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Zur diagnostischen Unterstützung bei der Befundung laryngealer Erkrankungen soll eine Farb- und Formanalyse der Stimmlippen durchgeführt werden. In diesem Beitrag wird ein Verfahren zur Trennung der spiegelnden und diffusen Reflexionsanteile in Farbbildern des Larynx vorgestellt. Die Farbe der diffusen Komponente entspricht dabei der beleuchtungsunabhängigen Objektfarbe, während deren Wichtungsfaktoren als Eingabe für Shape-from-Shading-Verfahren zur Oberflächenrekonstruktion dienen.
Quantitative Farbmessungen sollen die Diagnostik laryngealer Erkrankungen unterstützen. Dabei wird der Farbeindruck nicht nur durch die Reflexionseigenschaften des Gewebes sondern auch durch die Farbe der verwendeten Lichtquelle beeinflußt. Der hier vorgestellte Farbkonstanz-Algorithmus basiert auf dem dichromatischen Reflexionsmodell und liefert eine pixelweise Trennung des Farbbildes in seine beiden Faxbanteile. Die Körperfarbe entspricht dabei der gewebespezifischen Reflexion, die Oberfächenfarbe der Strahlung der Lichtquelle.
Laryngoscopic images of the vocal tract are used for diagnostic purposes. Quantitative mea-surements like changes of the glottis size or the surface of the vocal cords during an image sequence can be helpful to describe the healing process or to compare the findings of diffe-rent patients. Typically the endoscopic images are circulary symmetric distorted (barrel di-stortion). Therefore measurements of geometric dimensions depend on the object´s position in the image. In this paper an algorithm is presented which allows the computation of the translational invariant "real" object size by correcting the image distortion without using additional calibration of the optical environment.
Nutzung eines Farbkonstanz-Algorithmus zur Entfernung von Glanzlichtern in laryngoskopischen Bildern
(1998)
1 Einführung
Funktionelle und organische Störungen im Larynx beeinträchtigen die Ausdrucksfähigkeit des Menschen. Zur Diagnostik und Verlaufkontrolle werden die Stimmlippen im Larynx mit Hilfe der Video-Laryngoskopie aufgenommen. Zur optimalen Farbmessung wird dazu an das Lupenendoskop eine 3-Chip-CCD-Kamera angeschlossen, die eine unabhängige Aufnahme der drei Farbkanäle erlaubt. Die bisherige subjektive Befundung ist von der Erfahrung des Untersuchers abhängig und läßt nur eine grobe Klassifikation der Krankheitsbilder zu. Zur Objektivierung werden daher quantitative Parameter für Farbe, Textur und Schwingung entwickelt. Neben dem Einfluß der wechselnden Lichtquellenfarbe auf den Farbeindruck ist die Sekretauflage auf den Stimmlippen ein Problem bei der Farb-und Texturanalyse. Sie kann zu ausgedehnten Glanzlichtern führen und so weite Bereiche der Stimmlippen für die Farb-und Texturanalyse unbrauchbar machen. Dieser Beitrag stellt einen Farbkonstanz-Algorithmus vor, der unabhängig von der Lichtquelle quantitative Farbwerte des Gewebes liefert und die Glanzlichtdetektion und -elimination ermöglicht.
2 Methodik
Ziel des Farbkonstanz-Algorithmus ist die Trennung von Lichtquellen-und Gewebefarbe. Unter Verwendung des dichromatischen Reflexionsmodells [1] kann die Oberflächenreflexion mit der Farbe der Lichtquelle und die Körperreflexion mit der Gewebefarbe identifiziert werden. Der Farbeindruck entsteht aus der Linearkombination beider Farbkomponenten. Ihre Gewichtung ist von der Aufnahmegeometrie abhängig, insbesondere vom Winkel zwischen Oberflächennormalen und dem Positionsvektor der Lichtquelle. In einem zweistufigen Verfahren wird zunächst die Lichtquellenfarbe geschätzt, dann die Gewebefarbe ermittelt. Hieraus können beide Farbanteile durch die Berechnung der Gewichtsfaktoren pixelweise getrennt werden.
Video Documentation of endoscopic findings simplifies diagnostic counseling of the patient and aids pre-operative discussion among the medical team. Judgment of such images is still subjective and can not give a quantitative evaluation of the disease process regarding diagnosis or response to treatment. Modern treatment of early laryngeal cancer with laserablation requires intensive follow up and frequent direct laryngoscopy under general anesthesia with blind biopsies to detect any tumor residual or recurrence. Inflammatory conditions of the larynx are frequently confused with other causes of dysphonia. Mapping anddigital analysis of the documented image will suggest the tumor site and avoids undue blind biopsies under anesthesia. However, varying illumination results in different colors reflected from the same object. To achieve quantitative analysis, color constancy has to be assured. Inthis paper, the environment is presented which allow the objective judgment of larngoscopies.
