Ultrasound-Guided Cancer Imaging: The Future of Targeted Cancer Treatment

Tumor margins and malignant grade are best defined by vascular imaging modalities such as Doppler flow or contrast enhancement combined with videomicroscopy. The following are image-guided treatment options that can be performed on breast, prostate, liver, and skin cancers.

NEW DOPPLER APPLICATIONS

Blood vessel mapping using the various Doppler modalities is routinely used in both cancer treatment and reconstructive planning. In cancer surgery, it is critical to locate aberrant veins or arterial feeders in the operative site so postoperative blood loss is minimized. Advanced 3D Doppler systems allow for histogram vessel density measurement of neoplastic angiogenesis.

VESSEL DENSITY INDEX

(Fig 1) Baseline neovascularity is a treatment surrogate endpoint and therapy is maintained, increased, or suspended based on quantitative angiogenesis data.

SOLID ORGAN CANCER IMAGING UPDATES

Breast cancer, invading the lower dermis and nipple, discovered with high-resolution probes signifies the tumor has outflanked clinical observation essential for detecting the newly discovered entity of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). This capability is also vital for diagnosing the recent epidemic of male breast cancers arising near the mammographically difficult nipple areolar complex, occurring in our 911 First Responders.

For prostate cancer, 4D ultrasound can identify low-grade cancer delimited by the capsule and with low vessel density, and should be followed serially at 6-month intervals.

CONTRAST-ENHANCED ULTRASOUND (CEUS)

In 1990, Dr. Rodolfo Campani developed ultrasound contrast for liver imaging and Drs. Cosgrove (London) and Lassau (Paris) extended the use to breast, skin, and prostate tumors. CEUS is currently used worldwide but is not Food and Drug Administration (FDA)-approved in the United States.

One use for CEUS is microbubble neovascularity, which demonstrates therapeutic response since the Response Evaluation Criteria in Solid Tumors (RECIST) studies noted tumor enlargement during treatment might be related to cell death with cystic degeneration or immune cell infiltration destroying malignant tissue. Doppler ultrasound or CEUS reliably verifies decreased angiogenesis in place of contrast CT or dynamic contrast-enhanced (DCE) MRI. If vascular perfusion ceases, thermal treatments, such as cryotherapy, high-intensity focused ultrasound (HIFU), or laser ablation, should be completed.

Four-dimensional (4D) ultrasound imaging is real-time evaluation of a 3D volume so we can show the patient immediately the depth and the probability of recurrence. Specific echoes in skin cancer generated by nests of keratin are strong indicators of aggression and analyzed volumetrically. Highly suspect areas are checked for locoregional spread and a search is performed for lymphadenopathy so we can determine if the disease is confined and whether further surgical intervention is unlikely at this time. Patients are reassured because they simultaneously see the exam proceed in systematic stages. In serious cases, the patient is forewarned that the operation involves skin grafts and tissue construction.  4D ultrasound permits image-guided biopsy of the most virulent area of the dermal tumor and allows the pathologist to focus on the most suspicious region of the lymph node mass excised from the armpit, neck, or groin. Some laboratories are using postop radiography and sonography for better specimen analysis.

VIDEO DIGITAL MICROSCOPY VS BIOPSY

Fear of complications can deter patients from seeking medical opinion and surgical intervention, so many opt for noninvasive options. Imaging can help to reduce unnecessary biopsies because it can help identify the 1 out of every 33,000 moles that is malignant, while weeding out those that are not.

Once skin cancer is diagnosed, the treatment depends on depth penetration, possibly involving facial nerves, muscles around the eye and nasal bone or ear cartilage. Verified superficial tumors are treated topically or by low dose non-scarring radiation. Many cancers provoke a benign local immune response or coexistent inflammatory reaction that simulates a much larger area of malignancy, and cicatrix accompanies the healing response. 4D imaging combined with optical microscopy (RCM (reflectance confocal microscopy) or OCT (optical coherence tomography)) defines the true border during surgery, sparing healthy tissue, resulting in smaller excisional margins and less scar formation.

 

Do you have any tips on incorporating ultrasound in cancer imaging? Comment below, or, AIUM members, continue the conversation on Connect, the AIUM’s online community.

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Robert Bard, MD, DABR, FASLMS, currently runs a private consulting practice in New York City. He authored Image Guided Dermatologic Treatments, Image Guided Prostate Cancer Treatment, and DCE-MRI of Prostate Cancer and is a member of multiple leading international imaging societies. Since 1972, Dr. Bard has pioneered digital imaging technologies as alternatives to surgical biopsies for dermatologic and solid organ neoplastic disease.

