Contrast agents in dynamic contrast-enhanced magnetic resonance imaging

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI. In this review, we describe the recent research advances in this field and discuss properties of contrast agents, as well as their advantages and disadvantages. Finally, we discuss the research perspectives for improving this promising imaging method.

Keywords: DCE-MRI; contrast agent; low molecular contrast agent; macromolecular contrast agent; nanoparticle.

Figure 1. Diagram representing blood vessels in normal tissue A., tumor tissue B. and tumor tissue after treatment with anti-angiogenic drugs C

Tumor vessels have active angiogenesis, high permeability, hypoxia and the blood flow is chaotic and slow. After anti-angiogenic therapy, tumor blood vessels recover their normal functions.

Figure 2. Tofts Model: classical DCE-MRI model

(K^trans: the transfer constant from vascular to extravascular extracellular space (EES); K_ep: Rate constant between the EES and the blood plasma; V_e: The fractional tissue EES (light green). V_p: The fractional plasma volume (white)

Figure 3. structure and name of low olecular MR contrast agents

Figure 4. Example of three K

^trans parameter maps. The three K^trans maps showed are from a patient with a colorectal liver metastasis before and after treatment with bevacizumab. The distribution of K^trans is spatially heterogeneous with high values in the periphery and low values in the core. K^trans was reduced after 2 days and further reduced after 12 days of treatment when compared with baseline. Abbreviations: DCE-MRI, dynamic contrast-enhanced MRI; K^trans, volume transfer constant between plasma and the extracellular extravascular leakage space

Figure 5. Representative DCE-MRI data in one advanced HCC patient

A. Post-contrast T1-weighted MRI at baseline and B. after 14 days of study treatment. Color K^trans map of the tumors was greatly heterogeneous due to tumor necrosis and ROI was selected in the most enhanced tumor region. C. Corresponding color K^trans maps at baseline and D. after 14 days of study treatment. Hypervascular area is shown in red. The selected ROI (black cycle ) for K^trans measurement is indicated by white arrows, In this patient, the K^trans values at baseline and after study treatment were 798.6×10-3/min and 206.6 × 10-3/min, respectively. E. The initial area under the gadolinium concentration-time curves (IAUC) at baseline F. and after study treatment from the same patient. The IAUC values at baseline and after study treatment were 1526.2 mmol/kg×s and 1376.1 mmol/kg×s, respectively.

Figure 6. The trans endothelial transfer coefficient (Ki) maps produced from the PNs A. and Gd-DTPA B. The Ki map produced from PNs include discrete areas of high Ki within the tumor rim that are difficult to discern in the equivalent Gd-DTPA Ki map

This is largely due to the small molecular size and considerably greater extraction of Gd-DTPA relative to PNs.