Video-rate optical flow corrected intraoperative functional fluorescence imaging.

Intraoperative fluorescence molecular imaging based on targeted fluorescence agents is an emerging approach to improve surgical and endoscopic imaging and guidance. Short exposure times per frame and implementation at video rates are necessary to provide continuous feedback to the physician and avoid motion artifacts. However, fast imaging implementations also limit the sensitivity of fluorescence detection. To improve on detection sensitivity in video rate fluorescence imaging, we considered herein an optical flow technique applied to texture-rich color images. This allows the effective accumulation of fluorescence signals over longer, virtual exposure times. The proposed correction scheme is shown to improve signal-to-noise ratios both in phantom experiments and in vivo tissue imaging.

Multispectral optoacoustic tomography by means of normalized spectral ratio.

Quantification of biomarkers using multispectral optoacoustic tomography can be challenging due to photon fluence variations with depth and spatially heterogeneous tissue optical properties. Herein we introduce a spectral ratio approach that accounts for photon fluence variations. The performance and imaging improvement achieved with the proposed method is showcased both numerically and experimentally in phantoms and mice.

Reconstruction of fluorescence distribution hidden in biological tissue using mesoscopic epifluorescence tomography.

Mesoscopic epifluorescence tomography is a novel technique that discovers fluorescence bio-distribution in small animals by tomographic means in reflectance geometry. A collimated laser beam is scanned over the skin surface to excite fluorophores hidden within the tissue while a CCD camera acquires an image of the fluorescence emission for each source position. This configuration is highly efficient in the visible spectrum range where trans-illumination imaging of small animals is not feasible due to the high tissue absorption and scattering in biological organisms. The reconstruction algorithm is similar to the one used in fluorescence molecular tomography. However, diffusion theory cannot be employed since the source-detector separation for most image pixels is comparable to or below the scattering length of the tissue. Instead Monte Carlo simulations are utilized to predict the sensitivity functions. In a phantom study we show the effect of using enhanced source grid arrangements during the data acquisition and the reconstruction process to minimize boundary artefacts. Furthermore, we present ex vivo data that show high spatial resolution and quantitative accuracy in heterogeneous tissues using GFP-like fluorescence in B6-albino mice up to a depth of 1100 µm.

Optoacoustic tomography with varying illumination and non-uniform detection patterns.

Quantification of tissue morphology and biomarker distribution by means of optoacoustic tomography is an important and longstanding challenge, mainly caused by the complex heterogeneous structure of biological tissues as well as the lack of accurate and robust reconstruction algorithms. The recently introduced model-based inversion approaches were shown to mitigate some of reconstruction artifacts associated with the commonly used back-projection schemes, while providing an excellent platform for obtaining quantified maps of optical energy deposition in experimental configurations of various complexity. In this work, we introduce a weighted model-based approach, capable of overcoming reconstruction challenges caused by per-projection variations of object's illumination and other partial illumination effects. The universal weighting procedure is equally shown to reduce reconstruction artifacts associated with other experimental imperfections, such as non-uniform transducer sensitivity fields. Significant improvements in image fidelity and quantification are showcased both numerically and experimentally on tissue phantoms and mice.

Fast automatic segmentation of anatomical structures in x-ray computed tomography images to improve fluorescence molecular tomography reconstruction.

The recent development of hybrid imaging scanners that integrate fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) allows the utilization of x-ray information as image priors for improving optical tomography reconstruction. To fully capitalize on this capacity, we consider a framework for the automatic and fast detection of different anatomic structures in murine XCT images. To accurately differentiate between different structures such as bone, lung, and heart, a combination of image processing steps including thresholding, seed growing, and signal detection are found to offer optimal segmentation performance. The algorithm and its utilization in an inverse FMT scheme that uses priors is demonstrated on mouse images.

Functional malcentering of the humeral head and asymmetric long-term stress on the glenoid: potential reasons for glenoid loosening in total shoulder arthroplasty.

