EXPERT RADIOLOGY ASSISTANT

FEASIBILITY RESEARCH IS PROPOSED FOR THE DEVELOPMENT OF A COMPUTER-BASED EXPERT RADIOLOGY ASSISTANT (XRA) TO AID IN THE DIAGNOSIS OF BREAST CANCER. THE PROPOSED EXPERT SYSTEM HAS THE POTENTIAL TO ASSIST RADIOLOGISTS IN THE INTERPRETATION OF DIAGNOSTIC IMAGES AND CLINICAL DATA USING ARTIFICIAL INTELLIGENCE. THE SYSTEM WAS FORMED BY ENCODING IN THE COMPUTER SOFTWARE THE KNOWLEDGE OF HUMAN EXPERTS. THE SYSTEM WILL ASSIST IN THE DIAGNOSIS OF DIFFICULT CASES AND PROVIDE READY ACCESS TO THE KNOWLEDGE OF EXPERTS, LEADING TO INCREASED DISTRIBUTION AND APPLICATION OF MAMMOGRAPHIC EXPERTISE. SPECIFIC AIMS OF PHASE I ARE DESIGNED TO PROVIDE EXPERIMENTAL EVIDENCE TO TEST THE CAPABILITY OF AN EXPERT SYSTEM TO MAKE DIAGNOSES BASED UPON CLINICAL AND IMAGE DESCRIPTORS PROVIDED BY RADIOLOGISTS. A PROTOTYPE SYSTEM WILL BE IMPLEMENTED AND TESTED USING VERIFIED CLINICAL CASESTO AID IN THE DISCOVERY OF REASONING METHODS AND DATA DESCRIPTORS THAT CONSTITUTE SUFFICIENT KNOWLEDGE TO MAKE DIAGNOSES AT EXPERT LEVELS OF PERFORMANCE. HAVING DEFINED A SUFFICIENT SET OF IMAGE DESCRIPTORS, A PHASE II EFFORT WILL CONCENTRATE ON FULL IMPLEMENTATION OF THE INTERACTIVE IMAGE-UNDERSTANDING PORTION OF THE SYSTEM, INTEGRATION OF THE DIAGNOSTIC AND IMAGE ANALYSIS SUBSYSTEMS,EXPANSION OF THE KNOWLEDGE BASE, AND DEFINITIVE CLINICAL TESTING. A SPECIFIC CHROMOSOMAL ABNORMALITY, THE PHILADELPHIA TRANSLOCATION, IS CHARACTERISTIC OF LEUKEMIC CELLS IN OVER 95 PERCENT OF ALL PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA. THE PHILADELPHIA CHROMOSOME, GENERATED BY THIS TRANSLOCATION, IS THE RESULT OF A BREAK OCCURRING WITHIN THEBCR GENE ON CHROMOSOME 22; SEQUENCES 3' OF THE BREAKPOINT ARE TRANSLOCATED TO CHROMOSOME 9, FROM WHICH THE C-ABL ONCOGENE IS TRANSFERRED INTO THE BCR GENE. THE RESULTING CHIMERIC BCR-C-ABL GENE PRODUCES A CHIMERIC MRNA AND ABNORMAL ABL PROTEIN. FOUR BCR HOMOLOGOUS LOCI HAVE BEEN MOLECULARLY CLONED AND CHARACTERIZED IN PHASE I RESEARCH. IN ADDITION, THREE DIFFERENT ABL HOMOLOGOUS SEQUENCES HAVE BEEN ISOLATED. THE PRIMARY OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE POSSIBLE INVOLVEMENT OF BCR AND ABL HOMOLOGOUS SEQUENCES IN HUMAN CANCER. IN PHASE II, THE CHROMOSOMAL LOCATION OF THE BCR-RELATED GENES WILL BE DETERMINED AND CDNAS WILL BE ISOLATED FROM THOSE LOCI FOUND TO BE ACTIVELY TRANSCRIBED GENES. PROBES ISOLATED FROM THE CDNAS WILL BE USED TO SCREEN DNAS FROM LEUKEMIAS, LYMPHOMAS, AND SOLID TUMORS FOR REARRANGEMENTS AND TRANSLOCATIONS; PULSED-FIELD, GRADIENT GEL ELECTROPHORESIS MAY BE USED AS AN ALTERNATIVE SEPARATIONMETHOD FOR LARGE DNA FRAGMENTS. IN EACH INSTANCE WHERE THE ASSOCIATION OF A MEMBER OF THE BCR OR ABL GENE FAMILY WITH AMALIGNANCY CAN BE ESTABLISHED, DNA PROBE TESTS WILL BE FORMATTED FOR APPLICATION AS CLINICAL DIAGNOSTIC TESTS.