Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5528_Библиотеки_им_академика_М_И_Перельмана.pdf
170 M. Jain
et al.
for routine histopathologic diagnoses. Furthermore, none of the c ommercially available, confocal endoscopes to date generate three-dimensional
image sets; thus, the diagnostic potential of images generated from those
systems is dependent on operator skill. Therefore, MPM may have practical advantages that are not offered by other optical biopsy techniques when
incorporated into endoscopes or thoracoscopes, for enhanced diagnosis of
superficial lesions.
References
1. https://www.cancer.org/re searc h/can cer-f acts -statis tics/ all-cancer-facts-figures/
cancer-facts-figures-2018.html.
2. https://www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosisstaging/survival-rates.html.
3. Jain, M., Narula, N., Salamoon, B., Shevchuk, M. M., Aggarwal, A., Altorki, N.,
Stiles, B., Boccara, C., and Mukherjee, S. Full-field optical coherence tomography
for the analysis of fresh unstained human lobectomy specimens. Journal of Pathology
Informatics, 4: 26 (2013). doi:10.4103/2153-3539.119004.
4. Jain, M., Narula, N., Aggarwal, A., Stiles, B., Shevchuk, M. M., Sterling, J., Salamoon, B., Chandel, V., Webb, W. W., Altorki, N. K., and Mukherjee, S. Multiphoton
microscopy: A potential “optical biopsy” tool for real-time ev aluation of lung tumors
without the need for exogenous contrast agents. Archives of Pathology & Laboratory
Medicine, 138(8): 1037–1047 (2014).
5. Krishnamurthy, S., Cortes, A., Lopez, M., Wallace, M., Sabir, S., Shaw, K., and Mills,
G. Ex Vivo confocal fluorescence microscopy for rapid evaluation of tissues in surgical
pathology practice. Archives of Pathology & Laboratory Medicine, 142(3): 396–401
(2018).
6. Cui, D., Chu, K. K., Yin, B., Ford, T. N., Hyun, C., Leung, H. M., Gardecki, J. A.,
Solomon, G. M., Birket, S. E., Liu, L., Rowe, S. M., and Tearney, G. J. Flexible, highresolution micro-optical coherence tomography endobronchial probe toward in vivo
imaging of cilia. Optics Letters, 42(4): 867–870 (2017).
7. Shostak, E., Hariri, L. P., Cheng, G. Z., Adams, D. C., and Suter, M. J. Needle-based
optical coherence tomography to guide transbronchial lymph node biopsy. Journal of
Bronchology and Interventional Pulmonology, 25(3): 189–197 (2018).
8. d’Hooghe, J. N. S., Goorsenberg, A. W. M., de Bruin, D. M., Roelofs, J. J. T. H.,
Annema, J. T., and Bonta, P. I. Optical coherence tomography for identification and
quantification of human airway wall layers. PLoS One, 12(10): e0184145 (2017).
9. Hassan, T., Thiberville, L., Hermant, C., Lachkar, S., Piton, N., Guisier, F., and
Salaun, M. Assessing the feasibility of confocal laser endomicroscopy in solitary
Lungs 171
pulmonary nodules for different part of the lungs, using either 0.6 or 1.4 mm probes.
PLoS One, 12(12): (2017).
10. Thiberville, L., Salaün, M., Lachkar, S., Dominique, S., Moreno-Swirc, S., VeverBizet, C., and Bourg-Heckly, G. Confocal fluorescence endomicroscopy of the human
airways. Proceedings of the American Thoracic Society, 6(5): 444–449 (2009).
11. Jain, M., Rajadhyaksha, M., and Nehal, K. Implementation of fluorescence confocal
mosaicking microscopy by “early adopter” Mohs surgeons and dermatologists: Recent
progress. Journal of Biomedical Optics, 22(2): 24002 (2017).
12. Jain, M., Shukla, N., Manzoor, M., Nadolny, S., and Mukherjee, S. Modified full-field
optical coherence tomography: A novel tool for rapid histology of tissues. Journal of
Pathology Informatics, 2: 28 Epub (2011). doi:10.4103/2153-3539.82053.
13. He, P., Yao, G., Guan, Y., Lin, Y., and He, J. Diagnosis of lung adenocarcinoma in
situ and minimally invasive adenocarcinoma from intraoperative frozen sections: An
analysis of 136 cases. Journal of Clinical Pathology, 69(12): 1076–1080 Epub 2016
May 12 (2016). doi:10.1136/jclinpath-2016-203619.
14. Yeh, Y. C., Nitadori, J., Kadota, K., Yoshizawa, A., Rekhtman, N., Moreira, A. L.,
Sima, C. S., Rusch, V. W. , Adusumilli, P. S., and Travis, W. D. Using frozen section
to identify histological patterns in stage I lung adenocarcinoma of = 3 cm: Accuracy
and interobserver agreement. Histopathology, 66(7): 922–938 (2015).
