446
K. malek et al.
15.5 Tissue Analysis
the remainder of this chapter will concentrate on some of the many spectroscopic
studies undertaken from the 1990’s onwards, associated with medical diagnostics
of human diseases such as cervical cancer, neurodegenerative pathologies, and dysfunctions of cardiac and liver tissues. they will include investigations on animal
models as well as tissue samples collected from patients. these studies are mainly
based on searching for “infrared biomarkers” within the complex mid-infrared spectrum that are indicative of a pathological, physiological or a biological state (e.g.
different cell types within a tissue), which can be used to discriminate statistically
classes of samples. very often, this statistical approach is accompanied by attempts
of understanding the biochemical information delivered by IR spectra and their correlation with the existing diagnostic methods. Animal models usually serve to mimic
the progression of diseases or to assess therapeutic effects of the treatment. Investigations with the use of FtIR imaging have evidenced a powerful ability of the
technique to be a complementary tool in monitoring and understanding mechanisms
of the pathogenesis and the etiology of disease. this is actually the key to further
development of clinical applications of FtIR spectroscopy to disease detection.
15.5.1 Cervical Tissue
Worldwide, cervical cancer is one of the most prevalent forms of cancer in females,
especially in a form of invasive squamous cell carcinoma. this disease is screened
cytologically using the Papanicolaou test (Pap smear), while confirmation of the
diagnosis of cervical cancer or pre-cancer usually requires a biopsy of the cervix.
hPv dNA has been detected in 99.7 % of cervical cancer cases thus confirming
hPv as an etiological factor for the disease [89]. hPv types have been classified
into 5 genera (alpha, beta, gamma, mu and nu) and 33 species. the alpha genus is
clinically the most important and many of these types infect the mucosal epithelium. of these, a subset of 10–15 hPv types have been associated with cancerous
lesions [90]. hPv-16 and hPv-18 are found in 50–65 % and 7–20 % of cases of
cervical cancer, respectively [90].
the “gold standard” for diagnosis of cervical cancer is the staining and pathological analysis of a cone biopsy. the diagnosis of the cone biopsy is classified by
the three-tier cervical intraepithelial neoplasia (CIN I, II and III) system. CIN, a precursor to cervical dysplasia or carcinoma in situ (CIS), is diagnosed from biopsies.
CIN is classified as mild (CIN1), moderate (CIN2), and severe (CIN3) dysplasia.
Progression beyond CIN III is known as Carcinoma in situ (CIS). Since, CIN2 and
CIN3 have the highest risk of progressing to CIS, more recently, these groups have
been combined into CIN2/3. virology techniques including immunohistochemistry
and electron microscopy, lack the sensitivity and specificity for the routine detection of hPv [90]. on the other hand, serological assays for the detection of antihPv antibodies have limited accuracy and consequently their role in the clinical
K. malek et al.
15.5 Tissue Analysis
the remainder of this chapter will concentrate on some of the many spectroscopic
studies undertaken from the 1990’s onwards, associated with medical diagnostics
of human diseases such as cervical cancer, neurodegenerative pathologies, and dysfunctions of cardiac and liver tissues. they will include investigations on animal
models as well as tissue samples collected from patients. these studies are mainly
based on searching for “infrared biomarkers” within the complex mid-infrared spectrum that are indicative of a pathological, physiological or a biological state (e.g.
different cell types within a tissue), which can be used to discriminate statistically
classes of samples. very often, this statistical approach is accompanied by attempts
of understanding the biochemical information delivered by IR spectra and their correlation with the existing diagnostic methods. Animal models usually serve to mimic
the progression of diseases or to assess therapeutic effects of the treatment. Investigations with the use of FtIR imaging have evidenced a powerful ability of the
technique to be a complementary tool in monitoring and understanding mechanisms
of the pathogenesis and the etiology of disease. this is actually the key to further
development of clinical applications of FtIR spectroscopy to disease detection.
15.5.1 Cervical Tissue
Worldwide, cervical cancer is one of the most prevalent forms of cancer in females,
especially in a form of invasive squamous cell carcinoma. this disease is screened
cytologically using the Papanicolaou test (Pap smear), while confirmation of the
diagnosis of cervical cancer or pre-cancer usually requires a biopsy of the cervix.
hPv dNA has been detected in 99.7 % of cervical cancer cases thus confirming
hPv as an etiological factor for the disease [89]. hPv types have been classified
into 5 genera (alpha, beta, gamma, mu and nu) and 33 species. the alpha genus is
clinically the most important and many of these types infect the mucosal epithelium. of these, a subset of 10–15 hPv types have been associated with cancerous
lesions [90]. hPv-16 and hPv-18 are found in 50–65 % and 7–20 % of cases of
cervical cancer, respectively [90].
the “gold standard” for diagnosis of cervical cancer is the staining and pathological analysis of a cone biopsy. the diagnosis of the cone biopsy is classified by
the three-tier cervical intraepithelial neoplasia (CIN I, II and III) system. CIN, a precursor to cervical dysplasia or carcinoma in situ (CIS), is diagnosed from biopsies.
CIN is classified as mild (CIN1), moderate (CIN2), and severe (CIN3) dysplasia.
Progression beyond CIN III is known as Carcinoma in situ (CIS). Since, CIN2 and
CIN3 have the highest risk of progressing to CIS, more recently, these groups have
been combined into CIN2/3. virology techniques including immunohistochemistry
and electron microscopy, lack the sensitivity and specificity for the routine detection of hPv [90]. on the other hand, serological assays for the detection of antihPv antibodies have limited accuracy and consequently their role in the clinical