Quantification of tumor tissue populations by multispectral analysis.
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 mm(3)) were highly correlated (r = 0.81, P < 0.01) with histological estimates (117 +/- 51 mm(3)). In the treatment study, MS viable tumor volume (at day 10) was 77 +/- 67 mm(3) for the Apo2L/TRAIL+CPT-11 group, and was significantly reduced relative to the control group (292 +/- 127 mm(3), P < 0.01). This method shows promise as a means of detecting an early therapeutic response in vivo.
Department of Physiology, Genentech, Inc., South San Francisco, California 94080, USA. rcarano@gene.com
Richard A D
RA
Carano
Adrienne L
AL
Ross
Jed
J
Ross
Simon P
SP
Williams
Hartmut
H
Koeppen
Ralph H
RH
Schwall
Nicholas
N
Van Bruggen
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008562:Membrane Glycoproteins / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use; D019014:fas Receptor / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D059004:Topoisomerase I Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000077146:Irinotecan; D002166:Camptothecin