Elasticità e tessuto neoplastico Considerazioni di fisiopatologia Antonio Pio Masciotra

1. Elasticità e tessuto neoplastico Considerazioni di fisiopatologia Antonio Pio Masciotra Campobasso-Molise-Italia Email : antoniomasciotra@yahoo.it Skype : antonio.masciotra

2. Mechanical (elastic) propertiesof neoplastic tissue Physiopathology Antonio Pio Masciotra Campobasso-Molise-Italy Email : antoniomasciotra@yahoo.it Skype : antonio.masciotra

3. Elastografia mammaria : quantitativa o qualitativa? Antonio Pio Masciotra Campobasso Email : antoniomasciotra@yahoo.it Skype : antonio.masciotra

4. Breast sonoelastography : quantitative or qualitative? Antonio Pio Masciotra Campobasso-Molise-Italy Email : antoniomasciotra@yahoo.it Skype : antonio.masciotra

5. PRINCIPAL MECHANICAL PROPERTIES Those characteristics of the materials which describe their behaviour under external loads are known as Mechanical Properties. The most important and useful mechanical properties are: Strength It is the resistance offered by a material when subjected to external loading. So, stronger the material the greater the load it can withstand. Depending upon the type of load applied the strength can be tensile, compressive, shear or torsional. The maximum stress that any material will withstand before destruction is called its ultimate strength. Elasticity Elasticity of a material is its power of coming back to its original position after deformation when the stress or load is removed. Elasticity is a tensile property of its material. The greatest stress that a material can endure without taking up some permanent set is called elasticlimit. Stiffness (Rigidity) The resistance of a material to deflection is called stiffness or rigidity. Steel is stiffer or more rigid thanaluminium. Stiffness is measured by Young’s modulus E. The higher the value of the Young’s modulus, the stiffer the material. Hardness It is the ability of a material to resist scratching, abrasion, indentation or penetration.

6. PRINCIPALI PROPRIETA’ MECCANICHE Le caratteristichedeimaterialichedescrivonoillorocomportamentoquandovengonosottoposti a carichiesternivengono definite PROPRIETA’ MECCANICHE. Le piùimportantidiessesono: FORZA E’ la resistenzaoffertada un materialequandovienesottoposto ad un caricoesterno. Pertanto, quantopiù forte è un materialetantomaggioresaràilcaricocheessopuòsorreggere. ELASTICITA’ E’ la capacitàdi un materiale a recuperare le sue posizione e forma inizialidopo la rimozionedi un caricoodunaforza, la cui applicazione ne avevaindotto la deformazione. STIFFNESS (RIGIDITA’) E’ la resistenzache un materialeoppone al suo ‘piegamento’. L’acciaio è piùrigidodell’alluminio. La stiffness vienemisuratadalModulo di Young E. Quantomaggiore è ilvalore del modulo di Young tantomaggiore è la stiffness del materiale. DUREZZA E’ la capacità di un materiale a resistere al graffio, all’abrasione, alla scalfittura od alla penetrazione

8. ATOMIC FORCE MICROSCOPE

9. Stiffness distribution of cells and results of migration and invasion test Citation: Xu W, Mezencev R, Kim B, Wang L, McDonald J, et al. (2012) CellStiffnessIs a Biomarkerof the MetastaticPotentialofOvarianCancerCells. PLoS ONE 7(10): e46609. doi:10.1371/journal.pone.0046609

10. The distribution of the actin network plays an important role indetermining the mechanical properties of single cells. As cells transform from non-malignant to cancerous states, theircytoskeletal structure changes from anorganized to an irregularnetwork, and this change subsequently reduces the stiffness of single cells. Further progressive reduction of stiffness corresponds to an increase in invasive and migratory capacity of malignant cells. Less invasive Normalcelltowardcancercell Single cellstiffnessreduction More invasive

11. Mammary epithelial growth and morphogenesis is regulated by matrix stiffness. (A) 3D cultures of normal mammary epithelial cells within collagen gels of different concentration. Stiffening the ECM through an incremental increase in collagen concentration (soft gels: 1 mg/ml Collagen I, 140 Pa; stiff gels 3.6 mg/ml Collagen I, 1200 Pa) results in the progressive perturbation of morphogenesis, and the increased growth and modulated survival of MECs. Altered mammary acini morphology is illustrated by the destabilization of cell–cell adherens junctions and disruption of basal tissue polarity indicated by the gradual loss of cell–cell localized β-catenin (green) and disorganized β4 integrin (red) visualized through immunofluorescence and confocal imaging. Kass et al. Page 9 Int J Biochem Cell Biol. Author manuscript; available in PMC 2009 March 19. NIH-PA

13. Tumorcells’ stiffnessdecreases Extracellularmatrix’s stiffnessincreases

14. La rigidità delle cellule neoplastiche diminuisce La rigidità della matrice extracellulare aumenta

15. Colorazioniistopatologiche per evidenziare Cellularità HES NV V Densitàdeivasi CD 31 Fibrosis Masson’s Trichrome

16. Histopathology techniques show Cellularity HES NV V Microvascular density CD 31 Fibrosis Masson’s Trichrome

17. Stiffness in funzionedel volume 11 mm 5 mm 7 mm 16 mm ‘Molle’ (22 kPa) ‘Duro’ (50 kPa) Molto ‘duro’ (108 kPa) a) Molto ‘molle’ (9 kPa)

18. Stiffnessdepending on volume 11 mm 5 mm 7 mm 16 mm Soft (22 kPa) Stiff (50 kPa) Very stiff (108 kPa) a) Very soft (9 kPa)