We tested the hypothesis that functional malcentering of the humeral head during arm elevation exists in patients with glenohumeral osteoarthritis and influences long-term glenoid loading. Twenty-eight healthy volunteers and 10 patients with primary osteoarthritis, 10 with cuff-arthropathy, and 1 with dysplastic glenoid were examined. Open magnetic resonance imaging and 3-dimensional (3D) digital postprocessing techniques were applied in various arm positions. Osteoabsorptiometry was used to determine 3D subchondral mineralization patterns of the glenoid as an indicator of integral long-term stress distribution. At 30 degrees of abduction, 5 patients demonstrated malcentering of the humeral head posteriorly; all patients with cuff arthropathy had malcentering superiorly. At 90 degrees, most patients displayed significant (P < .001) malcentering in the superior and posterior direction. The shoulders showed maximal subchondral mineralization patterns in the direction of malcentering. Most patients with glenohumeral osteoarthritis displayed functional malcentering, which might be responsible for postoperative glenoid loosening in shoulder arthroplasty if not corrected intraoperatively.

Multimodal virtual bronchoscopy using PET/CT images.

OBJECTIVE: To demonstrate the possibilities, advantages and limitations of virtual bronchoscopy using data sets from positron emission tomography (PET) and computed tomography (CT). MATERIALS AND METHODS: Eight consecutive patients with non-small cell lung cancer (NSCLC) underwent PET/CT. PET was performed with a glucose analog, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG), using a state-of-the-art full-ring Pico-3D PET scanner. CT was performed with a venous-dominant contrast-enhanced phase using a 16-slice CT scanner. The tracheobronchial system was segmented using the CT data set with an interactive threshold interval volume-growing segmentation algorithm. The primary tumors and lymph node metastases were segmented for virtual CT-bronchoscopy using the CT data set and for virtual hybrid bronchoscopy using the PET/CT data set. The structures of interest were visualized with a color-coded shaded-surface rendering method. RESULTS: The use of CT and virtual CT-bronchoscopy primarily facilitates visualization of the anatomical details of the tracheobronchial system and detection of anatomical/morphologic structural changes caused by disease. PET/CT and virtual hybrid bronchoscopy, or virtual PET/CT-bronchoscopy, give superior results to virtual CT-bronchoscopy because the hybrid bronchoscopy uses both the CT information and the molecular/metabolic information about the disease obtained from PET. CONCLUSIONS: PET/CT imaging has proven to be a highly valuable oncological diagnostic modality. Virtual hybrid bronchoscopy can be performed using a low-dose CT scan or diagnostic CT. However, it is expected to improve diagnostic accuracy in identification and characterization of malignancies, verification of infections, and differentiation of viable tumor tissue from atelectases and scar tissue, as well as assessment of tumor staging and therapeutic response, and detection of early stage recurrences that are not detectable or are liable to be misjudged using virtual CT-bronchoscopy. It could also be useful as a screening examination method for patients with suspected endobronchial malignancy. Virtual hybrid bronchoscopy with a transparent color-coded shaded-surface rendering model offers a useful alternative to fiberoptic bronchoscopy, and is particularly promising for patients for whom fiberoptic bronchoscopy is not feasible, contraindicated or refused.

Virtual positron emission tomography/computed tomography-bronchoscopy: possibilities, advantages and limitations of clinical application.

The aim of this study was to demonstrate the possibilities, advantages and limitations of virtual bronchoscopy using data sets from positron emission tomography (PET) and computed tomography (CT). Twelve consecutive patients with lung cancer underwent PET/CT. PET was performed with F-18-labelled 2-[fluorine-18]-fluoro-2-deoxy-D: -glucose ((18)F-FDG). The tracheobronchial system was segmented with a volume-growing algorithm, using the CT data sets, and visualized with a shaded-surface rendering method. The primary tumours and the lymph node metastases were segmented for virtual CT-bronchoscopy using the CT data set and for virtual PET/CT-bronchoscopy using the PET/CT data set. Virtual CT-bronchoscopy using the low-dose or diagnostic CT facilitates the detection of anatomical/morphological structure changes of the tracheobronchial system. Virtual PET/CT-bronchoscopy was superior to virtual CT-bronchoscopy in the detection of lymph node metastases (P=0.001), because it uses the CT information and the molecular/metabolic information from PET. Virtual PET/CT-bronchoscopy with a transparent colour-coded shaded-surface rendering model is expected to improve the diagnostic accuracy of identification and characterization of malignancies, assessment of tumour staging, differentiation of viable tumour tissue from atelectases and scars, verification of infections, evaluation of therapeutic response and detection of an early stage of recurrence that is not detectable or is misjudged in comparison with virtual CT-bronchoscopy.

