16 research outputs found
Image enhancement in digital X-ray angiography
Anyone who does not look back to the beginning throughout a
course of action, does not look forward to the end. Hence it
necessarily follows that an intention which looks ahead, depends
on a recollection which looks back.
| Aurelius Augustinus, De civitate Dei, VII.7 (417 A.D.)
Chapter 1
Introduction and Summary
D
espite the development of imaging techniques based on alternative physical
phenomena, such as nuclear magnetic resonance, emission of single photons
( -radiation) by radio-pharmaceuticals and photon pairs by electron-positron
annihilations, re ection of ultrasonic waves, and the Doppler eect, X-ray based im-
age acquisition is still daily practice in medicine. Perhaps this can be attributed to
the fact that, contrary to many other phenomena, X-rays lend themselves naturally
for registration by means of materials and methods widely available at the time of
their discovery | a fact that gave X-ray based medical imaging an at least 50-year
head start over possible alternatives. Immediately after the preliminary communica-
tion on the discovery of the \new light" by R¨ ontgen [317], late December 1895, the
possible applications of X-rays were investigated intensively. In 1896 alone, almost
one 1,000 articles about the new phenomenon appeared in print (Glasser [119] lists
all of them). Although most of the basics of the diagnostic as well as the therapeutic
uses of X-rays had been worked out by the end of that year [289], research on im-
proved acquisition and reduction of potential risks for humans continued steadily in
the century to follow. The development of improved X-ray tubes, rapid lm changers,
image intensiers, the introduction of television cameras into uoroscopy, and com-
puters in digital radiography and computerized tomography, formed a succession of
achievements which increased the diagnostic potential of X-ray based imaging.
One of the areas in medical imaging where X-rays have always played an im-
portant role is angiography,y which concerns the visualization of blood vessels in the
human body. As already suggested, research on the possibility of visualization of the
human vasculature was initiated shortly after the discovery of X-rays. A photograph
of a rst \angiogram" | obtained by injection of a mixture of chalk, red mercury,
and petroleum into an amputated hand, followed by almost an hour of exposure to
X-rays | was published as early as January 1896, by Hascheck & Lindenthal [139].
Although studies on cadavers led to greatly improved knowledge of the anatomy of
the human vascular system, angiography in living man for the purpose of diagnosis
and intervention became feasible only after substantial progress in the development
yA term originating from the Greek words o (aggeion), meaning \vessel" or \bucket", and
-' (graphein), meaning \to write" or \to record". 2 1 Introduction and Summary
of relatively safe contrast media and methods of administration, as well as advance-
ments in radiological equipment. Of special interest in the context of this thesis is
the improvement brought by photographic subtraction, a technique known since the
early 1900s and since then used successfully in e.g. astronomy, but rst introduced
in X-ray angiography in 1934, by Ziedses des Plantes [425, 426]. This technique al-
lowed for a considerable enhancement of vessel visibility by cancellation of unwanted
background structures. In the 1960s, the time consuming lm subtraction process
was replaced by analog video subtraction techniques [156, 275] which, with the in-
troduction of digital computers, gave rise to the development of digital subtraction
angiography [194] | a technique still considered by many the \gold standard" for de-
tection and quantication of vascular anomalies. Today, research on improved X-ray
based imaging techniques for angiography continues, witness the recent developments
in three-dimensional rotational angiography [88, 185, 186, 341,373].
The subject of this thesis is enhancement of digital X-ray angiography images. In
contrast with the previously mentioned developments, the emphasis is not on the
further improvement of image acquisition techniques, but rather on the development
and evaluation of digital image processing techniques for retrospective enhancement
of images acquired with existing techniques. In the context of this thesis, the term
\enhancement" must be regarded in a rather broad sense. It does not only refer
to improvement of image quality by reduction of disturbing artifacts and noise, but
also to minimization of possible image quality degradation and loss of quantitative
information, inevitably introduced by required image processing operations. These
two aspects of image enhancement will be claried further in a brief summary of each
of the chapters of this thesis.
