Dynamic magnetic resonance imaging for tumor prognosis.
DYNAMIC MAGNETIC RESONANCE FOR CANCER PROGNOSIS
Publication No. ____________
The University of Texas Southwestern Medical Center at Dallas, 2006
Supervising Professor: Ralph P. Mason, Ph.D., C Sic., C. Chem.
Breast and prostate cancers are the most common non-smoking cancers among
American women and men. Radiotherapy and chemotherapy in conjunction with
surgery are the most common treatment protocols in the clinic. However, a lot of
experimental and clinical studies have shown that tumor hypoxia and the
microcirculation play a very important role in cancer progression and therapy. There
is strong evidence that hypoxic cells are one of the major reasons for failure to control
tumors with conventional radiotherapy and chemotherapy. Several approaches
(hyperthermia, and carbogen inhalation), which improve tumor oxygenation during
radiotherapy and chemotherapy, have been used in clinical trials. There is increasing
demand for tumor prognostic information in the clinical setting. So far, increasing
clinical data have indicated that poorly oxygenated tumors have poor prognosis. To
better understand the underlying tumor physiological mechanisms, it is very
important to develop novel non-invasive approaches to accurately assess tumor
microcirculation and oxygenation for further therapy planning. However, these
parameters have been extremely difficult to assess in routine clinical practice and
have therefore not been easily integrated in to general patient care.
With development of MRI the non-invasive technique, BOLD (Blood
Oxygenation Level Dependent) contrast MRI, has been widely used for neuroscience
research to detect brain activations. Because deoxyhemoglobin (dHbO2) is
paramagnetic and oxyhemoglobin (HbO2) is non-magnetic, the change of
concentration of deoxyhemoglobin and oxyhemoglobin can cause a Bulk Magnetic
Susceptibility (BMS) change and the T2* signal response during MR imaging. Here,
I applied this technique to assess tumor physiological characteristics. In order to study
the BOLD mechanism, I designed a phantom system and built it for in-vitro study.
Since inhalation of oxygen could cause variation in the blood flow and oxygenation,
and BOLD MRI is sensitive to both these factors, it becomes very important to
explore the correlation between the BOLD response and these two factors.
Considering the different vascular orientation, the angle between vessel and the static
magnetic field (B0) could be further analyzed in phantoms. The phantom study
showed that contribution of oxygenation was much higher than that of flow to the
BOLD signal. Interestingly, a signal decrease was observed in extra-vessel region
accompany increasing intra-vessel oxygenation.
The DCE (Dynamic Contrast Enhanced) and BOLD MRI have been compared in
the animal experiments and the clinical setting. The experimental pre-clinical results
showed that tumor sublines with different vascular development showed different
DCE and BOLD regional response. This correlation between DCE and BOLD in
regional response indicated the potential value of BOLD technique in tumor
Finally, the clinical results showed there is prognostic value in DCE and BOLD
MRI. There is high correlation between high BOLD response and good therapeutic
outcome. BOLD and DCE MRI provide novel non-invasive prognostic tools for the
clinic. It provides new insight into tumor physiological changes during chemotherapy
and radiotherapy. I found correlation between BOLD response in tumors
accompanying oxygen breathing and the clinical response of advanced local breast to
chemotherapy. This technique could early become a routine addition to the clinical
setting benefiting cancer patient population in near future.