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Posts Tagged ‘elastography’


Ultrasound imaging as an instrument for measuring tissue elasticity: “Shear-wave Elastography” VS. “Strain-Imaging”

Writer and curator: Dror Nir, PhD

In the context of cancer-management, imaging is pivotal. For decades, ultrasound is used by clinicians to support every step in cancer pathways. Its popularity within clinicians is steadily increasing despite the perception of it being less accurate and less informative than CT and MRI. This is not only because ultrasound is easily accessible and relatively low cost, but also because advances in ultrasound technology, mainly the conversion into PC-based modalities allows better, more reproducible, imaging and more importantly; clinically-effective image interpretation.

The idea to rely on ultrasound’s physics in order to measure the stiffness of tissue lesions is not new. The motivation for such measurement has to do with the fact that many times malignant lesions are stiffer than non-malignant lesions.

The article I bring below; http://digital.studio-web.be/digitalMagazine?issue_id=254 by Dr. Georg Salomon and his colleagues, is written for lay-readers. I found it on one of the many portals that are bringing quasi-professional and usually industry-sponsored information on health issues; http://www.dieurope.com/ – The European Portal for Diagnostic Imaging. Note, that when it comes to using ultrasound as a diagnostic aid in urology, Dr. Georg Salomon is known to be one of the early adopters for new technologies and an established opinion leader who published many peer-review, frequently quoted, papers on Elastography.

The important take-away I would like to highlight for the reader: Quantified measure of tissue’s elasticity (doesn’t matter if is done by ShearWave or another “Elastography” measure implementation) is information that has real clinical value for the urologists who needs to decide on the right pathway for his patient!

Note: the highlights in the article below are added by me for the benefit of the reader.

Improvement in the visualization of prostate cancer through the use of ShearWave Elastography

by:

Dr Georg Salomon1 Dr Lars Budaeus1, Dr L Durner2 & Dr K Boe1

1. Martini-Clinic — Prostate Cancer Center University Hospital Hamburg Eppendorf Martinistrasse 52, 20253 Hamburg, Germany

2. Urologische Kilnik Dr. Castringius Munchen-Planegg Germeringer Str. 32, 82152 Planegg, Germany

Corresponding author; PD Dr. Georg Salomon

Associate Professor of Urology

Martini Clinic

Tel: 0049 40 7410 51300

gsalornon@uke.de

 

Prostate cancer is the most common cancer in males with more than 910,000 annual cases worldwide. With early detection, excellent cure rates can be achieved. Today, prostate cancer is diagnosed by a randomized transrectal ultrasound guided biopsy. However, such randomized “blind” biopsies can miss cancer because of the inability of conventional TRUS to visualize small cancerous spots in most cases.

Elastography has been shown to improve visualization of prostate cancer.

The innovative ShearWave Elastography technique is an automated, user-friendly and quantifiable method for the determination of prostatic tissue stiffness.

The detection of prostate cancer (PCA) has become easier thanks to Prostate Specific Anti­gen (PSA) testing; the diagnosis of PCA has been shifted towards an earlier stage of the disease.

Prostate cancer is, in more than 80 % of the cases, a heterogeneous and multifocal tumor. Conventional ultra­sound has limitations to accurately define tumor foci within the prostate. This is due to the fact that most PCA foci are isoechogenic, so in these cases there is no dif­ferentiation of benign and malignant tissue. Because of this, a randomized biopsy is performed under ultrasound guidance with at least 10 to 12 biopsy cores, which should represent all areas of the prostate. Tumors, however, can be missed by this biopsy regimen since it is not a lesion-targeted biopsy. When PSA is rising — which usually occurs in most men — the originally negative biopsy has to be repeated.

What urologists expect from imag­ing and biopsy procedures is the detection of prostate cancer at an early stage and an accurate description of all foci within the prostate with different (Gleason) grades of differentiation for best treatment options.

In the past 10 years a couple of new innovative ultrasound techniques (computerized, contrast enhanced and real time elastography) have been introduced to the market and their impact on the detection of early prostate cancer has been evaluated. The major benefit of elastography compared to the other techniques is its ability to provide visualization of sus­picious areas and to guide the biopsy needle, in real time, to the suspicious and potentially malignant area.

Ultrasound-based elastography has been investigated over the years and has had a lot of success for increasing the detection rate of prostate cancer or reducing the number of biopsy sam­ples required. [1-3]. Different compa­nies have used different approaches to the ultrasound elastography technique (strain elastography vs. shear wave elastography). Medical centers have seen an evolution in better image qual­ity with more stable and reproducible results from these techniques.

