The identification and selection of potentially active drugs for use in treatment of diseases, (for example, cancer) has largely been based on the screening of large numbers of compounds and rational drug design (when the molecular structure of the target such as tumor is known). Once compounds have been chosen based on selectivity to the target and desired functional effect, the ultimate test for advancement of a compound to clinical testing is to show its safety and its efficacy in multiple animal models.
There are several current methods and devices that are used to assess the growth of abnormal external features such as tumors, lesions, sores, port stains and wounds in such animal models. The simplest is to measure a feature in two dimensions, length and width, with the aid of a mechanical or electronic caliper that is manually operated. An approximate volume formula is then used to calculate the area or the volume of the object by assuming an ellipsoid shape of the mass. This is the most commonly used method, since it is simple and the calipers cost very little.
Unfortunately, this approach has obvious pitfalls related to the instrument and methodology used to calculate volume as well as operator-related errors. First, a major source of inaccuracy or variability is caused by the operator's judgment on the choice of the ellipsoid axes. For example, in making a measurement, a different operator may select a different choice of ellipsoid axes. Second, this approach is fairly time consuming. In the case of cancer studies, for example, a single study may involve hundreds of animals, and because the tumor volume measurements have to be done at least twice a week and take a given amount of investigator time per measurement, there is a limit in the number of studies that a single investigator can handle at once. Therefore, a different approach is needed to eliminate the inaccuracies of the methodology and instrumentation used and the subjectivity introduced by the operator.
Other mechanical volume measuring devices come closer to being an automated volume measurement system. These mechanical devices include a cylindrical chamber filled with elongated pins or filaments which, when pressed over a tumor or any other mass, convert the shape of the mass into volume information. Such devices require direct contact to features such as tumors, however.
The most sophisticated methods for measuring a mass include Computer Aided Tomography (CAT) using X-rays, Magnetic Resonance Imaging (MRI) using magnetic scans, Positron Emission Tomography (PET) using electrons and Single Photon Emission Computer Tomography (SPECT) using gamma rays. Such methods are capable of obtaining more accurate size and volume information about both external and internal features such as tumors and organs. The use of such methods is not feasible in many cases, however, due to long and costly preparation times, the unwanted effects of the contrast agents and radioactive compounds and the necessity to anesthetize animals during measurement.
Notwithstanding the availability of the foregoing techniques, there is no method or device for non-contact and fast measurement of the volume of surface features of small animals that can be used in, for example, pre-clinical cancer and inflammation studies. All the methods discussed above suffer from a number of disadvantages. For example, manual caliper measurements are prone to significant subjective operator errors; CAT, PET, MRI and SPECT methods are unacceptably time consuming and expensive; and caliper and cylindrical chamber methods require direct contact with the object under measurement, which is a potential source of feature deformation and contamination that may negatively effect the measurements being made.
As a result there is a need for methods and systems that accurately and quickly measure the volume/size of surface features such as wounds on the surface of animals, plants and humans.