Biomedical Engineering Reference
In-Depth Information
At the dermo-epidermis junction (Figure 14.15d), the collagen fibers at the peak of the dermal papilla
are revealed by SHG microscopy. The THG-bright basal cells surround the collagen fibers with a circular
locus and the size of the locus increases as we move deeper into the dermis (Figure 14.15e). Depending
on the conditions (age, sex, position, color, etc.) of different normal skin specimens, the penetrability
can vary within 270-300 μm. The penetrability is simply defined as the maximum depth at which the
fine collagenous structures or the subcellular structures can still be distinguished.
In addition to the normal human skin, the
ex vivo
SHG/THG imaging was also demonstrated on
the excised diseased human skin, including three kinds of pigmented skin lesions—compound nevus,
pigmented basal cell carcinoma (BCC), and superficial spreading melanoma (SSM). Although the three
cases are all pigmented skin lesions, the pathological changes are greatly diverse and the major diag-
nostic characteristics are quite different. However, in clinical diagnosis, melanoma and other benign
or malignant pigmented skin tumors can significantly overlap in their clinical and dermoscopical pre-
sentations and thus, pigmented skin lesions may be misdiagnosed (Makino et al. 2007). For example,
melanoma at early stages may seem identical to benign nevi, while pigmented BCC and melanoma are
sometimes misdiagnosed due to their similar appearance. By using SHG/THG microscopy for investi-
gation, the typical characteristics of each skin lesion can easily be revealed for diagnosis of different skin
diseases and the ability to accurately distinguish between benign nevi from malignant melanoma and
between different types of malignant skin tumors can be provided.
14.3.4.2 Diseased Human Skin: compound nevus
According to the previous pathological evidences (Okun 1997; Gonzalez et al. 2003), compound nevus is
a common melanocytic lesion that demonstrates nevomelanocytes (i.e., nevus cells) at both the dermo-
epidermal junction and the superficial dermis. Figures 14.16a through 14.16h show a series of SHG/THG
images obtained at different depths in a compound nevus specimen, while Figures 14.16i through 14.16l
show a series of SHG/THG images obtained in the normal skin surrounding the compound nevus. In
the SHG images obtained in the dermis, the collagen fiber bundles can be revealed to be thicker in the
nevus (Figures 14.16d and 14.16e) than those in the normal skin (Figures 14.16k and 14.16l). Since the
thickening of fiber bundles and the increasing of fibroblasts are both characteristics of the hosts response
with fibrosis, the differences found in the dermis of the nevus and normal skin can indicate the higher
degree of fibrosis in the nevus. In addition to the collagenous structures, through THG modality, the
increasing number of the fibroblasts can be revealed as the other index for scoring the degree of fibrosis.
Even at 180 μm, the fibroblast (arrowhead in Figure 14.16e) can be easily observed in the nevus but no
obvious fibroblast can be found in the normal skin (Figure 14.16l). In the deeper dermis (Figures 14.16f
through 14.16h), intradermal nevomelanocytes, the most significant characteristic for diagnosis of the
compound nevus, are shown by THG modality to group in round clusters (arrows) and be surrounded
by the SHG-revealed collagen fibers. These results are in complete agreement with previous histologi-
cal conclusions. Even deep inside the reticular dermis at 300 μm, the grouping nevomelanocytes can
still be observed by THG modality, while the much stronger THG contrast is provided by the melanin
in the nevomelanocytes. Through the THG images, the individually distributed nevomelanocytes can
also be found at the dermo-epidermis junction (Figure 14.16d) of the nevus (arrowhead) but not in the
normal skin (Figure 14.16k), and this is another important characteristic of the compound nevus. In
the epidermis, the THG-revealed epidermal architectures are shown to remain unchanged in the nevus
(Figures 14.16a through 14.16c).
14.3.4.3 Diseased Human Skin: Superficial Spreading Melanoma
In contrast, SSM, the most common form of melanoma (Langley et al. 1998; Forman et al. 2008), is
characterized by large epithelioid melanocytes, called melanoma cells, distributed singularly or in nests
within all levels of epidermis. The normal architectures of epidermis are usually disrupted and even
replaced by the melanoma cells, while the pattern of the rete ridges is often effaced. SSM often tends
to be flat and asymmetric with varying colors. By performing SHG/THG imaging in two differently
