Análisis de las encuestas aplicadas a microempresarios que dirigen a los centros de acopios en el cantón Quevedo

A new technology must be rigorously evaluated in laboratory and clinical trials before being adopted for use in the clinic. Images must be acquired on the test system as well as on a reference system that is the clinical standard and/or identifies truth. Phantom imaging allows quantitative system characterization and optimization of imaging

parameters with designed truth parameters. The typical next step is to image breast tissue specimens, where truth is determined through histopathologic sectioning. Imaging tissue specimens allows initial measurements of sensitivity and specificity with control over population parameters. Together, phantom and specimen imaging allows the collection of preliminary safety data.

When a system has exhibited sufficient image quality and safety in laboratory studies, a clinical trial must be designed. Potential imaging applications of the technology (screening, diagnostic imaging, assessment of extent of disease, monitoring therapy response) will influence study design. Trial procedures include patient eligibility criteria (e.g. age, race/ethnicity, mammographic density, family history, breast size, prior cancer, prior surgery, implant), imaging parameters (e.g. subject radiation dose, contrast

(e.g. biopsy, genetic testing), and criteria for data inclusion (e.g. image quality). Statistical procedures include study design (e.g. prospective, retrospective, blinded), study hypotheses, sample size estimation, randomization protocol, as well as data and statistical monitoring for interim and final analyses.

As of 2006, the FDA has promoted adaptive trial design, such that modification of trial and/or statistical procedures based on interim data analysis can occur while a trial is ongoing in order to increase the likelihood of achievement of study endpoints without compromising the validity of the original trial (Chow 2008, Mehta 2009). Initial pilot clinical trials often start with small targeted patient populations, which provide

information on efficacy and system performance. The next step may be to compare the new technology to the gold standard in a head-to-head comparison by way of a

randomized or double-blind randomized, controlled trial controlling for and possibly matching as many variables as possible. Expert radiologists analyze the images, ranking their suspicion of malignancy on a confidence scale (as used for Likert or ROC). Head- to-head studies with competing breast imaging systems supply data for cost and diagnostic accuracy, and may demonstrate further where a system might fit within the slope of breast imaging technologies.

7.5 Summary

In order to be clinically valuable, a system must demonstrate an improvement over the current gold standard. Ideally, an improvement would represent an increased ability to detect and/or diagnose breast cancer at an earlier stage, as this may lead to reduced morbidity and mortality. However, a system might also demonstrate

ratio, or in terms of patient quality of life. For example, while an imaging system might detect certain lesions with high sensitivity and specificity, it might also expose the patient to excessive ionizing radiation, or be insensitive to other types of lesions. Such

demonstrations of clinical utility must be performed for every application of the imaging technology, such as for breast cancer screening, diagnostic and/or adjunct breast imaging, detection of multifocality or metastases, or tumor size quantification.

One must consider the population for which the system demonstrates clinical utility, and whether the results with this population can be generalized. Additional factors that should be considered in the evaluation of any new technology include the risk to operator health, effect on workflow capability, cost to patients (e.g. insurance

reimbursement), requirement for a skilled operator, and cost to operate and maintain equipment. Every imaging system is faced with fundamental tradeoffs with respect to image quality, diagnostic accuracy, and cost. Diffraction-enhanced imaging is a novel x- ray imaging system that has undergone laboratory studies to evaluate lesion visibility and explore potential clinical applications. The DEI system and the results of previous studies evaluating DEI for breast imaging applications will be discussed in the following chapter.

CHAPTER 8: DIFFRACTION-ENHANCED IMAGING 8.1 Overview

Synchrotron radiation applied to mammography has demonstrated improved contrast and resolution due to intense, smooth, and highly collimated synchrotron x-rays (Burattini 1992, Burattini 1995, Johnston 1996, Margaritondo 1988). In 1980, Förster proposed the Schlieren method of diffractometry using synchrotron radiation, a single- crystal collimator, and a one- or two-crystal analyzer (1980). The Schlieren method was modified by Chapman in 1996, renamed diffraction-enhanced imaging (DEI), and investigated as a breast imaging modality. DEI has traditionally utilized synchrotron radiation, and is capable of producing images based on the independent contrast mechanisms of refraction, absorption, and extinction due to unique properties of x-ray diffraction in perfect crystals (Davis 1995, Ingal 1995, Chapman 1997, Hasnah 2002b).

The following chapter presents general DEI concepts and DEI system design features. This is followed by a review of how the DEI system converts x-ray refraction into image contrast using Bragg diffraction from perfect crystals. The discussion of DEI image processing techniques presents the removal of analyzer-based artifacts, as well as post-processing techniques that generate images unique to medical imaging. This is followed by presentation of three-dimensional DEI using CT image acquisition and processing techniques.