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Mathematical models are increasingly proposed to describe tumor’s dynamic response to treatments with the aims of improving their efficacy. The most widely used are nonlinear ODE models, whose identification is often difficult due to experimental limitations. We focus on the issue of parameter estimation in model-based oncological studies. Given their complexity, many of these models are unidentifiable having an infinite number of parameter solutions. These equivalently describe experimental data but are associated with different dynamic evolution of unmeasurable variables. We propose a joint use of two different identifiability methodologies, structural identifiability and practical identifiability, which are traditionally regarded as disjoint. This new methodology provides the number of parameter solutions, the analytic relations between the unidentifiable parameters useful to reduce model complexity, a ranking between parameters revealing the most reliable estimates, and a way to disentangle the various causes of nonidentifiability. It is implementable by using available differential algebra software and statistical packages. This methodology can constitute a powerful tool for the oncologist to discover the behavior of inaccessible variables of clinical interest and to correctly address the experimental design. A complex model to study “in vivo” antitumor activity of interleukin-21 on tumor eradication in different cancers in mice is illustrated.

Purpose To investigate dose distribution variations due to setup errors and range uncertainties in image-guided carbon ion radiotherapy of head chordoma. Materials and methods Ten treatment plans were retrospectively tested with TRiP98 against ±1.0mm and ±1.0° setup errors, as observed in clinical routine, and 2.6% range uncertainty when 2mm CTV-to-PTV margins were applied. Single-fraction simulations were compared with the total treatment dose in terms of DVH bands, conformity and inhomogeneity. The contribution of image processing artifacts on reported results was also discussed, as a function of the imaging dataset resolution. Results Results showed that safety margins grant the conformal target coverage in presence of setup errors with D95 CTV variations below 10% in 7 patients out of 10. Instead, the inclusion of range uncertainty yielded to appreciable dose degradation, reporting larger effects for CTV and dose conformity, whereas reduced impact is found on the organ-at-risk. The fractionation scheme positively affects dose conformity and inhomogeneity; conversely its influence on DVH bands is strongly related to the patient anatomy. Conclusion Besides safety margins, setup and range uncertainties lead to non-negligible combined contribution. Systematical treatment plan robustness assessment against expected uncertainties is thus encouraged, selecting beam settings and fractionation schemes where homogeneity is preserved.

In an increasing number of clinical indications, radiotherapy with accelerated particles shows relevant advantages when compared with high energy X-ray irradiation. However, due to the finite range of ions, particle therapy can be severely compromised by setup errors and geometric uncertainties. The purpose of this work is to describe the commissioning and the design of the quality assurance procedures for patient positioning and setup verification systems at the Italian National Center for Oncological Hadrontherapy (CNAO). The accuracy of systems installed in CNAO and devoted to patient positioning and setup verification have been assessed using a laser tracking device. The accuracy in calibration and image based setup verification relying on in room X-ray imaging system was also quantified. Quality assurance tests to check the integration among all patient setup systems were designed, and records of daily QA tests since the start of clinical operation (2011) are presented. The overall accuracy of the patient positioning system and the patient verification system motion was proved to be below 0.5 mm under all the examined conditions, with median values below the 0.3 mm threshold. Image based registration in phantom studies exhibited sub-millimetric accuracy in setup verification at both cranial and extra-cranial sites. The calibration residuals of the OTS were found consistent with the expectations, with peak values below 0.3 mm. Quality assurance tests, daily performed before clinical operation, confirm adequate integration and sub-millimetric setup accuracy. Robotic patient positioning was successfully integrated with optical tracking and stereoscopic X-ray verification for patient setup in particle therapy. Sub-millimetric setup accuracy was achieved and consistently verified in daily clinical operation.

The purpose of this paper is to describe the experiments and methods that led to the geometrical interpretation of new-generation commercial PET-CT scanners, finalized to off-line PET-based treatment verification in ion beam therapy. Typically, the geometrical correspondence between the image domain (i.e., the dicom PET) and the sinogram domain (i.e., the PET raw data) is not explicitly described by scanner vendors. Hence, the proposed characterization can be applied to commercial PET-CT scanners used in biomedical research, for the development of technologies and methods requiring the use of PET raw data, without having access to confidential information from the vendors.

