Max Diem

• Northeastern University

In this contribution, data will be presented that suggest that certain cancer markers or their surrogates can be detected by infrared spectral imaging methodology. In particular, the co-localization of certain regions in spectral images with PD-L1-postitive immunohistochemical response suggests that either the PD-L1 protein or a surrogate associate...

Thyroglobulin is a glycoiodoprotein that is produced by thyroid follicular cells; it is stored in follicles in structures known as colloids. The main function of this protein is to stock the hormones triiodothyronine (T3) and thyroxine (T4) until the body requires them. This study aims to demonstrate that infrared spectral imaging with appropriate...

This paper summarizes results from two large lung cancer studies comprising over 700 samples that demonstrate the ability of SHP to distinguish cancerous tissue regions from normal tissue, to differentiate benign lesions from normal tissue and cancerous lesions, and to classify lung cancer types. Furthermore, malignancy‐associated changes (MACs) ca...

This paper reviews methods to arrive at optimum decision tree or label tree structures to analyze large SHP data sets. Supervised methods of analysis can utilize either sequential or (flat) multi-classifiers depending on the variance in the data, and on the number of spectral classes to be distinguished. For small number of spectral classes, multi-...

This paper reports the results of a collaborative lung cancer study between City of Hope Cancer Center (Duarte, California) and CIRECA, LLC (Cambridge, Massachusetts), comprising 328 samples from 249 patients, that used an optical technique known as spectral histopathology (SHP) for tissue classification. Because SHP is based on a physical measurem...

An application of FTIR spectroscopic imaging for the identification and visualization of early micrometastasis from breast cancer to lungs in a murine model is shown. Spectroscopic and histological examination is focused on lung cross-sections derived from animals at the early phase of metastasis (early micrometastasis, EM) as compared to healthy c...

New technologies to diagnose malaria at high sensitivity and specificity are urgently needed in the developing world where the disease continues to pose a huge burden on society. Infrared and Raman spectroscopy-based diagnostic methods have a number of advantages compared with other diagnostic tests currently on the market. These include high sensi...

Raman microscopic imaging of eukaryotic cells has become a well-established technique to address various biochemical questions related to cell biology. The combination of Raman spectroscopy with optical microscopy offers the possibility to study the composition of cells and alterations associated with metabolistic activity induced by internal or ex...

The search for disease markers in whole blood, or easily accessible blood components by spectral methods is a highly important aspect in the field of biophotonic research for disease diagnostics and screening, since it promises a minimally invasive approach to assess an individual's state of health. Fourier transform infrared spectroscopy, in parti...

Duncan Graham opened a general discussion of the paper by Pavel Matousek: Regarding the temperature measurements, how did you do them? Stokes/anti-Stokes measurement? The values are not what I'd expect and seem lower. What was the wavelength and power of the laser and did you calculate what you thought the temperature measurement should be based on...

Parvez Haris opened the discussion of the introductory lecture by Max Diem: Varying degrees of accuracy have been obtained for discrimination between cancerous and non-cancerous tissues using vibrational spectroscopic methods. What are the explanations for these variation in accuracy between cancerous and non-cancerous tissues and how do they corre...

Richard Dluhy opened a general discussion of the paper by Duncan Graham: In your example of a heterogeneous solution-based assay for multicomponent analysis, what is the concentration of the target fungal ssPCR DNA that is used, and how do you manage the kinetics of the reaction such that the target reaches the probe in a time frame appropriate for...

This article summarizes the methods employed, and the progress achieved over the past two decades in applying vibrational (Raman and IR) micro-spectroscopy to problems of medical diagnostics and cellular biology. During this time, several research groups have verified the enormous information content of vibrational spectra; in fact, information on...

Operando Raman micro-spectroscopy of the membrane electrode assembly (MEA) of a fully operating hydrogen/oxygen Nafion electrolyte fuel cell is described. Coarse depth profiling of the fuel cell system enabled appropriate positioning of the microspectroscopy laser focal point for MEA catalytic layer spectroscopy. An increase in the ionomer state-of...

Instrumental advances in infrared micro-spectroscopy have made possible the observation of individual human cells and even subcellular structures. The observed spectra represent a snapshot of the biochemical composition of a cell; this composition varies subtly but reproducibly with cellular effects such as progression through the cell cycle, cell...

