Publications

@article{Barkur2024-hv,

title = {Intraoperative spectroscopic evaluation of sentinel lymph nodes  in breast cancer surgery},

author = {Surekha Barkur and Radu A Boitor and Raluca Mihai and Navarasi S Raja Gopal and Samuel Leeney and Alexey A Koloydenko and Hazem Khout and Emad Rakha and Ioan Notingher},

doi = {10.1007/s10549-024-07349-z},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Breast Cancer Res. Treat.},

volume = {207},

number = {1},

pages = {223\textendash232},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy is a 

 standard procedure for patients with breast cancer and normal 

 axilla on imaging. Positive SLNs on histological examination can 

 lead to a subsequent surgery for axillary lymph node clearance 

 (ALNC). Here we report a non-destructive technique based on 

 autofluorescence (AF) imaging and Raman spectroscopy for 

 intra-operative assessment of SLNs excised in breast cancer 

 surgery. METHODS: A microscope integrating AF imaging and Raman 

 spectroscopy modules was built to allow scanning of lymph node 

 biopsy samples. During AF-Raman measurements, AF imaging 

 determined optimal sampling locations for Raman spectroscopy 

 measurements. After optimisation of the AF image analysis and 

 training of classification models based on data from 85 samples, 

 the AF-Raman technique was tested on an independent set of 81 

 lymph nodes comprising 58 fixed and 23 fresh specimens. The 

 sensitivity and specificity of AF-Raman were calculated using 

 post-operative histology as a standard of reference. RESULTS: 

 The independent test set contained 66 negative lymph nodes and 

 15 positive lymph nodes according to the reference standard, 

 collected from 78 patients. For this set of specimens, the area 

 under the receiver operating characteristic (ROC) curve for the 

 AF-Raman technique was 0.93 [0.83-0.98]. AF-Raman was then 

 operated in a regime that maximised detection specificity, 

 producing a 94% detection accuracy: 80% sensitivity and 97% 

 specificity. The main confounders for SLN metastasis were areas 

 rich in histiocytes clusters, for which only few Raman spectra 

 had been included in the training dataset. DISCUSSION: This 

 preliminary study indicates that with further development and 

 extension of the training dataset by inclusion of additional 

 Raman spectra of histiocytes clusters and capsule, the AF-Raman 

 may become a promising technique for intra-operative assessment 

 of SLNs. Intra-operative detection of positive biopsies could 

 avoid second surgery for axillary clearance.},

keywords = {Auto-fluorescence imaging, Breast cancer, Lymph node metastasis, Raman spectroscopy, Spectral imaging},

pubstate = {published},

tppubtype = {article}

}

@article{Woodhouse2023-wp,

title = {Quantification of drugs in brain and liver mimetic tissue models 

 using Raman spectroscopy},

author = {Nathan Woodhouse and Jan Majer and Peter Marshall and Steve Hood and Ioan Notingher},

year  = {2023},

date = {2023-03-01},

journal = {Appl. Spectrosc.},

volume = {77},

number = {3},

pages = {246\textendash260},

publisher = {SAGE Publications},

abstract = {Quantitative analysis of drug delivery with in biological 

 systems is an integral challenge in drug development. Analytical 

 techniques are important for assessing both drug target 

 delivery, target action, and drug toxicology. Using mimetic 

 tissue models, we have investigated the efficacy of Raman 

 spectroscopy in quantitative detection of alkyne group and 

 deuterated drugs in rat brain and rat liver tissue models. 

 Lasers with 671 nm and 785 nm wavelengths were assessed for 

 their feasibility in this application due to opposing relative 

 benefits and disadvantages. Thin tissue sections have been 

 tested as a practical means of reducing autofluorescent 

 background by minimizing out-of-focus tissue and therefore 

 maximizing photobleaching rates. Alkyne-tagged drugs were 

 quantitatively measured at 18 $±$ 5 μg/g drug/tissue mass 

 ratio in rat brain and at 34 $±$ 6 μg/g in rat liver. 

