A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging

Abstract

Fluorescence tomography (FT) is a promising molecular imaging technique that can spatially resolve both fluorophore concentration and lifetime parameters. However, recovered fluorophore parameters highly depend on the size and depth of the object due to the ill-posedness of the FT inverse problem. Structural a priori information from another high spatial resolution imaging modality has been demonstrated to significantly improve FT reconstruction accuracy. In this study, we have constructed a combined magnetic resonance imaging (MRI) and FT system for small animal imaging. A photo-multiplier tube is used as the detector to acquire frequency domain FT measurements. This is the first MR-compatible time-resolved FT system that can reconstruct both fluorescence concentration and lifetime maps simultaneously. The performance of the hybrid system is evaluated with phantom studies. Two different fluorophores, indocyanine green and 3-3' diethylthiatricarbocyanine iodide, which have similar excitation and emission spectra but different lifetimes, are utilized. The fluorescence concentration and lifetime maps are both reconstructed with and without the structural a priori information obtained from MRI for comparison. We show that the hybrid system can accurately recover both fluorescence intensity and lifetime within 10% error for two 4.2 mm-diameter cylindrical objects embedded in a 38 mm-diameter cylindrical phantom when MRI structural a priori information is utilized.

Figure 1

The schematic diagram of the PMT-based frequency domain fluorescence tomography system. The electric signals are indicated by solid lines, while the optical signals are indicated by dashed lines.

Figure 2

(a) The fiber optic interface. The 16-leg birdcage RF-coil is integrated into the interface, therefore, both optical and MRI measurements can be taken simultaneously. (b) The translational stage. A 1 mm single fiber was mounted on the translational stage to acquire data from the eight detector sites sequentially. The collected light is delivered to the shielded single PMT detection unit.

Figure 3

a) The picture of the prototype PMT-based detection unit. The collimation system (1), incoming fiber (2), RF-amplifier (3) and PMT (4) are fixed in the unit. b) The schematic figure of the band-pass filters and collimation system. Two aspheric lenses are used to collimate the light coming out of the bundle and focus it on the PMT. Two cascaded band-pass filters (BP) are used to eliminate the excitation light.

Figure 4

The standard deviation (STD) of the amplitude and phase measurements, with respect to the amplitude measurements, is shown in a) and b), respectively.

Figure 5

a) The axial MR image of the phantom. The ICG inclusion is held in the glass tube that is seen as a bright circle with a dark outline in the image. b) and c) The plot of the recovered mean ICG concentration with respect to true ICG concentration without and with background fluorescence, respectively. The circle and triangle dots represent the recovered values, with and without the structural a priori information, respectively. The least squares lines of best fit are the red dashed ones. The fitted equation is also shown in the Figure. The recovered ICG concentration shows a linear response with respect to true ICG concentration both with and without the structural a priori information. However, the true values are recovered only when structural a priori information is available.

Figure 6

The reconstructed ICG concentration maps for the first phantom study. When there is no ICG background, the reconstructed ICG concentration maps without (left column) and with (right column) structural a priori information from MRI are shown in the first and second columns. Meanwhile, when 34nM ICG is added to the background, the reconstructed ICG concentration maps without (left column) and with (right column) structural a priori information from MRI are shown in the third and forth columns. The color bars all have units of nM. The numbers on the right side present the true ICG concentration values.

Figure 7

The results for the second phantom study. The first column is the MRI images of the phantoms. Each case has an inclusion with a different location and size. The reconstructed ICG concentration maps, without and with structural a priori information from MRI, are shown in the second and third columns, respectively. The recovered ICG concentration value drastically depends on the size and location of the inclusion without any a priori information. However, the true concentration value can be recovered for all seven cases when MRI structural a priori information is used. The color bars all have the units of nM.

Figure 8

The results for the third phantom study. The first row shows the MR image of the phantom. The second and third rows show the reconstructed ημ_af maps, without and with MRI a priori information. Meanwhile, the fourth and fifth rows present the lifetime maps reconstructed without and with MRI a priori information.

Figure 9

The results for the fourth phantom study. The left column shows the reconstructed ημ_af maps (mm⁻¹) without and with MR a priori information. Meanwhile, the right column presents the lifetime maps reconstructed without and with MR a priori information.