New insights into the lacrimal pump.

PURPOSE: To date, there are many theories about tear transport through the canaliculi of the draining lacrimal system into the lacrimal sac but only few with supportive data. It is certain that the function of the lacrimal part of orbicularis oculi muscle (Horner-Duverney's muscle) is indispensable for the transport of "used" tears. However, the muscle's exact structure and the mechanisms of its functions are as yet unclear. To obtain deeper insights we undertook the present study. METHODS: Upper and lower canaliculi (including the entrance into the lacrimal sac) from donor cadavers were dissected. Some of the specimens were prepared for scanning electron microscopy (SEM) to analyze the course of muscle fibers surrounding the canaliculi. Others were sectioned for enzyme- (EHC) and immunohistochemistry (IHC) to learn about the distribution of slow and fast reacting muscle fibers in Horner-Duverney's muscle as well as to analyze the distribution of different neurotransmitters to learn more about the innervation of Horner-Duverney's muscle. Four tear duct systems taken from body donors were cut out en bloc after formalin fixation, serially sectioned and reconstructed using a newly developed technology for 3D reconstruction of histological serial sections named HiD® (Chimaera GmbH, Germany). Patients that had undergone dacryocystorhinostomy (DCR) were video-analyzed endonasally during active blinking, focusing on viewing the temporal wall of the lacrimal sac movement where the canaliculi penetrated the lacrimal sac. RESULTS: SEM revealed that muscle fibers of Horner-Duverney's muscle surround the vertical parts of the upper and lower canaliculus in a scissor like pattern whereas they ran in parallel to the first two thirds of the horizontal parts surrounding the respective canaliculus. Here, the muscle fibers were embedded in dense connective tissue forming a unique network. At the nasal third, muscle fibers left the canaliculi and ran to the posterior part of the fascia of the lacrimal sac and the lacrimal bone. EHC revealed that Horner-Duverney's muscle contained nearly an equal distribution of type I and type IIb muscle fibers compared to the superior rectus muscle which contains more type I and the masseter and iliopsoas muscles with more type IIb muscle fibers. IHC indicated presence of trigeminal, catecholaminergic and cholinergic nerve endings. 3D reconstructions supported the SEM data. Endonasal video analysis of patients after DCR with a nasally open lacrimal sac revealed bulging of the temporal wall of the lacrimal sac during blinking. On the basis of these findings, a modified lacrimal pump theory is proposed. CONCLUSION: The results support the hypothesis that contraction of Horner-Duverney's muscle leads to closure of the canaliculi in their first two thirds based on the special arrangement of muscle fibers and connective tissue fibers. This causes the tear fluid in the canaliculi to be pressed/transported towards the lacrimal sac. The medial third of the vertical portions of the canaliculi, the canaliculus communis and the intrasaccal portion of the canaliculus are compressed by the shortening and thickening of the Horner-Duverney muscle from dorsal, which leads to a compression of the canaliculi lumens in this part of the system, thereby pushing the lacrimal fluid further towards the lacrimal sac. The mix of fast contracting and fatigue resistant muscle fibers is ideally suited for the blink mechanism that is complexly regulated by the nervous system.

Statistical iterative reconstruction algorithm for X-ray phase-contrast CT.

Grating-based phase-contrast computed tomography (PCCT) is a promising imaging tool on the horizon for pre-clinical and clinical applications. Until now PCCT has been plagued by strong artifacts when dense materials like bones are present. In this paper, we present a new statistical iterative reconstruction algorithm which overcomes this limitation. It makes use of the fact that an X-ray interferometer provides a conventional absorption as well as a dark-field signal in addition to the phase-contrast signal. The method is based on a statistical iterative reconstruction algorithm utilizing maximum-a-posteriori principles and integrating the statistical properties of the raw data as well as information of dense objects gained from the absorption signal. Reconstruction of a pre-clinical mouse scan illustrates that artifacts caused by bones are significantly reduced and image quality is improved when employing our approach. Especially small structures, which are usually lost because of streaks, are recovered in our results. In comparison with the current state-of-the-art algorithms our approach provides significantly improved image quality with respect to quantitative and qualitative results. In summary, we expect that our new statistical iterative reconstruction method to increase the general usability of PCCT imaging for medical diagnosis apart from applications focused solely on soft tissue visualization.

