Computer analysis and biomedical interpretation of microscopic images: Current problems and future directions

Automated analysis and recognition of microscopic images of cells and tissue sections is undergoing active development. With regard to cells, the problems posed by samples of white and red blood cells presented in a monocellular layer are well under control, and automated laboratory devices are in the clinical testing stage. The analysis of white blood cell populations offers good promise in immunologic, radiation biologic, and experimental chemotherapeutic research. The situation encountered in prescreening for cervical cancer in Papanicolaou-stained gynecologic samples calls for significantly more stringent cell recognition and sample size requirements. Methods based on high-resolution digitized imagery appear currently to be the only approach with the required discriminatory power; they may evolve as practical devices, however, only when special computers with fully parallel processing capabilities are available. As applied to tissue sections, the complexity of the scene-segmentation, analysis, and classification problems has generally restricted research work to the area of feature extraction and to the determination of descriptive stereologic parameters. Processors are needed with an architecture more compatible with the two-dimensional information of pictorial data and with suitable operating systems. The field of microscopic image analysis demands competence in a wide range of disciplines, from the practical clinical situation to optics, electrooptical devices, digital logic design, computer architecture, software engineering, multivariate statistics, and decision theory. A truly interdisciplinary research team is difficult to form and maintain, but is rewarding: It is only in such close cooperation that one discovers such research needs as the fact that most of the basic applied mathematical tools for what the clinician really wants to know have not yet been developed.

[1]  J. F. Brenner,et al.  AUTOMATED CLASSIFICATION OF NORMAL AND ABNORMAL LEUKOCYTES , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  P H Bartels,et al.  Computer generated, synthetic cell images. , 1974, Acta cytologica.

[3]  M Eden,et al.  Image processing techniques in relation to studies of red cell shape. , 1972, Nouvelle revue francaise d'hematologie.

[4]  J. Bacus ERYTHROCYTE MORPHOLOGY AND CENTRIFUGAL "SPINNER" BLOOD FILM PREPARATIONS , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[5]  Ewald R. Weibel,et al.  Morphometry and lung models , 1967 .

[6]  P H Bartels,et al.  Computer discrimination of T and B lymphocytes. , 1975, Acta cytologica.

[7]  P. Bartels,et al.  A self-learning computer program for cell recognition. , 1970, Acta cytologica.

[8]  Theodosios Pavlidis,et al.  STRUCTURAL PATTERN RECOGNITION: PRIMITIVES AND JUXTAPOSITION RELATIONS* , 1972 .

[9]  Philip H. Enslow,et al.  Multiprocessors and parallel processing , 1974 .

[10]  I T Young,et al.  A technique for multiple-cell chromosome karyotyping. , 1976, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[11]  John A. Hartigan,et al.  Clustering Algorithms , 1975 .

[12]  Theodore H. Kehl,et al.  LM2— A Logic Machine Minicomputer , 1975, Computer.

[13]  P. Bartels,et al.  Evaluation of unsupervised learning algorithms in the computer analysis of lymphocytes. , 1974, Acta cytologica.

[14]  R. C. Amendola,et al.  Image processor for biomedical research. , 1974, Federation proceedings.

[15]  B. Dew,et al.  AN AUTOMATIC MICROSCOPE SYSTEM FOR DIFFERENTIAL LEUKOCYTE COUNTING , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  L. Lipkin,et al.  A REAL TIME PICTURE PROCESSOR FOR USE IN BIOLOGIC CELL IDENTIFICATION II. HARDWARE IMPLEMENTATION , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[17]  K. R. Castleman,et al.  An Automated System for Chromosome Analysis , 1976 .

[18]  J. Taylor,et al.  Cervical cytology: descriptive statistics for nuclei of normal and atypical cell types. , 1973, Acta cytologica.

[19]  M. Mendelsohn,et al.  COMPUTER‐ORIENTED ANALYSIS OF HUMAN CHROMOSOMES. II. INTEGRATED OPTICAL DENSITY AS A SINGLE PARAMETER FOR KARYOTYPE ANALYSIS * , 1969 .

[20]  T. G. Evans DESCRIPTIVE PATTERN-ANALYSIS TECHNIQUES: POTENTIALITIES AND PROBLEMS , 1969 .

[21]  P H Bartels,et al.  Cell recognition by multivariate gray value analysis in digitized images. , 1971, Acta Cytologica.

