Brain volume in infants with metopic synostosis: Less white matter volume with an accelerated growth pattern in early life.

Metopic synostosis patients are at risk for neurodevelopmental disorders despite a negligible risk of intracranial hypertension. To gain insight into the underlying pathophysiology of metopic synostosis and associated neurodevelopmental disorders, we aimed to investigate brain volumes of non-syndromic metopic synostosis patients using preoperative MRI brain scans. MRI brain scans were processed with HyperDenseNet to calculate total intracranial volume (TIV), total brain volume (TBV), total grey matter volume (TGMV), total white matter volume (TWMV) and total cerebrospinal fluid volume (TCBFV). We compared global brain volumes of patients with controls corrected for age and sex using linear regression. Lobe-specific grey matter volumes were assessed in secondary analyses. We included 45 metopic synostosis patients and 14 controls (median age at MRI 0.56 years [IQR 0.36] and 1.1 years [IQR 0.47], respectively). We found no significant differences in TIV, TBV, TGMV or TCBFV in patients compared to controls. TWMV was significantly smaller in patients (-62,233 mm3 [95% CI = -96,968; -27,498], Holm-corrected p = 0.004), and raw data show an accelerated growth pattern of white matter in metopic synostosis patients. Grey matter volume analyses per lobe indicated increased cingulate (1378 mm3 [95% CI = 402; 2355]) and temporal grey matter (4747 [95% CI = 178; 9317]) volumes in patients compared to controls. To conclude, we found smaller TWMV with an accelerated white matter growth pattern in metopic synostosis patients, similar to white matter growth patterns seen in autism. TIV, TBV, TGMV and TCBFV were comparable in patients and controls. Secondary analyses suggest larger cingulate and temporal lobe volumes. These findings suggest a generalized intrinsic brain anomaly in the pathophysiology of neurodevelopmental disorders associated with metopic synostosis.

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

BACKGROUND AND PURPOSE: Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation. MATERIALS AND METHODS: Three hundred ninety patients with a diagnosis of no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia were recruited from the memory clinic. Cerebral microbleeds and lacunes were categorized into strictly lobar, strictly deep, and mixed-location and enlarged perivascular spaces into the centrum semiovale and basal ganglia. Total and region-specific white matter hyperintensity volumes were segmented using FreeSurfer. CBF (n = 333) and the spatial coefficient of variation (n = 390) were analyzed with ExploreASL from 2D-EPI pseudocontinuous arterial spin-labeling images in white matter (WM) and gray matter (GM). To analyze the effect of demographic and vascular risk factors as well as the location and severity of cerebral small-vessel disease markers on arterial spin-labeling parameters, we constructed linear regression models, whereas logistic regression models were used to determine the association between arterial spin-labeling parameters and cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia. RESULTS: Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease, and smoking were associated with lower CBF and a higher spatial coefficient of variation. Higher numbers of lacunes and cerebral microbleeds were associated with lower CBF and a higher spatial coefficient of variation. Location-specific analysis showed mixed-location lacunes and cerebral microbleeds were associated with lower CBF. Higher total, anterior, and posterior white matter hyperintensity volumes were associated with a higher spatial coefficient of variation. No association was observed between enlarged perivascular spaces and arterial spin-labeling parameters. A higher spatial coefficient of variation was associated with the diagnosis of vascular cognitive impairment no dementia, Alzheimer's disease, and vascular dementia. CONCLUSIONS: Reduced CBF and an increased spatial coefficient of variation were associated with cerebral small-vessel disease, and more specifically lacunes, whereas cerebral microbleeds and white matter hyperintensities were associated with WM-CBF and GM spatial coefficient of variation. The spatial coefficient of variation was associated with cognitive impairment and dementia, suggesting that hypoperfusion might be the key underlying mechanism for vascular brain damage.

Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population.

