@ARTICLE{10.3389/fopht.2024.1340692,
  
AUTHOR={Pfäffle, Clara and Puyo, Léo and Spahr, Hendrik and Hillmann, Dierck and Miura, Yoko and Hüttmann, Gereon},   
	 
TITLE={Unraveling the Functional Signals of Rods and Cones in the Human Retina: Separation and Analysis},      
	
JOURNAL={Frontiers in Ophthalmology},      
	
VOLUME={4},           
	
YEAR={2024},      
	  
URL={https://www.frontiersin.org/articles/10.3389/fopht.2024.1340692},       
	
DOI={10.3389/fopht.2024.1340692},      
	
ISSN={2674-0826}   
   
}

@article{Puyo:23,
author = {L\'{e}o Puyo and Clara Pf\"{a}ffle and Hendrik Spahr and Jonas Franke and Daniel Bublitz and Dierck Hillmann and Gereon H\"{u}ttmann},
journal = {Opt. Express},
keywords = {Fourier optics; Full field optical coherence tomography; Image quality; Imaging techniques; Spatial frequency; Spatial light modulators},
number = {20},
pages = {33500--33517},
publisher = {Optica Publishing Group},
title = {Diffuse-illumination holographic optical coherence tomography},
volume = {31},
month = {Sep},
year = {2023},
url = {https://opg.optica.org/oe/abstract.cfm?URI=oe-31-20-33500},
doi = {10.1364/OE.498654},
abstract = {Holographic optical coherence tomography (OCT) is a powerful imaging technique, but its ability to reveal low-reflectivity features is limited. In this study, we performed holographic OCT by incoherently averaging volumes with changing diffuse illumination of numerical aperture (NA) equal to the detection NA. While the reduction of speckle from singly scattered light is only modest, we discovered that speckle from multiply scattered light can be arbitrarily reduced, resulting in substantial improvements in image quality. This technique also offers the advantage of suppressing noises arising from spatial coherence, and can be implemented with a partially spatially incoherent light source for further mitigation of multiple scattering. Finally, we show that although holographic reconstruction capabilities are increasingly lost with decreasing spatial coherence, they can be retained over an axial range sufficient to standard OCT applications.},
}

@article{RN5328,
   author = {Pfäffle, C;Spahr, H;Gercke, K;Puyo, L;Höhl, S;Melenberg, D;Miura, Y;Hüttmann, G and Hillmann, D},
   title = {Phase-Sensitive Measurements of Depth-Dependent Signal Transduction in the Inner Plexiform Layer},
   journal = {Frontiers in Medicine},
   volume = {9},
   ISSN = {2296-858X},
   DOI = {10.3389/fmed.2022.885187},
keywords = {optoretinography, optical coherence tomography, phase-sensitive OCT, functional imaging, inner
plexiform layer, retina},
   url = {https://www.frontiersin.org/articles/10.3389/fmed.2022.885187},
   year = {2022},
   type = {Journal Article}
}

@inproceedings{RN5321,
   author = {Pfäffle, C;Spahr, H;Gercke, K;Burhan, S;Melenberg, D;Miura, Y;Hüttmann, G and Hillmann, D},
   title = {Phase-sensitive measurements of depth dependent signal transduction in the inner plexiform layer},
   booktitle = {SPIE BiOS},
   publisher = {SPIE},
   volume = {11623},
   url = {https://doi.org/10.1117/12.2577605},
   type = {Conference Proceedings}
}

@article{Matkivsky2020,
   author = {Matkivsky, V;Moiseev, A;Shilyagin, P;Rodionov, A;Spahr, H;Pfäffle, C;Hüttmann, G;Hillmann, D and Gelikonov, G},
   title = {Determination and correction of aberrations in full field optical coherence tomography using phase gradient autofocus by maximizing the likelihood function},
   journal = {Journal of Biophotonics},
   volume = {13(10)},
   pages = {e202000112},
   ISSN = {1864-063X},
   DOI = {10.1002/jbio.202000112},
   year = {2020},
   type = {Journal Article}
}

@article{RN5217,
   author = {Spahr, Hendrik;Pfäffle, Clara;Burhan, Sazan;Kutzner, Lisa;Hilge, Felix;Hüttmann, Gereon and Hillmann, Dierck},
   title = {Phase-sensitive interferometry of decorrelated speckle patterns},
   journal = {Scientific Reports},
   volume = {9},
   number = {1},
   pages = {11748},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-019-47979-8},
   url = {https://doi.org/10.1038/s41598-019-47979-8},
   year = {2019},
   type = {Journal Article}
}