One drawback of real time strain elastography is that there is a sig­nificant learning curve to be climbed before reproducible elastograms can be generated. The technique has to be performed by compressing and then decompressing the ultrasound probe to derive a measurement of tissue displacement.

Today there are ultrasound scanners on the market, which have the ability to produce elastograms without this “manual” assistance: this technique is called shear-wave elastography. While the ultrasound probe is being inserted transrectally, the “elastograms” are generated automatically by the calcu­lation of shear wave velocity as the waves travel through the tissue being examined, thus providing measure­ments of tissue stiffness and not dis­placement measurements.

There are several different tech­niques for this type of elastography. The FibroScan system, which is not an ultrasound unit, uses shear waves (transient elastography) to evaluate the advancement of the stiffness of the liver. Another technique is Acous­tic Radiation Force Impulse or ARF1 technique, also used for the liver. These non-real-time techniques only provide a shear wave velocity estimation for a single region of interest and are not currently used in prostate imaging.

A shear wave technology that pro­vides specific quantification of tissue elasticity in real-time is ShearWave Elastography, developed by Super-Sonic Imagine. This technique mea­sures elasticity in kilopascals and can provide visual representation of tis­sue stiffness over the entire region of interest in a color-coded map on the ultrasound screen. On a split screen the investigator can see the conven­tional ultrasound B-mode image and the color-coded elastogram at the same time. This enables an anatomi­cal view of the prostate along with the elasticity image of the tissue to guide the biopsy needle.

In short, ShearWave Elastography (SWE) is a different elastography technique that can be used for several applications. It automatically gener­ates a real-time, reproducible, fully quantifiable color-coded image of tissue elasticity.

QUANTIFICATION OF TISSUE STIFFNESS Such quantification can help to increase the chance that a targeted biopsy is positive for cancer.

It has been shown that elastography-targeted biopsies have an up to 4.7 times higher chance to be positive for cancer than a randomized biopsy [4J. Shear-Wave Elastography can not only visual­ize the tissue stiffness in color but also quantify (in kPa) the stiffness in real time, for several organs including the prostate. Correas et al, reported that with tissue stiffness higher than 45 to 50 kPa the chance of prostate cancer is very high in patients undergoing a pros­tate biopsy. The data from Gorreas et al showed a sensitivity of 80 % and a high negative predictive value of up to 9096. Another group (Barr et A) achieved a negative predictive value of up to 99.6% with a sensitivity of 96.2% and specific­ity of 962%. With a cut-off of 4D kPa the positive biopsy rate for the ShearWave Elastography targeted biopsy was 50%, whereas for randomized biopsy it was 20.8 95. In total 53 men were enrolled in this study.

Our group used SWE prior to radical prostatectomy to determine if the Shear-Wave Elastography threshold had a high accuracy using a cutoff >55 kPa. (Fig 1)

We then compared the ShearWave results with the final histopathological results. [Figure I], Our results showed the accuracy was around 78 % for all tumor foci We were also able to verify that ShearWave Elastography targeted biopsies were more likely to be posi­tive compared to randomized biopsies. [Figures 2, 3]

F1

F2F3 

CONCLUSION

SWE is a non-invasive method to visualize prostate cancer foci with high accuracy, in a user-friendly way. As Steven Kaplan puts it in an edi­torial comment in the Journal of Urology 2013: “Obviously, large-scale studies with multicenter corroboration need to be performed. Nevertheless, SWE is a potentially promising modality to increase our efficiency in evaluating prostate diseases:’

 

REFERENCES

  1. Pallweln, L. et al-. Sonoelastography of the prostate: comparison with systematic biopsy findings in 492 patients. European journal of radiology, 2008. 65(2): p. 304-10.
  2. Pallwein, L., et al., Comparison of sono-elastography guided biopsy with systematic biopsy: Impact on prostate cancer detecton. European radiology, 2007_ 17.(9) p. 2278-85.
  3. Salomon, G., et al., Evaluation of prostate can cer detection with ultrasound real-time elas-tographyl a companion with step section path­ological analysis after radical prostatectomy. European urology, 2008. 5446): p. 135462-
  4. Aigner, F., at al., Value of real-time elastography targeted biopsy for prostate cancer detection in men with prostate specific antigen 125 ng/mi or greater and 4-00 ng/ml or Lass. The Journal of urology, 2010. 184{3): p. 813.7,

Other research papers related to the management of Prostate cancer and Elastography were published on this Scientific Web site:

Imaging: seeing or imagining? (Part 1)

Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

Today’s fundamental challenge in Prostate cancer screening

State of the art in oncologic imaging of Prostate.