Zur Analyse von Lippenbewegungsabläufen wird ein aktives Konturmodell eingesetzt. Probleme bereitet die hohe Sprechgeschwindigkeit, die in star ken Objektverschiebungen result iert und bislang nicht durch eine alleinige Konturanpassung kompensiert werden kann. In diesem Beitrag werden die klassischen aktiven Konturmodelle um eine Vorjustierung der Grobkonturen erweitert, die eine energiebasierte Konturanpassung erst möglich macht. Die Schätzung der Verschiebung zur Vorjustierung basiert auf dem Gradientenbild und einem prädikatenlogisch formulierten Regelwerk, das Annahmen und Nebenbedingungen als Wissensbasis enthält. Mit Hilfe dieser Erweiterungen ist eine automatisierte Konturverfolgung der Lippen möglich.
Statistische Eigenschaften natürlicher Grauwerttexturen werden mit Co-Occurrence Matrizen, basierend auf der Grauwertstatistik zweiter Ordnung, modelliert. Die Matrix gibt dann die apriori Wahrscheinlichkeiten aller Grauwertpaare an. Da in der medizinischen Bildverarbeitung verstärkt Multispektralbilder ausgewertet werden, wird das bekannte Konzept hier auf beliebige Vektorbilder erweitert. Dadurch kann bei der Texturklassifikation die zur Verfügung stehende Information vollständig genutzt werden. Insbesondere zur Detektion von Farbtexturen ist dieser Ansatz geeignet, da Wertepaare unterschiedlicher Spektralebenen ausgewertet werden können. Ebenso kann die Methode auch bei der Multiskalendekomposition von Intensitätsbildern zur Verbesserung der Texturerkennung beitragen. Die in den Matrizen entstehenden Muster lassen dann über die Extraktion geeigneter Texturdeskriptoren Rückschlüsse auf die Texturen des Bildes zu.
Bestimmung der Lichtquellenfarbe bei der Endoskopie mikrotexturierter Oberflächen des Kehlkopfes
(1999)
Zur Unterstützung der Diagnose von Stimmlippenerkrankungen werden innerhalb des Forschungsprojektes Quantitative Digitale Laryngoskopie objektive Parameter zur Beschreibung der Bewegung, der Farbe sowie der Form der Stimmlippen entwickelt und klinisch evaluiert. Während die Bewegungsanalyse Aufschluß über funktionelle Stimmstörungen gibt, beschreiben Parameter der Farb- und Formanalyse morphologische Veränderungen des Stimmlippengewebes. In diesem Beitrag werden die Methoden und bisherigen Ergebnisse zur Bewegungs- und Farbanalyse vorgestellt.
Die Bewegungsanalyse wurde mit einem erweiterten Konturmodell (Snakes) durchgeführt. Aufgrund des modifizierten Konturmodells konnten die Konturen der Stimmlippen automatisch über die gesmate Bildsequenz zuverlässig detektiert werden. Die Vermssung der Konturen liefert neue quantitative Parameter zur Befundung von laryngoskopischen Stimmlippenaufnahmen.
Um die Farbeigenschaften der Stimmlippen zu bestimmen, wurde ausgehend vom RGB-Bild die Objektfarbe unabhängig von der Farbe der Lichtquelle durch Verwendung von Clusterverfahren und der Viertelkreisanalyse berechnet. Mit dieser Farbanalyse konnte die Farbe der Lichtquelle ermittelt und das beleuchtungsunabhängige Farbbild berechnet werden. Die Quanitifizierung der Rötung der Stimmlippen ist z.B. ein entscheidendes Kriterium zur Diagnostik der akuten Laryngitis.
Objective:
Complex hue/saturation images as a new approach for color texture classification using Gabor filters are introduced and compared with common techniques.
Method:
The interpretation of hue and saturationas polar coordinates allows direct use of the HSV-colorspace for Fourier transform. This technique is applied for Gabor feature extraction of color textures. In contrast to other color features based on the RGB-colorspace [1] the combination of color bands is done previous to the filtering.
Results:
The performance of the new HS-featuresis compared with that of RGB based as well as grayscale Gabor features by evaluating the classifi-cation of 30 natural textures. The new HS-featuresshow same results like the best RGB features but allow a more compact representation. On the averagethe color features improve the results of grayscale features.
