Significance: Accurate and objective identification of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) is of major clinical importance due to the current lack of low-cost and noninvasive diagnostic tools to differentiate between the two. Developing an approach for such identification can have a great impact in the field of dementia diseases as it would offer physicians a routine objective test to support their diagnoses. The problem is especially acute because these two dementias have some common symptoms and characteristics, which can lead to misdiagnosis of DLB as AD and vice versa, mainly at their early stages.
Aim: The aim is to evaluate the potential of mid-infrared (IR) spectroscopy in tandem with machine learning algorithms as a sensitive method to detect minor changes in the biochemical structures that accompany the development of AD and DLB based on a simple peripheral blood test, thus improving the diagnostic accuracy of differentiation between DLB and AD.
Approach: IR microspectroscopy was used to examine white blood cells and plasma isolated from 56 individuals: 26 controls, 20 AD patients, and 10 DLB patients. The measured spectra were analyzed via machine learning.
Results: Our encouraging results show that it is possible to differentiate between dementia (AD and DLB) and controls with an ∼86 % success rate and between DLB and AD patients with a success rate of better than 93%.
Conclusions: The success of this method makes it possible to suggest a new, simple, and powerful tool for the mental health professional, with the potential to improve the reliability and objectivity of diagnoses of both AD and DLB.
Rapid identification of bacterial infection is very important and in many cases can save human life. Many pathogens can cause infections. While these infections share identical symptoms, the immune system responds differently to these pathogens. The current microbiology lab methods used to diagnose the infection type are time consuming (2-4 days). Thus, physicians may be tempted to start unnecessary antibiotic treatment, based on their wrong diagnosis (based on experience) of the infection. Uncontrolled use of antibiotics is the main driving force for the development of multi drug resistant bacteria which is considered a global health problem. We hypothesize that the different responses of the immune system to the infecting pathogens, cause some minute biochemical changes in the blood componentsthat can be detected by infrared spectroscopy which is known as a fast, accurate, sensitive and low cost method. In this study, we used infrared microscopy to measure the vibrational spectra of white blood cells (WBC) samples of 105 infected patients (69 bacterial and 36 with viral infection) and 90 controls (non-infected patients). The obtained spectra were analyzed using machine learning algorithms to identify the infection type as bacterial or viral in a time span of less than one hour after blood sample collection. Our study results showed that it is possible to determine the infection type with high success rates of 93% sensitivity and 85% specificity, based solely on WBC obtained from simple peripheral blood samples.
Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts’ middle sites.
Components present in the acellular fraction of blood influence the blood cell survival and function and the response to biotic and abiotic factors. Human plasma and sera have been used as therapeutic agents and are known to increase cell survival. White blood cells in normal blood are exposed to plasma components in vivo, but the effect of such plasma components in vitro on adherent peripheral blood mononuclear cells (PBMCs) that includes monocytes has not been fully investigated. We cultured human PBMCs with autologous plasma and observed structural variation due to plasma addition in PBMCs along with increased cell survival. Light microscopy of the cells showed increased granularity in plasma-treated cells. Fourier transform infrared (FTIR) spectroscopy was used to elucidate the possible mechanism by studying the changes in the biochemical composition of the cells that explained the observations. FTIR spectroscopy of plasma-treated cells show altered spectral pattern in the mid-IR region, indicating increased phospholipid levels. Heat-stable components in the plasma possibly increase the differentiation of PBMCs, as evident by increased phospholipid metabolism. The data suggest that plasma-stimulated membrane biogenesis may contribute to PBMC survival by inducing them to differentiate into antigen presenting cells (APCs) like macrophages and dendritic cells.
The early diagnosis of phytopathogens is of a great importance; it could save large economical losses due to crops damaged by fungal diseases, and prevent unnecessary soil fumigation or the use of fungicides and bactericides and thus prevent considerable environmental pollution. In this study, 18 isolates of three different fungi genera were investigated; six isolates of Colletotrichum coccodes, six isolates of Verticillium dahliae and six isolates of Fusarium oxysporum. Our main goal was to differentiate these fungi samples on the level of isolates, based on their infrared absorption spectra obtained using the Fourier transform infrared-attenuated total reflection (FTIR-ATR) sampling technique. Advanced statistical and mathematical methods: principal component analysis (PCA), linear discriminant analysis (LDA), and k-means were applied to the spectra after manipulation. Our results showed significant spectral differences between the various fungi genera examined. The use of k-means enabled classification between the genera with a 94.5% accuracy, whereas the use of PCA [3 principal components (PCs)] and LDA has achieved a 99.7% success rate. However, on the level of isolates, the best differentiation results were obtained using PCA (9 PCs) and LDA for the lower wavenumber region (800-1775 cm−1), with identification success rates of 87%, 85.5%, and 94.5% for Colletotrichum, Fusarium, and Verticillium strains, respectively.