@article{RN5085,
   author = {Spahr, H;Pfäffle, C;Hüttmann, G and Hillmann, D},
   title = {Artifacts in speckle tracking and multi-aperture
Doppler OCT imaging of lateral motion},
   journal = {Optics letters},
   volume = {44(5)},
   pages = {1315-1318},
   DOI = {https://doi.org/10.1364/OL.44001315},
   url = {https://doi.org/10.1364/OL.44001315},
   year = {2019},
   type = {Journal Article}
}

@article{Hillmann2019,
   author = {Hillmann, D.;Pfaffle, C.;Spahr, H.;Burhan, S.;Kutzner, L.;Hilge, F. and Hüttmann, G.},
   title = {Computational adaptive optics for optical coherence tomography using multiple randomized subaperture correlations},
   journal = {Opt Lett 44 (15)},
 
   pages = {3905-3908},
   ISSN = {1539-4794 (Electronic)
0146-9592 (Linking)},
   DOI = {10.1364/OL.44.003905},
   url = {https://www.ncbi.nlm.nih.gov/pubmed/31368998},
   year = {2019},
   type = {Journal Article}
}

@inbook{Hillmann2019,
   author = {Hillmann, Dierck;Pfäffle, Clara;Spahr, Hendrik;Sudkamp, Helge;Franke, Gesa and Hüttmann, Gereon},
   title = {In Vivo FF-SS-OCT Optical Imaging of Physiological Responses to Photostimulation of Human Photoreceptor Cells},
   booktitle = {High Resolution Imaging in Microscopy and Ophthalmology: New Frontiers in Biomedical Optics},
   editor = {Bille, Josef F.},
   publisher = {Springer International Publishing},
   address = {Cham},
   pages = {181-194},
   ISBN = {978-3-030-16638-0},
   
   url = {https://doi.org/10.1007/978-3-030-16638-0_8},
   year = {2019},
   type = {Book Section}
}

@article{Pfäffle2019,
   author = {Pfäffle, C;Spahr, H;Kutzner, L;Burhan, S;Hilge, F;Miura, Y;Hüttmann, G and Hillmann, D},
   title = {Simultaneous functional imaging of neuronal and photoreceptor layers in living human retina},
   journal = {Optics Letters 44(23)},
 
   pages = {5671-5674},
   DOI = {10.1364/OL.44.005671},
   
   year = {2019},
   type = {Journal Article}
}

@article{Sudkamp2018a,
   author = {Sudkamp, H; Hillmann, D; Koch, P;vom Endt, M; Spahr, H; Münst, M; Pfäffle, C; Birngruber, R and Hüttmann, G},
   title = {Simple approach for aberration-corrected OCT imaging of the human retina},
   journal = {Opt Lett},
   
   pages = {4224},
   ISSN = {0146-9592
1539-4794},
   DOI = {10.1364/ol.43.004224},
   year = {2018},
   type = {Journal Article},
   keyword = {Retome}
}

@inproceedings{Schulz-Hildebrandt2018a,
title = {Coherence and diffraction limited resolution in microscopic OCT by a unified approach for the correction of dispersion and aberrations},
author = {Schulz-Hildebrandt,H; M\"{u}nter, M; Ahrens,M; Spahr, H; Hillmann, D; K\"{o}nig, P and  H\"{u}ttmann, G},
doi = {10.1117/12.2303755},
isbn = {9781510616745},
year = {2018},
date = {2018-03-05},
booktitle = {2nd Canterbury Conference on OCT with Emphasis on Broadband Optical Sources},
volume = {10591},
pages = {105910O},
abstract = {Optical coherence tomography (OCT) images scattering tissues with 5 to 15 μm resolution. This is usually not sufficient for a distinction of cellular and subcellular structures. Increasing axial and lateral resolution and compensation of artifacts caused by dispersion and aberrations is required to achieve cellular and subcellular resolution. This includes defocus which limit the usable depth of field at high lateral resolution. OCT gives access the phase of the scattered light and hence correction of dispersion and aberrations is possible by numerical algorithms. Here we present a unified dispersion/aberration correction which is based on a polynomial parameterization of the phase error and an optimization of the image quality using Shannon’s entropy. For validation, a supercontinuum light sources and a costume-made spectrometer with 400 nm bandwidth were combined with a high NA microscope objective in a setup for tissue and small animal imaging. Using this setup and computation corrections, volumetric imaging at 1.5 μm resolution is possible. Cellular and near cellular resolution is demonstrated in porcine cornea and the drosophila larva, when computational correction of dispersion and aberrations is used. Due to the excellent correction of the used microscope objective, defocus was the main contribution to the aberrations. In addition, higher aberrations caused by the sample itself were successfully corrected. Dispersion and aberrations are closely related artifacts in microscopic OCT imaging. Hence they can be corrected in the same way by optimization of the image quality. This way microscopic resolution is easily achieved in OCT imaging of static biological tissues.},
keywords = {OCM},
pubstate = {published},
tppubtype = {inproceedings}
}