Systematic, standardized and comprehensive neurological phenotyping of inbred mice strains in the German Mouse Clinic.

Neurological and psychiatric disorders are among the most common and most serious health problems in developed countries. Transgenic mouse models mimicking human neurological diseases have provided new insights into development and function of the nervous system. One of the prominent goals of the German National Genome Research Network is the understanding of the in vivo function of single genes and the pathophysiological and clinical consequences of respective mutations. The German Mouse Clinic (GMC) offers a high-throughput primary screen of genetically modified mouse models as well as an in-depth analysis in secondary and tertiary screens covering various fields of mouse physiology. Here we describe the phenotyping methods of the Neurological Screen in the GMC, exemplified in the four inbred mouse lines C57BL/6J, C3HeB/FeJ, BALB/cByJ, and 129S2/SvPas. For our primary screen, we generated "standard operating procedures" that were validated between different laboratories. The phenotyping of inbred strains already showed significant differences in various parameters, thus being a prerequisite for the examination of mutant mouse lines.

Early detection of diabetes retinopathy by new algorithms for automatic recognition of vascular changes.

Diabetes mellitus often results in diabetic retinopathy caused by pathological changes of the retinal vessel tree. Early detection of these changes can delay the disease. Image processing can reduce the workload of screeners and can play a central role in quality assurance tasks. Therefore we aimed at the refinement and development of image processing algorithms to improve the quality and cost effectiveness of screening and diagnosis of diabetic retinopathy. In order to support ophthalmologists in their routine and to enable the quantitative assessment of vascular changes in colour fundus photographs a multi-resolution approach was developed which segments the vessel tree efficiently and precisely into digital images of the retina. The vessel tracker aims at determining as correctly as possible the retinal vascular network captured on a digital image irrespective of its origin. In addition to the tracker, algorithms were developed to detect the optic disk, bright lesions such as cotton wools spots, and dark lesions such as haemorrhages. The following classification of veins and arteries identifies arteries in 78.4 % and veins in 66.5% correctly. This helps selecting conspicuous images from a great number of patients.

TOSCA-Imaging--developing Internet based image processing software for screening and diagnosis of diabetic retinopathy.

The primary aim of TOSCA-Imaging, which was a part of the TOSCA Project financed by EU's Fifth Framework IST Programme, was to develop Internet based software and image data bases for screening and diagnosis of diabetic retinopathy and implementing it into a real life situation. The work consisted of: 1) Construction of an Internet based communication platform for transmitting and analyzing retinal images. 2) Implementation of routines for detecting the first microaneurysm (transition from normal to pathologic), detecting patients needing referral for treatment (presence of venous beading or hard exudates near the fovea), and for serial analysis (image alignment). 3) Construction of a reference image data base. A preliminary validation showed that decisions that depended on a precise detection of individual lesions, e.g. the detection of normality, had a sensitivity and specificity of around 80%, whereas decisions that depended on the detection of lesion patterns, e.g. clinically significant macular oedema, had a sensitivity and specificity of more than 95%. Validation of the reference image data base by double grading by two expert graders suggested a sensitivity and a specificity of just below 90% for any lesion and of more than 95% for predicting the overall retinopathy grade. TOSCA-Imaging has succeeded in its primary aim of developing Internet based software and implementing it into a real life situation, integrating work within image processing done in four different European countries (England, Germany, Ireland, and Denmark) to be accessed from one Internet web site.

Quantitative assessment of cartilage status in osteoarthritis by quantitative magnetic resonance imaging: technical validation for use in analysis of cartilage volume and further morphologic parameters.

