Biomedical Engineering Reference
In-Depth Information
are the most significant diagnostic characteristic of BCC, are found to replace the normal papillary and
reticular dermis in the pigmented BCC specimen (Figures 14.18c and 14.18d). Through SHG modality,
the loose collagen fibers can be revealed to enclose the tumor cells, while the specific nodular pattern
and parallel arrangement (palisading) of the tumor cells are clearly resolved by THG modality. Through
the THG signals, the tumor nodules can be resolved to be composed of tightly packed oval cells and have
parallel arrangements of the tumor cells (palisading) at the edge of the tumor nodules (arrows in Figure
14.18d). Moreover, within the tumor nodules, bright THG spots (circled in Figure 14.18d) are frequently
found to be randomly distributed and these spots with isolated THG signal enhancements indicate the
high melanin contents and also the melanophages in the nodules.
On the other hand, in the superficial epidermis, the stratum granulosum of the lesional specimen
(Figure 14.18a), the honeycomb pattern of the granular cells is shown by THG modality to remain
unchanged and the same as what is observed in the normal skin (Figure 14.18e); in the deeper epider-
mis, the disruption of the normal epidermal architecture in the lesional specimen (Figure 14.18b) can
be revealed by THG in contrast to normal skin (Figure 14.18f). Through the THG signals, the cells with
elongated and polarized shapes (arrowhead in Figures 14.18b and 14.18c) instead of the columnar basal
cells (Figure 14.18f) can be observed in the lesional specimen, and this cellular morphology is one of the
diagnostic characteristic of BCC. In addition, the skin around the lesion is also investigated. In contrast
to the normal skin, the spindle-like and disarrayed keratinocytes in the stratum spinous and stratum
basale of this surrounding skin specimen can be revealed by THG (arrowheads in Figure 14.18i). At the
dermo-epidermal junction, the basal cells around the dermal papilla are found to be unusually elon-
gated and parallel with one another (arrowheads in Figures 14.18j and 14.18k), while anomalous collag-
enous structures, ring-shaped (Figure 14.18l) but not areolar (Figure 14.18g) collagen fibers, are revealed
in the papillary dermis by SHG modality. Since the cellular morphology and collagenous structures
disagree with the findings in the normal skin, the skin specimen is suggested to be suspicious cancer-
ous or precancerous tissue. In the
ex vivo
study of the BCC, SHG/THG microscopy is shown to possess
the ability to reveal the most important diagnostic characteristic of BCC and also have the potential for
early diagnosis of the precancerous tissues.
14.3.4.5 conclusions
Comparing among the SHG/THG images of three different types of lesional skin, SHG modality can
help to reveal the pathological changes of the collagenous structures of the dermis. However, in the
cases with thicker epidermis and higher melanin contents in the epidermis like melanoma, even no SHG
signals can be observed and the morphological information provided by THG modality plays an impor-
tant role in the diagnoses. With abundant THG contrasts in both epidermis and dermis, THG modal-
ity has the ability to reveal the typical diagnostic characteristics of each kind of skin lesion with high
spatial resolution. Combining SHG with THG modality, it is able to histopathologically distinguish
among different skin diseases and between benign and malignant lesions. Based on the THG contrast
from melanin, THG microscopy demonstrates the unique capability for molecular imaging of melanin
distributions and for diagnosing and screening early melanocytic lesions. As shown in Table 14.2, the
significant diagnostic characteristics of three different types of skin diseases observed in the previous
histology studies and revealed by our epi-HGM system have been listed.
14.3.5 clinical Applications
Based on the noninvasiveness, high spatial resolution, and high penetrability of Cr:F-based SHG/THG
microscopy and abundant imaging contrasts of both SHG and THG modalities, the Cr:F-based SHG/
THG microscopy has been applied to clinical (
in vivo
) imaging of human skin. Through clinical dam-
age evaluation, the Cr:F SHG/THG imaging system has been further confirmed to possess essential
safety requirement. More than the static morphological and collagenous information, valuable dynamic
information like red blood flow in dermal capillaries can also be obtained from the
in vivo
observation.
