http://basicmed.med.ncku.edu.tw/admin/up_img/990319-2.pdf

Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling

Magnetic resonance elastography: Non-invasive mapping of tissue elasticity

http://ieeexplore.ieee.org/iel5/5/31047/01444179.pdf

Fundamentals of acoustics

Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.

https://www.cell.com/biophysj/pdf/S0006-3495(12)03025-1.pdf

The nanomechanical signature of breast cancer

This paper presents an initial clinical evaluation of in vivo elastography for breast lesion imaging using the concept of supersonic shear imaging. This technique is based on the combination of a radiation force induced in tissue by an ultrasonic beam and an ultrafast imaging sequence capable of catching in real time the propagation of the resulting shear waves. The local shear wave velocity is recovered using a time-offlight technique and enables the 2-D mapping of shear elasticity. This imaging modality is implemented on a conventional linear probe driven by a dedicated ultrafast echographic device. Consequently, it can be performed during a standard echographic examination. The clinical investigation was performed on 15 patients, which corresponded to 15 lesions (4 cases BI-RADS 3, 7 cases BI-RADS 4 and 4 cases BI-RADS 5). The ability of the supersonic shear imaging technique to provide a quantitative and local estimation of the shear modulus of abnormalities with a millimetric resolution is illustrated on several malignant (invasive ductal and lobular carcinoma) and benign cases (fibrocystic changes and viscous cysts). In the investigated cases, malignant lesions were found to be significantly different from benign solid lesions with respect to their elasticity values. Cystic lesions have shown no shear wave propagate at all in the lesion (because shear waves do not propage in liquid). These preliminary clinical results directly demonstrate the clinical feasibility of this new elastography technique in providing quantitative assessment of relative stiffness of breast tissues. This technique of evaluating tissue elasticity gives valuable information that is complementary to the B-mode morphologic information. More extensive studies are necessary to validate the assumption that this new mode potentially helps the physician in both false-positive and false-negative rejection.

Quantitative assessment of breast lesion viscoelasticity: initial clinical results using supersonic shear imaging.

MR elastography is a novel imaging technique for the visualization of elastic properties of tissue. It is expected that this method will have diagnostic value for the clarification of suspicious breast lesions. Low-frequency mechanical waves are coupled into the tissue and visualized via an MR sequence which is phase-locked to the mechanical excitation. Commonly, elasticity is assumed to be isotropic and reconstruction is performed in only two dimensions. The technique is extended to three dimensions such that the entire symmetric elasticity tensor is assessed. This is achieved by measuring different phases of the mechanical wave during one oscillatory cycle. Thereby it is possible to provide information about the anisotropy of the elasticity tensor. Finite-element simulations as well as phantom experiments are performed to demonstrate the feasibility of the method. Initial clinical results of a breast carcinoma are presented. The analysis of the eigenvalues of the elasticity tensor support the hypothesis that breast carcinoma might exhibit an anisotropic elasticity distribution. The surrounding benign tissue appears isotropic. Thereby new and additional diagnostic information is provided which might help in distinguishing between benign and malignant breast diseases.

https://iopscience.iop.org/article/10.1088/0031-9155/45/6/317/pdf

High-resolution tensor MR elastography for breast tumour detection.

MR-elastography is a new technique for assessing the viscoelastic properties of tissue. One current focus of elastography is the provision of new physical parameters for improving the specificity in breast cancer diagnosis. This analysis describes a technique to extend the reconstruction to anisotropic elastic properties in terms of a so-called transversely isotropic model. Viscosity is treated as being isotropic. The particular model chosen for the anisotropy is appealing because it is capable of describing elastic shear anisotropy of parallel fibers. The dependence of the reconstruction on the particular choice of Poisson's ratio is eliminated by extracting the compressional displacement contribution using the Helmholtz-Hodge decomposition. Results are presented for simulations, a polyvinyl alcohol breast phantom, excised beef muscle, and measurements in two patients with breast lesions (invasive ductal carcinoma and fibroadenoma). The results show enhanced anisotropic and viscous properties inside the lesions and an indication for preferred fiber orientation.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrm.20355

Imaging anisotropic and viscous properties of breast tissue by magnetic resonance-elastography

We study d-dimensional Conformal Field Theories (CFTs) on the cylinder, $$ {S}^{d-1}\times \mathrm{\mathbb{R}} $$
 , and its deformations. In d = 2 the Casimir energy (i.e. the vacuum energy) is universal and is related to the central charge c. In d = 4 the vacuum energy depends on the regularization scheme and has no intrinsic value. We show that this property extends to infinitesimally deformed cylinders and support this conclusion with a holographic check. However, for $$ \mathcal{N}=1 $$
 supersymmetric CFTs, a natural analog of the Casimir energy turns out to be scheme independent and thus intrinsic. We give two proofs of this result. We compute the Casimir energy for such theories by reducing to a problem in supersymmetric quantum mechanics. For the round cylinder the vacuum energy is proportional to a + 3c. We also compute the dependence of the Casimir energy on the squashing parameter of the cylinder. Finally, we revisit the problem of supersymmetric regularization of the path integral on Hopf surfaces.

