Contrast-enhanced near-infrared laser mammography with a prototype breast scanner: feasibility study with tissue phantoms and preliminary results of imaging experimental tumors

Abstract

Rationale and objectives: Near-infrared (NIR) optical mammography without contrast has a low specificity. The application of optical contrast medium may improve the performance. The concentration-dependent detectability of a new NIR contrast medium was determined with a prototype optical breast scanner. In vivo imaging of experimental tumors was performed.

Methods: The NIR contrast agent NIR96010 is a newly synthesized, hydrophilic contrast agent for NIR mammography. A concentration-dependent contrast resolution was determined for tissue phantoms consisting of whole milk powder and gelatin. A central part of the phantoms measuring 2 x 2 cm2 without contrast was replaced with phantom material containing 1 micromol/L to 25 nmol/L NIR96010. The composite phantoms were measured with a prototype NIR breast scanner with lasers of lambda1 = 785 nm and lambda2 = 850 nm wavelength. Intensity profiles and standard deviations of the transmission signal in areas with and without contrast were determined by linear fit procedures. Signal-to-noise ratios and spatial resolution as a function of contrast concentration were determined. Near-infrared imaging of five tumor-bearing SCID mice (MX1 breast adenocarcinoma, tumor diameter 5-10 mm) was performed before and after intravenous application of 2 micromol/kg NIR96010.

Results: Spectrometry showed an absorption maximum of the contrast agent at 755 nm. No spectral shifts occurred in protein-containing solution. Signal-to-noise ratio in the transmission intensity profiles ranged from 1.1 at 25 nmol/L contrast to 28 at 1 micromol/L. At concentrations <40 nmol/L, no differentiation from the background was possible. The transitional area between the contrast-free edge of the phantom and the central contrast-containing part appeared in the profiles as a steep increase with a width of 4.2 +/- 1.8 mm. The experimental tumors were detectable in nonenhanced images as well as contrast-enhanced images, with better delineation after contrast administration. In postcontrast absorption profiles, a 44.1% +/- 11.3% greater absorption increase was seen in tumor tissue compared with normal tissue.

Conclusions: The laser wavelength lambda1 of the prototype laser mammography device was not situated at maximum absorption of the contrast agent NIR96010 but on the descending shoulder of the absorption spectrum. This implies a 20% signal loss for contrast detection. Despite the nonideal measurement conditions, concentrations as low as 40 nmol/L were detectable in vitro. In vivo, all tumors were detectable in color-coded nonenhanced scans as well as in contrast-enhanced scans, with better delineation after contrast administration.