© Fraunhofer IIS

Fraunhofer IIS

Computer-assisted Analysis of Blood Cells with Smart Microscopes

Dr. Christian Münzenmayer

Group manager Medical image processing

Fraunhofer-Institute for Integrated Circuits IIS

Am Wolfsmantel 33, 91058 Erlangen

E-Mail: christian.muenzenmayer@iis.fraunhofer.de

Phone: +49-(0)9131-776-7310

© Fraunhofer IIS

Fraunhofer IIS

Fraunhofer Institute for Integrated Circuits IIS

Founded in 1985

More than 730 staff

Budget aprox. € 90 million

Revenue sources

> 75 % income from projects

< 25 % public funding

© Fraunhofer IIS

1% Thrombocytes (Platelets)

Hemostasis / coagulation

96% Erythrocytes (red blood cells)

Oxygen transport

3% Leukocytes (white blood cells)

Immune defense

55%

liquid

(Plasma

)

45%

cellular

Blood

Hematology

Components of blood

© Fraunhofer IIS

Hematology

Basics of hematopoesis

Hematopoesis:

formation of blood

cellular components

Blood cells develop from

haematopoietic stem

cells in the bone marrow

1011 – 1012 cells/day

From: http://commons.wikimedia.org/wiki/File:Hematopoiesis_simple.png

© Fraunhofer IIS

Hematology Laboratory Doctor‘s office

Blood

Withdrawal

Flow

Cytometry Smear Staining

Hematologist / Assistant

Slid

e

Inter-

pretation

Fin

din

g

Microscopy

Sample

Hematology

Laboratory workflow

© Fraunhofer IIS

Staining for microscopic examination

May-Grünwald-Giemsa (MGG) or

Pappenheim-Staining

(Artur Pappenheim, 1870-1916)

Component Staining

Erythrocytes Pink

Nuclei Red violet

Eosinophile Granula Brick-red to red brown

Basophile Granula Dark violet to black

Neutrophile Granula Lilght violet

Zytoplasma of Lymphocytes Light blue

Zytoplasma of Monocytes Gray blue

Hematology

Staining

© Fraunhofer IIS

Hematology

Manual blood differential

Counting of 100/200 leucocytes (WBC)

Erythrocyte morphology (RBC)

Qualitative results (atypical lymphocytes, …)

Still mostly manual process

© Fraunhofer IIS

Fast scanning robotic microscope

8x slide handler

Automatic calculation of white blood differential (7 classes)

< 3 Minutes per 100 leukocytes

Red blood cell morphology

Seemless LIS-Integration

Intuitive user interface

Certified Medical Product (IVD) since 10/2010 (98/79/EC Annex I)

Microscopy

HemaCAM™: Computer assisted microscopy in hematology

© Fraunhofer IIS

1. Insert slides, apply immersion oil

2. Identification of slide (barcode, OCR)

3. Automatic distribution of oil

4. Detection and Classification of leucocytes

5. Display of results

6. Optional user interaction

7. Storage, transfer to LIS

Microscopy

HemaCAM™: Process overview

© Fraunhofer IIS

Microscopy

HemaCAM™: Detection of valid area

Detection of valid area and overview image with 10x objective

© Fraunhofer IIS

Microscopy

HemaCAM™: Two-step Scanning & Analysis Process

Overview Image (10x) Detail image (100x)

Segmentation of Zytoplasm and Nucleus

Extraction of Features

Classification

© Fraunhofer IIS

Lymphocyte

Neutrophile

14

0

c

c

1

10

100

1000

10000

0 100 200 300 400 500C

ou

nt

Sum i

CorpusCardia

Blau

(x1,y

1)

(x2,y

2)

d

qGrün

(x1,y

1)

(x2,y

2)

d

qRot

(x1,y

1)

(x2,y

2)

d

q

Microscopy

Cell classification by sum-/difference histograms

Lymphocyte

Neutrophile

© Fraunhofer IIS

Microscopy

HemaCAM™: Cell classification view

© Fraunhofer IIS

Microscopy

HemaCAM™: Live cell view

© Fraunhofer IIS

Hematology Laboratory Doctor‘s office

Blood

Withdrawal

Flow

Cytometry Smear Staining

Hematologist / Assistant

Slid

e

Inter-

pretation

Fin

din

g

Sample

Hematology

Automated Laboratory workflow

Automated Process

Microscopy Image

Processing Visualization

© Fraunhofer IIS

Microscopy

Current Developments

Platform

Fully Automated Scanning

Cassette-based loading

Automated Immersion oil

Malaria

Automated Detection

and classification of

plasmodia

Bone Marrow

Automated segmentation,

classification and counting

© Fraunhofer IIS

Fraunhofer IIS – Medical Image Processing

Research and Development Services

Feasibility Studies

Technical Feasibility, laboratory prototypes

Concepts, risk and cost analysis

Technology & Market Research

Contract R&D Services

Individual R&D for systems / software

Complete Design/Implementation/Test cycle

Documentation, (pre-)clinical studies,

risk management (medical products, IVD)

Licensing of Methods, Systems

Dr. Christian Münzenmayer

Fraunhofer-Institute for Integrated Circuits IIS

Am Wolfsmantel 33, 91058 Erlangen

E-Mail: christian.muenzenmayer@iis.fraunhofer.de

Phone: +49-(0)9131-776-7310