15. Griffin, R. and Ramirez, R. A. Molecular targets in non-small cell lung cancer. Ochsner
Journal, 17(4): 388–392 (2017), Review.
16. Sholl, L. Molecular diagnostics of lung cancer in the clinic. Translational Lung Cancer
Research, 6(5): 560–569 (2017), Review. doi:10.21037/tlcr.2017.08.03.
17. Xu, L., Tavora, F., Battafarano, R., and Burke, A. Adenocarcinomas with prominent
lepidic spread: Retrospective review applying new classification of the American Thoracic Society. The American Journal of Surgical Pathology, 36(2): 273–282 (2012).
18. Lee, H. Y., Jeong, J. Y., Lee, K. S., Kim, H. J., Han, J., Kim, B. T., Kim, J., Shim,
Y. M., Kim, J. H., and Song, I. Solitary pulmonary nodular lung adenocarcinoma:
Correlation of histopathologic scoring and patient survival with imaging biomarkers.
Radiology, 264(3): 884–893 (2012).
19. Schneider, F. and Dacic, S. Histopathologic and molecular approach to staging of
multiple lung nodules. Translational Lung Cancer Research, 6(5): 540–549 (2017),
Review. doi:10.21037/tlcr.2017.06.11.
20. Chansky, K., Detterbeck, F. C., Nicholson, A. G., Rusch, V. W., Vallières, E., Groome,
P., Kennedy, C., Krasnik, M., Peake, M., Shemanski, L., Bolejack, V., Crowley, J. J.,
Asamura, H., and Rami-Porta, R. IASLC Staging and Prognostic Factors Committee,
Advisory Boards, and Participating Institutions. The IASLC lung cancer staging
project: External validation of the revision of the TNM stage groupings in the eighth
edition of the TNM classification of lung cancer. Journal of Thoracic Oncology, 12(7):
1109–1121 (2017).
21. Ylisirniö, S., Höyhtyä, M., Mäkitaro, R., Pääakkö, P., Risteli, J., Kinnula, V. L.,
Turpeenniemi-Hujanen, T., and Jukkola, A. Elevated serum levels of type I collagen
172 M. Jain
degradation marker ICTP and tissue inhibitor of metalloproteinase (TIMP) 1 are associated with poor prognosis in lung cancer. Clinical Cancer Research, 7(6): 1633–1637
(2001).
22. Matsuo, Y., Hashimoto, S., Koga, T., Yonemitsu, Y., Yoshino, I., Sugimachi, K.,
Honda, H., Masuda, K., and Sueishi, K. Growth pattern correlates with the distribution
of basement membrane and prognosis in lung adenocarcinoma. Pathology Research
and Practice, 200(7–8): 517–529 (2004).
23. ten Velde, G. P., Havenith, M. G., Volovics, A., and Bosman, F. T. Prognostic significance of basement membrane deposition in operable squamous cell carcinomas of
the lung. Cancer, 67(12): 3001–3005 (1991).
et al.
© 2024 World Scientific Publishing Company
https://doi.org/10.1142/9789813206984_0009
Breast Chapter
9
Daniel Schmolze
∗
Introduction
True in vivo microscopy of the breast is at a very early stage of development.
This is mostly due to historical technical constraints, such as the inability to
image thick tissues and the relatively large size of the instruments. Devices
are now small enough to be incorporated into needles and tiny fiber optic
probes, which will doubtless lead to exciting new applications in the breast
and other solid organs.
In the meantime, there has been much interest in near real-time ex vivo
applications (e.g. for intraoperative margin assessment) and in novel optical
techniques for imaging breast lesions. This chapter will focus on these latter
techniques since ex vivo breast cancer applications are discussed separately
in the ex vivo chapter. The definition of “in vivo microscopy” is used somewhat loosely here to include any technique that is capable of discerning
tissue ultrastructure via optical methods.
∗
Digital Pathology, City of Hope National Medical Center, Duarte, USA.
173
174 D. Schmolze
Optical Mammography
Optical mammography is an imaging method that uses near-infrared light to
image thick tissues. The technique is also known as diffuse optical imaging
(DOI) and near-infrared spectroscopy (NIRS). Compared to conventional
X-ray mammography, optical mammography is non-radioactive and is able
to characterize both functional and structural properties of breast tissue.
Unlike X-ray mammography, which achieves contrast through differential radiodensity, optical mammography exploits the differential absorption
and scattering of tissue constituents, such as hemoglobin, water, and lipids
(Figure 1). As in X-ray mammography, projection images of the breast in a
single plane of view are most often acquired, but 3D reconstruction along a
particular plane of view is also possible via a technique called tomography,
similar to X-ray tomosynthesis.