BACKGROUND: Asymptomatic cerebral lesions on MRI such as white matter lesions (WML), lacunes and microbleeds are commonly seen in older people. We examined the role of a series of candidate genes involved in blood pressure regulation and amyloid metabolism. MATERIALS AND METHODS: The study was embedded in a family-based cohort sampled from a Dutch genetically isolated population. We selected individuals between 55 and 75 years of age with hypertension (N=129). Volumes of WML and presence of lacunes and microbleeds were assessed with MRI. We studied three genes involved in blood pressure regulation (angiotensin, angiotensin II type 1 receptor, α-adducin) and two genes involved in the amyloid pathway (apolipoprotein E (APOE) and sortilin-related receptor gene (SORL1)). RESULTS: All participants had WML (median volume, 3.1 ml; interquartile range, 1.5-6.5 ml); lacunar infarcts were present in 15.5% and microbleeds in 23.3%. Homozygosity for the APOE ε4 allele was associated with lacunes (OR, 4.8; 95% CI, 1.2 to 19.3). Individuals carrying two copies of the variant allele of four single nucleotide polymorphism (SNPs) located at the 3'-end of SORL1 (rs1699102, rs3824968, rs2282649, rs1010159) had significantly more often microbleeds (highest OR, 6.87; 95% CI, 1.78 to 26.44). CONCLUSION: The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.

New method for quantification of the relative severity and (a)symmetry of isolated metopic synostosis.

Trigonocephaly is the result of premature fusion of the metopic suture and its severity can vary widely. However, there is no gold standard for quantification of the severity. This study was performed to quantify severity using the Utrecht Cranial Shape Quantifier (UCSQ) and to assess forehead symmetry. Nineteen preoperative non-syndromic trigonocephaly patients (age ≤1 year) were included for the analysis of severity and symmetry. Severity according to the UCSQ was based on the following combined variables: forehead width and relative skull elongation. The UCSQ was compared to the most established quantification methods. A high correlation was found between the UCSQ and visual score (r=0.71). Moderate to negligible correlation was found between the UCSQ and frontal angle, binocular distance, inter-ocular distance, and frontal stenosis. Additionally, correlation between the visual score and these established quantification methods was negligible. Assessment of the frontal peak (a)symmetry (ratio of right to left triangle area in the curve) showed a mean right versus left triangle area ratio of 1.4 (range 0.9-2.4). The results suggest that the UCSQ is appropriate for the quantification of severity based on the high correlation with clinical judgement. Furthermore, a larger triangle area right than left was unexpectedly found, indicating forehead asymmetry.

Differences Between MR Brain Region Segmentation Methods: Impact on Single-Subject Analysis.

For the segmentation of magnetic resonance brain images into anatomical regions, numerous fully automated methods have been proposed and compared to reference segmentations obtained manually. However, systematic differences might exist between the resulting segmentations, depending on the segmentation method and underlying brain atlas. This potentially results in sensitivity differences to disease and can further complicate the comparison of individual patients to normative data. In this study, we aim to answer two research questions: 1) to what extent are methods interchangeable, as long as the same method is being used for computing normative volume distributions and patient-specific volumes? and 2) can different methods be used for computing normative volume distributions and assessing patient-specific volumes? To answer these questions, we compared volumes of six brain regions calculated by five state-of-the-art segmentation methods: Erasmus MC (EMC), FreeSurfer (FS), geodesic information flows (GIF), multi-atlas label propagation with expectation-maximization (MALP-EM), and model-based brain segmentation (MBS). We applied the methods on 988 non-demented (ND) subjects and computed the correlation (PCC-v) and absolute agreement (ICC-v) on the volumes. For most regions, the PCC-v was good ( > 0.75 ), indicating that volume differences between methods in ND subjects are mainly due to systematic differences. The ICC-v was generally lower, especially for the smaller regions, indicating that it is essential that the same method is used to generate normative and patient data. To evaluate the impact on single-subject analysis, we also applied the methods to 42 patients with Alzheimer's disease (AD). In the case where the normative distributions and the patient-specific volumes were calculated by the same method, the patient's distance to the normative distribution was assessed with the z-score. We determined the diagnostic value of this z-score, which showed to be consistent across methods. The absolute agreement on the AD patients' z-scores was high for regions of thalamus and putamen. This is encouraging as it indicates that the studied methods are interchangeable for these regions. For regions such as the hippocampus, amygdala, caudate nucleus and accumbens, and globus pallidus, not all method combinations showed a high ICC-z. Whether two methods are indeed interchangeable should be confirmed for the specific application and dataset of interest.

Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.

BACKGROUND AND PURPOSE: Vulnerable carotid plaque components are reported to increase the risk of cerebrovascular events. Yet, the relation between plaque composition and subclinical ischemic brain disease is not known. We studied, in the general population, the association between carotid atherosclerotic plaque characteristics and ischemic brain disease on MR imaging. MATERIALS AND METHODS: From the population-based Rotterdam Study, 951 participants underwent both carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage, lipid core, and calcification and measures of plaque size was assessed in both carotid arteries. The presence of plaque characteristics in relation to lacunar and cortical infarcts and white matter lesion volume was investigated and adjusted for cardiovascular risk factors. Stratified analyses were conducted to explore effect modification by sex. Additional analyses were conducted per carotid artery in relation to vascular brain disease in the ipsilateral hemisphere. RESULTS: Carotid intraplaque hemorrhage was significantly associated with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1-3.3). None of the plaque characteristics were related to the presence of lacunar infarcts. Calcification was the only characteristic that was associated with higher white matter lesion volume. There was no significant interaction by sex. CONCLUSIONS: The presence of carotid intraplaque hemorrhage on MR imaging is independently associated with MR imaging-defined cortical infarcts, but not with lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is related to white matter lesion volume.

C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study.

BACKGROUND: Inflammatory processes are involved in the development and consequences of atherosclerosis. Whether these processes are also involved in cerebral small-vessel disease is unknown. Cerebral white matter lesions and lacunar brain infarcts are caused by small-vessel disease and are commonly observed on MRI scans in elderly people. These lesions are associated with an increased risk of stroke and dementia. We assessed whether higher C-reactive protein (CRP) levels were related to white matter lesion and lacunar infarcts. METHODS AND RESULTS: We based our study on 1033 participants of the population-based Rotterdam Scan Study for whom complete data on CRP levels were available and who underwent brain MRI scanning. Subjects were 60 to 90 years of age and free of dementia at baseline. Six hundred thirty-six subjects had a second MRI scan on average 3.3 years later. We used multivariate regression models to assess the associations between CRP levels and markers of small-vessel disease. Higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 [95% CI 1.3 to 7.2] and 2.5 [95% CI 1.1 to 5.6] for periventricular and subcortical white matter lesion progression, respectively). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts. CONCLUSIONS: Inflammatory processes may be involved in the pathogenesis of cerebral small-vessel disease, in particular, the development of white matter lesions.

Sources of error in lung densitometry with CT.

RATIONALE AND OBJECTIVES: To determine and analyze the most important error sources in lung CT densitometry in vivo. METHODS: The authors examined the influences of CT acquisition errors, physiologic changes, and image segmentation errors on lung densitometry. Among others, spatial dependency and long-term reproducibility of the density measurements of blood and air were examined over a period of 4 years in a group of 28 patients with pulmonary emphysema. These results were related to the measured lung densities in this group. RESULTS: The density measurement of blood and air is strongly dependent on the position in the thorax. Despite full-scanner calibrations, x-ray tube replacement can induce a significant increase in measured blood density. CONCLUSIONS: A change in a lung density parameter over time can actually be the result of tube replacement or changing blood density. A simple postprocessing technique can correct for these changes.

Assessment of the progression of emphysema by quantitative analysis of spirometrically gated computed tomography images.

