Reporter: Prabodh Kandala, PhD
The most common breast cancer screening method used today is called dual-view digital mammography, but it isn’t always successful in identifying tumors, said Jianwei (John) Miao, a UCLA professor of physics and astronomy and researcher with the California NanoSystems Institute at UCLA.
“While commonly used, the limitation is that it provides only two images of the breast tissue, which can explain why 10 to 20 percent of breast tumors are not detectable on mammograms,” Miao said. “A three-dimensional view of the breast can be generated by a CT scan, but this is not frequently used clinically, as it requires a larger dose of radiation than a mammogram. It is very important to keep the dose low to prevent damage to this sensitive tissue during screening.”
Recognizing these limitations, the scientists went in a new direction. In collaboration with the European Synchrotron Radiation Facility in France and Germany’s Ludwig Maximilians University, Miao’s international colleagues used a special detection method known as phase contrast tomography to X-ray a human breast from multiple angles.
They then applied equally sloped tomography, or EST — a breakthrough computing algorithm developed by Miao’s UCLA team that enables high-quality image-reconstruction — to 512 of these images to produce 3-D images of the breast at a higher resolution than ever before. The process required less radiation than a mammogram.
In a blind evaluation, five independent radiologists from Ludwig Maximilians University ranked these images as having a higher sharpness, contrast and overall image quality than 3-D images of breast tissue created using other standard methods.
“Even small details of the breast tumor can be seen using this technique,” said Maximilian Reiser, director of the radiology department at Ludwig Maximilians University, who contributed his medical expertise to the research.
The technology commonly used today for mammograms or imaging a patient’s bones measures the difference in an X-ray’s intensity before and after it passes through the body. But the phase contrast X-ray tomography used in this study measures the difference in the way an X-ray oscillates through normal tissue rather than through slightly denser tissue like a tumor or bone. While a very small breast tumor might not absorb many X-rays, the way it changes the oscillation of an X-ray can be quite large, Miao said. Phase contrast tomography captures this difference in oscillation, and each image made using this technique contributes to the overall 3-D picture.
Like cleaning the lenses of a foggy pair of glasses, scientists are now able to use a technique developed by UCLA researchers and their European colleagues to produce three-dimensional images of breast tissue that are two to three times sharper than those made using current CT scanners at hospitals. The technique also uses a lower dose of X-ray radiation than a mammogram.
The computational algorithm EST developed by Miao’s UCLA team is a primary driver of this advance. Three-dimensional reconstructions, like the ones created in this research, are produced using sophisticated software and a powerful computer to combine many images into one 3-D image, much like various slices of an orange can be combined to form the whole. By rethinking the mathematic equations of the software in use today, Miao’s group developed a more powerful algorithm that requires fewer “slices” to get a clearer overall 3-D picture.
“The technology used in mammogram screenings has been around for more than 100 years,” said Paola Coan, a professor of X-ray imaging at Ludwig Maximilians University. “We want to see the difference between healthy tissue and the cancer using X-rays, and that difference can be very difficult to see, particularly in the breast, using standard techniques. The idea we used here was to combine phase contrast tomography with EST, and this combination is what gave us much higher quality 3-D images than ever before.”
While this new technology is like a key in a lock, the door will only swing open — bringing high-resolution 3-D imaging from the synchrotron facility to the clinic — with further technological advances, said Alberto Bravin, managing physicist of the biomedical research laboratory at the European Synchrotron Radiation Facility. He added that the technology is still in the research phase and will not be available to patients for some time.
“A high-quality X-ray source is an absolute requirement for this technique,” Bravin said. “While we can demonstrate the power of our technology, the X-ray source must come from a small enough device for it to become commonly used for breast cancer screening. Many research groups are actively working to develop this smaller X-ray source. Once this hurdle is cleared, our research is poised to make a big impact on society.”