This chapter emphasizes results from all vibrational techniques, in particular those from vibrational circular dichroism (VCD) measurements. It reviews the basic results for peptides, proteins, nucleic acids, and lipids, and also explores some results that demonstrate how imaginative application of these techniques can reveal information that is no...

We report results on a statistical analysis of an infrared spectral dataset comprising a total of 388 lung biopsies from 374 patients. The method of correlating classical and spectral results and analyzing the resulting data has been referred to as spectral histopathology (SHP) in the past. Here, we show that standard bio-statistical procedures, su...

We report results of a study utilizing a novel tissue classification method, based on label-free spectral techniques, for the classification of lung cancer histopathological samples on a tissue microarray. The spectral diagnostic method allows reproducible and objective classification of unstained tissue sections. This is accomplished by acquiring...

We report results of a study utilizing a novel tissue classification method, based on label-free spectral techniques, for the classification of lung cancer histopathological samples on a tissue microarray. The spectral diagnostic method allows reproducible and objective classification of unstained tissue sections. This is accomplished by acquiring...

Results of a study comparing infrared imaging data sets collected on different instruments or instrument platforms are reported, along with detailed methods developed to permit such comparisons. It was found that different instrument platforms, although employing different detector technologies and pixel sizes, produce highly similar and reproducib...

We report results from a study utilizing infrared spectral cytopathology (SCP) to detect abnormalities in exfoliated esophageal cells. SCP has been developed over the past decade as an ancillary tool to classical cytopathology. In SCP, the biochemical composition of individual cells is probed by collecting infrared absorption spectra from each indi...

Instrumental advances in vibrational microspectroscopy have made possible the observation of individual human cells and even subcellular structures. The observed spectra represent a snapshot of the biochemical composition of a cell; this composition varies subtly but reproducibly with cellular effects such as progression through the cell cycle, cel...

Introduction Screening for Barrett’s oesophagus could allow early detection, enabling timely diagnosis and intervention for oesophageal adenocarcinoma. Recent studies have shown the acceptability of a swallowed cytology brush (‘Cytosponge’) for cell collection. If introduced, cytological assessment would pose several challenges. Firstly, oesophagea...

During the last 15years, vibrational spectroscopic methods have been developed, which can be viewed as molecular pathology methods that depend on sampling the entire genome, proteome, and metabolome of cells and tissues, rather than probing for the presence of selected markers. First, this review introduces the background and fundamentals of the sp...

During the last 15years, vibrational spectroscopic methods have been developed, which can be viewed as molecular pathology methods that depend on sampling the entire genome, proteome, and metabolome of cells and tissues, rather than probing for the presence of selected markers. First, this review introduces the background and fundamentals of the sp...

Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in vivo is expected to enhance therapeutic effect with significantly less non-specific toxicity. Active targeting is based on surface modification of nanoparticles with ligands that bind with extracellular targets and enhance payload delivery in the cells. In this study, we...

During the last 15 years, vibrational spectroscopic methods have been developed that can be viewed as molecular pathology methods that depend on sampling the entire genome, proteome and metabolome of cells and tissues, rather than probing for the presence of selected markers. First, this review introduces the background and fundamentals of the spec...

In this paper, we report the spectral patterns of normal human thyroid tissue and methodology to interpret hyperspectral imaging data and protein conformational changes observed therein. Raw image datasets were imported into software written in-house in the MATLAB environment and processed to yield pseudo-color images of the tissue sections. All sp...

In this chapter, the authors concentrate on the applications of Raman spectral imaging to three parts. First, the chapter explains the sensitivity of Raman imaging to subcellular organization for an unstained cell. Next, Raman images of cells incubated with nanoparticles are discussed as well as the potential for using Raman imaging to monitor the...

This paper presents a short review on the improvements in data processing for spectral cytopathology, the diagnostic method developed for large scale diagnostic analysis of spectral data of individual dried and fixed cells. This review is followed by the analysis of the confounding effects introduced by utilizing reflecting "low-emissivity" (low-e)...

A standoff detection system was assembled by coupling a reflecting telescope to a Fourier transform infrared spectrometer equipped with a cryo-cooled mercury cadmium telluride detector and used for detection of solid-phase samples deposited on substrates. Samples of highly energetic materials were deposited on aluminum substrates and detected at se...

