Detecting Extravascular Matrix Patterns Clinically:

A Non-Invasive Substitute for Biopsy


The in vitro formation of extravascular matrix patterns by aggressive tumor cells (but not by tumor cells lacking aggressive characteristics) validates the strong association between death from metastatic melanoma and the detection of these patterns in tissue sections made by multiple indpendent laboratories. If these patterns could be detected clinically - by non-invasive imaging techniques - then physicians might have a non-invasive method of extracting the same prognostic information available to the pathologist examining a tissue biopsy.

The non-invasive substitute for biopsy is important in ocular oncology because of the desire to avoid compromising vision when treating patients in intraocular cancers. Two imaging techniques show considerable promise in allowing ocular oncologists to detemine if a patient with uveal melanoma is at low or high risk or metastatic diease.

Ultrasonography. The power spectrum analysis of raw radiofrequency data can be used in patients to dectect the presence of areas of acoustic backscattering that correspond to tumor that is organized architecturally by extravascular matrix patterns. This ultrasound approach is independent of any flow of blood or plasma through this system.

Suggested References:

Silverman RH, et al. Correlation of ultrasound parameter imaging with microcirculatory patterns in uveal melanomas. Ultrasound Med Biol 1997;23:573-581.

Silverman RH, et al. Detection of prognostically significant histologic features in uveal melanoma with backscatter spectrum analysis. Ultrasound Med Biol 2003 (in press).

Laser Scanning Confocal Angiography with Indocyanine Green. Approximately 15 seconds after the injection of the contrast agent, indocyanine green, into the antecubital vein of patient with uveal melanoma, it is possible to visualize networks of back-to-back loops by laser scanning confocal imaging of the patient's eye. The presence of these patterns angiographically correlates with the presence of these patterns histologically. Furthermore, the detection of these angiographic patterns is predictive of clinical tumor growth and a rapid response to radiation therapy (an observation that has been linked to an aggressive clinical course).

Suggested References:

Mueller AJ, et al. Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy. Arch Ophthalmol 1998;116:31-39.

Mueller AJ, et al. Complex microcirculation patterns detected by confocal Indocyanine green angiography predict time to growth of small choroidal melanocytic tumors. MuSIC-Report II. Ophthalmology 2002;109:2207-2214.


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