RATIONALE AND OBJECTIVES: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images. METHODS: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.5 mm were acquired at the level of the carina and 5 cm above the carina; slices with a thickness of 1 cm were acquired 5 cm below the carina. The entire lung was scanned spirally at a respiratory status, corresponding with 75% of the total lung capacity at baseline. The mean lung densities (MLD) were calculated in an objective manner with new analytic software featuring automated detection of the lung contours. RESULTS: Mean lung densities decreased by 14.2 +/- 12.0 Hounsfield units (HU; P < 0.001) above the carina, by 18.1 +/- 14.4 HU (P < 0.001) at the carina level, by 23.6 +/- 15.0 HU (P < 0.001) below the carina, and by 12.8 +/- 22.2 HU (P < 0.01) for the entire lung. The decrease in MLD was most obvious in the lower lung lobes. For the same patient group, the annual decrease in the forced expiratory volume (FEV1) and the carbon monoxide-diffusion were 120 +/- 190 mL (P < 0.01) and 10 +/- 70 mmol/kg/minute ( P < 0.2), respectively. No significant correlation was found between the decrease in MLD and the decrease in FEV1. CONCLUSIONS: Progression of emphysema can be assessed in an objective manner based on the mean lung density (MLD), measured from computed tomography volume scans as well as from single-slice scans. Mean lung density has proved to be more sensitive than FEV1 and carbon monoxide-diffusion.

Automated calibration in vascular X-ray images using the accurate localization of catheter marker bands.

RATIONALE AND OBJECTIVES: To develop a new automated calibration method for vessel measurements in vascular x-ray images. METHODS: Radiopaque marker bands mounted equidistantly on a small catheter were acquired in vitro at five image intensifier (II) sizes in x-ray projection images. The positions of the marker centers were detected by using a Hough transform and were computed at subpixel precision by using either a novel, iterative center-of-gravity approach (CGA) or a symmetry filter. Curve-fitting procedures were used to reject false-positive marker detections and to calculate intermarker distances. The calibration factor was calculated from the true marker distance and the average of the measured distances in pixels. Results were compared statistically with a grid calibration method, which was taken as the gold standard. A simulation study was performed to assess the influence of image noise on the CGA method. RESULTS: The iterative CGA method was convergent and faster than the symmetry-based technique. For four II sizes (17, 20, 25, and 31 cm), the results from the CGA method were not significantly different from the results obtained with grid calibration. For the II size of 38 cm, a significant difference (0.3% of the grid calibration factor) was found; however, this was caused by the quantification error in the image data and was not clinically relevant. In general, the performance of the CGA method improved with increasing signal-to-noise ratio. CONCLUSIONS: A practical new calibration method for small catheter sizes was developed and validated for quantitative vascular arteriography.

Quantitative analysis of computed tomography scans of the lungs for the diagnosis of pulmonary emphysema. A validation study of a semiautomated contour detection technique.

RATIONALE AND OBJECTIVES: To develop an analytic software package based on automated contour detection for the objective and reproducible assessment of emphysema from computed tomography (CT) scans. METHODS: A semiautomated technique was developed for the definition of lung contours in CT cross-sections followed by the assessment of pulmonary CT parameters describing the disease state. For 78 images, the semiautomated contour detection was performed and compared with contours drawn by an experienced radiologist by calculating the systematic area difference (bias) and differences in pulmonary CT parameters such as the mean lung density (MLD). In addition, intraobserver and interobserver variabilities were determined in a subset of 15 images. RESULTS: The areas enclosed by the semiautomatically detected contours were slightly larger than the manual ones (bias < 2.1%). The biases in the observer studies were smaller in the semiautomated versus the manual case (0.3% vs. 1.3%). The standard deviation of the MLD differences with a manual analysis was larger by a factor of five than in the semiautomated case. On average, manual analysis required 2 minutes, 18 seconds per lung; this time was reduced to 11.5 to 29 seconds with the semiautomated approach, depending on the respiration state. CONCLUSIONS: The semiautomated approach is preferred over the manual approach because of its higher consistency and its shorter analysis time.

Optimization of chest films of equalization radiography (advanced multiple beam equalization radiography). Comparison by means of a receiver operating characteristic study of simulated nodular interstitial disease.

