Quantification of tumor tissue populations by multispectral analysis

• Published in: Magnetic resonance in medicine Vol. 51; no. 3; pp. 542 - 551
• Main Authors: Carano, Richard A.D., Ross, Adrienne L., Ross, Jed, Williams, Simon P., Koeppen, Hartmut, Schwall, Ralph H., Van Bruggen, Nicholas
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2004
• Subjects: Adipose Tissue - pathology; Animals; Antineoplastic Agents, Phytogenic - therapeutic use; Apo2L/TRAIL; Apoptosis Regulatory Proteins; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Cell Line, Tumor; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; diffusion; Disease Models, Animal; fas Receptor - therapeutic use; Female; Humans; K-means clustering; Ligands; Magnetic Resonance Imaging - methods; Magnetic Resonance Spectroscopy - methods; Membrane Glycoproteins - therapeutic use; Mice; Mice, Nude; multispectral analysis; Necrosis; Neoplasm Transplantation; Remission Induction; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Time Factors; TNF-Related Apoptosis-Inducing Ligand; Topoisomerase I Inhibitors; Transplantation, Heterologous; tumor; Tumor Necrosis Factor-alpha - therapeutic use
• ISSN: 0740-3194; 1522-2594
• DOI: 10.1002/mrm.10731

Tumor heterogeneity complicates the quantification of a therapeutic response by MRI. To address this issue, a novel approach has been developed that combines MR diffusion imaging with multispectral (MS) analysis to quantify tumor tissue populations. K‐means (KM) clustering of the apparent diffusion coefficient (ADC), T2, and proton density (M0) was employed to estimate the volumes of viable tumor tissue, necrosis, and neighboring subcutaneous adipose tissue in a human colorectal tumor xenograft mouse model. In a second set of experiments, the temporal evolution of the MS tissue classes in response to therapeutic intervention Apo2L/TRAIL and CPT‐11 was observed. The multiple parameters played complementary roles in identifying the various tissues. The ADC was the dominant parameter for identifying regions of necrosis, whereas T2 identified two necrotic subpopulations, and M0 contributed to the differentiation of viable tumor from subcutaneous adipose tissue. MS viable tumor estimates (mean volume = 275 ± 147 mm3) were highly correlated (r = 0.81, P < 0.01) with histological estimates (117 ± 51 mm3). In the treatment study, MS viable tumor volume (at day 10) was 77 ± 67 mm3 for the Apo2L/TRAIL+CPT‐11 group, and was significantly reduced relative to the control group (292 ± 127 mm3, P < 0.01). This method shows promise as a means of detecting an early therapeutic response in vivo. Magn Reson Med 51:542–551, 2004. © 2004 Wiley‐Liss, Inc.