Conclusion:
The consideration of the color information enhances the classification of color texture. The choice of colorspace cannot be adjudged finally, but the introduced features suggest the use of the HSV-colorspace with less features than RGB.
Zur Lösung komplexer Segmentierungsprobleme wird eine hierarchische und farbbasierte Wasserscheidentransformation vorgestellt. Geringe Modifikationen bezüglich Startpunktwahl und Flutungsprozess resultieren in signifikanten Verbesserungen der Segmentierung. Das Verfahren wurde zur Lippendetektion in Farbbildsequenzen eingesetzt, die zur quantitativen Beschreibung von Sprechbewegungsabläufen automatisch ausgewertet werden. Die Experimente mit 245 Bildern aus 6 Sequenzen zeigten eine Fehlerrate von 13%.
Color Texture Analysis of Moving Vocal Cords Using Approaches from Statistics and Signal Theory
(2000)
Textural features are applied for detection of morphological pathologies of vocal cords. Cooccurrence matrices as statistical features are presented as well as filter bank analysis by Gabor filters. Both methods are extended to handle color images. Their robustness against camera movement and vibration of vocal cords is evaluated. Classification results due to three in vivo sequences are in between 94.4 % and 98.9%. The classification errors decrease if color features are used instead of grayscale features for both statistical and Fourier features
Local gray level dependencies of natural images can be modelled by means of co-occurrence matrices containing joint probabilities of gray-level pairs. Texture, however, is a resolution-dependent phenomenon and hence, classification depends on the chosen scale. Since there is no optimal scale for all textures we employ a multiscale approach that acquires textural features at several scales. Thus linear and nonlinear scale-spaces are analyzed by multiscale co-occurrence matrices that describe the statistical behavior of a texture in scale-space. Classification is then performed on the basis of texture features taken from the individual scale with the highest discriminatory power. By considering cross-scale occurrences of gray level pairs, the impact of filters on the feature is described and used for classification of natural textures. This novel method was found to improve classification rates of the common co-occurrence matrix approach on standard textures significantly.
The estimation of illuminant color is mandatory for many applications in the field of color image quantification. However, it is an unresolved problem if no additional heuristics or restrictive assumptions apply. Assuming uniformly colored and roundly shaped objects, Lee has presented a theory and a method for computing the scene-illuminant chromaticity from specular highlights [H. C. Lee, J. Opt. Soc. Am. A 3, 1694 (1986)]. However, Lee’s method, called image path search, is less robust to noise and is limited in the handling of microtextured surfaces. We introduce a novel approach to estimate the color of a single illuminant for noisy and microtextured images, which frequently occur in real-world scenes. Using dichromatic regions of different colored surfaces, our approach, named color line search, reverses Lee’s strategy of image path search. Reliable color lines are determined directly in the domain of the color diagrams by three steps. First, regions of interest are automatically detected around specular highlights, and local color diagrams are computed. Second, color lines are determined according to the dichromatic reflection model by Hough transform of the color diagrams. Third, a consistency check is applied by a corresponding path search in the image domain. Our method is evaluated on 40 natural images of fruit and vegetables. In comparison with those of Lee’s method, accuracy and stability are substantially improved. In addition, the color line search approach can easily be extended to scenes of objects with macrotextured surfaces.
A method for automated segmentation of vocal cords in stroboscopic video sequences is presented.
In contrast to earlier approaches, the inner and outer contours of the vocal cords are independently delineated. Automatic segmentation of the low contrasted images is carried out by connecting the shape constraint of a point distribution model to a multi-channel regionbased balloon model. This enables us to robustly compute a vibration profile that is used as a new diagnostic tool to visualize several vibration parameters in only one graphic. The vibration profiles are studied in two cases: one physiological vibration and one functional pathology.
Whilst considerable progress has been made in enhancing the quality of indirect laryngoscopy and image processing, the evaluation of clinical findings is still based on the clinician's judgement. The aim of this paper was to examine the feasibility of an objective computer-based method for evaluating laryngeal disease. Digitally recorded images obtained by 90 degree- and 70 degree-angled indirect rod laryngoscopy using standardized white balance values were made of 16 patients and 19 healthy subjects. The digital images were evaluated manually by the clinician based on a standardized questionnaire, and suspect lesions were marked and classified on the image. Following colour separation, normal vocal cord areas as well as suspect lesions were analyzed automatically using co-occurrence matrices, which compare colour differences between neighbouring pixels over a predefined distance. Whilst colour histograms did not provide sufficient information for distinguishing between healthy and diseased tissues, consideration of the blue content of neighbouring pixels enabled a correct classification in 81.4% of cases. If all colour channels (red, green and blue) were regarded simultaneously, the best classification correctness obtained was 77.1%. Although only a very basic classification differentiating between healthy and diseased tissue was attempted, the results showed progress compared to grey-scale histograms, which have been evaluated before. The results document a first step towards an objective, machine-based classification of laryngeal images, which could provide the basis for further development of an expert system for use in indirect laryngoscopy.