RATIONALE AND OBJECTIVE: To optimize screen-film combinations for equalization radiography (advanced multiple beam equalization radiography [AMBER]), five different film-screen-technique combinations were compared by receiver operating characteristics study of simulated interstitial disease. MATERIALS AND METHODS: The Ortho C-Lanex Regular and the Insight Thoracic Imaging HC system were compared in conventional nonequalized technique; T-Mat G-Lanex Regular and T-Max L-Lanex Regular were compared in conventional, nonequalized, and AMBER technique; and an experimental high-contrast, low-noise, near-zero crossover film-screen combination was compared in AMBER technique. Interstitial disease was simulated by superimposing birdseed on the back of a humanoid phantom. Twenty-five posterior-anterior radiographs were made with each technique. Seven observers scored the presence of interstitial disease in each of the quadrants on a 5-point scale following receiver operating characteristic methodology. RESULTS: The highest performance was found with the experimental film-screen-AMBER combination (Az = 0.92) and the lowest with the T-Mat L-Lanex Regular-AMBER combination (Az = 0.83) and the Insight Thoracic Imaging HC system-conventional combination (Az = 0.85). T-Mat L-Lanex Regular-conventional ranked second (Az = 0.90) while T-Mat G-Lanex Regular-conventional (Az = 0.89), T-Mat L-Lanex Regular-AMBER (Az = 0.88) and Ortho-C-Lanex Regular-conventional (Az = 0.87) scored lower. CONCLUSION: Higher contrast films in AMBER improve diagnostic performance, whereas a loss of information is found if the AMBER system is combined with lower contrast films.

Quantitative assessment of the presence of a single leg separation in Björk-Shiley convexoconcave prosthetic heart valves.

RATIONALE AND OBJECTIVES: The authors developed an analytic software package for the objective and reproducible assessment of a single leg separation (SLS) in the outlet strut of Björk-Shiley convexoconcave (BSCC) prosthetic heart valves. METHODS: The radiographic cinefilm recordings of 18 phantom valves (12 intact and 6 SLS) and of 43 patient valves were acquired. After digitization of regions of interest in a cineframe, several processing steps were carried out to obtain a one-dimensional corrected and averaged density profile along the central axis of each strut leg. To characterize the degree of possible separation, two quantitative measures were introduced: the normalized pit depth (NPD) and the depth-sigma ratio (DSR). The group of 43 patient studies was divided into a learning set (25 patients) and a test set (18 patients). RESULTS: All phantom valves with an SLS were detected (sensitivity, 100%) at a specificity of 100%. The threshold values for the NPD and the DSR to decide whether a fracture was present or not were 3.6 and 2.5, respectively. On the basis of the visual interpretations of the 25 patient studies (learning set) by an expert panel, it was concluded that none of the patients had an SLS. To achieve a 100% specificity by quantitative analysis, the threshold values for the NPD and the DSR were set at 5.8 and 2.5, respectively, for the patient data. Based on these threshold values, the analysis of patient data from the test set resulted in one false-negative detection and three false-positive detections. CONCLUSIONS: An analytic software package for the detection of an SLS was developed. Phantom data showed excellent sensitivity (100%) and specificity (100%). Further research and software development is needed to increase the sensitivity and specificity for patient data.

Global estimation of myelination in the developing brain on the basis of magnetization transfer imaging: a preliminary study.

BACKGROUND AND PURPOSE: In the developing brain, myelination occurs in an orderly and predetermined sequence. The aim of this study was to determine whether such changes can be tracked using volumetric magnetization transfer imaging. METHODS: Three-dimensional magnetization transfer imaging was performed in 50 children (age range, 0.6-190 months) with no evidence of developmental delay or structural abnormalities. Volumetric magnetization transfer ratio (MTR) parameters generated of the whole brain were mean MTR and height and location of the MTR histogram peak. Relationships between volumetric MTR parameters and age were assessed using nonlinear regression analysis. RESULTS: With age, all volumetric MTR parameters changed exponentially in a way that was best expressed by the function y = a + b.exp(-x/c) (P < .0001). The peak height of the MTR histogram was the parameter that changed most predictably and that continued to change for the longest period of time. CONCLUSION: With this preliminary study, we show that by using volumetric MTR analysis, it is possible to monitor changes in the developing brain, presumably the myelination progress. This method has a potential role for detecting myelination disorders in the pediatric population, for studying the natural history of these diseases, and for monitoring the effects of treatment.

