Una imagen PET amiloide estática del primer minuto (FMF) se correlaciona con [18F]FDG PET en pacientes con afasia progresiva primaria / Static first-minute-frame (FMF) PET imaging after 18F-labeled amyloid tracer injection is correlated to [18F]FDG PET in patients with primary progressive aphasia

Objetivo Estudiar la correlación entre una imagen PET estática del primer minuto (FMF) adquirida con radiotrazadores de amiloide marcados con flúor-18 y la PET cerebral con [18F]FDG en pacientes con afasia primaria progresiva (APP). Material y métodos La cohorte de estudio incluyó a 17 pacientes diagnosticados de APP con la siguiente distribución: 9APP variante no fluente, 4APP variante logopénica, 1APP variante semántica, 3APP inclasificables. Se extrajeron los SUVR regionales de las FMF y sus correspondientes imágenes PET con [18F]FDG y se calcularon los coeficientes de correlación de Pearson. Resultados Los SUVR de ambas imágenes mostraron patrones similares de alteración cerebral regional. Los análisis de correlación intrapaciente dieron como resultado un coeficiente medio de r=0,94 ±0,06. Los coeficientes de correlación regional entre pacientes de la cohorte del estudio fueron superiores a 0,81. Las subcohortes específicas según el radiotrazador y la variante de APP no mostraron diferencias en la similitud de las imágenes. Conclusiones La FMF estática podría ser una alternativa válida a la PET dinámica de amiloide en fase inicial propuesta en la literatura, así como un biomarcador de neurodegeneración para el diagnóstico y la clasificación de la APP en los estudios de PET amiloide (AU)

Objective To study the correlation between a static PET image of the first-minute-frame (FMF) acquired with 18F-labeled amyloid-binding radiotracers and brain [18F]FDG PET in patients with primary progressive aphasia (PPA). Material and methods The study cohort includes 17 patients diagnosed with PPA with the following distribution: 9nonfluent variant PPA, 4logopenic variant PPA, 1semantic variant PPA, 3unclassifiable PPA. Regional SUVRs are extracted from FMFs and their corresponding [18F]FDG PET images and Pearson's correlation coefficients are calculated. Results SUVRs of both images show similar patterns of regional cerebral alterations. Intrapatient correlation analyses result in a mean coefficient of r=.94 ±.06. Regional interpatient correlation coefficients of the study cohort are greater than 0.81. Radiotracer-specific and variant-specific subcohorts show no difference in the similarity between the images. Conclusions The static FMF could be a valid alternative to dynamic early-phase amyloid PET proposed in the literature, and a neurodegeneration biomarker for the diagnosis and classification of PPA in amyloid PET studies (AU)

Automated hexahedral meshing of knee cartilage structures - application to data from the osteoarthritis initiative.

We propose a fully automated methodology for hexahedral meshing of patient-specific structures of the human knee obtained from magnetic resonance images, i.e. femoral/tibial cartilages and menisci. We select eight patients from the Osteoarthritis Initiative and validate our methodology using MATLAB on a laptop computer. We obtain the patient-specific meshes in an average of three minutes, while faithfully representing the geometries with well-shaped elements. We hope to provide a fundamentally different means to test hypotheses on the mechanisms of disease progression by integrating our patient-specific FE meshes with data from individual patients. Download both our meshes and software at http://im.engr.uconn.edu/downloads.php .

Modelling Ecological Cognitive Rehabilitation Therapies for Building Virtual Environments in Brain Injury.

