Diffuse optical tomography and spectroscopy of breast cancer and fetal brain

Abstract

Diffuse optical techniques utilize light in the near infrared spectral range to measure tissue physiology noninvasively. Based on these measurements, either average bulk optical properties or three-dimensional spatial maps of tissue properties such as total hemoglobin concentration, blood oxygen saturation and scattering can be obtained using model-based reconstruction algorithms. In this thesis, diffuse optical techniques were applied for in vivo breast cancer imaging and transabdominal fetal brain oxygenation monitoring. For clinical in vivo breast cancer imaging, diffuse optical tomography technique and related instrumentation were developed. The clinical diffuse optical tomography instrument utilized near infrared light sources of multiple wavelengths, and multiple source-detector positions in a parallel plate geometry. Transmission continuous-wave measurements by a lens-coupled CCD camera and remission frequency-domain measurements by fiber-coupled detector channels were performed simultaneously. Human subject measurements were carried out in the prone position. The breast was softly compressed and the space adjacent to the breast was filled with a matching fluid with similar optical properties to that of the breast. A nonlinear conjugate gradient inverse algorithm with a priori spectral constraints was utilized to reconstruct three-dimensional endogeneous optical and physiological breast properties. Bulk physiological properties were quantified for 52 healthy subjects in the parallel-plate transmission geometry. Three-dimensional images of the breast were reconstructed for 21 subjects with breast carcinomas. Tumor contrast with respect to normal tissue was found in total hemoglobin concentration and scattering coefficient. An optical index combining total hemoglobin concentration and scattering coefficient shows the tumor contrast to be 2–3 times larger compared to the healthy tissue. Tumor contrast and tumor volume changes during neoadjuvant chemotherapy were tracked for one subject and compared to the dynamic contrast-enhanced magnetic resonance imaging (MRI). Our measurement revealed tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. Finally, the feasibility of measuring blood flow of breast tumors using optical methods was demonstrated for seven subjects. In a qualitatively different set of experiments, the feasibility of transabdominal fetal brain oxygenation monitoring was demonstrated on pregnant ewes with induced transient fetal hypoxia. Preliminary noninvasive clinical measurements before and after human Cesarean sections were discussed, identifying future directions. Overall, this research has translated diffuse optical tomography techniques into a clinical research environment.