• Embed Doc
  • Copy Link
  • Readcast
  • Collections
  • CommentGo Back
Download
 
 ABSTRACT vii
 Abstract
NMR techniques have seen widespread use in the characterization of biological systems.Due to the different environments experienced by spins, the
T 
1
and
T 
2
relaxation behaviorcan differ significantly. Furthermore, the local environment can be altered by theintroduction of paramagnetic agents that alter the bulk magnetic susceptibility of asample, causing drastic changes in the relaxation behavior of spins. For spins situated inrestricted spaces, the diffusion characteristics as well as the relaxation properties of thesespins can differ from system to system.Normally, the relaxation (
T 
1
and
T 
2
) and diffusion measurements are performedindependently and system parameters are determined solely on the basis of theindependent behavior of the relaxation or diffusion. In the following experiments, theseparameters (
T 
1
,
T 
2
, and apparent diffusion coefficient) were used to characterizebiological systems. Furthermore, multi-dimensional analysis was performed on a systemwhere combined relaxometry and diffusimetry were used to characterize the system as afunction of both parameters.Radiotherapy studies in mice using perfluoro-15-crown-5-ether showed a decrease in
 p
O
2
 following a single large dose of radiation. In conjunction with spectroscopic data,Inversion-Recovery Echo-Planar-Imaging data were collected at 1-3 hours, 10-13 hours,and 19-26 hours post irradiation, and
T 
1
-maps generated in order to display localized
 
 ABSTRACT viii
changes in
 p
O
2
. The calculated
T 
1
-maps were then weighted by their respective
 M 
0
-mapsto find the weighted average of the
T 
1
-maps, and an equivalent
 p
O
2
of the tumor was thencalculated from the weighted average. Untreated control animals that were subjected tothe same time course showed no evidence of 
 p
O
2
decline, while the tumors irradiatedwith a single dose of 6 MeV electrons showed a decline in
 p
O
2
by approximately 9 torralmost immediately after irradiation. The calculation of 
 p
O
2
using the weighted averageof the
T 
1
-maps was not only highly correlated to the spectroscopic measurements, it wasapproximately equivalent to the spectroscopic measurements. It is speculated that thedecrease in the tissue oxygenation following radiation therapy is due to vascular damagecaused by such a high dose of radiation, or edema within the interstitium of the tumor.Edema can cause the interstitial pressure to increase, resulting in vascular collapse. Thisin turn would lead to decreased perfusion and thus decreased oxygen delivery.Water diffusion-coefficient mapping was used in conjunction with
19
F inversion-recoveryecho-planar imaging (IR-EPI) of a sequestered perfluorocarbon (PFC) emulsion toinvestigate the spatial correlation between the diffusion coefficient of water and the tissueoxygen tension (
 p
O
2
) in radiation-induced fibrosarcoma (RIF-1) tumors (n = 11). Thediffusion-time-dependent apparent diffusion coefficient,
 D
(
t 
), was determined byacquiring diffusion coefficient maps at 20 different diffusion times. Maps at fourrepresentative time points in different regions of the
 D
(
t 
) curve were selected for finalanalysis. An intravenously administered PFC emulsion, perfluoro-15-crown-5-ether, wasused to generate the
 p
O
2
maps.
 D
(
t 
) and
 p
O
2
data were acquired with the animal
 
 ABSTRACT ix
breathing either air or carbogen (95% O
2
– 5% CO
2
) to investigate the effects of increased tumor
 p
O
2
on
 D
(
t 
). The average increase in tumor
 p
O
2
was 22 torr when thebreathing gas was changed from air to carbogen. Correlating plots generated from pixeldata for
 D
(
t 
)(air breathing) versus
 D
(
t 
)(carbogen breathing) showed little deviation froma slope of unity. Correlation plots of 
 D
(
t 
) versus
 p
O
2
indicate that no correlation ispresent between these two parameters. This study also confirms that necrotic tissue wasbest differentiated from viable tumor tissue based on
 D
(
t 
) maps at long diffusion times.Diffusion-signal-attenuation curves in yeast-cell suspensions show non-monoexponentialsignal decay that is assumed to arise from separate compartmental contributions to theoverall signal. However, restricted diffusion effects also give rise to non-monoexponential signal decay and are difficult to separate from compartmental signalcontributions. Combined relaxometry and diffusion measurements allows differentiationbetween compartmental diffusion constants by first separating the compartmentalcontributions on the basis of differences in their respective relaxation times. Diffusion-weighted inversion-recovery spin-echo experiments were carried out at different
b
-values. Intra- and extracellular compartments in yeast-cell suspensions were separated onthe basis of 
T 
1
relaxation by adding an MR contrast agent to the extracellular space.Once the compartmental signals were distinguished on the basis of 
T 
1
, the relative signalattenuation for each compartment was used to calculate the separate compartmental
 ADC 
s. With this method, even compartmental diffusion coefficients with similar valuescan be distinguished.
of 00

Leave a Comment

You must be to leave a comment.
Submit
Characters: ...
You must be to leave a comment.
Submit
Characters: ...