 Quantification calibration curves were generated for a range of 

 concentrations from 0-500 μg/g. These results show the 

 potential of Raman spectroscopy as a diffraction-limited 

 spatially resolved imaging technique for assessing drug delivery 

 in tissue applications.},

keywords = {Drug delivery, drug quantification, microscopy, Raman spectroscopy},

pubstate = {published},

tppubtype = {article}

}

@article{Dooley2022-rt,

title = {Model-based optimization of laser excitation and detection 

 improves spectral contrast in noninvasive diffuse Raman 

 spectroscopy},

author = {Max Dooley and Thomas Paterson and Louise Dexter and Pavel Matousek and Hamid Dehghani and Ioan Notingher},

year  = {2022},

date = {2022-07-01},

journal = {Appl. Spectrosc.},

volume = {76},

number = {7},

pages = {801\textendash811},

publisher = {SAGE Publications},

abstract = {Spatially offset Raman spectroscopy (SORS) is a powerful 

 technique for subsurface molecular analysis of optically turbid 

 samples. Numerical modeling of light propagation has been used 

 to investigate opportunities for improving spectral contrast and 

 signal to noise ratio when imaging regions of interest located 

 0-4.5 mm below the surface in polymer bulk material. Two- and 

 three-dimensional modeling results demonstrate that when 

 analyzing a certain region of interest (ROI) of finite lateral 

 dimensions below the sample surface, offsetting both the laser 

 source and detector in opposite directions from the central 

 point of the ROI can increase the spectral contrast as compared 

 to conventional SORS approach where the detector or the laser 

 source is maintained at the central point (centered SORS). The 

 outlined modeling results have been validated experimentally 

 using a bulk polymer sample with a trans-stilbene ROI (cylinder) 

 below the sample surface. The results show that modeling of the 

 spatial configurations of laser excitation and detection points 

 can be used to optimize the instrument configuration to achieve 

 significant improvements (up to 2.25-fold) in performance over 

 the conventional centered SORS. Such optimal solutions can then 

 be implemented, for example, using robust fiber optic probes, 

 moveable optics, or flexible spatial light modulator instruments 

 for specific applications.},

keywords = {computational modeling, diffuse Raman, Raman spectroscopy, SORS, spatially offset Raman spectroscopy},

pubstate = {published},

tppubtype = {article}

}

@article{Sinjab2020-az,

title = {Induction and measurement of the early stage of a host-parasite 

 interaction using a combined optical trapping and Raman 

 microspectroscopy system},

author = {Faris Sinjab and Hany M Elsheikha and Max Dooley and Ioan Notingher},

year  = {2020},

date = {2020-02-01},

journal = {J. Biophotonics},

volume = {13},

number = {2},

pages = {e201960065},

publisher = {Wiley},

abstract = {Understanding and quantifying the temporal acquisition of host 

 cell molecules by intracellular pathogens is fundamentally 

 important in biology. In this study, a recently developed 

 holographic optical trapping (HOT)-based Raman microspectroscopy 

 (RMS) instrument is applied to detect, characterize and monitor 

 in real time the molecular trafficking of a specific molecular 

 species (isotope-labeled phenylalanine (L-Phe(D8)) at the single 

 cell level. This approach enables simultaneous measurement of 

 the chemical composition of human cerebrovascular endothelial 

 cells and the protozoan parasite Toxoplasma gondii in isolation 

 at the very start of the infection process. Using a model to 

 decouple measurement contributions from host and pathogen 

 sampling in the excitation volume, the data indicate that 

 manipulating parasites with HOT coupled with RMS chemical 

 readout was an effective method for measurement of L-Phe(D8) 

 transfer from host cells to parasites in real-time, from the 

 moment the parasite enters the host cell.},

keywords = {blood-brain-barrier, host-parasite interaction, optical trapping, Raman spectroscopy, Toxoplasma gondii},

pubstate = {published},

tppubtype = {article}

}