Presenting images from different modalities seems to be a trivial task considering the challenges to obtain registered images as a pre-requisite for image fusion. In combined tomographs like PET/CT, image registration is intrinsic. However, informative image fusion mandates careful preparation owing to the large amount of information that is presented to the observer. In complex imaging situations it is required to provide tools that are easy to handle and still powerful enough to help the observer discriminating important details from background patterns. We investigated several options for color tables applied to brain and non-brain images obtained with PET, MRI and CT.
Volumetric representations of autoradiographic and histological images gain ever more interest as a base to interpret data obtained with /spl mu/-imaging devices like microPET. Beyond supporting spatial orientation within rat brains especially autoradiographic images may serve as a base to quantitatively evaluate the complex uptake patterns of microPET studies with receptor ligands or tumor tracers. They may also serve for the development of rat brain atlases or data models, which can be explored during further image analysis or simulation studies. In all cases a consistent spatial representation of the rat brain, i.e. its anatomy and the corresponding quantitative uptake pattern, is required. This includes both, a restacking of the individual two-dimensional images and the exact registration of the respective volumes. We propose strategies how these volumes can be created in a consistent way and trying to limit the requirements on the circumstances during data acquisition, i.e. being independent from other sources like video imaging of the block face prior to cutting or high resolution micro-X-ray CT or micro MRI.
Integrative Co-occurrence matrices are introduced as novel features for color texture classification. The extended Co-occurrence notation allows the comparison between integrative and parallel color texture concepts. The information profit of the new matrices is shown quantitatively using the Kolmogorov distance and by extensive classification experiments on two datasets. Applying them to the RGB and the LUV color space the combined color and intensity textures are studied and the existence of intensity independent pure color patterns is demonstrated. The results are compared with two baselines: gray-scale texture analysis and color histogram analysis. The novel features improve the classification results up to 20% and 32% for the first and second baseline, respectively.
Although it has long been presumed that d-amino acids are uncommon in mammalians, substantial amounts of free d-serine have been detected in the mammalian brain. d-Serine has been demonstrated to be an important modulator of glutamatergic neurotransmission and acts as an agonist at the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors. The blood-to-brain transfer of d-serine is thought to be extremely low, and it is assumed that d-serine is generated by isomerization of l-serine in the brain. Stimulated by the observation of a preferred transport of the d-isomer of proline at the blood–brain barrier, we investigated the differential uptake of [3H]-d-serine and [3H]-l-serine in the rat brain 1 h after intravenous injection using quantitative autoradiography. Surprisingly, brain uptake of [3H]-d-serine was significantly higher than that of [3H]-l-serine, indicating a preferred transport of the d-enantiomer of serine at the blood–brain barrier. This finding indicates that exogenous d-serine may have a direct influence on glutamatergic neurotransmission and associated diseases.
3D rat brain tumors
(2005)
Evaluierung von Registrierungsstrategien zur multimodalen 3D-Rekonstruktion von Rattenhirnschnitten
(2006)
In dieser Arbeit werden drei Strategien zur 3D Stapelung von multimodalen Schnittbildern vorgestellt. Die Strategien werden experimentell anhand von Dualtracer-Autoradiographien evaluiert. Dazu werden neue Maße zur Beschreibung der Konsistenz innerhalb einer Modalität und der Konsistenz der Modalitäten untereinander entwickelt, die auf bekannten Registrierungsmetriken basieren. Gerade bezüglich der Konsistenz der Modalitäten untereinander zeigen zwei Strategien die besten Resultate: (1) abwechselnde multimodale Registrierung (2) monomodale Rekonstruktion einer Modalität und multimodale 2D Registrierung der zweiten Modalität.
Objectives: C-11-methionine (MET) is particularly useful in brain tumor diagnosis but unspecific uptake e.g. in cerebral ischemia has been reported (1). The F-18-labeled amino acid O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) shows a similar clinical potential as MET in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of FET and H-3-MET in focal cortical ischemia in rats by dual tracer autoradiography.
