Optimized temperature and deadspace correction improve analysis of multiple breath washout measurements by ultrasonic flowmeter in infants

BACKGROUND: Assessment of lung volume (FRC) and ventilation inhomogeneities with ultrasonic flowmeter and multiple breath washout (MBW) has been used to provide important information about lung disease in infants. Sub-optimal adjustment of the mainstream molar mass (MM) signal for temperature and external deadspace may lead to analysis errors in infants with critically small tidal volume changes during breathing. METHODS: We measured expiratory temperature in human infants at 5 weeks of age and examined the influence of temperature and deadspace changes on FRC results with computer simulation modeling. A new analysis method with optimized temperature and deadspace settings was then derived, tested for robustness to analysis errors and compared with the previously used analysis methods. RESULTS: Temperature in the facemask was higher and variations of deadspace volumes larger than previously assumed. Both showed considerable impact upon FRC and LCI results with high variability when obtained with the previously used analysis model. Using the measured temperature we optimized model parameters and tested a newly derived analysis method, which was found to be more robust to variations in deadspace. Comparison between both analysis methods showed systematic differences and a wide scatter. CONCLUSION: Corrected deadspace and more realistic temperature assumptions improved the stability of the analysis of MM measurements obtained by ultrasonic flowmeter in infants. This new analysis method using the only currently available commercial ultrasonic flowmeter in infants may help to improve stability of the analysis and further facilitate assessment of lung volume and ventilation inhomogeneities in infants.

Cerebral correlates of muscle tone fluctuations in restless legs syndrome: A pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography

BACKGROUND: The pathology of restless legs syndrome (RLS) is still not understood. To investigate the pathomechanism of the disorder further we recorded a surface electromyogram (EMG) of the anterior tibial muscle during functional magnetic resonance imaging (fMRI) in patients with idiopathic RLS. METHODS: Seven subjects with moderate to severe RLS were investigated in the present pilot study. Patients were lying supine in the scanner for over 50min and were instructed not to move voluntarily. Sensory leg discomfort (SLD) was evaluated on a 10-point Likert scale. For brain image analysis, an algorithm for the calculation of tonic EMG values was developed. RESULTS: We found a negative correlation of tonic EMG and SLD (p <0.01). This finding provides evidence for the clinical experience that RLS-related subjective leg discomfort increases during muscle relaxation at rest. In the fMRI analysis, the tonic EMG was associated with activation in motor and somatosensory pathways and also in some regions that are not primarily related to motor or somatosensory functions. CONCLUSIONS: By using a newly developed algorithm for the investigation of muscle tone-related changes in cerebral activity, we identified structures that are potentially involved in RLS pathology. Our method, with some modification, may also be suitable for the investigation of phasic muscle activity that occurs during periodic leg movements.

A novel 2D-based approach to the discovery of candidate substrates for the metalloendopeptidase meprin

In the past, protease-substrate finding proved to be rather haphazard and was executed by in vitro cleavage assays using singly selected targets. In the present study, we report the first protease proteomic approach applied to meprin, an astacin-like metalloendopeptidase, to determine physiological substrates in a cell-based system of Madin-Darby canine kidney epithelial cells. A simple 2D IEF/SDS/PAGE-based image analysis procedure was designed to find candidate substrates in conditioned media of Madin-Darby canine kidney cells expressing meprin in zymogen or in active form. The method enabled the discovery of hitherto unknown meprin substrates with shortened (non-trypsin-generated) N- and C-terminally truncated cleavage products in peptide fragments upon LC-MS/MS analysis. Of 22 (17 nonredundant) candidate substrates identified, the proteolytic processing of vinculin, lysyl oxidase, collagen type V and annexin A1 was analysed by means of immunoblotting validation experiments. The classification of substrates into functional groups may propose new functions for meprins in the regulation of cell homeostasis and the extracellular environment, and in innate immunity, respectively.

