Light offers unique wavelength-dependent contrast mechanisms in tissues; the scattering, absorption, and fluorescence of intrinsic tissue chromophores or extrinsically administered chromophores contain information about anatomy, physiology, biochemistry, and molecular function [1
]. These unique contrast mechanisms have driven recent developments for imaging deep into tissue using near-infrared (NIR) radiation [2–4
]. NIR light can penetrate several centimeters into tissue before it is attenuated below detection. The main intrinsic mechanisms of NIR light attenuation in tissue are the scattering due to index of refraction variations of the cellular organelles [5,6
], and absorption mainly due to oxy- and deoxyhemoglobin, and in lesser degree due to water and lipids [5
Diffusion theory [7
] has been employed over the last decade to model the propagation of highly scattered NIR photons in deep tissue and provided rigorous mathematical models for noninvasive quantification of the optical properties of large organs. Quantification of the average optical properties of tissue at multiple wavelengths constitutes diffuse optical spectroscopy (DOS), which has been used to investigate muscle [8,9
], brain activation [10–12
], and assess physiological responses from normal and malignant breast tissues [5
]. The combination of multiple NIR light measurements through tissue at several projections, using appropriate mathematical models based on diffusion theory, led to a new tomographic technique termed diffuse optical tomography (DOT). This technique has been recently applied clinically to produce quantified tomographic images of tissue chromophore concentrations in imaging brain function [4
] and breast cancer [2,3
In this paper, we present the clinical application of a method that combines concurrent optical and magnetic resonance (MR) measurements to perform magnetic resonance imaging (MRI)-guided DOS and noninvasively retrieve functional tumor characteristics in deep tissue. This approach originates a novel imaging and spectroscopic modality that merges the information content of MR and optical contrast into one scanner. Concurrent DOT and MRI as stand-alone imaging modalities have been performed recently for validation of DOT performance [3
]. But the combination of the optical and MR measurements into the same
tomographic scheme yields additional benefits that cannot be achieved simply by acquiring MR and optical images as stand-alone
techniques. This is because the use of a priori
information, such as the anatomical or functional information from MRI, can significantly improve the quantification accuracy of the optical method by constraining the DOT inverse problem [13–15
]. Therefore, tissue chromophores and fluorochromes associated with function and disease can be quantified with high accuracy and resolution compared to other noninvasive techniques. The optical and MR examinations are fully compatible and, given the cost efficiency of optical systems, it would be anticipated that hybrid MR-optical systems could be easily implemented to augment the information content of the MR examination.
This work had three aims. The first aim was to demonstrate the first reported clinical implementation of MR-guided DOS, and illustrate practical aspects of the technique. The second aim was to noninvasively quantify the optical properties of breast tumors in vivo and obtain localized measurements of hemoglobin concentration and oxygenation. Finally, the third aim was to obtain insight on the distribution of cancer-associated optically detected intrinsic signals. The assessment of tumor function, i.e., vascularization and oxygenation status, can be associated with angiogenesis and cancer-specific hypoxia and may correlate with malignancy and metastatic potential. Localized DOS may be the method of choice for such investigations because it can offer higher quantification accuracy than the existing conventional NIR spectroscopic and tomographic methods.
The remainder of this paper briefly describes the hybrid MR-DOT instrument and breast examination protocol, presents the theory and practical aspects of localized DOS, and reports our findings on 14 patients.