2.1. Diffuse Optical Spectroscopic Imaging technology
The current clinical DOSI instrument employed in ACRIN 6691combines frequency-domain and steady-state spectroscopies to provide quantitative broadband absorption and reduced scattering spectra from 650 to 1000 nm using a single source-detector pair [11
]. The frequency-domain portion of the instrument employs multiple amplitude-modulated laser diodes at discrete wavelengths (660, 680, 785, 810, 830, and 850 nm). A network analyzer measures the phase and amplitude of the detected modulated electronic signal from an avalanche photodiode (APD) over a broad range of source modulation frequencies (401 points spanning ~500MHz). The steady-state portion of the instrument is a combination of a broadband lamp and spectrometer. A combined broadband measurement currently takes about 5 seconds to complete. The entire system is cart-based. The only component in contact with the patient is a handheld probe which contains optical fibers and the APD inside a black plastic case.
2.2. General overview of ACRIN 6691 phantom use
Each ACRIN site is required to measure 2 different tissue-simulating phantoms per clinical measurement. One set of five identical phantoms (one for each ACRIN site) was constructed by the UC Irvine team (a.k.a. the “ACRIN” phantom series). The other set of identical phantoms was the “biomimic” soft phantom which was purchased from INO (Quebec, Canada), a.k.a. the “INO” phantom series. We purchased 2 sets of 5 phantoms from INO; one set was distributed to the ACRIN sites (1 phantom per site) and the other set is a backup. Note that by working in a strongly diffuse regime at depth, scattering in our context is always meant to be the “reduced scattering” (i.e., scattering × (1 – g), where g is the anisotropy).
The use of two phantoms offers both redundancy and validation insurance [12
]. For the purposes of redundancy, either the ACRIN or INO phantom can be used as calibration for tissue measurements. Both phantoms have “similar” optical properties at the six laser diode wavelengths which require the calibration. For the purposes of validation, one phantom is used as the calibration for the other to test optical property recovery. Instrument performance and operator compliance can be monitored at each clinical measurement date. The measurement protocol is built into the DOSI instrument control software. At the start of the clinical measurement, the operator measures both ACRIN and INO phantoms 3 times, each time picking up and re-placing the probe onto the phantom. These values are averaged together at each laser diode wavelength. This process is repeated after the first breast is scanned and repeated again at the conclusion of the measurement.
2.3. UC Irvine phantom construction method
Solid phantoms made at the Beckman Laser Institute contain the following four components: P4 silicone rubber base and p4 silicone activator (Eager Polymers, Chicago, IL), along with anatase titanium(IV) oxide and water-soluble nigrosin ink (Sigma-Aldrich, St. Louis, MO) for scattering and absorption features. Components were mixed together in a specific manner to achieve optimal homogeneity. First, 3.5 g of titanium(IV) oxide was stirred into 300 g of the silicone activator by hand. Next, the mixture was placed in a Branson 1200 ultrasonic cleaner (Branson Ultrasonics, Danbury, CT) for 3 hours to break apart coagulated titanium(IV) oxide particles. In a separate container, 5 mL of nigrosin solution (1.5 g/1 Liter H2O) was added to a 3000 g of the silicone base and mixed with a plunge mixer (Freeman Manufacturing & Supply Company, Avon, OH) for 5 minutes at 2000-2500 rpm. The titanium(IV) oxide suspension was then mixed into the nigrosin and silicone base mixture. The full set of components was mixed for 2 additional minutes with the plunge mixer and immediately placed into a Gas Vac II industrial vacuum degassing unit (Freeman Manufacturing & Supply Company, Avon, OH). The phantom mixture sat in the degassing chamber for approximately 2 minutes until a pressure of −29 mmHg was achieved. When the pressure reached −29 mmHg, bubbles began to collapse and the mixture was returned to normal atmospheric pressure. The mixture was evenly divided into five identical plastic containers and all containers were returned to the degassing unit for further degassing. After a pressure of −29 mmHg was reached, the chamber was vented, the containers were removed and placed on a flat surface, and phantoms were allowed to cure for 24 hours.
2.4. Commercial phantoms
Phantoms purchased from INO were specified to have absorption and reduced scattering in the range of 0.01 mm−1and 1 mm−1. The phantoms were prepared from a soft polyurethane matrix. Titanium dioxide particles (mean particle size 3 µm) were added as a scattering agent. A NIR dye was added to obtain an absorption feature at 750 nm. Carbon black was further added to raise the absorption at other wavelengths. INO made the phantom dimensions the same as the “ACRIN” phantoms using a mold supplied by the UC Irvine team (
Setup for calibration measurement. In order to measure the same phantom volume each time, a mask was prepared to fit the phantom (left) and lock the probe in place (right).