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METHOD FOR AUTOMATIC RECOGNITION OF NEOPLASTIC LYMPHOID CELLS USING PERIPHERAL BLOOD CELL IMAGES Santiago Alférez Anna Merino José Rodellar

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METHOD FOR AUTOMATIC RECOGNITION OF

NEOPLASTIC LYMPHOID CELLS USING

PERIPHERAL BLOOD CELL IMAGES

Santiago Alférez

Anna Merino

José Rodellar

Morphology

Immunophenotype

Cytogenetic

Molecular Studies

PROGNOSIS TREATMENT

DIAGNOSIS

CLINICAL

INFORMATION

SAMPLE

DIAGNOSIS IN HEMATOLOGY

Is it possible to automatically detect blood atypical lymphoid cells through their morphological characteristics and other quantitative parameters ?

SUBJECTIVITY -

SKILLED EXPERIENCE

AUTOMATIC SYSTEMS DO NOT CLASSIFY

ATYPICAL LYMPHOID CELLS

CLINICAL DIAGNOSIS OF 80% OF HEMATOLOGICAL DISEASES IS MADE BY MORPHOLOGICAL STUDIES OF PERIPHERAL BLOOD

Design of a new methodology for the automatic classification of atypical lymphoid cells by using digital images from peripheral blood

OBJECTIVE

Method implemented in a computer, whose

inputs are digital images from individual

patients.

Through a newly designed digital image

processing procedure, the output is an

automatic classification of the different cells

corresponding to specific diseases.

Images

Preprocessing

Segmentation

Feature extraction

1834 x 1429

Information theory feature

selection: CMIM

SVM

classification

N HCL

CLL M

CL FL

PBL

Image processing

Database features

10

CELLSIMATIC

inputs

output

Images

Preprocessing

Segmentation

Feature extraction

N x M

Feature selection

SVM

classification

N HCL CLL

MCL FL PBL

Image processing

Database features

10

Normal lymphocytes (NL)

Chronic lymphocytic leukemia (CLL)

B Prolymphocytes (B-PLL)

Hairy cell leukemia (HCL)

Follicular lymphoma

Mantle cell lymphoma (MCL)

Reactive lymphocytes

TARGETS

CLL

HCL

Follicular

lymphoma

MCL

B

Prolymphocytes

Reactive

lymphocytes

N cell images

Preprocessing

Segmentation

Feature extraction

N x 6435

Feature

selection

Digital image processing

Feature database

N x 95

SVM classification

N HCL CLL MCL

FL BPL RL

10

SVM classifier

Training set

SYSTEM DEVELOPMENT: BUILDING THE CLASSIFIER

OBJECTIVE

Results of completed segmentation for different cells

Cytoplasm, nucleus and external region are automatically identified.

SEGMENTATION

Size

N/C ratio

Nuclear contour

Chromatin texture

Mature Condensed Inmature

Lax nucleolus

Cytoplasm

High basophilia

Low basophilia

Vacuoles

MORPHOLOGIC FEATURES OF WBC’s

Reactive lymphocytes (RL)

3617 Cells 70 patients

Training set

SYSTEM DEVELOPMENT

Accuracy

92,3%

TRUE PREDICTED

N HCL CLL FL MCL BPL RL

N 85,94 1,56 6,88 0,94 1,25 0,94 2,50

HCL 1,70 94,33 0,57 0,00 0,57 0,57 2,27

CLL 1,85 0,35 96,18 0,93 0,23 0,23 0,23

FL 0,36 0,36 2,54 90,93 5,63 0,00 0,18

MCL 0,27 0,27 0,41 5,19 90,71 1,78 1,37

BPL 0,00 0,93 0,00 0,47 3,74 89,25 5,61

RL 0,49 3,43 0,25 0,00 1,72 0,98 93,14

SYSTEM DEVELOPMENT RESULTS

PRECISION, SENSITIVITY, SPECIFICITY

n cell images of a single

patient

n x 95

Feature database

Validation set

SVM classification

N

HCL

CLL

MCL

FL

BPL

RL

Preprocessing

Segmentation

Feature extraction

SVM

classifier

SYSTEM VALIDATION: PROOF OF CONCEPT

Image processing

INPUT

OUTPUT

69

84

236

93136

117

175

N

HCL

CLL

MCL

FL

BPL

RL

910 Cells 21 patients

Validation set

SYSTEM VALIDATION RESULTS

Reactive lymphocytes (RL)

