breast elastography

Elasticità e tessuto neoplastico

Considerazioni di fisiopatologia

Antonio Pio Masciotra

Campobasso-Molise-Italia

Email : antoniomasciotra@yahoo.itSkype : antonio.masciotra

Mechanical (elastic) properties of neoplastic tissue

Physiopathology

Antonio Pio Masciotra

Campobasso-Molise-Italy

Email : antoniomasciotra@yahoo.itSkype : antonio.masciotra

Elastografia mammaria :

quantitativa o qualitativa?

Antonio Pio Masciotra

Campobasso

Email : antoniomasciotra@yahoo.itSkype : antonio.masciotra

Breast sonoelastography :

quantitative or qualitative?

Antonio Pio Masciotra

Campobasso-Molise-Italy

Email : antoniomasciotra@yahoo.itSkype : antonio.masciotra

HardnessIt 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 Young’s modulus E. The higher the value of the Young’s modulus, the stiffer the material.

ElasticityElasticity 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:

StrengthIt 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.

DUREZZAE’ la capacità di un materiale a resistere al graffio, all’abrasione, alla scalfittura od alla penetrazione

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.

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:

FORZAE’ 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.

ATOMIC FORCE MICROSCOPE

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

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

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 throughimmunofluorescence and confocal imaging.

Kass et al. Page 9Int J Biochem Cell Biol. Author manuscript; available in PMC 2009 March 19.NIH-PA

Tumor cells’ stiffness decreases

Extracellular matrix’s stiffness increases

La rigidità delle cellule neoplastiche diminuisce

La rigidità della matrice extracellulare aumenta

NVV

Colorazioni istopatologiche per evidenziare

HES

CD 31

Masson’s Trichrome

Cellularità

Fibrosis

Densità dei vasi

NVV

Histopathology techniques show

HES

CD 31

Masson’s Trichrome

Cellularity

Fibrosis

Microvascular density

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

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

Stiffness in funzione della composizione

Densità dei vasi

Cellularità

Fibrosi

Molto ‘molle’ ‘Duro’ Molto ‘duro’‘Molle’

Stiffness depending on composition

Microvascular density

Cellularity

Fibrosis

Very soft Stiff Very stiffSoft

Pathological stiffness score

Very soft Soft Stiff Very stiff0

2

4

6

8

10

12

14

16

18

20

MVD score

Cellularity score

Fibrosis score

"Pathological Stiffness Score

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

Going from a morphologic to a physiopathologic ‘imaging’?

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

SOFTVUESOFTVUE

Going from a morphologic to a physiopathologic ‘imaging’?

SOFTVUESOFTVUE

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.

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.

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, …

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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 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).

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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

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

External

Mechanical force

Natural

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.

Esempio di viscosità La sostanza in basso ha maggior viscosità

della sostanza acquosa in alto

Viscosity demonstration The bottom substance has higher viscosity

than the clear liquid above

Strain vs. Shear Wave Elastography

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Strain Elastography tends to produce abinary 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.

Shear Wave Elastography

Highly-localized estimationof tissue elasticity • Especially, inside hard lesions

Phantom with liquid center inside hard lesion

Strain Elastography interprets the wholelesion as hard, because the applied manualcompression cannot penetrate the hard shell.

Shear Wave Elastography can “see” insidethe hard lesion, because the shear waves can propagate through the hard shell.

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Tipo di tessuto/organo Young’s modulus E (kPa)

Densità(kg/L)

Mammella Tessuto adiposo normale 18-24

1.0 ± 10%

~ Acqua

Tessuto ghiandolare normale 28-66

Tessuto fibroso 96-244

Carcinoma 22-560

Prostata Parte anteriore normale 55-63

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

Breast multiple fibroadenomas – Directional PD

• Mother (58 years old) • Daughter (29 years old)

Breast multiple fibroadenomas – SW Elastography

• Mother (58 years old) • Daughter (29 years old)

Breast SWE – Normal• Fat 53.5 kPa• Gland 29.0 kPa

Breast SWE – Hyperechoic nodule in fat• Fat 7.8 kPa

• Nodule 4.8 kPa

Breast SWE – unilateral gynecomastia 16 years

• Nodule 14.8 kPa• Parenchima 21.3 kPa

RT induced effects on breastBidimensional US

6 months after RT 13 years after RT

RT induced effects on breastSW Elastography

6 months after RT 135 kPa 13 years after RT 25 kPa

RT induced breast subacute effects3D US

RT induced breast subacute effects3D SWE

Breast complicated cystBidimensional US

First study 7 days after therapy

Breast complicated cystPowerdoppler

First study 7 days after therapy

Breast complicated cystSW Elastography

First study 7 days after therapy

Breast complicated cyst3D US

First study 7 days after therapy

Breast complicated cyst3D SWE

First study 7 days after therapy

Breast complicated cyst SWE different settings

Resolution mode Penetration mode

Breast fibroadenomas Bidimensional US

Almost homogeneous Inhomogeneous

Breast fibroadenomas SW Elastography

Different kPa 26kPa Vs 83 kPa

Similar elasticity ratio2.1 Vs 2.5

Breast papillary carcinoma

2008

2009

2010

2011

2008200920102011

Breast carcinoma – Mammography

Benign Malignant

Breast carcinoma – US

Bidimensional – 0.89 cm 3D – 1.86 xm

Breast carcinoma – SWE

Bidimensional 3D

Breast carcinoma – SWE

• High transparence • Low transparence

Breast carcinoma Vs Fibroadenoma SWE

• High transparence • High transparence

2 more nodules in the same breast Bidimensional US

Nodule n. 1 Nodule n. 2

2 more nodules in the same breast SW Elastography (both benign at histology)

Nodule n. 1 Nodule n. 2

Breast carcinoma – Axilla US

Bidimensional 3D

Breast carcinoma – Axilla SWE

Bidimensional 3D

Lymphnodes 2D US

B cell Lymphoma Breast cancer metastasis

Lymphnodes US 3D

B cell Lymphoma Breast cancer metastasis

Lymphnodes SWE

B cell Lymphoma Breast cancer metastasis

Lymphnodes in different sites in the same patientBidimensional US

B cell Lymphoma inguinal B cell Lymphoma ext. iliac

Lymphnodes in different sites in the same patientSW Elastography

B cell Lymphoma inguinal B cell Lymphoma ext. iliac

Lymphnodes SWE Different stiffness depending on histology

• B cell Lymphoma - 21 kPa • Breast cancer metastasis – 16 kPa

• NET metastasis -209 kPa

Aims of elastography

Correct tissue elasticity quantification

Identification of ‘cut off’ elasticity values for the right diagnostic workup of

diffuse and focal diseases

Breast lipomas SW Elastography precision and repeatibility

Fat 19.9 kPa Lipoma 20.5 kPaSW Ratio 1.03

Ore 10:07:09

Fat 8.0 kPa Lipoma 7.8 kPaSW Ratio 1.03

Ore 10:07:34

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.itSkype : antonio.masciotra

Email : antoniomasciotra@yahoo.itSkype : antonio.masciotra