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Terahertz endoscopic imaging for colorectal cancer detection:Current status and future perspectives

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World Journal of Gastrointestinal Endoscopy 2017年第8期9卷 346-358页

作者： Pallavi Doradla Cecil Joseph Robert H Giles Wellman Center for Photomedicine Harvard Medical School Biomedical Terahertz Technology center Department of PhysicsUniversity of Massachusetts Lowell

Terahertz(THz) imaging is progressing as a robust platform for myriad applications in the field of security,health,and material science.The THz regime,which comprises wavelengths spanning from microns to millimeters,is non-ionizing and has very low photon energy:Making it inherently safe for biological imaging.Colorectal cancer is one of the most common causes of death in the world,while the conventional screening and standard of care yet relies exclusively on the physician's experience.Researchers have been working on the development of a flexible THz endoscope,as a potential tool to aid in colorectal cancer screening.This involves building a single-channel THz endoscope,and profiling the THz response from colorectal tissue,and demonstrating endogenous contrast levels between normal and diseased tissue when imaging in reflection modality.The current level of contrast provided by the prototype THz endoscopic system represents a significant step towards clinical endoscopic application of THz technology for invivo colorectal cancer screening.The aim of this paper is to provide a short review of the recent advances in THz endoscopic technology and cancer imaging.In particular,the potential of single-channel THz endoscopic imaging for colonic cancer screening will be highlighted.

关键词：内视镜检查法兆兆赫成像 Colonoscopy 冒号癌症察觉灵活波导金属涂极化敏感极化 Cross-pol

Regenerative capacity of Müller cells and their modulation as a tool to treat retinal degenerations

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Neural Regeneration Research 2023年第1期18卷 139-140页

作者： Federica M.Conedera Volker Enzmann Advanced Microscopy Program Center for Systems BiologyMassachusetts General HospitalBostonMAUSA Wellman Center for Photomedicine Massachusetts General HospitalBostonMAUSA(Conedera FM)Department of OphthalmologyUniversity HospitalUniversity of BernBernSwitzerland Department of BioMedical Research University of BernBernSwitzerland

Vision is one of our most precious senses,and its impairment has a high socio-economic impact.In the industrialized world,degenerative diseases of the retina lead to vision loss,particularly among the elderly.These degenerations include,for instance,retinitis pigmentosa,age-related macular degeneration,and diabetic retinopathy.Although treatments are evolving to manage late-stage symptoms of retinal degenerations,no effective therapies to recover vision loss exist.Retinal degeneration often involves loss or damage to specialized neural cells,such as photoreceptors,and their death stimulates the activation and proliferation of Müller cells(Salman et al.,2021).

关键词： degeneration diseases impairment

Laser particles with omnidirectional emission for cell tracking

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Light(Science & Applications) 2021年第2期10卷 197-207页

作者： Shui-Jing Tang Paul H.Dannenberg Andreas C.Liapis Nicola Martino Yue Zhuo Yun-Feng Xiao Seok-Hyun Yun Harvard Medical School and Wellman Center for Photomedicine Massachusetts General HospitalBostonMAUSA State Key Laboratory for Mesoscopic Physics and Frontiers Science center for Nano-optoelectronics School of PhysicsPeking University100871 BeijingChina Harvard-MIT Health Sciences and Technology Massachusetts Institute of TechnologyCambridgeMAUSA

The ability to track individual cells in space over time is crucial to analyzing heterogeneous cell populations.Recently,microlaser particles have emerged as unique optical probes for massively multiplexed single-cell tagging.However,the microlaser far-field emission is inherently direction-dependent,which causes strong intensity fluctuations when the orientation of the particle varies randomly inside cells.Here,we demonstrate a general solution based on the incorporation of nanoscale light scatterers into microlasers.Two schemes are developed by introducing either boundary defects or a scattering layer into microdisk lasers.The resulting laser output is omnidirectional,with the minimum-to-maximum ratio of the angle-dependent intensity improving from 0.007(-24 dB)to>0.23(-6dB).After transfer into live cells in vitro,the omnidirectional laser particles within moving cells could be tracked continuously with high signal-to-noise ratios for 2 h,while conventional microlasers exhibited frequent signal loss causing tracking failure.