From AUA2013: “HistoScanning”- aided template biopsies for patients with previous negative TRUS biopsies 

On the road to improve prostate biopsy

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New development in measuring mechanical properties of tissue

Author – Writer: Dror Nir, PhD

Measuring the effects induced onto imaging by the mechanical properties of tissue is a common approach to differentiate tissue abnormalities. In previous posts I discussed the applicability of imaging applications that visualize variations in tissue stiffness; e.g. ultrasound-elastography and MRI-elastography as aid in the diagnosis workflow of cancer. Today, I would like to report on a recent publication made in SPIE Newsroom describing an optical-imaging system to measure tissue stiffness at high resolution. I think that such emerging technologies should be followed up as they bear promise to bridge deficiencies of the traditional modalities currently in use.

Reporting on: Optical elastography probes mechanical properties of tissue at high resolution

By: David Sampson, Kelsey Kennedy, Robert McLaughlin and Brendan Kennedy

Information published at: SPIE Newsroom – Biomedical Optics & Medical Imaging

Probing the micro-mechanical properties of tissue using optical imaging might offer new surgical tools that enable improved differentiation of tissue pathologies, such as cancer or atherosclerosis.

11 January 2013, SPIE Newsroom. DOI: 10.1117/2.1201212.004605

Elastography is an emerging branch of medical imaging that uses mechanical contrast to better characterize tissue pathology than can be achieved with structural imaging alone. It achieves this by imaging a tissue’s response to mechanical loading. Although commercial products based on ultrasonography and magnetic resonance imaging (MRI) have been available for several years, these new modalities offer superior tissue differentiation deep in the human body. However, elastography is limited by its low resolution compared with the length scales relevant to many diseases. Increasing the resolution with optical techniques might offer new opportunities for elastography in medical imaging and surgical guidance.

An elastography system requires a means of loading the tissue to cause deformation and an imaging system with sufficient sensitivity and range to capture this deformation. Implicit in these requirements is access to the tissue of interest. Optical elastography has previously been largely based on schemes that suit small tissue samples rather than intact tissue in living humans. Additionally, such schemes have not had the sensitivity or range to produce high-fidelity images of mechanical properties. We have addressed both these issues in our recent work, developing the means to access tissues in vivo and improve the sensitivity and range of optical elastography using phase-sensitive optical coherence tomography as the underlying modality. The use of optical coherence tomography to perform elastography has come to be referred to as optical coherence elastography.1

To make optical coherence elastography on human subjects feasible, we designed an annular piezoelectric loading transducer (see Figure 1), through which we could simultaneously image, enabling the first in vivo dynamic optical coherence elastography on human subjects.2 We were subsequently able to extend this to three dimensions (see Figure 2), in collaboration with Stephen Boppart’s group at the University of Illinois at Urbana-Champaign.3 This extension took advantage of the high speed of spectral-domain optical coherence tomography, and the maturity of phase-sensitive detection techniques originally developed for Doppler flowmetry and microangiography.

Figure 1. Schematic (left) and photograph (right) of the annular load transducer and imaging optics for in vivo optical coherence elastography.

 

Figure 2. 2D images of in vivo human skin selected from 3D stacks. (a) Optical coherence tomography image and (b) the same image overlaid by the 2D dynamic elastogram recorded at 125Hz load frequency, highlighting the greater strain in the epidermis. Reprinted in modified form with permission.3

For general access to tissues in the body, optical coherence elastography faces two basic limitations. The free-space probe requires miniaturization for versatile access to tissue in confined or convoluted geometries. We addressed this in studies of the elastic properties of human airways using catheter-based anatomical optical coherence tomography.4

 

Figure 3. (a) Schematic diagram of needle optical coherence elastography. The phase difference Δφ=φ1– φ2 determines the displacement, d, when scaled by the wavelength, λ, and refractive index, n. (b) Needle and pig trachea. (c) Local displacement versus distance, with tissue boundaries indicated by red stars. (d) Representative histology. Reprinted in modified form with permission.6