The rst three chapters deal with the problem of patient motion artifacts in digital
subtraction angiography (DSA). In DSA imaging, a sequence of 2D digital X-ray
projection images is acquired, at a rate of e.g. two per second, following the injection
of contrast material into one of the arteries or veins feeding the part of the vasculature
to be diagnosed. Acquisition usually starts about one or two seconds prior to arrival
of the contrast bolus in the vessels of interest, so that the rst few images included
in the sequence do not show opacied vessels. In a subsequent post-processing step,
one of these \pre-bolus" images is then subtracted automatically from each of the
contrast images so as to mask out background structures such as bone and soft-
tissue shadows. However, it is clear that in the resulting digital subtraction images,
the unwanted background structures will have been removed completely only when
the patient lied perfectly still during acquisition of the original images. Since most
patients show at least some physical reaction to the passage of a contrast medium, this
proviso is generally not met. As a result, DSA images frequently show patient-motion
induced artifacts (see e.g. the bottom-left image in Fig. 1.1), which may in uence the
subsequent analysis and diagnosis carried out by radiologists.
Since the introduction of DSA, in the early 1980s, many solutions to the problem
of patient motion artifacts have been put forward. Chapter 2 presents an overview
of the possible types of motion artifacts reported in the literature and the techniques
that have been proposed to avoid them. The main purpose of that chapter is to
review and discuss the techniques proposed over the past two decades to correct for 1 Introduction and Summary 3
Figure 1.1. Example of creation and reduction of patient motion artifacts in
cerebral DSA imaging. Top left: a \pre-bolus" or mask image acquired just prior
to the arrival of the contrast medium. Top right: one of the contrast or live images
showing opacied vessels. Bottom left: DSA image obtained after subtraction of
the mask from the contrast image, followed by contrast enhancement. Due to patient
motion, the background structures in the mask and contrast image were not perfectly
aligned, as a result of which the DSA image does not only show blood vessels, but
also additional undesired structures (in this example primarily in the bottom-left
part of the image). Bottom right: DSA image resulting from subtraction of the
mask and contast image after application of the automatic registration algorithm
described in Chapter 3. 4 1 Introduction and Summary
patient motion artifacts retrospectively, by means of digital image processing. The
chapter addresses fundamental problems, such as whether it is possible to construct
a 2D geometrical transformation that exactly describes the projective eects of an
originally 3D transformation, as well as practical problems, such as how to retrieve
the correspondence between mask and contrast images by using only the grey-level
information contained in the images, and how to align the images according to that
correspondence in a computationally ecient manner.
The review in Chapter 2 reveals that there exists quite some literature on the
topic of (semi-)automatic image alignment, or image registration, for the purpose of
motion artifact reduction in DSA images. However, to the best of our knowledge,
research in this area has never led to algorithms which are suciently fast and robust
to be acceptable for routine use in clinical practice. By drawing upon the suggestions
put forward in Chapter 2, a new approach to automatic registration of digital X-ray
angiography images is presented in Chapter 3. Apart from describing the functionality
of the components of the algorithm, special attention is paid to their computationally
optimal implementation. The results of preliminary experiments described in that
chapter indicate that the algorithm is eective, very fast, and outperforms alterna-
tive approaches, in terms of both image quality and required computation time. It is
concluded that the algorithm is most eective in cerebral and peripheral DSA imag-
ing. An example of the image quality enhancement obtained after application of the
algorithm in the case of a cerebral DSA image is provided in Fig 1.1.
Chapter 4 reports on a clinical evaluation of the automatic registration technique.
The evaluation involved 104 cerebral DSA images, which were corrected for patient
motion artifacts by the automatic technique, as well as by pixel shifting | a manual
correction technique currently used in clinical practice. The quality of the DSA images
resulting from the two techniques was assessed by four observers, who compared the
images both mutually and to the corresponding original images. The results of the
evaluation presented in Chapter 4 indicate that the dierence in performance between
the two correction techniques is statistically signicant. From the results of the mutual
comparisons it is concluded that, on average, the automatic registration technique
performs either comparably, better than, or even much better than manual pixel
shifting in 95% of all cases. In the other 5% of the cases, the remaining artifacts are
located near the borders of the image, which are generally diagnostically non-relevant.
In addition, the results show that the automatic technique implies a considerable
reduction of post-processing time compared to manual pixel shifting (on average, one
second versus 12 seconds per DSA image).
