Computed tomography laser mammography (CTLM) is the trademark of Imaging Diagnostic Systems, Inc. (IDSI, United States) for its optical tomographic technique for female breast imaging.
This medical imaging technique uses laser energy in the near-infrared region of the spectrum to detect angiogenesis in the breast tissue. It is optical molecular imaging for hemoglobin, both oxygenated and deoxygenated. The technology uses laser in the same way computed tomography uses X-rays; the beams travel through tissue and suffer attenuation.
A laser detector measures the intensity drop and the data is collected as the laser detector moves across the breast creating a tomography image. CTLM images show hemoglobin distribution in a tissue and can detect areas of angiogenesis surrounding malignant tumors, that stimulate this angiogenesis to obtain nutrients for growth.
Breast cancer affects 1 in 8 women, and an estimated 27% of people live at least 5 years after being diagnosed with stage IV cancer according to the National Cancer Institute. [1] Mammography is the most commonly used method to screen for cancer, but there are three major drawbacks. [2] The first is ionizing radiation. Since mammography uses low-energy x-rays to image the breast, the breast is exposed to ionizing radiation. Too much repeated exposure can elevate the risk of cancer down the road. The second drawback is inaccuracy. Mammography has low specificity and this can lead to false positives, which detect abnormalities that never progress to cause symptoms or death and also false negatives, especially in dense breast tissue, when it is especially difficult to detect tumors. 60 to 80 out of every 100 biopsies performed after mammography are actually negative for cancer. [3] Lastly, pain is a major drawback to mammography. 23–95% experience discomfort, [4] and pain is a significant inhibitor to re-attending screenings. [5]
CTLM was therefore developed as an alternative to X-ray mammography. Its technology is based on two important principles: [2]
Neovascularization is the natural formation of new blood vessels.
CTLM takes 15–20 minutes per picture and uses non-ionizing near-infrared light, which allows patients to take repeat images. It also suspends the breast, which prevents pain while imaging. [2] [6]
It is undergoing FDA approval,[ as of? ] and is proposed as an adjunct to mammography. [6] [ needs update ]
CTLM is a non-invasive practical system that uses near-infrared laser light propagation through the tissue to assess its optical properties. [7] It is based on two basic principles: different tissue components have unique scattering and absorption characteristics for each wavelength and the malignant tumor growth requires neovascularization to grow beyond 2 mm in size. In new forming tumors, the blood flow increases and the CTLM then looks for high hemoglobin concentration (angiogenesis) in the breast that are structurally and functionally abnormal, and to detect neovascularization, which may be hidden in mammography images especially in dense breast. [8] [9] [3] This neovascularization, which results in a greater volume of hemoglobin in a confined area, can be visualized using absorption measurements of laser light. Malignant lesions will be detected based on their higher optical attenuation compared to the surrounding tissue, which is mainly related to the increase in light absorption by their higher hemoglobin content. [10]
The CTLM device uses a laser diode than emits laser light at an 808 nm wavelength in the near-infrared (NIR) spectrum that matches the crossover point of strong absorption of both oxygenated and deoxygenated hemoglobin. [11] At this wavelength, water, fat, and skin can only weakly absorb light, having little effect on data acquisition. The 808 nm laser beam can penetrate breast tissue of any density, and thus can work equally well in the examination and imaging of extremely dense and heterogeneous breast tissue. CTLM looks for the areas of high absorption, where there is a high hemoglobin concentration indicating rich network of blood vessels, or angiogenesis. The area of angiogenesis is generally much larger than the tumor itself, and hence CTLM can detect small tumors that are sometimes invisible if using other imaging modalities, such as mammogram. However, the dispersion of photons in the tissue, although safe, can create a problem in the prediction of the path of the light in the tissue due to scattering. To solve this problem, CTLM system uses a large number of source and detector positions to take into account the diffusion approximation of light propagation in tissue, and to show the location of the increased vascularity in the breast. [12]
The data acquisition of CTLM is very similar to standard computed tomography (CT). The major difference is that CTLM uses near-infrared light, not X-ray, to produce the images. The patient lies on a padded table in the prone position with one breast suspended in the scanning chamber with nothing in contact with the pendant breast. The breast is surrounded by the laser source-detector unit that consists of a well containing two rings with 84 detectors each and a single laser mounted on a circular platform. This working array of CTLM device rotates 360 degrees around the breast and takes approximately 16,000 absorption measurements per slice. It then descends to scan the next level after each rotation, creating a slice at each step of thickness 2 or 4 mm, depending on the size of the breast. [3] A total of at least 10 slices is obtained, and the duration of the examination ranges from 10 to 15 minutes for an average-sized patient.