1
Figure 1. Optical mammography images at various wavelengths. A cranio-caudal optical image
of both breasts is displayed on the right, along with the corresponding X-ray mammogram on the
left. A tumor in the left breast is readily identified via strong absorption at 685 nm, likely due to
high deoxyhemoglobin content, while benign cysts are identified via their low scattering across
wavelengths. Adipose tissue is identified via absorption at 915 nm, corresponding to the radiopaque
region on the X-ray mammogram. Adapted from Ref. [2].
Breast 175
The earliest efforts at applying in vivo imaging methods to breast cancer detection date to the late 1920s, when Cutler
3
developed a technique
he called “diaphanography”, which involved simply shining a powerful light source through the breast and observing the transmitted pattern (i.e. the shadow image). The technique could detect lesions with
increased absorption due to vascularization but was unable to determine benign from malignant and thus proved unhelpful for diagnostic
purposes.
Over the ensuing decades, interest in optical imaging experienced a
resurgence with the development of near-infrared laser light sources and
technicaladvances that enabled the de-coupling of absorptionand scattering
measurements. These advances led to devices capable of discerning tissue
structure via scattering measurements made at different wavelengths, and
several studies demonstrated reasonable specificity and sensitivity for the
detection of breast lesions.
For example,a large European multi-institutionalstudy dubbed OPTIMAMM used time-resolved pulsed infrared lasers to collect optical images
from both breasts, using the standard cranio-caudaland medio-lateral views
4
used in X-ray mammography. One group
developed an instrument that
used three wavelengths and depended primarily on total hemoglobin concentration as a source of contrast. They imaged 154 patients with suspicious
breast lesions, of whom 102 were subsequently found to have histologically
confirmed carcinoma. 92 of these cases (90%) were detected in one or both
views.
Another group within the same study
5
developed a four-wavelength
instrument with two long wavelengths (above 900 nm) for increased sensitivity to lipids and water. They detected 50 of 52 histologically confirmed
carcinomas (96%). A number of benign cysts were also correctly classified,
with a detection rate of 90% in one or both views.
These studies and others have generally demonstrated good results
with optical mammography, but performance has thus far suffered due to
the inherently limited spatial resolution achievable by near-infrared light
sources. This limitation hampers the detection of small lesions in particular,
which is problematic for screening purposes where early-stage lesions are
the focus.
176 D. Schmolze
As a result, there has been a shift away from envisioning optical mammography as a standalone screening modality and toward a multimodal
model where it is incorporated as a complementary technique alongside
more traditional imaging methods. Optical imaging is well suited for this
purpose, as the functional information it generates cannot be obtained via
X-ray mammography or magnetic resonance imaging (MRI), which largely
provide structural data. When combined, the structural information constrains the optical image reconstruction, providing enhanced sensitivity,
while the functional information from the optical image improves specificity. The result is not unlike positron emission tomography-computed
tomography (PET-CT) but can be achieved more quickly with less expense
and with less radiation exposure to the patient.
The multimodal approach appears very promising and is under active
investigation by a number of research groups. Various traditional techniques have been proposed in combination with optical imaging, includ-
6
ing conventional X-ray mammography,
9
ultrasound.
In a representative study,726 malignant lesions and 25 benign
X-ray tomosynthesis,7MRI,8and
lesions were imaged using a combined optical/X-ray tomosynthesis system (Figure 2). Significant differences in total hemoglobin concentration
were observed between malignant tumors, solid benign lesions, and cysts,
and significant differences in oxygen saturation were seen between solid
benign lesions and cysts. A follow-up study by the same group
6
used separately obtained X-ray mammograms and optical images and developed
an algorithm to effectively co-register the two image types with similar results. Such an approach might ease clinical adoption since existing
imaging devices would not have to be retrofitted to incorporate an optical
component.
The multimodal studies to date are promising but have generally been
exploratory and preliminary with an emphasis on validation of device engineering and image analysis. In the next phase of development, some degree
of device standardization will be required, followed by randomized clinical
trials to assess the clinical performance of multimodal systems in a robust
manner.
Besides screening, two other potential use cases for optical imaging of
the breast deserve discussion. The first is for following treatment response
Breast 177
Figure 2. Combined optical mammographyand X-raytomosynthesis. Combined X-ray tomosynthesis
(left) and optical imaging (right) results are shown. The arrow highlights an invasive carcinoma. The
structural information provided by the X-ray image guides the optical image reconstruction process,
while the optical image provides functional data to enhance specificity. https://www.photonics.com/
Article.aspx?AID=53277.
in patients receiving neoadjuvant chemotherapy (NAC). Such treatment is
becoming increasingly common, even for patients without locally advanced
disease, since it provides an early indication of treatment efficacy and prog-
10
nosis.
to provide the best correlation with histopathologic assessment.
