LLTech atlas of images

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    1 LLTECH 2011

    LLTech

    Light-CT Scanner

    Atlas of images

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    2 LLTECH 2011

    TABLE OF CONTENTS

    BREAST Page 5

    SKIN Page 11

    CORNEA Page 15

    PROSTATE Page 18

    LUNG Page 23

    KIDNEY Page 27

    BRAIN Page 30

    HEAD & NECK Page 35

    COSMETOLOGY Page 39

    CELLS Page 44

    DEVELOPMENTAL BIOLOGY Page 49

    PLANTS Page 61

    CLINICAL APPLICATIONS RESEARCH APPLICATIONS

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    3 LLTECH 2011

    CLINICAL APPLICATIONS

    Back to Table of Contents

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    BREAST AND LYMPH NODES- Extemporaneous analysis for cancer surgery

    - Biobanking selection

    Back to Table of Contents

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    5 LLTECH 2011

    Grainy aspect of normal

    fibrous tissue

    Duct with

    calcification

    Lobule Adipocytes Vessel

    Healthy breast tissue

    Courtesy of Hpital Tenon, Paris, FranceAssayag et al, TCRT Express 1(1):e600254

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    Ductal Carcinoma In Situ (DCIS)

    Enlarged lobule

    Duct with necrosis

    Histology and LightCT images reveal the enlarged abnormal lobules and ducts characteristic of DCIS

    Assayag et al, TCRT Express 1(1):e600254

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    Lobular carcinoma

    In-situ carcinoma cells

    Invasive carcinoma cells

    1 mm100 m

    100 m

    Tumorous cells are visible in in-situ and invasive carcinoma

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    100m

    Highly scattering

    thin trabeculae

    aspect: fibrous

    tissue in the

    tumourous part

    Grainy medium

    scattering aspect:

    healthy fibrous

    tissue

    Invasive adenocarcinoma: nodular tumor

    Interface of the tumourous and normal

    appearing part :

    Grey zones corresponding to foci

    of carcinomatous cells

    Tumour margin

    500m

    500m

    Courtesy of Hpital Tenon, Paris, France

    Assayag et al, TCRT Express 1(1):e600254

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    Nodules containing

    lymphoid tissue

    Normal Sentinel Node

    Adipocytes in hilum

    Capsule Grieve et al Proc SPIE 2013

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    Lymphoid zone

    Invaded zone

    Invaded Sentinel Node

    Bright white aspect,

    highly scattering dense

    collagen meshwork

    Grieve et al Proc SPIE 2013

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    SKIN

    - Extemporaneous margin analysis for cancersurgery

    - Biobanking selection

    Back to Table of Contents

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    Epidermis

    Collagen

    Pilosebaceous

    unit

    Sweat gland

    Adipocytes

    b

    a

    c

    e

    d

    500 m

    Normal skin morphology: vertical section

    Dalimier and Salomon Dermatology 224, 84-92 (2012)

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    Skin pathologies: basal cell carcinoma discrimination

    at structural level

    Dense peritumoral stroma

    Dalimier and Salomon Dermatology 224, 84-92 (2012)

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    Zoom on basal cell carcinoma:

    discrimination at cellular level

    200 m

    100 m

    Peritumoral stroma

    High cell density

    Courtesy of Hopitaux Universitaires de Genve, Genve, Switzerland

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    CORNEA

    - Biobanking selection

    Back to Table of Contents

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    Surface epithelium Intermediary epithelium Basal epithelium

    Bowmans layer Stromal keratocytes Endothelial cells

    Cross sectional view En face views

    Normal human cornea

    100 m 100 m

    LightCT imaging reveals the structures of normal cornea: epithelium, Bowmans layer, stroma, Descemets membrane,

    and endothelium.

    Use of LightCT in Eye Banks would allow graft cornea integrity to be assessed prior to transplant.Current practice examines only the epithelial surface and endothelial cells under a traditional specular microscope.