Risk analysis of light-frame wood construction due to multiple hazards

Light-frame wood buildings are widely built in the United States (U.S.). Natural hazards cause huge losses to light-frame wood construction. This study proposes methodologies and a framework to evaluate the performance and risk of light-frame wood construction. Performance-based engineering (PBE) aims to ensure that a building achieves the desired performance objectives when subjected to hazard loads. In this study, the collapse risk of a typical one-story light-frame wood building is determined using the Incremental Dynamic Analysis method. The collapse risks of buildings at four sites in the Eastern, Western, and Central regions of U.S. are evaluated. Various sources of uncertainties are considered in the collapse risk assessment so that the influence of uncertainties on the collapse risk of lightframe wood construction is evaluated. The collapse risks of the same building subjected to maximum considered earthquakes at different seismic zones are found to be non-uniform. In certain areas in the U.S., the snow accumulation is significant and causes huge economic losses and threatens life safety. Limited study has been performed to investigate the snow hazard when combined with a seismic hazard. A Filtered Poisson Process (FPP) model is developed in this study, overcoming the shortcomings of the typically used Bernoulli model. The FPP model is validated by comparing the simulation results to weather records obtained from the National Climatic Data Center. The FPP model is applied in the proposed framework to assess the risk of a light-frame wood building subjected to combined snow and earthquake loads. The snow accumulation has a significant influence on the seismic losses of the building. The Bernoulli snow model underestimates the seismic loss of buildings in areas with snow accumulation. An object-oriented framework is proposed in this study to performrisk assessment for lightframe wood construction. For home owners and stake holders, risks in terms of economic losses is much easier to understand than engineering parameters (e.g., inter story drift). The proposed framework is used in two applications. One is to assess the loss of the building subjected to mainshock-aftershock sequences. Aftershock and downtime costs are found to be important factors in the assessment of seismic losses. The framework is also applied to a wood building in the state of Washington to assess the loss of the building subjected to combined earthquake and snow loads. The proposed framework is proven to be an appropriate tool for risk assessment of buildings subjected to multiple hazards. Limitations and future works are also identified.

Hierarchical Markov Random Fields Applied to Model Soft Tissue Deformations on Graphics Hardware

Many methodologies dealing with prediction or simulation of soft tissue deformations on medical image data require preprocessing of the data in order to produce a different shape representation that complies with standard methodologies, such as mass–spring networks, finite element method s (FEM). On the other hand, methodologies working directly on the image space normally do not take into account mechanical behavior of tissues and tend to lack physics foundations driving soft tissue deformations. This chapter presents a method to simulate soft tissue deformations based on coupled concepts from image analysis and mechanics theory. The proposed methodology is based on a robust stochastic approach that takes into account material properties retrieved directly from the image, concepts from continuum mechanics and FEM. The optimization framework is solved within a hierarchical Markov random field (HMRF) which is implemented on the graphics processor unit (GPU See Graphics processing unit ).

Validation of targeting the ventrointermediate thalamic nucleus using Q-ball calculation in deep brain stimulation for tremor

Objective: Identification of the ventrointermediate thalamic nucleus (Vim) in modern 3T high-field MRI for image-based targeting in deep brain stimulation (DBS) is still challenging. To evaluate the usefulness and reliability of analyzing the connectivity with the cerebellum using Q-ball-calculation we performed a retrospective analysis. Method: 5 patients who underwent bilateral implantation of electrodes in the Vim for treatment of Essential Tremor between 2011 and 2012 received additional preoperative Q-ball imaging. Targeting was performed according to atlas coordinates and standard MRI. Additionally we performed a retrospective identification of the Vim by analyzing the connectivity of the thalamus with the dentate nucleus. The exact position of the active stimulation contact in the postoperative CT was correlated with the Vim as it was identified by Q-ball calculation. Results: Localization of the Vim by analysis of the connectivity between thalamus and cerebellum was successful in all 5 patients on both sides. The average position of the active contacts was 14.6 mm (SD 1.24) lateral, 5.37 mm (SD 0.094 posterior and 2.21 mm (SD 0.69) cranial of MC. The cranial portion of the dentato-rubro-thalamic tract was localized an average of 3.38 mm (SD 1.57) lateral and 1.5 mm (SD 1.22) posterior of the active contact. Conclusions: Connectivity analysis by Q-ball calculation provided direct visualization of the Vim in all cases. Our preliminary results suggest, that the target determined by connectivity analysis is valid and could possibly be used in addition to or even instead of atlas based targeting. Larger prospective calculations are needed to determine the robustness of this method in providing refined information useful for neurosurgical treatment of tremor.

