Adaptive functional reorganization in amyotrophic lateral sclerosis: coexisting degenerative and compensatory changes.

BACKGROUND AND PURPOSE: Considerable functional reorganization takes place in amyotrophic lateral sclerosis (ALS) in face of relentless structural degeneration. This study evaluates functional adaptation in ALS patients with lower motor neuron predominant (LMNp) and upper motor neuron predominant (UMNp) dysfunction. METHODS: Seventeen LMNp ALS patients, 14 UMNp ALS patients and 14 controls participated in a functional magnetic resonance imaging study. Study-group-specific activation patterns were evaluated during preparation for a motor task. Connectivity analyses were carried out using the supplementary motor area (SMA), cerebellum and striatum as seed regions and correlations were explored with clinical measures. RESULTS: Increased cerebellar, decreased dorsolateral prefrontal cortex and decreased SMA activation were detected in UMNp patients compared to controls. Increased cerebellar activation was also detected in UMNp patients compared to LMNp patients. UMNp patients exhibit increased effective connectivity between the cerebellum and caudate, and decreased connectivity between the SMA and caudate and between the SMA and cerebellum when performing self-initiated movement. In UMNp patients, a positive correlation was detected between clinical variables and striato-cerebellar connectivity. CONCLUSIONS: Our findings indicate that, despite the dysfunction of SMA-striatal and SMA-cerebellar networks, cerebello-striatal connectivity increases in ALS indicative of compensatory processes. The coexistence of circuits with decreased and increased connectivity suggests concomitant neurodegenerative and adaptive changes in ALS.

Relationship between renal capacity to reabsorb glucose and renal status in patients with diabetes.

AIMS: Interindividual variability in capacity to reabsorb glucose at the proximal renal tubule could contribute to risk of diabetic kidney disease. Our present study investigated, in patients with diabetes, the association between fractional reabsorption of glucose (FRGLU) and degree of renal disease as assessed by urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR). METHODS: FRGLU [1-(glucose clearance/creatinine clearance)] was assessed in 637 diabetes patients attending our tertiary referral centre, looking for correlations between FRGLU and UAE (normo-, micro-, macro-albuminuria) and Kidney Disease: Improving Global Outcomes (KDIGO) eGFR categories: >90 (G1); 90-60 (G2); 59-30 (G3); and<30-16 (G4) mL/min/1.73 m2. Patients were stratified by admission fasting plasma glucose (FPG) into three groups: low (<6mmol/L); intermediate (6-11mmol/L); and high (>11mmol/L). RESULTS: Median (interquartile range, IQR) FRGLU levels were blood glucose-dependent: 99.90% (0.05) for low (n=106); 99.90% (0.41) for intermediate (n=288); and 96.36% (12.57) for high (n=243) blood glucose categories (P<0.0001). Also, FRGLU increased with renal disease severity in patients in the high FPG group: normoalbuminuria, 93.50% (17.74) (n=135); microalbuminuria, 96.56% (5.94) (n=77); macroalbuminuria, 99.12% (5.44) (n=31; P<0.001); eGFR G1, 94.13% (16.24) (n=111); G2, 96.35% (11.94) (n=72); G3 98.88% (7.59) (n=46); and G4, 99.11% (2.20) (n=14; P<0.01). On multiple regression analyses, FRGLU remained significantly and independently associated with UAE and eGFR in patients in the high blood glucose group. CONCLUSION: High glucose reabsorption capacity in renal proximal tubules is associated with high UAE and low eGFR in patients with diabetes and blood glucose levels>11mmol/L.

Controlled growth of a bicomponent supramolecular network by the sergeants & soldiers principle.

The co-deposition of 1,4-di(4',4''-pyridyl)benzene and 1,4-di(4',4''-bromophenyl)benzene on Si(111)-B surface leads to the formation of a highly regular self-assembly. The formation of this network has been investigated by STM and has been elucidated in the light of sergeants & soldiers principle due to halogen bonding on a silicon surface.

[Osteoid osteoma on distal phalanx tip of second toe, without scintigraphy fixation]. / Ostéome ostéoïde de la phalange distale sans hyperfixation scintigraphique.

Osteoid osteoma is a very small painful, benign tumor, located preferentially on long bones. Cases on the phalanxes of the toes are very rare. Pain takes up nearly all the clinical presentation. Poor clinical signs and atypical location make diagnosis difficult and delayed. Sometimes, it can be confused with local infection. Various additional tests are described to help diagnosis. Technetium 99-m scintigraphy coupled with CT is the key exam with high sensitivity and morphological accuracy. We report on the case of a 10-year-old boy with an atypical location of osteoid osteoma on the distal phalanx tip of the second toe, without scintigraphy fixation and obvious nidus on X-ray and CT scan.

