Image-derived arterial input function for quantitative fluorescence imaging of receptor-drug binding in vivo.
Receptor concentration imaging (RCI) with targeted-untargeted optical dye pairs has enabled in vivo immunohistochemistry analysis in preclinical subcutaneous tumors. Successful application of RCI to fluorescence guided resection (FGR), so that quantitative molecular imaging of tumor-specific receptors could be performed in situ, would have a high impact. However, assumptions of pharmacokinetics, permeability and retention, as well as the lack of a suitable reference region limit the potential for RCI in human neurosurgery. In this study, an arterial input graphic analysis (AIGA) method is presented which is enabled by independent component analysis (ICA). The percent difference in arterial concentration between the image-derived arterial input function (AIFICA ) and that obtained by an invasive method (ICACAR ) was 2.0 ± 2.7% during the first hour of circulation of a targeted-untargeted dye pair in mice. Estimates of distribution volume and receptor concentration in tumor bearing mice (n = 5) recovered using the AIGA technique did not differ significantly from values obtained using invasive AIF measurements (p = 0.12). The AIGA method, enabled by the subject-specific AIFICA , was also applied in a rat orthotopic model of U-251 glioblastoma to obtain the first reported receptor concentration and distribution volume maps during open craniotomy.
Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA. jonathan.t.elliott@dartmouth.edu.
Jonathan T
JT
Elliott
Department of Surgery, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
Kimberley S
KS
Samkoe
Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.
Scott C
SC
Davis
Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.
Jason R
JR
Gunn
Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.
Keith D
KD
Paulsen
Department of Surgery, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.|Section of Neurosurgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03756, USA.
David W
DW
Roberts
Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.|Department of Surgery, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
Brian W
BW
Pogue
D000818:Animals; D002339:Carotid Arteries / Q000503:physiopathology*; D045744:Cell Line, Tumor; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D011955:Receptors, Drug
brain imaging; cerebral hemodynamics; kinetic modeling; neurooncology; neurosurgery