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

2. Mechanical (elastic) properties
of 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 elastic limit.
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 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 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.
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.
STIFFNESS (RIGIDITA’)
E‟ la resistenza che un materiale oppone al suo „piegamento‟.
L‟acciaio è più rigido dell‟alluminio.
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.
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)
Cell Stiffness Is a Biomarker of the Metastatic Potential of Ovarian Cancer Cells.
PLoS ONE 7(10): e46609. doi:10.1371/journal.pone.0046609

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.
Less invasive
Normal cell toward cancer cell
Single cell stiffness reduction
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. Tumor cells‟ stiffness decreases
Extracellular matrix‟s stiffness increases

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

15. Cellularità
HES
NV
V
CD 31 Densità dei vasi
Fibrosis
Masson‟s
Trichrome

16. Cellularity
HES
NV
V
CD 31 Microvascular density
Fibrosis
Masson‟s
Trichrome

17. Stiffness in funzione del volume
5 mm 7 mm 11 mm 16 mm
a) Molto „molle‟ (9 kPa) „Molle‟ (22 kPa) „Duro‟ (50 kPa) Molto „duro‟ (108 kPa)

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

19. Cellularità
Densità dei vasi
Fibrosi
Molto „molle‟ „Molle‟ „Duro‟ Molto „duro‟

20. Cellularity
Microvascular
density
Fibrosis
Very soft Soft Stiff Very stiff

21. 20
18
16
14 MVD score
12
Cellularity score
10
8 Fibrosis score
6
"Pathological
4 Stiffness Score
2
0
Very soft Soft Stiff Very stiff

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

23. Going from a morphologic to a
physiopathologic ‘imaging’?

24. Transizione da un ‘imaging’ ‘morfologico’
ad un’imaging fisiopatologico?

25. Going from a morphologic to a
physiopathologic ‘imaging’?

26.  Nell‟Antico Egitto il riscontro di una massa dura
nel corpo veniva correlata ad uno stato di
malattia.
 Nella Medicina Ippocratica la palpazione era
parte essenziale dell‟esame 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.

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.  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:
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
29
a qualitative elasticity image.

30. Strain Elastography Summary
 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).
 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 Natural
Mechanical force Heart
 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
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
34 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
35
compression cannot penetrate the hard shell.

36. Tipo di tessuto/organo Young‟s modulus Densità
E (kPa) (kg/L)
Mammella Tessuto adiposo normale 18-24
Tessuto ghiandolare normale 28-66
Tessuto fibroso 96-244
Carcinoma 22-560
Prostata Parte anteriore normale 55-63 1.0 10%
~ Acqua
Parte posteriore normale 62-71
Iperplasia benigna 36-41
Carcinoma 96-241
Muscolo 6-7
Fegato Parenchima sano 0.4-6
Rene Tessuto fibroso 10-55

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
• Fat 53.5 kPa
• Gland 29.0 kPa

40. Breast SWE – Hyperechoic nodule in fat
• Fat 7.8 kPa
• Nodule 4.8 kPa

41. Breast SWE – unilateral gynecomastia 16 years
• Nodule 14.8 kPa
• Parenchima 21.3 kPa

42. RT induced effects on breast
Bidimensional US
6 months after RT 13 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

47. Breast complicated cyst
Bidimensional US
First study 7 days after therapy

48. Breast complicated cyst
Powerdoppler
First study 7 days after therapy

49. Breast complicated cyst
SW Elastography
First study 7 days after therapy

50. Breast complicated cyst
3D US
First study 7 days after therapy

51. Breast complicated cyst
3D SWE
First study 7 days after therapy

52. Breast complicated cyst
SWE different settings
Resolution mode Penetration mode

53. Breast fibroadenomas
Bidimensional US
Almost homogeneous Inhomogeneous

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

55. Breast papillary carcinoma
2008
2009
2010
2009
2008
2011
2010
2011

56. Breast carcinoma – Mammography
Benign Malignant

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 • 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 Lymphoma Breast 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

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 Fat 8.0 kPa Lipoma 7.8 kPa
SW Ratio 1.03 SW Ratio 1.03
Ore 10:07:09 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
Email : antoniomasciotra@yahoo.it
Skype : antonio.masciotra

75. Email : antoniomasciotra@yahoo.it
Skype : antonio.masciotra