Digital automated RSA compared to manually operated RSA.

The accuracy of digital Roentgen stereophotogrammetric analysis (RSA) was compared to the accuracy of a manually operated RSA system. For this purpose, we used radiographs of a phantom and radiographs of patients. The radiographs of the patients consisted of double examinations of 12 patients that had a tibial osteotomy and of double examinations of 12 patients that received a total hip prosthesis. First, the radiographs were measured manually with an accurate measurement table. Subsequently, the images were digitized by a film scanner at 150 DPI and 300 DPI resolutions and analyzed with the RSA-CMS software. In the phantom experiment, the manually operated system produced significantly better results than the digital system, although the maximum difference between the median values of the manually operated system and the digital system was as low as 0.013mm for translations and 0.033 degrees for rotations. In the radiographs of the patients, the manually operated system and the digital system produced equally accurate results: no significant differences in translations and rotations were found. We conclude that digital RSA is an accurate, fast, and user friendly alternative for manually operated RSA. Currently, digital RSA systems are being used in a growing number of clinical RSA-studies.

Model-based Roentgen stereophotogrammetry of orthopaedic implants.

Attaching tantalum markers to prostheses for Roentgen stereophotogrammetry (RSA) may be difficult and is sometimes even impossible. In this study, a model-based RSA method that avoids the attachment of markers to prostheses is presented and validated. This model-based RSA method uses a triangulated surface model of the implant. A projected contour of this model is calculated and this calculated model contour is matched onto the detected contour of the actual implant in the RSA radiograph. The difference between the two contours is minimized by variation of the position and orientation of the model. When a minimal difference between the contours is found, an optimal position and orientation of the model has been obtained. The method was validated by means of a phantom experiment. Three prosthesis components were used in this experiment: the femoral and tibial component of an Interax total knee prosthesis (Stryker Howmedica Osteonics Corp., Rutherfort, USA) and the femoral component of a Profix total knee prosthesis (Smith & Nephew, Memphis, USA). For the prosthesis components used in this study, the accuracy of the model-based method is lower than the accuracy of traditional RSA. For the Interax femoral and tibial components, significant dimensional tolerances were found that were probably caused by the casting process and manual polishing of the components surfaces. The largest standard deviation for any translation was 0.19mm and for any rotation it was 0.52 degrees. For the Profix femoral component that had no large dimensional tolerances, the largest standard deviation for any translation was 0.22mm and for any rotation it was 0.22 degrees. From this study we may conclude that the accuracy of the current model-based RSA method is sensitive to dimensional tolerances of the implant. Research is now being conducted to make model-based RSA less sensitive to dimensional tolerances and thereby improving its accuracy.

Fast and accurate automated measurements in digitized stereophotogrammetric radiographs.

Until recently, Roentgen Stereophotogrammetric Analysis (RSA) required the manual definition of all markers using a high-resolution measurement table. To automate this tedious and time-consuming process and to eliminate observer variabilities, an analytical software package has been developed and validated for the detection, identification, and matching of markers in RSA radiographs. The digital analysis procedure consisted of the following steps: (1) the detection of markers using a variant of the Hough circle-finder technique; (2) the identification and labeling of the detected markers; (3) the reconstruction of the three-dimensional position of the bone markers and the prosthetic markers; and (4) the computation of micromotion. To assess the influence of film digitization, the measurements obtained from nine phantom radiographs using two different film scanners were compared with the results obtained by manual processing. All markers in the phantom radiographs were automatically detected and correctly labeled. The best results were obtained with a Vidar VXR-12 CCD scanner, for which the measurement errors were comparable to the errors associated with the manual approach. To assess the in vivo reproducibility, 30 patient radiographs were analyzed twice with the manual as well as with the automated procedure. Approximately, 85% of all calibration markers and bone markers were automatically detected and correctly matched. The calibration errors and the rigid-body errors show that the accuracy of the automated procedure is comparable to the accuracy of the manual procedure. The rigid-body errors had comparable mean values for both techniques: 0.05 mm for the tibia and 0.06 mm for the prosthesis. The reproducibility of the automated procedure showed to be slightly better than that of the manual procedure. The maximum errors in the computed translation and rotation of the tibial component were 0.11 mm and 0.24, compared to 0.13 mm and 0.27 for the manual RSA procedure. The total processing time is less than 10 min per radiograph, including interactive corrections, compared to approximately 1 h for the manual approach. In conclusion, a new and widely applicable, computer-assisted technique has become available to detect, identify, and match markers in RSA radiographs and to assess the micromotion of endoprostheses. This new technique will be used in our clinic for our hip, knee, and elbow studies.