Methods: Focal cortical ischemia was induced in 12 Fisher CDF rats using the photothrombosis model (PT). One day (n=3) , two days (n=5) and 7 days (n=4) after induction of the lesion FET and H-3-MET were injected intravenously. One hour after tracer injection animals were killed, the brains were removed immediately and frozen in 2-methylbutane at -50°C. Brains were cut in coronal sections (thickness: 20 µm) and exposed first to H-3 insensitive photoimager plates to measure FET distribution. After decay of F-18 the distribution of H-3-MET was determined. The autoradiograms were evaluated by regions of interest (ROIs) placed on areas with increased tracer uptake in the PT and the contralateral brain. Lesion to brain ratios (L/B) were calculated by dividing the mean uptake in the lesion and the brain. Based on previous studies in gliomas a L/B ratio > 1.6 was considered as pathological for FET.
Results: Variable increased uptake of both tracers was observed in the PT and its demarcation zone at all stages after PT. The cut-off level of 1.6 for FET was exceeded in 9/12 animals. One day after PT the L/B ratios were 2.0 ± 0.6 for FET vs. 2.1 ± 1.0 for MET (mean ± SD); two days after lesion 2.2 ± 0.7 for FET vs. 2.7 ± 1.0 for MET and 7 days after lesion 2.4 ± 0.4 for FET vs. 2.4 ± 0.1 for MET. In single cases discrepancies in the uptake pattern of FET and MET were observed.
Conclusions: FET like MET may exhibit significant uptake in infarcted areas or the immediate vincinity which has to be considered in the differential diagnosis of unkown brain lesions. The discrepancies in the uptake pattern of FET and MET in some cases indicates either differences in the transport mechanisms of both amino acids or a different affinity for certain cellular components.
Quantification of growth in experimental F98 and C6 rat brain tumours was performed on 51 rat brains, 17 of which have been further assessed by 3D tumour reconstruction. Brains were cryosliced and radio-labelled with a ligand of the peripheral type benzodiazepine-receptor (pBR), 3H-Pk11195 [(1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propylene)-3-isoquinoline-carboxamide)] by receptor autoradiography. Manually segmented and automatically registered tumours have been 3D-reconstructed for volumetric comparison on the basis of 3H-Pk11195-based tumour recognition. Furthermore automatically computed areas of −300 μm inner (marginal) zone as well as 300 μm and 600 μm outer tumour space were quantified. These three different regions were transferred onto other adjacent slices that had been labelled by receptor autoradiography with the A1 Adenosine receptor (A1AR)-ligand 3H-CPFPX (3H-8-cyclopentyl-3-(3-fluorpropyl)-1-propylxanthine) for quantitative assessment of A1AR in the three different tumour zones. Hence, a method is described for quantifying various receptor protein systems in the tumour as well as in the marginal invasive zones around experimentally implanted rat brain tumours and their representation in the tumour microenvironment as well as in 3D space. Furthermore, a tool for automatically reading out radio-labelled rat brain slices from auto radiographic films was developed, reconstructed into a consistent 3D-tumour model and the zones around the tumour were visualized. A1AR expression was found to depend upon the tumour volume in C6 animals, but is independent on the time of tumour development. In F98 animals, a significant increase in A1AR receptor protein was found in the Peritumoural zone as a function of time of tumour development and tumour volume.
Time-Dependent Joint Probability Speed Function for Level-Set Segmentation of Rat-Brain Slices
(2008)
The segmentation of rat brain slices suffers from illumination inhomogeneities and staining effects. State-of-the-art level-set methods model slice and background with intensity mixture densities defining the speed function as difference between the respective probabilites. Nevertheless, the overlap of these distributions causes an inaccurate stopping at the slice border. In this work, we propose the characterisation of the border area with intensity pairs for inside and outside estimating joint intensity probabilities. Method - In contrast to global object and background models, we focus on the object border characterised by a joint mixture density. This specifies the probability of the occurance of an inside and an outside value in direct adjacency. These values are not known beforehand, because inside and outside depend on the level-set evolution and change during time. Therefore, the speed function is computed time-dependently at the position of the current zero level-set. Along this zero level-set curve, the inside and outside values are derived as mean along the curvature normal directing inside and outside the object. Advantage of the joint probability distribution is to resolve the distribution overlaps, because these are assumed to be not located at the same border position. Results - The novel time-dependent joint probability based speed function is compared expermimentally with single probability based speed functions. Two rat brains with about 40 slices are segmented and the results analysed using manual segmentations and the Tanimoto overlap measure. Improved results are recognised for both data sets.
