Magnetic resonance–coupled fluorescence tomography scanner for molecular imaging of tissue

Abstract

A multichannel spectrally resolved optical tomography system to image molecular targets in small animals from within a clinical MRI is described. Long source/detector fibers operate in contact mode and couple light from the tissue surface in the magnet bore to 16 spectrometers, each containing two optical gratings optimized for the near infrared wavelength range. High sensitivity, cooled charge coupled devices connected to each spectrograph provide detection of the spectrally resolved signal, with exposure times that are automated for acquisition at each fiber. The design allows spectral fitting of the remission light, thereby separating the fluorescence signal from the nonspecific background, which improves the accuracy and sensitivity when imaging low fluorophore concentrations. Images of fluorescence yield are recovered using a nonlinear reconstruction approach based on the diffusion approximation of photon propagation in tissue. The tissue morphology derived from the MR images serves as an imaging template to guide the optical reconstruction algorithm. Sensitivity studies show that recovered values of indocyanine green fluorescence yield are linear to concentrations of 1 nM in a 70 mm diameter homogeneous phantom, and detection is feasible to near 10 pM. Phantom data also demonstrate imaging capabilities of imperfect fluorophore uptake in tissue volumes of clinically relevant sizes. A unique rodent MR coil provides optical fiber access for simultaneous optical and MR data acquisition of small animals. A pilot murine study using an orthotopic glioma tumor model demonstrates optical-MRI imaging of an epidermal growth factor receptor targeted fluorescent probe in vivo.

Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers

“…Take the Born Ratio of the data (fluorescence divided by transmittance) for each source-detector position and multiply with a forward model simulation of transmittance based on the finite-element animal mesh for uniform optical properties. This is done to mitigate errors associated with source-or detector-tissue coupling 21 , to calibrate the data to the model 22 , and to adjust data for other aspects of model-data mismatch 23,24 . 7.…”

Spectral distortion in diffuse molecular luminescence tomography in turbid media

“…A detailed description of this instrument can be found in Davis et al 10 The imaging array used in the studies reported here consisted of 16 source/detector fibers surrounding a cylindrical tissue phantom as shown in Fig. 3.…”

“…[1][2][3][4] Broad efforts to develop these strategies for tissue diagnosis and characterization have included exploiting novel biochemical probes, engineering new detection techniques, improving image recovery methods, [5][6][7][8] and coupling luminescence detectors to standard imaging systems. 9,10 Extracting meaningful spectroscopic measurements or accurate images of the luminescent activity in tissue requires accurate light transport modeling, which, through substantial growth since the early 1990s, 11 has become fairly mature field of research. While fluorescence molecular imaging and spectroscopy systems for use in small animals 4,10,[12][13][14][15][16] have evolved to the point of commercial availability and clinical trials in humans are underway, 17 some of the more subtle complexities of the signal acquisition remain to be examined.…”

“…9,10 Extracting meaningful spectroscopic measurements or accurate images of the luminescent activity in tissue requires accurate light transport modeling, which, through substantial growth since the early 1990s, 11 has become fairly mature field of research. While fluorescence molecular imaging and spectroscopy systems for use in small animals 4,10,[12][13][14][15][16] have evolved to the point of commercial availability and clinical trials in humans are underway, 17 some of the more subtle complexities of the signal acquisition remain to be examined. One important consideration that has not been investigated in detail, especially in the near-infrared ͑NIR͒, is the interaction between the remission spectrum of the reporter and the intervening tissue through which the light transport occurs prior to detection.…”

Simulation of optical response functions in molecular junctions

“…In molecular systems nonlinear optical spectroscopy is utilized to study transient molecular phenomena [1][2][3][4][5][6][7][8] and local interactions [9,10], for driving [11] and coherent control [12][13][14], and for molecular imaging [15,16]. Theory of nonlinear optical spectroscopy was developed [17,18] and successfully utilized in numerous studies [19][20][21][22][23][24][25][26][27][28][29][30][31].…”