In vivo pathology: microendoscopy as a new endoscopic imaging modality

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Earlier detection

Almost all cancers are easier to successfully treat if caught early. This principle is particularly true for the approximately 85% of cancers that are epithelial in origin. Most of these cancers do not originate fully malignant from normal tissue but progress through one or more pre-invasive pathologically recognizable steps. Currently for the majority of internal organs topologically connected to the outside environment, endoscopy is the primary method to screen for and diagnose pre-invasive

Comparison to traditional endoscopy and other optical biopsy techniques

The targeted resolution of most of the existing in vivo confocal systems or those under development is approximately 1 to 3 microns in the lateral dimensions [3], [12], [13], [14]. This resolution along with the optical sectioning capability of confocal imaging enables the acquisition of fields of histopathology like images of cells and nuclei in vivo without the need to excise the tissue. Confocal microendoscopy provides a means to visualize the size and arrangement of cells and nuclei and

Confocal principle

Enabled by advancing technology, confocal imaging [20] is an increasingly common form of microscopy that allows enhanced lateral resolution, improvements in axial resolution, and most importantly for in vivo confocal microendoscopy, improved rejection of out-of-focus information from material above and below the plane of focus (Fig. 2). For endoscopy, these benefits translate into cellular-level image resolution at depths of resolution up to hundreds of microns into epithelial tissue.

The key to

Image analysis

Most confocal microendoscopy systems produce images of cell nuclei over hundreds of cells. The skilled observer with a familiarity of the histopathologic changes associated with the disease states being examined can interpret this population of cells. Further, there are groups developing automated quantitative analysis tools to examine the spatial arrangement of cells in tissue to assist in the diagnostic evaluation of the images produced by confocal microendoscopy systems Fig. 23, Fig. 24.

Future developments

In the future, one can expect to see these systems demonstrate higher resolution, increased imaging speeds, and further reductions in the size of the distal probes. In the near term as these systems are used in the clinical research setting, one can expect a number of correlative studies with conventional histopathologic assessment of excised tissue as started for the cervix [32] and as preformed for the new high magnification endoscopy systems [33]. Two of the commercial systems expect to be

Adoption issues

Numerous issues are likely to play a large role in the adoption of confocal microendoscopy by clinicians. The issues include the need to visually interpret a new level of in vivo images similar to pathology. Preliminary market research by the investigators suggest this clinical interpretation is not likely to present a significant problem in that many gastroenterologists are already familiar with the visual changes in the organization of tissue during the neoplastic progression from their own

Screening for Barrett's esophagus

Barrett's esophagus is a precursor lesion for cancer of the esophagus and is associated with a 30 to 125× increase in risk of getting cancer of the esophagus [37], [38], [39], [40], [41]. In the United States, approximately 20 to 30 million individuals suffer from chronic (weekly) acid reflux and, therefore, are at high risk of cancer of the esophagus [37]. Approximately 10% of this population (two to three million individuals) will develop Barrett's esophagus [37], [38], [39], [42]. Barrett's

Screening for esophageal cancer

There is a well-recognized risk of developing adenocarcinoma in the esophagus of patients with Barrett's esophagus with specialized intestinal metaplasia. Most experts agree that surveillance endoscopy for patients with Barrett's esophagus and no history of dysplasia should be performed every 1 to 3 years [37], [39], [44], [45]. For people with a history of dysplasia who have not been treated, endoscopy should occur more frequently. The goal of surveillance is the detection of dysplasia.

Surveillance of inflammatory bowel disease

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, causes inflammation of the intestine. Ulcerative colitis occurs when sores, or ulcers, form on the inner lining of the colon (large intestine). Crohn's disease occurs when ulcers form throughout the entire tissue of the colon and other areas of the GI tract. Five percent of patients with ulcerative colitis are expected to die from colon cancer. Although the figure for Crohn's disease is not known, it is

Screening for colon cancer

There are a significant number of individuals whose risk for colorectal cancer is approximately twice that of the general population due to their personal or family history. Clinical guidelines suggest that these individuals should be screened periodically (typically ranging from every 1 to 5 years) for the detection of precancerous and cancerous conditions beginning at age of 40. Screening for all individuals is suggested at age 50 every 5 to 10 years. The number of individuals requiring

Additional applications

  • As indicated, confocal microendoscopy offers benefits to a wide-ranging number of potential applications. The applications identified previously seem likely as initial applications. Other applications are likely to be pursued as researchers and clinicians become comfortable with the technology. Applications of particular promise for research and clinical relevance include: assessing/monitoring treatment and post-treatment conditions (eg, chemotherapy).

  • Mid-surgery optical biopsy to limit time

Summary

Confocal microendoscopy represents a compelling new imaging modality that brings pathologic information to the point of patient care. The technology permits direct observation of pathologic change at the microscopic level rather than traditional inference based on indirect changes at the macroscopic level. The targeted key benefit addresses earlier detection of precancerous and cancer conditions through improved biopsy selection and examination and more cost-effective solutions to screening and

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