Accurate dose delivery to extra-cranial lesions requires tumor motion compensation. An effective compensation can be achieved by real-time tracking of the target position, either measured in fluoroscopy or estimated through correlation models as a function of external surrogate motion. In this work, we integrated two internal/external correlation models (a state space model and an artificial neural network-based model) into a custom infra-red optical tracking system (OTS). Dedicated experiments were designed and conducted at GSI (Helmholtzzentrum für Schwerionenforschung). A robotic breathing phantom was used to reproduce regular and irregular internal target motion as well as external thorax motion. The position of a set of markers placed on the phantom thorax was measured with the OTS and used by the correlation models to infer the internal target position in real-time. Finally, the estimated target position was provided as input for the dynamic steering of a carbon ion beam. Geometric results showed that the correlation models transversal (2D) targeting error was always lower than 1.3 mm (root mean square). A significant decrease of the dosimetric error with respect to the uncompensated irradiation was achieved in four out of six experiments, demonstrating that phase shifts are the most critical irregularity for external/internal correlation models. © 2013 Institute of Physics and Engineering in Medicine.

Adaptive radiation therapy (ART) aims at compensating for anatomic and pathological changes to improve delivery along a treatment fraction sequence. Current ART protocols require time-consuming manual updating of all volumes of interest on the images acquired during treatment. Deformable image registration (DIR) and contour propagation stand as a state of the ART method to automate the process, but the lack of DIR quality control methods hinder an introduction into clinical practice. We investigated the scale invariant feature transform (SIFT) method as a quantitative automated tool (1) for DIR evaluation and (2) for re-planning decision-making in the framework of ART treatments. As a preliminary test, SIFT invariance properties at shape-preserving and deformable transformations were studied on a computational phantom, granting residual matching errors below the voxel dimension. Then a clinical dataset composed of 19 head and neck ART patients was used to quantify the performance in ART treatments. For the goal (1) results demonstrated SIFT potential as an operator-independent DIR quality assessment metric. We measured DIR group systematic residual errors up to 0.66 mm against 1.35 mm provided by rigid registration. The group systematic errors of both bony and all other structures were also analyzed, attesting the presence of anatomical deformations. The correct automated identification of 18 patients who might benefit from ART out of the total 22 cases using SIFT demonstrated its capabilities toward goal (2) achievement.

The ability to perform dose recalculation on the anatomy of the day is important in the context of adaptive proton therapy. The objective of this study was to investigate the use of deformable image registration (DIR) and cone beam CT (CBCT) imaging to generate the daily stopping power distribution of the patient. We investigated the deformation of the planning CT scan (pCT) onto daily CBCT images to generate a virtual CT (vCT) using a deformable phantom designed for the head and neck (H & N) region. The phantom was imaged at a planning CT scanner in planning configuration, yielding a pCT and in deformed, treatment day configuration, yielding a reference CT (refCT). The treatment day configuration was additionally scanned at a CBCT scanner. A Morphons DIR algorithm was used to generate a vCT. The accuracy of the vCT was evaluated by comparison to the refCT in terms of corresponding features as identified by an adaptive scale invariant feature transform (aSIFT) algorithm. Additionally, the vCT CT numbers were compared to those of the refCT using both profiles and regions of interest and the volumes and overlap (DICE coefficients) of various phantom structures were compared. The water equivalent thickness (WET) of the vCT, refCT and pCT were also compared to evaluate proton range differences. Proton dose distributions from the same initial fluence were calculated on the refCT, vCT and pCT and compared in terms of proton range. The method was tested on a clinical dataset using a replanning CT scan acquired close in time to a CBCT scan as reference using the WET evaluation. Results from the aSIFT investigation suggest a deformation accuracy of 2-3 mm. The use of the Morphon algorithm did not distort CT number intensity in uniform regions and WET differences between vCT and refCT were of the order of 2% of the proton range. This result was confirmed by proton dose calculations. The patient results were consistent with phantom observations. In conclusion, our phantom study suggests the vCT approach is adequate for proton dose recalculation on the basis of CBCT imaging.

