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 threedimensional 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 threedimensional endogeneous optical and physiological breast properties. Bulk physiological properties were quantified for 52 healthy subjects in the parallel-plate transmission geometry. Threedimensional 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 ͑MRI͒. 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.

Frequency-domain Diffuse Optical Tomography System Adopting Lock-in Amplifier

“…DOT는 광원의 변조방식에 따 라 크게 3가지 형태의 측정방법이 존재한다. 즉, 빛의 세기에 대한 감쇄만을 측정하는 연속파(CW, continuous-wave) 시스템, 수십~수백 MHz의 정현파로 변조된 광원을 이용하여 진폭 감쇄 및 위상 천이를 측정하는 주파수영역(FD, frequencydomain) 시스템, 1 ns 이하의 펄스폭을 가지는 펄스파로 변 조된 광원을 이용하여 펄스의 퍼짐과 지연을 측정하는 시간 영역(TD, time-domain) 시스템이 있다 [1][2][3] . 본 논문에서는 위의 시스템중 주파수영역 DOT 시스템을 채택하였다.…”

“…Intralipid(정제 대두유)를 이용하여 구현하였고 [10] , 흡수계수 는 분광계(Ocean Optics, USB2000)를 이용하여 그림 4에 나 타낸 바와 같이 광원으로 사용된 LD의 파장에 대한 흑색 잉 크의 흡수도를 측정하여 구현하였다 [3] . …”

Implementation of Multi-channel Concurrent Detection Homodyne Frequency-domain Diffuse Optical Imaging System

“…일반적으로 DOI 시스템에서는 보다 많은 수의 측정 데이 터를 수집하여 동일한 영역에 대하여 흡수계수 및 산란계수 를 미지수로 가지는 방정식의 수를 증가시켜 역방향문제(inverse problem)의 정확성을 향상시키기 위하여, 채널수, 즉 광원-광 검출기 쌍(source-detector pair)의 수를 늘린다 [1] . [1][2][3][4][5] . [4,5] .…”

Clinical Translation of a Novel Hand-held Optical Imager for Breast Cancer Diagnosis

“…Parallely, a different CW-based device (Device #7, Table 3.1) was developed by another research group at the University of Pennsylvania [60,71], employing a long coherence laser source (4 sources) and fast photoncounting avalanche photodiodes as detectors (four of them) coupled via detector fibers. In contrast, a hand-held device (termed as a tissue oximeter) developed at the Ohio State University (Device #6, Table 3.1) contained embedded laser diode and photodiode modules for CW-based NIR imaging [57][58]71].…”

“…� A hand-held device (Device #7, Table 3.1) was designed to measure blood flow heterogeneity [58][59] in order to show that blood flow in a breast containing a palpable tumor is different than that in a normal breast. The device was used to obtain measurements from a 2.0 cm diameter lesion located at a depth of 1.0 cm.…”