Laryngeal tumor volume measurements determined with CT: a study on intra- and interobserver variability.

PURPOSE: To investigate the intra- and interobserver variability of computed tomography-based volume measurements of laryngeal tumors. METHODS AND MATERIALS: The volume of 13 laryngeal tumors was repeatedly measured by five independent observers in four different sessions, using the summation-of-areas technique. Mean tumor volume and its standard deviation were calculated for each tumor. Statistical analysis was done with analysis of variance, Spearman rank correlation, and linear regression. RESULTS: Both the effect of the observers (p < 0.0001) and the effect of the session (p < 0.01) on tumor volume was statistically significant. Interobserver variability was the most important component of total variability (89.3%). A significant rank correlation was found between mean volume and standard deviation (p < 0.01); the relationship between mean tumor volume and standard deviation can be described using linear regression [standard deviation = 0.28 volume + 0.35 (R = 0.79)]. CONCLUSION: Total variability in the computed tomography-based measurement of laryngeal tumor volume can be reduced by having the measurements done by a single trained observer.

The relation of CT-determined tumor parameters and local and regional outcome of tonsillar cancer after definitive radiation treatment.

PURPOSE: To investigate the value of CT-derived tumor parameters as predictor of local and regional outcome of tonsillar squamous cell carcinoma treated by definitive radiation therapy. METHODS AND MATERIALS: The pretreatment CT studies of 112 patients with tonsillar squamous cell carcinoma were reviewed. After redigitizing the films, primary and nodal tumor volume was calculated with the summation-of-areas technique. The nodal CT aspect was graded using a 3-point scale (homogenous, inhomogeneous, and necrotic). Mean follow-up time was 33 months. Actuarial statistical analysis of local and regional outcome was done for each of the covariates; multivariate analysis was performed using Cox's proportional hazards model. RESULTS: In the actuarial analysis, CT-determined primary tumor volume was significantly correlated with local recurrence rate (p < 0.05) when all patients were considered, but primary tumor volume did not predict local control within the T2, T3, and T4 category. CT-determined nodal volume was significantly related to regional outcome (p < 0.01), but nodal density was not. Total tumor volume was not significantly related to locoregional outcome (p = 0.1). In the multivariate analysis, the T and N categories were the independent predictors of local and regional outcomes, respectively. CONCLUSION: Compared to other head-and-neck sites, primary and nodal tumor volume have only marginal predictive value regarding local and regional outcome after radiation therapy in tonsillar cancer.

The contribution of magnetic resonance imaging to the three-dimensional treatment planning of localized prostate cancer.

PURPOSE: To investigate whether the use of transaxial and coronal MR imaging improves the ability to localize the apex of the prostate and the anterior part of the rectum compared to the use of transaxial CT alone, and whether the incorporation of MR could improve the coverage of the prostate by the radiotherapy field and change the volume of rectum irradiated. METHODS AND MATERIALS: Ten consecutive patients with localized prostate carcinoma underwent a CT and an axial and coronal MR scan in treatment position. The CT and MR images were mathematically aligned, and three observers were asked to contour independently the prostate and the rectum on CT and on MR. The interobserver variability of the prostatic apex location and of the delineation of the anterior rectal wall were assessed for each image modality. A dosimetry study was performed to evaluate the dose to the rectum when MR was used in addition to CT to localize the pelvic organs. RESULTS: The interobserver variation of the prostatic apex location was largest on CT ranging from 0.54 to 1.07 cm, and smallest on coronal MR ranging from 0.17 to 0.25 cm. The interobserver variation of the delineation of the anterior rectum on MR was small and constant along the whole length of the prostate (0.09+/-0.02 cm), while for CT it was comparable to that for the MR delineation at the base of the prostate, but it increased gradually towards the apex, where the variation reached 0.39 cm. The volume of MR rectum receiving more than 80% of the prescribed dose was on average reduced by 23.8+/-11.2% from the CT to the MR treatment plan. CONCLUSION: It can be concluded that the additional use of axial and coronal MR scans, in designing the treatment plan for localized prostate carcinoma, improves substantially the localization accuracy of the prostatic apex and the anterior aspect of the rectum, resulting in a better coverage of the prostate and a potential to reduce the volume of the rectum irradiated to a high dose.

