Technology Overview
Recently, MIT's Technology Review magazine described molecular imaging as “one of the emerging technologies that will change the world”. As well, the National Cancer Institute characterized it as one of six extraordinary opportunities for development.
Molecular imaging is an integral part of ART's technology platform and its future.
Already, ART's success in developing its molecular imaging capabilities for small animals is influencing the way basic research is carried out. The transition to ART's medical imaging applications for humans could have sweeping implications for radiological practice in the future.
ART’s time domain (TD) optical imaging technology is powerful, unique and broad enough to support a variety of pharmaceutical and clinical applications. This technology platform, on which rest two of the company’s products, SoftScan and Optix, offers unmatched advantages in biological tissue imaging and the potential to expand into other clinical, diagnostic and therapeutic applications.
- What is molecular imaging?
- What is optical imaging?
- ART’s TD optical imaging technology: unique benefits
- ART’s TD optical imaging technology: how it works
- Applications for ART’s technology
What is molecular imaging?
The terms functional imaging and molecular imaging describe a new direction in imaging methodology. Functional imaging refers to the capability of monitoring physiological processes in a non-invasive manner, primarily based on blood flow and cellular metabolism. Molecular imaging is a subfield of functional imaging, which refers to imaging specifically targeted processes and pathways in cells and tissue in real time at a molecular level. ART's time domain imaging technology falls under both categories.
Molecular imaging often requires the use of exogenous contrast agents. These agents consist of a molecule (called a probe) chosen to target an intrinsic molecule in the living organism and a marker, which allows the particular molecule to be visualized. For example, drug candidates can be tagged and monitored in this way during preclinical studies in small animals to determine how quickly and where they are metabolized. This kind of information gives researchers early indicators of how successful the proposed drug may be later on in the discovery process, in humans.
What is optical imaging?
As an emerging subfield of molecular imaging, optical imaging technologies analyze the propagation of light particles (photons) through a medium such as tissue. The optical imaging technologies rely on non-ionizing radiation, typically produced by a low-intensity laser, that interacts with tissue to emit a signal captured by a high sensitivity photon detector. For in vivo optical imaging, observing the behaviour of photons in the near-infrared (NIR) region is favoured because tissue has low absorption properties in that spectral band (typically between 650 and 1100 nm) so light can penetrate several centimetres.
Some studies use fluorescent markers to generate images with high molecular specificity and contrast.
ART’s TD optical imaging technology: unique benefits
Near-infrared (NIR) photons travelling through biological tissue are highly scattered before either being totally absorbed by the tissue or emerging at the surface where they are detected. Since scattered photons have no preferred direction or orientation, they can be statistically differentiated from one another by observing the temporal response at which they emerge from the scattering medium following an ultra-short laser pulse; this is known as time domain (TD) optical imaging.
In the NIR region, optical imaging provides information on natural compounds (chromophores), including fat, water, oxyhemoglobin and deoxyhemoglobin. These two forms of hemoglobin indicate tissue perfusion and metabolism and allow the formation of new blood vessels (angiogenesis) to be detected. The abundance or lack of angiogenesis is associated with multiple diseases, such as cancer and cardiovascular disease. By using a fluorescent marker (fluorophore) in preclinical studies, TD optical imaging allows particular receptors, antibodies, genes or drugs to be tagged. This allows compound biodistribution and pharmacokinetics to be measured, which could lead to a better understanding of disease processes and treatment efficacy.
Furthermore, using TD optical imaging with fluorescent markers enables the intensity, absorption and also the lifetime of fluorescence to be measured. This added image parameter measures the average time a fluorophore emits light of one wavelength when excited by another wavelength of light, giving more detailed information and contrast to the image. For example, it is possible to discriminate between two or more fluorophores whose emission spectra overlap but may be separated by the contrast in their fluorescence lifetimes. This permits drugs to be analyzed when used in combination therapy. Changes in fluorescence lifetime are known to occur with varying tissue pH and oxygenation levels, providing rich physiological information on the local tissue environment.
TD optical imaging technology has tremendous advantages for biological tissue imaging:
- Separation of scattering and absorption coefficients in tissue: precise data on pharmacokinetics and the biodistribution of fluorophores or chromophores.
- Greater depth sensitivity: discrimination of photons at different depths and concentrations.
- Fluorescence lifetime measurement: distinction between different fluorescent materials in preclinical models.
ART’s TD optical imaging technology: how it works
By measuring the absorption and scatter characteristics of light in the visible and near-infrared (NIR) region of the spectrum, TD optical imaging provides a detailed description of biological tissue. This allows the characterization of diseases, such as breast cancer, and the analysis of molecular pathways leading to diseases.
- The organism is placed in the device and scanned by a harmless, computer-controlled, pulsed-laser beam that operates in the visible and NIR region of the spectrum.
- A highly sensitive detector measures the light that passes through the tissue or that is reflected from a point for a fixed time.
- Using mathematical algorithms, a computer converts the acquired data into an image that is rich in detail and depth sensitivity.
Applications for ART’s technology... today
Molecular imaging in drug research
By tagging a target molecule, antibody, gene or protein with fluorescent agents, scientists can view a physiological process in a laboratory animal in vivo. For example, in ADME Toxicology, researchers can see how a potential new drug is absorbed, distributed, metabolized and excreted at the functional and molecular levels.
ART’s TD imaging technology is not limited to structural data, as are X-rays, MRI and CT scans. This technology allows biological processes to be detected at the molecular level, providing earlier, more sensitive and quantifiable measures of disease progression and therapeutic efficacy in vivo.
Breast cancer diagnosis
As an adjunct to mammography, ART’s technology enables health professionals to confirm the presence of a tumour and to characterize it as malignant or benign. This has the potential to reduce the great number of invasive breast biopsies currently carried out and, consequently, to reduce the suffering and anxiety of women and their families.
... and tomorrow
Although ART’s product development and regulatory approval paths currently focus on helping to diagnose malignant breast tumours through functional imaging, this is just the beginning…
Drug efficacy in humans
Combining TD optical imaging capabilities and functional imaging, it may be possible to monitor drug efficacy in humans, thereby opening the door to countless research and clinical applications.
Neurobiology
Near-infrared light, on which ART’s imaging technology is based, penetrates safely through bone, making it the ideal tool for non-invasive brain studies. In co-operation with the Massachusetts General Hospital, ART has conducted R&D on monitoring brain function particularly as it applies to stroke, head injury, brain cancer and Alzheimer’s Disease.
Surface applications
The same technology developed to detect breast cancer could be adapted to detect diseases and monitor treatment in the pancreas and other organs.
Endoscopy
Minimally invasive endoscopes could more easily diagnose and treat prostate and œsophageal cancers, as well as other diseases.
Agri-food
ART’s technology could detect unwanted substances, such as bacteria, pathogens or pesticides in meats, produce and processed food. It could also improve quality control by precisely measuring the percentage of protein, fat and water in industries such as meat processing.