BACKGROUND: Brain Injury (BI) has become one of the most common causes of neurological disability in developed countries. Cognitive disorders result in a loss of independence and patients' quality of life. Cognitive rehabilitation aims to promote patients' skills to achieve their highest degree of personal autonomy. New technologies such as virtual reality or interactive video allow developing rehabilitation therapies based on reproducible Activities of Daily Living (ADLs), increasing the ecological validity of the therapy. However, the lack of frameworks to formalize and represent the definition of this kind of therapies can be a barrier for widespread use of interactive virtual environments in clinical routine. OBJECTIVES: To provide neuropsychologists with a methodology and an instrument to design and evaluate cognitive rehabilitation therapeutic interventions strategies based on ADLs performed in interactive virtual environments. METHODS: The proposed methodology is used to model therapeutic interventions during virtual ADLs considering cognitive deficit, expected abnormal interactions and therapeutic hypotheses. It allows identifying abnormal behavioural patterns and designing interventions strategies in order to achieve errorless-based rehabilitation. RESULTS: An ADL case study ('buying bread') is defined according to the guidelines established by the ADL intervention model. This case study is developed, as a proof of principle, using interactive video technology and is used to assess the feasibility of the proposed methodology in the definition of therapeutic intervention procedures. CONCLUSIONS: The proposed methodology provides neuropsychologists with an instrument to design and evaluate ADL-based therapeutic intervention strategies, attending to solve actual limitation of virtual scenarios, to be use for ecological rehabilitation of cognitive deficit in daily clinical practice. The developed case study proves the potential of the methodology to design therapeutic interventions strategies; however our current work is devoted to designing more experiments in order to present more evidence about its values.

Automated Delineation of Vessel Wall and Thrombus Boundaries of Abdominal Aortic Aneurysms Using Multispectral MR Images.

A correct patient-specific identification of the abdominal aortic aneurysm is useful for both diagnosis and treatment stages, as it locates the disease and represents its geometry. The actual thickness and shape of the arterial wall and the intraluminal thrombus are of great importance when predicting the rupture of the abdominal aortic aneurysms. The authors describe a novel method for delineating both the internal and external contours of the aortic wall, which allows distinguishing between vessel wall and intraluminal thrombus. The method is based on active shape model and texture statistical information. The method was validated with eight MR patient studies. There was high correspondence between automatic and manual measurements for the vessel wall area. Resulting segmented images presented a mean Dice coefficient with respect to manual segmentations of 0.88 and a mean modified Hausdorff distance of 1.14 mm for the internal face and 0.86 and 1.33 mm for the external face of the arterial wall. Preliminary results of the segmentation show high correspondence between automatic and manual measurements for the vessel wall and thrombus areas. However, since the dataset is small the conclusions cannot be generalized.

iCarer: AAL for the Informal Carers of the Elderly.

In the context of the long-term care for older adults, informal carers play a key role. Daily competing priorities or a care-skills deficit may lead them to stress, anxiety and/or depression. The iCarer project (AAL-2012-5-239) proposes the design and implementation of a cloud-inspired personalised and adaptive platform which will offer support to informal carers of older adults with cognitive impairment. By means of a holistic approach comprising technologies and services addressing the intelligent and interactive monitoring of activities, knowledge management for personalised guidance and orientation, virtual interaction, e-learning, care coordination facilities and social network services, iCarer aims to reduce the informal carer stress and to enhance the quality of care they provide, thus improving their quality of life. The iCarer platform will be evaluated through a multi-centre non-controlled study (4 months; 48 homes located in England and in Slovenia). Currently the iCarer project is completing the development work. The evaluation trial is expected to start in August 2015.

High-quality conforming hexahedral meshes of patient-specific abdominal aortic aneurysms including their intraluminal thrombi.

In order to perform finite element (FE) analyses of patient-specific abdominal aortic aneurysms, geometries derived from medical images must be meshed with suitable elements. We propose a semi-automatic method for generating conforming hexahedral meshes directly from contours segmented from medical images. Magnetic resonance images are generated using a protocol developed to give the abdominal aorta high contrast against the surrounding soft tissue. These data allow us to distinguish between the different structures of interest. We build novel quadrilateral meshes for each surface of the sectioned geometry and generate conforming hexahedral meshes by combining the quadrilateral meshes. The three-layered morphology of both the arterial wall and thrombus is incorporated using parameters determined from experiments. We demonstrate the quality of our patient-specific meshes using the element Scaled Jacobian. The method efficiently generates high-quality elements suitable for FE analysis, even in the bifurcation region of the aorta into the iliac arteries. For example, hexahedral meshes of up to 125,000 elements are generated in less than 130 s, with 94.8 % of elements well suited for FE analysis. We provide novel input for simulations by independently meshing both the arterial wall and intraluminal thrombus of the aneurysm, and their respective layered morphologies.

