Dual-Contrast Dynamic MRI-DOT for Small Animal Imaging

Abstract

In this paper we present first-of-its-kind spatially resolved enhancement kinetics of optical and magnetic resonance (MR) agents obtained by a combined MR and Diffuse Optical Tomography (MR-DOT) animal imaging system. A unique MR compatible fiber optic interface allows co-registration of MR and DOT data in space and time. High temporal resolution of the hybrid system permits acquisition of data in dynamic mode. Rats bearing a R3230 AC breast cancer tumor model are used for in vivo studies. Thirty-two optical and thirty MR images are acquired during a single imaging session that lasts nearly ten minutes. Both optical, indocyanine green (ICG), and MR contrast agents, gadolinium-DTPA (Gd-DTPA), are injected simultaneously after the acquisition of several baseline frames. Contrast enhancement time curves obtained by MR and DOT systems both indicate higher average enhancement in tumor regions, up to ten-fold for MRI and 3-fold for DOT, compared to close by non-tumor regions. This feasibility study is the first step towards clinical translation of this hybrid imaging platform. The ultimate aim is to use the enhancement kinetics of the optical agent ICG, which binds to plasma proteins, as complementary information to the kinetics of the MR agent Gd-DTPA, a small molecular agent that does not bind to plasma proteins, to better differentiate benign and malignant lesions.

Clinical Application of Fluorescence Imaging of Liver Cancer Using Indocyanine Green

“…The nature of fluorescence imaging of hepatocellular carcinoma (HCC) [1,2], which was first described in Japan in 2009, is very different from that of other techniques: it allows visualization of the HCC itself by fluorescence imaging of the ICG that is taken up and remains in the cancer tissues as a result of biliary excretion disorders. This gives high lesion-to-background contrast [median (range), 2.6 (0.6-16.6) fold, unpublished data] for well-or moderately differentiated HCC, which is higher than that for other kinds of cancer tissues (up to 2 fold) [15,16].…”

Using In-Vivo Fluorescence Imaging in Personalized Cancer Diagnostics and Therapy, an Image and Treat Paradigm

“…Using fluorescent probes that can turn on in specific conditions and turn off in other conditions can improve the image quality and signal to background ratio (61). Fluorescence imaging has the potential to monitor multiple biomarkers simultaneously by using different fluorescent probes with different emission wavelengths (11,66-67). In these applications, the excitation spectrum of each dye has to be narrow and as separate as possible.…”

“…The tissue scattering reduces the resolution of the optical imaging significantly. Co-registration of optical imaging with high resolution imaging modalities, such as CT, MRI and US can provide functional information within the framework of anatomical structures (66-75). In deep tissue imaging, the absorption and scattering of the tissue has a big impact on the detected fluorescence intensity and lifetime and has to be considered in the imaging reconstruction algorithms.…”

A multimodal contrast agent for simultaneous magnetic resonance and optical imaging of small animal

“…We have previously demonstrated that our combined DOT/MRI system can monitor the enhancement kinetics of an optical and a MR agent simultaneously 1,6 . Such an approach is powerful in that each agent-imaging modality pair provides different information that can be used as complementary information.…”

“…However, it is hard to validate one system with the other using similar approach. Even after the perfect co-registration, the distribution of the contrast agents in the body differs due to their varying size 6,7 . On the other hand, instead of using separate contrast agents, it is desirable to use an integrated contrast agent that is detectable by both the MRI and the DOT system for validation studies.…”