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    Subepithelial fibrosis

    Intraepithelial edema

    LightCT cross section LightCT en face

    Cornea with bullous keratopathy

    Sub-epithelial

    fibrosis

    Optovue OCT in vivo on patientHistology

    Histology, conventional OCT and Light CT views of the same region are compared.

    The improvement in resolution with LightCT compared to conventional OCT is appreciated.

    Pathological areas of subepithelial fibrosis and intraepithelial edema are identified.

    Bowmans layer is clearly visible under the area of fibrosis.

    150 m 150 m 100 m

    Ghouali et alARVO (2013)

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    PROSTATE

    - Biobanking selection- Biopsy quality assessment

    Back to Table of Contents

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    1 mm

    Human prostatic glands with hyperplasia

    Courtesy of Hpital Tenon, Paris, France

    Zoom on hyperplasic gland

    100 m

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    3D imaging of glands

    Stack of 150 images with 1 m step

    50 m

    50 m

    50 m

    sagittal

    coronal

    oblique

    Sagittal reconstruction

    Coronal reconstruction

    Oblique reconstruction

    Courtesy of Hpital Tenon, Paris, France

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    1 mm

    1 mm

    Biopsy imaging

    Courtesy of Hpital Cochin, Paris, France

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    Tumorous glands

    200 m

    Courtesy of Hpital Cochin, Paris, France

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    LUNG

    - Biobanking selection- Biopsy quality assessment

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    Cross section of rat lung

    Jain et al.J Pathol Inform 2011, 2:28.Courtesy of Weill Medical College, NY, USA

    500 m

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    Non-neoplastic human lung tissue

    Alveoli

    Blood vessel

    Collapsed lung

    Jain et al. Pathology Visions 2013.

    Courtesy of Weill Medical College, NY, USA

    500 m

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    Adenocarcinoma of lung with lepidic & invasive

    components

    Lepidic

    Invasive Invasive

    Lepidic

    InvasiveInvasive

    500 m

    100 m 100 m

    Courtesy of Weill Medical College, NY, USA

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    KIDNEY

    - Biobanking selection- Biopsy quality assessment

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    Non-neoplastic kidney tissue

    Glomerulus

    Tubules

    Blood

    vessel

    Caron et al. Proc SPIE 2013

    Blood vesselGlomerulus

    Tubules

    200 m

    Courtesy of Weill Medical College, NY, USA

    100 m

    100 m

    100 m

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    Chromophobe renal cell carcinoma

    Sheets of cells

    Normal

    architecture is

    replaced by

    sheets of cells

    Sheets of cells

    Courtesy of Weill Medical College, NY, USA

    100 m

    50 m

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    BRAIN AND SPINAL CORD- Biobank selection

    - In-vivo potential for surgical guidance

    Back to Table of Contents

    LightCT imaging of human epileptic brain and cerebellum identifies myelinated

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    Neuron cell bodies (dark dots)

    Axons/myelin fibers

    Capillary

    Cortex

    White matter

    Axon bundles

    LightCT imaging of human epileptic brain and cerebellum identifies myelinated

    axon fibers, a subpopulation of neuronal cell bodies and CNS vasculature.

    Varlet et al 2013(submitted)

    50 m

    50 m

    80 m

    500 m

    50 m

    80 m

    50 m

    Hippocampus: Coronal section (left side)

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    CA4 field

    Hippocampal sulcus

    Alveus

    Sub-Ependymal

    zone

    CA1 field of the cornus ammonis

    Stratum radiatus

    of the CA1 field

    Stratum granulosum of the dentate gyrus

    Pyramidal neurons of the CA4 field

    responsible for memory

    Hippocampus: Coronal section (left side)

    900 m

    40 m

    40 m

    80 m

    80 m

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    Choroid Plexus Papilloma : Xanthomatous changes

    Characteristic cauliflower-like masses

    Empty papilla

    Papilla filled with blood

    Single layer of plexus cellsRare (0.5%) benign tumors

    Diagnosis possible directly on FF-OCT imageVarlet et al 2013 (submitted)

    50 m

    50 m

    20 m150 m

    50 m

    50 m

    20 m

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    LightCT images allow the distinction of meningiomas

    from meningeal haemangiopericytoma

    Collagen bundles

    Whorls

    Calcification

    Collagen balls

    Meningioma psammoma diagnosis possible directly on FF-OCT image

    80% of meningiomas are benign.