In ion beam radiotherapy, PET-based treatment verification provides a consistency check of the delivered treatment with respect to a simulation based on the treatment planning. In this work the region-based MLEM reconstruction algorithm is proposed as a new evaluation strategy in PET-based treatment verification. The comparative evaluation is based on reconstructed PET images in selected regions, which are automatically identified on the expected PET images according to homogeneity in activity values. The strategy was tested on numerical and physical phantoms, simulating mismatches between the planned and measured β(+) activity distributions. The region-based MLEM reconstruction was demonstrated to be robust against noise and the sensitivity of the strategy results were comparable to three voxel units, corresponding to 6 mm in numerical phantoms. The robustness of the region-based MLEM evaluation outperformed the voxel-based strategies. The potential of the proposed strategy was also retrospectively assessed on patient data and further clinical validation is envisioned.

In this contribution we describe the implementation of a novel solution for image guided particle therapy, designed to ensure the maximal accuracy in patient setup. The presented system is installed in the central treatment room at Centro Nazionale di Adroterapia Oncologica (CNAO, Italy), featuring two fixed beam lines (horizontal and vertical) for proton and carbon ion therapy. Treatment geometry verification is based on robotic in-room imaging acquisitions, allowing for 2D/3D registration from double planar kV-images or 3D/3D alignment from cone beam image reconstruction. The calculated six degrees-of-freedom correction vector is transferred to the robotic patient positioning system, thus yielding automated setup error compensation. Sub-millimetre scale residual errors were measured in absolute positioning of rigid phantoms, in agreement with optical- and laser-based assessment. Sub-millimetre and sub-degree positioning accuracy was achieved when simulating setup errors with anthropomorphic head, thorax and pelvis phantoms. The in-house design and development allowed a high level of system customization, capable of replicating the clinical performance of commercially available products, as reported with preliminary clinical results in 10 patients.

Mathematical modeling of the tumor response to radiotherapy may provide a meaningful contribution to enhance the therapeutic planning and adjust the treatment on the run. Clinical translation of modeling results is currently prevented by the lack of sufficient validation on a patient-specific basis while imaging techniques along with the latest treatments (e.g. IGRT) can make available a large number of patient data at macroscopic scale. In this work, tissue-scale tumor growth and radio-response models are proposed and validated on volume regression data measured on serial CBCT imaging, concurrent with the treatment fractions, of 16 cervix cancer patients.

Display Omitted SAPS is an algorithm for markers optimization in IR optical tracking in hadrontherapy.Two optimization methods are integrated in SAPS: simulated annealing and pattern search.Prior knowledge, such as visibility and spatial constraints, is taken into account.SAPS has better performance than state of art methods, especially when a high number of markers is used.The SAPS algorithm is a valuable strategy for the patient set-up error reduction. PurposeIn high precision photon radiotherapy and in hadrontherapy, it is crucial to minimize the occurrence of geometrical deviations with respect to the treatment plan in each treatment session. To this end, point-based infrared (IR) optical tracking for patient set-up quality assessment is performed. Such tracking depends on external fiducial points placement. The main purpose of our work is to propose a new algorithm based on simulated annealing and augmented Lagrangian pattern search (SAPS), which is able to take into account prior knowledge, such as spatial constraints, during the optimization process. Material and methodsThe SAPS algorithm was tested on data related to head and neck and pelvic cancer patients, and that were fitted with external surface markers for IR optical tracking applied for patient set-up preliminary correction. The integrated algorithm was tested considering optimality measures obtained with Computed Tomography (CT) images (i.e. the ratio between the so-called target registration error and fiducial registration error, TRE/FRE) and assessing the marker spatial distribution. Comparison has been performed with randomly selected marker configuration and with the GETS algorithm (Genetic Evolutionary Taboo Search), also taking into account the presence of organs at risk. ResultsThe results obtained with SAPS highlight improvements with respect to the other approaches: (i) TRE/FRE ratio decreases; (ii) marker distribution satisfies both marker visibility and spatial constraints. We have also investigated how the TRE/FRE ratio is influenced by the number of markers, obtaining significant TRE/FRE reduction with respect to the random configurations, when a high number of markers is used. ConclusionsThe SAPS algorithm is a valuable strategy for fiducial configuration optimization in IR optical tracking applied for patient set-up error detection and correction in radiation therapy, showing that taking into account prior knowledge is valuable in this optimization process. Further work will be focused on the computational optimization of the SAPS algorithm toward fast point-of-care applications.

International audience; Purpose/Objective: To develop and evaluate a tumor tracking method for extracranial radiotherapy treatments based on the indirect estimation of intrafraction target motion from patient's surface displacement, by using external-internal correlation models built from Cone-Beam CT (CBCT).