These results represent the collaborative efforts of senior authors Miao, Bravin and Coan. Significant contributions were provided by co-first authors Yunzhe Zhao, a recent UCLA doctoral graduate in Miao’s laboratory, and Emmanuel Brun, a scientist working with Bravin and Coan. Other co-authors included Zhifeng Huang of UCLA and Aniko Sztrókay, Paul Claude Diemoz, Susanne Liebhardt, Alberto Mittone and Sergei Gasilov of Ludwig Maximilians University.
The research was funded by UC Discovery/Tomosoft Technologies; the National Institute of General Medical Sciences, a division of the National Institutes of Health; and the Deutsche Forschungsgemeinschaft-Cluster of Excellence Munich-Centre for Advanced Photonics.
Abstract:
Mammography is the primary imaging tool for screening and diagnosis of human breast cancers, but ∼10–20% of palpable tumors are not detectable on mammograms and only about 40% of biopsied lesions are malignant. Here we report a high-resolution, low-dose phase contrast X-ray tomographic method for 3D diagnosis of human breast cancers. By combining phase contrast X-ray imaging with an image reconstruction method known as equally sloped tomography, we imaged a human breast in three dimensions and identified a malignant cancer with a pixel size of 92 μm and a radiation dose less than that of dual-view mammography. According to a blind evaluation by five independent radiologists, our method can reduce the radiation dose and acquisition time by ∼74% relative to conventional phase contrast X-ray tomography, while maintaining high image resolution and image contrast. These results demonstrate that high-resolution 3D diagnostic imaging of human breast cancers can, in principle, be performed at clinical compatible doses.
Ref:
breast tumors in 3-D with great clarity, reduced radiation. ScienceDaily. Retrieved October 23, 2012, from http://www.sciencedaily.com/releases/2012/10/121022162710.htm
http://www.pnas.org/content/early/2012/10/17/1204460109
This is an eye opener.
Very nice reporting touching an emerging trend in breast imaging by Prabodh. It is worthwhile noting that in the last 3 years several 3D imaging systems aiming at breast cancer detection were introduced into the market. some of them not at all based on ionising energy emission; e.g. MRI and ultrasound. Just recently, U-systems received FDA clearance for applying it’s ABUS in breast cancer screening: http://www.bloomberg.com/news/2012-09-27/u-systems-seeks-partner-as-fda-approves-breast-ultrasound.html.
As for 3D mammography systems that are based on low-dose technologies, the one by Hologic has FDA clearance is already installed in many leading centers in the USA: Hologic 3D mammogram cleard by FDA http://abcnews.go.com/Health/OnCallPlusBreastCancerNews/3d-imaging-detects-breast-cancer/story?id=12229413#.UIbsnsXA_8c
Use of thomosyntesis in TOPS Comprehensive Breast Center Huston Texas
http://www.yourhoustonnews.com/cypresscreek/living/at-tops-the-power-and-promise-of-d-mammography-is/article_bc0df44c-c651-5f11-8b30-a018b5da874d.html
Finally, see my own posts in this blog; imagining or seeing (1&2) and Imaging-guided biopsies: Is there a preferred strategy to choose? where I describe 3D systems for breast imaging and also mentioned the promising preliminary results of HistoScanning for breast; a technology I invented and tested for feasibility for breast cancer detection that is based on 3D ultrasound scanning of breast lesions [WILKINSON (L.S.), COLEMAN (C.), SKIPPAGE (P.), GIVEN-WILSON (R.), THOMAS (V.). Breast HistoScanning: The development of a novel technique to improve tissue characterization during breast ultrasound. European Congress of Radiology (ECR), A.4030, C-0596, 03-07/03/2011.]. .
Dr. Nir:
It will be much appreciated if the category of Medical imaging will have a spreadsheet along the lines we have for our THRUST on Nitric Oxide, namely
Type of cancer: breast, ovarian, prostate, brain, etc.
Imaging Methods: CT, PET, Ultrasound, X-Ray, etc.
Post title, Role, Name, Date, URL
We a new post in this space is posted, EAW, will go to the spreadsheet and copy references into the new post. We will get pingbacks.
I hope you will create this resource for all EAWs that post on Medical Imaging. I did it for Nitric Oxide and for Cardiovascular
Thank you
Very Interesting!
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
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