The first study interpreting B-lymphocyte activation in normal lymph nodes using vibrational micro-spectral imaging is reported. Lymphocyte activation indicates the presence and response against a pathogen, regardless of the inciting pathogen's etiology, whether a benign, reactive or malignant process. Understanding the biochemical makeup of lympho...

During the past years, many studies have shown that infrared spectral histopathology (SHP) can distinguish different tissue types and disease types independently of morphological criteria. In this manuscript, we report a comparison of immunohistochemical (IHC), histopathological and spectral histopathological results for colon cancer tissue section...

Recent results suggest that infrared microspectroscopy, coupled to methods of multivariate analysis, can distinguish normal from virally infected cells. This was established for infection of the oral cavity by the herpes simplex virus, which is associated with the outbreak of cold sores, and for infection of the cervix uteri by the human papillomav...

This paper explores different phenomena that cause distortions of infrared absorption spectra by mixing of reflective and absorptive band shape components of infrared spectra, and the resulting distortion of observed band shapes. In the context of this paper, we refer to the line shape of the variations of the refractive index in spectral regions o...

This paper summarizes the progress achieved over the past fifteen years in applying vibrational (Raman and IR) spectroscopy to problems of medical diagnostics and cellular biology. During this time, a number of research groups have verified the enormous information content of vibrational spectra; in fact, genomic, proteomic, and metabolomic informa...

We report results of a study utilizing a recently developed tissue diagnostic method, based on label-free spectral techniques, for the classification of lung cancer histopathological samples from a tissue microarray. The spectral diagnostic method allows reproducible and objective diagnosis of unstained tissue sections. This is accomplished by acqu...

This study proposed and demonstrated the application of a new Raman microscopy-based method for metabolic state-based identification and quantification of functionally relevant populations, namely polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs), in enhanced biological phosphorus removal (EBPR) system via simul...

We have optimized an imaging methodology capable of monitoring individual live HeLa cells using non-synchrotron FTIR in an aqueous environment. This methodology, in combination with MATLAB based pre-processing techniques, allows fast and efficient collection of data with high signal-to-noise ratio in comparison with previous methods using point mod...

Nanotechnology is playing an increasing role in targeted drug delivery into pathological tissues. Drug-loaded pharmaceutical nanocarriers can be delivered into diseased sites by passive targeting (spontaneous accumulation of nanocarriers in the areas with affected vasculature) or by active targeting (via site-specific ligands attached to the surfac...

A detailed comparison of six multivariate algorithms is presented to analyze and generate Raman microscopic images that consist of a large number of individual spectra. This includes the segmentation algorithms for hierarchical cluster analysis, fuzzy C-means cluster analysis, and k-means cluster analysis and the spectral unmixing techniques for pr...

Spectral cytopathology (SCP) is a novel approach for disease diagnosis that utilizes infrared spectroscopy to interrogate the biochemical components of cellular samples and multivariate statistical methods, such as principal component analysis, to analyze and diagnose spectra. SCP has taken vast strides in its application for disease diagnosis over...

a b s t r a c t Isomorphous substitutions of transition metal (TM) ions into the vanadosilicate AM-6 framework have been investigated. X-ray powder diffraction and FTIR spectroscopy showed no impurities due to TM oxi-des (i.e., cobalt oxide, chromium oxide or iron oxide for Co-AM-6, Cr-AM-6 and Fe-AM-6, respectively) in all TM ion-substituted AM-6...

A review of recent developments in MIR spectroscopy that have potential for field deployment in defense and homeland security applications for standoff detection of highly energetic materials (HEM) and homemade explosives (HME), as well as in forensic sciences applications

The present study investigated the impact of nano titanium dioxide (nTiO 2) exposure on the cellular structures of the nitrogen-fixing cyanobacteria Anabaena variabilis. Results of the present study showed that nTiO 2 exposure led to observable alteration in various intracellular structures and induced a series of recognized stress responses, inclu...

The detection of micro-metastases and individual metastatic cells in lymph node tissue by spectral methods is summarized. These methods are based on instrument-based acquisition of thousands of infrared spectra of individual tissue pixels from the tissue section, and analysis of the resulting spectral hypercube by multivariate algorithms. The metho...

