A single subject was recruited for this case study. The subject provided informed written consent to participate in this research study, which was approved by the University of California, Irvine, Institutional Review Board (Protocol #95-563). The subject was a 31-year-old female with a suspicious mass in the right breast at the 3 o'clock position 1 to 3 cm from the nipple. Standard clinical ultrasound indicated that the lesion was well circumscribed and homogeneous, measuring 3.7 by 1.8 by 2.0 cm.
LBS measurements were performed on the subject over an 8-week cycle (Table 1). The initial LBS measurement was taken 4 days prior to a standard core biopsy. Pathology indicated that the sampled lesion was a benign fibroadenoma. Subsequent LBS measurements were performed weekly thereafter to monitor breast optical properties throughout the wound-healing process, as outlined in Table 1; a total of eight postbiopsy LBS measurements were performed. Because the subject was premenopausal, we also related LBS measurement dates to patient menstrual cycle phases. In order to approximate the subject's phase in menstrual cycle, menses onset dates were recorded. The menstrual cycle length was calculated as the first day of the menses to the last day before next menses. The assumption that the luteal phase is approximately 14 days prior to the onset of menses was used to postulate when the ovulatory phase occurred.
Care was taken to perform LBS measurements with the patient in a consistent position. The subject laid supine with her arm up above her head on a recliner at about 30 deg from horizontal for all LBS measurements. An ultrasound was then performed to visualize the breast lesion position at the time of the baseline LBS measurement. A steady-state broadband-only scan was done to quickly visualize the areas of greatest optical attenuation over the lesion localized by ultrasound. The point of highest attenuation was assumed to be the best representation of the lesion and was chosen as the center of the LBS scan area (Fig. 1(a)). A 10-mm-spaced point grid measuring 50 by 100 mm was marked on the breast using a nonpermanent surgical skin marker. Within our coordinate system, the nipple was taken to be the origin, with the LBS scan area centered on the (30 mm, 0 mm) location. The large scan area was chosen to cover regions of the breast both with and without the lesion. The top leftmost point of the grid (0 mm, 50 mm) was measured with respect to the nipple and recorded to remark the LBS scan area on the subject during subsequent LBS measurements. On the contralateral normal breast, a partial grid covering the same area as the lesion was also marked and measured as a control. LBS measurements were performed at each spatial grid location by moving the handheld probe to each marked location. The instrument probe was placed with light gravitational pressure without compression on the skin surface. The average penetration depth of the light was calculated to be approximately 15 mm below the surface of the skin.
Maps of breast tissue physiological properties were generated by calculating the DOS-measured parameters at each grid location. No tomographic reconstructions were used, and the tissue within the field of view was assumed to be homogeneous in accordance with the standard diffusion approximation. Map points were interpolated using 2-D nearest-neighbor cubic splines to round out the discrete shapes. All image thresholds were performed using the maximum and minimum values of the image. A four-stage color bar was used with RGB values of (0,0,0), (0,0,255), (0,255,255), and (255,255,255) to display all functional maps.
The lesion center was defined as the spatial location of the TOI maximum in accordance with our previous studies. The spatial extent of the lesion was then defined as the full width at half maximum (FWHM) of the TOI image, as we have done for a single axis in previous nonimaging studies. The TOI FWHM image then formed a mask for the images of other optical properties. Because of the limited spatial sampling of the lesion (i.e., only a few points are typically found inside the uninterpolated lesion masks), we have reported the maximum value within the FWHM as a value representative of the lesion Feature-based stratification was preferred to a strict spatial segmentation of lesion area to guard against possible movement of the lesion and/or optically scanned area. Normal tissue values were taken to be the average of DOS-measured parameters from the same spatial location on the contralateral normal breast. The calculated standard deviations, typically from the background and other normal tissue regions, represents the variation in the measured parameter across the image area. Images were rethresholded by TOI FWHM for each measurement date.
An ultrasound of the lesion was performed in order to determine the position, orientation depth, and size (Fig. 2). Ultrasound showed a well-circumscribed, solid mass at the 3 o'clock position of the right breast, 1 to 3 cm from the nipple. The ultrasound was taken in two views: transverse and longitudinal. The lesion dimensions in the transverse and longitudinal orientations were measured to be approximately 26.8x21.3 mm and 20.6x20.8 mm, respectively.
A needle core biopsy was administered by a general surgeon 4 days after a baseline DOS measurement session. An incision was made at the surface of the breast at a site away from the lesion [Fig. 1(a)]. Figure 1(b) depicts the orientation of the biopsy needle in relationship to the lesion location and the DOS scan in a medial-lateral view. The needle was inserted through the incision site and tracked through the lesion in the breast (dotted line). The LBS scan area was performed in the direction indicated in the figure. The position of the incision site was noted at each DOS measurement. On day 9, the incision scar was red and about the same size as the tip of the surgical marker used to mark the breast. The patient claimed the area was tender, but there was no irritation or bruising visible. By day 23, the redness at the site of incision had completely dissipated. On day 44, the patient reported that her breasts felt swollen. Her menses began on day 46.