Blueprint for Imaging in Biomedical Research1

Memorial Sloan-Kettering Cancer Center, New York, New York, United States
Radiology (Impact Factor: 6.87). 08/2007; 244(1):12-27. DOI: 10.1148/radiol.2441070058
Source: PubMed


Research in biomedical imaging and bioengineering is yielding remarkable capabilities for unraveling the complexity of biologic systems, eliminating long-standing barriers in basic medical science, and providing powerful new tools to improve health care. 1. Imaging encompasses more than any one discipline or any one level of analysis. It brings together researchers from many disciplines to address unmet needs and advance discovery. 2. Interdisciplinary research teams that foster pathways for progress across the discovery-development-delivery continuum of biomedical research are crucial. 3. Government support of research in biomedical imaging is critical to the growth of new knowledge in the biomedical sciences. 4. There is a need for scientific societies to collaborate with industry and the different federal agencies to develop standards for quantitative measurements for drug response, by using anatomic, functional, and molecular imaging methods. 5. The ability of imaging technology to interrogate at the cellular level has facilitated investigations about fundamental biological processes, as well as specific disease pathophysiology. 6. The ability of MR imaging techniques to enable identification of areas of increased neuronal activity in the brain has opened the field of functional brain mapping as an important approach to the study of brain function, including cognition. 7. US imaging is a versatile technology that continues to advance in many areas, including the development of novel contrast agents that will offer unique capabilities to probe biological systems. 8. Optical imaging probes that respond to cellular activity and emit near-infrared wave lengths offer the ability to track molecular activity within the cell. 9. Engineering advances in electron microscopy continue to push the limits of spatial resolution. Tomographic techniques have been developed to allow three-dimensional imaging at cellular and molecular levels. 10. Fusion imaging, led by PET/CT scanners, combines the functional properties of radionuclide imaging with the detailed anatomic imaging of CT. Other combinations of imaging modalities promise further enhancements to improve our ability to predict the biologic behavior of tissue. 11. The development of new imaging probes - radiopharmaceuticals, microbubbles, nanoparticles, and reporter molecules - will enhance the scope and specificity of imaging technologies. 12. The dramatic increasing in imaging data generated by imaging technologies has been made possible by improvements in computational capacity. More powerful algorithms for extracting information from the raw data must be developed. 13. In preclinical translational research, imaging can enhance the use of animal models for validating new targeted probes and illuminating key physiologic differences between animal models and humans. 14. Biomedical imaging can identify surrogate endpoints that, when combined with computational simulations, will predict the effectiveness of a therapeutic approach much earlier than traditional clinical trials, thereby reducing the costs and shortening the time to the delivery of effective agents into the marketplace. 15. Imaging has become essential not only for the detection and monitoring of disease but also for intervention. Methods of acquiring, analyzing, and displaying this information in real time during the intervention must be improved. 16. Methods to assess the effect of imaging on patient outcomes are needed.

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    • "Experimental infections of O. viverrini in hamsters have been used to understand how CCA could develop [14] [15]. Biomedical imaging [16] is an important tool in all phases of cancer management [17], including prediction [18], screening [19], "
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    ABSTRACT: A 3T MR scanner was used to investigate the relationship between the alteration of bile duct lesions and the hepatic metabolic changes in hamsters infected with Opisthorchis viverrini by using 3T MRI and (1)H MR spectroscopy. Animals were divided into control and infected groups. Five normal hamsters were used as control; fifty-five hamsters were infected with O. viverrini to induce bile duct lesions and hepatic metabolic changes. T2-weighted image sequence in three orthogonal planes were conducted by MRI scans. Single-voxel (1)H MRS was performed to obtain the relative choline-to-lipid ratios. The livers and bile ducts were excised for the histologic examination. The progression of bile duct changes by histology and metabolic changes in O. viverrini infected hamsters were co-investigated. In the O. viverrini-infected group, the T2-weighted images revealed the time-dependent intra- and extra-hepatic duct dilatations in the liver. The mean (±SD) choline-to-lipid ratios were 0.11±0.035 in the control group, whereas the ratio in the infected group increased significantly with the progression of time. Histologic grading of hepatic inflammation and fibrosis were correlated well with the MRI grading (Spearman rank correlation test; r=0.746 and p<0.001). The control group showed no dilatation of the bile ducts and showed normal liver patterns. Noninvasive technique, MRI and (1)H MRS can demonstrated and applied to evaluate not only the inflammation-related fibrosis in the small bile ducts but also the metabolic changes in the liver induced by O. viverrini infection. A significant increase in the choline-to-lipids ratios were observed in parallel with the time-course of infection. O. viverrini infected in human is detected by stool examination. Hepatobiliary morbidity is detected and followed up by ultrasonography. MRI and MRS can be used in conjunction with ultrasonography for evaluation of progression of the disease.
    Full-text · Article · Jul 2013 · Magnetic Resonance Imaging
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    • "Optical imaging is typically limited by tissue penetration depth and relatively poor quantification. Fluorescence imaging is limited to tissue depths of 1 to 2 mm in the visible range and as much as 1 to 2 cm in the NIR range [28,29]. Clinically, the detection of the sentinel lymph node using ICG was restricted to 5 mm of tissue depth in oropharyngeal cancer patients [30]. "
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    ABSTRACT: Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy.
    Full-text · Article · Apr 2013 · EJNMMI Research
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    ABSTRACT: The role of radiology in biomedical research has changed drastically during the last 10 years. It used to be a science with two main lines, namely technical development and clinical applications. There was an awareness of the need for more cost-benefit studies of the higher states of the Thornbury scale (Thornbury 1994). However, there were rarely any such studies performed and this lack of scientific efforts was probably explained by the complex biases of treatment and multiple sociological factors on the outcome of imaging examinations.
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