The last two chapters deal with somewhat dierent topics. Chapter 5 is concerned
with visualization and quantication of vascular anomalies in three-dimensional rota-
tional angiography (3DRA). Similar to DSA imaging, 3DRA involves the acquisition
of a sequence of 2D digital X-ray projection images, following a single injection of
contrast material. Contrary to DSA, however, this sequence is acquired during a 180
rotation of the C-arch on which the X-ray source and detector are mounted antipo-
dally, with the object of interest positioned in its iso-center. The rotation is completed
in about eight seconds and the resulting image sequence typically contains 100 images,
which form the input to a ltered back-projection algorithm for 3D reconstruction. In
contrast with most other 3D medical imaging techniques, 3DRA is capable of provid- 1 Introduction and Summary 5
Figure 1.2. Visualizations of a clinical 3DRA dataset, illustrating the qualitative
improvement obtained after noise reduction ltering. Left: volume rendering of
the original, raw image. Right: volume rendering of the image after application
of edge-enhancing anisotropic diusion ltering (see Chapter 5 for a description of
this technique). The visualizations were obtained by using the exact same settings
for the parameters of the volume rendering algorithm.
ing high-resolution isotropic datasets. However, due to the relatively high noise level
and the presence of other unwanted background variations caused by surrounding
tissue, the use of noise reduction techniques is inevitable in order to obtain smooth
visualizations of these datasets (see Fig. 1.2). Chapter 5 presents an inquiry into the
eects of several linear and nonlinear noise reduction techniques on the visualization
and subsequent quantication of vascular anomalies in 3DRA images. The evalua-
tion is focussed on frequently occurring anomalies such as a narrowing (or stenosis)
of the internal carotid artery or a circumscribed dilation (or aneurysm) of intracra-
nial arteries. Experiments on anthropomorphic vascular phantoms indicate that, of
the techniques considered, edge-enhancing anisotropic diusion ltering is most suit-
able, although the practical use of this technique may currently be limited due to its
memory and computation-time requirements.
Finally, Chapter 6 addresses the problem of interpolation of sampled data, which
occurs e.g. when applying geometrical transformations to digital medical images for
the purpose of registration or visualization. In most practical situations, interpola-
tion of a sampled image followed by resampling of the resulting continuous image
on a geometrically transformed grid, inevitably implies loss of grey-level information,
and hence image degradation, the amount of which is dependent on image content,
but also on the employed interpolation scheme (see Fig. 1.3). It follows that the
choice for a particular interpolation scheme is important, since it in uences the re-
sults of registrations and visualizations, and the outcome of subsequent quantitative
analyses which rely on grey-level information contained in transformed images. Al-
though many interpolation techniques have been developed over the past decades, 6 1 Introduction and Summary
Figure 1.3. Illustration of the fact that the loss of information due to interpola-
tion and resampling operations is dependent on the employed interpolation scheme.
Left: slice of a 3DRA image after rotation over 5:0, by using linear interpolation.
Middle: the same slice, after rotation by using cubic spline interpolation. Right:
the dierence between the two rotated images. Although it is not possible with
such a comparison to come to conclusions as to which of the two methods yields
the smallest loss of grey-level information, this example clearly illustrates the point
that dierent interpolation methods usually yield dierent results.
thorough quantitative evaluations and comparisons of these techniques for medical
image transformation problems are still lacking. Chapter 6 presents such a compar-
ative evaluation. The study is limited to convolution-based interpolation techniques,
as these are most frequently used for registration and visualization of medical image
data. Because of the ubiquitousness of interpolation in medical image processing and
analysis, the study is not restricted to XRA and 3DRA images, but also includes
datasets from many other modalities. It is concluded that for all modalities, spline
interpolation constitutes the best trade-o between accuracy and computational cost,
and therefore is to be preferred over all other methods.
