David Thayer

Tumor characterization in small animals using magnetic resonance-guided dynamic contrast enhanced diffuse optical tomography

We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.

Dual-Contrast Dynamic MRI-DOT for Small Animal Imaging

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.

Laser-induced photo-thermal magnetic imaging

Due to the strong scattering nature of biological tissue, optical imaging beyond the diffusion limit suffers from low spatial resolution. In this letter, we present an imaging technique, laser-induced photo-thermal magnetic imaging (PMI), which uses laser illumination to induce temperature increase in a medium and magnetic resonance imaging to map the spatially varying temperature, which is proportional to absorbed energy. This technique can provide high-resolution images of optical absorption and can potentially be used for small animal as well as breast cancer and lymph node imaging. First, we describe the theory of PMI, including the modeling of light propagation and heat transfer in tissue. We also present experimental data with corresponding predictions from theoretical models, which show excellent agreement.

Atypical Magnetic Resonance Imaging Findings in Hepatocellular Carcinoma

Magnetic resonance imaging (MRI) is currently the modality of choice to evaluate liver lesions in patients with cirrhosis and hepatitis B and C. Hepatocellular carcinoma demonstrates typical imaging findings on contrast-enhanced MRI, which are usually diagnostic. Unfortunately, a subgroup of hepatocellular carcinoma presents with atypical imaging features, and awareness of these atypical presentations is important in ensuring early diagnosis and optimal patient outcomes. Herein, we review some of the more common atypical presentations with a focus on MRI.

Development of a combined multifrequency MRI-DOT system for human breast imaging using a priori information

Breast cancer is a significant cause of mortality and morbidity among women with early diagnosis being vital to successful treatment. Diffuse Optical Tomography (DOT) is an emerging medical imaging modality that provides information that is complementary to current screening modalities such as MRI and mammography, and may improve the specificity in determining cancer malignancy. Using high-resolution anatomic images as a priori information improves the accuracy of DOT. Measurements are presented characterizing the performance of our system. Preliminary data is also shown illustrating the use of a priori MRI data in phantom studies.ä

Differentiation of tumor vasculature heterogeneity levels in small animals based on total hemoglobin concentration using magnetic resonance-guided diffuse optical tomography in vivo.

Insight into the vasculature of the tumor in small animals has the potential to impact many areas of cancer research. The heterogeneity of the vasculature of a tumor is directly related to tumor stage and disease progression. In this small scale animal study, we investigated the feasibility of differentiating tumors with different levels of vasculature heterogeneity in vivo using a previously developed hybrid magnetic resonance imaging (MRI) and diffuse optical tomography (DOT) system for small animal imaging. Cross-sectional total hemoglobin concentration maps of 10 Fisher rats bearing R3230 breast tumors are reconstructed using multi-wavelength DOT measurements both with and without magnetic resonance (MR) structural a priori information. Simultaneously acquired MR structural images are used to guide and constrain the DOT reconstruction, while dynamic contrast-enhanced MR functional images are used as the gold standard to classify the vasculature of the tumor into two types: high versus low heterogeneity. These preliminary results show that the stand-alone DOT is unable to differentiate tumors with low and high vascular heterogeneity without structural a priori information provided by a high resolution imaging modality. The mean total hemoglobin concentrations comparing the vasculature of the tumors with low and high heterogeneity are significant (p-value 0.02) only when MR structural a priori information is utilized.

Evaluation of a multi-wavelength laser array with diffuse optical tomography

Diffuse Optical Tomography (DOT) is a new and promising medical imaging modality which uses near-infrared light to probe tissue properties. Using multiple wavelengths of light can provide important information about tissue metabolism and cancer malignancy. Unfortunately, in most DOT acquisition schemes, acquiring data for each wavelength has a multiplicative effect on the overall imaging time. In this paper, we evaluate a new multiple wavelength laser module (Praevium Research Inc.) with 12 laser diodes all coupled to a single output fiber. When used in conjunction with a cooled spectrometer, it allows simultaneous multi-wavelength data acquisition and hence, higher temporal resolution.

A True Multi-modality Approach for High Resolution Optical Imaging: Photo-Magnetic Imaging

Multi-modality imaging leverages the competitive advantage of different imaging systems to improve the overall resolution and quantitative accuracy. Our new technique, Photo-Magnetic Imaging (PMI) is one of these true multi-modality imaging approaches, which can provide quantitative optical absorption map at MRI spatial resolution. PMI uses laser light to illuminate tissue and elevate its temperature while utilizing MR thermometry to measure the laser-induced temperature variation with high spatial resolution. The high-resolution temperature maps are later converted to tissue absorption maps by a finite element based inverse solver that is based on modeling of photon migration and heat diffusion in tissue. Previously, we have demonstrated the feasibility of PMI with phantom studies. Recently, we have managed to reduce the laser power under ANSI limit for maximum skin exposure therefore, we have well positioned PMI for in vivo imaging. Currently we are expanding our system by adding multi-wavelength imaging capability. This will allow us not only to resolve spatial distribution of tissue chromophores but also exogenous contrast agents. Although we test PMIs feasibility with animal studies, our future goal is to use PMI for breast cancer imaging due to its high translational potential.

A true multi-modality approach for high resolution optical imaging: photo-magnetic imaging

Multi-modality imaging leverages the competitive advantage of different imaging systems to improve the overall resolution and quantitative accuracy. Our new technique, Photo-Magnetic Imaging (PMI) is one of these true multi-modality imaging approaches, which can provide quantitative optical absorption map at MRI spatial resolution. PMI uses laser light to illuminate tissue and elevate its temperature while utilizing MR thermometry to measure the laser-induced temperature variation with high spatial resolution. The high-resolution temperature maps are later converted to tissue absorption maps by a finite element based inverse solver that is based on modeling of photon migration and heat diffusion in tissue. Previously, we have demonstrated the feasibility of PMI with phantom studies. Recently, we have managed to reduce the laser power under ANSI limit for maximum skin exposure therefore, we have well positioned PMI for in vivo imaging. Currently we are expanding our system by adding multi-wavelength imaging capability. This will allow us not only to resolve spatial distribution of tissue chromophores but also exogenous contrast agents. Although we test PMIs feasibility with animal studies, our future goal is to use PMI for breast cancer imaging due to its high translational potential.

A novel high-resolution optical imaging modality: photo-magnetic imaging

We introduce an entirely new technique, termed Photo-Magnetic Imaging (PMI), which overcomes the limitation of pure optical imaging and provides optical absorption at MRI spatial resolution. PMI uses laser light to heat the medium under investigation and employs MR thermometry for the determination of spatially resolved optical absorption in the probed medium. A FEM-based PMI forward solver has been developed by modeling photon migration and heat diffusion in tissue to compare simulation results with measured MRI maps. We have successfully performed PMI using 2.5 cm diameter agar phantom with two low optical absorption contrast (x 4) inclusions under the ANSI limit. Currently, we are developing the PMI inverse solver and undertaking further phantom and in vivo experiments.