Automatic quantitation of multiple sclerosis lesions on MR images

A two-pronged approach for the automatic quantitation of multiple sclerosis (MS) lesions on magnetic resonance (MR) images has been developed. This method includes the design and use of a pulse sequence for improved lesion-to-tissue contrast (LTC) and seeks to identify and minimize the sources of false lesion classifications in segmented images. The new pulse sequence, referred to as AFFIRMATIVE (Attenuation of Fluid by Fast Inversion Recovery with MAgnetization Transfer Imaging with Variable Echoes), improves the LTC, relative to spin-echo images, by combining Fluid-Attenuated Inversion Recovery (FLAIR) and Magnetization Transfer Contrast (MTC). In addition to acquiring fast FLAIR/MTC images, the AFFIRMATIVE sequence simultaneously acquires fast spin-echo (FSE) images for spatial registration of images, which is necessary for accurate lesion quantitation. Flow has been found to be a primary source of false lesion classifications. Therefore, an imaging protocol and reconstruction methods are developed to generate "flow images" which depict both coherent (vascular) and incoherent (CSF) flow. An automatic technique is designed for the removal of extra-meningeal tissues, since these are known to be sources of false lesion classifications. A retrospective, three-dimensional (3D) registration algorithm is implemented to correct for patient movement which may have occurred between AFFIRMATIVE and flow imaging scans. Following application of these pre-processing steps, images are segmented into white matter, gray matter, cerebrospinal fluid, and MS lesions based on AFFIRMATIVE and flow images using an automatic algorithm. All algorithms are seamlessly integrated into a single MR image analysis software package. Lesion quantitation has been performed on images from 15 patient volunteers. The total processing time is less than two hours per patient on a SPARCstation 20. The automated nature of this approach should provide an objective means of monitoring the progression, stabilization, and/or regression of MS lesions in large-scale, multi-center clinical trials. ^

Pion emission from the T2K replica target: method, results and application

The T2K long-baseline neutrino oscillation experiment in Japan needs precise predictions of the initial neutrino flux. The highest precision can be reached based on detailed measurements of hadron emission from the same target as used by T2K exposed to a proton beam of the same kinetic energy of 30 GeV. The corresponding data were recorded in 2007-2010 by the NA61/SHINE experiment at the CERN SPS using a replica of the T2K graphite target. In this paper details of the experiment, data taking, data analysis method and results from the 2007 pilot run are presented. Furthermore, the application of the NA61/SHINE measurements to the predictions of the T2K initial neutrino flux is described and discussed.

Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted MR imaging

PURPOSE To prospectively assess the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging in the detection of pelvic lymph node metastases in patients with prostate and/or bladder cancer staged as N0 with preoperative cross-sectional imaging. MATERIALS AND METHODS This study was approved by an independent ethics committee. Written informed consent was obtained from all patients. Patients with no enlarged lymph nodes on preoperative cross-sectional images who were scheduled for radical resection of the primary tumor and extended pelvic lymph node dissection were enrolled. All patients were examined with a 3-T MR unit, and examinations included conventional and DW MR imaging of the entire pelvis. Image analysis was performed by three independent readers blinded to any clinical information. Metastases were diagnosed on the basis of high signal intensity on high b value DW MR images and morphologic features (shape, border). Histopathologic examination served as the standard of reference. Sensitivity and specificity were calculated, and bias-corrected 95% confidence intervals (CIs) were obtained with the bootstrap method. The Fleiss and Cohen κ and median test were applied for statistical analyses. RESULTS A total of 4846 lymph nodes were resected in 120 patients. Eighty-eight lymph node metastases were found in 33 of 120 patients (27.5%). Short-axis diameter of these metastases was less than or equal to 3 mm in 68, more than 3 mm to 5 mm in 13, more than 5 mm to 8 mm in five; and more than 8 mm in two. On a per-patient level, the three readers correctly detected metastases in 26 (79%; 95% CI: 64%, 91%), 21 (64%; 95% CI: 45%, 79%), and 25 (76%; 95% CI: 60%, 90%) of the 33 patients with metastases, with respective specificities of 85% (95% CI: 78%, 92%), 79% (95% CI: 70%, 88%), and 84% (95% CI: 76%, 92%). Analyzed according to hemipelvis, lymph node metastases were detected with histopathologic examination in 44 of 240 pelvic sides (18%); the three readers correctly detected these on DW MR images in 26 (59%; 95% CI: 45%, 73%), 19 (43%; 95% CI: 27%, 57%), and 28 (64%; 95% CI: 47%, 78%) of the 44 cases. CONCLUSION DW MR imaging enables noninvasive detection of small lymph node metastases in normal-sized nodes in a substantial percentage of patients with prostate and bladder cancer diagnosed as N0 with conventional cross-sectional imaging techniques.

Noninvasive pressure difference mapping derived from 4D flow MRI in patients with unrepaired and repaired aortic coarctation.

PURPOSE To develop a method for computing and visualizing pressure differences derived from time-resolved velocity-encoded three-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) and to compare pressure difference maps of patients with unrepaired and repaired aortic coarctation to young healthy volunteers. METHODS 4D flow MRI data of four patients with aortic coarctation either before or after repair (mean age 17 years, age range 3-28, one female, three males) and four young healthy volunteers without history of cardiovascular disease (mean age 24 years, age range 20-27, one female, three males) was acquired using a 1.5-T clinical MR scanner. Image analysis was performed with in-house developed image processing software. Relative pressures were computed based on the Navier-Stokes equation. RESULTS A standardized method for intuitive visualization of pressure difference maps was developed and successfully applied to all included patients and volunteers. Young healthy volunteers exhibited smooth and regular distribution of relative pressures in the thoracic aorta at mid systole with very similar distribution in all analyzed volunteers. Patients demonstrated disturbed pressures compared to volunteers. Changes included a pressure drop at the aortic isthmus in all patients, increased relative pressures in the aortic arch in patients with residual narrowing after repair, and increased relative pressures in the descending aorta in a patient after patch aortoplasty. CONCLUSIONS Pressure difference maps derived from 4D flow MRI can depict alterations of spatial pressure distribution in patients with repaired and unrepaired aortic coarctation. The technique might allow identifying pathophysiological conditions underlying complications after aortic coarctation repair.

A computer-assisted microscopic analysis of bone tissue developed inside a polyactive plymer implanted into an equine articular surface

One of the most promising applications for the restoration of small or moderately sized focal articular lesions is mosaicplasty (MP). Although recurrent hemarthrosis is a rare complication after MP, recently, various strategies have been designed to find an effective filling material to prevent postoperative bleeding from the donor site. The porous biodegradable polymer Polyactive (PA; a polyethylene glycol terephthalate - polybutylene terephthalate copolymer) represents a promising solution in this respect. A histological evaluation of the longterm PA-filled donor sites obtained from 10 experimental horses was performed. In this study, attention was primarily focused on the bone tissue developed in the plug. A computer-assisted image analysis and quantitative polarized light microscopic measurements of decalcified, longitudinally sectioned, dimethylmethylene blue (DMMB)- and picrosirius red (PS) stained sections revealed that the coverage area of the bone trabecules in the PA-filled donor tunnels was substantially (25%) enlarged compared to the neighboring cancellous bone. For this quantification, identical ROIs (regions of interest) were used and compared. The birefringence retardation values were also measured with a polarized light microscope using monochromatic light. Identical retardation values could be recorded from the bone trabeculae developed in the PA and in the neighboring bone, which indicates that the collagen orientation pattern does not differ significantly among these bone trabecules. Based on our new data, we speculate that PA promotes bone formation, and some of the currently identified degradation products of PA may enhance osteo-conduction and osteoinduction inside the donor canal.