Cognitive neurorehabilitation based on interactive video technology.

Cognitive impairment is the main cause of disability in developed societies. New interactive technologies help therapists in neurorehabilitation in order to increase patients' autonomy and quality of life. This work proposes Interactive Video (IV) as a technology to develop cognitive rehabilitation tasks based on Activities of Daily Living (ADL). ADL cognitive task has been developed and integrated with eye-tracking technology for task interaction and patients' performance monitoring.

Minimally invasive surgical video analysis: a powerful tool for surgical training and navigation.

Analysis of minimally invasive surgical videos is a powerful tool to drive new solutions for achieving reproducible training programs, objective and transparent assessment systems and navigation tools to assist surgeons and improve patient safety. This paper presents how video analysis contributes to the development of new cognitive and motor training and assessment programs as well as new paradigms for image-guided surgery.

AMELIE: Authoring Multimedia-Enhanced Learning Interactive Environment for medical contents.

This paper presents the AMELIE Authoring Tool for medical e-learning applications. The tool allows for the creation of enhanced-video based didactic contents, and can be adjusted to any number of platforms and applications. Validation provides preliminary good results on its acceptance and usefulness.

Characterization of nerve growth factor-induced mechanical and thermal hypersensitivity in rats.

BACKGROUND: Injection of nerve growth factor (NGF) produces mechanical and thermal hypersensitivity in rodents and humans. Treatment with sequestering antibodies demonstrates the importance of NGF in various pain states, with efficacy seen in a number of animal pain models and in painful human conditions. However, these phenomena have not been evaluated in the context of using NGF-induced hypersensitivities as a model of pain. METHODS: NGF-induced behaviours were characterized using von Frey filament, pinprick and thermal endpoints and then pharmacologically evaluated with known reference agents. RESULTS: Intraplantar NGF injection produced a dose-dependent increase in thermal sensitivity that lasted through 24 h post-injection and an immediate long-lasting (2 week) increase in mechanical sensitivity at the injection site, with no effects detected at secondary sites. NGF-induced mechanical sensitivity was pharmacologically characterized at 4 h and 1 week post-NGF injection. The nonsteroidal anti-inflammatory drugs (NSAIDs), celecoxib and diclofenac, were minimally effective against both thermal and mechanical endpoints. Gabapenitn and duloxetine were only moderately effective against thermal and mechanical hypersensitivity. Morphine was effective against thermal and mechanical endpoints at every time point examined. Treatment with the transient receptor potential vanilloid 1 (TRPV1) antagonist A-784168 partially attenuated NGF-induced thermal and mechanical sensitivity at all time points examined. CONCLUSIONS: The results reported here suggest that effects of NGF on thermal and mechanical sensitivity in rats are similar to those reported in human and are partially driven by TRPV1. The rat NGF model may serve as a potential translational model for exploring the effects of novel analgesic agents.

Methodology for registration of distended rectums in pelvic CT studies.

PURPOSE: Accurate delineation of the rectum is of high importance in off-line adaptive radiation therapy since it is a major dose-limiting organ in prostate cancer radiotherapy. The intensity-based deformable image registration (DIR) methods cannot create a correct spatial transformation if there is no correspondence between the template and the target images. The variation of rectal filling, gas, or feces, creates a non correspondence in image intensities that becomes a great obstacle for intensity-based DIR. METHODS: In this study the authors have designed and implemented a semiautomatic method to create a rectum mask in pelvic computed tomography (CT) images. The method, that includes a DIR based on the demons algorithm, has been tested in 13 prostate cancer cases, each comprising of two CT scans, for a total of 26 CT scans. RESULTS: The use of the manual segmentation in the planning image and the proposed rectum mask method (RMM) method in the daily image leads to an improvement in the DIR performance in pelvic CT images, obtaining a mean value of overlap volume index = 0.89, close to the values obtained using the manual segmentations in both images. CONCLUSIONS: The application of the RMM method in the daily image and the manual segmentations in the planning image during prostate cancer treatments increases the performance of the registration in presence of rectal fillings, obtaining very good agreement with a physician's manual contours.

