Non-invasive detection of early retinal neuronal degeneration by ultrahigh resolution optical coherence tomography.
Optical coherence tomography (OCT) has revolutionises the diagnosis of retinal disease based on the detection of microscopic rather than subcellular changes in retinal anatomy. However, currently the technique is limited to the detection of microscopic rather than subcellular changes in retinal anatomy. However, coherence based imaging is extremely sensitive to both changes in optical contrast and cellular events at the micrometer scale, and can generate subtle changes in the spectral content of the OCT image. Here we test the hypothesis that OCT image speckle (image texture) contains information regarding otherwise unresolvable features such as organelle changes arising in the early stages of neuronal degeneration. Using ultrahigh resolution (UHR) OCT imaging at 800 nm (spectral width 140 nm) we developed a robust method of OCT image analyses, based on spatial wavelet and texture-based parameterisation of the image speckle pattern. For the first time we show that this approach allows the non-invasive detection and quantification of early apoptotic changes in neurons within 30 min of neuronal trauma sufficient to result in apoptosis. We show a positive correlation between immunofluorescent labelling of mitochondria (a potential source of changes in cellular optical contrast) with changes in the texture of the OCT images of cultured neurons. Moreover, similar changes in optical contrast were also seen in the retinal ganglion cell- inner plexiform layer in retinal explants following optic nerve transection. The optical clarity of the explants was maintained throughout in the absence of histologically detectable change. Our data suggest that UHR OCT can be used for the non-invasive quantitative assessment of neuronal health, with a particular application to the assessment of early retinal disease.
School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom.
Debbie
D
Tudor
Center for Medical Physics and Biomedical Engineering, Medical University Vienna, Vienna, Austria.
Vedran
V
Kajić
School of Biosciences, Cardiff University, Cardiff, United Kingdom.
Sara
S
Rey
School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom; School of Biosciences, Cardiff University, Cardiff, United Kingdom.
Irina
I
Erchova
Center for Medical Physics and Biomedical Engineering, Medical University Vienna, Vienna, Austria.
Boris
B
Považay
Center for Medical Physics and Biomedical Engineering, Medical University Vienna, Vienna, Austria.
Bernd
B
Hofer
School of Biosciences, Cardiff University, Cardiff, United Kingdom.
Kate A
KA
Powell
School of Computer Science and Informatics, Cardiff University, Cardiff, United Kingdom.
David
D
Marshall
School of Computer Science and Informatics, Cardiff University, Cardiff, United Kingdom.
Paul L
PL
Rosin
Center for Medical Physics and Biomedical Engineering, Medical University Vienna, Vienna, Austria.
Wolfgang
W
Drexler
School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom; Department of Neurology and Ophthalmology, School of Medicine, Cardiff University, Cardiff, United Kingdom.
James E
JE
Morgan
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D042241:Early Diagnosis; D008928:Mitochondria / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods*
D045304:Cytochromes c; D020169:Caspases