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Biomedical subjects

Johannes F de Boer

Publications and source records attributed to Johannes F de Boer.

At least 19 recordsLinked to original sources

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Angioplasty↗

Histologic correlation of in vivo optical coherence tomography images of the human retina.

PURPOSE: To correlate in vivo human retina optical coherence tomography (OCT)3 images with histology. DESIGN: Case series. METHODS: Linear OCT3 scans through the macula and optic nerve were obtained in three eyes of three patients who then underwent exenteration surgery for orbital cancers. OCT3 images were then correlated with histology. RESULTS: On histology, two eyes were normal, and one eye had dry macular degeneration. The plexiform layers on histology correlated with the green/yellow areas on the OCT3 scans, and the nuclear layers correlated with the black areas on the OCT3 scans. CONCLUSIONS: The authors are unaware of previous reports correlating histology to in vivo human retina OCT3 images. Our findings using human eyes are not different from previous animal studies, in that the plexiform layers are optically highly backscattering and the nuclear layers are not.

Aged↗

Imaging the human vocal folds in vivo with optical coherence tomography: a preliminary experience.

OBJECTIVES: Optical coherence tomography (OCT) and polarization-sensitive OCT (PS-OCT) are promising noninvasive methods for in vivo, cross-sectional imaging of the microstructure of the vocal folds. Previous studies in other tissues have shown an axial resolution of less than 10 microm and a maximum imaging depth of about 2 mm. The objectives of this pilot study were to obtain images from the vocal folds of subjects who were being evaluated and/or treated for vocal fold disease and to evaluate how well normal and pathologic microstructure could be seen in these images. METHODS: Twenty-six vocal folds in 13 subjects were imaged with a flexible OCT probe. The images were successfully collected from subjects who were either topically anesthetized or under general anesthesia for microlaryngoscopic procedures. RESULTS: The thickness of the epithelium, the relative collagen content of the subepithelial connective tissue, and certain characteristic features of lesions (including cysts, scarring, and papilloma) were seen in the OCT and PS-OCT images. CONCLUSIONS: "Live microscopy" of the human vocal folds is very promising for improved diagnosis, mapping, and treatment planning. To our knowledge, this study is the first application of PS-OCT for in vivo imaging of the human vocal folds.

Humans↗

Optic axis determination accuracy for fiber-based polarization-sensitive optical coherence tomography.

We present a generalized analysis of fiber-based polarization-sensitive optical coherence tomography with an emphasis on determination of sample optic axis orientation. The polarization properties of a fiber-based system can cause an overall rotation in a Poincaré sphere representation such that the plane of possible measured sample optic axes for linear birefringence and diattenuation no longer lies in the QU-plane. The optic axis orientation can be recovered as an angle on this rotated plane, subject to an offset and overall indeterminacy in sign such that only the magnitude, but not the direction, of a change in orientation can be determined. We discuss the accuracy of optic axis determination due to a fundamental limit on the accuracy with which a polarization state can be determined as a function of signal-to-noise ratio.

Algorithms↗

Spectral-domain optical coherence phase microscopy for quantitative phase-contrast imaging.

We describe a novel microscopy technique for quantitative phase-contrast imaging of a transparent specimen. The technique is based on depth-resolved phase information provided by common path spectral-domain optical coherence tomography and can measure minute phase variations caused by changes in refractive index and thickness inside the specimen. We demonstrate subnanometer level path-length sensitivity and present images obtained on reflection from a known phase object and human epithelial cheek cells.

Cells, Cultured↗

Spectral domain optical coherence tomography: ultra-high speed, ultra-high resolution ophthalmic imaging.

OBJECTIVE: To introduce a new ophthalmic optical coherence tomography technology that allows unprecedented simultaneous ultra-high speed and ultra-high resolution. METHODS: Using a superluminescent diode source, a clinically viable ultra-high speed, ultra-high resolution spectral domain optical coherence tomography system was developed. RESULTS: In vivo images of the retina, the optic nerve head, and retinal blood flow were obtained at an ultra-high speed of 34.1 microseconds (ms) per A-scan, which is 73 times faster than commercially available optical coherence tomography instruments. Single images (B-scans) consisting of 1000 A-scans were acquired in 34.1 ms, allowing video rate imaging at 29 frames per second with an axial resolution of 6 mum. Using a different source in a slightly slower configuration, single images consisting of 500 A-scans were acquired in 34 ms, allowing imaging at 29 frames per second at an axial resolution of 3.5 microm, which is 3 times better than commercially available optical coherence tomography instruments. The amount of energy directed into the eye in both cases, 600 microW, is less than that of the Stratus OCT3 and is safe for intrabeam viewing for up to 8 hours at the same retinal location. CONCLUSION: Spectral domain optical coherence tomography technology enables ophthalmic imaging with unprecedented simultaneous ultra-high speed and ultra-high resolution.

Adult↗

Measurement of morphologic changes induced by trauma with the use of coherence tomography in porcine vocal cords.

