# Presentation: 175977

## Please note: 
Due to technical difficulties the medical contrast images (pictures outlined in red) will not be in motion, they will appear as still pictures.

For these images please refer to the transcript, Part 2 page 195 to Part 3 page 203, for the description of the image provided by the presenter.

- Due to technical difficulties the medical contrast images (pictures outlined in red) will not be in motion, they will appear as still pictures.
- For these images please refer to the transcript, Part 2 page 195 to Part 3 page 203, for the description of the image provided by the presenter.

## Benefits of Ultrasound Contrast Agents for Non-Cardiac Applications 

- Benefits of Ultrasound Contrast Agents for Non-Cardiac Applications

- Barry B. Goldberg, MD
- Professor of Radiology and Director
- The Jefferson Ultrasound Research and Education Institute
- Department of Radiology
- Thomas Jefferson University Hospital
- Philadelphia, Pennsylvania

## I am here as a representative of the following organizations: 

- American College of Radiology (ACR)
- American Institute of Ultrasound in Medicine (AIUM)
- Society of Radiologists in Ultrasound (SRU)

## My Background

- Involved with diagnostic ultrasound since 1964
- Started research with ultrasound contrast agents in 1987
- Conducted research with all commercially available contrast agents
- Published 314 peer-reviewed papers, 96 book chapters and 26 text books
- Recipient of 145 grants

## Disclosures

- I have no financial interests with any manufacturer of ultrasound contrast agents or equipment
- I have participated in animal research and clinical trials that were funded in part or wholly by a variety of companies
- All such grants were conducted through my institution under IRB or IACCUC approval

## Diagnostic Imaging Technologies

- It is important that physicians have the _full gamut_ of imaging options available to them so that they can exercise their medical judgment to select the imaging modality that best meets the needs of any given patient

- All imaging modalities have value
- They all have advantages and disadvantages and may be more or less appropriate in a given circumstance

## Real-time imaging 
Allows assessment of dynamics
Non-ionizing radiation
Used since the 1950s, US is considered one of the safest medical imaging modalities
Portability
Allows use at the bedside, intraoperatively, etc
Relative low cost
More affordable than CT and MRI

- Allows assessment of dynamics
- Non-ionizing radiation
- Used since the 1950s, US is considered one of the safest medical imaging modalities
- Portability
- Allows use at the bedside, intraoperatively, etc
- Relative low cost
- More affordable than CT and MRI

- Diagnostic Ultrasound Imaging: *Benefits over other imaging modalities*

## Diagnostic Imaging Technologies

- A key element in the evolution of medical imaging technology has been the advancement from plain imaging to techniques enhanced by the addition of contrast agents** **
- The introduction of ultrasound contrast agents in the mid-1990s has significantly changed the practice of ultrasound imaging in those countries where they are available

## Contrast Agents in Medical Imaging*

- It is well known that there are finite risks associated with the use of contrast media in medical imaging
- The adverse reaction rates of intravenous CT contrast agents are 4% to 12% for ionic contrast and 1% to 3% for nonionic
- The serious adverse event rate for gadolinium (Gd-DTPA) in MR imaging is ~ 1 to 2 per 100,000
- The death rate from intravenous CT contrast agents is 1 to 3 per 100,000 (0.002%)
- The death rate associated with US contrast agents is significantly less than that of CT contrast agents
- The general safety profile is as good as or better than that of other imaging agents that are routinely used and currently deemed as acceptable risks given the benefits to the patient

- * Source: *J Ultrasound Med *2007; 26:705-716.** **

## Limitations of other imaging modalities

- Over-utilization of CT scanning has lead to an increase in ionizing radiation exposure to patients placing them at greater risk for cancer
- The use of contrast-enhanced CT and MRI can be problematic especially in patients with renal insufficiency
- Recent reports of  nephrogenic systemic fibrosis / nephrogenic fibrosing dermopathy (NSF/NFD)  raise concerns over the use of MRI contrast agents in patients with renal insufficiency

## Ultrasound contrast agents 
Remain in the vascular system
Are not excreted into the renal collecting system 

These agents are not nephrotoxic and can be administered in patients with renal insufficiency

- Remain in the vascular system
- Are not excreted into the renal collecting system
- These agents are not nephrotoxic and can be administered in patients with renal insufficiency

- Contrast-Enhanced Ultrasound Imaging

## Currently in the United States the detection of a liver mass with conventional ultrasound imaging often leads to additional imaging examinations such as contrast-enhanced CT or MRI 