Sonographers and Contrast-Enhanced Ultrasound

Now that contrast-enhanced ultrasound (CEUS) has been approved in the United States for several abdominal applications in adults and pediatrics, I decided to take a deeper look into the sonographer’s role in CEUS. Traditionally, sonographers perform ultrasound examinations based on a protocol, construct a preliminary ultrasound findings worksheet, and perhaps discuss the findings with a radiologist. And now CEUS has transformed traditional ultrasound and gives physicians and sonographers additional diagnostic information related to the presence and patterns of contrast enhancement.DSC00125

Based on sonographers’ traditional scope of practice, some questions came to mind. What is the training process for sonographers to learn CEUS? How should CEUS images be obtained and stored? How should CEUS findings be communicated?

I envision CEUS training for sonographers broken down into stages, where they begin by learning the basics and eventually transition to where they can perform and record the studies independently. The first stage for sonographers is the ‘CEUS learning curve.’ In this stage, sonographers become familiar with basic CEUS concepts, eg, understanding physics of contrast agents and contrast-specific image acquisition modes, CEUS protocols, and typical patterns of contrast enhancement seen in various organs. In addition, an important part of the training is recognizing contrast reactions, and learning IV placement, documentation and billing related to CEUS.

The next stage involves sonographers performing more patient care and gaining scanning responsibilities. Sonographers place the IV and prepare the contrast agent. The scope of sonographer responsibilities does not generally include contrast injection (although it is reasonable since CT, MR, nuclear medicine, and echocardiography technologists routinely place IV lines and inject contrast). It should be noted that CEUS examination usually requires an additional person (physician, nurse, or another sonographer) to assist with contrast injection while the sonographer performs the ultrasound examination. In the beginning of sonographer training, it is very beneficial to have a radiologist present in the room to guide scanning and appropriate image recording.

In the third stage, a well-trained sonographer is more independent. At the completion of the examination, the sonographer will either send clips or still images to a physician to document the CEUS findings and discuss the procedure. Ideally, a worksheet is filled out, comparable to what is done today with “regular” ultrasound.

The majority of CEUS examinations are performed based on pre-determined protocols, usually requiring a 30–60-sec cineloop to document contrast wash-in and arterial phase enhancement. After that continuous scanning should be terminated and replaced with intermittent acquisition of short 5–10-sec cineloops obtained every 30–60 sec to document late phase contrast enhancement. These short clips have the advantage of limiting stored data while providing the interpreting physician with real-time imaging information. Detailed information on liver imaging CEUS protocols could be found in the recently published technical guidelines of the ACR CEUS LI-RADS committee.[i] Some new users might acquire long 2–3-minute cineloops instead, producing massive amounts of CEUS data. As a result, studies can slow down a PACS system if departments are not equipped to deal with large amounts of data. In addition, prolonged continuous insonation of large areas of vascular tissue could result in significant ultrasound contrast agent degradation limiting our ability to detect late wash-out, a critical diagnostic parameter required to diagnose well-differentiated HCC. Any solution requires identifying and capturing critical moments, which will be determined by a sonographer’s expertise. Exactly how sonographers can ensure CEUS will successfully capture the most important images is a critical question that must be answered and standardized.

Ideally, leading academic institutions should provide CEUS training for physicians and sonographers. I have seen and attended CEUS continuing medical education courses and they are a great way for physicians and sonographers to learn CEUS imaging. CEUS is a step forward for sonographers and will potentially transform our scope of practice. The technology will advance the importance of sonographers and diagnostic ultrasound, and importantly it will improve the care of our patients.

Acknowledgements:
Dr. Laurence Needleman, MD
Dr. Andrej Lyshchik, MD
Dr. John Eisenbrey, PhD
Joanna Imle, RDMS, RVT

[i] Lyshchik A, Kono Y, Dietrich CF, Jang HJ, Kim TK, Piscaglia F, Vezeridis A, Willmann JK, Wilson SR. Contrast-enhanced ultrasound of the liver: technical and lexicon recommendations from the ACR CEUS LI-RADS working group. Abdom Radiol (NY). 2017 Nov 18. doi: 10.1007/s00261-017-1392-0. [Epub ahead of print]

Has CEUS helped your sonography career? How do you envision CEUS being incorporated in your work? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Corinne Wessner BS, RDMS, RVT is the Research Sonographer for Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Corinne has an interest in contrast-enhanced ultrasound, ultrasound research, medical education, and sonographer advocacy.