[22]  Kanti V. Mardia,et al.  Statistics of Directional Data , 1972 .

[23]  P. Bartels,et al.  Computer analysis of defined populations of lymphocytes irradiated in vitro: I. Evaluation of murine thoracic duct lymphocytes. , 1975, Acta cytologica.

[24]  Judith M. S. Prewitt,et al.  Parametric and Nonparametric Recognition by Computer: An Application to Leukocyte Image Processing , 1972, Adv. Comput..

[25]  R S Ledley,et al.  Introduction to chromosome analysis. , 1972, Computers in biology and medicine.

[26]  P. Bartels,et al.  Differentiation of murine thoracic duct lymphocytes into T and B subpopulations by computer cell-scanning techniques. , 1974, Cellular immunology.

[27]  P. Bartels,et al.  Modeling of histologic images by computer. , 1976, Acta cytologica.

[28]  F. Marriott Practical problems in a method of cluster analysis. , 1971, Biometrics.

[29]  J. Taylor,et al.  Computer discrimination between benign and malignant urothelial cells. , 1975, Acta cytologica.

[30]  P. Bartels,et al.  EVALUATION OF CORRELATIONAL INFORMATION IN DIGITIZED CELL IMAGES , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[31]  P. H. BARTELS,et al.  OBJECTIVE CELL IMAGE ANALYSIS , 1972, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[32]  J. Wolfe A Monte Carlo Study of the Sampling Distribution of the Likelihood Ratio for Mixtures of Multinormal Distributions , 1971 .

[33]  P. Bartels,et al.  Differentiation of chicken thymic and bursal lymphocytes by cell image analysis. , 1973, Acta cytologica.

[34]  P. Bartels,et al.  Computer discrimination of cells in serous effusions. II. Peritoneal fluid. , 1973, Acta cytologica.

[35]  N. J. Pressman Markovian analysis of cervical cell images. , 1976, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[36]  P H Bartels,et al.  Self-optimizing, self-learning system in pictorial pattern recognition. , 1970, Applied optics.

[37]  N. B. Atkin,et al.  Deoxyribonucleic Acid in Human Tumours as Measured by Microspectrophotometry of Feulgen Stain: A Comparison of Tumours Arising at Different Sites , 1956, British Journal of Cancer.

[38]  P. K. Bhattacharya,et al.  Estimation procedure for the cellular composition of cervical smears. , 1975, Acta cytologica.

[39]  P. Bartels,et al.  Computerized microdissection of cellular images. , 1970, Acta cytologica.

[40]  J. Taylor,et al.  Cytoplasmic and nuclear shape analysis for computerized cell recognition. , 1976, Acta cytologica.

[41]  M L Mendelsohn,et al.  THE ANALYSIS OF CELL IMAGES * , 1966, Annals of the New York Academy of Sciences.

[42]  P. Neurath,et al.  Individualized human karyotyping through quantitative analysis. , 1972, Computers in Biology and Medicine.

[43]  P. K. Bhattacharya Order of Dependence in a Stationary Normally Distributed Two-Way Series , 1972 .

[44]  P. K. Bhattacharya,et al.  A test statistic for detecting the presence of abnormal cells in a sample. , 1971, Acta cytologica.

[45]  Brian Everitt,et al.  Cluster analysis , 1974 .

[46]  T. Caspersson,et al.  SCANNING MICROSCOPY TECHNIQUES FOR HIGH RESOLUTION QUANTITATIVE CYTOCHEMISTRY , 1962, Annals of the New York Academy of Sciences.

[47]  Ian T. Young,et al.  An Analysis Technique for Biological Shape. I , 1974, Inf. Control..

[48]  L. Ornstein The distributional error in microspectrophotometry. , 1952, Laboratory investigation; a journal of technical methods and pathology.

[49]  B H Mayall,et al.  DEOXYRIBONUCLEIC ACID CYTOPHOTOMETRY OF STAINED HUMAN LEUKOCYTES II. THE MECHANICAL SCANNER OF CYDAC, THE THEORY OF SCANNING PHOTOMETRY AND THE MAGNITUDE OF RESIDUAL ERRORS , 1970, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[50]  J. Taylor,et al.  Computer recognition of cell nuclei from the uterine cervix. , 1973, Acta cytologica.