Accuracy

85,2%

TRUE PREDICTED

N HCL LLC LF LCM PLB LR

N 92,75 0,00 2,90 1,45 1,45 0,00 1,45

HCL 1,19 98,81 0,00 0,00 0,00 0,00 0,00

LLC 2,97 1,27 80,51 10,17 3,81 0,85 0,42

LF 0,00 0,00 2,21 80,15 17,65 0,00 0,00

LCM 2,15 0,00 1,08 31,18 64,52 1,08 0,00

PLB 3,42 0,00 0,00 0,00 11,11 83,76 1,71

LR 0,57 1,14 0,00 0,00 0,00 0,57 97,71

SYSTEM VALIDATION RESULTS

• Patient 30 year-old. Anemia during the last 2 months

• Peripheral blood analysis showing: Hb: 89 g/L WBC: 6.98 x 109/L Platelets: 51000 x 109/L

CLINICAL CYTOLOGIC CASE 1

CellsiMatic: 100% HCL, 0% N, 0% RL, 0% LLC, 0% LCM, 0% FL, 0% PL

CellaVision Images

• Patient 73 year-old in which a finding of lymphocytosis is referred to the Hospital. No symptoms. Small cervical lymphadenopathy are detected.

Hb: 99 g/L WBC: 19.37 x 109/L Platelets: 153000 x 109/L

CLINICAL CYTOLOGIC CASE 2

CellsiMatic: 0% HCL, 0% N, 0% RL, 0% LLC, 4.1% LCM, 95.9% FL, 0% PL

CellaVision Images

• Patient 79 year-old in which a finding of leukocytosis and lymphocytosis is referred to the Hospital. No symptoms.

Hb: 133 g/L WBC: 53.0 x 109/L Platelets: 163 x 109/L

CLINICAL CYTOLOGIC CASE 3

CellsiMatic: 2.8% HCL, 15.5% N, 1.4% RL, 73.2% LLC, 4.2% LCM, 0% FL, 2.8% PL

Digital Images

• Patient 64 year-old with a MCL diagnosed in 2006. He received an allogeneic THP. In 2014 lymphadenopathy and skin lesions are detected.

Hb: 84 g/L WBC: 8.98 x 109/L Platelets: 220 x 109/L

CLINICAL CYTOLOGIC CASE 4

CellsiMatic: 0% HCL, 0% N, 0% RL, 0% LLC, 62.5% LCM, 36.3% FL, 1.3% PL

Digital Images

• Patient 20 year-old visited in the emergency Service because of high fever.

Hb: 149 g/L WBC: 17.13 x 109/L Platelets: 99 x 109/L

CLINICAL CYTOLOGIC CASE 5

CellsiMatic: 0% HCL, 0% N, 100% RL, 0% LLC, 0% LCM, 0% FL, 0% PL

Digital Images

1. Our strategy includes a robust segmentation method, a complete feature extraction and a successful classification procedure.

2. It is important to remark the high number (7) of groups of lymphoid cells involved in the classification.

3. The contribution of this work combining medical, engineering and mathematical backgrounds is the development of a complete method that could allow the design of a practical diagnosis support tool in the future.

CONCLUSIONS

José Rodellar [email protected]

Santiago Alférez [email protected]

Anna Merino [email protected]

“Cytology is like to see

the stars and through

them to see the origin of

the universe”