@article{Hillmann2017,
   author = {Hillmann, D; Spahr, H; Sudkamp, H; Hain, C; Hinkel, L; Franke, G and Hüttmann, G},
   title = {Off-axis reference beam for full-field swept-source OCT and holoscopy},
   journal = {Opt Expr},
   
   pages = {27770-27784},
   DOI = {10.1364/OE.25.027770},
   year = {2017},
   type = {Journal Article}
}

@article{Pfäffle2017,
   author = {Pfäffle, Clara and Spahr, Hendrik and Hillmann, Dierck and Sudkamp, Helge and Franke, Gesa and Koch, Peter and Hüttmann, Gereon},
   title = {Reduction of frame rate in full-field swept-source optical coherence tomography by numerical motion correction [Invited]},
   journal = {Biomedical Optics Express},
   volume = {8},
   number = {3},
   pages = {1499-1511},
   keywords = {Image reconstruction-restoration
Optical coherence tomography},
   url = {http://www.osapublishing.org/boe/abstract.cfm?URI=boe-8-3-1499},
   year = {2017},
   type = {Journal Article}
}

@article{RN4897,
   author = {Sudkamp, Helge and Koch, Peter and Spahr, Hendrik and Hillmann, Dierck and Franke, Gesa and Münst, Michael and Reinholz, Fred and Birngruber, Reginald and Hüttmann, Gereon},
   title = {In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography},
   journal = {Optics Letters},
   volume = {41},
   number = {21},
   pages = {4987-4990},
   DOI = {10.1364/OL.41.004987},
   url = {http://ol.osa.org/abstract.cfm?URI=ol-41-21-4987},
   year = {2016},
   type = {Journal Article}
}

@article{Spahr2016,
   author = {Spahr, H. and Hillmann, D. and Hain, C. and Pfäffle, C. and Sudkamp, H. and Franke, G. and Koch, P. and Hüttmann, G.},
   title = {Darstellung von Blutfluss und Pulsation in retinalen Gefäßen mit Full-Field-Swept-Source-OCT},
   journal = {Klin Monatsbl Augenheilkd},
   volume = {233},
   number = {12},
   pages = {1324-1330},
   ISSN = {0023-2165},
   DOI = {10.1055/s-0042-120279},
   year = {2016},
   type = {Journal Article}
}

@article{Hillmann2016,
   author = {Hillmann, Dierck and Spahr, Hendrik and Hain, Carola and Sudkamp, Helge and Franke, Gesa and Pfäffle, Clara and Winter, Christian and Hüttmann, Gereon},
   title = {Aberration-free volumetric high-speed imaging of in vivo retina},
   journal = {Scientific Reports},
   volume = {6},
   pages = {1-11},
   url = {http://dx.doi.org/10.1038/srep35209},
   year = {2016},
   type = {Journal Article}
}

@inproceedings{Spahr2016,
   author = {Spahr, Hendrik and Hillmann, Dierck and Hain, Carola and Pfäffle, Clara and Sudkamp, Helge and Franke, Gesa and Hüttmann, Gereon},
   title = {Imaging vascular dynamics in human retina using full-field swept-source optical coherence tomography (Conference Presentation)},
   volume = {9697},
   pages = {96970E-96970E-1},
   note = {10.1117/12.2214303},
   abstract = {We demonstrate a new non-invasive method to assess the functional condition of the retinal vascular system. Phase-sensitive full-field swept-source optical coherence tomography (PhS-FF-SS-OCT) is used to investigate retinal vascular dynamics at unprecedented temporal resolution. Motion of retinal tissue, that is induced by expansion of the vessels therein, is measured with an accuracy of about 10 nm. The pulse shape of arterial and venous pulsation, their temporal delay as well as the frequency dependent pulse propagation through the capillary bed are determined. For the first time, imaging speed and motion sensitivity are sufficient for a direct measurement of pulse waves propagating with more than 600 mm/s in retinal vessels of a healthy young subject.},
   url = {http://dx.doi.org/10.1117/12.2214303},
   type = {Conference Proceedings},
year = { 2016}
}