    Histologically, meningioma cells are relatively uniform, with a tendency to encircle one another, forming

    whorls and psammoma bodies (laminated calcific concretions). They have a tendency to calcify and are

    highly vascularized. Areas of fibrosis may be present.Varlet et al 2013 (submitted)

    50 m

    10 m

    10 m500 m

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    HEAD AND NECK TISSUE

    - Biobanking selection- Extemporaneous margin analysis for

    cancer surgery

    - In-vivo potential for surgical guidance

    Back to Table of Contents

    Gl t500 m

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    Glossectomy

    Tumorous tongue tissue

    Courtesy of Institut Gustave Roussy, Villejuif, France

    Thin trabeculae aspect of

    the fibrous tissue

    Cell nuclei1 mm

    500 m 500 m

    Gl t

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    Glossectomy

    Mouth floor

    Courtesy of Institut Gustave Roussy, Villejuif, France

    Epithelial cell

    nuclei

    Spinous cells

    1 mm

    500 m 500 m

    500 m

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    RESEARCH APPLICATIONS

    Back to Table of Contents

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    COSMETOLOGY- In-vivo layer thickness measurement, cell count,

    epidermis/dermis junction analysis, for ageing

    and hydration evaluation

    - Skin model analysis

    Back to Table of Contents

    En face skin slicing shows structural and cellular details

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    Stratum corneum Stratum spinosum

    Stratum basale Reticular region

    Epidermis

    Dermis

    En-face skin slicing shows structural and cellular details

    Melanin

    papillary caps

    Keratinocyte

    nuclei

    Blood vessels

    Collagen

    Corneocytes

    100 m 100 m

    100 m100 m

    LLTech 2012 Courtesy of Hopitaux Universitaires de Genve, Genve, Switzerland

    V ti l t ti f f li i

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    Vertical reconstructions from en-face slicing:

    Layer count and measurement

    50 m

    Stratum corneum

    Stratum spinosum

    Dermis

    Human skin (in-vivo)

    Skin model

    Dalimier and Salomon Dermatology 224, 84-92 (2012)

    Stack of images

    -> vertical sections

    Keratinocyte nuclei

    Melanin caps at the

    epidermis/dermis

    junction

    Blood vessel50 m

    Evaluation of stratumcorneum thickness:

    10 m

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    Naevus imaging

    500 microns

    Dermal papillae

    Hair follicule

    100 m

    50 m

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    3D views

    Wrinkle

    Stratum corneum Stratum spinosum

    Epidermis (separated by sodium bromide)

    50 m

    Reconstructed vertical slice

    Dalimier and Salomon Dermatology 224, 84-92 (2012)

    100 m

    Corneocytes

    Fingerprints (in-vivo)

    Sweat duct

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    CELL IMAGING- Cell count in native tissues and scaffolds

    - Volume and shape analysis

    Back to Table of Contents

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    Adipocytes in human tissue

    9 m depth 27 m depth 60 m depth

    Reconstructed

    depth slice

    200 m

    50 m

    200 m 200 m

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    46 LLTECH 2011 Courtesy of Centre de Recherche des Cordeliers and ESPCI, Paris, France

    Effect of fibrosis on adipocyte shape

    Reconstructed vertical views of adipocytes in gel 3D modelling of adipocyte

    No fibrosis

    With fibrosis

    50 m

    50 m

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    Cell scaffold

    Scaffold en-face view

    Scaffold reconstructed depth slice

    100 m

    100 m

    Courtesy of University of Toronto, Canada

    Hepatocytes

    nuclei are visible

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    Individual cells

    100 m

    Courtesy of Universit de Reims, France

    Isolate collagen cells

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    DEVELOPMENTAL BIOLOGY

    - Time series analysis- Reconstructed depth slices and 3D imaging

    Back to Table of Contents

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    Developmental biology: Drosophila

