Automatic measurement of the evolutionary process. Dynamics of primary biliary cirrhosis (PBC) Nicola Dioguardi, Milano

Transcription

1 Automatic measurement of the evolutionary process. Dynamics of primary biliary cirrhosis (PBC) 1 Why devote efforts to dynamics processes and evolutionary phenomena are actually described by the simple and understandable laws of statics. But their simplicity led to evaluations that remain semiquantitative, and thus subjective. This has generated antinomias. 2

2 The main antinomia is the use of laws suggested by statics to study the living systems behaviours. These bodies are continuously changing in time and their behaviour, in reality, follows the very different laws of dynamics. This is a long story never concluded. 3 The theory of the dynamical systems opens new orizons but up to now, utilization of dynamics has been limited by the inconsistent capacity or by now suitability of both calculation power and measurement of the available tools. 4

3 This speech refers to a proposal of a method with a friendly technology useful to study process * enhancements adopting dynamics criteria. * As defined by Aristotles 5 The experimental archetype Primary Biliary Cirrhosis (PBC) is a chronic liver autoimmune destructive, non suppurative process, which is described in 4 phases, somehow according dynamics logics 6

4 Therefore, the liver biopsy of the PBC affected livers was chosen as reference archetype to project first the automatic technical model and then the actual machine, the Metrizer 7 A technology for dynamics The technology of Metrizer uses criteria of dynamics that allow, at actual state of art, to make some first limited previsions 8

5 Measurable marker of a dynamic process is the progressive deposition in every tissue of inactive irreversible matter. It is to underline that irreversibility is deeply rooted in dynamics. 9 Ilya Prigogine, Bertrand Russell and others consider this kind of emergence an effect of entropy and one of factors of chronic enhancement of any process. 10

6 A definition To enter into the dynamic behaviour context of my speech let me begin with a definition that describes the aim of our research: measurement of the dynamic state of a chronic pathologic process means the identification of the position it actually takes on its course from α to ω. 11 A corollary of this definition might be that dynamic vision is a different way of observing the world through the relationships between three concepts: entropy, irreversibility and change in time. 12

7 Machine workings The moments of the histological section analysis concerning our new method that studies PBC dynamics are resolved by Metrizer with following four points: 13 1.The machine with its total automation discriminates and metrically measures four notable structures PBC dependent: i. inflammatory cluster cells, ii. fibrosis Sirius-Red positive fibres, iii. natural blended with the neo-regenerating bile ductules, iv. the tectonic index. 14

8 The image shows inflammation cluster, the biliary ductules fragments and the fibrosis islets. The black structure is glissonian fragment present in the fibrosis catalogue is automatically eliminated by the machine. 15 The next image shows a inflammatory cell cluster treated with a triangulation method to metrically measure their extension. 16

9 The slide shows the algorithm from natural to perimetrized cluster with triangulation of Delaunay using the sum of the most periferal segments between two lymphocytes distance of 20 µm. 17 The image shows a particular of the stantial cluster inflammation cells triangulation 18

10 and the next slide shows triangulation of extra cluster pelagic inflammations cells 19 Inflammation is excluded from dynamic factors, because its entropy is dispersed in the environment and does not accumulate within the system, thus the process is totally reversible and cannot institutionally be used for dynamic studies. 20

11 2. In the second moment simultaneously the machine discriminates other new parameters. An example is shown in the following projection 21 22

12 We have used fractal dimension to correct the irregular outlines of biological bodies from The interest of the tectonic index is due to its quantitative marking of the changes of the configuration of living tissues. The slide shows the algorithm to obtain this interesting index. We do not intend to discuss in this meeting this parameter that is used as processes timer. 24

13 TCI=1-H TCI describes the loss of tissue organization or any deviation from natural order: a high TCI indicates a high degree of tissue disorder, and a low TCI indicates a low degree of tissue disorder. 25 We derived the tectonic index from an idea of the engineer Hurst to control the irregular changes of flows of the Nile estuary canals after the Assuan dam construction. 26

14 This image shows the hepatogram given by Metrizer in about four minutes, in C-Virus Chronic Hepatitis 27 This projection shows the hepatogram obtainable in seven minutes of a PBC affected patient. The data of bile duct fragments are added to the application. 28

15 3. At third point of its program the Metrizer i. describes what it sees with its words, and ii. thinks and writes with its words the automatic electronic diagnosis on the basis of parameters it has drawn from the histological section metrical portrait At this point the machine automatically after the traditional static description measures the dynamic state of PBC process with the following steps 30

16 It selects and measures two notable structures of the pathologic metrical portrait that are considered dependent from the entropy that are i) natural and neo regenerated bile ducts and ii) fibrosis. This image shows CK7 positive biliary matter pattern formed by the mixture of natural and new formed functional inactive bile ducts. 31 The image shows the catalogue of measured ductular fragments of all the section, i.e. the first notable structure to construct PBC trajectory 32

17 This image shows the pattern of collagen forming fibrosis of liver tissues i.e. the second notable structure to construct PBC trajectory 33 This image shows the entire section catalogue of collagen islets measured by the machine forming the liver sections fibrosis. 34

18 With their irreversible cumulation within the liver tissue, these material masses are identified as the factors of the chronic process enhancement. 35 This image shows the cumulative curves that demonstrate the continuity of the progression of both parameters (CK7 positive matter and fibrosis) within the PBC affected liver system of our case list 36

19 In the following step the machine reduces in a dot-like geometrical figure the blending in a One, the set standardized fibrosis and of the CK7 positive natural and neo-generated biliary ductules. 37 Construction of particula Now the machine constructs the dot-like particola that will design the trajectory of the PBC process This is obtained transforming the couple of metrical data into oriented vectors, putting the two notable parameters on x/y orthogonal semiaxes and taking the lengths of each segment as modulus of a vector. The sum of such two-vectorial magnitudes produces a new vector that gathers into a One the couple of the two cumulant entropic structures representable with a dual point particola of the process. The modules are its values 38

20 The set of particolae of our case list distributed on the quarter of the orthogonal space in which were calculated, recall the cloud of Gibbs. Among the particolae cloud were discriminated three sub-clouds that when plotted in function of their fibrosis components on the x considered as timer and biliary ductules on the y considered as disease parameter generates an ogive. 39 trajectory dynamic reference ideal trajectory The image shows the set of cloud particle locations with a potential function on the oriented line of real number state space that represents the standardised trajectory of the process. Each particola of a new patient divides the trajectory into two sections defining the patient dynamic evolution in the percentage covered by the disease and the rest to be made. 40

21 The image in brief presents The set of dynamic particolae cloud. The points of the cloud are transferred to the oriented line of real numbers representing the standardised trajectory of the process. Ogival cumulative curve orders the dynamic particola within the three clouds in panel A. This curve is sub-divided into three tertiles marked by blue points and represents the trajectory of the overall dynamic process of PBC from α to ω. 41 In conclusion of this very ingenuous research we can only say firstly that the dot-like particle value expressed by one vectorial scalar is the main dynamic measurable operator able to map a trajectory 42

22 secondly that the work of the robot is absolutely essential for the performance of the method. 43 To close my speech, let me say that any correlation is recognizable between the metrical data of our case-list, divided into three phases by the matematicians rules of dynamics and the semi-quantitative data, divided into four stages (see Table). For example the 20 specimen classified by the semiquantitative Scheuer classification at minor levels of staging. Where is the truth? This is the problem. 44

23 But every result and acquired notion needs to be discussed. 45