Simulated cystic renal lesions: quantitative X-ray phase-contrast CT--an in vitro phantom study.

PURPOSE: To determine if grating-based x-ray phase-contrast computed tomography (CT) can allow differentiation of simulated simple, protein-rich, hemorrhagic, and enhancing cystic renal lesions in an in vitro phantom. MATERIALS AND METHODS: An in vitro phantom specifically designed to simulate simple, protein-rich, hemorrhagic, and enhancing renal cysts was scanned with an experimental grating-based phase-contrast CT setup consisting of a Talbot-Lau interferometer with a rotating anode x-ray tube and a single photon counting detector. Various combinations of serum and saline (100% and 0% to 0% and 100%), blood and saline, blood and serum (100% and 0% to 6.25% and 93.75% for both), and an iodinated contrast agent and saline (7.6-1.6 mg per milliliter of saline) were used to reproduce the chemical composition of the different types of cysts. A thickened solution of an iodinated contrast agent calibrated with a clinical multidetector CT scanner served as contrast agent-enhanced renal parenchyma (195 HU at 80 kVp, 400 mAs and 98 HU at 140 kVp, 200 mAs). Standard attenuation- and phase-contrast images were reconstructed from the raw projection data. Quantitative values for attenuation and phase contrast and image noise were determined. Contrast-to-noise ratios were calculated. Simulated lesions were assessed for visual differentiability by means of pairwise comparison of the attenuation- and phase-contrast images and both images simultaneously. RESULTS: Attenuation-contrast imaging showed large differences in Hounsfield units with increasing concentrations of iodine (118.9 HU for 1.6 mg/mL vs 331.4 HU for 7.6 mg/mL). Values for phase-contrast imaging were substantially distinguishable for saline, serum, and blood (7.9, 23.7, and 52.8 HU, respectively). Both imaging modalities combined allowed differentiation of all four types of simulated cysts (100% saline, 100% serum, 100% blood, and 1.6-7.6 mg of iodine per milliliter of saline) with one imaging acquisition. CONCLUSION: Grating-based phase-contrast CT allows differentiation of simulated simple, protein-rich, hemorrhagic, and enhancing renal cysts in an in vitro phantom through simultaneous assessment of their distinct attenuation- and phase-contrast signal.

Evaluation of the potential of phase-contrast computed tomography for improved visualization of cancerous human liver tissue.

PURPOSE: Phase-contrast X-ray computed tomography (PCCT) is currently investigated and developed as a potentially very interesting extension of conventional CT, and can offer several advantages for specific indications in diagnostic imaging. Current absorption-based computed tomography (CT) without the application of contrast material is limited in the detection of minor density differences in soft-tissue. The purpose of this study is to test whether PCCT can improve soft tissue contrast in healthy and tumorous human liver specimens. MATERIALS AND METHODS: Two specimens of human liver (one healthy and one metastasized liver sample) were imaged with brilliant X-ray beam at the synchrotron radiation source ESRF in Grenoble, France. For correlation the same specimens were imaged with a magnetic resonance imaging system at 1.5 T. The histopathology confirmed our findings in the corresponding sections of the specimens. RESULTS: In the phase-contrast CT images we observed a significantly enhanced soft-tissue contrast when compared to simultaneously recorded standard absorption CT measurements. Further, we found that the pathological and morphological information in the PCCT reconstructions show significant improvement when compared to those performed on MRI. Based on matching of prominent features, a good correlation between PCCT and the histological section is demonstrated; especially the tumor capsule and the surrounding vascular structures are visible in PCCT. In addition, our study revealed the ability of PCCT to visualize the blood vessels structure in the tumorous liver without the need of any contrast agents. CONCLUSION: Grating-based PCCT significantly improves the soft-tissue contrast in ex-vivo liver specimens and holds the potential to overcome the need of contrast materials for visualization of the tumor vascularization.