One of the major public health hazards is colon cancer. There is a great necessity to develop new methods for early
detection of cancer. If colon cancer is detected and treated early, cure rate of more than 90% can be achieved.
In this study we used FTIR microscopy (MSP), which has shown a good potential in the last 20 years in the fields of
medical diagnostic and early detection of abnormal tissues.
Large database of FTIR microscopic spectra was acquired from 230 human colonic biopsies. Five different subgroups
were included in our database, normal and cancer tissues as well as three stages of benign colonic polyps, namely, mild,
moderate and severe polyps which are precursors of carcinoma.
In this study we applied advanced mathematical and statistical techniques including principal component analysis (PCA)
and linear discriminant analysis (LDA), on human colonic FTIR spectra in order to differentiate among the mentioned
subgroups' tissues. Good classification accuracy between normal, polyps and cancer groups was achieved with
approximately 85% success rate.
Our results showed that there is a great potential of developing
FTIR-micro spectroscopy as a simple, reagent-free viable
tool for early detection of colon cancer in particular the early stages of premalignancy among the benign colonic polyps.
Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a technique for detection of abnormal cell proliferation and premalignant conditions. In the present study, we investigate the absorbance in the sensitive wavenumber region between 2800 and 3000 cm–1, which has been known to be due to the antisymmetric and symmetric stretching vibrations of CH2 and CH3 groups of proteins and lipids. We report common biomarkers from this region that distinguish between normal and malignant tissues and cell lines. Based on our findings, we propose that the wavenumber region around 2800 to 3000 cm–1 in the FTIR spectra of cells and tissues could provide valuable scientific evidence at the onset of premalignancy and may be used for ex vivo and in vitro detection of carcinogenesis. To further examine the utility of these markers in cancer diagnosis and management, they are tested successfully in monitoring the changes occurring in leukemia patients during chemotherapy.
Shaul Mordechai, Shlomo Mark, A. Podshyvalov, Keren Kantarovich, Y. Bernshtain, Ahmad Salman, Vitaly Erukhimovitch, Hugo Guterman, Jed Goldstein, Shmuel Argov, R. Jagannathan
IR spectroscopy provides a new diagnostic tool due to its sensitivity to molecular composition and structure in cells, which accompany transformation from healthy to diseased state. The IR spectrum of a sample is, therefore, a biochemical fingerprint. It has been found that the most significant changes occur in the mid-IR spectral range 3-25 mm. Encouraging results have been reported in the literature on various types of cancers, such as human breast, lung, colon, cervical, and leukemia using FT-IR microspectroscopy. Much progress has also been made by several groups on IR spectral maps and IR imaging with good agreement between the data and the histopathological information. In an attempt to characterize healthy and diseased tissues, infrared microspectroscopy of cervical and colon human tissues was studied using an infrared microscopy. The comparative qualitative and quantitative changes detected using FTIR microspectroscopy are discussed.
KEYWORDS: Luminescence, Tissues, Laser induced fluorescence, Chromophores, In vitro testing, Proteins, Tumor growth modeling, Cancer, Systems modeling, In vivo imaging
Light-induced Fluorescence (LIF) technique is based on fluorescence emitted from intracellular chromophores upon illumination of cells by monochromatic light. We compared LIF emitted from a pair of normal and malignant murine cell lines, differing in H-ras expression. The malignant cells fluoresced significantly less than the normal cells, upon excitation at 290 +/- 10 nm. For both cell types, fluorescence decreased with decreasing cell concentration, but at each concentration, the normal cells fluoresced more than the malignant cells. The effect of viability and metabolic stage of the cells on this pattern was compared. The difference among the cells was not due to a difference in protein or DNA content. Thus, this model system demonstrates the specific contribution of H-ras to sub-cellular chromophores, resulting in a significant difference in their autofluorescence intensity, while measuring both emission and excitation scans. This study suggests a potential use of the LIF technique to distinguish between normal and malignant cells and tissues.
Infrared (IR) absorption spectra are well known for their selectivity and minutiae fingerprint of molecular structure. The biochemical changes in the sub-cellular levels developing in abnormal cells, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in infrared spectroscopy. The molecular vibrational modes which are responsible for IR absorption spectra, are characteristic of the biochemistry of the cells and their sub-cellular components. We measured the infrared absorption spectra of monolayers of cultured normal and ras gene transformed mouse fibroblasts, using microscopic infrared system (micro-FTIR) technique. The absorption for normal cells was higher than the malignant ones in the spectral range 1000 - 1500 and 2800 - 3000 cm-1. The effect on phospholipid metabolism due to ras gene incorporation is also discussed.
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