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Elasticità e tessuto neoplastico Considerazioni di fisiopatologia Antonio Pio Masciotra Campobasso-Molise-Italia

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Presentazione sul tema: "Elasticità e tessuto neoplastico Considerazioni di fisiopatologia Antonio Pio Masciotra Campobasso-Molise-Italia"— Transcript della presentazione:

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

2 Mechanical (elastic) properties of neoplastic tissue Physiopathology Antonio Pio Masciotra Campobasso-Molise-Italy Skype : antonio.masciotra

3 Elastografia mammaria : quantitativa o qualitativa? Antonio Pio Masciotra Campobasso Skype : antonio.masciotra

4 Breast sonoelastography : quantitative or qualitative? Antonio Pio Masciotra Campobasso-Molise-Italy Skype : antonio.masciotra

5 Hardness It is the ability of a material to resist scratching, abrasion, indentation or penetration. Stiffness (Rigidity) The resistance of a material to deflection is called stiffness or rigidity. Steel is stiffer or more rigid than aluminium. Stiffness is measured by Youngs modulus E. The higher the value of the Youngs modulus, the stiffer the material. 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 elastic limit. 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.

6 DUREZZA E la capacità di un materiale a resistere al graffio, allabrasione, alla scalfittura od alla penetrazione STIFFNESS (RIGIDITA) E la resistenza che un materiale oppone al suo piegamento. Lacciaio è più rigido dellalluminio. La stiffness viene misurata dal Modulo di Young E. Quanto maggiore è il valore del modulo di Young tanto maggiore è la stiffness del materiale. ELASTICITA E la capacità di un materiale a recuperare le sue posizione e forma iniziali dopo la rimozione di un carico od una forza, la cui applicazione ne aveva indotto la deformazione. PRINCIPALI PROPRIETA MECCANICHE Le caratteristiche dei materiali che descrivono il loro comportamento quando vengono sottoposti a carichi esterni vengono definite PROPRIETA MECCANICHE. Le più importanti di esse sono: FORZA E la resistenza offerta da un materiale quando viene sottoposto ad un carico esterno. Pertanto, quanto più forte è un materiale tanto maggiore sarà il carico che esso può sorreggere.

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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) Cell Stiffness Is a Biomarker of the Metastatic Potential of Ovarian Cancer Cells. PLoS ONE 7(10): e doi: /journal.pone

10 The distribution of the actin network plays an important role in determining the mechanical properties of single cells. As cells transform from non-malignant to cancerous states, their cytoskeletal structure changes from an organized to an irregular network, 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. Single cell stiffness reduction Less invasive More invasive Normal cell toward cancer cell

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

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13 Tumor cells stiffness decreases Extracellular matrixs stiffness increases

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

15 NV V HES CD 31 Massons Trichrome Cellularità Fibrosis Densità dei vasi

16 NV V HES CD 31 Massons Trichrome Cellularity Fibrosis Microvascular density

17 Stiffness in funzione del volume a) Molto molle (9 kPa) Duro (50 kPa)Molto duro (108 kPa) Molle (22 kPa) 5 mm 11 mm 16 mm7 mm

18 Stiffness depending on volume a) Very soft (9 kPa) Stiff (50 kPa)Very stiff (108 kPa) Soft (22 kPa) 5 mm 11 mm 16 mm7 mm

19 Densità dei vasi Cellularità Fibrosi Molto molle Duro Molto duro Molle

20 Microvascular density Cellularity Fibrosis Very soft Stiff Very stiff Soft

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22 Transizione da un imaging morfologico ad unimaging fisiopatologico?

23 Going from a morphologic to a physiopathologic imaging?

24 Transizione da un imaging morfologico ad unimaging fisiopatologico?

25 Going from a morphologic to a physiopathologic imaging?

26 NellAntico Egitto il riscontro di una massa dura nel corpo veniva correlata ad uno stato di malattia. Nella Medicina Ippocratica la palpazione era parte essenziale dellesame fisico del paziente. Nel Terzo Millennio la «Palpazione Remota» sta diventando realtà grazie all Imaging Elastografico. NellAntico Egitto il riscontro di una massa dura nel corpo veniva correlata ad uno stato di malattia. Nella Medicina Ippocratica la palpazione era parte essenziale dellesame fisico del paziente. Nel Terzo Millennio la «Palpazione Remota» sta diventando realtà 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. 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 imaging modalities. 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, … 28

29 The basic principle used is the one proposed by Ophirs group in the early 1990s: 1.Tissue compression (Stress) is induced manually by the user. 2.Multiple images are recorded using conventional imaging at standard frame rates. 3.The relative deformation (Strain) is estimated using Tissue Doppler techniques. 4.The derived strains are displayed as a qualitative elasticity image. Initially introduced by Hitachi, and later on Siemens, in the early 2000s. More manufacturers have followed in the last year(s). 29

