title: Monitoring of tumor response to Cisplatin using optical spectroscopy.
abstract: BACKGROUND
  Anatomic imaging alone is often inadequate for tuning systemic treatment for individual tumor response. Optically based techniques could potentially contribute to fast and objective response monitoring in personalized cancer therapy. In the present study, we evaluated the feasibility of dual-modality diffuse reflectance spectroscopy-autofluorescence spectroscopy (DRS-AFS) to monitor the effects of systemic treatment in a mouse model for hereditary breast cancer.
  
  
  METHODS
  Brca1(-/-); p53(-/-) mammary tumors were grown in 36 mice, half of which were treated with a single dose of cisplatin. Changes in the tumor physiology and morphology were measured for a period of 1 week using dual-modality DRS-AFS. Liver and muscle tissues were also measured to distinguish tumor-specific alterations from systemic changes. Model-based analyses were used to derive different optical parameters like the scattering and absorption coefficients, as well as sources of intrinsic fluorescence. Histopathologic analysis was performed for cross-validation with trends in optically based parameters.
  
  
  RESULTS
  Treated tumors showed a significant decrease in Mie-scattering slope and Mie-to-total scattering fraction and an increase in both fat volume fraction and tissue oxygenation after 2 days of follow-up. Additionally, significant tumor-specific changes in the fluorescence spectra were seen. These longitudinal trends were consistent with changes observed in the histopathologic analysis, such as vital tumor content and formation of fibrosis.
  
  
  CONCLUSIONS
  This study demonstrates that dual-modality DRS-AFS provides quantitative functional information that corresponds well with the degree of pathologic response. DRS-AFS, in conjunction with other imaging modalities, could be used to optimize systemic cancer treatment on the basis of early individual tumor response.
authors.affiliation: Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: j.spliethoff@nki.nl.
authors.forename: Jarich W
authors.initials: JW
authors.lastname: Spliethoff
authors.affiliation: Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Evers
authors.affiliation: Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Janneke E
authors.initials: JE
authors.lastname: Jaspers
authors.affiliation: Department of Minimally Invasive Healthcare, Philips Research, Eindhoven, The Netherlands.
authors.forename: Benno H W
authors.initials: BH
authors.lastname: Hendriks
authors.affiliation: Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Sven
authors.initials: S
authors.lastname: Rottenberg
authors.affiliation: Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands; MIRA Institute, Technical University Twente, Enschede, The Netherlands.
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Ruers
references.citation: Lasers Surg Med. 2001;29(2):118-27
references.pmid: 11553898
references.citation: Med Phys. 1992 Jul-Aug;19(4):879-88
references.pmid: 1518476
references.citation: Cell Death Differ. 2012 Sep;19(9):1561-70
references.pmid: 22460322
references.citation: Neoplasia. 2009 Sep;11(9):889-900
references.pmid: 19724683
references.citation: J Biomed Opt. 2005 Jul-Aug;10(4):44004
references.pmid: 16178638
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-892
references.pmid: 22397650
references.citation: J Vasc Interv Radiol. 2005 Nov;16(11):1473-8
references.pmid: 16319153
references.citation: Lasers Surg Med. 2010 Jan;42(1):15-23
references.pmid: 20077490
references.citation: Cancer Res. 2012 Sep 1;72(17):4318-28
references.pmid: 22777823
references.citation: Photochem Photobiol Sci. 2011 Jul;10(7):1189-95
references.pmid: 21487628
references.citation: Opt Express. 2009 Feb 2;17(3):1256-67
references.pmid: 19188953
references.citation: Eur J Cancer. 2009 Jan;45(2):228-47
references.pmid: 19097774
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4014-9
references.pmid: 17360469
references.citation: Chest. 2006 Apr;129(4):995-1001
references.pmid: 16608949
references.citation: Ann Oncol. 2008 Feb;19(2):348-52
references.pmid: 17962202
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12111-6
references.pmid: 17626182
references.citation: J Biomed Opt. 2010 May-Jun;15(3):037015
references.pmid: 20615044
references.citation: Appl Opt. 2001 Sep 1;40(25):4633-46
references.pmid: 18360504
references.citation: Eur J Cancer. 2008 Sep;44(13):1807-19
references.pmid: 18640028
references.citation: Lung Cancer. 2013 May;80(2):165-71
references.pmid: 23402823
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12117-22
references.pmid: 17626183
references.citation: J Nucl Med. 2009 May;50 Suppl 1:122S-50S
references.pmid: 19403881
references.citation: Ann Oncol. 2012 Jul;23(7):1687-93
references.pmid: 22112970
references.citation: AJR Am J Roentgenol. 2012 Oct;199(4):809-15
references.pmid: 22997372
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19494-9
references.pmid: 18042710
references.citation: Am J Obstet Gynecol. 2002 Mar;186(3):374-82
references.pmid: 11904594
references.citation: Radiographics. 2006 Jan-Feb;26(1):143-56
references.pmid: 16418249
references.citation: J Biomed Opt. 2008 Mar-Apr;13(2):024012
references.pmid: 18465975
references.citation: Ann Surg Oncol. 2004 Jan;11(1):65-70
references.pmid: 14699036
references.citation: Opt Lett. 2000 Oct 1;25(19):1451-3
references.pmid: 18066245
references.citation: Q J Nucl Med Mol Imaging. 2009 Apr;53(2):210-23
references.pmid: 19293769
references.citation: Gastroenterology. 2000 Sep;119(3):677-82
references.pmid: 10982761
references.citation: Cancer Res. 2009 Apr 1;69(7):2919-26
references.pmid: 19293184
references.citation: J Biomed Opt. 2013 Feb;18(2):27009
references.pmid: 23400402
references.citation: J Biomed Opt. 2011 Aug;16(8):087010
references.pmid: 21895337
references.citation: J Biomed Opt. 2002 Oct;7(4):587-94
references.pmid: 12421125
references.citation: Eur J Surg Oncol. 2013 Jan;39(1):68-75
references.pmid: 22963834
references.citation: Transl Oncol. 2012 Aug;5(4):238-46
references.pmid: 22937175
references.citation: Mol Imaging. 2008 Jan-Feb;7(1):21-7
references.pmid: 18384720
references.citation: Lasers Surg Med. 2001;28(1):56-66
references.pmid: 11430444
references.citation: Ann Oncol. 2009 Jun;20(6):1057-61
references.pmid: 19164458
references.citation: Cancer. 2003 Apr 1;97(7):1681-92
references.pmid: 12655525
references.citation: Cancer Res. 2010 Jun 1;70(11):4759-66
references.pmid: 20460512
references.citation: Int J Cancer. 1995 May 29;61(5):732-7
references.pmid: 7768649
references.citation: FEBS J. 2012 Aug;279(15):2610-23
references.pmid: 22621751
references.citation: Acad Radiol. 2010 Aug;17(8):1031-9
references.pmid: 20542448
references.citation: Cancer Res. 2001 Feb 1;61(3):991-9
references.pmid: 11221895
references.citation: Breast Cancer Res. 2013 Feb 22;15(1):R14
references.pmid: 23433249
references.citation: Biomed Opt Express. 2010 Nov 17;1(5):1432-1442
references.pmid: 21258560
references.citation: Cancer Imaging. 2005 May 24;5:27-31
references.pmid: 16154816
references.citation: AJR Am J Roentgenol. 2005 Jun;184(6):1774-81
references.pmid: 15908529