Bioluminescence tomography

Bioluminescence tomography (BLT) is a non-invasive optical imaging technique used to reconstruct the three-dimensional distribution of bioluminescent sources from emitted light signals. It is primarily used in preclinical research to study molecular and cellular processes in living organisms. BLT emerged from bioluminescence imaging as a tomographic approach for estimating three-dimensional source distributions.

Background

Bioluminescence, the emission of light by living organisms, has been documented since antiquity. Aristotle and Pliny the Elder described luminous organisms including fireflies, glow-worms, jellyfish, and mollusks.[1][2] In laboratory research, bioluminescent reporter systems have made it possible to follow biological processes in living animals using emitted light. Conventional bioluminescence imaging records two-dimensional optical signals at the surface, which limits its ability to localize deeper sources. This limitation contributed to the development of bioluminescence tomography as a three-dimensional reconstruction method for improved source localization. Early BLT research addressed the mathematical and computational basis for estimating internal source distributions from surface measurements.[3] Early work by Ge Wang and colleagues at the University of Iowa was also associated with patented systems and methods for multi-spectral bioluminescence imaging.[4]

Principles

BLT uses light emitted by bioluminescent markers within a living subject. These markers may be genetically encoded or introduced chemically into specific tissues or cells. Following reaction with a substrate, the markers emit light, which is detected using imaging systems such as CCD cameras.[5]

The reconstruction process generally involves surface signal acquisition, light propagation modeling, and computational image reconstruction. Signal collection may be performed by acquiring multiple two-dimensional images from different angles around the subject.[6][7] Light propagation modeling describes the scattering and absorption of light as it travels through biological tissue, based on mathematical representations of optical transport.[8]

Because light propagation in tissue is highly scattering and attenuating, BLT reconstruction is an ill-posed inverse problem that usually requires regularization and anatomical or optical priors.[9][10] Reconstruction algorithms then estimate the three-dimensional location and intensity of internal bioluminescent sources from the surface measurements.[10]

Applications

BLT is used in preclinical biomedical research. In cancer research, it has been used to monitor tumor growth and metastasis in animal models, including breast tumor models.[11] Model-based BLT has also been used to estimate the three-dimensional location and strength of luciferase-expressing sources in vivo.[12] In preclinical radiotherapy research, BLT has been used to guide small-animal radiation delivery and to assess radiation-induced tumor response.[13]

References

  1. ↑ "Luciferase: A Powerful Bioluminescent Research Tool". The Scientist Magazine.
  2. ↑ "Lighting the Way". SPIE.
  3. ↑ Wang, Ge; Li, Yi; Jiang, Ming (2004). "Uniqueness theorems in bioluminescence tomography". Medical Physics. 31 (8): 2289–2299. doi:10.1118/1.1766420.
  4. ↑ "Systems and methods for multi-spectral bioluminescence". University of Iowa.
  5. ↑ Deng, Zijian; Xu, Xiangkun; Iordachita, Iulian; Dehghani, Hamid; Zhang, Bin; Wong, John W.; Wang, Ken Kang-Hsin (30 August 2022). "Mobile bioluminescence tomography-guided system for pre-clinical radiotherapy research". Biomedical Optics Express. 13 (9): 4970–4989. Bibcode:2022BOpEx..13.4970D. doi:10.1364/BOE.460737. ISSN 2156-7085. PMC 9484421. PMID 36187243.
  6. ↑ Han, Weimin; Wang, Ge (2008). "Bioluminescence Tomography: Biomedical Background, Mathematical Theory, and Numerical Approximation". Journal of Computational Mathematics. 26 (3): 324–335. ISSN 0254-9409. PMC 2898173. PMID 20617105.
  7. ↑ Lewis, Matthew A.; Richer, Edmond; Slavine, Nikolai V.; Kodibagkar, Vikram D.; Soesbe, Todd C.; Antich, Peter P.; Mason, Ralph P. (9 July 2013). "A Multi-Camera System for Bioluminescence Tomography in Preclinical Oncology Research". Diagnostics. 3 (3): 325–343. doi:10.3390/diagnostics3030325. ISSN 2075-4418. PMC 4665465. PMID 26824926.
  8. ↑ Xu, Xiangkun; Deng, Zijian; Dehghani, Hamid; Iordachita, Iulian; Lim, Michael; Wong, John W.; Wang, Ken Kang-Hsin (1 December 2021). "Quantitative Bioluminescence Tomography-Guided Conformal Irradiation for Preclinical Radiation Research". International Journal of Radiation Oncology*Biology*Physics. 111 (5): 1310–1321. Bibcode:2021IJROB.111.1310X. doi:10.1016/j.ijrobp.2021.08.010. ISSN 0360-3016. PMC 8602741. PMID 34411639.
  9. ↑ Cheng, Xiaoliang; Gong, Rongfang; Han, Weimin (2009). "Numerical approximation of bioluminescence tomography based on a new formulation". Journal of Engineering Mathematics. 63 (1): 121–133. Bibcode:2009JEnMa..63..121C. doi:10.1007/s10665-008-9246-y.
  10. 1 2 Jiang, Ming; Zhou, Tie; Cheng, Jiantao; Cong, Wenxiang; Wang, Ge (2007). "Image reconstruction for bioluminescence tomography from partial measurement". Optics Express. 15 (18): 11095–11116. Bibcode:2007OExpr..1511095J. doi:10.1364/OE.15.011095. PMID 19547465.
  11. ↑ Mollard, Séverine; Fanciullino, Raphaelle; Giacometti, Sarah; Serdjebi, Cindy; Benzekry, Sébastien; Ciccolini, Joseph (4 November 2016). "In Vivo Bioluminescence Tomography for Monitoring Breast Tumor Growth and Metastatic Spreading: Comparative Study and Mathematical Modeling". Scientific Reports. 6 36173. Bibcode:2016NatSR...636173M. doi:10.1038/srep36173. ISSN 2045-2322. PMC 5095884. PMID 27812027.
  12. ↑ Gu, Xuejun; Zhang, Qizhi; Larcom, Lyndon; Jiang, Huabei (2004). "Three-dimensional bioluminescence tomography with model-based reconstruction". Optics Express. 12 (17): 3996–4000. Bibcode:2004OExpr..12.3996G. doi:10.1364/OPEX.12.003996. PMID 19483937.
  13. ↑ Shi, Junwei; Udayakumar, Thirupandiyur S.; Xu, Keying; Dogan, Nesrin; Pollack, Alan; Yang, Yidong (15 November 2018). "Bioluminescence Tomography Guided Small-Animal Radiation Therapy and Tumor Response Assessment". International Journal of Radiation Oncology*Biology*Physics. 102 (4): 848–857. doi:10.1016/j.ijrobp.2018.01.068. PMID 29534897.
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