More fundamentally, optical coherence tomography can only penetrate, at best, 1–2mm into most tissues, limiting it to superficial applications. To address this issue, we combined optical coherence elastography with needle probes, an active research area in our group (see Figure 3).5 We conveniently use the needle probe itself to deform the tissue during insertion.6 The deformation ahead of the needle tip depends on the mechanical properties of the tissue encountered, as well as on the nearby tissue environment, particularly on any interfaces ahead of it. We measure the local sub-micrometer displacement of the tissue between two positions of the moving needle probe. We plot this displacement versus distance ahead of the probe: see Figure 3(c). The slope of the displacement at location z is a measure of the local strain. A change in slope signifies a change in tissue stiffness; the steeper the slope, the softer the tissue (other things being equal). Figure 3 highlights this effect in a layered sample of pig trachea. The positions of the changes in slope correlate well with the tissue interfaces shown in the accompanying histology: see Figure 3(d).

The other key area of improvement we have focused on is lowering the optical coherence elastography noise floor by increasing the detection sensitivity, which is vital to make clinical imaging practical. We firstly showed that Gaussian-smoothed, weighted-least squares strain estimation improved the sensitivity of estimates by up to 12dB over conventional finite-difference methods.7 Next, we showed that performance could be further improved at low optical coherence tomo- graphy signal-to-noise ratios (and, therefore, at greater depths in tissue) by employing a 2D Fourier transform technique.8Combined with other system refinements, these improvements have enabled us to reach a displacement sensitivity of 300pm for typical optical coherence tomography signal-to-noise ratios in tissue, with room for improvement.

The Young’s modulus of soft tissue varies from kPa to tens of MPa, whereas the scattering coefficient of such tissues—which is largely responsible for determining the contrast of optical coherence tomography—is typically in the range 2–20mm−1. This apparent native advantage in mechanical over optical contrast (see the example in Figure 4), combined with the maturation of optical coherence elastography methods, bodes well for the future. In our group, we are pursuing tumor-margin identification using elastography; others have begun to consider corneal elastography,9, 10 and still others are examining shear wave schemes with the aim of probing Young’s modulus much deeper in tissues.11,12

 

Figure 4. Optical coherence tomography (a) and optical coherence elastography (b) images of the same phantom with two inclusions visible, showing enhanced mechanical over scattering contrast.

Optical elastography currently sits at a similar stage of development as ultrasound elastography did in 1999. Based on a similar trajectory, this field will rapidly expand over the next decade. Our recent results point to the first convincing applications of optical elastography being just around the corner.

We acknowledge funding for this work from Perpetual Trustees, the Raine Medical Research Foundation, the Cancer Council of Western Australia, the Australian Research Council, the National Health and Medical Research Council (Australia), and the National Breast Cancer Foundation (Australia).


David Sampson

Optical+Biomedical Engineering Laboratory
School of Electrical, Electronic and Computer Engineering

and
Centre for Microscopy, Characterisation and Analysis
The University of Western Australia

Perth, Australia
Kelsey Kennedy, Robert McLaughlin, Brendan Kennedy

Optical+Biomedical Engineering Laboratory
School of Electrical, Electronic and Computer Engineering
The University of Western Australia

Perth, Australia

References:
1. J. Schmitt, OCT elastography: imaging microscopic deformation and strain of tissue, Opt. Express 3(6), p. 199-211, 1998.doi:10.1364/OE.3.000199
2. B. F. Kennedy, T. R. Hillman, R. A. McLaughlin, B. C. Quirk, D. D. Sampson, In vivo dynamic optical coherence elastography using a ring actuator, Opt. Express 17(24), p. 21762-21772, 2009.doi:10.1364/OE.17.021762
3. B. F. Kennedy, X. Liang, S. G. Adie, D. K. Gerstmann, B. C. Quirk, S. A. Boppart, D. D. Sampson, In vivo three-dimensional optical coherence elastography, Opt. Express 19(7), p. 6623-6634, 2011.doi:10.1364/OE.19.006623
4. J. P. Williamson, R. A. McLaughlin, W. J. Noffsingerl, A. L. James, V. A. Baker, A. Curatolo, J. J. Armstrong, Elastic properties of the central airways in obstructive lung diseases measured using anatomical optical coherence tomography, Am. J. Resp. Crit. Care 183(5), p. 612-619, 2011.doi:10.1164/rccm.201002-0178OC
5. R. A. McLaughlin, B. C. Quirk, A. Curatolo, R. W. Kirk, L. Scolaro, D. Lorenser, P. D. Robbins, B. A. Wood, C. M. Saunders, D. D. Sampson, Imaging of breast cancer with optical coherence tomography needle probes: Feasibility and initial results, IEEE J. Sel. Topics Quantum Electron. 18(3), p. 1184-1191, 2012. doi:10.1109/JSTQE.2011.2166757
6. K. M. Kennedy, B. F. Kennedy, R. A. McLaughlin, D. D. Sampson, Needle optical coherence elastography for tissue boundary detection, Opt. Lett. 37(12), p. 2310-2312, 2012. doi:10.1364/OL.37.002310
7. B. F. Kennedy, S. H. Koh, R. A. McLaughlin, K. M. Kennedy, P. R. T. Munro, D. D. Sampson, Strain estimation in phase-sensitive optical coherence elastography, Biomed. Opt. Express 3(8), p. 1865-1879, 2012.doi:10.1364/BOE.3.001865
8. B. F. Kennedy, M. Wojtkowski, M. Szkulmowski, K. M. Kennedy, K. Karnowski, D. D. Sampson, Improved measurement of vibration amplitude in dynamic optical coherence elastography, Biomed. Opt. Express 3(12), p. 3138-3152, 2012. doi:10.1364/BOE.3.003138
9. R. K. Manapuram, S. R. Aglyamov, F. M. Monediado, M. Mashiatulla, J. Li, S. Y. Emelianov, K. V. Larin, In vivo estimation of elastic wave parameters using phase-stabilized swept source optical coherence elastography, J. Biomed. Opt. 17(10), p. 100501, 2012.doi:10.1117/1.JBO.17.10.100501
10. W. Qi, R. Chen, L. Chou, G. Liu, J. Zhang, Q. Zhou, Z. Chen, Phase-resolved acoustic radiation force optical coherence elastography, J. Biomed. Opt. 17(11), p. 110505, 2012. doi:10.1117/1.JBO.17.11.110505
11. C. Li, G. Guan, S. Li, Z. Huang, R. K. Wang, Evaluating elastic properties of heterogeneous soft tissue by surface acoustic waves detected by phase-sensitive optical coherence tomography, J. Biomed. Opt. 17(5), p. 057002, 2012. doi:10.1117/1.JBO.17.5.057002
12. M. Razani, A. Mariampillai, C. Sun, T. W. H. Luk, V. X. D. Yang, M. C. Kolios, Feasibility of optical coherence elastography measurements of shear wave propagation in homogeneous tissue equivalent phantoms,Biomed. Opt. Express 3(5), p. 972-980, 2012. doi:10.1364/BOE.3.00097

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Author and Curator: Dror Nir, PhD

 

That is the question…

We are all used to clichés such as “seeing is believing”, “seeing is knowing”, “don’t be blind” and so on. Out of our seven (natural and supernatural) senses we tend to use and trust our eyes the most. Especially, when it comes to learning, accumulation of experience and acceptance of information as correct. On the other hand, we are taught from childhood to be aware of illusions and not to judge according to looks but rather according to matter. The problem is, does one recognise the substance inside an image? To answer this, a wide-ranging discipline of image interpretation was developed alongside with imaging technology. In order not to fatigue the innocent reader, I’ll review the state of the art of imaging in medicine in subsequent posts, each dedicated to a specific modality. This post is dedicated to…

Current main trends in ultrasound imaging in cancer patients’ management;

The most used imaging modality in medicine is ultrasound. This is due to the fact that it is noninvasive, practically harmless, relatively inexpensive and fairly accessible; i.e. everyone can operate it, even a layman! No formal training or certification is required!

Interesting enough, ultrasound is labeled by the regulatory agencies, FDA and CE, as a diagnostic medical device! This is real demonstration of the aforementioned tendency to believe our eyes, even if these eyes do not see well or the brain behind them is lacking the experience required for ultrasound image interpretation.

Since “ultrasound imaging in medicine” is the subject of many text books and articles I found it  appropriate, for the sake of this post, simply  to refer the reader to Wikipedia’s page (http://en.wikipedia.org/wiki/Medical_ultrasonography) on ultrasound in medicine: “Diagnostic Sonography (ultrasonography) is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendonsmuscles, joints, vessels and internal organs for possible pathology or lesionsObstetric sonography is commonly used during pregnancy and is widely recognized by the public. In physics, the term “ultrasound” applies to all sound waves with a frequency above the audible range of normal human hearing, about 20 kHz. The frequencies used in diagnostic ultrasound are typically between 2 and 18 MHz.”

When it comes to cancer patients’ management, ultrasound provides real-time imaging of body organs at a relatively cost effective workflow. However, it suffers from lack of sensitivity and specificity, especially if the investigator is still fairly inex­perienced. Therefore, no diagnosis is confirmed without biopsy of the suspected lesion discovered during the ultrasound scan. As mentioned in my previous post; identification of suspicious lesions in the prostate during TRUS is so inconclusive that in order to reach diagnosis biopsies are taken randomly.

Did we hit the target?

To improve prostate cancer detection, various biopsy strategies to increase the diagnostic yield of prostate biopsy have been devised: sampling of visually abnormal areas; more lateral placement of biopsies; anterior biop­sies; and obtaining an increased number of cores, with up to 45 biopsy cores [1-5].

In recent years, new features such as 3D and contrast-enhanced sonography, elastography and HistoScanning were added to the basic video image in order to improve the quality of ultrasound based investiga­tion of cancer patients.

3-D Sonography.

3-D ultrasound allows si­multaneous biplanar imaging of the organ with com­puter reconstructions providing a coronal plane as well as a rendered 3-D image. This promises to improve the detection and pre-clinical grading of cancer lesions. Still, the interpretation is very much “image quality” and “user experience” dependent.

3D imaging of breast using ABUS by Siemens; using the coronal view to better investigate a lesion.

  

 

3D imaging of breast using Voluson 730 by GE; three planes are presented for review by the radiologist.

 

 

 Contrast-Enhanced Sonography.

Using intravenous micro-bubble agents in combination with color and pow­er Doppler imaging contributes to increase in the signal obtained in areas of increased vascularity. The underlying assumption is that vascularization in the tumor’s area will be more pronounced than in normal tissue. Hot off the press: The UK National Institute for Health and Clinical Excellence (NICE) has published guidance that supports the use of contrast-enhanced ultrasound with Bracco’s SonoVue ultrasound contrast agent for the diagnosis of liver cancer [6].  The main use of contrast-enhanced ultrasound is directing biopsies to the “most suspicious” areas; i.e. those who presents higher vascularity. Never­theless, in reported clinical studies [7] targeted biopsies’ sensitivity on contrast-enhanced ultrasound was only 68%.

 

Elastography.

Elastography is an imaging technique that evaluates the elasticity of the tissue. The underlying assumption is that tumors present greater stiffness than normal tissue and therefore will be characterized by limited compressibility. The first person to introduce this concept was  Professor Jonathan Ophir, University of Huston, Texas [http://www.uth.tmc.edu/schools/med/rad/elasto/]:
Estimation of differences in lesions’ stiffness relies  on computing the level of correlation between consecutive imaging frames while the tissue that is being imaged is subjected to changing compression, usually applied by the sonographer who manipulates the ultrasound probe. Since malignant and benign lesions exhibit similar elasticity, elastography is not suitable for lesion characterisation. Therefore, as in the previous example, elastography’s main use is identifying suspicious areas in which to take biopsies [8, 9].  Furthermore, users’ experiences related to elastography reveal a lot of controversy.  For example, according to Prof. Bruno Fornage of MD. Anderson [http://www.auntminnie.com/index.aspx?sec=sup&sub=wom&pag=dis&ItemID=99028]; “current commercially available scanners are confounded by a lack of intraobserver reliability, so that it’s not unusual to produce an opposite result on repeat testing a few seconds later”. “There are very few evidence-based non-industry sponsored studies reporting substantial superiority [of elastography] over standard grayscale ultrasound,” he said. “In fact, a sensitivity of 82% in the diagnosis of breast cancer has been reported for elastography, versus 94% for conventional grayscale ultrasound. More disturbing is that even if the technology of elastography worked flawlessly, the huge overlap in breast pathology between very firm solid benign lesions and less firm malignancies gives this technology no practical place in the differential diagnosis of solid breast masses.”

 

HistoScanning.

HistoScanning™ is a novel ultrasound-based software technology that utilizes advanced tissue characterization algorithms to address the clinical requirements for tissue characterization. It visualizes the position and extent of tissue suspected of being malignant in the target organ. In this respect its design is unique and superior to other ultrasound based-technologies [10, 11]. HistoScanning’s first clinically available application (since 2009) is in the management of prostate cancer patients.

 

 

HistoScanning indicating suspicious lesions superimposed on 3-D ultrasound of the prostate. The three imaging plans and 3D reconstruction of the segmented prostate are presented.

 

 

 To conclude; if we are looking to improve the current state of the art in ultrasound-based cancer patients’ management we should strive to introduce systems which will enable the medical practitioners to rule in or rule out suspicious lesions at imaging before they biopsy them. Using ultrasound just as a tool for directing biopsies as done today is not enough. Indeed, this requires capability of ultrasound-based tissue characterisation in addition to detection of ultrasound-based abnormality (i.e. circumstantial evidence for cancer). To-date, the only available system that bears the promise to provide such improvement is HistoScanning. Obviously, the level of confidence in the Negative Predictive Value of HistoScanning and future systems alike must be built to become high enough to provide the medical practitioner the reassurance and comfort that he is not missing any significant cancer by not taking a biopsy. Such confidence can only be built by subjecting these systems (i.e. HistoScanning and alike) to properly designed clinical studies and, not less important, by reporting the experience of early adopters who will test them in a controlled routine use.

 

References

  1. Flanigan RC, Catalona WJ, Richie JP, Ah-mann FR, Hudson MA, Scardino PT, de-Kernion JB, Ratliff TL, Kavoussi LR, Dalkin BL: Accuracy of digital rectal examination and transrectal ultrasonography in localiz­ing prostate cancer: results of a multicenter clinical trial of 6,630 men. J Urol 1994; 152: 1506–1509.
  2. Eichler K, Hempel S, Wilby J, Myers L, Bach­mann LM, Kleijnen J: Diagnostic value of systematic biopsy methods in the investiga­tion of prostate cancer: a systematic review. J Urol 2006; 175: 1605–1612.
  3. Delongchamps NB, de la Roza G, Jones R, Jumbelic M, Haas GP: Saturation biopsies on autopsied prostates for detecting and charac­terizing prostate cancer. BJU Int 2009; 10: 49–54.
  4. Rifkin MD, Dähnert W, Kurtz AB: State of the art: endorectal sonography of prostate gland. AJR Am J Roentgenol 1990; 154: 691– 700.
  5. Chrouser KL, Lieber MM: Extended and sat­uration needle biopsy. Curr Urol Rep 2004; 5: 226–230.
  6. http://www.auntminnieeurope.com/index.aspx?sec=nws&sub=rad&pag=dis&ItemID=607068&wf=284
  7. Yi A, Kim JK, Park SH, Kim KW, Kim HS, Kim JH, Eun HW, Cho KS: Contrast-en­hanced sonography for prostate cancer de­tection in patients with indeterminate clini­cal findings. Am J Roentgenol 2006; 186: 1431–1435.
  8. König K, Scheipers U, Pesavento A, Lorenz A, Ermert H, Senge T: Initial experiences with real-time elastography guided biopsies of the prostate. J Urol 2005; 174: 115–117.
  9. 32 Pallwein L, Mitterberger M, Struve P, Hor-ninger W, Aigner F, Bartsch G, Gradl J, Schurich M, Pedross F, Frauscher F: Com­parison of sonoelastography guided biopsy with systematic biopsy: impact on prostate cancer detection. Eur Radiol 2007; 17: 2278– 2285.
  10. SALOMON (G.), SPETHMANN (J.), BECKMANN (A.), AUTIER (P.), MOORE (C.), DURNER (L.), SANDMANN (M.), HASE (A.), SCHLOMM (T.), MICHL (U.), HEINZER (H.), GRAFEN (M.), STEUBER (T.).Accuracy of HistoScanning for the prediction of a negative surgical margin in patients undergoing radical prostatectomy. Published online in British Journal of Urology International (BJUI). 09/08/2012.
  11. SIMMONS (L.A.M.), AUTIER (P.), ZATURA (F.), BRAECKMAN (J.G.), PELTIER (A.), ROMICS (I.), STENZL (A.), TREURNICHT (K.), WALKER (T.), NM (D.), MOORE (C.M.), EMBERTON (M.).  Detection, localisation and characterisation of prostate cancer by Prostate Hist°Scanning; Published in British Journal of Urology International (BJUI). Issue 1 (July). Vol 110, P 28-35.

 

 Written by Dror Nir

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The Incentive for “Imaging based cancer patient’ management”


Author and Curator: Dror Nir, PhD

It is generally agreed by radiologists and oncologists that in order to provide a comprehensive work-flow that complies with the principles of personalized medicine, future cancer patients’ management will heavily rely on “smart imaging” applications. These could be accompanied by highly sensitive and specific bio-markers, which are expected to be delivered by pharmaceutical companies in the upcoming decade. In the context of this post, smart imaging refers to imaging systems that are enhanced with tissue characterization and computerized image interpretation applications. It is expected that such systems will enable gathering of comprehensive clinical information on cancer tumors, such as location, size and rate of growth.

What is the main incentive for promoting cancer patients’ management based on smart imaging? 

It promises to enable personalized cancer patient management by providing the medical practitioner with a non-invasive and non-destructive tool to detect, stage and follow up cancer tumors in a standardized and reproducible manner. Furthermore, applying smart imaging that provides valuable disease-related information throughout the management pathway of cancer patient will eventually result in reducing the growing burden of health-care costs related to cancer patients’ treatment.

Let’s briefly review the segments that are common to all cancer patients’ pathway: screening, treatment and costs.

 

Screening for cancer: It is well known that one of the important factors in cancer treatment success is the specific disease staging. Often this is dependent on when the patient is diagnosed as a cancer patient. In order to detect cancer as early as possible, i.e. before any symptoms appear, leaders in cancer patients’ management came up with the idea of screening. To date, two screening programs are the most spoken of: the “officially approved and budgeted” breast cancer screening; and the unofficial, but still extremely costly, prostate cancer screening. After 20 years of practice, both are causing serious controversies:

In trend analysis of WHO mortality data base [1], the authors, Autier P, Boniol M, Gavin A and Vatten LJ, argue that breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment is the same: “The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality”.

In prostate cancer mortality at 11 years of follow-up [2],  the authors,Schröder FH et. al. argue regarding prostate cancer patients’ overdiagnosis and overtreatment: “To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected”.

The lobbying campaign (see picture below)  that AdmeTech (http://www.admetech.org/) is conducting in order to raise the USA administration’s awareness and get funding to improve prostate cancer treatment is a tribute to patients’ and practitioners’ frustration.

 

 

 

Treatment: Current state of the art in oncology is characterized by a shift in  the decision-making process from an evidence-based guidelines approach toward personalized medicine. Information gathered from large clinical trials with regard to individual biological cancer characteristics leads to a more comprehensive understanding of cancer.

Quoting from the National cancer institute (http://www.cancer.gov/) website: “Advances accrued over the past decade of cancer research have fundamentally changed the conversations that Americans can have about cancer. Although many still think of a single disease affecting different parts of the body, research tells us through new tools and technologies, massive computing power, and new insights from other fields that cancer is, in fact, a collection of many diseases whose ultimate number, causes, and treatment represent a challenging biomedical puzzle. Yet cancer’s complexity also provides a range of opportunities to confront its many incarnations”.

Personalized medicine, whether it uses cytostatics, hormones, growth inhibitors, monoclonal antibodies, and loco-regional medical devices, proves more efficient, less toxic, less expensive, and creates new opportunities for cancer patients and health care providers, including the medical industry.

To date, at least 50 types of systemic oncological treatments can be offered with much more quality and efficiency through patient selection and treatment outcome prediction.

Figure taken from presentation given by Prof. Jaak Janssens at the INTERVENTIONAL ONCOLOGY SOCIETY meeting held in Brussels in October 2011

For oncologists, recent technological developments in medical imaging-guided tissue acquisition technology (biopsy) create opportunities to provide representative fresh biological materials in a large enough quantity for all kinds of diagnostic tests.

 

Health-care economics: We are living in an era where life expectancy is increasing while national treasuries are over their limits in supporting health care costs. In the USA, of the nation’s 10 most expensive medical conditions, cancer has the highest cost per person. The total cost of treating cancer in the U.S. rose from about $95.5 billion in 2000 to $124.6 billion in 2010, the National Cancer Institute (www.camcer.gov) estimates. The true sum is probably higher as this estimate is based on average costs from 2001-2006, before many expensive treatments came out; quoting from www.usatoday.com : “new drugs often cost $100,000 or more a year. Patients are being put on them sooner in the course of their illness and for a longer time, sometimes for the rest of their lives.”

With such high costs at stake, solutions to reduce the overall cost of cancer patients’ management should be considered. My experience is that introducing smart imaging applications into routine use could contribute to significant savings in the overall cost of cancer patients’ management, by enabling personalized treatment choice and timely monitoring of tumors’ response to treatment.

 

 References

  1. 1.      BMJ. 2011 Jul 28;343:d4411. doi: 10.1136/bmj.d4411
  2. 2.      (N Engl J Med. 2012 Mar 15;366(11):981-90):

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