Background: Recently, SPN has become a much more frequently encountered issue in bronchology. Efficient and reliable guidance method for SPN morphological proof is highly needed. Objectives: The aim of study was to compare the diagnostic values of NIR (near infrared) spectroscopy with EBUS for SPN diagnostic. Fluoroscopic guidance with TBB and needle biopsy were done in all patients. Methods: In our study, we used two types of monitoring systems. Fluoroscopic guidance was combined with either a radial EBUS or a NIR spectroscopy probe for tissue confirmation. 139 male and 71 female patients, having a medial age of 68 years with CT/PET findings of metabolically active SPN were examined between 2/2010 and 2/2013. We designed an instrument for measurement of the penetration of the NIR through lung tissue. Indicating and source fibers were navigated towards the SPN. An EBUS radial probe was used, during fluoroscopic navigation. Results: The statistical analysis of the results obtained showed a comparative specificity and sensitivity of the NIR spectroscopy, with radial EBUS. Conclusions: NIR spectroscopy produced similar efficacies as the radial EBUS. However, the number of positive biopsies was more dependent upon the ability to direct the confirmatory device to the SPN during fluoroscopic guidance than on the type of the device.
A solitary pulmonary nodule (SPN) is a single abnormality in the lung on a chest X-ray that is smaller than 3 cm, surrounded by normal lung tissue, and is not associated with any other abnormality in the lung.
Recently, SPN has more often been encountered due to the widespread use of CT for diagnostic and screening purposes. According to a recent study [
Due to ACCP Evidence-Based Clinical Practice Guidelines, neither the “time-honored” rule of 2-year radiographic stability, nor the radiological characteristics of SPN are reliable in distinguishing malignant from benign lesions [
There has been a similar accuracy between the imaging modalities (dynamic CT, Dynamic NMR, FDG-PET, and Tc-dep SPECT) in distinguishing of malignant from benign SPN in a recent meta-analytic comparison [
In order to obtain histological or cytological proofs of the SPN origin, we can employ several bronchologic and invasive radiology methods.
Transthoracic needle aspiration with CT guidance is a well established method, which has a diagnostic accuracy of about 90% with SPN larger than 2 cm in diameter. The accuracy decreases (to 60% - 80%) in nodules that are smaller than 2 cm in diameter. The risk of pneumothorax precludes its use in respiratory unfit patients.
Until recently, bronchoscopy used to have a limited role in the evaluation of SPN. Transbronchial biopsy under fluoroscopic guidance has approximately a 60% diagnostic success for peripheral, endobronchially unreachable nodules, and the hit rate drops further (to 25% - 30%) for those SPNs smaller than 2 cm [
However, the list of bronchological methods used for the diagnosis of SPN has recently been enlarged; we can now employ: ultrathin bronchoscopy, endobronchial ultrasound (EBUS), electromagnetic navigation, and virtual bronchoscopic navigation. According to the literature, radial EBUS guided transbronchial biopsy has obtained a 67% success rate in the diagnosis SPN smaller than 2 centimeters [
In our work, we utilized NIR spectroscopy of penetrated light, in order to enhance the diagnostic value of the fluoroscopically guided transbronchial biopsy technique.
Near-infrared radiation (NIR) is defined as light with wavelengths from 700 to 2500 nm. Such radiation passes fairly easily through several centimeters of biological samples, due to its relatively low absorbance [
The ratio between the transmitted radiant flux and total radial flux coming to the surface is defined as the transmittance coefficient
Figure1. Interaction of photons with biological tissues.
or as the spectral transmittance coefficient
respectively, for a certain wavelength.
As can be seen, this transmittance coefficient depends on the optical characteristics of the tissue being investigated, represented by the absorption coefficient
Therefore our question was: can NIR light penetrating through the parenchyma bring forth the information about the presence of a SPN; and secondarily, is it able to give us some information about its morphological properties? The scattering of light in a tissue is caused by inhomogeneities, such as cell membranes or intracellular structures. The scattering arises due to the relative refractive index mismatches at the boundaries between two such media or structures (e.g. between the extracellular fluid and the cell membrane).
Light scattering and absorption can provide information both about the tissue structure and on the chromophore content; these are features that can be used to distinguish between normal tissues, malignant lesions, and other pathologies. This is why we speculated that NIR light penetrating normal lung parenchyma will have different spectral and intensity characteristics than will the light from the same source when penetrating a solitary pulmonary nodule.
For that purpose, we designed and carried out a number of ex-vivo studies on tissue models and cadavers, which confirmed the rationale behind this idea.
Due to the fact that human tissues are comprised of a physical medium characterized by both prominent absorbance and dispersion of penetrating light, the spectral transmittance coefficient of the measured flux
This method enables us to compare the results that have been acquired from sources of different spectral emission curves [
That is why we carried out a randomized prospective comparative study, in order to discriminate the efficiency of the two techniques: transbronchial biopsy under fluoroscopic guidance, and NIR spectroscopy guided transbronchial biopsy.
This Work Was Conducted under the Clinical Protocol Thermo/03/07, and Was Approved by the Local Ethics Committee of Na Homolce Hospital’s IRB.