    200 m

    Courtesy of ESPCI, Paris, France

    In vivo imaging of drosophila melanogaster:

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    automated time series over 72 hours

    Prepupa (0-2 h)Transition to

    pupal stage (24 h)

    Pupal stage (48 h)Advanced pupal phase

    before eclosion (72 h)

    Courtesy of ESPCI, Paris, France

    In vivo imaging of drosophila melanogaster

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    100 um

    4 days

    Courtesy of ESPCI, Paris, France

    Xenopus Laevis

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    Otic vesicle

    Cartilage

    Xenopus Laevis

    100 um

    Pigmented cells

    Courtesy of Muse National dHistoire Naturelle, Paris, France

    Xenopus Laevis: back/tail

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    Xenopus Laevis: back/tail

    100 um

    30 m depth 60 m depth

    MyoseptumEpithelial

    cells

    Neural

    cells

    Courtesy of Muse National dHistoire Naturelle, Paris, France

    Xenopus Laevis

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    Xenopus Laevis

    50 um

    Reconstructed vertical slices from stacks of images

    Courtesy of Muse National dHistoire Naturelle, Paris, France

    Xenopus Laevis eye en face slices

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    Xenopus Laevis eye: en face slices

    Surface 10 m depth 20 m depth 30 m depth

    40 m depth 50 m depth 60 m depth 70 m depth

    80 m depth200 um

    230 m depth140 m depth 180 m depth

    Courtesy of Muse National dHistoire Naturelle, Paris, France

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    Copepod

    100 um

    Courtesy of Laboratoire de Rgulation des Signaux de Division, EA4479, University of Lille

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    Zebra fish eye

    100 m

    100 m

    En face slices

    Reconstructed depth slice

    Courtesy of Inserm, Paris, France

    10 m depth 20 m depth 45 m depth

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    Zebrafish brain female, 1 year old

    50 um

    Courtesy of Laboratoire Hubert Curien, Saint Etienne

    Reconstructed view from stack of images

    C Elegans Fast identification of anatomy

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    30 m depth

    ovocytes

    intestine

    100 m

    C. Elegans Fast identification of anatomy

    Body wall - cuticle

    gonad arm

    uterus100 m

    15 m depth

    LLTech 2012 Courtesy of ENS, Paris, France

    3D reconstruction

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    PLANTS

    - High resolution reconstructed depthslices and 3D imaging

    Back to Table of Contents

    Leaf veins fresh leaf sample

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    Leaf veins fresh leaf sample

    Fibers

    Veins

    100 m

    500 m

    Courtesy of ESPCI, Paris, France

    Apple

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    Apple

    100 m

    Wax

    Skin

    Flesh

    500 m

    Water

    Courtesy of ESPCI, Paris, France

    Sorghum : cross section

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    g

    Wide field en face

    14 mm x 15 mm

    Courtesy of Plate-forme d'Histocytologie et d'Imagerie Cellulaire Vgtale (PHIV), Montpellier RIO Imaging

    Sorghum cross section: native field view

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    800 m x 800 m en face field

    Courtesy of Plate-forme d'Histocytologie et d'Imagerie Cellulaire Vgtale (PHIV)Montpellier RIO Imaging

    Sorghum cross section: native field view

    Reconstructed

    depth slices

    500 m sample

    thickness

    Rice: hypocotyle

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    Rice: hypocotyle

    Wide field en face

    5mm x 2mm

    Reconstructed depth slice, 200um penetration depth

    Courtesy of Plate-forme d'Histocytologie et d'Imagerie Cellulaire Vgtale (PHIV), Montpellier RIO Imaging

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    Contacts

    LLTech, Inc.

    103 Carnegie Center Drive

    Suite 300

    Princeton, NJ 08540, USA

    Phone: +1 609 995 3506

    LLTech

    Ppinire Paris Sant Cochin

    29 rue du Faubourg Saint Jacques

    75014 Paris

    Phone: +33 1 82 72 61 25

    www.lltechimaging.com

    [email protected]