The additional imaging procedure results in
 delays in final diagnosis
 increased patient anxiety
 increased costs

- The additional imaging procedure results in
-  delays in final diagnosis
-  increased patient anxiety
-  increased costs

- Diagnostic Imaging Technologies

## Appropriate Use of Contrast Agents

- In the absence of specific evidence of risk and with demonstrated patient benefit, the prudent use of contrast agents should be appropriate
- When the use of a contrast agent provides clinically significant diagnostic information, *not* performing such a procedure may also increase medical risk to the patient

## Contrast Specific US Technology

- “Contrast-specific” imaging modes are currently available on ultrasound systems
- These modes improve the detection of US contrast agents and increase their clinical effectiveness

- Conventional US of the liver was considered  normal

- CEUS demonstrates
-  gross metastases

- Courtesy Dr. Stephanie Wilson, Canada

## Clinical Utility of CEUS

- CEUS is currently being utilized (outside the USA) for the following applications
- Detection of blood flow in large and small vessels
- Evaluation of organ perfusion
- Detection of tumors
- Characterization of masses
- Monitoring tumor treatment effectiveness (during treatment and long term)

## Clinical Utility of Contrast-Enhanced US

- Numerous investigations have shown that CEUS is comparable to contrast-enhanced CT or MRI for both the detection and characterization of liver masses
- In many countries outside the United States it is no longer considered sufficient to perform only non-CEUS imaging of the liver for detection and characterization of focal liver masses

## Contrast-Enhanced US: Enhanced detection of liver lesions

- Multicentric hepatocellular carcinoma

## Contrast-Enhanced US: Liver lesion characterization

- Hepatocellular carcinoma

- Contrast-specific imaging

- Conventional US imaging

## Indeterminate renal mass on CT

- Indeterminate renal mass on CT

- Contrast-enhanced CT
- was indeterminate

- Non-contrast US
- was indeterminate

- CEUS demonstrates vascularity in this cystic renal cell carcinoma resolving the indeterminate CT diagnosis

- Courtesy Dr. Stephanie Wilson, Canada

## Contrast-Enhanced US: Detection of blood flow in breast cancer

## CEUS: Monitoring tumor therapy response

- CEUS: *Monitoring tumor therapy response*

**After 3 weeks **
**of treatment**

- Two different patients with renal cell carcinoma metastasis treated with Sorafenib®

- Patients were considered “good responders” or “bad responders”  based on the results of CT done at 6 months

- Courtesy Dr. Lassau, France

## Investigational uses of CEUS

- Investigational uses of US contrast include
- Plaque characterization / assessment of cardiovascular risks
- Evaluation of trauma  / detection of bleeding
- Detection and characterization of sentinel lymph nodes / staging of cancer
- Therapeutic procedures / treatment of thrombus and malignant tumors

## Contrast-enhanced ultrasound in trauma: 

- Contrast-enhanced ultrasound in trauma:
*Splenic rupture*

- Conventional US

- CEUS

- Surgical specimen

**Notes:**
Post car accident

## Contrast-enhanced ultrasound detection of sentinel lymph nodes (SLNs)

- Evaluation of sentinel lymph nodes in patients with cancer is necessary to
- stage disease
- determine proper therapy
- predict patient prognosis

*Three-dimensional CEUS of multiple lymphatic channels (arrows) and SLNs (S)  identified after injection of contrast at tumor site*

## CEUS appearance of SLNs

- SLNs with metastases demonstrate filling defects (i.e., non-uniform enhancement)

- 6mm

- 4mm

- SLNs as small as 4mm can be detected

**T**

**T**

**T**

## Conclusions

- US contrast agents have a proven safety profile
- Detection and characterization of lesions with CEUS is a significant improvement over conventional US and has been proven to be comparable to contrast-enhanced CT and MRI
- CEUS is diagnostically effective for a variety of applications including:
- Indeterminate CT and MRI cases
- For patients with renal insufficiency

## Conclusions

- It is our considered opinion that the lack of availability of CEUS for non-cardiac imaging in the United States *hinders the delivery of optimal diagnostic imaging services to our patients*
- As a result, *the United States lags behind the rest of the world* in the appropriate and proven applications of ultrasound contrast agents
- The ultrasound community believes that *this is having an adverse impact on clinical care* in the United States

## Thank you for your attention

*Thank you for your attention*