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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.
Purpose: In this trial, we used a previously developed prototype software to assess aesthetic results after reconstructive surgery for congenital breast asymmetry using automated anthropometry. To prove the consensus between the manual and automatic digital measurements, we evaluated the software by comparing the manual and automatic measurements of 46 breasts.
Methods: Twenty-three patients who underwent reconstructive surgery for congenital breast asymmetry at our institution were examined and underwent 3D surface imaging. Per patient, 14 manual and 14 computer-based anthropometric measurements were obtained according to a standardized protocol. Manual and automatic measurements, as well as the previously proposed Symmetry Index (SI), were compared.
Results: The Wilcoxon signed-rank test revealed no significant differences in six of the seven measurements between the automatic and manual assessments. The SI showed robust agreement between the automatic and manual methods.
Conclusion: The present trial validates our method for digital anthropometry. Despite the discrepancy in one measurement, all remaining measurements, including the SI, showed high agreement between the manual and automatic methods. The proposed data bring us one step closer to the long-term goal of establishing robust instruments to evaluate the results of breast surgery.
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.
Virtual training of bone milling requires realtime and realistic haptics of the interaction between the ”virtual mill” and a ”virtual bone”. We propose an exponential abrasion model between a virtual one and the mill bit and combine it with a coarse representation of the virtual bone and the mill shaft for collision detection using the Bullet Physics Engine. We compare our exponential abrasion model to a widely used linear abrasion model and evaluate it quantitatively and qualitatively. The evaluation results show, that we can provide virtual milling in real-time, with an abrasion behavior similar to that proposed in the literature and with a realistic feeling of five different surgeons.
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.
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
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.
Signal transmission between different brain regions requires connecting fiber tracts, the structural basis of the human connectome. In contrast to animal brains, where a multitude of tract tracing methods can be used, magnetic resonance (MR)-based diffusion imaging is presently the only promising approach to study fiber tracts between specific human brain regions. However, this procedure has various inherent restrictions caused by its relatively low spatial resolution. Here, we introduce 3D-polarized light imaging (3D-PLI) to map the three-dimensional course of fiber tracts in the human brain with a resolution at a submillimeter scale based on a voxel size of 100 μm isotropic or less. 3D-PLI demonstrates nerve fibers by utilizing their intrinsic birefringence of myelin sheaths surrounding axons. This optical method enables the demonstration of 3D fiber orientations in serial microtome sections of entire human brains. Examples for the feasibility of this novel approach are given here. 3D-PLI enables the study of brain regions of intense fiber crossing in unprecedented detail, and provides an independent evaluation of fiber tracts derived from diffusion imaging data.
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.