Reconstruction of the CTLM images is performed slice by slice. The forward model, an estimate of the average optical absorption, is computed for each slice, using the diffusion approximation of the transport equation. [13] It is then compared to the computed tomographic fan-beam measurement of the absorbing perturbations in the slice. [3] These perturbation data are then reconstructed into slice images using a highly modified proprietary filtered back-projection algorithm that converts the fan-beam data into sinograms. It also corrects for geometric distortions due to bulk light-tissue interaction, and compensates for a spatially variant blurring effect that is typical of diffuse optical imaging.
3D images visualization is available immediately after data acquisition. The areas containing well-perfused structures with high hemoglobin concentration are visualized in white or light green, and the areas with no vascularization are seen as dull green or black. Mathematical algorithms reconstruct three-dimensional translucent images that can be rotated along any axis in real time. In 3D space, the images are analyzed in two different projections, maximum intensity projection (MIP) and front to back projection (FTB), also known as a Surface Rendering Mode. [14] These two modes combined are used to evaluate the vascularization patterns and to distinguish a normal vessel from an abnormal vascularization. Although some benign lesion also showed angiogenesis, increased absorption was observed significantly more often in malignant than in benign lesions. Studies have shown that the shape and texture of angiogenesis in CTLM images are significant characteristics to differentiate malignancy or benign lesions. A computer-aided diagnosis framework containing three main stages, volume of interest (VOI), feature extraction and classification, is used to enhance the performance of radiologist in the interpretation of CTLM images. 3D Fuzzy segmentation technique has been implemented to extract the VOI. [7]
Three independent views are offered: the coronal, sagittal, and transverse views. These views can also form a composite 3D view. [15] An inverse factor is applied to the image so that the high vasculature areas appear white on the image while the black or green areas are relatively avascular segments. [16] The majority of benign lesions are not visualized due to a lack of increased absorption. [14]
Two reconstruction modes are offered with CTLM: Front to Back Reconstruction and Maximal Intensity Projection. [14] These two modes are used to evaluate the vascularization patterns to determine whether the images have normal or abnormal vascularization. [14] Also, because tumor neovasculature is not limited to the tumor's anatomical border, CTLM will also reveal all recruited arteries and areas of increased circulation. This is an advantage to identify very small tumors.[ citation needed ]
Dr. Eric Milne conducted a small localized study using CTLM as an adjunct to mammography; out of 122 cases, the number of biopsies required reduced from 89 to 47. Additionally, the sensitivity of CTLM is equal to mammography, but has much greater specificity.[ citation needed ]
Imaging Diagnostic Systems is a Florida-based company that has created a CTLM imaging device. In 2011 it was classified as a Class III medical device, and it is still undergoing approval.[ as of? ][ needs update ]
CTLM has uses a near infrared laser of wavelength ~808 nm which is not impeded by the dense breast tissue. The sensitivity of mammography, CTLM and mammography + CTLM was 34.4%, 74.4% and 81.57% respectively among extremely dense breasts and 68.29%, 85.00% and 95.34% respectively among heterogeneously dense breasts. [12] The combination of CTLM and mammography is able to distinguish between benign and malignant tumors with higher accuracy.
Mammography is the process of using low-energy X-rays to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through detection of characteristic masses, microcalcifications, asymmetries, and distortions.
The term biophotonics denotes a combination of biology and photonics, with photonics being the science and technology of generation, manipulation, and detection of photons, quantum units of light. Photonics is related to electronics and photons. Photons play a central role in information technologies, such as fiber optics, the way electrons do in electronics.
Medical optical imaging is the use of light as an investigational imaging technique for medical applications, pioneered by American Physical Chemist Britton Chance. Examples include optical microscopy, spectroscopy, endoscopy, scanning laser ophthalmoscopy, laser Doppler imaging, and optical coherence tomography. Because light is an electromagnetic wave, similar phenomena occur in X-rays, microwaves, and radio waves.
Phyllodes tumors, are a rare type of biphasic fibroepithelial mass that form from the periductal stromal and epithelial cells of the breast. They account for less than 1% of all breast neoplasms. They were previously termed cystosarcoma phyllodes, coined by Johannes Müller in 1838, before being renamed to phyllodes tumor by the World Health Organization in 2003. Phullon, which means 'leaf' in Greek, describes the unique papillary projections characteristic of phyllodes tumors on histology. Diagnosis is made via a core-needle biopsy and treatment is typically surgical resection with wide margins (>1 cm), due to their propensity to recur.