Reconstruction of 3D Vertebral Models from a Single 2D Lateral Fluoroscopic Image

Accurate three-dimensional (3D) models of lumbar vertebrae are required for image-based 3D kinematics analysis. MRI or CT datasets are frequently used to derive 3D models but have the disadvantages that they are expensive, time-consuming or involving ionizing radiation (e.g., CT acquisition). In this chapter, we present an alternative technique that can reconstruct a scaled 3D lumbar vertebral model from a single two-dimensional (2D) lateral fluoroscopic image and a statistical shape model. Cadaveric studies are conducted to verify the reconstruction accuracy by comparing the surface models reconstructed from a single lateral fluoroscopic image to the ground truth data from 3D CT segmentation. A mean reconstruction error between 0.7 and 1.4 mm was found.

Graphical Model-Based Vertebra Identification from X-Ray Image(s)

Automated identification of vertebrae from X-ray image(s) is an important step for various medical image computing tasks such as 2D/3D rigid and non-rigid registration. In this chapter we present a graphical model-based solution for automated vertebra identification from X-ray image(s). Our solution does not ask for a training process using training data and has the capability to automatically determine the number of vertebrae visible in the image(s). This is achieved by combining a graphical model-based maximum a posterior probability (MAP) estimate with a mean-shift based clustering. Experiments conducted on simulated X-ray images as well as on a low-dose low quality X-ray spinal image of a scoliotic patient verified its performance.

Development of a balanced experimental–computational approach to understanding the mechanics of proximal femur fractures

The majority of people who sustain hip fractures after a fall to the side would not have been identified using current screening techniques such as areal bone mineral density. Identifying them, however, is essential so that appropriate pharmacological or lifestyle interventions can be implemented. A protocol, demonstrated on a single specimen, is introduced, comprising the following components; in vitro biofidelic drop tower testing of a proximal femur; high-speed image analysis through digital image correlation; detailed accounting of the energy present during the drop tower test; organ level finite element simulations of the drop tower test; micro level finite element simulations of critical volumes of interest in the trabecular bone. Fracture in the femoral specimen initiated in the superior part of the neck. Measured fracture load was 3760 N, compared to 4871 N predicted based on the finite element analysis. Digital image correlation showed compressive surface strains as high as 7.1% prior to fracture. Voxel level results were consistent with high-speed video data and helped identify hidden local structural weaknesses. We found using a drop tower test protocol that a femoral neck fracture can be created with a fall velocity and energy representative of a sideways fall from standing. Additionally, we found that the nested explicit finite element method used allowed us to identify local structural weaknesses associated with femur fracture initiation.

Evaluation and Comparison of Anatomical Landmark Detection Methods for Cephalometric X-Ray Images: A Grand Challenge

Cephalometric analysis is an essential clinical and research tool in orthodontics for the orthodontic analysis and treatment planning. This paper presents the evaluation of the methods submitted to the Automatic Cephalometric X-Ray Landmark Detection Challenge, held at the IEEE International Symposium on Biomedical Imaging 2014 with an on-site competition. The challenge was set to explore and compare automatic landmark detection methods in application to cephalometric X-ray images. Methods were evaluated on a common database including cephalograms of 300 patients aged six to 60 years, collected from the Dental Department, Tri-Service General Hospital, Taiwan, and manually marked anatomical landmarks as the ground truth data, generated by two experienced medical doctors. Quantitative evaluation was performed to compare the results of a representative selection of current methods submitted to the challenge. Experimental results show that three methods are able to achieve detection rates greater than 80% using the 4 mm precision range, but only one method achieves a detection rate greater than 70% using the 2 mm precision range, which is the acceptable precision range in clinical practice. The study provides insights into the performance of different landmark detection approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques.