Posts Tagged ‘contrast enhanced ultrasound imaging’


Author – Writer: Dror Nir, PhD

To those of you who did not know, 2013 is the year of the ultrasound: This initiative was launched by AIUM and its objectives:

  • Raise awareness of the value and benefits of ultrasound among patients, health care providers, and insurers
  • Provide ultrasound education and evidence-based guidelines for health care providers
  • Educate insurers about the cost savings and patient benefits associated with performing an ultrasound study when scientific evidence supports its potential effectiveness compared to other imaging modalities
  • Educate patients about the benefits of ultrasound as the appropriate imaging modality for their care
  • Encourage the incorporation of ultrasound into medical education

 Quoting from the ultrasound first web-site:

The initiative is designed to call attention to the safe, effective, and affordable advantages of ultrasound as an alternative to other imaging modalities that are more costly and/or emit radiation. For a growing number of clinical conditions, ultrasound has been shown to be equally effective in its diagnostic capability, with a distinct advantage in safety and cost over computed tomography and magnetic resonance imaging. Despite this advantage, evidence suggests that ultrasound is vastly underutilized. Ultrasound First focuses on educating health care workers, medical educators, insurers, and patients of the benefits of ultrasound in medical care. “There is growing support and public awareness for the need to reduce and carefully monitor patients’ exposure to radiation during medical imaging. The use of ultrasound as an alternative imaging modality will help achieve that goal while reducing cost,” states AIUM President Alfred Abuhamad, MD. “Many health care workers and insurers are unacquainted with the range of conditions for which ultrasound has been shown to have superior diagnostic capabilities. Disseminating this knowledge to health care workers and incorporating ultrasound in medical protocols where scientific evidence has shown its diagnostic efficacy will undoubtedly improve patient safety and reduce cost. The time to act is now.”

 A primary component of Ultrasound First is providing clinical evidence for the use of ultrasound. To that aim, the Journal of Ultrasound in Medicine has launched a special feature, the Sound Judgment Series, consisting of invited articles highlighting the clinical value of using ultrasound first in specific clinical diagnoses where ultrasound has shown comparative or superior value. Clinical conditions that will be addressed in the series include postmenopausal bleeding, right lower quadrant pain, pelvic pain, right upper quadrant pain, and shoulder pain, among others. This series will serve as an important educational resource for health care workers and educators.  On the clinical evidence page one can find reasoning for why ultrasound first. Not much related to cancer diagnosis and management. The only interesting claim is:Ultrasound-guided surgery: Its use to remove tumors from women who have palpable breast cancer is much more successful than standard surgery in excising all the cancerous tissue while sparing as much healthy tissue as possible.”

In support of this initiative The Journal of Ultrasound in Medicine has launched a special series, Sound Judgment, comprised of invited articles highlighting the clinical value of using ultrasound first in specific clinical diagnoses where ultrasound has shown comparative or superior value. So far it includes only two items related to management of cancer: Sonography of Facial Cutaneous Basal Cell Carcinoma, A First-line Imaging Technique; by Ximena Wortsman, MD, and Quantitative Assessment of Tumor Blood Flow Changes in a Murine Breast Cancer Model After Adriamycin Chemotherapy Using Contrast-Enhanced Destruction-Replenishment Sonography; by Jian-Wei Wang, MD et. al. The devoted readers of our Open Access Scientific Journal might find the article by Dr. Wortsman, MD bringing complementary information to a previous post of mine: Virtual Biopsy – is it possible?. Qouting from this article: “Cutaneous basal cell carcinoma is the most common cancer in human beings, and the face is its most frequent location. Basal cell carcinoma is rarely lethal but can generate a high degree of disfigurement. Of all imaging techniques, sonography has proven to support the diagnosis and provide detailed anatomic data on extension in all axes, the exact location, vascularity, and deeper involvement. This information can be used for improving management and the cosmetic results of patients.”

 The article gives clear presentation of the problem and includes demonstrative pictures:


Figure: Basal cell carcinoma with dermal involvement (transverse view, nasal tip). Grayscale sonography (A) and 3-dimensional reconstruction (B, 5- to 8-second sweep) show a 10.1-mm (wide) × 1.4-mm (deep) well-defined hypoechoic oval lesion (between markers in A and outlined in B) that affects the dermis (d) of the left nasal wing. Notice the hyperechoic spots (arrowheads) within the lesion. The nasal cartilage (c) is unremarkable; asterisk indicates basal cell carcinoma.

Basal cell carcinoma with dermal and subcutaneous involvement (transverse view, frontal region). A, Grayscale sonography shows a 11.4-mm (wide) × 6.6-mm (deep) well-defined oval hypoechoic lesion that involves the dermis (d) and subcutaneous tissue (st). There are hyperechoic spots (arrowheads) within the tumor. B, Color Doppler sonography shows increased vascularity within the tumor (asterisk). C, Three-dimensional sonographic reconstruction (5- to 8-second sweep) highlights the lesion (asterisk, outlined); b indicates bony margin of the skull.

Basal cell carcinoma with dermal and subcutaneous involvement (transverse view, frontal region). A, Grayscale sonography shows a 11.4-mm (wide) × 6.6-mm (deep) well-defined oval hypoechoic lesion that involves the dermis (d) and subcutaneous tissue (st). There are hyperechoic spots (arrowheads) within the tumor. B, Color Doppler sonography shows increased vascularity within the tumor (asterisk). C, Three-dimensional sonographic reconstruction (5- to 8-second sweep) highlights the lesion (asterisk, outlined); b indicates bony margin of the skull.


Figure: Pleomorphic presentations of basal cell carcinoma lesions on grayscale sonography (transverse views). Notice the variable shapes of the tumors.


Figure: Frequently, blood flow can be detected within the tumor and its periphery, with slow-flow arteries or veins. The latter vascular data can orient the clinician about the distribution and amount of blood flow that he or she will face during surgery. Despite the fact that basal cell carcinomas usually do not present high vascularity, it should be kept in mind that many of basal cell carcinoma operations are performed in the offices of clinicians and not in the main operating rooms of large hospitals. Nevertheless, the finding of high vascularity within a clinically diagnosed basal cell carcinoma may suggest another type of skin cancer that could occasionally mimic basal cell carcinoma, such as squamous cell carcinoma, Merkel cell carcinoma, or a metastatic tumor. The above figure presents variable degrees of vascularity in basal cell carcinoma lesions going from hypovascular to hypervascular on color and power Doppler sonography (transverse views)


Figure: The depth correlation between sonography (variable frequency) and histologic analysis in facial basal cell carcinoma has been reported to be excellent. Thus, the intraclass correlation coefficient for comparing thickness for the two methods (sonography and histologic analysis) that has been described in literature is 0.9 (intraclass correlation coefficient values ≥0.9 are very good; 0.70–0.89 are good; 0.50–0.69 are moderate; 0.30–049 are mediocre; and ≤0.29 are bad). Two rare sonographic artifacts have been described in basal cell carcinoma. One is the “angled border” that is produced by an inflammatory giant cell reaction underlying the tumor, which may falsely increase the apparent size of the tumor. The other is the “blurry border,” which is produced by large hypertrophy of the sebaceous glands surrounding the lesion. According to the literature, both artifacts can be recognized by a well-trained operator. The figure above presents the sonographic involvement of deeper layers such as the nasal cartilage and orbicularis muscles in the face is of critical importance and may change the decision about the type of surgery. Basal cell carcinoma with nasal cartilage involvement (3-dimensional reconstruction, 5- to 8-second sweep, transverse view, left nasal wing). Notice the extension of the tumor (asterisk, outlined) to the nasal cartilage region (c); d indicates dermis.

Basal cell carcinoma with involvement of the orbicularis muscle of the eyelid (m). Grayscale sonography (transverse view, right lower eyelid) shows that the tumor (asterisk) affects the muscle layer (arrows).

Basal cell carcinoma with involvement of the orbicularis muscle of the eyelid (m). Grayscale sonography (transverse view, right lower eyelid) shows that the tumor (asterisk) affects the muscle layer (arrows).


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Writer: 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 ( 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 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 []:
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 []; “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™ 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.



  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.
  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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