Three-dimensional quantitative evaluation method of nonrigid registration algorithms for adaptive radiotherapy.

PURPOSE: Current radiotherapy is progressing to the concept of adaptive radiotherapy, which implies the adaptation of planning along the treatment course. Nonrigid registration is an essential image processing tool for adaptive radiotherapy and image guided radiotherapy, and the three-dimensional (3D) nature of the current radiotherapy techniques requires a 3D quantification of the registration error that existing evaluation methods do not cover appropriately. The authors present a method for 3D evaluation of nonrigid registration algorithms' performance, based on organ delineations, capable of working with near-spherical volumes even in the presence of concavities. METHODS: The evaluation method is composed by a volume shape description stage, developed using a new ad hoc volume reconstruction algorithm proposed by the authors, and an error quantification stage. The evaluation method is applied to the organ delineations of prostate and seminal vesicles, obtained by an automatic segmentation method over images of prostate cancer patients treated with intensity modulated radiation therapy. RESULTS: The volume reconstruction algorithm proposed has been shown to accurately model complex 3D surfaces by the definition of clusters of control points. The quantification method, inspired by the Haussdorf-Chebysev distance, provides a measure of the largest registration error per control direction, defining a valid metric for concave-convex volumes. Summarizing, the proposed evaluation methodology presents accurate results with a high spatial resolution in a negligible computation time in comparison with the nonrigid registration time. CONCLUSIONS: Experimental results show that the metric selected for quantifying the registration error is of utmost importance in a quantitative evaluation based on measuring distances between volumes. The accuracy of the volume reconstruction algorithm is not so relevant as long as the reconstruction is tight enough on the actual volume of the organ. The new evaluation method provides a smooth and accurate volume reconstruction for both the reference and the registered organ, and a complete 3D description of nonrigid registration algorithms' performance, resulting in a useful tool for study and comparison of registration algorithms for adaptive radiotherapy.

Artificial neural network algorithm for online glucose prediction from continuous glucose monitoring.

BACKGROUND AND AIMS: Continuous glucose monitoring (CGM) devices could be useful for real-time management of diabetes therapy. In particular, CGM information could be used in real time to predict future glucose levels in order to prevent hypo-/hyperglycemic events. This article proposes a new online method for predicting future glucose concentration levels from CGM data. METHODS: The predictor is implemented with an artificial neural network model (NNM). The inputs of the NNM are the values provided by the CGM sensor during the preceding 20 min, while the output is the prediction of glucose concentration at the chosen prediction horizon (PH) time. The method performance is assessed using datasets from two different CGM systems (nine subjects using the Medtronic [Northridge, CA] Guardian and six subjects using the Abbott [Abbott Park, IL] Navigator. Three different PHs are used: 15, 30, and 45 min. The NNM accuracy has been estimated by using the root mean square error (RMSE) and prediction delay. RESULTS: The RMSE is around 10, 18, and 27 mg/dL for 15, 30, and 45 min of PH, respectively. The prediction delay is around 4, 9, and 14 min for upward trends and 5, 15, and 26 min for downward trends, respectively. A comparison with a previously published technique, based on an autoregressive model (ARM), has been performed. The comparison shows that the proposed NNM is more accurate than the ARM, with no significant deterioration in the prediction delay. CONCLUSIONS: The proposed NNM is a reliable solution for the online prediction of future glucose concentrations from CGM data.

Tissue consistency perception in laparoscopy to define the level of fidelity in virtual reality simulation.