关键词： scattering directional intensity

Laser facilitates vaccination

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Journal of Innovative Optical Health Sciences 2016年第1期9卷 12-20页

作者： Ji Wang Peiyu Li Xinyuan Chen Mei X.Wu Wellman Center for Photomedicine Massachusetts General Hospital and Department of Dermotology Harvard Medical SchoolBostonMA 02114USA Biomedical and Pharmaceutical Science College of Pharmacy University of Rhode IslandKingstonRI 02881USA

Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces:to improve vaccine efficacy without compromising safety.Harnessing the specific effects of laser on biological systems,a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way.The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical e®ects with no foreign chemicals administered into the body.Here,we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

关键词： Laser vaccine delivery adjuvant

A Comparative Study on the Enhancement Efficacy of Specific and Non-specific Iron Chelators for Protoporphyrin Ⅸ Production and Photosensitization in HaCat Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第6期29卷 765-770页

作者：夏育民黄樱樱林隆德刘小明江珊熊腊元 Department of Dermatology Renmin Hospital of Wuhan University Aesthetic and Plastic center of Guangxi Medical University Wellman Center for Photomedicine Massachusetts General Hospital Harvard Medical School School of Public Health Guangxi Medical University

The iron chelators can be utilized in target cells to improve 5-aminolaevulinic acid （ALA）-based photodynamic therapy （PDT）. The purpose of this study is to compare the effect of two kinds of iron chelators, desferrioxamine （DFO） and ethylenediaminetetraacetic acid （EDTA） on the enhancement of ALA-PDT. HaCat cells were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or EDTA. After 3-h incubation in the dark, the concentration of cellular pro-toporphyrin Ⅸ （PpⅨ） was detected by high performance liquid chromatography （HPLC）, and the fluorescence of PpⅨ was observed at 630 nm emission under confocal laser scanning microscope. For PDT, HaCat cells were irradiated using 632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow cytometrically assayed. Related differences in morphology and ultrastructure of Ha-Cat cells were observed using optical microscope or transmission electron microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA increased the concentration of cellular PpⅨ and the fluorescent density of PpⅨ, and also increased cell death ratio after PDT. PDT using ALA plus DFO produced the highest cellular PpⅨ level, greatest cell death ratio and most severe structural damage to the cells. It was concluded that both DFO and EDTA could enhance ALA-based PpⅨ production and PDT. Compared to the non-specific iron chelator of EDTA, the specific chelator, DFO, showed more potential for the enhancement.

关键词： aminolaevulinic acid desferrioxamine ethylenediaminetetraacetic acid keratinocytes photodynamic therapy protoporphyrin Ⅸ

Label-free imaging immune cells and collagen in atherosclerosis with two-photon and second harmonic generation microscopy

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Journal of Innovative Optical Health Sciences 2016年第1期9卷 39-46页

作者： Chunqiang Li Riikka K.Pastila Charles P.Lin Department of Physics The University of Texas at El Paso El Paso Texas 79968USA Wellman Center for Photomedicine and center for Systems Biology Massachusetts General Hospital Harvard Medical School 185 Cambridge St. Boston Massachusetts 02114USA TUK-Radiation and Nuclear Safety Authority Laippatie 4 FI-00880 HelsinkiFinland

Atherosclerosis has been recognized as a chronic inflammation disease,in which many types of cells participate in this process,including lymphocytes,macrophages,dendritic cells(DCs),mast cells,vascular smooth muscle cells(SMCs).Developments in imaging technology provide the capability to observe cellular and tissue components and their interactions.The knowledge of the functions of immune cells and their interactions with other cell and tissue components will facilitate our discovery of biomarkers in atherosclerosis and prediction of the risk factor of rupture-prone plaques.Nonlinear optical microscopy based on two-photon excited autofluorescence and second harmonic generation(SHG)were developed to image mast cells,SMCs and collagen in plaque ex vivo using endogenous optical signals.Mast cells were imaged with two-photon tryptophan autofluorescence,SMCs were imaged with two-photon NADH auto fluorescence,and collagen were imaged with SHG.This development paves the way for further study of mast cell degranulation,and the effects of mast cell derived mediators such as induced synthesis and activation of matrix metalloproteinases(MMPs)which participate in the degradation of collagen.

关键词： Two-photon microscopy mast cells atherosclerosis

Is tumor cell specificity distinct from tumor selectivity in vivo?A quantitative NIR molecular imaging analysis of nanoliposome targeting

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Nano Research 2021年第5期14卷 1344-1354页

作者： Girgis Obaid Kimberley Samkoe Kenneth Tichauer Shazia Bano Yeonjae Park Zachary Silber Sassan Hodge Susan Callaghan Mina Guirguis Srivalleesha Mallidi Brian Pogue Tayyaba Hasan Wellman Center for Photomedicine Massachusetts General Hospital and Harvard Medical SchoolBostonMA02114USA Department of Bioengineering University of Texas at DallasRichardsonTX75080USA Thayer School of Engineering Dartmouth CollegeHanoverNH037551USA Armour College of Engineering Illinois Institute of TechnologyChicagoIL60616USA Division of Health Sciences and Technology Harvard University and Massachusetts Institute of TechnologyCambridgeMA02139USA