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

31 External Mechanical force Natural Hear t 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 Viscosity demonstration The bottom substance has higher viscosity than the clear liquid above

34 Strain vs. Shear Wave Elastography 34 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 many cases 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 Highly-localized estimation of tissue elasticity Especially, inside hard lesions Phantom with liquid center inside hard lesion Strain Elastography interprets the whole lesion as hard, because the applied manual compression cannot penetrate the hard shell. Shear Wave Elastography can see inside the hard lesion, because the shear waves can propagate through the hard shell. 35

36 Tipo di tessuto/organoYoungs modulus E (kPa) Densità (kg/L) MammellaTessuto adiposo normale ± 10% ~ Acqua Tessuto ghiandolare normale28-66 Tessuto fibroso Carcinoma ProstataParte anteriore normale55-63 Parte posteriore normale62-71 Iperplasia benigna36-41 Carcinoma Muscolo6-7 FegatoParenchima sano0.4-6 ReneTessuto fibroso10-55

37 Breast multiple fibroadenomas – Directional PD Mother (58 years old)Daughter (29 years old)

38 Breast multiple fibroadenomas – SW Elastography Mother (58 years old)Daughter (29 years old)

39 Breast SWE – Normal Fat53.5 kPa Gland29.0 kPa

40 Breast SWE – Hyperechoic nodule in fat Fat7.8 kPa Nodule4.8 kPa

41 Breast SWE – unilateral gynecomastia 16 years Nodule14.8 kPa Parenchima21.3 kPa

42 RT induced effects on breast Bidimensional US 6 months after RT13 years after RT

43 RT induced effects on breast SW Elastography 6 months after RT 135 kPa 13 years after RT 25 kPa

44 RT induced breast subacute effects 3D US

45 RT induced breast subacute effects 3D SWE

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47 Breast complicated cyst Bidimensional US First study7 days after therapy

48 Breast complicated cyst Powerdoppler First study7 days after therapy

49 Breast complicated cyst SW Elastography First study7 days after therapy

50 Breast complicated cyst 3D US First study7 days after therapy

51 Breast complicated cyst 3D SWE First study7 days after therapy

52 Breast complicated cyst SWE different settings Resolution modePenetration mode

53 Breast fibroadenomas Bidimensional US Almost homogeneousInhomogeneous

54 Breast fibroadenomas SW Elastography Different kPa 26kPa Vs 83 kPa Similar elasticity ratio 2.1 Vs 2.5

55 Breast papillary carcinoma

56 Breast carcinoma – Mammography BenignMalignant

57 Breast carcinoma – US Bidimensional – 0.89 cm 3D – 1.86 xm

58 Breast carcinoma – SWE Bidimensional 3D

59 Breast carcinoma – SWE High transparence Low transparence

60 Breast carcinoma Vs Fibroadenoma SWE High transparence

61 2 more nodules in the same breast Bidimensional US Nodule n. 1 Nodule n. 2

62 2 more nodules in the same breast SW Elastography (both benign at histology) Nodule n. 1 Nodule n. 2

63 Breast carcinoma – Axilla US Bidimensional 3D

64 Breast carcinoma – Axilla SWE Bidimensional 3D

65 Lymphnodes 2D US B cell LymphomaBreast cancer metastasis

66 Lymphnodes US 3D B cell Lymphoma Breast cancer metastasis

67 Lymphnodes SWE B cell Lymphoma Breast cancer metastasis

68 Lymphnodes in different sites in the same patient Bidimensional US B cell Lymphoma inguinal B cell Lymphoma ext. iliac

69 Lymphnodes in different sites in the same patient SW Elastography B cell Lymphoma inguinal B cell Lymphoma ext. iliac

70 Lymphnodes SWE Different stiffness depending on histology B cell Lymphoma - 21 kPa Breast cancer metastasis – 16 kPa NET metastasis -209 kPa

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72 Aims of elastography Correct tissue elasticity quantification Identification of cut off elasticity values for the right diagnostic workup of diffuse and focal diseases

73 Breast lipomas SW Elastography precision and repeatibility Fat 19.9 kPa Lipoma 20.5 kPa SW Ratio 1.03 Ore 10:07:09 Fat 8.0 kPa Lipoma 7.8 kPa SW Ratio 1.03 Ore 10:07:34

74 Breast sonoelastography : Question n. 1 : quantitative or qualitative? Answer n. 1 Quantitative! Question n. 2 : SW or Strain Elastography? Answer n. 2 SW Elastography Antonio Pio Masciotra Campobasso-Molise-Italy Skype : antonio.masciotra

75 Skype : antonio.masciotra


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