Interobserver variations in gross tumor volume delineation of brain tumors on computed tomography and impact of magnetic resonance imaging.

PURPOSE: (1) To assess the interobserver variability of brain tumor delineation on computed tomography (CT). (2) To assess the impact of the addition of magnetic resonance imaging (MRI) information. METHODS: Nine physicians were asked to delineate the gross tumor volume (GTV) of five patients with supratentorial inoperable brain tumors on CT scans and 2 weeks (or more) later on MRIs. The delineations were performed on a computer screen. During delineation on MRI, the registered CT images (without delineation) were displayed on the screen (MRI+CT). RESULTS: A high interobserver variability in GTV delineation on CT is found: the ratio of the largest to the smallest defined volumes varies for the five patients by factors of resp. 2.8, 1.8, 1.8, 1.9 and 1.7. The interobserver variability is as large on MRI+CT as on CT alone (ratio largest/smallest volume: 2.4, 1.7, 1.9, 2.7 and 1.5). Volumes delineated on MRI+CT (mean: 69.6 cm(3)) are larger than on CT alone (mean: 59.5 cm(3)). Residual volumes (volume delineated on one image modality but not on the other) are >0 for CT alone and for MRI+CT. CONCLUSIONS: A large interobserver variability in GTV delineation of brain tumors is demonstrated. The addition of MRI to CT does not reduce interobserver variability. GTVs delineated on MRI+CT are larger than on CT alone, but some volumes are delineated on CT and not on MRI. Therefore, a combination of the two image modalities is recommended for brain tumor delineation for treatment planning.

Tracheal autotransplantation: a reliable reconstructive technique for extended hemilaryngectomy defects.

OBJECTIVES: Current surgical treatment for a glottic cancer with significant subglottic extension is a total laryngectomy. The objective of this study was to expand laryngeal conservation procedures by using a reconstructive technique that allows for the repair of hemicricolaryngectomy defects. STUDY DESIGN: After resection of the ipsilateral thyroid, cricoid, and arytenoid for advanced T3 glottic cancer, the laryngeal defect was reconstructed by means of an autotransplanted segment of trachea in four patients. The reconstruction consisted of a transferable patch that was constructed from a segment of revascularized cervical trachea. METHODS: During a 14-day period, a 4-cm segment of cervical trachea was wrapped by a free radial forearm fascial flap. In the second stage, the glottic cancer was removed and the cervical trachea was isolated on its fascial blood supply and transformed into a patch that was used to repair the extended hemilaryngectomy defect. Two different patch designs were used. Two patients underwent reconstruction with a patch augmented at the glottic level (group A); two patients underwent reconstruction without glottic augmentation on the patch (group B). Tracheal continuity was restored by an end-to-end reanastomosis. The postreconstruction morphology of the two patch designs was compared with the preoperative laryngeal morphology. RESULTS: The autotransplantation technique led to complete restoration of the subglottic airway lumen in all four patients. Although the anterior-posterior glottic diameter was reduced by 36% in group A patients and by 43.5% in group B patients, a sufficient glottic airway lumen was obtained. The glottic sphincteric function was restored in both groups. CONCLUSIONS: Tracheal autotransplantation may be used reliably to repair hemicricolaryngectomy defects. Augmentation of the patch at the level of the glottis is not essential for successful rehabilitation.

Integrating digital ICU viewing into the global working environment.

We illustrate that to benefit from the advantages of Picture Archiving and Communication Systems (PACS) for the Intensive Care Unit (ICU), the PACS must be strongly integrated within the overall working environment. This includes adaptation of the PACS toward specific working patterns and integrating it with the Hospital Information System (HIS). This is reflected in our prototype system in different ways. The user interface of the viewing station is centered around often used patterns in ICU viewing. Information about bed occupancy is retrieved from the HIS and exploited in the viewing station. A digital connection between the phosphorplate scanner and the HIS ensures that images are correctly related to other patient information and to previous images. Using minor adaptations to the existing HIS, PACS and HIS have been made to cooperate in integrated presentation of images and radiological reports, as a step towards a multi-media medical information system. We discuss the relation between PACS and the global information environment, emphasizing organizational issues rather than technological aspects.

Web-access to a central medical record to improve cooperation between hospital and referring physicians.

We set up Web-access to the central electronic medical record of the University Hospitals Leuven. Purpose was to enable external physicians to more actively participate in the care process as full members of the multidisciplinary treatment team. They get a view on the complete care process in the hospital, and can access results as these become available instead of being provided summary information post factum. This complements traditional electronic exchange between healthcare records. We report on technical setup and results from an extended pilot. We believe that this approach can enrich the discussion on how to provide the "global medical record".

