Tumor Margin Detection Using Fiber Spectroscopy

With approximately 14 million new cases emerging each year combined with a mortality rate of 8.2 million worldwide, cancer has been determined by the World Health Organization (WHO) as one of the leading causes of both morbidity and mortality around the world1. Currently, the recommended management strategies to address this epidemic involve early diagnostic and treatments that have been shown to significantly reduce the cancer mortality.

Despite the promise of these preliminary protocols, cancer diagnostic treatment typically involves the clinical examination of a suspicious lesion that is subsequently followed by biopsy and histopathology. Each of these procedures can become invasive, costly, and time-consuming.

The non-invasive spectroscopic investigation, which is otherwise referred to as “spectral histopathology,” is a novel alternative technique that has been successful in providing physicians with a rapid method of cancer diagnosis without requiring the use of labels that can alter the validity of pathological tests.

More specifically, art photonics’ spectroscopy fiber probe technology has allowed cancer specialists to identify fatal diseases prior to the appearance of any symptoms. In fact, recently developed endoscopic fiber probes are capable of detecting inflammation present within the thinnest folds of the human digestive system that are otherwise invisible to the naked eye.

Spectroscopy in Disease and Cancer Diagnosis

Dr. V. Artyushenko, who is founder and CEO of Art Photonics, recently stated that his company has developed and successfully applied various single and combined fiber optic probes and sensors for spectroscopic measurements. When utilized in the broad spectral region, these probes have been shown to increase the efficiency, efficacy and success rates of cancer surgeries.

Additionally, these specialized fiber optic probes also provide a remote sensing tool for the annotation of tissues; a useful tool for both laboratory and clinical purposes.

For example, thin Raman endoscopic probes have provided users with an increased sensitivity in measurements taken during surgical procedures. To increase the detection sensitivity and efficiency of diagnostics in these situations, a synergy of key spectroscopic methods in multi spectral optical fiber system including Fluorescence spectroscopy, NIR-diffuse reflection, Raman and Fourier transform infrared (FTIR) have shown great potential for the identification of tumor cells present within tissues during the surgical operations, as shown below.

To differentiate between malignant and healthy tissues, various non-invasive techniques including NIR-diffuse reflection, Raman scattering, Mid IR absorption and fluorescence spectroscopy have been successful. Each of these methods were previously used for the analysis of kidney cancer samples in an effort to evaluate their potential for cancer detection.

Researchers are hopeful that the combination of some of these techniques in the future will further enhance their sensitivity, specificity, accuracy and level of predictive value for their applicability in in vivo diagnostics.

Malignant and healthy tissue can be differentiated by NIR-diffuse reflection, Raman scattering, Mid IR absorption, or fluorescence spectroscopy. All these methods were tested on kidney cancer samples to evaluate their potential for cancer detection. Eventually, they can also be combined in any configuration to enhance sensitivity, specificity, accuracy and level of predictive value for in-vivo diagnostics.

Multispectral fiber system

Figure 1. Multispectral fiber system

The potential use of multi-spectral fiber MSF-systems coupled with flexible fiber probes (as shown in Figure 1) in future clinical trials is expected to provide most sensitive, specific and accurate method for the determination of malignant tissue, as previously demonstrated during previous research experiments. The success of these systems is expected to lead to the development of special spectral fiber sensors that are specifically created to detect specific tumor margins.

Miniaturized Fiber Probes

The miniaturization of fiber probes used for both MSF-systems and Tumor Margin Sensors (as shown in Figure 2) is anticipated to enable their integration in endoscopes. Prior to this occurring, these probes must also be able to be produced as either disposable and/or capable of being sterilized if used for clinical applications. For example, polycrystalline IR (PIR-) fiber ATR-probes have already been useful in the in vivo analysis of molecular tissues as a result of the ability to fit extremely small needles into the mono-fiber probe design2.

a) TM-Sensor; b) Fluorescence probe; c) MIR-needle; d) Raman probe

Figure 2. a) TM-Sensor; b) Fluorescence probe; c) MIR-needle; d) Raman probe

Tissue Spectra in MIR Range

The collection of ATR-Absorption spectra, as shown in Figure 3, has been successful in distinguishing between normal and cancer kidney tissues when combined with an ATR PIR-fiber probe. The main differences that were observed through this technique at 1000 cm-1 primarily involved changes in the glucose levels between these two tissues.

