Computed Tomography (micro-CT)

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Computed Tomography (micro-CT) Dianna D. Cody,
Ph.D., Evan Johnson and Daniel Leventhal Small
Animal Cancer Imaging Research Facility
Achondroplasia Gene Therapy Study The Dental
Branch of the University of Texas Health Science
Center conducted a study led by Dr. Pauline Duke
seeking a gene therapy treatment for
Achondroplasia, the most common form of dwarfism.
Dr. Dukes team modified a gene in mice, hoping
that modifying this gene would cause
Achondroplasia. To prove this hypothesis, a
control group of natural mice and a mutated group
were imaged using both conventional X-Ray and
MicroCT. The MicroCT produced 3-D images of the
skulls that showed something that the original
investigators had not considered. The dome of
the skull in the mutant mice was significantly
less dense than the control group, which cannot
be seen in X-Rays. MicroCT images were also used
to measure the length of some bones.
Ongoing Projects and Results NASA Bioreactor
Skull Analysis The Dental Branch of the
University of Texas Health Science Center
conducted a study led by Dr. Pauline Duke where
embryonic limb bud cells were grown in NASAs
Synthecon zero-G bioreactor. These cells
differentiated into cartilage cells, some of
which were fixed for histological study. Others
were implanted in two mm circular defects in
mouse skulls. The MicroCT was used to image the
skulls with the implanted cells, and a control
group with defects, but no implanted cells.
Imaging proved that the defect had been
completely filled in in the implanted mice, but
not in the control mice. Furthermore, the CT
scan showed that the filled-in defects had the
same mineral density as the surrounding bone.
Overview of Modality The EVS Corp RS-9 In Vivo
MicroCT Scanner is designed to image small
laboratory animals, such as mice and rats. It is
an ideal instrument for biomedical research
laboratories to non-destructively acquire 3-D
images of both in vivo and ex vivo specimens.
Instrument Description EVS Corps RS-9 MicroCT
utilizes a cone-shaped X-Ray beam and a two
dimensional detector, the latest in CT
technology. Cone beam CT takes an entire image
in one rotation of the gantry, without any
movement necessary in the axial direction. This
results in a true volume image instead of the
slices commonly associated with CT in the past.
Scans can be taken with resolution as high as 27
microns, with 90 micron resolution possible for
the shortest scan.
A
Defect
Healed Defect
X-Ray Source
Figure 3 (left) A control mouse skull with the
defect still present. (right) A mouse skull with
a healed defect due to implanted cartilage cells.
Note MicroViews line segment function is used
to measure the diameter of the defects, and even
though the defect is filled in on the mouse on
the right, the defect diameter is slightly larger.
2-D Detector
Vitamin D Bone Tumor Treatment Dr. Sara Peleg
conducted a study analyzing the effectiveness of
vitamin D in protecting against local bone loss
in tumor-bearing bones. The right distal femur
of each mouse had been inoculated with
osteoclastic prostate cancer cells (PC3), which
proceeded to destroy the surrounding bone tissue.
The left hind leg of each mouse was not treated.
A vitamin D analog treatment was applied
systemically to protect against local bone loss,
at two doses (4 and 10 ?g/kg) to 5 mice per dose
group. Both legs were disarticulated and scanned
in the 25 ?m isotropic voxel mode. Specific
volumes of bone tissue were analyzed with respect
to bone mineral density in the tibia of each
leg. Significant differences (p0.002) were
observed between paired bone samples (tumor vs
non-tumor bearing bones). Sampling errors
(17-25 variation in repeated measures) could
have somewhat obscured significance. The ability
to re-orient the 3D data sets to a standard
position prior to volume analysis is expected to
improve this result.
Wild type mouse 3D and sagittal view (left).
Mutant mouse 3D and sagittal view (middle).
Illustration of the plane location tool in
MicroView (right).
Figure 1 (left) A n illustration of the volume
cone beam system. (right) The actual EVS RS-9
Micro-CT.
Lung Tumor Imaging When attempting to study the
effect of new drugs, researchers often employ
animal models who already have the disease.
Unfortunately, in most cases, not every animal
possesses the disease to the same degree. Dr. Oh
and Dr. Kurie are attempting to employ the
scanner to image live animals and assess the lung
tumor density in each animal before the start of
treatment. These images can then be matched up
with post-sacrifice histological sections to
assess the effectiveness of the treatment. This
application of the MicroCT is not yet perfected,
but is improving with experience and upgrades,
including a respirator and infusion pump for
contrast dye.
Technical Capabilities The RS-9 is capable of
both In Vivo and Ex Vivo scanning. Ex Vivo scans
often utilize the high resolution scanning mode,
in which a scan takes approximately 80 minutes.
However, a low resolution In Vivo scan can be
completed in around 20 minutes. To perform an In
Vivo scan, the veterinary team anesthetizes the
animal using isoflourane. While an anesthetized
animal remains relatively still during the scan,
imaging of the lungs is difficult because of
motion artifact. Hopefully, the use of a
newly-acquired respirator synchronized with the
scanner will allow imaging of the lungs
exclusively in the inflated position.
Cross-sectional views of both control and
tumor-bearing bones (left). Examples of
MicroViews system for measuring bone density
(right). A 3D cylinder is placed over the area
to be measured. Average bone density within the
cylinder can then be displayed.
Figure 2 A rat is anesthetized for a scan.
(left) View before the bed is moved into scanner.
(right) View of the rat during the scan. The
scan lasts approximately 20 minutes.
Various views from a volume created by a 20
minute in vivo scan of a rat with no contrast dye
or respiratory gating. With hardware upgrades
and use of secondary software packages, the
quality of these images are expected to improve
dramatically.