Quantitative X-ray phase-contrast computed tomography at 82 keV.

Potential applications of grating-based X-ray phase-contrast imaging are investigated in various fields due to its compatibility with laboratory X-ray sources. So far the method was mainly restricted to X-ray energies below 40 keV, which is too low to examine dense or thick objects, but a routine operation at higher energies is on the brink of realisation. In this study, imaging results obtained at 82 keV are presented. These comprise a test object consisting of well-defined materials for a quantitative analysis and a tooth to translate the findings to a biomedical sample. Measured linear attenuation coefficients ? and electron densities ?e are in good agreement with theoretical values. Improved contrast-to-noise ratios were found in phase contrast compared to attenuation contrast. The combination of both contrast modalities further enables to simultaneously assess information on density and composition of materials with effective atomic numbers Z? > 8. In our biomedical example, we demonstrate the possibility to detect differences in mass density and calcium concentration within teeth.

Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up.

OBJECTIVE: Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS). METHODS: Grating-based PC-CT was performed on one breast specimen containing an invasive ductal carcinoma and DCIS using monochromatic radiation of 23 keV. Phase-contrast and absorption-based images were compared qualitatively and quantitatively with histopathology in a blinded fashion. RESULTS: Grating-based PC-CT showed improved differentiation of soft-tissue components. Circular structures of high phase-shift contrast corresponding to the walls of the dilated ductuli of the DCIS were visualised with a contrast-to-noise ratio (CNR) of 9.6 using PC-CT but were not detectable on absorption-based images (CNR = 0.27). The high phase-shift structures of the dilated ductuli were identifiable in the PC-CT volume data set allowing for 3D characterisation of DCIS. CONCLUSIONS: Our results indicate that unlike conventional CT, grating-based PC-CT may allow the differentiation between invasive carcinoma and intraductal carcinoma and healthy breast tissue and provide 3D visualisation of DCIS.

Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue.

PURPOSE: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. MATERIALS AND METHODS: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. RESULTS: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p=0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p=0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p=0.03). CONCLUSION: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI.

Computer-aided evaluation of the anatomical accuracy of hybrid SPECT/spiral-CT imaging of lesions localized in the neck and upper abdomen.

OBJECTIVE: The purpose of this study was to investigate the anatomical accuracy of hardware-based single-photon emission computed tomography/computed tomography (SPECT/CT) registration in the upper abdomen and neck. METHODS: The database consisted of 90 patients referred for SPECT/CT for diagnostic workup of either thyroid/parathyroid disease (n=46) or abdominal neuroendocrine tumours (n=44). In the first group, 99mTc-MIBI was used as the tracer and in the second 123I-metaiodobenzylguanidine (n=13), 111In-octreotide (n=28) or 99mTc-octreotide (n=3). For predefined structures represented by both modalities, the distances between the centres of gravity of their CT and SPECT representation were determined in a semiautomated manner. In cervical data sets, this analysis was performed for the submandibular salivary glands (n=92) and in abdominal data sets for 69 neoplastic foci. RESULTS: The mean distances were 5.7 ± 2.0 mm (range: 1.84-9.67 mm) in the neck and 6.8 ± 3.3 mm (range: 1.4-19.7 mm) in the abdomen. In 42 out of 92 of the cervical and 40 out of 69 of the abdominal data sets at least one of the X-direction-determined, Y-direction-determined, and Z-direction-determined distances was greater than the SPECT pixel width of 4.6 mm. CONCLUSION: The anatomical accuracy of hardware-based SPECT/CT fusion depends also on the region of the body studied. For example, in the neck and upper abdomen the accuracy is lower than in the lower lumbar spine. In clinical routine, SPECT/CT data sets acquired for the neck and upper abdomen should be regularly checked and corrected for SPECT/CT misalignment. This is, in particular, important when CT-based corrections of SPECT involving pixelwise data integration such as for attenuation correction are made.