SummaryBackground: Similarity measures in medical images do not uniquely determine the correspondence between two voxels in deformable image registration. Uncertainties in the final computed deformation exist, questioning the actual physiological consistency of the deformation between the two images.Objectives: We developed a deformable image registration method that regularizes the deformation field in order to model a deformation with physiological properties, relying on vector calculus based operators as a regularization function.Method: We implemented a 3D multi-resolution parametric deformable image registration, containing divergence and curl of the deformation field as regularization terms. Exploiting a BSpline model, we fit the transformation to optimize histogram-based mutual information similarity measure. In order to account for compression/expansion, we extract sink/source/circulation components as irregularities in the warped image and compensate them. The registration performance was evaluated using Jacobian determinant of the deformation field, inverse-consistency, landmark errors and residual image difference along with displacement field errors. Finally, we compare our results to a robust combination of second derivative regularization, as well as to non-regularized methods.Results: The implementation was tested on synthetic phantoms and clinical data, leading to increased image similarity and reduced inverse-consistency errors. The statistical analysis on clinical cases showed that regularized methods are able to achieve better image similarity than non regularized methods. Also, divergence/curl regularization improves anatomical landmark errors compared to second derivative regularization.Conclusion: The implemented divergence/ curl regularization was successfully tested, leading to promising results in comparison with competitive regularization methods. Future work is required to establish parameter tuning and reduce the computational cost.

The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in 20.3(2.3)% and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation. © Adenine Press (2014).

The purpose of the study is to evaluate the performance of a novel strategy, referred to as “virtual 4D PET”, aiming at the optimization of hybrid 4D CT-PET scan for radiotherapy treatment planning. The virtual 4D PET strategy applies 4D CT motion modeling to avoid time-resolved PET image acquisition. This leads to a reduction of radioactive tracer administered to the patient and to a total acquisition time comparable to free-breathing PET studies. The proposed method exploits a motion model derived from 4D CT, which is applied to the free-breathing PET to recover respiratory motion and motion blur. The free-breathing PET is warped according to the motion model, in order to generate the virtual 4D PET. The virtual 4D PET strategy was tested on images obtained from a 4D computational anthropomorphic phantom. The performance was compared to conventional motion compensated 4D PET. Tests were also carried out on clinical 4D CT-PET scans coming from seven lung and liver cancer patients. The virtual 4D PET strategy was able to recover lesion motion, with comparable performance with respect to the motion compensated 4D PET. The compensation of the activity blurring due to motion was successfully achieved in terms of spill out removal. Specific limitations were highlighted in terms of partial volume compensation. Results on clinical 4D CT-PET scans confirmed the efficacy in 4D PET count statistics optimization, as equal to the free-breathing PET, and recovery of lesion motion. Compared to conventional motion compensation strategies that explicitly require 4D PET imaging, the virtual 4D PET strategy reduces clinical workload and computational costs, resulting in significant advantages for radiotherapy treatment planning.

The synergy between in-room imaging and optical tracking, in co-operation with highly accurate robotic patient handling represents a concept for patient-set-up which has been implemented at CNAO (Centro Nazionale di Adroterapia Oncologica). In-room imaging is based on a double oblique X-ray projection system; optical tracking consists of the detection of the position of spherical markers placed directly on the patient's skin or on the immobilization devices. These markers are used as external fiducials during patient positioning and dose delivery. This study reports the results of a comparative analysis between in-room imaging and optical tracking data for patient positioning within the framework of high-precision particle therapy. Differences between the optical tracking system (OTS) and the imaging system (IS) were on average within the expected localization accuracy. On the first 633 fractions for head and neck (HN) set-up procedures, the corrections applied by the IS, after patient positioning using the OTS only, were for the mostly sub-millimetric regarding the translations (0.4 ± 1.1 mm) and sub-gradual regarding the rotations (0.0° ± 0.8°). On the first 236 fractions for pelvis localizations the amplitude of the corrections applied by the IS after preliminary optical set-up correction were moderately higher and more dispersed (translations: 1.3 ± 2.9 mm, rotations 0.1 ± 0.9°). Although the indication of the OTS cannot replace information provided by in-room imaging devices and 2D-3D image registration, the reported data show that OTS preliminary correction might greatly support image-based patient set-up refinement and also provide a secondary, independent verification system for patient positioning.

