Header Forschung

Innovative endoscopy for label-free optical biopsies in surgery of colorectal liver metastases and hepatocellular carcinoma

Summary of the Project

For many cancer patients, the primary treatment plan is tumor resection, but in the quest of retaining as much healthy tissue as possible, it is impossible for surgeons to know whether they have removed all traces of the cancerous tissue without immediate analysis of resection borders. Therefore, extracted tissue is currently delivered to pathology to ascertain whether tumor cells are found near the resection edges, indicating incomplete tumor removal. This process is work intensive and time consuming, leading to prolonged operation time. In case of postoperative finding of positive resection margins, the patient has to return to the operating theater.

A new imaging technique may give doctors the ability to analyze the tumor right in the OR, and know immediately which tissue areas need to be removed. Multiphoton microscopy enables analysis of tissue structures down to subcellular resolution based on the morpho-chemical information retrieved from optical signals generated by endogenous tissue constituents by irradiation with short-pulsed lasers. The technique is gaining increasing attention in medicine for fast pathology without tissue preparation as well as for intravital microscopy. For instance, label-free multimodal multiphoton microscopy (thereafter indicated as LF3M) combining simultaneous acquisition of CARS, TPEF and SHG allows imaging of lipid-rich structures (e.g. lipid droplets), of collagen (e.g. in fibrotic tissue and blood vessels) and of other endogenous intra- and extra-cellular fluorophores (elastin, NAD(P)H, FAD, lipofuscin).

LF3M is still unexplored for hepatic tumors, whose treatment may gain great benefit from intraoperative precise detection of tumor boundaries. Complete resection with tumor-free resection margins is crucial for patients’ oncological outcome. This is true for primary hepatic cancers as hepatocellular carcinomas as well as secondary hepatic cancers as colorectal liver metastases. Until present, medical applications of LF3M in medicine were limited to large scanning microscopes that could only be used in research laboratories.

Scientific Goals

  • develop multiphoton microscopic methods for label-free intraoperative detection of tumor borders and infiltrations by performing optical biopsies in situ, i.e., before and after tissue resection.
  • definition of morpho-chemical parameters that enable to discriminate primary and metastatic cancer from normal or cirrhotic liver tissue based on LF3M images.
  • development of tools for automated liver cancer recognition in those images
  • assessment of a compact multiphoton microscopy device in the operating theater, for inspection of resected tissue directly during surgeries either inside or before the OR
@ Roberta Galli, KSM, TU Dresden

Figure 1: (A) LF3M image and reference HE staining of a cryosection of human hepatic cancer biopsy (colon carcinoma metastasis) (B) LF3M image and reference HE staining of the tumor border and details showing normal hepatocytes and tumor cells. (C) Endoscopic LF3M image of mouse liver tissue and reference HE staining. Color coding of LF3M images: red=CARS; green=TPEF, blue=SHG. @ Roberta Galli, KSM, TU Dresden

R. Galli, K.H. Sitoci-Ficici, O. Uckermann, R. Later, M. Mareckova, M. Koch, E. Leipnitz, G. Schackert, E. Koch, M. Gelinsky, G. Steiner, M. Kirsch „Label-free multiphoton microscopy reveals relevant tissue changes induced by alginate hydrogel implantation in rat spinal cord injury“, Scientific Reports 8(1), 10841, doi:10.1038/s41598-018-29140-z, (2018)

O. Uckermann, T.A. Juratli, R. Galli, M. Conde, R. Wiedemuth, D. Krex, K.D. Geiger, A. Temme, G. Schackert, E. Koch, G. Steiner, M. Kirsch “Optical analysis of glioma: Fourier-transform infrared spectroscopy reveals the IDH1 mutation status”, Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-17-1795, (2018)

Galli R, Uckermann O, Temme A, Leipnitz E, Meinhardt M, Koch E, Schackert G, Steiner G, Kirsch M, Assessing the efficacy of coherent anti-stokes raman scattering microscopy for the detection of infiltrating glioblastoma in fresh brain samples. J Biophotonics 10(3): 404–414, doi: 10.1002/jbio.201500323 (2017)

O. Uckermann, R. Galli, S. Leupold, R. Coras, M. Meinhardt, S. Hallmeyer-Elgner, T. Mayer, A. Storch, G. Schackert, E. Koch, I. Blümcke, G. Steiner, M. Kirsch „Label-free multiphoton microscopy reveals altered tissue architecture in hippocampal sclerosis“, Epilepsia, 58(1), S. e1-e5, doi: 10.1111/epi.13598, (2017)

Galli R, Sablinskas V, Dasevicius D, Laurinavicius A, Jankevicius F, Koch E, Steiner G, “Non-linear optical microscopy of kidney tumours”. J Biophotonics 7(1-2):23-27, doi: 10.1002/jbio.201200216 (2014)

R. Galli, O. Uckermann, E.F. Andresen, K.D. Geiger, E. Koch, G. Schackert, G. Steiner, M. Kirsch “Intrinsic indicator of photodamage during label-free multiphoton microscopy of cells and tissues”, PLOS One 9(10), e110295, (2014)

Contact

Prof. Edmund Koch
Clinical Sensoring and Monitoring, Carl Gustav Carus Faculty of Medicine at TU Dresden
Phone: +49 (0)351 458 6131
Email: edmund.koch(at)tu-dresden.de