The ability to detect DNA conformation in eukaryotic cells is of paramount importance in understanding how some cells retain functionality in response to environmental stress. It is anticipated that the B to A transition might play a role in resistance to DNA damage such as heat, desiccation and toxic damage. To this end, conformational detail abou...

A remote infrared spectroscopy (RIRS) detection system was assembled using a mid infrared (MIR) Fourier Transform interferometer useful in open-path (OP) mode, a reflective infrared telescope and a cryocooled wide band, MCT detector. The system was used for passive mode IR thermal emission measurements and was also coupled to another Newtonian tele...

The lipid distribution in the mouse meibomian gland was examined with picosecond spectral anti-Stokes Raman scattering (CARS) imaging. Spectral CARS data sets were generated by imaging specific localized regions of the gland within tissue sections at consecutive Raman shifts in the CH(2) stretching vibrational range. Spectral differences between th...

Raman spectroscopy in combination with optical microscopy provides a new non-invasive method to examine and image cellular processes. Based on the spectral parameters of a cell’s components it is possible to image cellular organelles, such as the nucleus, chromatin, mitochondria, or lipid bodies, at the resolution of conventional microscopy. Severa...

Sensitivity of tumors to chemotherapy greatly relies on capability of the administered drug to traverse the tumor via its leaky vasculature and eradicate cancer cells. Unfortunately, in order for the drug to exhibit a toxic effect it must traverse the tumor interstitium which, due to its abnormal physiology, poses a barrier to efficacy of the drug....

Confocal Raman micro-spectral imaging (CRMI) is a relatively novel technique for the construction of label-free images of biological entities, such as cells or tissue sections. This method utilizes thousands of spatially resolved Raman spectra, and sophisticated image analysis algorithms, to construct images which are based strictly on the inherent...

Fourier Transform Infrared (FTIR) spectroscopic measurements of individual, live HeLa cells in culture and buffer media are presented. Spectral data were acquired using a newly designed live cell chamber developed in the authors' laboratory. Data were processed using MATLAB-based routines that correct for the overcompensation of water encountered d...

Scitation is the online home of leading journals and conference proceedings from AIP Publishing and AIP Member Societies

In this paper we describe the advantages of collecting infrared microspectral data in imaging mode opposed to point mode. Imaging data are processed using the PapMap algorithm, which co-adds pixel spectra that have been scrutinized for R-Mie scattering effects as well as other constraints. The signal-to-noise quality of PapMap spectra will be compa...

Scitation is the online home of leading journals and conference proceedings from AIP Publishing and AIP Member Societies

Raman microspectroscopy-based, label-free imaging methods for human cells at sub-micrometre spatial resolution are presented. Since no dyes or labels are used in this imaging modality, the pixel-to-pixel spectral variations are small and multivariate methods of analysis need to be employed to convert the hyperspectral datasets to spectral images. T...

In this manuscript, we report the application of EMSC to correct infrared micro-spectral data recorded from tissue that describe resonant Mie scattering contributions. Small breast micro-metastases previously undetectable using the raw measured spectra were provided clear contrast from the surrounding tissue after signal correction. The technique a...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Aim Spectral Cytopathology (SCP) is a novel spectroscopic method for objective and unsupervised classification of individual exfoliated cells. The limitations of conventional cytopathology are well-recognized within the pathology community. In SCP, cellular differentiation is made by observing molecular changes in the nucleus and the cytoplasm, whi...

Originally identified in cultured cells, oncogenic cellular senescence is a growth-arrest mechanism which may inhibit tumor development by limiting the ability of cells to divide. However, literature shows that these cells secrete tumor-inducing and tumor-suppressing proteins leading to poor prognosis. Understanding the progression of oncogenic cel...

Noise reduction algorithms for improving Raman spectroscopy signals while preserving signal information were implemented. Algorithms based on Wavelet denoising and Kalman filtering are presented in this work as alternatives to the well-known Savitky-Golay algorithm. The Wavelet and Kalman algorithms were designed based on the noise statistics of re...

Charge-Coupled Device (CCD) detectors are becoming more popular in spectroscopy instrumentation. In spite of technological advances, spurious signals and noise are unavoidable in Raman spectroscopes. In general, the noise comes from two major sources, impulsive noise caused by high energy radiation from local or extraterrestrial sources (cosmic ray...