BACKGROUND: What degree of fidelity must a laparoscopic simulator have to achieve a training objective? This difficult question is addressed by studying the sensory interaction of surgeons in terms of a surgical skill: tissue consistency perception. METHODS: A method for characterizing surgeon sensory interaction has been defined and applied in an effort to determine the relative importance of three components of perceptual surgical skill: visual cues, haptic information, and previous surgical knowledge and experience. Expert, intermediate, and novel surgeons were enrolled in the study. Users were asked to rank tissue consistency in four different conditions: a description of the tissue alone (Q), visual information alone (VI), tactile information alone (TI), and both visual and tactile information (VTI). Agreement between these stages was assessed by a coefficient of determination (R2). RESULTS: Tissue is a determinant factor (p < 0.001) in the perception of tissue consistency, whereas the expertise of the surgeon is not (p = 0.289). Tissue consistency perception is based mainly on tactile information (TI-VTI agreement is high, R2 = 0.873), although little sensory substitution is present (VI-VTI agreement is low, R2 = 0.509). Agreement of Q-VI increases with experience (R2 = 0.050, 0.290, and 0.573, corresponding with to novel, intermediate, and expert surgeons), which has been associated with the "visual haptics" concept. CONCLUSIONS: Virtual reality simulators need haptic devices with force feedback capability if tissue consistency information is to be delivered. On the other hand, the visual haptics concept has been associated with a kind of tactile memory developed by surgical experience.

Idiopathic hypertrophic cranial pachymeningitis successfully treated with weekly subcutaneous methotrexate.

Idiopathic hypertrophic cranial pachymeningitis is a very infrequent disorder. Adequate management is still a matter of debate. We describe the use of low-dose pulse methotrexate in treating a 63-year-old woman with idiopathic hypertrophic cranial pachymeningitis. A weekly scheme with subcutaneous methotrexate was tried. Clinical improvement occurred in one week. Total remission of the clinical and neuro-imaging abnormalities was evident 6 months later, with minimal side effects. The patient is in complete remission after one year of follow-up without treatment. Hence, low-dose weekly subcutaneous methotrexate may be safe and effective in inducing complete and sustained remission of this condition. The experience with subcutaneous methotrexate to treat this entity has never been reported.

The M2DM Project--the experience of two Italian clinical sites with clinical evaluation of a multi-access service for the management of diabetes mellitus patients.

OBJECTIVES: This paper presents a multi-access service for the management of diabetes mellitus patients and the results of its assessment in two Italian clinical sites. METHODS: The service was evaluated for one year in order to prove the advantages of these kind of systems from different points of view. In this paper the clinical, usability and technical outcomes are presented. RESULTS: The evaluation results show that, thanks to the high flexibility of the implemented service, the telemedicine management of diabetes patients is feasible, well accepted by patients and clinically effective. However, in Italy the problem of quantifying the reimbursement rate of telematic services and the impact they have on the organization are factors that may hamper their introduction in routine clinical practice. CONCLUSIONS: The evaluation study showed that the telemedicine intervention has been satisfactory both for physicians because it allows to constantly monitor the patients' blood glucose level and for patients because it strengthens their motivation to self-monitor the metabolic situation.

Analysis and Specification of Telemedical Systems Using Modelling and Simulation: the MOSAIK-M Approach.