19. Stiffness in funzionedellacomposizione Cellularità Densitàdeivasi Fibrosi Molto ‘duro’ ‘Molle’ ‘Duro’ Molto ‘molle’

20. Stiffnessdepending on composition Cellularity Microvascular density Fibrosis Very stiff Soft Stiff Very soft

21. Pathologicalstiffness score

22. Transizione da un ‘imaging’ ‘morfologico’ ad un’imagingfisiopatologico?

23. Goingfrom a morphologic to a physiopathologic ‘imaging’?

24. Transizione da un ‘imaging’ ‘morfologico’ ad un’imagingfisiopatologico? SOFTVUE SOFTVUE

25. Goingfrom a morphologic to a physiopathologic ‘imaging’? SOFTVUE SOFTVUE

26. Nell’AnticoEgittoilriscontrodiunamassaduranelcorpovenivacorrelata ad unostatodimalattia. • NellaMedicinaIppocraticala palpazione era parte essenzialedell’esamefisico del paziente. • NelTerzoMillenniola «PalpazioneRemota»stadiventandorealtà grazie all’ Imaging Elastografico.

27. In ancient Egypt, a link was established between • a hard mass within the human body & pathology. • In Hippocratic medicine, palpation was • an essential part of a physical examination. • In the 21st century, «remote palpation» by means • of elastographic imaging is becoming a reality.

28. Many R& D techniques have emerged since the 1990s, based on the Ultrasound and Magnetic Resonance imagingmodalities. • Sonoelasticity: KJ Parker et al, 1990 • Ultrasound Strain Elastography: J Ophir et al, 1991 • MR Elastography: R Sinkus et al, 2000 • Shear Wave Elastography: J Bercoff et al, 2004 • All techniques are based on the same principle: • Generate a stress, and then use an imaging technique to map the tissue response to this stress in every point of the image. • but differ substantially in terms of their performance characteristics: • Qualitative / quantitative nature, absolute / relative quantification. • Accuracy / precision / reproducibility, … • Spatial / temporal resolution, sensitivity / penetration, …

29. Initially introduced by Hitachi, and later on Siemens,in the early 2000s. • More manufacturers have followed in the last year(s). • The basic principle used is the one proposed • by Ophir’s group in the early 1990s: • Tissue compression (Stress) is induced • manually by the user. • Multiple images are recorded using • conventional imaging at standard frame rates. • The relative deformation (Strain) is estimated • using Tissue Doppler techniques. • The derived strains are displayed as • a qualitativeelasticity image.

30. StrainElastography Summary • Stress Source  Manual Compression (user-dependent). • Stress Frequency  Static (user-induced vibration < 2 Hz). • Result Type  Qualitative image (E=Stress/Strain, but Stress isunknown). • Relative quantification (Background-to-Lesion-Ratio). • Straightforward implementationon • current scanners (standard acquisition • architecture,plus Tissue-Doppler-like processing).. • Stress penetration / uniformity issues. • User-applied compression is attenuated by • soft objects & depthand cannot penetrate hard-shelled lesions. • User-dependence. • User-applied compression is attenuated by soft objects & depth, and cannot penetrate hard-shelled lesions.

31. Heart Mechanical force Natural External • SuperSonic Imagine has developed a novel method called SonicTouch, • which is based on focused ultrasound, and can remotely generate • Shear Wave-fronts providing uniform coverage of a 2D area interest.

32. Esempio di viscosità La sostanza in basso ha maggior viscosità della sostanza acquosa in alto

33. Viscositydemonstration The bottomsubstancehashigherviscositythan the clearliquidabove

34. Strain vs. Shear Wave Elastography Strain Elastography tends to produce a binary classification, where the whole lesion is either hard or soft. Shear Wave Elastography provides richer& more complex information with manycases of hard borders plus soft centers. The differences between Strain and Shear Wave Elastography are not surprising, given the very different principles on which they are based.

35. Shear Wave Elastography Phantom with liquid center inside hard lesion • Highly-localized estimation • of tissue elasticity • Especially, inside hard lesions Shear Wave Elastography can “see” inside the hard lesion, because the shear waves can propagate through the hard shell. Strain Elastography interprets the whole lesion as hard, because the applied manual compression cannot penetrate the hard shell.

37. Breast multiple fibroadenomas – Directional PD Mother (58 yearsold) Daughter (29 yearsold)

38. Breast multiple fibroadenomas – SW Elastography Mother (58 yearsold) Daughter (29 yearsold)

39. Fat 53.5 kPa Gland 29.0 kPa Breast SWE – Normal

40. Fat 7.8 kPa Nodule 4.8 kPa Breast SWE – Hyperechoicnodule in fat

41. Nodule 14.8 kPa Parenchima 21.3 kPa Breast SWE – unilateralgynecomastia 16 years

42. RT inducedeffects on breastBidimensional US 6 monthsafter RT 13 yearsafter RT

43. 13 yearsafter RT 25 kPa RT inducedeffects on breastSW Elastography 6 monthsafter RT 135 kPa

44. RT inducedbreast subacute effects3D US

45. RT inducedbreast subacute effects3D SWE

47. Breast complicatedcystBidimensional US First study 7 days after therapy

48. Breast complicatedcystPowerdoppler First study 7 days after therapy

49. Breast complicatedcystSW Elastography First study 7 daysaftertherapy

50. Breast complicatedcyst3D US First study 7 daysaftertherapy