PMID- 36217225
OWN - NLM
STAT- MEDLINE
DCOM- 20221012
LR  - 20230106
IS  - 1560-2281 (Electronic)
IS  - 1083-3668 (Print)
IS  - 1083-3668 (Linking)
VI  - 27
IP  - 10
DP  - 2022 Oct
TI  - Protoporphyrin IX delayed fluorescence imaging: a modality for hypoxia-based 
      surgical guidance.
LID - 10.1117/1.JBO.27.10.106005 [doi]
LID - 106005
AB  - SIGNIFICANCE: Hypoxia imaging for surgical guidance has never been possible, yet 
      it is well known that most tumors have microregional chronic and/or cycling 
      hypoxia present as well as chaotic blood flow. The ability to image oxygen 
      partial pressure (pO2) is therefore a unique control of tissue metabolism and can 
      be used in a range of disease applications to understand the complex biochemistry 
      of oxygen supply and consumption. AIM: Delayed fluorescence (DF) from the 
      endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique 
      reporter of the local oxygen partial pressure in tissue. PpIX is endogenously 
      synthesized by mitochondria in most tissues, and the particular property of DF 
      emission is directly related to low microenvironmental oxygen concentration. 
      Here, it is shown that PpIX has a unique emission in hypoxic tumor tissue 
      regions, which is measured as a DF signal in the red to near-infrared spectrum. 
      APPROACH: A time-gated imaging system was used for PpIX DF for wide field direct 
      mapping of pO2 changes. Acquiring both prompt and DF in a rapid sequential cycle 
      allowed for imaging oxygenation in a way that was insensitive to the PpIX 
      concentration. By choosing adequate parameters, the video rate acquisition of pO2 
      images could be achieved, providing real-time tissue metabolic information. 
      RESULTS: In this report, we show the first demonstration of imaging hypoxia 
      signals from PpIX in a pancreatic cancer model, exhibiting >5X contrast relative 
      to surrounding normal oxygenated tissues. Additionally, tissue palpation 
      amplifies the signal and provides intuitive temporal contrast based upon 
      neoangiogenic blood flow differences. CONCLUSIONS: PpIX DF provides a mechanism 
      for tumor contrast that could easily be translated to human use as an intrinsic 
      contrast mechanism for oncologic surgical guidance.
FAU - Petusseau, Arthur
AU  - Petusseau A
AD  - Thayer School of Engineering at Dartmouth, United States.
FAU - Bruza, Petr
AU  - Bruza P
AD  - Thayer School of Engineering at Dartmouth, United States.
FAU - Pogue, Brian
AU  - Pogue B
AD  - Univ. of Wisconsin-Madison, United States.
LA  - eng
GR  - P01 CA084203/CA/NCI NIH HHS/United States
GR  - R01 EB032337/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biomed Opt
JT  - Journal of biomedical optics
JID - 9605853
RN  - 0 (Photosensitizing Agents)
RN  - 0 (Protoporphyrins)
RN  - 88755TAZ87 (Aminolevulinic Acid)
RN  - C2K325S808 (protoporphyrin IX)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Aminolevulinic Acid/metabolism
MH  - Fluorescence
MH  - Humans
MH  - Hypoxia/diagnostic imaging
MH  - *Neoplasms
MH  - Oxygen/metabolism
MH  - Photosensitizing Agents/metabolism
MH  - *Protoporphyrins/metabolism
PMC - PMC9549807
OTO - NOTNLM
OT  - fluorescence-guided surgery
OT  - hypoxia
OT  - molecular imaging
OT  - protoporphyrin IX
OT  - time-gated imaging
EDAT- 2022/10/12 06:00
MHDA- 2022/10/13 06:00
PMCR- 2022/10/10
CRDT- 2022/10/11 00:03
PHST- 2022/06/28 00:00 [received]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/10/11 00:03 [entrez]
PHST- 2022/10/12 06:00 [pubmed]
PHST- 2022/10/13 06:00 [medline]
PHST- 2022/10/10 00:00 [pmc-release]
AID - JBO-220143GR [pii]
AID - 220143GR [pii]
AID - 10.1117/1.JBO.27.10.106005 [doi]
PST - ppublish
SO  - J Biomed Opt. 2022 Oct;27(10):106005. doi: 10.1117/1.JBO.27.10.106005.