Fusion of histology and MRI is frequently demanded in biomedical research to study in vitro tissue properties in an in vivo reference space. Distortions and artifacts caused by cutting and staining of histological slices as well as differences in spatial resolution make even the rigid fusion a difficult task. State-of- the-art methods start with a mono-modal restacking yielding a histological pseudo-3D volume. The 3D information of the MRI reference is considered subsequently. However, consistency of the histology volume and consistency due to the corresponding MRI seem to be diametral goals. Therefore, we propose a novel fusion framework optimizing histology/histology and histology/MRI consistency at the same time finding a balance between both goals. Method - Direct slice-to-slice correspondence even in irregularly-spaced cutting sequences is achieved by registration-based interpolation of the MRI. Introducing a weighted multi-image mutual information metric (WI), adjacent histology and corresponding MRI are taken into account at the same time. Therefore, the reconstruction of the histological volume as well as the fusion with the MRI is done in a single step. Results - Based on two data sets with more than 110 single registrations in all, the results are evaluated quantitatively based on Tanimoto overlap measures and qualitatively showing the fused volumes. In comparison to other multi-image metrics, the reconstruction based on WI is significantly improved. We evaluated different parameter settings with emphasis on the weighting term steering the balance between intra- and inter-modality consistency.
Whole-body PET/CT imaging
(2008)
Aim
Combined whole-body (WB) PET/CT imaging provides better overall co-registration compared to separate CT and PET. However, in clinical routine local PET-CT mis-registration cannot be avoided. Thus, the reconstructed PET tracer distribution may be biased when using the misaligned CT transmission data for CT-based attenuation correction (CT-AC). We investigate the feasibility of retrospective co-registration techniques to align CT and PET images prior to CT-AC, thus improving potentially the quality of combined PET/CT imaging in clinical routine.
Methods
First, using a commercial software registration package CT images were aligned to the uncorrected PET data by rigid and non-rigid registration methods. Co-registration accuracy of both alignment approaches was assessed by reviewing the PET tracer uptake patterns (visual, linked cursor display) following attenuation correction based on the original and co-registered CT. Second, we investigated non-rigid registration based on a prototype ITK implementation of the B-spline algorithm on a similar targeted MR-CT registration task, there showing promising results.
Results
Manual rigid, landmark-based co-registration introduced unacceptable misalignment, in particular in peripheral areas of the whole-body images. Manual, non-rigid landmark-based co-registration prior to CT-AC was successful with minor loco-regional distortions. Nevertheless, neither rigid nor non-rigid automatic co-registration based on the Mutual Information image to image metric succeeded in co-registering the CT and noAC-PET images. In contrast to widely available commercial software registration our implementation of an alternative automated, non-rigid B-spline co-registration technique yielded promising results in this setting with MR-CT data.
Conclusion
In clinical PET/CT imaging, retrospective registration of CT and uncorrected PET images may improve the quality of the AC-PET images. As of today no validated and clinically viable commercial registration software is in routine use. This has triggered our efforts in pursuing new approaches to a validated, non-rigid co-registration algorithm applicable to whole-body PET/CT imaging of which first results are presented here. This approach appears suitable for applications in retrospective WB-PET/CT alignment.
Ziel
Kombinierte PET/CT-Bildgebung ermöglicht verbesserte Koregistrierung von PET- und CT-Daten gegenüber separat akquirierten Bildern. Trotzdem entstehen in der klinischen Anwendung lokale Fehlregistrierungen, die zu Fehlern in der rekonstruierten PET- Tracerverteilung führen können, falls die unregistrierten CT-Daten zur Schwächungskorrektur (AC) der Emissionsdaten verwendet werden. Wir untersuchen daher die Anwendung von Bildregistrierungsalgorithmen vor der CT-basierten AC zur Verbesserung der PET-Aufnahmen.
Methoden
Mittels einer kommerziellen Registrierungssoftware wurden die CT-Daten eines PET/CT- Tomographen durch landmarken- und intensitätsbasierte rigide (starre) und nicht-rigide Registrierungsverfahren räumlich an die unkorrigierten PET-Emissionsdaten angepasst und zur AC verwendet. Zur Bewertung wurden die Tracerverteilungen in den PET-Bildern (vor AC, CT-AC, CT-AC nach Koregistrierung) visuell und mit Hilfe korrelierter Fadenkreuze verglichen. Zusätzlich untersuchten wir die ITK-Implementierung der bekannten B-spline basierten, nicht-rigiden Registrierungsansätze im Hinblick auf ihre Verwendbarkeit für die multimodale PET/CT-Ganzkörperregistrierung.
Ergebnisse
Mittels landmarkenbasierter, nicht-rigider Registrierung konnte die Tracerverteilung in den PET-Daten lokal verbessert werden. Landmarkenbasierte rigide Registrierung führte zu starker Fehlregistrierung in entfernten Körperregionen. Automatische rigide und nicht-rigide Registrierung unter Verwendung der Mutual-Information-Ähnlichkeitsmetrik versagte auf allen verwendeten Datensätzen. Die automatische Registrierung mit B-spline-Funktionen zeigte vielversprechende Resultate in der Anwendung auf einem ähnlich gelagerten CT–MR-Registrierungsproblem.