The aim of this work is to provide insights into multiple metrics clinical validation of deformable image registration and contour propagation methods in 4D lung radiotherapy planning. The following indices were analyzed and compared: Volume Difference (VD), Dice Similarity Coefficient (DSC), Positive Predictive Value (PPV) and Surface Distances (SD). The analysis was performed on three patient datasets, using as reference a ground-truth volume generated by means of Simultaneous Truth And Performance Level Estimation (STAPLE) algorithm from the outlines of five experts. Significant discrepancies in the quality assessment provided by the different metrics in all the examined cases were found. Metrics sensitivity was more evident in presence of image artifacts and particularly for tubular anatomical structures, such as esophagus or spinal cord. Volume Differences did not account for position and DSC exhibited criticalities due to its intrinsic symmetry ( i.e. over- and under-estimation of the reference contours cannot be discriminated) and dependency on the total volume of the structure. PPV analysis showed more robust performance, as each voxel concurs to the classification of the propagation, but was not able to detect inclusion of propagated and ground-truth volumes. Mesh distances could interpret the actual shape of the structures, but might report higher mismatches in case of large local differences in the contour surfaces. According to our study, the combination of VD and SD for the validation of contour propagation algorithms in 4D could provide the necessary failure detection accuracy.

Deformable image registration provides a robust mathematical framework to quantify morphological changes that occur along the course of external beam radiotherapy treatments. As clinical reliability of deformable image registration is not always guaranteed, algorithm regularization is commonly introduced to prevent sharp discontinuities in the quantified deformation and achieve anatomically consistent results. In this work we analyzed the influence of regularization on two different registration methods, i.e. B-Splines and Log Domain Diffeomorphic Demons, implemented in an open-source platform. We retrospectively analyzed the simulation computed tomography (CTsim) and the corresponding re-planning computed tomography (CTrepl) scans in 30 head and neck cancer patients. First, we investigated the influence of regularization levels on hounsfield units (HU) information in 10 test patients for each considered method. Then, we compared the registration results of the open-source implementation at selected best performing regularization levels with a clinical commercial software on the remaining 20 patients in terms of mean volume overlap, surface and center of mass distances between manual outlines and propagated structures. The regularized B-Splines method was not statistically different from the commercial software. The tuning of the regularization parameters allowed open-source algorithms to achieve better results in deformable image registration for head and neck patients, with the additional benefit of a framework where regularization can be tuned on a patient specific basis.

Claudia Tarantola, Paolo Giudici - Università degli studi di Pavia MCM Model Determination for Discrete Graphical Models. Fabio Millo - Allenza Assicurazioni Determinazioni del valore di una compagnia di assicurazioni e principi di gestione congiunta di attivi e passivi.

Ricostruire in laboratorio, ossia ex situ, ghiandole endocrine bioartificiali è una prospettiva innovativa della ricerca traslazionale applicata alla medicina rigenerativa dei disturbi endocrino-metabolici. Utilizzando cellule staminali o primarie è possibile ingegnerizzare organoidi funzionali mediante ricellularizzazione sia di matrici tridimensionali (3D) acellulari allogeniche o xenogeniche, derivate da una ghiandola endocrina come quella che si vuole riprodurre, sia supporti reticolari 3D biocompatibili amorfi o che mimano la morfologia originaria delle ghiandola, cioè organomorfi. Con questo metodo sono stati ricostruiti in modelli animali insule pancreatiche, follicoli ovarici e tiroidei, tubuli seminiferi del testicolo e parte della corteccia surrenale. Utilizzando cellule umane è stato riprodotto un abbozzo di ovaio e microaggregati di paratiroide. Le ghiandole endocrine bioartificiali promet- tono di fornire un’alternativa alla terapia sostitutiva con ormoni di sintesi, che richiede compliance da parte del paziente, integrandosi nei circuiti naturali di feed-back. Inoltre, quando generate con cellule autologhe e sup- porti organomorfi individualizzati, è plausibile riproducano una condizione secretiva simile a quella originale del soggetto donatore (terapia personaliz- zata). Infine, il loro uso potrebbe ridurre i costi sostenuti dal Servizio Sanitario Nazionale per le terapie croniche, superando i limiti etici e farma- cologici connessi al trapianto cellulare/tissutale da cadavere e donatore viven- te allogenico o xenogenico e promuovendo il mercato della salute attraverso lo sviluppo delle biotecnologie mediche, analogamente a quanto accadde, oltre un trentennio addietro, per quello delle tecnologie informatiche, con l’avvento dei semiconduttori e dei calcolatori elettronici.

