CT Laser Mammography

In some countries, diagnostic and screening mammography have been credited with saving lives through early detection of breast cancer. But, mammography, whether conventional or digital, has been thoroughly documented as missing between 25 percent and 40 percent of breast cancers. 

The miss rate is even higher for women with dense breasts, which constitute 40 percent of the female population. In the dense breast group, which is comprised predominantly of young women, the incidence of cancer is four to six times higher than in non-dense breasts. But, the sensitivity of mammography is very low, ranging from 24.5 percent to 37 percent.

And mammography has additional drawbacks. Of every 100 cases deemed “positive” and, therefore, resulting in biopsy, between 60 percent and 80 percent are actually negative or benign.
A huge number of women undergo these biopsies that would not be necessary if a more accurate imaging procedure were used; they are subjected to the mental trauma of being told they may have breast cancer and the subsequent agony of awaiting biopsy results.

These unnecessary biopsies also add significant costs to the healthcare system. Every 500 cases that have been confirmed positive are actually false positives and cost at least a half of a million dollars. 

The principal reason for the low sensitivity of mammography is that it only images anatomic detail and provides no functional information. Functional information is essential for early and accurate diagnosis of breast cancer and can be expected to significantly reduce the number of unnecessary biopsies. 

Imaging Diagnostic Systems Inc. (IDSI), of Plantation, Fla., a pioneer in laser breast imaging, has developed the CT Laser Mammography (CTLM) system. CTLM combines morphologic and functional information that could change the current diagnostic and clinical management of breast cancer by detecting angiogenesis, the very first visible sign of breast cancer growth. 

Angiogenesis is the process by which new blood vessels are formed in response to a chemical signal emitted out by a collection of cancer cells. Without angiogenesis, tumors cannot grow larger than 1 mm to 2 mm and cannot metastasize throughout the body. Therefore, detecting angiogenesis is, therefore, one of the most important ways functional information can be utilized to diagnose cancer at an early stage.

CTLM has the potential to determine whether a mass seen on mammography is benign or malignant and – because the volume of the angiogenesis is usually considerably larger than the tumor tissue itself – to detect tumors that are invisible on mammography. 

CTLM

Early light methods of imaging the breast, such as diaphonography, produced poorly defined images that made it impossible to visualize anything other than large cancers. The poor definition was due to intense scattering of light within the breast.

The CTLM system, however, utilizes patented continuous wave laser technology and computer algorithms to create 3-D and tomographic sections of the breast. A monochromatic laser beam is used at a selected wavelength that is absorbed by hemoglobin, which is contained within the blood vessels of the breast, but is not absorbed by fat or water.

Since water and fat do not absorb light at this wavelength, the system works equally well in dense and non-dense breasts. Patented algorithms mathematically correct for scatter, resulting in well-defined tomographic and 3-D images of the distribution of blood within the breast, which can reveal the presence of abnormal vascularity, including angiogenesis. 

CTLM is somewhat similar to MRI in that both techniques image a single molecule naturally occurring in the tissues: the water molecule in MRI and the hemoglobin molecule in CTLM. And, both modalities also reveal anatomic and functional data.

However, MRI exams are lengthy, complex and expensive. They also require the injection of potentially hazardous contrast material and are most often utilized in individual cases as a problem-solver.

The CTLM exam, on the other hand, does not require contrast injection, does not utilize ionizing radiation – which is of particular importance to the younger women with dense breasts – and requires no breast compression. In addition, the U.S. FDA has categorized CTLM as a non-significant risk study. 

CT Detector Array

During a CTLM examination, the patient lies in the prone position with the breast suspended naturally and comfortably through an aperture in the tabletop, in the center of the gantry. The gantry, containing the detectors and laser diode, which replaces the X-ray tube, rotates quietly around the breast for 360 degrees, then descends automatically, as with a conventional X-ray CT, until it reaches the nipple. 

Slice thicknesses are programmable from 1 mm to 4 mm. As the gantry descends, volumetric image data is reconstructed. The radiologist then views the resulting 3-D and tomographic images on a 3-D workstation with window and level controls and extensive software, allowing the reader to visualize the image in 3-D or tomographic maximum intensity projections, front-to-back projections and surface-rendered projections. 

The animated 3-D projection is of great clinical value for visualizing the distribution of blood within the entire breast, picking up any abnormalities of the normal distribution, such as angiogenesis, and determining their location and extent. 

Experts are also developing new approaches to solve the problems of poor sensitivity and specificity in mammography. However, several of these, such as digital mammography, computer-aided detection, tomosynthesis and X-ray CT of the breast, do not provide functional information. For this reason, they cannot be expected to provideanything other than minor improvements in diagnostic accuracy. 

But, by replacing the X-ray tube with a laser, using optical detectors and patented image-reconstruction algorithms, the new CTLM modality is able to supply functional information. Because of CTLM’s nature and the prospect of imaging human tissue with a laser, the system is subject to the U.S. FDA Premarket Approval process for devices that have no substantially equivalent device currently marketed in the United States.

CTLM has already been approved for use in Canada, Europe and Asia, with more than 9,000 scans having been performed to date. IDSI is currently collecting clinical data at various sites throughout the U.S. for the future filing of an FDA Premarket Approval application for the CTLM system. 

Future Applications

Molecular imaging is recognized as the new frontier in diagnostic imaging. CTLM, for instance, is already a molecular imaging technique that utilizes absorption of near-infrared light by the hemoglobin molecule, a natural marker of angiogenesis. 

The CTLM system is designed for a second ring of detectors that are sensitive to fluorescent light. IDSI has already carried out experiments in the human breast, using ICG and proprietary dyes, to demonstrate the feasibility of breast imaging using fluorescence imaging in vivo.

As breast cancer-specific fluorophores, such as bioluminescent substances attached to a protein or enzyme exclusive to breast cancer metabolism, are developed, CTLM is in a position to image such fluorophores with the possibility of detecting a mass of tumor cells that are too small to be imaged morphologically and too small to have developed angiogenesis.

Because the fluorophore would be breast cancer-specific, CTLM imaging of a volume of emitted radiation could indicate with certainty that breast cancer is present even at an early stage. If no emitted light is detected, the likelihood of a cancer being present would be extremely low. 

Other future applications include the use of multiple wavelength lasers to provide separate images of water, fat and blood that could further increase the sensitivity and specificity of CTLM; the detection, quantification and clearance rates of post-biopsy and post-surgical bleeding; the stratification of malignancy risk in ductal carcinoma in situ; and the monitoring of the success of neoadjuvant chemotherapy.

Work-in-progress studies in Europe suggest that CTLM may have greater sensitivity than MRI for this purpose, revealing the continued presence of angiogenesis confirmed by biopsy in cases where MRI has shown no residual angiogenesis.

The incidence of breast cancer is growing steadily throughout the world. There is an urgent need for a simple, easily installed, inexpensive – but reliable – method of detecting breast cancer at an early stage that does not employ ionizing radiation or require the injection of contrast media, and has greater sensitivity and specificity than current mammographic techniques.

Healthcare systems, governments and the medical community are searching for a better methodology. Fortunately, CTLM shows great promise of becoming just that. 

— Eric Milne, MD, FRCR, FRCP, is the director of clinical research at Imaging Diagnostic Systems Inc. (www.imds.com), Plantation, Fla. Questions and comments can be directed to editorial@rt-image.com.