| dc.description.abstract |
<p>Dynamic contrast-enhanced (DCE) MRI has been widely used as a quantitative imaging
method for monitoring tumor response to therapy. The pharmacokinetic parameters derived
from this technique have been used in more than 100 phase I trials and investigator
led studies. The simultaneous challenges of increasing the temporal and spatial resolution,
in a setting where the signal from the much smaller voxel is weaker, have made this
MR technique difficult to implement in small-animal imaging. Existing preclinical
DCE-MRI protocols acquire a limited number of slices resulting in potentially lost
information in the third dimension. Furthermore, drug efficacy studies measuring the
effect of an anti-angiogenic treatment, often compare the derived biomarkers on manually
selected tumor regions or over the entire volume. These measurements include domains
where the interpretation of the biomarkers may be unclear (such as in necrotic areas).</p><p>This
dissertation describes and compares a family of four-dimensional (3D spatial + time),
projection acquisition, keyhole-sampling strategies that support high spatial and
temporal resolution. An interleaved 3D radial trajectory with a quasi-uniform distribution
of points in k-space was used for sampling temporally resolved datasets. These volumes
were reconstructed with three different k-space filters encompassing a range of possible
keyhole strategies. The effect of k-space filtering on spatial and temporal resolution
was studied in phantoms and in vivo. The statistical variation of the DCE-MRI measurement
is analyzed by considering the fundamental sources of error in the MR signal intensity
acquired with the spoiled gradient-echo (SPGR) pulse sequence. Finally, the technique
was applied for measuring the extent of the opening of the blood-brain barrier in
a mouse model of pediatric glioma and for identifying regions of therapeutic effect
in a model of colorectal adenocarcinoma. </p><p>It is shown that 4D radial keyhole
imaging does not degrade the system spatial and temporal resolution at a cost of 20-40%
decrease in SNR. The time-dependent concentration of the contrast agent measured in
vivo is within the theoretically predicted limits. The uncertainty in measuring the
pharmacokinetic parameters with the sequences is of the same order, but always higher
than, the uncertainty in measuring the pre-injection longitudinal relaxation time.
The histogram of the time-to-peak provides useful knowledge about the spatial distribution
of K^trans and microvascular density. Two regions with distinct kinetic parameters
were identified when the TTP map from DCE-MRM was thresholded at 1000 sec. The effect
of bevacizumab, as measured by a decrease in K^trans, was confined to one of these
regions. DCE-MRI studies may contribute unique insights into the response of the tumor
microenvironment to therapy.</p>
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