The results of this preliminary investigation of the in vitro kidney samples obtained from 10 patients was confirmed. Similarly, ex vivo samples acquired from patients 2 hours following their operation were also analyzed and found to exhibit a substantial difference in comparing the spectra of normal kidney tissue to cancerous tissue.

ATR-spectra of kidney & ex-vivo samples

Figure 3. ATR-spectra of kidney & ex-vivo samples

Fluorescence

Auto-fluorescence can also be a useful tool for the determination of cancerous kidney tissue when compared to healthy kidney tissue as shown in Figure 4. In fact, flavins, bile and porphyrins are the major endogenous fluorophores present within the body whose emissions range between 450 to 650 nm. When analyzed in malignant tissue, the ratio of the fluorescence intensity of polyphorins, which exhibits a wavelength of 625-630 nm in normal kidney tissue, was found to significantly3.

Fluorescence spectra of kidney

Figure 4. Fluorescence spectra of kidney

Diffuse Reflection Spectroscopy

The use of NIR-DRS has allowed for the ratio between water to lipids in tissue to be measured, which is a particularly crucial advantage as this proportion is considered to be a specific biomarker for various health purposes. Figure 5 further demonstrates the value of this biomarker in health diagnostic procedures, particularly when used for the detection of cancer.

It can be seen here that clear differences exist between the averaged spectra of healthy tissue as compared to that obtained from cancerous tissue. More specifically, the largest differences in the spectra of these two tissues were observed for first overtones and combination vibrations of OH, NH and CH bonds4, all of which correspond to the reduced level of carbohydrates and phosphates present in cancerous tissue as compared to normal tissues.

NIR-DRS-spectra of kidney tissue

Figure 5. NIR-DRS-spectra of kidney tissue

Raman Scattering Spectroscopy

Since Raman scattering spectroscopy is complementary to MIR absorption, this technique provides further information when used to distinguish between two different tissue samples. For example, Figure 6 demonstrates the differences in spectra obtained from healthy tissue as compared to cancerous samples.

In these spectra, a period of overlapping occurs prior to normalization of the normal tissue spectra, thereby indicating that the Raman spectra obtained from healthy samples can be weak as compared to the more intensive fluorescence, option, whereas Raman used for the detection of cancer in this situation remains useful.

Raman spectra of kidney tissue

Figure 6. Raman spectra of kidney tissue

Conclusion

Optical fiber spectroscopy enables oncology physicians and researchers the resources to develop fiber sensors for cancer diagnosis research, as these techniques have already proven useful for the differentiating between cancer and normal tissue in both in vitro and ex vivo experiments.

While all spectroscopy methods can be used for the detection and measurement of tumor margins to provide a complete and minimally invasive cancer removal procedure, the main challenge of applying this analysis procedure involves the selection of the most sensitive, specific and accurate spectroscopy technique.

References

  1. Stewart B. et al., International Agency for Research on Cancer, 2014.
  2. US Patent US 7,956,317 B2.
  3. Vengadesan N. et al., British journal of cancer, 1998, 77.
  4. Kondepati V.R. et al., Analyt. and Bioanalyt. Chem. 2015, 387.

About art photonics GmbH

In the global market, art photonics GmbH is the leader in manufacturing and suppying InfraRed chalcogenide and polycrystalline specialty optical fibers, spectroscopy fiber probes and fiber bundles, high power fiber cables for industrial and medical applications.

With over 30 years of experience, art photonics' aims to engineer, design, development and produce specialty optical fibers and various fiber systems for the broad spectral range from 200nm to 18µm with their unique technology.

Clubbed with innovation, art photonics aims to provides optimumised solution to suit specific customer requirment. The products FlexiSpec® and FlexiRay® stands testimony to their success.


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Last updated: Jul 18, 2018 at 5:29 AM

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