In summary, this thesis is concerned with the improvement of image quality and the
reduction of image quality degradation and loss of quantitative information. The
subsequent chapters describe techniques for reduction of patient motion artifacts in
DSA images, noise reduction techniques for improved visualization and quantication
of vascular anomalies in 3DRA images, and interpolation techniques for the purpose
of accurate geometrical transformation of medical image data. The results and con-
clusions of the evaluations described in this thesis provide general guidelines for the
applicability and practical use of these techniques
Sensors for Vital Signs Monitoring
Sensor technology for monitoring vital signs is an important topic for various service applications, such as entertainment and personalization platforms and Internet of Things (IoT) systems, as well as traditional medical purposes, such as disease indication judgments and predictions. Vital signs for monitoring include respiration and heart rates, body temperature, blood pressure, oxygen saturation, electrocardiogram, blood glucose concentration, brain waves, etc. Gait and walking length can also be regarded as vital signs because they can indirectly indicate human activity and status. Sensing technologies include contact sensors such as electrocardiogram (ECG), electroencephalogram (EEG), photoplethysmogram (PPG), non-contact sensors such as ballistocardiography (BCG), and invasive/non-invasive sensors for diagnoses of variations in blood characteristics or body fluids. Radar, vision, and infrared sensors can also be useful technologies for detecting vital signs from the movement of humans or organs. Signal processing, extraction, and analysis techniques are important in industrial applications along with hardware implementation techniques. Battery management and wireless power transmission technologies, the design and optimization of low-power circuits, and systems for continuous monitoring and data collection/transmission should also be considered with sensor technologies. In addition, machine-learning-based diagnostic technology can be used for extracting meaningful information from continuous monitoring data
Intraoperative Photoacoustic Imaging of Breast Cancer
Breast cancer is one of the most common cancers to affect women, presenting a lifetime risk of 1 in 8. Treatment of stage 1 and 2 cancers usually involves breast conserving surgery (BCS). The goal of BCS is to remove the entire tumour with a surrounding envelope of healthy tissue, referred to as a negative margin. Unfortunately, up to 50% of surgeries fail to remove the whole tumour. To minimize the risk of cancer recurrence, a second surgery, must therefore be performed. Currently, there is no widely accepted intraoperative tool to significantly mitigate this problem. Employed systems are usually based on imaging, such as x-ray or ultrasonography. Unfortunately, sensitivity and specificity deficits, especially related to breast density, reduce the effectiveness of these methods. Photoacoustic tomography (PAT) is a relatively new imaging modality which uses safe near-infrared laser illumination to generate 3-D images of soft tissues to a depth of up to several cm. We used a custom designed and built intraoperative PAT system, called iPAT, to perform a 100 patient study on freshly excised breast lumpectomy specimens within the surgical setting. The system enabled the evaluation of tumour extent, shape, morphology and position within lumpectomy specimens measuring up to 11 cm in diameter. Scan results were used to compare iPAT-derived tumour size to the gold-standard pathologic examination, and when available, to x-ray, ultrasonography and DCE-MRI. Imaging results were also used to classify specimen margins as close or wide, and positive predictive values (PPV), negative predictive values (NPV), sensitivity and specificity were then calculated to estimate the effectiveness of the iPAT system at predicting lumpectomy margin status. With a close margin prevalence of 35%, the PPV, NPV, sensitivity and specificity of iPAT were found to be 71%, 83%, 69%, and 84%, respectively. Information provided by the iPAT system identified 9 out of the 12 positive specimens, potentially reducing the positive margin rate by 75%. . Contrary to expected photoacoustic contrast mechanisms, iPAT images of hemoglobin distribution correlated poorly with US and X-ray tumour imaging, while hypo-intense regions in lipid-weighted iPAT images were in excellent agreement
Segmentation and Deformable Modelling Techniques for a Virtual Reality Surgical Simulator in Hepatic Oncology
Liver surgical resection is one of the most frequently used curative therapies. However,
resectability is problematic. There is a need for a computer-assisted surgical planning and
simulation system which can accurately and efficiently simulate the liver, vessels and
tumours in actual patients. The present project describes the development of these core
segmentation and deformable modelling techniques.
For precise detection of irregularly shaped areas with indistinct boundaries, the
segmentation incorporated active contours - gradient vector flow (GVF) snakes and level sets.
To improve efficiency, a chessboard distance transform was used to replace part of the GVF
effort. To automatically initialize the liver volume detection process, a rotating template was
introduced to locate the starting slice. For shape maintenance during the segmentation
process, a simplified object shape learning step was introduced to avoid occasional
significant errors. Skeletonization with fuzzy connectedness was used for vessel
segmentation.
To achieve real-time interactivity, the deformation regime of this system was based
on a single-organ mass-spring system (MSS), which introduced an on-the-fly local mesh
refinement to raise the deformation accuracy and the mesh control quality. This method was
now extended to a multiple soft-tissue constraint system, by supplementing it with an
adaptive constraint mesh generation. A mesh quality measure was tailored based on a wide
comparison of classic measures. Adjustable feature and parameter settings were thus
provided, to make tissues of interest distinct from adjacent structures, keeping the mesh
suitable for on-line topological transformation and deformation.
