Alexander Dietzel

Repeatability of Autofluorescence Lifetime Imaging at the Human Fundus in Healthy Volunteers

Abstract Purpose: We aim to evaluate the repeatability of a new fluorescence lifetime imaging (FLIM) technique which measures time-resolved autofluorescence to assess metabolism of the retina. Materials and methods: We performed FLIM with two spectral channels (channel 1: 490–560 nm and channel 2: 560–700 nm) on 10 healthy volunteers, with 10 replicates per volunteer. From the 30° fundus FLIM images, we selected three regions: the fovea, the optic disc and the papillo-macular bundle. For each channel in these regions, we determined an average multi-exponential approximation with three components, and the six resulting parameters, α1–α3 (amplitudes) and τ1–τ3 (fluorescence lifetimes), were analyzed in terms of the coefficient of variation (CV). Results: Repeatability was highest in the papillo-macular bundle, followed by the fovea and the optic disc. Repeatability was higher in channel 1 (mean CV of 7.9%) than in channel 2 (mean CV of 17.7%). The average CV for the diagnostically most relevant channel 1 and the most relevant parameters was as follows: τ1 (5.5%) and τ2 (4.7%) in the papillo-macular bundle, and τ1 (6.8%) and τ2 (6.9%) in the fovea. Conclusions: We demonstrated repeatability of FLIM measurement results within acceptable ranges of variation. Based on the detailed coefficients of variation, we derived recommendations for parameter ranges suitable for diagnostic applications.

Evaluation of a novel method to measure the intraocular pressure based on a mechanical eye model

The different biomechanical properties of the human cornea were simulated using artificial corneas made from silicon with shore hardnesses of 0.6 and 1.0 MPa and cornea thicknesses of 0.2 and 0.5 mm. The different inner pressures in the BiomechEye (10 to 30 in steps of 5 mmHg) were emulated with a stepping motor with screw gearing and piston. Errors in sensor positioning are emulated (0.01 to 1.0 mm in steps of 10 μm) by moving the sensor head relative to the cornea via a linear table.

Automated detection of microaneurysm for fundus images

Chronic hyperglycemia of diabetes may lead to failure in various organs, especially the blood vessels, eyes, kidneys, nerves and heart. It happens due to the faults either in insulin secretion, insulin action, or both. As diabetes developed, the vision of patient starts to deteriorate, leading to Diabetic Retinopathy (DR). Microaneurysm (MA) are the earliest sign of DR where it appears in clusters as tiny, dark red spots or tiny hemorrhages-like within the retina light-sensitive area. Thus, the objectives of this study are to develop an automated algorithm to perform early detection of MA presence in fundus images, and to evaluate the performance of the proposed system design by evaluating the accuracy of the segmented MA. The methods involved in the pre-processing stage are the green component extraction and bottom hat filtering with gamma correction. As the characteristics of blood vessel and MA are the same, the extraction of vessels is needed. This is done by applying the Gaussian matched filter. It is then segmented out by using certain threshold value. In template learning, wavelet coefficient is used in separating the pattern and background image by following the Gaussian distribution curve. Texture energy filter is used to extract the true features where MA are identified. As a result, 84.15% of accuracy is obtained.

Bioelectric and biomagnetic measurements are differentially sensitive to spiral currents.

Abstract Observations indicate that different information is contained in electrocardiograms and magnetocardiograms in both patients and healthy volunteers. Closed loop currents could explain this phenomenon. We hypothesized that open loops, such as the spirally shaped currents in the heart, also contribute to these differences. We modeled two types of open spiral-shaped loops, based on the heart geometry, using 12 artificial current dipoles in a physical torso phantom. The electric potentials and magnetic fields were measured simultaneously with increasing numbers of active dipoles in the spiral source geometries. We found a continuous increase in the measured amplitudes of the magnetic fields, up to a plateau value when 10 active dipoles were enabled. For the electric potentials, we found that the amplitudes increased when up to six or eight active dipoles had been enabled, and then decreased thereafter. We conclude that open loop currents also contribute to the experimentally observed differences in magnetocardiograms and electrocardiograms in both patients and healthy volunteers. Combined bioelectric and biomagnetic measurements should provide greater insight into heart activity than do single modality measurements.

Agreement Between Eyes in Wide-Field Fluorescence Lifetime Imaging Ophthalmoscopy Measurements at the Human Retina in Healthy Volunteers

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new imaging technique for measuring the time-resolved in vivo autofluorescence generated by endogenous fluorophores in the ocular fundus. The aim is to assess the metabolism of the retina. Based on the fluorescence lifetime, different fluorescent compounds in the eye can be distinguished. Pathologic changes may be observed by detecting changes in the fluorescence lifetime. Until now, FLIO is performed using 30° fundus images. For certain diseases section of the fundus is of interest. In this work, observational clinical study in young healthy volunteers was performed to examine the usability of 55° wide-field fluorescence lifetime images. The time-resolved retina autofluorescence was measured (scanning laser ophthalmoscope: 55° of fundus, 62x62 µm2 per pixel; excitation: diode laser with pico-second pulses, 473nm, 80MHz repetition rate; detection: spectral channels 498-560nm (ch1) and 560-720nm (ch2), time-correlated single photon counting method) in both eyes of 11 healthy volunteers (28.7±3.6 years). Three repetitive measurements on different days within one week at a similar time have been performed. All subjects had a crystalline lens and an undilated pupil. A modified 3-exponential approach was applied to determine the mean fluorescence lifetimes tm. tm were computed on the ETDRS grid and in a 15x15 pixel region 25° superior to the fovea. The Wilcoxon rank-sum test was used to test for statistical significant differences between left and right eye. The coefficient of variation in the superior region is 5.6% (right) and 4.7% (left) in ch1 and 2.5% (right) and 2.1% (left) in ch2. No statistical significant differences have been found between right and left eye. FLIO measurements in young healthy volunteers using a 55° lens are repeatable in both eyes and show no significant differences. Spectral channel 2 should be preferred because of its lower variability. The data analysis was done with FLIMX (available at http://www.flimx.de).

Mechanical eye model for evaluation of intraocular pressure measuring under consideration of the biomechanical characteristics

A mechanical eye model has been developed which offers the possibility to set up, carry out and to evaluate intraocular pressure (IOP) measurements under consideration of different biomechanical characteristics. These characteristics are realized by designing model components with various geometries and material properties. Two different cornea thicknesses have been investigated, simulating different inner pressures via a controlled mechanical system, consisting of eyeball-like fluid-filled chamber whose pressure could be altered and measured. Results show significant characteristics in the signals recorded via test sensor as tonometry system, which are in line with medical predications. Using this model the evaluation of tonometry systems under considerations of biomechanical characteristics and environmental conditions can be done.