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作者 Connelly, Patrick Raymond
書名 Functional MRI at 9.4 tesla for the evaluation of vascular volume and deoxygenated hemoglobin content in murine tumors
說明 168 p
附註 Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7192
Adviser: Jianhui Zhong
Thesis (Ph.D.)--University of Rochester, 2006
The development of non-invasive Magnetic Resonance Imaging methods, to analyze the functionality of physiological attributes in tumors, is of great importance in the laboratory and the clinic. In the studies presented in this treatise, Blood oxygen Level Dependent (BOLD) MRI contrast was utilized at a field strength of 9.4 Tesla (T), for the spatial and temporal evaluation of physiological correlates in two murine mammary carcinoma tumor lines. The two lines, MCa-4 and MCa-35, were chosen primarily based on drastic differences of their microcirculatory properties. The initial goal of this work was to confirm that using a double gradient echo (DGE) image acquisition sequence, the estimation of the total transverse relaxation rate, R2* will not be affected by flow through large vessels. This was done in two separate flowing phantom systems and in human blood. The results confirmed that there were no significant contributions to the estimation of R2*, from flow through large cylinders (bulk laminar flow) or through superporous agarose gels (random microscopic flow). In vivo studies presented here utilized imaging and BOLD contrast imaging in MCa-4 and MCa-35 tumors. The percentage of tumor vascular volumes (%VV) were estimated using diffusion weighted (DW) imaging and the intravoxel incoherent motion (IVIM) model. R2*, R2, %VV and the apparent diffusion coefficients (ADC) were estimated, in control tumors and those treated with an angiogenesis inhibitor (DC101). MCa-4 tumors had significant reductions in R2* and %VV (reduction in deoxygenated hemoglobin (Hb) due to a reduced blood volume), three days following initiation of treatment with DC101. MCa-35 tumors had significant increases in R2, three days following initiation of treatment with DC101, with no changes in the %VV (decrease in Hb saturation). Neither tumor type demonstrated significant alterations in their ADC values, leading to the assumption that the BOLD parameter (R2 and R2*) changes were indicative of changes in deoxygenated Hb, in those tumors. The results in control tumors demonstrated that the estimated %VV in MCa-4 tumors was double that of MCa-35 tumors
Non-invasive BOLD MRI has previously been evaluated for monitoring tumors in animals exposed to hyper-oxygenated gases. The relative changes of the transverse relaxation rate, R2*, was determined, to evaluate the response of MCa-4 and MCa-35 tumors, in animals exposed to 95%O2/5%CO 2 gas (carbogen). Experiments were performed at two specific tumor volumes. Whole tumor results demonstrated that there was a significant decrease in R2*, only in the large MCa-4 tumor volume group. By setting a baseline threshold R2* value, above the mean R2* of the whole tumor, voxels with relatively elevated levels of deoxygenated hemoglobin (Hb), were isolated. These voxels were shown to have significant and large responses to carbogen in both tumor types (decreases in R2* as expected with decreases in deoxygenated Hb). The responses, of baseline voxels with elevated R2* levels, were shown to be significantly less in smaller volume MCa-35 tumors, demonstrating a tumor type and tumor volume specificity for responses to carbogen
The %VV results, in MCa-35 and MCa-4 tumors, provide evidence for the evaluation of tumor vascular volumes, using MRI without contrast agents. The carbogen data demonstrated the utility of using carbogen for the perturbation of pathological processes to alter MRI contrast mechanisms. Use of additional non-invasive imaging techniques, such as near infrared spectroscopy for the absolute determination of Hb saturation levels, along with transverse relaxation rate estimates, may provide a comprehensive non-invasive method for the evaluation of the functionality of the tumor microcirculation in the clinic
School code: 0188
Host Item Dissertation Abstracts International 67-12B
主題 Engineering, Biomedical
Health Sciences, Radiology
Biophysics, Medical
Alt Author University of Rochester
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