More than 20 actual patient CT and 2 magnetic resonance imaging (MRI) liver
datasets were tested to evaluate the performance of the segmentation method. Instrument
manipulations of probing, grasping, and simple cutting were successfully simulated on
deformable constraint liver tissue models. This project was implemented in conjunction with
the Division of Surgery, Hammersmith Hospital, London; the preliminary reality effect was
judged satisfactory by the consultant hepatic surgeon
A multi-technique hierarchical X-ray phase-based approach for the characterization and quantification of the effects of novel radiotherapies
Cancer is the first or second leading cause of premature deaths worldwide with an overall rapidly growing burden. Standard cancer therapies include surgery, chemotherapy and radiotherapy (RT) and often a combination of the three is applied to improve the probability of tumour control. Standard therapy protocols have been established for many types of cancers and new approaches are under study especially for treating radio-resistant tumours associated to an overall poor prognosis, as for brain and lung cancers. Follow up techniques able to monitor and investigate the effects of therapies are important for surveying the efficacy of conventionally applied treatments and are key for accessing the curing capabilities and the onset of acute and late adverse effects of new therapies.
In this framework, this doctoral Thesis proposes the X-ray Phase Contrast Im-aging - Computed Tomography (XPCI-CT) technique as an imaging-based tool to study and quantify the effects of novel RTs, namely Microbeam and Minibeam Radiation therapy (MRT and MB), and to compare them to the standard Broad Beam (BB) induced effects on brain and lungs. MRT and MB are novel radiotherapies that deliver an array of spatially fractionated X-ray beamlets issued from a synchrotron radiation source, with widths of tens or hundreds of micrometres, respectively. MRT and MB exploit the so-called dose-volume effect: hundreds of Grays are well tolerated by healthy tissues and show a preferential effect on tumour cells and vasculature when delivered in a micrometric sized micro-plane, while induce lethal effects if applied over larger uniform irradiation fields. Such highly collimated X-ray beams need a high-resolution and a full-organ approach that can visualize, with high sensitivity, the effects of the treatment along and outside the beamlets path. XPCI-CT is here suggested and proven as a powerful imaging technique able to determine and quantify the effects of the radiation on normal and tumour-bearing tissues. Moreover, it is shown as an effective technique to complement, with 3D information, the histology findings in the follow-up of the RT treatments.
Using a multi-scale and multi-technique X-ray-based approach, I have visualized and analysed the effects of RT delivery on healthy and glioblastoma multiforme (GBM)-bearing rat brains as well as on healthy rat lungs. Ex-vivo XPCI-CT datasets acquired with isotropic voxel sizes in the range 3.253 – 0.653 μm3 could distinguish, with high sensitivity, the idiopathic effects of MRT, MB and BB therapies. Histology, immunohistochemistry, Small- and Wide-Angle X-ray Scattering and X-ray Fluorescence experiments were also carried out to accurately interpret and complement the XPCI-CT findings as well as to obtain a detailed structural and chemical characterization of the detected pathological features. Overall, this multi-technique approach could detect: i) a different radio-sensitivity for the MRT-treated brain areas; ii) Ca and Fe deposits, hydroxyapatite crystals formation; iii) extended and isolated fibrotic contents. Full-organ XPCI-CT datasets allowed for the quantification of tumour and mi-crocalcifications’ volumes in treated brains and the amount of scarring tissue in irradiated lungs.
Herein, the role of XPCI-CT as a 3D virtual histology technique for the follow-up of ex-vivo RT effects has been assessed as a complementary method for an accurate volumetric investigation of normal and pathological states in brains and lungs, in a small animal model. Moreover, the technique is proposed as a guidance and auxiliary tool for conventional histology, which is the gold standard for pathological evaluations, owing to its 3D capabilities and the possibility of virtually navigating within samples. This puts a landmark for XPCI-CT inclusion in the pre-clinical studies pipeline and for advancing towards in-vivo XPCI-CT imaging of treated organs.Weltweit gilt Krebs als häufigste bzw. zweithäufigste Ursache eines zu früh erfolgenden Todes, wobei die Zahlen rasch ansteigen. Standardmäßige Krebstherapien umfassen chirurgische Eingriffe, Chemotherapie und Strahlentherapie (radiotherapy, RT); oft kommt eine Kombination daraus zur Anwendung, um die Wahrscheinlichkeit der Tumorkontrolle zu erhöhen. Es wurden Standardtherapieprotokolle für zahlreiche Krebsarten eingerichtet und es wird vor allem in der Behandlung von strahlenresistenten Tumoren mit allgemein schlechter Prognose wie bei Hirn- und Lungentumoren an neuen Ansätzen geforscht. Nachverfolgungstechniken, welche die Auswirkungen von Therapien überwachen und ermitteln, sind zur Überwachung der Wirksamkeit herkömmlich angewandter Behandlungen wichtig und auch maßgeblich am Zugang zu den Fähigkeiten zur Heilung sowie zum Auftreten akuter und verzögerter Nebenwirkungen neuer Therapien beteiligt.
