Laser speckle contrast imaging, the future DBF imaging technique for TRP target engagement biomarker assays

Bamps, Dorien; Macours, Laura; Buntinx, Linde; Hoon, Jan de

doi:10.1016/j.mvr.2019.103965

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…LSCI, on the other hand, guarantees the recognition of blood vessels underneath the CAM as long as they are located close to the membrane and display a high perfusion status. This can be attributed to the fact that LSCI has to reach a penetration depth of approximately 300 µm when used for the measurement of dermal blood flow [ 61 , 62 , 63 ]. Therefore, the CAM assay application does not fully display the angiogenic development of deeper vessels and LSCI could be used as an additional tool here.…”

Section: Discussionmentioning

confidence: 99%

Deep Learning-Based Image Analysis for the Quantification of Tumor-Induced Angiogenesis in the 3D In Vivo Tumor Model—Establishment and Addition to Laser Speckle Contrast Imaging (LSCI)

Kuri

Pion

Mahl

et al. 2022

Cells

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(1) Background: angiogenesis plays an important role in the growth and metastasis of tumors. We established the CAM assay application, an image analysis software of the IKOSA platform by KML Vision, for the quantification of blood vessels with the in ovo chorioallantoic membrane (CAM) model. We added this proprietary deep learning algorithm to the already established laser speckle contrast imaging (LSCI). (2) Methods: angiosarcoma cell line tumors were grafted onto the CAM. Angiogenesis was measured at the beginning and at the end of tumor growth with both measurement methods. The CAM assay application was trained to enable the recognition of in ovo CAM vessels. Histological stains of the tissue were performed and gluconate, an anti-angiogenic substance, was applied to the tumors. (3) Results: the angiosarcoma cells formed tumors on the CAM that appeared to stay vital and proliferated. An increase in perfusion was observed using both methods. The CAM assay application was successfully established in the in ovo CAM model and anti-angiogenic effects of gluconate were observed. (4) Conclusions: the CAM assay application appears to be a useful method for the quantification of angiogenesis in the CAM model and gluconate could be a potential treatment of angiosarcomas. Both aspects should be evaluated in further research.

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Section: Discussionmentioning

confidence: 99%

Deep Learning-Based Image Analysis for the Quantification of Tumor-Induced Angiogenesis in the 3D In Vivo Tumor Model—Establishment and Addition to Laser Speckle Contrast Imaging (LSCI)

Kuri

Pion

Mahl

et al. 2022

Cells

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“…Notably, LSCI and LDI reported comparable results on all measures, confirming the high correlation between the two techniques when assessing cinnamaldehyde-induced DBF changes. 26…”

Section: Articlementioning

confidence: 99%

“…In total, 16 subjects were randomized to the study treatment. They were, on average (range), 29 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) years of age with a BMI of 23.3 (18.4-27.4) kg/m 2 . Fourteen ( 14) participants completed the study as per protocol.…”

Section: Pharmacology Of Ly3526318 In Humansmentioning

confidence: 99%

“…Topical application of cinnamaldehyde was used to activate local TRPA1 channels expressed on peripheral sensory nerve endings, thereby provoking neurogenic inflammation, including vasodilation. The latter can be observed as an increase in cutaneous blood flow and objectively quantified using laser Doppler and laser speckle contrast imaging (LDI and LSCI, respectively) 25,26 . Both techniques utilize the Doppler effect produced by moving red blood cells to image the microcirculation in a noninvasive manner.…”

Section: Figurementioning

confidence: 99%

“…The latter can be observed as an increase in cutaneous blood flow and objectively quantified using laser Doppler and laser speckle contrast imaging (LDI and LSCI, respectively). 25,26 Both techniques utilize the Doppler effect produced by moving red blood cells to image the microcirculation in a noninvasive manner. Whereas temporal resolution has improved with the introduction of LSCI, target engagement experiments have been mainly performed with LDI.…”

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confidence: 99%

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TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde‐Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology

Bamps,

Blockeel,

Dreesen

et al. 2023

Clin Pharma and Therapeutics

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Transient receptor potential Ankyrin 1 (TRPA1) is an ion channel expressed by sensory neurons, where it mediates pain signalling. Consequently, it has emerged as a promising target for novel analgesics, yet to date no TRPA1 antagonists have been approved for clinical use. In the present translational study, we utilized dermal blood flow changes evoked by TRPA1 agonist cinnamaldehyde as a target engagement biomarker to investigate the in vivo pharmacology of LY3526318, a novel TRPA1 antagonist. In rats, LY3526318 (1, 3 and 10 mg/kg, p.o.) dose‐dependently reduced the cutaneous vasodilation typically observed following topical application of 10% v/v cinnamaldehyde. The inhibition was significant at the site of cinnamaldehyde application and also when including an adjacent area of skin. Similarly, in a cohort of 16 healthy human volunteers, LY3526318 administration (10, 30 and 100 mg, p.o.) dose‐dependently reduced the elevated blood flow surrounding the site of 10% v/v cinnamaldehyde application, with a trend towards inhibition at the site of application. Comparisons between both species reveal that the effects of LY3526318 on the cinnamaldehyde‐induced dermal blood flow are greater in rats relative to humans, even when adjusting for cross‐species differences in potency of the compound at TRPA1. Exposure‐response relationships suggest that a greater magnitude response may be observed in humans if higher antagonist concentrations could be achieved. Taken together, these results demonstrate that cinnamaldehyde‐evoked changes in dermal blood flow can be utilized as a target engagement biomarker for TRPA1 activity and that LY3526318 antagonizes the ion channel both in rats and humans.

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Laser speckle contrast analysis (LASCA) technology for the semiquantitative measurement of angiogenesis in in-ovo-tumor-model

Pion

Asam

Feder

et al. 2021

Microvascular Research

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Laser speckle contrast imaging, the future DBF imaging technique for TRP target engagement biomarker assays

Cited by 7 publications

References 18 publications

Deep Learning-Based Image Analysis for the Quantification of Tumor-Induced Angiogenesis in the 3D In Vivo Tumor Model—Establishment and Addition to Laser Speckle Contrast Imaging (LSCI)

Deep Learning-Based Image Analysis for the Quantification of Tumor-Induced Angiogenesis in the 3D In Vivo Tumor Model—Establishment and Addition to Laser Speckle Contrast Imaging (LSCI)

TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde‐Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology

Laser speckle contrast analysis (LASCA) technology for the semiquantitative measurement of angiogenesis in in-ovo-tumor-model

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