Volume 36, Issue 6, June 2009
Index of content:
- Industrial Physics Forum: Joint Imaging/Therapy Symposium: Room 303A
- Nanotechnology in Imaging and Therapy
36(2009); http://dx.doi.org/10.1118/1.3182385View Description Hide Description
Molecular Imaging is a promising new approach that facilitates early stage disease diagnosis and evaluation of treatment effectiveness. It spans multiple technologies that range from low energy optical photons, to high energy ionizing radiation and from single cell analysis to small animals and whole body human imaging. The unifying concept is the use of specific molecular markers that are the signatures of the underlying molecular processes.
In this presentation, we will discuss the design of technologies that are used for handling and detecting the full range of possible signal, some of their strengths and practical limitations, and will provide some examples of possible applications. We will start from optical imaging in the visible wavelength and its use in cell cultures and preclinical in‐vivo models. Further, we will discuss radionuclide technologies and their use for preclinical drug screening in the single cell level, to clinical human studies.
1. Understand the origin of the created optical and radionuclide signal
2. Understand the nature of signal propagation in different media
3. Understand the detection limits of different imaging modalities
36(2009); http://dx.doi.org/10.1118/1.3182386View Description Hide Description
36(2009); http://dx.doi.org/10.1118/1.3182387View Description Hide Description
Nanotechnology, an interdisciplinary research field involving chemistry, engineering, biology, medicine, and more, has great potential for early detection, accurate diagnosis, and personalized treatment of diseases. Molecular imaging refers to the characterization and measurement of biological processes at the cellular and/or molecular level. It can give whole‐body readout in an intact system, dramatically decrease the workload and reduce the cost of biomedical research and drug development, provide more statistically relevant results since longitudinal studies can be performed in the same animals, aid in early lesion detection in patients and patient stratification, and help in individualized treatment monitoring and dose optimization.
This talk will exemplify the use of various inorganic nanoparticles for optical imaging,magnetic resonance imaging,computed tomography, and radionuclide imaging. The advantages of nanoplatform‐based molecular imaging over conventional approaches will be elaborated. However, several issues, such as biocompatibility, pharmacokinetics, in vivo targeting efficacy, cost‐effectiveness, and acute/chronic toxicity, that limit the clinical translation and wide spread use will also be discussed.
1. Understand the basics of nanotechnology and molecular imaging
2. Understand the chemistry required for nanoparticle surface modification
3. Understand the pros and cons of inorganic nanoparticles for in vivo imaging.
36(2009); http://dx.doi.org/10.1118/1.3182388View Description Hide Description
Liposomes are the prototypical nanodevices for delivery of therapeutics. These nanovesicles are structures comprising a phospholipid membrane, an encapsulated aqueous phase (usually) containing the therapeutic agent and surface grafted polymer chains. Typical diameters are in the hundred nanometer range. The extended structure provides a platform that can increase circulation time, protect the therapeutic from enzymes in the circulation and reduce the interaction of toxic therapeutics with normal organs. Several liposomal drug delivery formulations are now FDA approved. Immunoliposomes or “targeted” liposomes are engineered with surface grafted antibodies or antibody fragments reactive against tumor or other target cell antigens or receptors. Studies have demonstrated that targeted liposomes do not provide a tumor‐targeting advantage in terms of gross localization to the tumor site. For both targeted and untargeted liposomes,tumor localization is accomplished by the enhanced permeability effect that arises because tumor vasculature is “leakier” than normal organ vasculature. Targeted liposomes provide a delivery advantage because of increased interaction with the target cell population once localized to the tumor site. The increased interaction can take on the form of fusion with the cellularmembrane or internalization by endocytosis. We have developed immunoliposomes for the targeted delivery of alpha‐particle emitting radionuclides. Pre‐clinical studies evaluating the efficacy of such constructs will be presented.
1. Provide an overview of liposomes as therapeutics
2. Explain how liposomes target
3. Understand the distinction between targeted and untargeted liposomes
4. Understand the possible advantages of using liposomes to target alpha‐particle emitters
- Screening, Diagnosis, and Treatment of Breast Cancer
36(2009); http://dx.doi.org/10.1118/1.3182422View Description Hide Description
Digital breast tomosynthesis (DBT) is on the verge of routine clinical use in the United States; every major mammography manufacturer has a prototype under development, numerous clinical trials are in progress and one manufacturer is selling systems in Europe. DBT has been shown to have clear value in increasing the conspicuity of lesions by removing overlaying structures present in mammograms.
Regardless of the advances, DBT is currently limited to the depiction of tumor morphology. We have recently installed a Hologic Dimensions DBT prototype that has been modified to allow contrast‐enhanced (CE) imaging. Both dual‐energy and temporal CE‐DBT are under investigation. In previous work, we have shown that CE‐DBT can provide results concordant with dynamic contrast‐enhanced MR in a group of 17 women with known or suspected breast cancer. Our work continues with technique optimization, reconstruction algorithm development, motion correction, and scatter and other signal dependent corrections. With appropriate corrections, CE‐DBT can accurate quantify contrast agent uptake.