Detection of areas with viable remnant tumor in postchemotherapy patients with Ewing's sarcoma by dynamic contrast-enhanced MRI using pharmacokinetic modeling.

An approach is presented for monitoring the effects of neoadjuvant chemotherapy in patients with Ewing's sarcoma using dynamic contrast-enhanced perfusion magnetic resonance (MR) images. For that purpose, we modify the three-compartment pharmacokinetic permeability model introduced by Tofts et al. (Magn Reson Med 1991;17:357-67) to a two-compartment model. Perfusion MR images acquired using an intravenous injection with Gadolinium (Gd-DTPA) are analyzed with this two-compartment pharmacokinetic model as well as the with an extended pharmacokinetic model that includes the (local) arrival time t(0) of the tracer as an endogenous (estimated) parameter. For each MR section, a wash-in parameter associated with each voxel is estimated twice by fitting each of the two pharmacokinetic models to the dynamic MR signal. A comparison of the two wash-in parametric images (global versus local arrival time) with matched histologic macroslices demonstrates a good correspondence between areas with viable remnant tumor and a high wash-in rate. This can be explained by the high number and permeability of the (leaking) capillaries in viable tumor tissue. The novel pharmacokinetic model based on a local arrival time of tracer results in the best fit of the wash-in rate, the most important factor discerning viable from nonviable tumor components. However, parameter estimates obtained with this model are also more sensitive to noise in the MR signal. The novel pharmacokinetic model resulted in a sensitivity between 0.22 and 0.60 and a specificity between 0.61 and 1. The model based on a global arrival time gave sensitivities between 0.33 and 0.77 and specificities between 0.58 and 0.99. Both statistics are computed as the fraction of correctly labeled voxels (viable or nonviable tumor) within a specified ROI, which delineates the tumor. We conclude that the added value of estimating the local arrival time of tracer first manifests itself for moderate noise levels in the MR signal. The novel pharmacokinetic model should moreover be preferred when pharmacokinetic modeling is applied on the average signal intensity within a ROI, where noise has less effect on the fitted parameters.

A review of technical advances in virtual colonoscopy.

Early detection of polyps has proven to lead to a decrease in incidence of colon cancer. In the past few years, virtual colonoscopy has been developed as a patient-friendly screen-ing technique. The procedure comprises the following steps. First, the patient's colon is cleansed and transanally inflated with air. Subsequently, a 3D image volume is acquired of the abdomen by CT or MRI. Finally, the bowel surface is extracted and visualized, after which the physician virtually navigates through the colon and examines the surface for abnormalities. This paper describes the progress in research for virtual colonoscopy.

Inter-frame motion correction for MR thermometry.

Noninvasive temperature measurement is feasible with MRI to monitor changes in thermal therapy. Phase shift based MR thermometry gives an estimate of the relative temperature variation between thermal and baseline images. This technique is limited, however, when applied on targets under inter-frame motion. Simple image registration and subtraction are not adequate to recover the temperature properly since the phase shift due to temperature changes is corrupted by an unwanted phase shift. In this work, the unwanted phase shift is predicted from the raw registered phase shift map itself. To estimate the unwanted phase shift, a thin plate smoothing spline is fitted to the values outside the heated region. The spline value in the heated area serves as an estimate for the offset. The estimation result is applied to correct errors in the temperature maps of an ex-vivo experiment.