Photoacoustic imaging or optoacoustic imaging is a biomedical imaging modality based on the photoacoustic effect. Non-ionizing laser pulses are delivered into biological tissues and part of the energy will be absorbed and converted into heat, leading to transient thermoelastic expansion and thus wideband ultrasonic emission. The generated ultrasonic waves are detected by ultrasonic transducers and then analyzed to produce images. It is known that optical absorption is closely associated with physiological properties, such as hemoglobin concentration and oxygen saturation. As a result, the magnitude of the ultrasonic emission, which is proportional to the local energy deposition, reveals physiologically specific optical absorption contrast. 2D or 3D images of the targeted areas can then be formed.
Molecular imaging is a field of medical imaging that focuses on imaging molecules of medical interest within living patients. This is in contrast to conventional methods for obtaining molecular information from preserved tissue samples, such as histology. Molecules of interest may be either ones produced naturally by the body, or synthetic molecules produced in a laboratory and injected into a patient by a doctor. The most common example of molecular imaging used clinically today is to inject a contrast agent into a patient's bloodstream and to use an imaging modality to track its movement in the body. Molecular imaging originated from the field of radiology from a need to better understand fundamental molecular processes inside organisms in a noninvasive manner.
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Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye. Choroidal neovascularization is a common cause of neovascular degenerative maculopathy commonly exacerbated by extreme myopia, malignant myopic degeneration, or age-related developments.
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A lung nodule or pulmonary nodule is a relatively small focal density in the lung. A solitary pulmonary nodule (SPN) or coin lesion, is a mass in the lung smaller than three centimeters in diameter. A pulmonary micronodule has a diameter of less than three millimetres. There may also be multiple nodules.
Indocyanine green (ICG) is a cyanine dye used in medical diagnostics. It is used for determining cardiac output, hepatic function, liver and gastric blood flow, and for ophthalmic and cerebral angiography. It has a peak spectral absorption at about 800 nm. These infrared frequencies penetrate retinal layers, allowing ICG angiography to image deeper patterns of circulation than fluorescein angiography. ICG binds tightly to plasma proteins and becomes confined to the vascular system. ICG has a half-life of 150 to 180 seconds and is removed from circulation exclusively by the liver to bile.
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Dynamic angiothermography (DATG) is a technique for the diagnosis of breast cancer. This technique, though springing from the previous conception of thermography, is based on a completely different principle. DATG records the temperature variations linked to the vascular changes in the breast due to angiogenesis. The presence, change, and growth of tumors and lesions in breast tissue change the vascular network in the breast. Consequently, through measuring the vascular structure over time, DATG effectively monitors the change in breast tissue due to tumors and lesions. It is currently used in combination with other techniques for diagnosis of breast cancer. This diagnostic method is a low-cost one compared with other techniques.
Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body.
In medicine, breast imaging is a sub-speciality of diagnostic radiology that involves imaging of the breasts for screening or diagnostic purposes. There are various methods of breast imaging using a variety of technologies as described in detail below. Traditional screening and diagnostic mammography uses x-ray technology and has been the mainstay of breast imaging for many decades. Breast tomosynthesis is a relatively new digital x-ray mammography technique that produces multiple image slices of the breast similar to, but distinct from, computed tomography (CT). Xeromammography and galactography are somewhat outdated technologies that also use x-ray technology and are now used infrequently in the detection of breast cancer. Breast ultrasound is another technology employed in diagnosis and screening that can help differentiate between fluid filled and solid lesions, an important factor to determine if a lesion may be cancerous. Breast MRI is a technology typically reserved for high-risk patients and patients recently diagnosed with breast cancer. Lastly, scintimammography is used in a subgroup of patients who have abnormal mammograms or whose screening is not reliable on the basis of using traditional mammography or ultrasound.
The Beckman Laser Institute is an interdisciplinary research center for the development of optical technologies and their use in biology and medicine. Located on the campus of the University of California, Irvine in Irvine, California, an independent nonprofit corporation was created in 1982, under the leadership of Michael W. Berns, and the actual facility opened on June 4, 1986. It is one of a number of institutions focused on translational research, connecting research and medical applications. Researchers at the institute have developed laser techniques for the manipulation of structures within a living cell, and applied them medically in treatment of skin conditions, stroke, and cancer, among others.
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Diffuse optical mammography, or simply optical mammography, is an emerging imaging technique that enables the investigation of the breast composition through spectral analysis. It combines in a single non-invasive tool the capability to implement breast cancer risk assessment, lesion characterization, therapy monitoring and prediction of therapy outcome. It is an application of diffuse optics, which studies light propagation in strongly diffusive media, such as biological tissues, working in the red and near-infrared spectral range, between 600 and 1100 nm.
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