The significance and ability for receptor targeted nanoliposomes(tNLs)to bind to their molecular targets in solid tumors in vivo has been questioned,particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity.This study presents,for the first time,in situ near-infrared(NIR)molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors,as opposed to tumor selectivity,which includes influences of enhanced tumor permeability and retention.Results show that neither tumor delivery nor selectivity(tumor-to-normal ratio)of cetuximab and IRDye conjugated tNLs correlate with epidermal growth factor receptor(EGFR)expression in U251,U87,and 9L tumors,and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%.Conversely,their in vivo specificity,which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging,correlates positively with EGFR expression levels in vitro and ex vivo(Pearson’s r=0.92 and 0.96,respectively).This study provides a unique opportunity to address the problematic disconnect between tNL synthesis and in vivo specificity.The findings encourage their continued adoption as platforms for precision medicine,and facilitates intelligent synthesis and patient customization in order to improve safety profiles and therapeutic outcomes.

关键词： molecular recognition receptors nanoparticles specificity cancer

Efficient dispersion modeling in optical multimode fiber

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Light(Science & Applications) 2023年第2期12卷 194-206页

作者： Szu-Yu Lee Vicente J.Parot Brett E.Bouma Martin Villiger Harvard Medical School and Massachusetts General Hospital Wellman Center for PhotomedicineBostonMA 02114USA Harvard-MIT Health Sciences and Technology Massachusetts Institute of TechnologyCambridgeMA 02140USA Institute for Biological and Medical Engineering Pontificia Universidad Catolica de ChileSantiago 7820244Chile institute for Medical Engineering and Science Massachusetts Institute of TechnologyCambridgeMA 02140USA

Dispersion remains an enduring challenge for the characterization of wavelength-dependent transmission through optical multimode fiber(MMF).Beyond a small spectral correlation width,a change in wavelength elicits a seemingly independent distribution of the transmitted field.Here we report on a parametric dispersion model that describes mode mixing in MMF as an exponential map and extends the concept of principal modes to describe the fiber's spectrally resolved transmission matrix(TM).We present computational methods to fit the model to measurements at only a few,judiciously selected,discrete wavelengths.We validate the model in various MMF and demonstrate an accurate estimation of the full TM across a broad spectral bandwidth,approaching the bandwidth of the best-performing principal modes,and exceeding the original spectral correlation width by more than two orders of magnitude.The model allows us to conveniently study the spectral behavior of principal modes,and obviates the need for dense spectral measurements,enabling highly effcient reconstruction of the multispectral TM of MMF.

关键词： fiber optical dispersion

Supramolecular hybrid hydrogels as rapidly on-demand dissoluble,self-healing,and biocompatible burn dressings

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Bioactive Materials 2023年第7期25卷 415-429页

作者： A.Aslihan Gokaltun Letao Fan Luca Mazzaferro Delaney Byrne Martin L.Yarmush Tianhong Dai Ayse Asatekin O.Berk Usta center for Engineering in Medicine and Surgery Massachusetts General HospitalHarvard Medical School55 Fruit St.BostonMA02114USA Shriners Hospitals for Children 51 Blossom St.BostonMA02114USA Department of Chemical and Biological Engineering Tufts University4 Colby St.MedfordMA02474USA Department of Chemical Engineering Hacettepe University06532BeytepeAnkaraTurkey Department of Biomedical Engineering Rutgers University599 Taylor Rd.PiscatawayNJ08854USA Wellman Center for Photomedicine Massachusetts General HospitalDepartment of DermatologyHarvard Medical School50 Blossom StreetBostonMA02114USA

Despite decades of efforts,state-of-the-art synthetic burn dressings to treat partial-thickness burns are still far from ideal.Current dressings adhere to the wound and necessitate debridement.This work describes the first“supramolecular hybrid hydrogel(SHH)”burn dressing that is biocompatible,self-healable,and on-demand dissoluble for easy and trauma-free removal,prepared by a simple,fast,and scalable method.These SHHs leverage the interactions of a custom-designed cationic copolymer via host-guest chemistry with cucurbit[7]uril and electrostatic interactions with clay nanosheets coated with an anionic polymer to achieve enhanced mechanical properties and fast on-demand dissolution.The SHHs show high mechanical strength(>50 kPa),self-heal rapidly in~1 min,and dissolve quickly(4-6 min)using an amantadine hydrochloride(AH)solution that breaks the supramolecular interactions in the SHHs.Neither the SHHs nor the AH solution has any adverse effects on human dermal fibroblasts or epidermal keratinocytes in vitro.The SHHs also do not elicit any significant cytokine response in vitro.Furthermore,in vivo murine experiments show no immune or inflammatory cell infiltration in the subcutaneous tissue and no change in circulatory cytokines compared to sham controls.Thus,these SHHs present excellent burn dressing candidates to reduce the time of pain and time associated with dressing changes.

关键词： Supramolecular hybrid hydrogels Cationic copolymer On-demand dissoluble Self-healable Biocompatible Burn injury