Ultrasound News: Noninvasive Cancer Imaging — The Future of Targeted Cancer Treatments
By Robert Bard, MD, DABR, FASLM
Radiology Today
Vol. 20 No. 8 P. 6

New imaging technologies offer one-step image-guided cancer treatment. This is especially important since the size, depth, margins, and tumor aggression parameters are now quantifiably measured.

Identifying Skin Cancers
Skin cancers are the most common malignancy worldwide, and, while basal cell cancers are rarely fatal, aggressive squamous cell types have devastating health consequences. Malignant melanoma, the leading cause of death in the 25 to 45 age range, has a 98% diagnostic accuracy with 15- to 22-MHz ultrasound systems. More importantly, using quantitative Doppler technologies, we have specific criteria identifying which cancers are most aggressive and whether a tumor is likely to metastasize.

Digital Scanning vs Biopsy
The new optical dermatologic modalities of reflectance confocal microscopy and optical coherence tomography are highly accurate in ruling out malignant disorders and often alert us that a benign-looking lesion requires a biopsy, as is the case with amelanotic melanoma and pigmented basal cell cancers that mimic benign entities. 4D ultrasound imaging provides real-time evaluation of a 3D volume so we can immediately tell the patient the depth and the probability of recurrence.

Specific echoes generated by nests of keratin are strong indicators of aggression and are analyzed volumetrically. Highly suspect areas are then checked for spread in the area under the skin, and a search is performed for lymphadenopathy so we can show our patients that the disease is local and the need for further surgical intervention is unlikely at this stage. Patients are reassured because they simultaneously see the 3D image as the exam proceeds in systematic stages.

4D 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. In serious cases, patients are forewarned that the operation may be complex, involving skin grafts and advanced tissue construction, and can make plans in advance of any definitive treatment.

Reducing Complications
Fear of complications and life-altering posttreatment sequelae concerns deter patients from seeking medical opinions and possible surgical intervention, so many opt for noninvasive options. One out of 33,000 moles are malignant, meaning imaging reduces unnecessary biopsies. Cancer treatment depends on the depth of penetration, possibly involving facial nerves, muscles around the eye, and nasal bone or ear cartilage. Verified superficial tumors may be treated topically or by low-dose nonscarring radiation therapies.

Many cancers provoke a benign local immune response or coexistent inflammatory reaction that simulates a much larger area of malignancy. There is often cicatrix formation accompanying the body’s healing response. 4D imaging highlights the true border of the tumor, sparing healthy tissue and resulting in smaller excisional margins and less scar formation.

Doppler Applications
Blood vessel mapping using various Doppler modalities is routinely used in both cancer treatment and reconstructive preoperative planning. In cancer surgery, it is important to know whether there are any aberrant large veins or significant arteries in the operative site so that postoperative blood loss may be minimized.

Before initiating cosmetic procedures or aesthetic treatments, many plastic and reconstructive surgeons routinely perform a screening overview scan of the facial tissue including the eye, nose, jaw, and neck to check for forgotten fillers or postprocedure complications such as subdermal scar formation, calcific deposits from healing injured ligaments, or retained silicone and other fillers that may have been injected in the past. Particular attention is focused on the nasal area between the eyes because instances of total, permanent blindness have been occurring for more than 10 years due to the inadvertent deposition of injectable filler material into the draining veins that supply the back of the eye.

Advance warning of this danger zone means injectables may be deposited in safer locations. Fat transplants around the eye’s orbit occasionally put pressure on the ophthalmic arteries, cutting off blood supply to the face, resulting in tissue discoloration and, sometimes, death and sloughing of the affected skin. Advanced 3D Doppler systems allow for histogram vessel density measurement of neoplastic angiogenesis (Figure 1). This baseline of neovascularity is used as a treatment surrogate endpoint.

Glandular Cancer Imaging Updates
Breast cancer invading the lower dermis and nipple, discovered with high-resolution probes, signifies that a tumor has spread farther than clinically judged. This finding is essential for detecting the newly discovered entity of breast implant–associated anaplastic lymphoma. This capability is vital for diagnosing the recent epidemic of male breast cancer occurring in first responders from 9/11. The cancer arises near the mammographically difficult nipple areolar complex.

Prostate cancer identified by 4D to be delimited by the capsule and of low vessel density is being followed serially in six-month intervals. Subsequent capsular invasion or increase in vessel density histogram analysis requires urologic measures. Bladder cancer is evaluated concomitantly with the prostate, and neovascularity and wall invasion are noted before surgical referral.

Testicular and thyroid tumors are similarly evaluated by 3D Doppler investigation protocols.

Contrast-Enhanced Ultrasound
In 1990, Rodolfo Campani, MD, director of the radiology department at the University of Pavia in Italy, developed contrast-enhanced ultrasound (CEUS) cancer imaging, which is currently used worldwide but not fully FDA approved. Microbubble media show tumor neovascularity with exquisite detail and are used to evaluate therapeutic response in solid organ disease. This is important, since the Response Evaluation Criteria in Solid Tumors, or RECIST, studies demonstrated that tumor enlargement during treatment may be related to apoptotic cell death with cystic degeneration or immune cell infiltration destroying malignant tissue.

Doppler ultrasound or CEUS reliably verifies decreased angiogenesis in these cases instead of using contrast CT or dynamic contrast-enhanced MRI for confirmation. Thermal treatments such as cryotherapy, high-intensity focused ultrasound, or laser ablation are designated complete when penetrating cancer arteries are no longer visible to the imager.

Margin Delineation
Advances in laser/optical devices allow near-microscopic tissue analysis of the cells by rapid, noninvasive testing. Real-time microscopy is performed during surgery to ensure, in cases of skin cancer, that a tumor border is clear. Future uses in breast and prostate cancer treatments are under clinical study.

Autoimmune Disease and Cancer
Abnormal immune responses that initially appear in the skin are associated with increased cancer incidence. Inflammatory vessels in psoriasis and infection are visibly catalogued, since successful treatment is quantified by a measured decrease in the number and types of abnormal vessels. High vascular immune vessel density is proportional to increased risk of future neoplastic tissue manifestations. Many arthritic conditions have coexistent dermal manifestations, alerting us to the probability of more extensive subclinical joint involvement.

— Robert Bard, MD, DABR, FASLM, has pioneered digital imaging technologies as alternatives to surgical biopsies for dermatologic and solid organ neoplastic disease since 1972. He is the author of Image Guided Dermatologic Treatments, Image Guided Prostate Cancer Treatment, and DCE-MRI of Prostate Cancer and is a member of leading international imaging societies.