CE‐DBT has potential benefit in a number of roles, as illustrated by breast MR. These roles include screening high‐risk populations, staging cancer patients through identification of multifocal, multicentric and contralateral cancer, and assessment of tumor response to neoadjuvant chemotherapy. Research is also ongoing in the field of targeted radiographicimaging agents for breast cancer.
1. Review the state‐of‐the‐art in DBT system design
2. Describe adaptations necessary to perform quantitative CE‐DBT
3. Exemplify the clinical applications of CE‐DBT
Research support for this project has been provide in part by XCounter AB, General Electric Health Care, and Hologic Corp, in addition to the Komen for the Cure Foundation, the Department of Defense and the Radiological Society of North America.
TU‐E‐303A‐02: Breast Cancer Applications of Optical Imaging Biomarkers Measured with Diffuse Optical Spectroscopic Imaging36(2009); http://dx.doi.org/10.1118/1.3182423View Description Hide Description
Optical imaging biomarkers measured by Diffuse Optical SpectroscopicImaging(DOSI) provide unique physiological profiles of tissue biochemistry that may be useful in breast cancer for detecting/characterizing lesions and evaluating tumor response to therapy.
Imaging technologies have long played an important role in oncology, covering early detection, therapeutic planning, and remission management. Imaging biomarkers, such as tumor volume, are being considered as surrogate endpoints in place of traditional endpoints such as morbidity and mortality. Yet there is a need and a desire to see more. Spectral information content is often added to increase information content, and thus improve tumor detection and classification. For example, dual energy mammography can improve the visibility of microcalcifications. The capabilities of Magnetic Resonance Imaging(MRI) can also be augmented through the inclusion of spectroscopy (MRS). MRS applied to breast cancer has yielded some promising results, namely via the detection of choline, which may distinguish between benign and malignant as well as signal early changes in tumors responding to neoadjuvant chemotherapy.
Optical imaging offers a new class of imaging biomarkers, although their clinical significance has yet to be firmly established. These “optical imaging biomarkers” emerge from modeling specific near‐infrared (NIR) molecular absorption signatures, which may be surrogate markers for traditional molecular biomarkers of disease from processes such as angiogenesis, apoptosis, and proliferation. Optical imaging in the 1980's generated lots of enthusiasm but fell short of expectations. By modeling the physics of light transport, improving technology, and increasing spectroscopic information content, the past limitations of optical imaging can be overcome. Modern optical imaging such as DOSI can measuretumor total hemoglobin, in both oxygenated and deoxygenated states. By increasing spectral bandwidth, new optical imaging biomarkers emerge. Tissue water, in various biochemical states, and bulk lipids, have also been used to identify and even stage malignant lesions. Deoxy‐hemoglobin and water have predicted final pathological response of breast cancer patients treated with neoadjuvant chemotherapy in pilot studies, in similar fashion to choline. Novel NIRspectroscopic signatures that are unique to cancer have been discovered, and may also distinguish between benign and malignant lesions.
Our long‐term goal is to develop the concept of optical imaging biomarkers for the prevention, detection, and treatment of malignancy, particularly in breast cancer. Through novel technological and analytical methods, we are developing DOSI as the optical analogue to MRS/MRI, yet DOSI will have significantly reduced barriers for access. DOSI can be made highly portable, and may find use in the doctor's office setting, or even in the field.
Conflict of Interest Statement
While the authors have not received any funds or assistance from companies for this research, authors hold patents on technologies that are being licensed by companies. The University of California Irvine Conflict of Interest Committee reviewed these interests and considered them acceptable and do not interfere with research integrity.
1. Learn the physical basis for Diffuse Optical SpectroscopicImaging
2. Learn how increasing spectroscopic bandwidth improves tissue characterization
3. Learn how Diffuse Optical SpectroscopicImaging may be useful in breast cancer applications
36(2009); http://dx.doi.org/10.1118/1.3182424View Description Hide Description
Dedicated breast computed tomography(CT)systems were designed and fabricated in our laboratory using off‐the‐shelf components (x‐ray system,detector, and bearing) integrated into a custom designed system. For imaging, a 360 degree acquisition using cone beam geometry is used to acquire 500 projection images which are reconstructed to produce a high resolution ∼512 × 512 × 512 CT volume data set. In addition to the diagnostic imaging capabilities of the bCT scanner, the system appears to be an excellent platform for image guidance of interventional procedures such as robotic biopsy, radiofrequency ablation, and cryoablation. In addition to percutaneous procedures, the bCT system may also be an excellent platform for rotational beam radiation therapy. Computer simulations and physical phantom‐based experiments were used to define the dose distributions possible using the bCT system for radiation therapy. A number of beam energies from 120 kVp to 480 kVp were simulated. Initial results suggest that in addition to homogeneous dose distributions for treating the whole breast, that focused therapeutic approaches using collimators may be possible. The pendent position of the breast with the women prone is also thought to be a more reproducible approach to fractionated radiotherapy of the breast.
Educational goals are to inform the attendee of the possible benefits of breast cancer therapies delivered from a breast CT platform
Research support for this project has been provide in part by Varian Medical Systems, Fuji Medical Systems, and Hologic Corporation, in addition to the NIH