Numerical comparison of X-ray differential phase contrast and attenuation contrast.

We present a numerical tool to compare directly the contrast-to-noise-ratio (CNR) of the attenuation- and differential phase-contrast signals available from grating-based X-ray imaging for single radiographs. The attenuation projection is differentiated to bring it into a modality comparable to the differential phase projection using a Gaussian derivative filter. A Relative Contrast Gain (RCG) is then defined as the ratio of the CNR of image values in a region of interest (ROI) in the differential phase projection to the CNR of image values in the same ROI in the differential attenuation projection. We apply the method on experimental data of human breast tissue acquired using a grating interferometer to compare the two contrast modes for two regions of interest differing in the type of tissue. Our results indicate that the proposed method can be used as a local estimate of the spatial distribution of the ratio δ/ß, i.e., real and imaginary part of the complex refractive index, across a sample.

Automatic parameter selection for multimodal image registration.

Over the past ten years similarity measures based on intensity distributions have become state-of-the-art in automatic multimodal image registration. An implementation for clinical usage has to support a plurality of images. However, a generally applicable parameter configuration for the number and sizes of histogram bins, optimal Parzen-window kernel widths or background thresholds cannot be found. This explains why various research groups present partly contradictory empirical proposals for these parameters. This paper proposes a set of data-driven estimation schemes for a parameter-free implementation that eliminates major caveats of heuristic trial and error. We present the following novel approaches: a new coincidence weighting scheme to reduce the influence of background noise on the similarity measure in combination with Max-Lloyd requantization, and a tradeoff for the automatic estimation of the number of histogram bins. These methods have been integrated into a state-of-the-art rigid registration that is based on normalized mutual information and applied to CT-MR, PET-MR, and MR-MR image pairs of the RIRE 2.0 database. We compare combinations of the proposed techniques to a standard implementation using default parameters, which can be found in the literature, and to a manual registration by a medical expert. Additionally, we analyze the effects of various histogram sizes, sampling rates, and error thresholds for the number of histogram bins. The comparison of the parameter selection techniques yields 25 approaches in total, with 114 registrations each. The number of bins has no significant influence on the proposed implementation that performs better than both the manual and the standard method in terms of acceptance rates and target registration error (TRE). The overall mean TRE is 2.34 mm compared to 2.54 mm for the manual registration and 6.48 mm for a standard implementation. Our results show a significant TRE reduction for distortion-corrected magnetic resonance images.

Segmentation of kidneys using a new active shape model generation technique based on non-rigid image registration.

Active shape models (ASMs) are widely used for applications in the field of image segmentation. Building an ASM requires to determine point correspondences for input training data, which usually results in a set of landmarks distributed according to the statistical variations. State-of-the-art methods solve this problem by minimizing the description length of all landmarks using a parametric mapping of the target shape (e.g. a sphere). In case of models composed of multiple sub-parts or highly non-convex shapes, these techniques feature substantial drawbacks. This article proposes a novel technique for solving the crucial correspondence problem using non-rigid image registration. Unlike existing approaches the new method yields more detailed ASMs and does not require explicit or parametric formulations of the problem. Compared to other methods, the already built ASM can be updated with additional prior knowledge in a very efficient manner. For this work, a training set of 3-D kidney pairs has been manually segmented from 41 CT images of different patients and forms the basis for a clinical evaluation. The novel registration based approach is compared to an already established algorithm that uses a minimum description length (MDL) formulation. The presented results indicate that the use of non-rigid image registration to solve the point correspondence problem leads to improved ASMs and more accurate segmentation results. The sensitivity could be increased by approximately 10%. Experiments to analyze the dependency on the user initialization also show a higher sensitivity of 5-15%. The mean squared error of the segmentation results and the ground truth manually classified data could also be reduced by 20-34% with respect to varying numbers of training samples.