Biomedical Engineering Reference
In-Depth Information
to acquire a dataset is the rate-limiting step. Hence the application of fast imaging protocols will
have a major impact on the throughput achievable. Parallelization of data acquisition enabling the
collection of data sets from several animals simultaneously is a strategy that has been recently
introduced.
Quantii cation
: A quantitative comparison of efi cacy readouts for various drug candidates and
placebo groups are essential in DDD. This requires the derivation of quantitative information from
imaging data set based on morphometric and densitometric analyses (Section 7.2.1). While such
tools are largely available, there is need for further developments. The biomedical researcher is not
interested in expressing treatment efi cacy in terms of changes in method-specii c imaging param-
eters such as relaxation time, l uorescence intensity, or local activity measures. Results should be
provided in terms of physiological parameters such as tissue perfusion, oxygenation levels, or tracer
concentrations. Frequently, biological processes are regulated in a discrete manner; a threshold
parameter has to be maintained in order to ascertain proper cell function. For example, there is a
minimal CBF level to ensure cell survival and there is another higher CBF threshold to allow proper
cell function (i ring). Hence, expressing perfusion in relation to values in the nonaffected tissue is
less relevant in predicting outcome than would be absolute values in relation to these thresholds.
Derivation of absolute values of biological parameters from imaging data sets requires a detailed
understanding of the underlying biochemical and biophysical processes and the development of
sophisticated tissue models.
Target-specii c probes
: A critical aspect for exploiting the power of molecular imaging applica-
tions in DDD is the availability of target-specii c imaging probes. Extrapolating past experience
with developing generic imaging probes, diagnostics industry seems to hesitate in embarking into
molecular imaging agents. Specii city of a potential probe will limit its potential market volume.
In this context, pharmaceutical industry will have to play a pioneering role in order to have the
agents available to support the DDD programs, following the theranostics concept.
7.6 CONCLUSIONS
Imaging methods providing quantitative structural, functional, and more recently also cellular and
molecular information in a noninvasive manner have become valuable tools for the preclinical and
clinical evaluation of drug candidates.
The i eld of noninvasive imaging is in rapid development: established modality such as CT,
MRI, and PET are being optimized with respect to efi ciency of data acquisition, data analysis, and
operating comfort. For all these modalities small animal versions are currently available aimed at
facilitating translational application. Novel modalities such as bioluminescence and l uorescence
imaging have emerged and are rapidly becoming an attractive tool for the biologist. These tech-
niques are attractive as they are cheap, use stable reporter systems, and are characterized by high
sensitivity. They exploit readouts widely used in molecular biology, which can be further developed
for in vivo application. However, translation to the clinics is not straightforward due to biophysical
limitations (penetration of light) and due to the fact that many of the reporter systems are difi cult
or virtually impossible to apply in humans. Yet, for experimental research, optical imaging methods
will become highly relevant.
A combination of the various imaging techniques currently available either by postprocessing
(image fusion) or by simultaneous recording will allow a comprehensive characterization of a
biological problem. Disease processes might be studied at the receptor level, by monitoring
individual signaling cascades, and finally the morphological, physiological, and metabolic
consequences of these molecular events. As such, multimodal imaging might become an interesting
tool for system biology. For the drug developer, on the other hand, multimodality imaging should
become an important instrument to understand drug effects in the intact individual.