In diesem Rahmenwerk unterbreitet diese Doktorarbeit die Technik der Röntgen-Phasenkontrast-Bildgebung über Computertomographie (X-ray Phase Contrast Imaging - Computed Tomography, XPCI‑CT) als bildverarbeitungs-basiertes Tool zur Untersuchung und Quantifizierung der Auswirkungen neuartiger Strahlentherapien, nämlich der Mikrobeam- und Minibeam-Strahlentherapie (MRT und MB), sowie zum Vergleich derselben mit den herkömmlichen durch Breitstrahlen (Broad Beam, BB) erzielten Auswirkungen auf Gehirn und Lunge. MRT und MB sind neuartige Strahlentherapien, die ein Array räumlich aufgeteilter Röntgenstrahlenbeamlets aus einer synchrotronen Strahlenquelle mit einer Breite von Zehnteln bzw. Hundersteln Mikrometern abgeben. MRT und MB nutzen den sogenannten Dosis-Volumen-Effekt: Hunderte Gray werden von gesundem Gewebe gut vertragen und wirken bei der Abgabe in einer Mikroebene im Mikrometerbereich vorrangig auf Tumorzellen und Blutgefäße, während sie bei einer Anwendung über größere gleichförmige Strahlungsfelder letale Auswirkungen aufweisen. Solche hoch kollimierten Röntgenstrahlen erfordern eine hohe Auflösung und einen Zugang zum gesamten Organ, bei dem die Auswirkungen der Behandlung entlang und außerhalb der Beamletpfade mit hoher Empfindlichkeit visualisiert werden können. Hier empfiehlt und bewährt sich die XPCI‑CT als leistungsstarke Bildverarbeitungstechnik, welche die Auswirkungen der Strahlung auf normale und tumortragende Gewebe feststellen und quantifizieren kann. Außerdem hat sich gezeigt, dass sie durch 3‑D-Informationen eine effektive Technik zur Ergänzung der histologischen Erkenntnisse in der Nachverfolgung der Strahlenbehandlung ist.
Anhand eines mehrstufigen und multitechnischen röntgenbasierten Ansatzes habe ich die Auswirkungen der Strahlentherapie auf gesunde und von Glioblastomen (GBM) befallene Rattenhirne sowie auf gesunde Rattenlungen visualisiert und analysiert. Mit isotropen Voxelgrößen im Bereich von 3,53 bis 0,653 μm3 erfasste Ex-vivo-XPCI-CT-Datensätze konnten die idiopathischen Auswirkungen der MRT-, MB- und BB‑Behandlung mit hoher Empfindlichkeit unterscheiden. Es wurden auch Experimente zu Histologie, Immunhistochemie, Röntgenklein- und ‑weitwinkelstreuung und Röntgenfluoreszenz durchgeführt, um die XPCI‑CT-Erkenntnisse präzise zu interpretieren und zu ergänzen sowie eine detaillierte strukturelle und chemische Charakterisierung der nachgewiesenen pathologischen Merkmale zu erhalten. Im Allgemeinen wurde durch diesen multitechnischen Ansatz Folgendes ermittelt: i) eine un-terschiedliche Strahlenempfindlichkeit der mit MRT behandelten Gehirnbereiche; ii) Ca- und Fe-Ablagerungen und die Bildung von Hydroxylapatitkristallen; iii) ein ausgedehnter und isolierter Fibrosegehalt. XPCI‑CT-Datensätze des gesamten Organs ermöglichten die Quantifizierung der Volume von Tumoren und Mikroverkalkungen in den behandelten Gehirnen und der Menge des Narbengewebes in bestrahlten Lungen.
