<i>In situ</i>
            biodistribution and residency of a topical anti‐inflammatory using fluorescence lifetime imaging microscopy

Alex, Aneesh; Frey, Steve; Angelene, H.; Neitzel, Craig D.; Li, J.; Bower, Andrew J.; Spillman, Darold R.; Marjanović, Marina; Chaney, Eric J.; Medler, J.L.; Lee, W.; Johnson, Litty; Boppart, Stephen A.; Arp, Zane

doi:10.1111/bjd.16992

Cited by 17 publications

(22 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in previous studies 10,15 , fluorescence lifetime depends on the chemical composition of the imaged region, and is an indicator of the metabolic state of the cells in that region. Figure 1e shows FLIM images of different skin layers from the 4 study groups.…”

Section: Resultsmentioning

confidence: 60%

“…Optical biopsies. We captured optical biopsy images using the procedure described in 10 . A commercial optical medical imaging system (MPTflex CARS, JenLab GmbH, Germany) was utilized to collect optical biopsies in this study (Fig.…”

Section: Psoriasis Area and Severity Index (Pasi) And Local Inflammatmentioning

confidence: 99%

“…Optical biopsies collected from study subjects presented cellular and sub-cellular structural information based on femtosecond multiphoton (two-photon) excitation of fluorescent biomolecules like nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), flavins, porphyrins, elastin, and melanin. As previously reported, FLIM measures fluorescence lifetimes of fluorophores to generate image contrast, and can be used as a marker for metabolic, biochemical, and morphological changes in vivo 10,11,[15][16][17] . Therefore, the FLIM modality was utilized to monitor metabolic changes in the imaged skin regions.…”

mentioning

confidence: 91%

“…In recent years, significant advancements have been made in optical imaging technologies suitable for in vivo studies. Among these, multiphoton microscopy (MPM) has been widely used in research studies related to applications in dermatology [9][10][11][12][13] . However, all of the studies employing optical microscopy so far have relied on targeting and imaging of sub-millimeter patches of psoriatic lesions that have inherent structural heterogeneity.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin

Žurauskas

Barkalifa

Alex

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Patients with psoriasis represent a heterogeneous population with individualized disease expression. Psoriasis can be monitored through gold standard histopathology of biopsy specimens that are painful and permanently scar. A common associated measure is the use of non-invasive assessment of the Psoriasis Area and Severity Index (PASI) or similarly derived clinical assessment based scores. However, heterogeneous manifestations of the disease lead to specific PASI scores being poorly reproducible and not easily associated with clinical severity, complicating the efforts to monitor the disease. To address this issue, we developed a methodology for non-invasive automated assessment of the severity of psoriasis using optical imaging. Our analysis shows that two-photon fluorescence lifetime imaging permits the identification of biomarkers present in both lesional and non-lesional skin that correlate with psoriasis severity. This ability to measure changes in lesional and healthy-appearing skin provides a new pathway for independent monitoring of both the localized and systemic effects of the disease. Non-invasive optical imaging was conducted on lesions and non-lesional (pseudo-control) skin of 33 subjects diagnosed with psoriasis, lesional skin of 7 subjects diagnosed with eczema, and healthy skin of 18 control subjects. Statistical feature extraction was combined with principal component analysis to analyze pairs of two-photon fluorescence lifetime images of stratum basale and stratum granulosum layers of skin. We found that psoriasis is associated with biochemical and structural changes in nonlesional skin that can be assessed using clinically available two-photon fluorescence lifetime microscopy systems.

show abstract

Section: Resultsmentioning

confidence: 60%

Section: Psoriasis Area and Severity Index (Pasi) And Local Inflammatmentioning

confidence: 99%

mentioning

confidence: 91%

mentioning

confidence: 99%

See 2 more Smart Citations

Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin

Žurauskas

Barkalifa

Alex

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In their article, Alex et al . demonstrate the feasibility of in vivo and in situ FLIM for the visualization of topically delivered investigational drugs during a first‐of‐its‐kind clinical trial . By capturing both the spectral and temporal profiles of fluorophores, FLIM enables the identification of unique molecular species, even in the crowded and complex biological milieu.…”

mentioning

confidence: 99%

Shedding light on topical drug uptake

Jeong

Evans

2018

Br J Dermatol

View full text Add to dashboard Cite

show abstract

Longitudinal monitoring of cell metabolism in biopharmaceutical production using label‐free fluorescence lifetime imaging microscopy

Sternisha

Mukherjee

Alex

et al. 2021

Biotechnology Journal

View full text Add to dashboard Cite

Chinese hamster ovary (CHO) cells are routinely used in the biopharmaceutical industry for production of therapeutic monoclonal antibodies (mAbs). Although multiple offline and time‐consuming measurements of spent media composition and cell viability assays are used to monitor the status of culture in biopharmaceutical manufacturing, the day‐to‐day changes in the cellular microenvironment need further in‐depth characterization. In this study, two‐photon fluorescence lifetime imaging microscopy (2P‐FLIM) was used as a tool to directly probe into the health of CHO cells from a bioreactor, exploiting the autofluorescence of intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H), an enzymatic cofactor that determines the redox state of the cells. A custom‐built multimodal microscope with two‐photon FLIM capability was utilized to monitor changes in NAD(P)H fluorescence for longitudinal characterization of a changing environment during cell culture processes. Three different cell lines were cultured in 0.5 L shake flasks and 3 L bioreactors. The resulting FLIM data revealed differences in the fluorescence lifetime parameters, which were an indicator of alterations in metabolic activity. In addition, a simple principal component analysis (PCA) of these optical parameters was able to identify differences in metabolic progression of two cell lines cultured in bioreactors. Improved understanding of cell health during antibody production processes can result in better streamlining of process development, thereby improving product titer and verification of scale‐up. To our knowledge, this is the first study to use FLIM as a label‐free measure of cellular metabolism in a biopharmaceutically relevant and clinically important CHO cell line.

show abstract

In situ biodistribution and residency of a topical anti‐inflammatory using fluorescence lifetime imaging microscopy

Cited by 17 publications

References 11 publications

Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin

Assessing the severity of psoriasis through multivariate analysis of optical images from non-lesional skin

Shedding light on topical drug uptake

Longitudinal monitoring of cell metabolism in biopharmaceutical production using label‐free fluorescence lifetime imaging microscopy

Contact Info

Product

Resources

About