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Combined diffuse optical spectroscopy and contrast-enhanced MRI for monitoring breast cancer neoadjuvant chemotherapy: a case study

(In press, Journal of Biomedical Optics, 2005)
Natasha Shah1, Jessica Gibbs2, Dulcy Wolverton2, Albert Cerussi1, Nola Hylton2 and Bruce J. Tromberg1
1Laser Microbeam and Medical Program, Beckman Laser Institute and Medical Clinic, University of California, Irvine 92162-1475,
2Magnetic Resonance Science Center, University of California San Francisco, San Francisco, CA

Monitoring tumor response to therapy can allow assessment of treatment efficacy, maximizing patient outcome and survival. In this study we employ a non-invasive, handheld Laser Breast Scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess tumor response to pre-surgical neoadjuvant chemotherapy. DOS and cMRI scans were performed after the first and fourth cycles of a doxorubicin/cyclophosphamide regimen in a patient with invasive ductal carcinoma.

DOS measurements were used to quantify optical and physiological parameters which were mapped to T2- and T1-weighted cMRI images. Initial DOS measurements showed high tumor/normal contrast in total hemoglobin concentration (THC, 56µM vs. 18-25µM) and water fraction (81% vs. 13-16%) co-localized with regions of strongly enhancing T2-wieghted and cMRI signals. After the fourth cycle of chemotherapy, decreases in peak MRI contrast-enhancement values (36.7%) and apparent lesion volume (21.7cc vs. 13.4cc) which corresponded to physiological changes measured by DOS including a 20-25% reduction in the spatial extent of the tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6µM vs. 23.4µM). These data provide in vivo validation of the accuracy of broadband DOS and the sensitivity of optical methods to changes in tumor physiology.

Reconstructed axial images of the lesion in figure 1. The eleven images correspond to the discrete DOS measurement sites. Fiducial at position 1 appeared on axial image #106 and fiducial at position 11 appeared on image #206. Thus every tenth image was chosen to approximate a DOS measurement point.

Maximum intensity projections of the lesion (a) after 1 cycle of chemotherapy and (b) after 4 cycles of chemotherapy. The lesion measures 3.7 x 3.9 x 3.9 cm in (a) vs. 3.1 x 3.5 x 2.8 in (b).

Comparison of DOS-derived a) water content b) Total hemoglobin concentration c) tissue oxygen saturation and d) lipid content for the lesion after 1 cycle of chemotherapy and 4 cycles of chemotherapy. The full-width half maximum (FWHM) is indicated on each linescan.

  Tumor Volume (cc) Peak Enhancement (top 5% of voxels, %above t0) Percentage of tumor volume with Gd-DTPA wash-out THC (peak values, µM) StO2(peak values, %) THC Average values (µM) Water content Average Values (%) Lipid Content Average Values (%)
Post Chemo 1 21.9 271.8 51.3 56.02 74.9 41.6 44.4 48.6
Post Chemo 4 13.7 163.9 26.1 34.3 68.1 23.4 36.8 71.9
Difference (%) -37.6 -39.7 -49.1 -38.7 -9.1 -43.7 -17.1 +33.0

Comparisons of changes in MR and DOS-derived parameters demonstrating response to therapy.

References

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