scholarly journals FLAME: Macroscopic imaging with microscopic resolution. Optical biopsy of human skin

2020 ◽  
Author(s):  
Alexander Fast ◽  
Akarsh Lal ◽  
Amanda F. Durkin ◽  
Christopher B. Zachary ◽  
Anand K. Ganesan ◽  
...  
Keyword(s):  
Human Skin ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Counting ◽  
Optical Biopsy ◽  
Large Area ◽  
Time Resolved ◽  
Distribution Maps ◽  
Imaging Tool

AbstractWe introduce a compact, fast large area multiphoton exoscope (FLAME) system with enhanced molecular contrast for macroscopic imaging of human skin with microscopic resolution. A versatile imaging platform with multiple modes of operation for comprehensive analysis of live or resected thick human skin tissue, it produces 3D images that encompass sub-mm2 to cm2 scale areas of tissue within minutes. The FLAME imaging platform, which expands on a design recently introduced by our group, features deep learning, additional scanning hardware elements and time-resolved single photon counting detection to uniquely allow fast discrimination and 3D virtual staining of melanin. We demonstrate its performance and utility by fast ex vivo and in vivo imaging of human skin. With the ability to provide rapid access to depth resolved images of skin over cm2 area and to generate 3D distribution maps of key sub-cellular skin components such as melanocytic dendrites and melanin, FLAME represents a promising imaging tool for enhancing diagnosis accuracy, guiding therapy and understanding skin biology.

scholarly journals Fast, large area multiphoton exoscope (FLAME) for macroscopic imaging with microscopic resolution of human skin

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander Fast ◽  
Akarsh Lal ◽  
Amanda F. Durkin ◽  
Griffin Lentsch ◽  
Ronald M. Harris ◽  
...  
Keyword(s):  
Human Skin ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Counting ◽  
Large Area ◽  
Time Resolved ◽  
Distribution Maps ◽  
Imaging Tool ◽  
Molecular Contrast

Abstract We introduce a compact, fast large area multiphoton exoscope (FLAME) system with enhanced molecular contrast for macroscopic imaging of human skin with microscopic resolution. A versatile imaging platform, FLAME combines optical and mechanical scanning mechanisms with deep learning image restoration to produce depth-resolved images that encompass sub-mm2 to cm2 scale areas of tissue within minutes and provide means for a comprehensive analysis of live or resected thick human skin tissue. The FLAME imaging platform, which expands on a design recently introduced by our group, also features time-resolved single photon counting detection to uniquely allow fast discrimination and 3D virtual staining of melanin. We demonstrate its performance and utility by fast ex vivo and in vivo imaging of human skin. With the ability to provide rapid access to depth resolved images of skin over cm2 area and to generate 3D distribution maps of key sub-cellular skin components such as melanocytic dendrites and melanin, FLAME is ready to be translated into a clinical imaging tool for enhancing diagnosis accuracy, guiding therapy and understanding skin biology.

scholarly journals A pilot study of the dynamics of tissue oxygenation in vivo using time-resolved phosphorescence imaging

2021 ◽  
pp. 2142001
Author(s):  
Natalia Kazachkina ◽  
Julia Lymar ◽  
Vladislav Shcheslavskiy ◽  
Alexander Savitsky
Keyword(s):  
Solid Tumor ◽  
Single Photon ◽  
Photon Counting ◽  
Time Resolved ◽  
Phosphorescence Lifetime ◽  
Phosphorescence Quenching ◽  
Single Photon Counting ◽  
Normal Tissues ◽  
Phosphorescence Lifetime Imaging

Oxygenation of tissues plays an important role in the development and progression of tumor to treatment effects. Method of metalloporphyrines phosphorescence quenching by oxygen is one of the ways to measure dynamics of the oxygen concentration in the tissues by phosphorescence lifetime imaging of meso-tetra(sulfopheny1)tetrabenzoporphyrin Pd (II) (TBP) using the time-correlated single photon counting (TCSPC) method. It has been shown that phosphorescence lifetime of the sensor in S37 tumor in vivo varied in the range of 130 to 290 [Formula: see text]s after both topical and intravenous administration of TBP. It indicates that oxygen level in tumors was lower compared to normal tissues where TBP phosphorescence has not been detected. Phosphorescence lifetimes of TBP increased in the solid tumor and in the muscle after photodynamic therapy of solid tumor that demonstrates oxygen consumption during treatment and possibly stopping the blood flow and hence the oxygen supply to the tissues.