@article{Hillmann2016,
   author = {Hillmann, Dierck and Spahr, Hendrik and Pfäffle, Clara and Sudkamp, Helge and Franke, Gesa and Hüttmann, Gereon},
   title = {In vivo optical imaging of physiological responses to photostimulation in human photoreceptors},
   journal = {PNAS Early Edition},
   pages = {1-6},
   abstract = {Noninvasive functional imaging of molecular and cellular processes of vision may have immense impact on research and clinical diagnostics. Although suitable intrinsic optical signals (IOSs) have been observed ex vivo and in immobilized animals in vivo, detecting IOSs of photoreceptor activity in living humans was cumbersome and time consuming. Here, we observed clear spatially and temporally resolved changes in the optical path length of the photoreceptor outer segment as a response to an optical stimulus in the living human eye. To witness these changes, we evaluated phase data obtained with a parallelized and computationally aberration-corrected optical coherence tomography system. The noninvasive detection of optical path length changes shows neuronal photoreceptor activity of single cones in living human retina, and therefore, it may provide diagnostic options in ophthalmology and neurology and could provide insights into visual phototransduction in humans.},
   url = {http://www.pnas.org/content/early/2016/10/10/1606428113.abstract},
   year = {2016},
   type = {Journal Article}
}

@article{Hüttmann2016,
   author = {Huttmann, Gereon and Moltmann, Moritz and Spahr, Hendrik and Tode, Jan and de Roeck, Anna and Theisen-Kunde, Dirk and Birngruber, Reginald and Koinzer, Stefan and Brinkmann, Ralf},
   title = {Retinal lesion formation during photocoagulation investigated by high-speed 1060 nm Doppler-OCT: first clinical results},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {57},
   number = {12},
   pages = {5852-5852},
   abstract = {Abstract Purpose : The molecular processes during heating with a photocoagulation laser, particularly in sub-visible or mere thermal stimulation treatment, have only partly been understood, and different theories exist that try to explain its clinical efficacy. Optical coherence tomography (OCT) was successfully used to grade lesions with high accuracy 1 hour after the treatments and beyond. During the irradiation, changes in tissue scattering and, by use of the Doppler signal, tissue motion caused by thermal expansion and coagulation-induced tissue contraction were shown to correlate ex-vivo and in rabbits with the strength of photocoagulation lesions. Aim of this study was to validate feasibility and reproducibility of these results in humans. Methods : In an ongoing study more than 100 lesions of three patients have been imaged with a slitlamp-based OCT (1060 nm, 90,000 A-scans/s) with varying irradiance during laser exposure. Durations of the exposure were 50 ms and 200 ms; spot size was 300 µm. Eye movements and heart beat were corrected by cross-correlation of the images. Increased tissue scattering and movement of the neuronal retina due to thermal expansion were determined from the image sequences with 3 ms temporal resolution. Results : In the first treatments with this prototype device, we received acceptable image quality in 1/3 of the lesions. Changes in the neuronal retina were successful visualized during and after the laser irradiation, demonstrating the feasibility of a real-time assessment of initial effects of photocoagulation in humans. Lesion visibility in standard, reflection-based OCT was much weaker during treatment compared to 1 hour afterwards. Increased tissue scattering was observed in stronger lesions already during the laser irradiation. At reduced irradiance, scattering increase was only observed after the end of irradiation. However, tissue motion towards the vitreous was still observed in these cases. Conclusions : In conclusion, high-speed OCT recording during photocoagulation measures initial tissue changes during photocoagulation in humans. It may enhance our understanding of the tissue dynamics right after laser irradiation. It may provide useful information for a real-time dosage control as well. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.},
   ISSN = {1552-5783},
   url = {http://dx.doi.org/},
   year = {2016},
   type = {Journal Article}
}