Typically, MRI is used to assess response to NAC, as it appears
11
However, sensitivity for residual disease is suboptimal, with one study reporting a negative predictive value of only 65%.
12
A more accurate method
for assessing response to NAC would s ignificantly improve individualized
treatment planning in this expanding group of patients.
Many studies haveinvestigatedoptical imaging systems for this appli-
cation with promising initial results. Since the first case study demonstrating
13
feasibility,
numerous additional studies have consistently demonstrated
the ability of optical imaging to detect physiologic changes that accompany
14
response to NAC (Figure 3). In one such study,
11 patients receiving
NAC were monitored with optical imaging during the course of therapy,
and their pre- and post-treatment pathology specimens were evaluated for
tumor angiogenesis by immunohistochemistry. For patients who obtained
a pathologic complete response (pCR), a significant correlation was found
between total hemoglobin concentration as assessed by optical imaging
and the level of tumor angiogenesis, providing a mechanistic explanation
178 D. Schmolze
Figure 3. Optical mammography for monitoring NAC response. Optical mammography findings in a
patient achieving complete pathologic response to NAC (Residual Cancer Burden Score 0) versus
a patient with residual disease (RCB II). In the responding patient, a marked decline in [HbO
seen starting at week 2, while in the non-responder, there is persistently high (HbO
Ref. [15].
). Adapted from
2
2
]is
for the imaging findings. In addition, for patients who achieved pCR (but
not those achieving a partial pathologic response), a significant decrease in
mean total hemoglobin was observed via imaging.
These studies and others suggest a role for optical imaging in monitoring NAC response, but as for multimodal screening/detection applications,
robust data in the form of prospective clinical trials are currently lacking.
The low numbers enrolled in most of the studies thus far suggest that a
multi-institutional effort may be necessary, which again will n eed to be
preceded by technical standardization.
A final potential application for optical mammography lies in screening women with dense breasts. X-ray mammography performs poorly in
16
this context with drastically reduced sensitivity.
This fact informs breast
cancer screening guidelines since the risks of screening in younger populations (with denser breasts) are thought to outweigh the potential benefits,
given the poor performance of conventional mammography in this cohort
of patients.
17,18
While the risk of breast cancer is relatively low for women in their
40s, it is not negligible; at least a quarter of new breast cases arise in
younger women,
sive than tumors occurring in older women.
18
and moreover, these tumors tend to be more aggres-
19
In addition, some younger
patients require screening because they are at high risk of breast cancer
(e.g. because of BRCA mutations or a strong family history). Independent
of patient age, breast density itself appears to be an independent risk factor
Breast 179
for the development of breast cancer,20and any woman with particularly
dense breast tissue may not be well served by conventional mammography. In such cases, MRI is typically used, since it appears to offer superior
21,22
sensitivity.
specific, with a relatively high false positive rate,
However, there is concern that MRI may be insufficiently
23
and the procedure itself
is time-consuming, expensive, and uncomfortable.
Preliminary studies have been performed investigating the utility of
optical imaging for dense breast tissue. The initial studies focused primarily on quantifying density for the purposes of assessing cancer risk. For
example, one study
24
developed an optical index incorporating the effects
of collagen and showed correlation with mammographic density. More
recently, a pilot study investigated the ability of optical imaging to specifically detect lesions in dense breast tissues.
25
They imaged 24 patients with
dense breasts and known diagnoses of breast cancer and applied previously
developed optical indices in conjunction with a hand-held imaging probe.
21 of 24 tumors were distinguishable from the surrounding dense normal
tissue, including cases close to the nipple–areola complex that could not be
imaged using X-ray mammography.
In summary, optical mammography is an exciting and rapidly developing imaging modality with several promising potential applications in
breast cancer. As an a djunct to traditional X-ray mammography, optical
mammography provides functional information that may increase specificity, reducing false-positive rates and unnecessarybiopsies. The technique
may allow for earlier assessment of response to neoadjuvant chemotherapy,
improving individualized treatment planning. Finally, optical mammography may have a role in evaluating patients with dense breasts, perhaps as
part of a multimodal imaging platform. In the near future, large-scale clinical trials and device standardization are needed to prove clinical efficacy
and advance the field.
Photoacoustic Imaging
Photoacoustic Imaging (PAI) can be considered a subtype of optical mammography with some important differences. When tissue is exposed to a
pulsed near-infrared light source, thermal and elastic expansion occurs,