Endomicroscopy - Biomedical Optical Imaging Technologies: Design and Applications - page 271

and acquired at 30 frames per second. Pillai et al. also showed confocal fluorescence
imaging by raster scanning proximal to a GRIN lens assembly [ 51 ]. This assembly
is noteworthy in that the optical design permitted a relatively large aspect ratio to
be realized; 25 mm long with a diameter of only 350 m, allowing the imaging
lens to be passed through the lumen of a 22-gauge needle and advanced deep into
tissue. These GRIN-lens-based systems generate a magnified image of the tissue
located at the object plane, which is oriented parallel to the distal face of the GRIN
lens, usually with a small working distance .10-100 m/. Kim et al. demonstrated
a method, similar to that used in rotary OCT catheters, which provides a sideways-
viewing probe by bonding an aluminum-coated microprism to the distal face of a
GRIN lens assembly, folding the optical path by 90 ı [ 22 ]. When inserted into tissue,
this configuration provides a cross-sectional or transverse image of tissue along the
wall of the insertion hole, oriented as in conventional histopathology. A second
application of this GRIN lens-prism combination is in imaging the epithelial lining
within narrow lumen organs such as the mouse colon. By rotating the probe about
its axis, an image of the entire wall circumference can be collected. When a spiral
scan pattern is used (probe rotation combined with pullback), the lumen of an entire
organ can be imaged.
While these and other studies have taken advantage of the small size and
availability of GRIN lens components, a fundamental limitation is that GRIN lens
objectives are still quite short and must be fixed in position relative to the scanning
beam and tissue site. Imaging through flexible, narrow, fiber-optic components can
permit imaging in freely moving animals and thus might be more practical for
clinical application. More recently, higher-performance lenses (see Table 8.5 )were
added to the list of available GRIN-based components and enabled more challenging
applications like nonlinear tissue imaging [ 52 ].
The three major types of GRIN or GRIN related lenses used in endomicroscopy
are single element GRIN lenses (see Fig. 8.11 a), two different GRIN lenses
(Fig. 8.11 b), and hybrid hemisphere-GRIN lens objectives (Fig. 8.11 c) (versions
with hemispherical lens and two GRIN lenses are also available see Table 8.5 ).
Two-element confocal miniature objectives combine two different focal length
components. For example, following [ 53 ], short focal length objective lens can
be made by silver/sodium ion exchange in glass. This allows reaching refractive
index gradient between 1.626 and 1.547 on axis and at the edge, respectively.
Component 2 - imaging lens of a shorter focal length can use lithium/sodium
exchange process. Examples of focal lengths for both components are 0.93 and 2.41,
respectively, to provide 0.5 NA lens [ 53 ]. These types of lenses can be integrated
with miniature scanning mechanisms or build as long rigid systems. The use of a
compound GRIN lens assembly comprising a short pitch length (high NA) GRIN
lens optically bonded to a one-quarter, three-quarter, five-quarter, etc., pitch lower
NA relay GRIN lens, results in a GRIN assembly below 1 mm in diameter and up
to several centimeters in length. The length of the assembly ultimately determines
the available imaging depth on insertion into tissue. It should be noted though, that
optical aberrations accumulate with increasing pitch (or multiple components), so
excess length should be avoided. As with conventional wide-field epifluorescence,