Mapping breast cancer blood flow index, composition, and metabolism in a human subject using combined diffuse optical spectroscopic imaging and diffuse correlation spectroscopy

Abstract

Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are model-based near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, ? a , and reduced scattering, ? s ? ) and blood flow (blood flow index, BFI), respectively. DOSI-derived ? a values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin ( HbO 2 , HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 ?? mm ? 1 (37%) in ? s ? and 0.003 ?? mm ? 1 (33%) in ? a lead to ? 53 % and 9% errors in BFI, respectively. DOSI/DCS imaging of a solid tissue-simulating flow phantom and

Fig. 1

(a) The semi-infinite measurement geometry for DCS including a positive isotropic light sources and a negative isotropic light (imaging) source for DCS theory; see Sec. 2.1 and Ref.  for details. (b) Block diagram of the DOSI/DCS instrument, red color represents the multimode source fibers. Collection fiber bundle is shown by black, which contains a DOSI spectrometer fiber and two DCS single mode fibers (shown with yellow), and orange is an RF cable. (c) Photograph of the entire system on a portable cart and (d) diagram and photograph of handheld probe.

Fig. 2

DCS characterization. (a) Measured intensity autocorrelation functions $g_2$, during liquid phantom depth/flow experiment for flow tube 5 mm below the surface. (b) The relative change of blood flow, rBF, versus pump flow rates, for various flow tube depths. Depth is the distance between the top of the flow tube and the handheld probe. Data are the average of 10 samples, and error bars indicate standard deviation. The DOS-measured optical properties of the liquid phantom were ${\mu }_{\mathrm{s}}^{\prime }=0.75{\mathrm{mm}}^{-1}$ and ${\mu }_{\mathrm{a}}=0.005{\mathrm{mm}}^{-1}$ at 785 nm.

Fig. 3

Effect of absorption and scattering on BFI. BFI calculated with DOSI-corrected and constant optical properties are shown for (a) constant scattering and varied absorption and (b) constant absorption and varied scattering. The flow rate was constant during the measurements.

Fig. 4

DOSI and DCS images of silicone phantom with an embedded flow channel. (a, b) Absorption coefficient ${\mu }_{\mathrm{a}}$, (c, d) reduced scattering coefficient ${\mu }_{\mathrm{s}}^{\prime }$, and (e, f) BFI. Images on left represent no flow (a, c, and e), where the images on the right represent, flow (b, d, and f). Tick mark separation equals 5 mm.

Fig. 5

Integrated DOSI and DCS imaging during the clinical measurement of a breast cancer patient (a) ${\mu }_{\mathrm{s}}^{\prime }$ and (b) ${\mu }_{\mathrm{a}}$ ${\mathrm{mm}}^{-1}$ at 785 nm, (c) BFI (${\mathrm{mm}}^2/\mathrm{s}$) reconstructed with ${\mu }_{\mathrm{s}}^{\prime }$ and ${\mu }_{\mathrm{a}}$ values measured by DOSI at 785 nm in each, (d) BFI (${\mathrm{mm}}^2/\mathrm{s}$) calculated with constant ${\mu }_{\mathrm{s}}^{\prime }$ and ${\mu }_{\mathrm{a}}$ values (0.8 and $0.005{\mathrm{mm}}^{-1}$, respectively). Dashed lines (a and b) represent the region where the lesion was located and DOSI/DCS data were taken. The areola region is outlined with a semicircle. Tick marks represent 10 mm separations.

Fig. 6

Integrated DOSI and DCS imaging during the clinical measurement of a breast cancer patient. (a) ${\mathrm{HbO}}_2$ ($\mu \mathrm{M}$), (b) HbR ($\mu \mathrm{M}$), (c) water (%), (d) lipid (%), (e) tissue optical index ($\mathrm{TOI}=[\mathrm{HbR}]\times [\text{water}]/[\text{lipid}]$), (f) ${\mathrm{rMMRO}}_2$ ($T/N$), and (g) BFI (${\mathrm{mm}}^2/\mathrm{s}$). Dashed lines (a–e) represent the region where the lesion was located and DOSI/DCS data were taken. The areola region is outlined with a semicircle. (f and g) The region that DOSI/DCS data were collected. Tick marks represent 10 mm separations.