scene were taken at different times. Changes
occuring with time shall be detected (e.g., growth of a tumor).
Two images of the same object were taken in different imaging modalities. Registration brings both acquisitions into the same coordinate
frame, so that complementary information from both techniques can be
integrated (e.g., a functional modality (PET) with an anatomical modality (MRI)).
An electronic atlas shall be adapted to a 3D dataset of a human head.

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Registration II
The registration problem is written as:
T = arg min(S(T (O), R) + E(T )),
T

where O corresponds to the object image, T to the transformation, R to the

reference image and S() to a function that returns a similarity measure of
both images. The energy term E(T ) is required for non-linear registration
and ensures the smoothness of the transformation. The parameter weights
between registration accuracy and smoothness of the transformation.
For = 0, we have a linear transformation. The most common cases are a
rigid transformation (rotation and translation only), and an affine transformation (rotation, translation, and scaling).
Registration algorithms require the definition of an image similarity criterion
S(), a smoothness term E(), and a (non)linear optimization approach.
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Volume-based registration I
The most common approach is to use the whole image information in the
registration process. Suitable similarity criteria are:
The squared intensity difference:
S(O, R) =

n
X

(T (o)i ri )2 ,

i=0

where T (o)i , ri correspond to a voxels intensity level in the transformed

object resp. reference image. This cost function depends on image contrast.
If both images have a similar histogram (e.g., acquired using the same
imaging technique), cross-correlation provides a much better metric:

Pn 2
Pn
2
T
(o)
i=0 ri
,
S(O, R) = 1 pi=0Pn i
(

2 2
i=0 T (o)i ri )

If the histogram differs (e.g., different MRI weightings), an informationbased criterion, mutual information, is used as a similarity criterion.
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Linear registration - example

Voxel-based registration of two volume datasets. Reference image (top row),
object image (middle) and registered datasets (below).

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Nonlinear registration I
If registration is performed across different objects, or objects are distorted,
nonlinear registration is required. Consider the brain images below, acquired
by Echoplanar Imaging (EPI), a fast MR imaging technique.

We want to find the best transformation that maps images from the upper
row to the row below. Here, a nonlinear transformation is sought.
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Example deformation field

Some example deformation fields are given as contour diagrams below:

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Nonlinear registration - example

Anatomical (top left) and EPI (top right) images before registration. Below:
EPI image after automatic registration (left) and manual registration (right).

Kybic (2002): Elastic Image Registration using Parametric Deformation

Models, Thesis ETH Lausanne.
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Summary: preprocessing
Preprocessing of anatomical images is used to standardize images in terms
of intensity, contrast, spatial resolution, and head orientation.
As a result, we have all datasets of a subject group aligned with the same
coordinate frame, and in the same spatial resolution. The average intensity
(within a tissue class) is the same across all datasets.
Note that spatial normalization and the adaptation of a coordinate system are
often combined in a single registration step, i.e., by aligning with a reference
brain.
The usefulness of mapping datasets into the same reference space (e.g.,
Talairach-Fox coordinates) is under discussion. This problem will be studied
further in the seminar section.

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