[51]  L E Lipkin,et al.  THE ANALYSIS, SYNTHESIS, AND DESCRIPTION OF BIOLOGICAL IMAGES , 1966, Annals of the New York Academy of Sciences.

[52]  R. Feulgren,et al.  Mikroskopisch-chemischer Nachweis einer Nucleinsäure vom Typus der Thymonucleinsäure und die- darauf beruhende elektive Färbung von Zellkernen in mikroskopischen Präparaten. , 1924 .

[53]  P H Bartels,et al.  The TICAS-RTCIP real time cell identification processor. , 1975, Acta cytologica.

[54]  W. Sandritter,et al.  DNA in heterochromatin cytophotometric pattern recognition image analysis among cell nuclei in duct epithelium and in carcinoma of the human breast. , 1974, Beitrage zur Pathologie.

[55]  L. P. Huelsman,et al.  GOSPEL - A general optimization software package for electrical network design , 1968 .

[56]  P. K. Bhattacharya,et al.  A decision procedure for automated cytology: test statistic for detecting sample abnormality, and inadequacy. , 1973, Acta cytologica.

[57]  J. Taylor,et al.  Development and evaluation of automatic nucleus finding routines: thresholding of cervical cytology images. , 1975, Acta cytologica.

[58]  K PRESTON,et al.  MACHINE TECHNIQUES FOR AUTOMATIC LEUKOCYTE PATTERN ANALYSIS * , 1962, Annals of the New York Academy of Sciences.

[59]  T. Kline,et al.  Diagnostic Cytology and Its Histopathologic Bases , 1969 .

[60]  C. Lundsteen,et al.  Microphotometry of banded human chromosomes: High resolving power by direct scanning of the specimen compared with scanning on microphotographs , 1974, Journal of medical genetics.

[61]  B H Mayall,et al.  High-speed quantitative karyotyping by flow microfluorometry. , 1975, Clinical chemistry.

[62]  M. Ingram,et al.  Automatic analysis of blood cells. , 1970, Scientific American.

[63]  P. Bartels,et al.  PERFORMANCE TESTING FOR AUTOMATED PRESCREENING DEVICES IN CERVICAL CYTOLOGY , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[64]  P. Bartels,et al.  Computer discrimination of cells in serous effusions. I. Pleural fluids. , 1973, Acta cytologica.

[65]  M. Mendelsohn,et al.  13 – Chromosome Identification by Image Analysis and Quantitative Cytochemistry , 1974 .

[66]  D. N. Sparks Euclidean Cluster Analysis , 1973 .

[67]  Björn Kruse,et al.  A Parallel Picture Processing Machine , 1973, IEEE Transactions on Computers.

[68]  B H Mayall,et al.  COMPUTER-ORIENTED ANALYSIS OF HUMAN CHROMOSOMES IV. DEOXYRIBONUCLEIC ACID-BASED CENTROMERIC INDEX , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[69]  R. Narasimhan,et al.  Syntax-directed interpretation of classes of pictures , 1966, CACM.

[70]  J. A. Subach,et al.  Significance Probability Mappings and Automated Interpretation of Complex Pictorial Scenes , 1976 .

[71]  R A Kirsch,et al.  Computer determination of the constituent structure of biological images. , 1971, Computers and biomedical research, an international journal.

[72]  T. Kiehn COMPUTER ANALYSIS OF TRANSFORMING LYMPHOCYTES , 1972 .

[73]  P. Bartels,et al.  Taxonomic intra-cellular analytic system (TIICAS) for cell identification. , 1968, Acta cytologica.

[74]  P. Bartels,et al.  Cell recognition from line scan transition probability profiles. , 1969, Acta cytologica.

[75]  P H Bartels,et al.  Implementation of a hierarchical cell classification procedure. , 1974, Acta cytologica.

[76]  J W Bacus,et al.  Image processing for automated erythrocyte classification. , 1976, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[77]  Keinosuke Fukunaga,et al.  Introduction to Statistical Pattern Recognition , 1972 .

[78]  Hans Elias,et al.  Stereology of the human renal glomerulus , 1967 .

[79]  W. Sandritter,et al.  NUCLEAR IMAGES OF CELLS IN DIFFERENT FUNCTIONAL STATES , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[80]  G. Megla The LARC automatic white blood cell analyzer. , 1973, Acta cytologica.