Dabei wurde die Rolle der XPCI‑CT als virtuelle 3‑D-Histologietechnik für die Nachverfolgung von Ex-vivo-RT‑Auswirkungen als ergänzende Methode für eine präzise volumetrische Untersuchung des normalen und pathologischen Zustands von Gehirnen und Lungen im Kleintiermodell untersucht. Darüber hinaus wird die Technik aufgrund ihrer 3‑D-Fähigkeiten und der Möglichkeit zur virtuellen Navigation in den Proben als Leitfaden und Hilfstool für die herkömmliche Histologie vorgeschlagen, die der Goldstandard für die pathologische Evaluierung ist. Dies markiert einen Meilenstein für die Übernahme der XPCI‑CT in die Pipeline präklinischer Studien und für den Übergang zur In-vivo-XPCI‑CT von behandelten Organen
Image Registration Workshop Proceedings
Automatic image registration has often been considered as a preliminary step for higher-level processing, such as object recognition or data fusion. But with the unprecedented amounts of data which are being and will continue to be generated by newly developed sensors, the very topic of automatic image registration has become and important research topic. This workshop presents a collection of very high quality work which has been grouped in four main areas: (1) theoretical aspects of image registration; (2) applications to satellite imagery; (3) applications to medical imagery; and (4) image registration for computer vision research
Evaluation of a diffraction-enhanced imaging (DEI) prototype and exploration of novel applications for clinical implementation of DEI
Conventional mammographic image contrast is derived from x-ray absorption, resulting in breast structure visualization due to density gradients that attenuate radiation without distinction between transmitted, scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for increased contrast with decreased radiation dose compared to conventional mammographic imaging due to monochromatic x-rays, its unique refraction-based contrast mechanism, and excellent scatter rejection. Although laboratory breast imaging studies have demonstrated excellent breast imaging, important clinical translation and application studies are needed before the DEI system can be established as a useful breast imaging modality. This dissertation focuses on several important studies toward the development of a clinical DEI system. First, contrast-enhanced DEI was explored using commercially available contrast agents. Phantoms were imaged at a range of x-ray energies and relevant contrast agent concentrations. Second, we performed a reader study to determine if superior DEI contrast mechanisms preserve image quality as tissue thickness increases. Breast specimens were imaged at several thicknesses, and radiologist perception of lesion visibility was recorded. Lastly, a prototype DEI system utilizing an x-ray tube source was evaluated through a reader study. Breast tissue specimens were imaged on the traditional and prototype DEI systems, and expert radiologists evaluated image quality and pathology correlation. This dissertation will demonstrate proof-of-principle for contrast-enhanced DEI, establishing the feasibility of contrast-enhanced DEI using commercially available contrast agents. Further, it will show that DEI might be able to reduce breast compression, and thus the perception of pain during mammography, without significantly decreasing breast lesion visibility. Finally, this research shows the successful implementation of a DEI prototype, displaying breast features with approximately statistically equivalent visibility to the traditional DEI system. Together, this research is an important step toward the clinical translation of DEI, a technology with the potential to facilitate early breast cancer detection and diagnosis
Endoscopic Fluorescence Imaging:Spectral Optimization and in vivo Characterization of Positive Sites by Magnifying Vascular Imaging
Since several decades, the physicians are able to access hollow organs with endoscopic methods, which serve both as diagnostic and surgical means in a wide range of disciplines of the modern medicine (e.g. urology, pneumology, gastroenterology). Unfortunately, white light (WL) endoscopy displays a limited sensitivity to early pre-cancerous lesions. Hence, several endoscopic methods based on fluorescence imaging have been developed to overcome this limitation. Both endogenous and exogenously-induced fluorescence have been investigated, leading to commercial products. Indeed, autofluorescence bronchoscopy, as well as porphyrin-based fluorescence cystoscopy, are now on the market. As a matter of fact, fluorescence-based endoscopic detection methods show very high sensitivity to pre-cancerous lesions, which are often overlooked in WL endoscopy, but they still lack specificity mainly due to the high false-positive rate. Although most of these false positives can easily be rejected under WL observation, tissue abnormalities such as inflammations, hyperplasia, and metaplasia are more difficult to identify, often resulting in supplementary biopsies. Therefore, the purpose of this thesis is to study novel, fast, and convenient method to characterize fluorescence positive spots in situ during fluorescence endoscopy and, more generally, to optimize the existing endoscopic setup. In this thesis, several clinical evaluations were conducted either in the tracheo-bronchial tree and the urinary bladder. In the urinary