Single Point PICA Probing with an Avalanche Photo-Diode

2001 ◽  
Author(s):  
Mike Bruce ◽  
Rama R. Goruganthu ◽  
Shawn McBride ◽  
David Bethke ◽  
J.M. Chin
Keyword(s):  
Single Photon ◽  
Single Point ◽  
Photon Counting ◽  
Ring Oscillator ◽  
Time Resolved ◽  
Single Photon Counting ◽  
Photo Diode ◽  
Avalanche Photo Diode ◽  
Photo Multiplier Tube ◽  
Channel Plate

Abstract For time resolved hot carrier emission from the backside, an alternate approach is demonstrated termed single point PICA. The single point approach records time resolved emission from an individual transistor using time-correlated-single-photon counting and an avalanche photo-diode. The avalanche photo-diode has a much higher quantum efficiency than micro-channel plate photo-multiplier tube based imaging cameras typically used in earlier approaches. The basic system is described and demonstrated from the backside on a ring oscillator circuit.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET

2021 ◽  
Vol 22 (4) ◽  
pp. 1645
Author(s):  
Daniel Gündel ◽  
Masoud Sadeghzadeh ◽  
Winnie Deuther-Conrad ◽  
Barbara Wenzel ◽  
Paul Cumming ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ex Vivo ◽  
Specific Binding ◽  
Monocarboxylate Transporters ◽  
Binding Potential ◽  
Kidney Cortex ◽  
Binding Studies ◽  
Imaging Tool ◽  
Pre Treatment

The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [18F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [18F]FACH in healthy mice and piglets. We measured the [18F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [18F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a KD of 118 ± 12 nM and Bmax of 6.0 pmol/mg wet weight. The specificity of [18F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC0–60min after pre-treatment with α-CCA-Na in mice (−47%) and in piglets (−66%). [18F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [18F]FACH binding potential (BPND) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [18F]FACH uptake was confirmed by displacement studies in 4T1 cells. [18F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

scholarly journals A Versatile Setup for Time-Resolved Functional Near Infrared Spectroscopy Based on Fast-Gated Single-Photon Avalanche Diode and on Four-Wave Mixing Laser

2019 ◽  
Vol 9 (11) ◽  
pp. 2366 ◽  
Author(s):  
Laura Di Sieno ◽  
Alberto Dalla Mora ◽  
Alessandro Torricelli ◽  
Lorenzo Spinelli ◽  
Rebecca Re ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Single Photon ◽  
Wave Mixing ◽  
Functional Near Infrared Spectroscopy ◽  
Time Resolved ◽  
Diffusive Medium ◽  
Spectroscopy System

In this paper, a time-domain fast gated near-infrared spectroscopy system is presented. The system is composed of a fiber-based laser providing two pulsed sources and two fast gated detectors. The system is characterized on phantoms and was tested in vivo, showing how the gating approach can improve the contrast and contrast-to-noise-ratio for detection of absorption perturbation inside a diffusive medium, regardless of source-detector separation.

Single Photon Counting Module Based on Large Area APD and Novel Logic Circuit for Quench and Reset Pulse Generation

2007 ◽  
Vol 13 (4) ◽  
pp. 926-933 ◽  
Author(s):  
Vinit H. Dhulla ◽  
Georgiy Gudkov ◽  
Dmitri Gavrilov ◽  
Andrey Stepukhovich ◽  
Andriy Tsupryk ◽  
...  
Keyword(s):  
Single Photon ◽  
Photon Counting ◽  
Logic Circuit ◽  
Pulse Generation ◽  
Large Area ◽  
Single Photon Counting ◽  
Reset Pulse

scholarly journals Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2

2018 ◽  
Vol 78 (2) ◽  
pp. 218-227 ◽  
Author(s):  
Janine Schniering ◽  
Martina Benešová ◽  
Matthias Brunner ◽  
Stephanie Haller ◽  
Susan Cohrs ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Single Photon ◽  
Ex Vivo ◽  
Somatostatin Receptor ◽  
Photon Emission ◽  
Nuclear Imaging ◽  
Integrin Αvβ3 ◽  
Biodistribution Studies

ObjectiveTo evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD).MethodsThe pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting 177Lu-DOTA-RGD and the SSTR2-targeting 177Lu-DOTA-NOC radiotracer. The specific pulmonary accumulation of the radiotracers over time was assessed by in vivo and ex vivo SPECT/CT scans and by biodistribution studies.ResultsExpression of integrin αvβ3 and SSTR2 was substantially increased in human ILD regardless of the subtype. Similarly, in lungs of BLM-challenged mice, but not of controls, both imaging targets were stage-specifically overexpressed. While integrin αvβ3 was most abundantly upregulated on day 7, the inflammatory stage of BLM-induced lung fibrosis, SSTR2 expression peaked on day 14, the established fibrotic stage. In agreement with the findings on tissue level, targeted nuclear imaging using SPECT/CT specifically detected both imaging targets ex vivo and in vivo, and thus visualised different stages of experimental ILD.ConclusionOur preclinical proof-of-concept study suggests that specific visualisation of molecular processes in ILD by targeted nuclear imaging is feasible. If transferred into clinics, where imaging is considered an integral part of patients’ management, the additional information derived from specific imaging tools could represent a first step towards precision medicine in ILD.

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