OBJECTIVE: Quantitative diagnostic tools for osteoarthritis (OA) are important for evaluating the treatment response to structure-modifying drugs. This study was undertaken to test the technical validity (accuracy) of quantitative magnetic resonance imaging (qMRI) for reliable determination of the total bone interface area, percentage of cartilaginous (denuded) joint surface area, and cartilage thickness in OA. METHODS: High-resolution MRIs of femorotibial and patellar cartilage were acquired in 21 patients prior to total knee arthroplasty, using a T1-weighted gradient-echo sequence with water excitation. After segmentation of original bone interface areas (before disease onset) and the actual cartilage layer, the percentages of cartilaginous joint surface area, cartilage thickness, and cartilage volume were determined using proprietary software. During surgery, the patella and the medial and lateral tibia were resected. Results obtained with qMRI were compared with those obtained by direct image analysis of surface area, cartilage thickness, and cartilage volume of the surgically removed tissue. RESULTS: Pairwise differences between results obtained with qMRI and morphologic analysis were +/-4.6% for percentage of cartilaginous surface area, +/-8.9% for cartilage thickness, and +/-9.1% for cartilage volume. Correlation coefficients ranged from 0.92 (thickness) to 0.98 (volume). CONCLUSION: Quantitative MRI permits technically accurate and differential assessment of increases in eroded joint surface area and reductions in cartilage thickness in OA. The surrogate validity of these parameters requires testing in longitudinal studies. These parameters may be advantageous over determination of cartilage volume alone when diagnosing OA, exploring its progression, or testing responsiveness to new therapies.

Femoro-tibial cartilage metrics from coronal MR image data: Technique, test-retest reproducibility, and findings in osteoarthritis.

MRI-based measures of cartilage morphology are being increasingly used as surrogate markers in osteoarthritis. In contrast to other knee joint surfaces, quantitative analysis of the femoral condyles from sagittal MRI suffers from limited precision. The objective, therefore, was to develop a technique for reproducible assessment of femoral cartilage morphology from coronal image data. Coronal MR images (3D T(1)-w FLASHwe) of the knee were obtained in 16 healthy volunteers and in 7 patients with severe osteoarthritis (OA, prior to knee arthroplasty), with repositioning between repeated scans. After segmentation the cartilage volume, thickness, and joint surface areas were quantified in the tibia and in an anatomically defined region of the femoral condyle. Immediate test-retest interscan precision errors (CV%) for femoral cartilage volume were 3.0% (SD = 26 microl) and 3.2% (29 microl) medially and laterally in volunteers, and 3.0% (34 microl) and 7.0% (37 microl) in OA patients. The estimated loss, from cross sectional data, in the patients in the medial femoral condyle (-61%/-4.4 SD) was higher than that in the medial tibia (-45%/-3.1 SD) and compared favorably with precision errors (ratio > 16:1). The technique proposed overcomes some of the problems associated with sagittal scans and thus shows high promise for reliable assessment of femoro-tibial cartilage loss in OA.

Correlation of knee-joint cartilage morphology with muscle cross-sectional areas vs. anthropometric variables.

We tested the hypothesis that muscle cross-sectional areas (MCSAs) are more highly (and independently) correlated with cartilage morphology than are body height and weight, and that the physiological reduction of cartilage thickness with aging is associated with a proportional, age-dependent decrease in MCSAs. In 59 asymptomatic individuals (23-75 years old), morphological parameters of the knee cartilages (volume, thickness, and bone-cartilage interface area), and MCSAs were determined from magnetic resonance imaging (MRI) data. Multiple regression models were used to calculate which proportion of the variability of the normal cartilage morphology can be predicted based on independent variables. MCSAs and body height and weight showed correlation coefficients of +0.66, +0.60, and +0.25, respectively, with knee-joint cartilage volume. The correlation coefficients with cartilage thickness were +0.44, +0.35, and +0.24, respectively. Age accounted for a significant (P<0.01) reduction in cartilage thickness, but there was no proportional change of MCSAs. Approximately 76% of the variability of the knee cartilage volume could be predicted from independent variables in a multiple regression model with MCSAs contributing significant, independent information. In conclusion, we find that MCSAs are more highly correlated with cartilage morphology than are body height and weight. The significant decrease in cartilage volume and thickness with age is not associated with a proportional decrease in MCSAs.

Relevance of arm position and muscle activity on three-dimensional glenohumeral translation in patients with traumatic and atraumatic shoulder instability.