none 13 Ricostruire in laboratorio, ossia ex situ, ghiandole endocrine bioartificiali è una prospettiva innovativa della ricerca traslazionale applicata alla medicina rigenerativa dei disturbi endocrino-metabolici. Utilizzando cellule staminali o primarie è possibile ingegnerizzare organoidi funzionali mediante ricellularizzazione sia di matrici tridimensionali (3D) acellulari allogeniche o xenogeniche, derivate da una ghiandola endocrina come quella che si vuole riprodurre, sia supporti reticolari 3D biocompatibili amorfi o che mimano la morfologia originaria delle ghiandola, cioè organomorfi. Con questo metodo sono stati ricostruiti in modelli animali insule pancreatiche, follicoli ovarici e tiroidei, tubuli seminiferi del testicolo e parte della corteccia surrenale. Utilizzando cellule umane è stato riprodotto un abbozzo di ovaio e microaggregati di paratiroide. Le ghiandole endocrine bioartificiali promet- tono di fornire un’alternativa alla terapia sostitutiva con ormoni di sintesi, che richiede compliance da parte del paziente, integrandosi nei circuiti naturali di feed-back. Inoltre, quando generate con cellule autologhe e sup- porti organomorfi individualizzati, è plausibile riproducano una condizione secretiva simile a quella originale del soggetto donatore (terapia personaliz- zata). Infine, il loro uso potrebbe ridurre i costi sostenuti dal Servizio Sanitario Nazionale per le terapie croniche, superando i limiti etici e farma- cologici connessi al trapianto cellulare/tissutale da cadavere e donatore viven- te allogenico o xenogenico e promuovendo il mercato della salute attraverso lo sviluppo delle biotecnologie mediche, analogamente a quanto accadde, oltre un trentennio addietro, per quello delle tecnologie informatiche, con l’avvento dei semiconduttori e dei calcolatori elettronici. Articolo su invito. L'Endocrinologo: rivista bimestrale. ISSN stampa: 1590-170X; ISSN online: 1720-8351 V. Strusi; S. Mastrogiacomo; N. Zini; D. Dallatana; G. Spaletta; E. Bassoli; A. Gatto; A. Zamparelli; G. Lippi; M. Iafisco; M. Sandri; A. Tampieri; R. Toni V. Strusi; S. Mastrogiacomo; N. Zini; D. Dallatana; G. Spaletta; E. Bassoli; A. Gatto; A. Zamparelli; G. Lippi; M. Iafisco; M. Sandri; A. Tampieri; R. Toni

Il trattamento dei difetti condrali estesi, rappresenta un problema rilevante nella pratica ortopedica. Promettenti risultati sono stati ottenuti grazie all’ausilio dell’ingegneria tissutale ed al giorno d’oggi il trapianto di condrociti di seconda generazione (matrix-assisted) è ampiamente utilizzato in Europa. I risultati ottenuti per il trattamento delle lesioni cartilaginee sono però ancora oggetto di discussione. Inoltre, il trattamento di lesioni osteocondrali presenta problematiche di ancor più difficile soluzione coinvolgendo due tessuti con caratteristiche biologiche differenti e le tecniche attualmente più utilizzate come il trapianto autologo (mosaicoplastica) od il trapianto omologo presentano alcuni limiti. L'ingegneria tissutale possiede le potenzialità per superare tali problematiche. Gli innesti 3-D bioingegnerizzati possono essere ottenuti coltivando le cellule del paziente su scaffold composti da biomateriali porosi, che rappresentano il substrato per lo sviluppo del tessuto. Gli impianti osteocondrali bioingegnerizzati permettono in questo modo di evitare la morbosità del sito donatore e possono essere adattati facilmente alle dimensioni ed alla posizione del difetto. Inoltre, l’approccio con l’ingegneria tissutale consente di adattare le caratteristiche biologiche e biomeccaniche dell’impianto alla specifica articolazione da trattare in modo da indurre una riparazione biologica e quindi durevole nel tempo. The treatment of large chindral articular defects represents a relevant problem in orthopaedic practice

Il corpo clandestino. Dei vantaggi e dei limiti dello sviluppo della biologia e delle neuroscienze.