BACKGROUND AND MOTIVATION: INCA (Intelligent Control Assistant for Diabetes) is a project funded by the EU with the objective to improve diabetes therapy by creating a personal control loop interacting with telemedical remote control. Development of telemedical systems generally is a complex task especially in international projects where engineering and user groups with different social and cultural background have to be included into the system development process. OBJECTIVES: To explore if and how sophisticated information system modelling and simulation techniques can improve the development of telemedical systems. METHODS: For system analysis and design the MOSAIK-M approach was chosen. MOSAIK-M means "Modelling, simulation, and animation of information and communication systems in medicine". It includes a generic process scheme, a meta model and a tool environment. The generic process scheme guides modelling projects to produce models of high quality in terms of correctness, completeness and validity. The meta model defines the modelling language.In INCA MOSAIK-M is used for analysis of the problem domain, specification of the telemedical system and cost/benefit-analysis. RESULTS: The MOSAIK-M approach was used to create two models: an "As Is"-model of the problem domain and a "To Be"-model of the INCA system. The "As Is"-model of conventional insulin pump based diabetes care comprises submodels of diabetes management, ambulatory and clinical care. The "To Be"-model describes a patient's diabetes management using a smart phone that controls an insulin pump based on continuously measured interstitial glucose. It also describes telemedical care of a patient by diabetologists and a call centre. Both models can be simulated enhanced by visualisation capabilities to explore specific cases or scenarios. This feature proved valuable for the evaluation of both models through domain experts. The "To Be" model is used to guide the implementation of the system. Both models are being augmented by cost structures to support cost/benefit-analysis. CONCLUSIONS: Even a complex telemedical system like the INCA system can be successfully specified using sophisticated modelling and simulation based approaches like MOSAIK-M. The resulting specification is a result of its own and ensures a lasting effect of the definitions and specifications produced during the project. International cooperation and evaluation of the system design prior to its implementation profit from simulation and visualisation capabilities of MOSAIK-M.

Telemedicine as a tool for intensive management of diabetes: the DIABTel experience.

This paper presents the current features of the DIABTel telemedicine system and the evaluation outcomes of its use in clinical routine. This telemedicine system is designed to complement the daily care and intensive management of diabetic patients through telemonitoring and telecare services. The system comprises a patient unit (PU) used by patients in their day-to-day activities and a Medical Workstation used by physicians and nurses at hospitals. Both applications offer tools to collect, manage, view and interpret data and to exchange data and messages. The system was evaluated for usability, telemedical protocols, metabolic control and quality of life. This evaluation consisted in a 6-month cross-over pilot study with ten Type I diabetic patients. The results of the evaluation allowed assessment of the telemedicine protocols in terms of the number of communications/patient (21.6+/-7.7); days between communications (5.4+/-2.66); messages sent by physicians (118 text messages); and data and messages transmitted by patients (3524 blood glucose readings, 1649 day-to-day insulin adjustments, 24 exercise reports, ten diet modifications and 63 text messages). Physicians performed more therapeutic changes during the DIABTel period than in the control period. There was a trend towards HbA1c improvement during DIABTel use with no incidence in the number of hypoglycaemias. This pilot study demonstrates the feasibility of the DIABTel system in clinical routine use and its potential benefits for diabetes care: improving the availability of information necessary for therapy adjustments; offering new physician-patient communication tools; increasing patient empowerment and education; and showing a positive trend towards improving the metabolic control of patients. Further studies are needed to validate these findings and to promote telemedicine as an opportunity to better diabetes care.

A telemedicine support for diabetes management: the T-IDDM project.

In the context of the EU funded Telematic Management of Insulin-Dependent Diabetes Mellitus (T-IDDM) project, we have designed, developed and evaluated a telemedicine system for insulin dependent diabetic patients management. The system relies on the integration of two modules, a Patient Unit (PU) and a Medical Unit (MU), able to communicate over the Internet and the Public Switched Telephone Network. Using the PU, patients are allowed to automatically download their monitoring data from the blood glucose monitoring device, and to send them to the hospital data-base; moreover, they are supported in their every day self monitoring activity. The MU provides physicians with a set of tools for data visualization, data analysis and decision support, and allows them to send messages and/or therapeutic advice to the patients. The T-IDDM service has been evaluated through the application of a formal methodology, and has been used by European patients and physicians for about 18 months. The results obtained during the project demonstration, even if obtained on a pilot study of 12 subjects, show the feasibility of the T-IDDM telemedicine service, and seem to substantiate the hypothesis that the use of the system could present an advantage in the management of insulin dependent diabetic patients, by improving communications and, potentially, clinical outcomes.