Noise reduction algorithms for improving Raman spectroscopy signals while preserving signal information were implemented. Algorithms based on Wavelet denoising and Kalman filtering are presented in this work as alternatives to the well-known Savitky-Golay algorithm. The Wavelet and Kalman algorithms were designed based on the noise statistics of re...

Spectral cytopathology (SCP) is a novel approach for diagnostic differentiation of disease in individual exfoliated cells. SCP is carried out by collecting information on each cell's biochemical composition through an infrared micro-spectral measurement, followed by multivariate data analysis. Deviations from a cell's natural composition produce sp...

Novel optical imaging methods, such as Raman microspectroscopy, have been gaining recognition in their ability to obtain noninvasively the distribution of biochemical components of a sample. Raman spectroscopy in combination with optical microscopy provides a label-free method to assess and image cellular processes, without the use of extrinsic flu...

A Raman microscopy method was developed and successfully applied to evaluate the dynamics of intracellular polyphosphate in polyphosphate-accumulating organisms (PAOs) in enhanced biological phosphorus removal (EBPR) processes. Distinctive Raman spectra of polyphosphates allowed for both identification of PAOs and quantification of intracellular po...

IntroductionMethods Results and DiscussionConclusions AcknowledgmentsReferences

We report the ability of infrared micro-spectral imaging, coupled with completely unsupervised methods of multivariate statistical analysis, to accurately reproduce the histological architecture of axillary lymph nodes and detect metastatic breast cancer cells. The acquisition of spectral data from tissue embedded in paraffin provided spectra free...

The first detection of breast cancer micrometastases in lymph nodes by infrared spectral imaging and methods of multivariate analysis is reported. Micrometastases are indicators of early spread of cancer from the organ originally affected by disease, and their detection is of prime importance for the staging and treatment of cancer. Infrared spectr...

A newly developed Raman microscopy method was applied to evaluate the intracellular inclusion and dynamics of polyphosphate in PAOs in EBPR processes. Observation of polyphosphate at individual cell level indicated that there are distributed states of cells in terms of polyphosphate content at any given time, suggesting that agent-based distributiv...

Synchrotron Fourier transform-infrared (FT-IR) and Raman microspectroscopy were applied to investigate changes in the molecular architecture of mouse oocytes and demonstrate the overall morphology of the maturing oocyte. Here we show that differences were identified between immature mouse oocytes at the germinal vesicle (GV) and mature metaphase II...

We report microscopically collected infrared spectra of cells found in human urine in an effort to develop automatic methods for bladder cancer screening. Unsupervised multivariate analysis of the observed spectral patterns reveals distinct spectral classes, which correlated very well with visual cytology. Therefore, we believe that spectral analys...

This chapter introduces the field of vibrational spectroscopic imaging and discusses the advances made to date in terms of biomedical diagnosis. The reader is introduced to the spectral signatures of typical cellular components, and the need for an objective method for cancer diagnosis is discussed. Besides an overview of typical instrumentation an...

Spectral cytology, the diagnosis of disease based on objective physical measurements on individual cells and subsequent computer‐based algorithmic interpretation, promises to provide faster and more reliable results than classical cytology. The measurements described in this review are based on well‐established vibrational microspectroscopic techni...

Raman spectroscopy, in combination with optical microscopy provides a new non-invasive method to asses and image cellular processes. Based on the spectral signatures of a cell's components, it is possible to image cellular organelles such as the nucleus, chromatin, mitochondria or lipid bodies, at the resolution of conventional microscopy. Several...

Recent developments, combining Raman spectroscopy with optical microscopy, provide a new noninvasive technique to assess and image cellular processes. Of particular interest are the uptake mechanisms of various cytologically active compounds. In order to distinguish the species of interest from their cellular environment spectroscopically, compound...

Histopathologic evaluation of surgical specimens is a well established technique for disease identification, and has remained relatively unchanged since its clinical introduction. Although it is essential for clinical investigation, histopathologic identification of tissues remains a time consuming and subjective technique, with unsatisfactory leve...

This chapter presents novel microscopic methods to monitor cell biological processes of live or fixed cells without the use of any dye, stains, or other contrast agent. These methods are based on spectral techniques that detect inherent spectroscopic properties of biochemical constituents of cells, or parts thereof. Two different modalities have be...