BACKGROUND AND OBJECTIVE: To evaluate the ability of optical coherence tomography (OCT) (a noncontact, high-resolution imaging technique that generates detailed cross-sectional images of tissue structure) to image and document acute response to trauma in the larynx. MATERIALS AND METHODS: Porcine larynges were dissected to expose the vocal cords. Vocal cords were imaged with 1310 nanometer (nm) light source with a bandwidth of 75 nm at 1 frame/second (s). Vocal cord injuries were simulated by applying topical phenolic acid, injecting titanium dioxide into the submucosa, and carbon dioxide laser irradiation. RESULTS: The epithelium, basement membrane, and lamina propria were clearly delineated, and the effect of each intervention could be monitored as lesions progressed. The OCT image corresponded closely with histology. CONCLUSION: OCT is a powerful imaging tool with the potential for use in real time and has potential for multiple clinical applications in the larynx.

Administration, Topical↗

Imaging the mucosa of the human vocal fold with optical coherence tomography.

OBJECTIVES: Discerning the layered microstructure of the vocal folds is critical for effective phonomicrosurgery. Optical coherence tomography (OCT), a noncontact, noninvasive technology that provides cross-sectional images by means of backscattered light, offers the potential for delineating these layers in vivo. METHODS: The glottal mucosa of 3 human cadaver larynges was imaged with conventional OCT and polarization-sensitive OCT (PS-OCT). Images were obtained through the epithelium and lamina propria. RESULTS: Although the superficial layer of the lamina propria appeared quite homogeneous, the outer surface of the superficial lamina propria was correlated with an increase in backscatter with OCT. The superficial lamina propria and vocal ligament were correlated with a marked increase in tissue birefringence with PS-OCT. CONCLUSIONS: This preliminary study demonstrates the capacity of OCT and PS-OCT for visualizing the layered microstructure of the vocal fold mucosa. We believe that these imaging techniques will have applications in the exploration of solutions to vocal fold scarring and in imaging vocal fold disorders in the clinic and operating room.

Cadaver↗

Comment on "Optical-fiber-based Mueller optical coherence tomography".

We comment on the recent Letter by Jiao et al. [Opt. Lett. 28, 1206 (2003)] in which a polarization-sensitive optical coherence tomography system was presented. Interrogating a sample with two orthogonal incident polarization states cannot always recover birefringence correctly. A previously presented fiber-based polarization-sensitive system was inaccurately characterized, and its method of eliminating the polarization distortion caused by single-mode optical fiber was presented earlier by Saxer et al. [Opt. Lett. 25, 1355 (2000)].

Algorithms↗

Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components.

We present an analysis for polarization-sensitive optical coherence tomography that facilitates the unrestricted use of fiber and fiber-optic components throughout an interferometer and yields sample birefringence, diattenuation, and relative optic axis orientation. We use a novel Jones matrix approach that compares the polarization states of light reflected from the sample surface with those reflected from within a biological sample for pairs of depth scans. The incident polarization alternated between two states that are perpendicular in a Poincaré sphere representation to ensure proper detection of tissue birefringence regardless of optical fiber contributions. The method was validated by comparing the calculated diattenuation of a polarizing sheet, chicken tendon, and muscle with that obtained by independent measurement. The relative importance of diattenuation versus birefringence to angular displacement of Stokes vectors on a Poincaré sphere was quantified.

Algorithms↗

In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography.

An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 microm at ultrahigh speed and with an ocular exposure level of less than 600 microW.

Humans↗

Collagen denaturation can be quantified in burned human skin using polarization-sensitive optical coherence tomography.

Quantifiable prognostic indicators are of considerable practical value following thermal injury. Collagen is a major component of the skin, and is known to undergo denaturation at the elevated temperatures associated with burns. The purpose of this study was to determine whether a recently developed, non-invasive imaging technique could detect and quantify collagen denaturation in burned human skin. Polarization-sensitive optical coherence tomography (PS-OCT) imaging was used to quantify collagen birefringence in normal human skin, and in skin excised from burn patients. Images were acquired and displayed in 1s, and demonstrated qualitative differences between normal and partial-thickness burned human skin. Birefringence loss due to thermal denaturation of collagen was quantified, with mean phase retardation rates for samples of 26 normal and 26 burned skin sites determined to be 0.401 +/- 0.020 and 0.249 +/- 0.017 degrees /microm, respectively (mean +/- S.E.M.), with this difference in sample means shown to be statistically significant (P < 0.000001). Analysis of the accuracy of the technique indicated that PS-OCT measurements may be made with resolution sufficient to distinguish between burns of varying severity. In conclusion, PS-OCT is capable of imaging and quantifying collagen denaturation in burned human skin, providing a new parameter against which post-injury outcome may be compared.

Adolescent↗

Advances in optical coherence tomography imaging for dermatology.