BACKGROUND: No quantitative data on glenohumeral translation exist allowing one to distinguish insufficiency of the active or passive stabilizers in different forms of shoulder instability. HYPOTHESIS: To determine whether 1) in traumatic or atraumatic shoulder instability an increase of glenohumeral translation can be observed in specific relevant arm positions, 2) muscle activity leads to recentering of the humeral head, and 3) there exist differences between traumatic and atraumatic instability. STUDY DESIGN: Prospective clinical trial. METHODS: In 12 patients with traumatic and 10 patients with atraumatic instability, both shoulders were examined in different arm positions-with and without muscle activity-by using open magnetic resonance imaging and a three-dimensional postprocessing technique. RESULTS: At 90 degrees of abduction and external rotation, translation (anterior-inferior) was significantly higher in patients with traumatic unstable shoulders compared with their contralateral side (3.6 +/- 1.5 versus 0.7 +/- 1.6 mm). In patients with atraumatic instability, significantly increased translation (4.7 +/- 2.0 mm) was observed, with the direction being nonuniform. Muscle activity led to significant recentering in traumatic but not in atraumatic instability. CONCLUSIONS: In traumatic instability, increased translation was observed only in functionally important arm positions, whereas intact active stabilizers demonstrate sufficient recentering. In atraumatic instability, a decentralized head position was recorded also during muscle activity, suggesting alterations of the active stabilizers. CLINICAL RELEVANCE: These data are relevant for optimizing diagnostics and therapeutic strategies.

Three-dimensional analysis and visualization of regional MR signal intensity distribution of articular cartilage.

The aim of this study was to develop a technique for analyzing and visualizing the regional, three-dimensional signal intensity distribution of articular cartilage in MR images, as a potential surrogate marker of structural or biochemical alterations in early osteoarthritis. Exemplary MR-images of human patellae were acquired at a resolution of 1.5 x 0.31 x 0.31 mm(3), using a gradient-echo sequence with water excitation, and by combining three data sets to secondary images of proton density. After segmentation of the cartilage outlines, these were transferred to the other images. Contiguous slices were automatically divided into sub-regions that extend from the surface to the bone interface (layers) as well as from medial to lateral (sections). The signal intensity was then calculated and projected onto a three-dimensional representation of the articular surface, either by averaging through the depth (sections) or by visualizing the signal intensity at distinct levels in depth (layers). The exemplary data indicate that the reproducibility for regional analyses is in the same range as for the entire patellar cartilage, and that the distribution patterns of proton density delineated with MRI are in agreement with the literature. In conjunction with suitable MR protocols, this post-processing technique has potential to allow for detection and quantification of early degenerative processes in cartilage, before macro-morphological lesions occur.

Surface size, curvature analysis, and assessment of knee joint incongruity with MRI in vivo.

The purpose of this study was to develop an MR-based technique for quantitative analysis of joint surface size, surface curvature, and joint incongruity and to assess its reproducibility under in vivo imaging conditions. The surface areas were determined after 3D reconstruction of the joint by triangulation and the incongruity by Gaussian curvature analysis. The precision was tested by analyzing four replicated MRI datasets of human knees in 14 individuals. The algorithms were shown to produce accurate data in geometric test objects. The interscan precision was <4% (CV%) for surface area, 2.9-5.7 m(-1) (SD) for the mean principal curvature, and 4.1-7.4 m(-1) for congruence indices. Incongruity was highest in the femoropatellar joint (79.7 m(-1)) and lowest in the medial femorotibial joint (28.6 m(-1)). This technique will permit identification of the specific role of surface size, curvature, and incongruity as potential risk factors for osteoarthritis.

Quantitative cartilage imaging of the human hind foot: precision and inter-subject variability.

Alterations of ankle cartilage are observed in degenerative and inflammatory joint disease, but cartilage cannot be directly visualized by radiography. The purpose of this study was therefore to analyze the feasibility and precision of quantitative cartilage imaging in the human hind foot (talocrural, talotarsal, and intertarsal joints), and to report the inter-subject variability for cartilage volume, thickness and surface areas. The feet of 16 healthy volunteers were imaged using a 3D gradient-echo magnetic resonance imaging sequence with water-excitation. After interpolation to a resolution of 1 x 0.125 x 0.125 mm3 the cartilage plates were segmented, and the cartilage volume, thickness, and surface areas determined. The precision (four repeated measurements) was examined in eight volunteers, the RMS average CV% being 2.1% to 10.9% in single joint surfaces, and < or = 3% for the cumulative values of all joints. The mean cartilage thickness ranged from 0.57+/-0.08 (navicular surface) to 0.89+/-0.19 mm (trochlear surface for tibia). In conclusion this study shows that it is feasible to quantify thin cartilage layers in the hind foot under in vivo imaging conditions, and that the precision errors are substantially smaller than the inter-subject variability in healthy subjects.