Quantitative multiparametric imaging for the evaluation of nasopharyngeal carcinoma using PET and DCE-MRI

Abstract

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer ranked

as the 5th most common in Hong Kong. We aimed to study the role of dynamic

contrast-enhanced MRI (DCE-MRI) and dynamic 2-deoxy-2-[fluorine-18]fluoro

-D-glucose positron emission tomography (FDG-PET) for characterizing NPC

tumors in newly-diagnosed patients, and to quantitatively evaluate the

intratumoral heterogeneity of NPC.

In Chapter 2 we employed semi-quantitative analysis of DCE-MRI to study the

dynamic enhancement pattern by analyzing the time-intensity curves in 25 NPC

patients. Our findings suggested that high blood flow caused a high initial

intensity enhancement rate (ER), and that neovasculature due to tumor

angiogenesis in tumors of larger volume or higher T-stage caused more

accumulation of contrast agent which can be detected by DCE-MRI. PET and

semi-quantitative DCE-MRI parameters were not correlated and may reflect

different physiological/molecular processes in the microenvironment of NPC

tumor. However the major limitation of semi-quantitative analysis was that the

physiological correlates of these parameters were unclear.

In Chapter 3 we applied quantitative analysis of DCE-MRI to study the

permeability and perfusion characteristics in the same cohort as in Chapter 2.

Our findings implied that the permeability may be high compared to blood flow

in NPC tumor. We also observed significant correlations between iAUC (the

initial area under the time-intensity curve) by semi-quantitative analysis and ve

(the volume fraction of extravascular extracellular space) by quantitative analysis,

and between the two rate constants (kep’s) from these two methods, which

showed that semi-quantitative analysis was a feasible alternative in reflecting the

physiological characteristics of NPC. However, we did not observe any

significant correlation between PET and DCE-MRI quantitative parameters, also

suggesting that PET and DCE-MRI reflected different physiological information

in NPC.

In Chapter 4 we applied dynamic PET scan to study the glucose metabolism in

18 NPC tumors (16 included in DCE-MRI cohort). Our findings showed that

the overall FDG uptake was mainly composed of the FDG in tissue compartment

(Ki), which was governed by the phosphorylation (k3) but not the transport of

FDG (K1). This finding may further indicate a potential role of the

phosphorylation rate k3 in NPC. Dynamic PET parameters did not correlate

with DCE-MRI, indicating that the two modalities reflect different molecular

information in NPC.

In Chapter 5, intratumoral heterogeneity in NPC tumors of 40 patients was

studied using 18F-FDG PET scan. Our findings showed that as tumors grew to

a larger volume and higher T-stage, they showed more heterogeneous glucose

metabolism. It was found that more heterogeneous tumor was associated with

worse disease-free survival, indicating that tumor metabolic heterogeneity may

play an important role for NPC patient prognosis.

To summarize, these results showed that DCE-MRI and dynamic PET improved

our understanding about the physiological/molecular process of NPC, and, these

two modalities reflected different physiological information in the

microenvironment of NPC tumors. This indicated that the relationship between

supply of nutrients such as glucose and blood flow/permeability is complex and

not directly related. Moreover, intratumoral heterogeneity by PET scan was

also of importance in prognostication.