Fazit
Retrospektive, nicht-rigide Registrierung unkorrigierter PET- und CT-Aufnahmen aus kombinierten Aufnahmensystemen vor der AC kann die Qualität von PET-Aufnahmen im klinischen Einsatz verbessern. Trotzdem steht bis heute im klinischen Alltag keine validierte, automatische Registrierungssoftware zur Verfügung. Wir verfolgen dazu Ansätze für validierte, nicht-rigide Bildregistrierung für den klinischen Einsatz und präsentieren erste Ergebnisse.
Purpose
MR-based attenuation correction (AC) will become an integral part of combined PET/MR systems. Here, we propose a toolbox to validate MR-AC of clinical PET/MRI data sets.
Methods
Torso scans of ten patients were acquired on a combined PET/CT and on a 1.5-T MRI system. MR-based attenuation data were derived from the CT following MR–CT image co-registration and subsequent histogram matching. PET images were reconstructed after CT- (PET/CT) and MR-based AC (PET/MRI). Lesion-to-background (L/B) ratios were estimated on PET/CT and PET/MRI.
Results
MR–CT histogram matching leads to a mean voxel intensity difference in the CT- and MR-based attenuation images of 12% (max). Mean differences between PET/MRI and PET/CT were 19% (max). L/B ratios were similar except for the lung where local misregistration and intensity transformation leads to a biased PET/MRI.
Conclusion
Our toolbox can be used to study pitfalls in MR-AC. We found that co-registration accuracy and pixel value transformation determine the accuracy of PET/MRI.
Object
The consistency of parametric registration in multi-temporal magnetic resonance (MR) imaging studies was evaluated.
Materials and methods
Serial MRI scans of adult patients with a brain tumor (glioma) were aligned by parametric registration. The performance of low-order spatial alignment (6/9/12 degrees of freedom) of different 3D serial MR-weighted images is evaluated. A registration protocol for the alignment of all images to one reference coordinate system at baseline is presented. Registration results were evaluated for both, multimodal intra-timepoint and mono-modal multi-temporal registration. The latter case might present a challenge to automatic intensity-based registration algorithms due to ill-defined correspondences. The performance of our algorithm was assessed by testing the inverse registration consistency. Four different similarity measures were evaluated to assess consistency.
Results
Careful visual inspection suggests that images are well aligned, but their consistency may be imperfect. Sub-voxel inconsistency within the brain was found for allsimilarity measures used for parametric multi-temporal registration. T1-weighted images were most reliable for establishing spatial correspondence between different timepoints.
Conclusions
The parametric registration algorithm is feasible for use in this application. The sub-voxel resolution mean displacement error of registration transformations demonstrates that the algorithm converges to an almost identical solution for forward and reverse registration.
Reduktion von Rissartefakten durch nicht-lineare Registrierung in histologischen Schnittbildern
(2009)
In dieser Arbeit wird ein Verfahren vorgestellt, das Rissartefakte, die in histologischen Rattenhirnschnitten vorkommen können, durch nicht-lineare Registrierung reduziert. Um die Optimierung in der Rissregion zu leiten, wird der Curvature Registrierungsansatz um eine Metrik basierend auf der Segmentierung der Bilder erweitert. Dabei erzielten Registrierungen mit der ausschließlichen Segmentierung des Risses bessere Ergebnisse als Registrierungen mit einer Segmentierung des gesamten Hirnschnitts. Insgesamt zeigt sich eine deutliche Verbesserung in der Rissregion, wobei der verbleibende reduzierte Riss auf die Glattheitsbedingungen des Regularisierers zurückzuführen ist.
In dieser Arbeit wird die Segmentierung von Gehirngewebe aus Kopfaufnahmen von Ratten mittels Level-Set-Methoden vorgeschlagen. Dazu wird ein zweidimensionaler, kontrastbasierter Ansatz zu einem dreidimensionalen, lokal an die Bildintensität adaptierten Segmentierer erweitert. Es wird gezeigt, dass mit diesem echten 3D-Ansatz die lokalen Bildstrukturen besser berücksichtigt werden können. Insbesondere Magnet-Resonanz-Tomographien (MRTs) mit globalen Helligkeitsgradienten, beispielsweise bedingt durch Oberflächenspulen, können auf diese Weise zuverlässiger und ohne weitere Vorverarbeitungsschritte segmentiert werden. Die Leistungsfähigkeit des Algorithmus wird experimentell an Hand dreier Rattenhirn-MRTs demonstriert.
