Diagnostic imaging of early-stage breast cancer is essential for decreasing the cancer death rate in women in the United States. The conventional anatomical based screening techniques are neither comprehensive nor infallible, especially in women with dense breast tissues. Over the past 20 years, near-infrared (NIR) optical imaging approaches have been developed for breast cancer diagnosis, based upon the endogenous absorption contrast owing to the non-specific process of angiogenesis1-10
NIR light between 700-900 nm wavelengths is minimally absorbed and preferentially scattered, allowing its propagation through deep tissues. In recent years, external contrast agents are used to enhance the optical contrast between the diseased and normal tissue regions (i.e. fluorescence-enhanced optical imaging) and thus molecularly target metastatic cancer cells within the breast tissue.11-15
NIR optical imaging (with our without fluorescence) employs different source-detector imaging configurations during actual experimental studies. These imaging configurations can be broadly classified into10,16
: (i) compressed tissue-based configuration, (ii) circular configuration, and (iii) sub-surface configuration. To date, most three-dimensional (3-D) optical imaging studies towards breast cancer diagnosis are restricted either to compressed tissue configuration2,17-21
or circular configuration22-36
. The compressed tissue configuration is analogous to x-ray mammography, and is disadvantageous due to minimal patient comfort from tissue compression and limited information obtained around the entire breast tissue volume. The circular configuration has minimal patient discomfort, but is limited by the bulky and non-portable instrumentation. Sub-surface configuration is a relatively new method that requires notissue compression, and can be designed to mimic a portable and flexible imaging probe.32,37-50
However, 3-D tomography studies using the sub-surface imaging configuration are limited32,49-50
and challenging due to limited depth information obtained using only reflectance-based measurements during imaging reconstructions.
In recent years, hand-held based optical imaging systems, employing the sub-surface imaging configuration are developed in an attempt to translate the technology to the clinic, with maximum patient comfort and portability (against the bulky optical imagers available). However, the hand-held optical imagers available to date37-48
are not capable of: (i) performing 2-D or 3-D optical tomography, since the source and detector points are not co-registered onto the tissue contours, thus limiting them to only surface imaging and 2-D target localization; and (ii) contouring along tissue curvatures with good surface contact, since the hand-held probes have a flat surface..
Herein, a novel hand-held probe based optical imaging system is developed and 3-D optical tomography using fluorescence contrast agents has been demonstrated under different experimental conditions. A frequency-domain intensified charge-coupled device (ICCD) based detection system was coupled to a unique hand-held optical probe, such that simultaneous multiple point illumination and collection is possible over large areas (5×10 cm2). The effect of simultaneous multiple point illumination measurement geometry over sequential single point illumination geometry, in terms of total area of detected fluorescence amplitude and overall signal strength, has been demonstrated experimentally. Three-dimensional (fluorescence-enhanced) optical tomography has been successfully performed for the first time using a hand-held based optical imager, accounting for the excitation leakage issues as well.