@article{Spahr2015,
   author = {Spahr, Hendrik and Hillmann, Dierck and Hain, Carola and Pfäffle, Clara and Sudkamp, Helge and Franke, Gesa and Hüttmann, Gereon},
   title = {Imaging pulse wave propagation in human retinal vessels using full-field swept-source optical coherence tomography},
   journal = {Optics Letters},
   volume = {40},
   number = {20},
   pages = {4771-4774},
   abstract = {We demonstrate a new noninvasive method to assess biomechanical properties of the retinal vascular system. Phase-sensitive full-field swept-source optical coherence tomography (PhS-FF-SS-OCT) is used to investigate retinal vascular dynamics at unprecedented temporal resolution. The motion of retinal tissue that is induced by expansion of the vessels therein is measured with an accuracy of about 10 nm. The pulse shapes of arterial and venous pulsations, their temporal delays, as well as the frequency-dependent pulse propagation through the capillary bed, are determined. For the first time, imaging speed and motion sensitivity are sufficient for a direct measurement of pulse waves propagating with more than 600 mm/s in retinal vessels of a healthy young subject.},
   keywords = {Optical coherence tomography
Ophthalmology
Time-resolved imaging
Functional monitoring and imaging},
   DOI = {10.1364/OL.40.004771},
   url = {http://ol.osa.org/abstract.cfm?URI=ol-40-20-4771},
   year = {2015},
   type = {Journal Article}
}

@article{Spahr2015,
   author = {Spahr, Hendrik and Hain, Carola and Sudkamp, Helge and Franke, Gesa and Hillmann, Dierck and Huttmann, Gereon},
   title = {Functional Microangiography of in vivo human retina by Full-Field OCT},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {56},
   number = {7},
   pages = {5974-5974},
   abstract = { PurposeOCT based functional microangiography of the retina requires high speed acquisition of a large number of volumetric datasets. Imaging speed of conventional scanning OCT devices is limited by the applicable radiant power and the mechanics used to scan the focused beam over the desired field of view. Full-Field Swept-Source OCT (FF-SS-OCT) resolves both issues, using an areal illumination, which dramatically increases the allowed amount of radiation, and an ultrafast camera for a highly parallelized acquisition.  MethodsThe retina of healthy volunteers was illuminated with wavelengths between 816 and 867 nm by the extended beam of a tunable laser (Broadsweeper, Superlum). Retinal irradiance was below the maximum permissable exposure (MPE). Light backscattered from the retina was imaged onto an ultrafast CMOS camera (SA-Z, Photron), where it interfered with an extended reference beam. From a series of interference images at different wavelengths, volumetric OCT images of the retina were reconstructed.  ResultsWe demonstrate in vivo retinal imaging at 9.9 billion voxels per second (40 million A-scans/s with 256 axial pixels). Sacrificing depth resolution by reducing the number of axial pixels, the A-scan rate was increased to more than 1 billion A-scans per second. FF-SS-OCT allowed imaging of all important retinal structures with good quality at unprecedented imaging speed (see fig. 1). Fast volumetric imaging at up to 3000 volumes/s was used to visualize small capillaries and to analyze the pulsation of retinal arteries and veins (see fig. 2). Imaging time for an area of 4 mm x 2 mm (896 x 368 A-scans) was only 316 µs. The high volume rate and the inherent phase stability enabled quantitative measurement of the change of retinal thickness due to blood pulsation with approx. 10 nm precision. A delay of the venous pulsation with respect to the arteries was observed (approx. 11 ms). The amplitudes of higher frequency components of the venous pulsation were considerably attenuated.  ConclusionsFF-SS-OCT provides fast volumetric imaging of the retina with good image quality. The capillary network can be analyzed with high spatial and temporal resolution. Analysis of retinal pulsation may provide information on pathological changes of vessels and capillaries. Angiographic OCT acquired with the FF-SS-OCT setup. Functional angiography showing the pulsation of retinal artery and vein.},
   ISSN = {1552-5783},
   url = {http://dx.doi.org/},
   year = {2015},
   type = {Journal Article}
}

@inproceedings{Spahr2012,
   author = {Spahr, Hendrik and Rudolph, Linda and Muller, Heike and Birngruber, Reginald and Huttmann, Gereon},
   title = {Imaging of photothermal tissue expansion via phase sensitive optical coherence tomography},
   editor = {Joseph, A. Izatt and James, G. Fujimoto and Valery, V. Tuchin},
   publisher = {SPIE},
   volume = {8213},
   pages = {82131S},
year = { 2012},
url = { https://doi.org/10.1117/12.911429}

}