/pdf/the-casimir-energy-in-curved-space-and-its-supersymmetric-1d7i93w6qo.pdf

The Casimir energy in curved space and its supersymmetric counterpart

Purpose To analyze the initial assessment of the technical feasibility of in-vivo MR elastography (MRE) of the prostate gland in healthy volunteers. Materials and methods Dynamic sinusoidal MR elastography was performed in 7 healthy volunteers in prone position. The mechanical wave was induced via an external oscillator attached to the pubic bone. A 1.5 Tesla MR system (Philips Medical Systems, Netherland) was used with 4 combined surface coils for signal reception. MRE data acquisition was performed with a motion-sensitive spin-echo MR sequence that was phase-locked to the mechanical oscillation. Subsequently, these images were used to reconstruct the local distribution of elasticity inside the prostate gland. The applied reconstruction algorithm was tested by means of phantom measurements. Results Sufficient penetration of the mechanical wave into the prostate gland was achieved in all volunteers, allowing the acquisition of utilizable image data sets. The reconstructed distribution of elasticity (shear-modulus) inside the healthy prostate gland correlated with the zonal anatomy of the gland. The elasticity of the central portion (2.2 +/- 0.3 kPa) appeared to be lower than the peripheral prostatic portion (3.3 +/- 0.5 kPa). Conclusion In-vivo MRE of the prostate gland is technically feasible. The proposed experimental set-up allows the efficient insertion of the mechanical wave into the prostate gland and provides a successful MR data acquisition.

MR elastography of the prostate: Initial in-vivo application

Purpose: Imaging of breast tumors and various breast tissues using magnetic resonance (MR) elastography (MRE) to explore the potential of elasticity as a new parameter for the diagnosis of breast lesions. Methods: Low-frequency mechanical waves are transmitted into breast tissue by means of an oscillator. The local characteristics of the mechanical wave are determined by the underlying elastic properties of the tissue. Theses waves can be displayed by means of a motion-sensitive spin-echo MR sequence within the phase of the MR image. Elasticity reconstruction is performed on the basis of 8 “snapshots” of each wave within the three spatial directions. We performed in-vivo measurements in 15 female patients with malignant tumors of the breast, 5 patients with benign breast tumors, and 15 healthy volunteers. Results: Malignant invasive breast tumors documented the highest values of elasticity with a median of 15.9 kPa and a wide range of stiffnesses between 8 and 28 kPa. In contrast, benign breast lesions represented low values of elasticity, which were significantly different from malignant breast tumors (median elasticity: 7.0 kPa; p = 0.0012). This was comparable to the stiffest tissue areas in healthy volunteers (median elasticity 7.0 kPa), whereas breast parenchyma (median: 2.5 kPa) and fatty breast tissue (median: 1.7 kPa) showed the lowest values of elasticity. Two invasive ductal carcinomas had elasticity values of 8 kPa and two stiff parenchyma areas in healthy volunteers had elasticities of 13 and 15 kPa. These lesions could not be differentiated by their elasticity. Conclusion: We conclude that MRE is a promising new imaging modality with the capability to assess the viscoelastic properties of breast tumors and the surrounding tissues. However, from our preliminary results in a small number of patients it is obvious that there is an overlap in the elasticity ranges of soft malignant tumors and stiff benign lesions. Ziel: Validierung der Darstellungsmoglichkeiten der MR-Elastographie bei Brusttumoren und verschiedenen Brustgewebearten. Methode: Mittels eines Oszillators werden niederfrequente mechanische Schallwellen in das Brustgewebe eingekoppelt. Die lokale Beschaffenheit der Welle wird durch die elastischen Eigenschaften des Gewebes bestimmt. Durch eine bewegungssensitive MR-Spinechosequenz werden die mechanischen Wellen in der Phase des MR-Bildes dargestellt. Die Rekonstruktion der lokalen Elastizitatswerte geschieht auf der Basis von jeweils 8 Messungen der Welle in allen drei Raumrichtungen. Wir untersuchten 15 Patientinnen mit jeweils einem malignen Brusttumor und 5 Patientinnen mit einem benignen Tumor der Brust. Zusatzlich wurden 15 gesunde Probandinnen untersucht. Ergebnisse: Maligne Tumore erreichten die hochsten Elastizitatwerte mit einem Median von 15,9 kPa und einer grosen Streuung der Werte (8 - 28 kPa). Im Gegensatz zu malignen Tumoren zeigten benigne Brusttumore eine signifikant niedrigere Elastizitat (Median: 7,0 kPa; p = 0,0012). Diese Werte waren vergleichbar mit den hartesten Gewebearealen bei gesunden Probandinnen mit einem Median von 7,0 kPa, wohingegen Brustparenchym (Median: 2,5 kPa) und fetthaltige Gewebeareale (Median: 1,7 kPa) erwartungsgemas die niedrigsten Elastizitatswerte aufwiesen. Zwei invasiv-duktale Brustkarzinome wiesen mit 8 kPa eine niedrige Elastizitat auf, wohingegen zwei Parenchymareale bei gesunden Probandinnen Werte bis zu 15 kPa erreichten. Diese Lasionen konnten anhand ihrer Elastizitat nicht differenziert werden. Schlussfolgerung: MRE ist eine neue Art der Bildgebung, die eine Bestimmung der viskoelastischen Eigenschaften von Brusttumoren und dem umgebenden Gewebe ermoglicht. Allerdings zeigt sich an dem bisher untersuchten kleinen Patientenkollektiv eine Uberschneidung der Elastizitatsbereiche von weichen malignen Brusttumoren und verharteten Brustparenchymarealen.

Jakob Lorenzen

Papers

High-resolution tensor MR elastography for breast tumour detection.

Imaging anisotropic and viscous properties of breast tissue by magnetic resonance-elastography

The Casimir energy in curved space and its supersymmetric counterpart

MR elastography of the prostate: Initial in-vivo application

MR elastography of the breast:preliminary clinical results.