The purpose of this paper is to describe a system for the rapid spot check of the accuracy of stabilometric platforms used in clinical posturography and, if needed, for estimating a recalibration matrix. It is based on a simple mechanical device which can be applied to any stabilometric platform; it consists of a ballast and a rotating mass which can generate a spiral-shaped training set of posturographic data. A software package has been developed whose purpose is to estimate a calibration matrix and to provide a figure of merit for the calibrated system. The data analysis is organized into two phases: a preliminary global phase, which uses the covariance matrix of the training set, and a refinement, iterative phase, which exploits the equation of the spiral. The characteristic features of the proposed system are: 1) it uses dynamic, not static loading, 2) loading is not applied manually, 3) it uses distributed, not point loads, 4) there is no need to bolt the system to the platform. Although these features are found, separately, in different prototypes described in the literature, their combination can only be found in the proposed system. Moreover, while most systems in the literature are intended for gait analysis, the proposed one is specifically designed for posturography.

BACKGROUND: The role of amylin, which is cosecreted together with insulin by the pancreatic B-cells, in the pathogenesis of type-2 diabetes is still unclear. To elucidate a possible relation between amylin and glucagon we directly evaluated the respective prehepatic secretions following administration of a 75-g oral glucose load (OGL) in humans. MATERIALS AND METHODS: We studied six healthy controls (C), six obese, insulin resistant subjects (O) and six patients with type 2 diabetes (D). Catheters were placed in the femoral artery and hepatic vein according to the hepatic vein catheterization technique. Splanchnic blood flow was assessed by infusion of indocyanine-green dye. The measured variables were analyzed by a general circulatory model for calculation of prehepatic secretion. RESULTS: The total amount of released glucagon was not different between the respective groups (20.5 +/- 2.3 in C, 27.7 +/- 5.1 in O and 27.9 +/- 5.4 micro g/4 h in D). When considered as the difference from the fasting profile, however, glucagon secretion was reduced by 3.5 +/- 14% in C, 25 +/- 12% in O and increased by 36 +/- 21% in D (P = 0.051, D vs. C). Amylin secretion was increased in O (1.10 +/- 0.15) vs. C (0.63 +/- 0.05, P < 0.05) and D (0.24 +/- 0.10 nmol, P < 0.01). Following glucose administration, glucagon secretion significantly inversely correlated with secretion of amylin (r = -0.6, P < 0.01), but not with that of insulin (r =-0.23, P = 0.36). CONCLUSIONS: The inverse correlation between amylin and glucagon secretion suggests that amylin modulates glucagon secretion following oral glucose administration. This study proves for the first time a role of endogenous amylin in the regulation of glucose homeostasis.

Dear Editor, I was interested to read the papers by Fassi and colleagues, published in the January 2014 issue of Journal of Applied Clinical Medical Physics (JACMP).(1) The authors aimed to evaluated the reproducibility of deep inspiration breath hold (DIBHs) controlled by a spirometric device, by assessing the variability of the external surface position within a single DIBH (intra-DIBH) and between DIBHs performed in the same treatment session (intrafraction) or in different sessions (interfraction).(1) As the authors pointed out, displacements of the external surface between different sessions were up to 6.3 mm along a single direction, even at constant inspired volumes. The median value of the interfraction variability in the position of breast passive markers was 2.9 mm (range 1.9–4.8 mm) in the latero–lateral direction, 3.6 mm (range 2.2–4.6 mm) in the antero–posterior direction, and 4.3 mm (range 2.8–6.2 mm) in the cranio–caudal direction.(1) Such descriptive results has nothing to do with reliability analysis.(2-8) Why did the authors not used well-known tests for reliability, such as intraclass correlation coefficient (ICC) or weighted kappa?(2-8) Regarding reliability or agreement, it is good to know that ICC should be used for quantitative variables and weighted kappa (not simple kappa, because kappa has its own limitations, too) for qualitative ones.(2-8) Moreover, Fassi and colleagues reported no significant dose distribution variations in their study.(1) It is crucial to know that statistically significant is completely different from clinically importance, and should not be confused with each other. Moreover, statistics cannot provide a simple substitute for clinical judgment.(2-8) As the authors pointed out in their conclusion, spirometer-based control does not guarantee a reproducible position of the external surface in left-breast DIBH radiotherapy. Such a conclusion is simply a misinterpretation, due simply to inappropriate use of statistical test.