Optical coherence tomography (OCT) is a non-invasive imaging technique, which has previously demonstrated potential for use in dermatology. The purpose of this study is to demonstrate how improvements in image quality, speed, and functionality enable qualitative and quantitative information to be obtained from in vivo human skin. We developed a portable fiber-optic based OCT imaging device that requires only 1 second to simultaneously provide high-resolution images of skin structure, collagen birefringence, and blood flow. Images of normal human skin were acquired in vivo, and features compared with clinical and histologic observations. The layered structure and appendages of skin were apparent in conventional OCT images, and correlated well with corresponding histology. Polarization-sensitive OCT images simultaneously revealed birefringent regions within the dermis corresponding to the location of collagen fibers, as confirmed with polarized light microscopy. Properties of collagen-rich tissues including tendon and scar tissues were quantified. Location of blood flow was also displayed alongside structural and polarization-sensitive images. Significant improvements in OCT technology have been made since its early application in dermatology. In particular, combining the previously described structural and Doppler imaging functions with polarization-sensitive imaging increases the utility of the technique for rapid, non-invasive investigations in the skin.

Cicatrix↗

Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography.

PURPOSE: Thinning of the retinal nerve fiber layer and changes in retinal nerve fiber layer (RNFL) birefringence may both precede clinically detectable glaucomatous vision loss. Early detection of RNFL changes may enable treatment to prevent permanent loss of vision. Polarization-sensitive optical coherence tomography (PS-OCT) can provide objective information on RNFL thickness and birefringence. METHODS: PS-OCT scans around the optic nerve head (ONH) of two healthy young volunteers were made using 10 concentric circles of increasing radius. Both the mean RNFL thickness and mean retinal nerve fiber birefringence for each of 48 sectors on a circle were determined with data analysis. RESULTS: Both the RNFL thickness and birefringence varied as a function of sector around the ONH. The RNFL became thinner with increasing distance from the ONH. In contrast, the birefringence did not vary significantly as a function of radius. CONCLUSIONS: Birefringence of healthy RNFL is constant as a function of scan radius but varies as a function of position around the ONH, with higher thickness values occurring superior and inferior to the ONH. Measured double-pass phase retardation per unit depth around the ONH ranged between 0.10 and 0.35 deg/microm, equivalent to birefringences of 1.2 x 10(-4) and 4.1 x 10(-4) respectively, measured at a wavelength of 840 nm. Consequently, when a spatially constant birefringence around the ONH is assumed, the conversion of scanning laser polarimetry (SLP) phase-retardation measurements to RNFL thickness may yield incorrect values. The data do not invalidate the clinical value of a phase-retardation measurement, but affect the conversion of phase retardation to RNFL thickness.

Adult↗

Review of polarization sensitive optical coherence tomography and Stokes vector determination.

Polarization sensitive optical coherence tomography (PS-OCT) provides depth resolved measurements of the polarization state of light reflected from turbid media such as tissue. The theory and calculation of the Stokes vector of light reflected from turbid media is described and application of PS-OCT to contemporary biomedical imaging problems is given. Measurement of the depth resolved Stokes parameters allows determination of the degree of polarization and optical axis orientation in turbid media that can be modeled as a linear retarder. Effect of multiple scattering and speckle on the accuracy and noise of the computed Stokes parameters is discussed. Future directions for development of PS-OCT instrumentation for biological and medical applications is given.

Animals↗

In vivo birefringence and thickness measurements of the human retinal nerve fiber layer using polarization-sensitive optical coherence tomography.

Glaucoma causes damage of the nerve fiber layer, which may cause loss of retinal birefringence. Therefore, PS-OCT is a potentially useful technique for the early detection of glaucoma. We built a fiber-based PS-OCT setup that produces real-time images of the human retina in vivo, coregistered with retinal video images of the location of PS-OCT scans. Preliminary measurements of a healthy volunteer show that the double-pass phase retardation per unit of depth of the RNFL is not constant and varies with location, with values between 0.18 and 0.37 deg/microm. A trend in the preliminary measurements shows that the nerve fiber layer located inferior and superior to the optic nerve head is more birefringent than the thinner layer of nerve fiber tissue in the temporal and nasal regions.

Adult↗

Determination of burn depth by polarization-sensitive optical coherence tomography.

An assessment of burn depth is a key step in guiding the treatment of patients who have sustained thermal injuries. Polarization-sensitive optical coherence tomography (PS-OCT) might eventually provide the physician with a quantitative estimate of actual burn depth. Burns of various depths were induced by contacting rat skin with a brass rod preheated to 75 degrees C for 5, 15, or 30 s. Thermal injury denatured the collagen in the skin, and PS-OCT imaged the resulting reduction of birefringence through the depth-resolved changes in the polarization state of light propagated and reflected from the sample. Stokes vectors were calculated for each point in the PS-OCT images and the reduction in the rate of phase retardation between two orthogonal polarizations of light (deg/microm) was found to show a consistent trend with burn exposure time. PS-OCT is a noninvasive technique with potential to give the physician the information needed to formulate an optimal treatment plan for burn patients.

Animals↗