The patient population consisted of 210 patients with CT/PET findings of metabolically active solitary pulmonary nodes from 1.1 to 3 cm in diameter. They consisted of 139 male and 71 female patients, with a median age of 68 years. Out of this population 82% were smokers, with a homogenous distribution in both groups. The patients were randomized into the groups: fluoroscopic + EBUS TBB, and the NIR confirmed fluoroscopic TBB, in a fashion leading to a ratio of 1:1. The fluoroscopic + EBUS TBB group vindicated the standard TBB process, as described elsewhere [
The principle of a technical solution of the spectroscopic probe and NIR spectroscope is shown in
Total number of positive findings | 156 | |
---|---|---|
NSCL | 83 | |
Adenoca | 55 | |
Epidermoid | 15 | |
BAC | 6 | |
Large cell carcinoma | 7 | |
SCLC | 16 | |
Sarcoidosis | 21 | |
Tuberculoma | 13 | |
Pulmonary embolism | 2 | |
Inflammatory changes | 14 | |
Nonprimary tumor generalized to the lung | 7 |
Spectral measurements were carried out using an AVANTES AVS-PC 2000, Plug-in Spectrometers PC2E1260 Master. The spectrometer has a linear CCD detector with 2048 pixels. Its working range is from 200 to 1100 nm. The integration time for the whole spectrum is from 3 ms to 60 s. The spectral grating UV/VIS/NIR#13 works in the spectral band from 300 to 1100 nm, and it has 7 lines/mm. The calibration curves of the spectrometer are presented in
We designed a simple instrument for the measurement of the penetrated NIR light through the lung tissue. It consists of two fibers, 1 mm in diameter, contained in one bundle covered with an insulation sleeve. One of the fibers is the detector, while the other is the source fiber. The indicator fiber is 0.3 cm longer than source fiber, and it is separately covered with insulation up to its end. The end is cut at the angle of 60 degrees and is titanium coated in order to facilitate NIR light transmission toward the detector fiber. The detector fiber is connected to the NIR spectroscope and the source fiber to the NIR source, the parameters of which are shown at
Data from the NIR spectroscopy has been displayed and interpreted in real-time during the bronchoscopic examination. Whenever a spectral pattern and intensity change that were not characteristic of normal lung parenchyma appeared on the spectroscopic monitor (
In order to quantify the results of the NIR spectroscopy, we calculated the intensity ratio of I673nm/694nm for each spectral curve of the normalized transmittance (see
Of the 210 eligible patients examined from 2/2010 to 2/2013, evaluable biopsies were obtained.
Method | No. of lesions | No. of positive histologies in all lesions | No. of negative histologies in all lesions | Sensitivity | TBB hit rate (%) |
---|---|---|---|---|---|
FLUORO + NIR | 106 | 82 | 24 | 0.77 | 77 |
FLUORO + EBUS | 104 | 74 | 30 | 0.71 | 71 |
the results of the histology with both of the navigational methods.
The level of significance, reached after testing the hypothesis of inequality of the mean for the pathological intensity ratio values and normal intensity ratio values, was 0.0001. Also based on the results of this statistical analysis, we can state that the cut-off value of the intensity ratio I673nm/I694nm for the diagnosis of pathological tissue at 1.3, while that for the diagnosis of normal tissue is 0.95.
NIR light is used routinely in numerous applications in modern medicine [
From our first data, we concluded that the use of NIR spectroscopy for ideal biopsy area confirmation has been useful in increasing the sensitivity of fluoroscopically guided TBB and comparable to EBUS navigated TBB. Such a device, or its modification, could easily be included e.g. into an examination by electromagnetic navigation or single use, low cost catheters.
The main disadvantage of the method appears to be its limitation to point monitoring, and hence the necessity of a trial and error method in the guidance. This shortcoming is the same one as in the case of radial endoscopic ultrasound.
This work originated with financial support from the industrial research project of the Ministry of Industry and Trade of the Czech Republic-project code FR-TI4/765: “Research and development of technologies and
N | SD | Mean | CI 95% L | CI 95% U | p≤ | |
---|---|---|---|---|---|---|
I673nm/I694nm pathological | 82 | 1.11 | 2.29 | 1.31 | 3.05 | |
I673nm/I694nm normal | 24 | 0.28 | 0.78 | 0.64 | 0.91 | 0.0001 |
Method | No. of lesions smaller than 2 cm | No. of positive histologies in lesions smaller than 2 cm | No. of negative histologies in Lesions smaller than 2 cm | Sensitivity | TBB hit rate (%) |
---|---|---|---|---|---|
FLUORO + NIR | 38 | 25 | 13 | 0.66 | 66 |
FLUORO + EBUS | 45 | 33 | 12 | 0.73 | 73 |
methods for the early diagnosis of lung cancer using NIR spectroscopy”, the Ministry of Health of the Czech Republic (project No. NT13259) and the Czech Science Foundation (project No. P208/11/0105).
VotrubaJiri,BrůhaTomas,BalazTeodor, (2015) Bronchoscopic Diagnosis of Solitary Pulmonary Nodules with the Use of NIR Spectroscopy. Advances in Chemical Engineering and Science,05,490-498. doi: 10.4236/aces.2015.54051