bladder, fluorescence imaging for detection of non-muscle invasive bladder cancer is based on the selective production and accumulation of fluorescing porphyrins, mainly protoporphyrin IX (PpIX), in cancerous tissues after the instillation of Hexvix® during one hour. In this thesis, we adapted a rigid cystoscope to perform high magnification (HM) cystoscopy in order to discriminate false from true fluorescence positive findings. Both white light and fluorescence modes are possible with the magnification cystoscope, allowing observation of the bladder wall with magnification ranging between 30× – for standard observation – and 650×. The optical zooming setup allows adjusting the magnification continuously in situ. In the high magnification regime, the smallest diameter of the field of view is 600 microns and the resolution is 2.5 microns, when in contact with the bladder wall. With this HM cystoscope, we characterized the superficial vascularization of the fluorescing sites in WL (370–700 nm) reflectance imaging in order to discriminate cancerous from non-cancerous tissues. This procedure allowed us to establish a classification based on observed vascular patterns. 72 patients subject to Hexvix® f luorescence cystoscopy were included in the study. Comparison of HM cystoscopy classification with histopathology results confirmed 32/33 (97%) cancerous biopsies, and rejected 17/20 (85%) non-cancerous lesions. No vascular alteration could be observed on the only positive lesion that was negative in HM mode, probably because this sarcomatoid carcinoma was not originating in the bladder mucosa. We established with this study that a magnification ranging between 80× and 100× is an optimal tradeoff to perform both macroscopic PDD and HM reflectance imaging. In order to make this approach more quantitative, different algorithms of image processing (vessel segmentation and skeletonisation, global information extraction) were also implemented in this thesis. In order to better visualize the vessels, we improved their contrast with respect to the background. Since hemoglobin is a very strong absorber, we targeted the two hemoglobin absorption peaks by placing appropriate bandpass filters (blue 405±50 nm, green 550±50 nm) in the light source. HM cystoscopy was then performed sequentially with WL, blue and green illumination. The two latter showed higher vessel-to-background contrast, identifying different layers of vascularization due to the light penetration depth. During fluorescence cystoscopy, we often observed that the images are somehow "blurred" by a greenish screen between endoscope tip and bladder mucosa. Since this effect is enhanced by the urine production, it is more visible with flexible scopes (lower flushing capabilities) and imaging systems that collect only autofluorescence as background. Indeed, when the bladder is not flushed regularly, greenish flows coming out of the ureters can easily be observed. For this reason, it is supposed that some fluorophores contained in the urine are excited by the photodetection excitation light, and appear greenish on the screen. This effect may impair the visualization of the bladder mucosa, and thus cancerous lesions, and lowers sensitivity of the fluorescence cystoscopy. In this thesis, we identified the main metabolites responsible for the liquid fluorescence, and optimized the spectral design accordingly. In the tracheo-bronchial tree, the fluorescence contrast is based on the sharp autofluorescence (AF) decrease on early cancerous lesions in the green spectral region (around 500 nm) and a relatively less important decrease in the red spectral region (> 600 nm) when excited with blue-violet light (around 410 nm). It has been shown over the last years, that this contrast may be attributed to a combined effect of epithelium thickening and higher concentration of hemoglobin in the tissues underneath the (pre-)cancerous lesions. In this thesis, we contributed to the definition of the input design of several new prototypes, that were subsequently tested in the clinical environment. We first showed that narrow-band excitation in the blue-violet could increase the tumor-to-normal spectral contrast in the green spectral region. Then, we quantified the intra- and inter-patient variations in the AF intensities in order to optimize the spectral response of the endoscopic fluorescence imaging system. For this purpose, we developed an endoscopic reference to be placed close to the bronchial mucosa during bronchoscopy. Finally, we evaluated a novel AF bronchoscope with blue-backscattered light on 144 patients. This new device showed increased sensitivity for pre-neoplastic lesions. Similar to what we observed in the bladder, it is likely that developing new imaging capabilities (including vascular imaging) will facilitate discriminating true from false positive in AF bronchoscopy. Here, we demonstrated that this magnification allowed us to resolve vessels with a diameter of about 30 µm. This resolution is likely to be sufficient to identify Shibuya's vascular criteria (loops, meshes, dotted vessels) on AF positive lesions. This criteria allow him to recognize pre-cancerous lesions, and thus can potentially decrease the false-positive rate with our AF imaging system. This magnification was also showed to be better for routine bronchoscopy, since it delivers sharper and more structured images to the operator