In neuroscience, small-animal studies frequently involve dealing with series of images from multiple modalities such as histology and autoradiography. The consistent and bias-free restacking of multi-modality image series is obligatory as a starting point for subsequent non-rigid registration procedures and for quantitative comparisons with positron emission tomography (PET) and other in vivo data. Up to now, consistency between 2D slices without cross validation using an inherent 3D modality is frequently presumed to be close to the true morphology due to the smooth appearance of the contours of anatomical structures. However, in multi-modality stacks consistency is difficult to assess. In this work, consistency is defined in terms of smoothness of neighboring slices within a single modality and between different modalities. Registration bias denotes the distortion of the registered stack in comparison to the true 3D morphology and shape. Based on these metrics, different restacking strategies of multi-modality rat brain slices are experimentally evaluated. Experiments based on MRI-simulated and real dual-tracer autoradiograms reveal a clear bias of the restacked volume despite quantitatively high consistency and qualitatively smooth brain structures. However, different registration strategies yield different inter-consistency metrics. If no genuine 3D modality is available, the use of the so-called SOP (slice-order preferred) or MOSOP (modality-and-slice-order preferred) strategy is recommended.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful technique for the determination of metal and nonmetal distributions within biological systems with high sensitivity. An imaging LA-ICP-MS technique for Fe, Cu, Zn, and Mn was developed to produce large series of quantitative element maps in native brain sections of mice subchronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) as a model of Parkinson’s disease. Images were calibrated using matrix-matched laboratory standards. A software solution allowing a precise delineation of anatomical structures was implemented. Coronal brain sections were analyzed crossing the striatum and the substantia nigra, respectively. Animals sacrificed 2 h, 7 d, or 28 d after the last MPTP injection and controls were investigated.
We observed significant decreases of Cu concentrations in the periventricular zone and the fascia dentata at 2 h and 7d and a recovery or overcompensation at 28 d, most pronounced in the rostral periventricular zone (+40%). In the cortex Cu decreased slightly to −10%. Fe increased in the interpeduncular nucleus (+40%) but not in the substantia nigra. This pattern is in line with a differential regulation of periventricular and parenchymal Cu, and with the histochemical localization of Fe, and congruent to regions of preferential MPTP binding described in the rodent brain.
The LA-ICP-MS technique yielded valid and statistically robust results in the present study on 39 slices from 19 animals. Our findings underline the value of routine micro-local analytical techniques in the life sciences and affirm a role of Cu availability in Parkinson’s disease.
Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography.
Bioimaging of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS)
(2010)
The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non‐metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) using double‐focusing sector field (LA‐ICP‐SFMS) or quadrupole‐based mass spectrometers (LA‐ICP‐QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA‐ICP‐QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA‐ICP‐MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal‐containing proteins and also phosphoproteins. Metal‐containing proteins were imaged in a two‐dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA‐ICP‐MS imaging as a stand‐alone technique and in combination with MALDI/ESI‐MS for selected life science applications is summarized.
For accurate registration of histological sections blockface images are frequently used as three dimensional reference. However, due to the use of endocentric lenses the images suffer from perspective errors such as scaling and seemingly relative movement of planes which are located in different distances parallel to the imaging sensor. The suggested correction of those errors is based on the estimation of scaling factors derived from image registration of regions characterized by differing distances to the point of view in neighboring sections. The correction allows the generation of a consistent three dimensional blockface volume.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson’s disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.
Polarized light imaging (PLI) enables the evaluation of fiber orientations in histological sections of human postmortem brains, with ultra-high spatial resolution. PLI is based on the birefringent properties of the myelin sheath of nerve fibers. As a result, the polarization state of light propagating through a rotating polarimeter is changed in such a way that the detected signal at each measurement unit of a charged-coupled device (CCD) camera describes a sinusoidal signal. Vectors of the fiber orientation defined by inclination and direction angles can then directly be derived from the optical signals employing PLI analysis. However, noise, light scatter and filter inhomogeneities interfere with the original sinusoidal PLI signals. We here introduce a novel method using independent component analysis (ICA) to decompose the PLI images into statistically independent component maps. After decomposition, gray and white matter structures can clearly be distinguished from noise and other artifacts. The signal enhancement after artifact rejection is quantitatively evaluated in 134 histological whole brain sections. Thus, the primary sinusoidal signals from polarized light imaging can be effectively restored after noise and artifact rejection utilizing ICA. Our method therefore contributes to the analysis of nerve fiber orientation in the human brain within a micrometer scale.