19-03 Proteins and Protein Engineering
The latest advances in biochemistry have made it possible to begin to build proteins from scratch, and so in principle create a molecule to do a specific task. Because it is the structure of the protein which controls its function, very precise information about the structure is essential and high-resolution NMR is one of the few ways of uncovering it.
Magnetic resonance can help determine the structures of large biomolecules in proteonomics, and add information in metabolomics research.
The NMR spectra reveal information about the neighboring atoms for each atom in the molecule. With even a small protein containing hundreds of atoms, one of the major problems is too much information. The spectroscopist can design the NMR experiment to keep the amount of information to a manageable level, and then molecular modeling computer programs are used to generate three-dimensional structures from the NMR data. Such research programs have for instance been applied in the development of new antibiotics as well as x-ray and magnetic resonance contrast agents.
19-04 Computer Applications and Pattern Recognition Techniques
With manifold tissue parameters, MR imaging has a great variety of image contrast and substantial potential for tissue discrimination and even characterization in different organs. This, on the one hand, is a major advantage of MR imaging compared with other imaging modalities, on the other hand, it may prove to be disadvantageous because several series of images with different parameter weighting (i.e., proton density-, T1, and T2-weighting, pre- and post-contrast) of the same region of the body have to be acquired.
This easily leads to hundreds of images per examination which have to be read by the responsible physician. Image reading and interpretation is basically done as (a) analysis of morphology, and (b) analysis of signal behavior. In general, MR imaging is a qualitative and subjective examination with a high level of uncertainty.
For routine clinical imaging, a simplification of the diagnostic procedure would be advantageous. This might both cut down time and costs, as well as diagnostic uncertainty. In addition, pattern recognition techniques might lead to a preliminary diagnosis before images are read and increase diagnostic performance.
Tissue discrimination and characterization on the basis of relaxation time calculations has been shown to be unfeasible. Thus, other methods have to be considered. Basic considerations must include: (a) MR imaging possesses several physical parameters; (b) there are difficulties in computing and exploiting these parameters; and (c) there is the possibility to devise a multivariate test (pattern recognition techniques), which will decrease the level of uncertainty in the diagnosis and increase the diagnostic performance.
In general, MR images are crude and it is inappropriate to process them by pattern recognition techniques, mainly because of geometrical distortion, intensity distortion, and noise. However, first results have demonstrated that computers can recognize certain normal structures and distinguish them from pathology. These methods could also be applied to industrial use of MR imaging or other imaging techniques, e.g., for quality assurance programs.
19-05 Non-Destructive Testing
Some applications of NMR in non-destructive testing have been described before, e.g., the examination of plastic and ceramic components. Here, a broad range of applications has been developed, but the spectrum of possible new applications is wide. MR imaging, particularly diffusion studies, are used for nondestructive testing of, e.g., ceramics. Quality assurance by non-destructive testing is applied for chemical, including pharmaceutical and dietary, raw material.
Space technology will exploit the possibilities of NMR to assess the influence of microgravity, acceleration, and vibration upon materials and their possible degradation. Monitoring could be performed before and after space flights, and with suitable equipment even in space.
Quality assurance programs with NMR include also measurement and control of other techniques such as chromatography. Small, robust NMR machines are already available, and machines for particular applications custom-tailored for specific technical solutions can be developed at competitive prices, and sample changers with high throughput for uninterrupted operation are available.