Integrating images into a central medical information system.

Of the information items that must be easily available to the different actors involved in the care process, radiological images are not the least important. While until recently it was not feasible to include these into the medical information system, this situation has changed. Still, emphasis in PACS (Picture Archiving and Communication Systems) is primarily on the technological aspects. In this paper, in contrast, we stress the importance of integration of images into the overall workflow and into the overall medical record. We do so using illustrations from the PACS project of the University Hospitals Leuven. We briefly indicate that tight integration at the user interface level is needed, and that this requires more than standardized communication between subsystems.

Factors influencing the accuracy of volume measurements in spiral CT: a phantom study.

PURPOSE: The purpose of this study was to investigate the influence of different parameters (object size, shape, orientation, contrast, observer, and window setting) on the accuracy of volume measurements in spiral CT. METHOD: The phantom study consisted of two parts. First, well-circumscribed ellipsoid objects were scanned with conventional and spiral CT. Volumes were determined by two observers using manual contour delineation and summation-of-areas. The influence of object size, CT technique, and observer was assessed. Second, irregularly shaped gingerroots were scanned and the effect of observer, contrast, and orientation was investigated. Also assessed in both parts of the study was the effect of window setting. RESULTS: Spiral CT offered higher accuracy and reproducibility than conventional CT did. The accuracy of volume measurements was mainly determined by the window setting used for image display. Using an "optimized" window center value halfway between object density and background density resulted in overestimation of true object volumes if the number of slices through the object (number of samples) was low. Other factors (contrast, observer-related errors in contour delineation) were less important. CONCLUSIONS: Volume measurements of small objects, obtained with spiral CT and using manual contour delineation, may be grossly erroneous. Major causes of inaccuracy are an inappropriate window center selection and undersampling.

Design for user efficiency in a dedicated ICU viewing station.

The intensive care unit (ICU) is one application where significant benefit is expected from the use of digital technology in the acquisition, management and presentation of images. However, the potential benefits should not be outweighed by disadvantages of current digital technology. One of the bottlenecks is the efficiency of image viewing using a workstation, especially if this viewing station is implemented using affordable commonly available hardware. In this paper we describe the design concepts of a relatively low-cost but efficient viewing station for chest images, and discuss clinical experience with this system at an ICU ward. The user interface has been optimized towards the specific patterns of ICU image viewing. By anticipating user requests and preparing images during idle times of the computer, the mean image access time could be reduced by a factor of 4, while most images could be presented instantaneously. Information from the hospital information system (HIS) is exploited in the user interface, and a simplified PAC-HIS coupling has been implemented for the simultaneous presentation of images and reports.

Evaluation of manual vs semi-automated delineation of liver lesions on CT images.

In this paper we compare a semi-automated delineation method with totally manual delineation for area quantification, with respect to efficiency, quality, and intra- and interobserver variability. Liver lesions on 28 CT images were delineated by three observers, twice using completely manual delineation and twice using a semi-automated method. Quantitative comparisons were performed with respect to delineated area and time required for the delineation tasks. Subjective comparisons were performed with respect to efficiency and perceived quality of the semi-automated method. The areas obtained using semi-automated delineation were significantly smaller (11 %) than those obtained using totally manual delineation. Intraobserver and interobserver variability with the semi-automated method were approximately three times lower than with manual delineation. Efficiency of the semi-automated method was subjectively rated favorable, although further improvements are possible. With respect to quality, the semi-automated method was ranked better than the manual method in 73 % of cases.

Using WWW and JAVA for image access and interactive viewing in an integrated PACS.

We start from the observations that (1) potential benefits from PACS can only be realized if PACS and HIS are integrated into a 'multimedia medical information system', and (2) that this also requires integration at the level of the user interface. The user interface should allow integrated interaction with information from different subsystems, of which PACS is one. However, in the real world, different information systems are constructed using different technologies. Moreover, radiological image viewing is a highly interactive task that puts a particular burden on the graphical user interface. We describe our experiences in applying technology emerging around the 'World Wide Web' (WWW) for interactive access to an integrated PACS/HIS. We illustrate the use of Web browsers to access new medical services, touch technologies for interactive access to HIS-PACS information, and emphasize the potential of JAVA applets. We argue that JAVA may become an important tool for providing highly interactive user interfaces to larger multimedia information systems. We discuss Web technology in the general context of HIS/PACS integration.