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Digital and computational morphology in hematology: current platforms, clinical evidence, and future requirements.

INTRODUCTION: Morphologic examination of peripheral blood and bone marrow remains central to the diagnosis and classification of hematologic disorders. Conventional optical microscopy, however, is labor-intensive, dependent on operator expertise, and affected by interobserver variability. Digital morphology has developed from automated image acquisition and cell pre-classification into a broader field that includes whole-slide imaging, remote review, quantitative morphometry, and artificial intelligence-based analysis. CONTENT: This review examines current applications of digital morphology in peripheral blood, bone marrow aspirates, malaria detection, and body-fluid analysis. Commercial platforms are evaluated with particular attention to the distinction between raw automated pre-classification, expert digital post-classification, and comparison with independent optical microscopy. Digital systems generally perform well for common mature leukocyte populations but remain less reliable for rare or diagnostically critical cells, including blasts, abnormal lymphoid cells, plasma cells, and intermediate maturation stages. Research systems increasingly extend analysis from individual-cell classification to whole-slide, specimen-level, and patient-level assessment. SUMMARY: Digital morphology can improve standardization, image traceability, remote consultation, education, proficiency testing, quality assurance, and selected aspects of laboratory workflow. Its clinical value depends on appropriate validation, transparent reporting of reference methods, recognition of algorithm-specific failure modes, and clearly defined criteria for expert review and conventional microscopy. Human expertise remains essential not only for validating results but also for adapting cell taxonomies and interpretive rules to evolving classifications of hematologic diseases. OUTLOOK: Future progress will require representative multicenter datasets, harmonized morphologic terminology, external validation, interoperability with laboratory information systems, and continuous monitoring after software or hardware updates. Integration of morphology with quantitative hematology, flow cytometry, cytogenetics, genomics, and clinical data may support more comprehensive computational diagnosis. Digital platforms may also broaden access to specialist expertise, training, and quality programs in resource-limited institutions and regions, provided that infrastructure, governance, and professional competency are adequately supported.

artificial intelligence

Physical reconfiguration of limb electrodes for Precordial Bipolar Lead acquisition: Morphological validation against digital subtraction.

BACKGROUND: The V2 - V1 Precordial Bipolar Lead (PBL) selectively evaluates the right-to-left retrosternal axis and has shown diagnostic value beyond the standard 12‑lead electrocardiogram. However, its use has been limited by the need for raw electrocardiographic data and post-processing software. This study evaluated whether a simple physical reconfiguration of limb electrodes could reproduce the digitally derived V2 - V1 morphology with sufficient accuracy for clinical application. METHODS: Thirty-seven subjects underwent two sequential 10-s 12‑lead recordings using a Cardiovit FT-1 electrocardiograph sampled at 1000 Hz. In the standard recording, the digital PBL was calculated as V2 - V1. In the second recording, the right-arm and left-arm electrodes were repositioned to the V1 and V2 sites so that Lead I directly recorded the retrosternal dipole. Signals were filtered, synchronized, and analyzed using median beats. Morphological agreement was assessed with Pearson correlation on Z-normalized signals, while absolute agreement was evaluated using Lin's concordance correlation coefficient (CCC), intraclass correlation coefficient (ICC (Lewis, 1931; Nehb, 1938 [1,2])), root mean square error (RMSE), and Bland-Altman analysis. RESULTS: Mean Pearson correlation between digital and physical PBL was 0.955 (SD 0.043), with segment-specific correlations of 0.953 (SD 0.054) for QRS and 0.967 (SD 0.052) for ST-T. Lin's CCC and ICC(2,1) were both 0.871 (SD 0.110), and RMSE was 0.091 (SD 0.049) mV. Bland-Altman analysis showed minimal bias (-0.008 mV). CONCLUSIONS: Physical acquisition of the V2 - V1 PBL achieved high agreement with the digitally derived signal, supporting a simplified analog method for broader clinical implementation.

Humans

AI In Leukemia Diagnostics: Complementing the Pathologist's Role.

Artificial intelligence (AI) is reshaping every stage of leukemia diagnostics, from digital morphology and multiparameter flow cytometry to next-generation sequencing, multi-omics analysis, and emerging computational frontiers such as quantum-inspired feature selection. This review outlines how contemporary AI tools can automate labor-intensive quantitation, flag diagnostically salient patterns, and standardize interpretation, while the pathologist or hematologist retains authority over validation, context-specific integration, and clinical decision-making. We present an illustrative "human-in-the-loop" workflow that embeds AI modules within current laboratory information systems, emphasizing points where expert oversight mitigates algorithmic bias and resolves discordant findings. We further map the validator-integrator role across morphology, flow cytometry, and genomic/multi-omic interpretation and provide practical training competencies and use cases for AI-assisted hematopathology. Beyond technical deployment, the article addresses the educational transformation required for sustainable adoption. Drawing on international competency frameworks, including the Digital Health Competencies in Medical Education Framework and recently proposed AI-specific Entrustable Professional Activities, we map core skills that future hematopathologists must master: data-science literacy, critical appraisal of AI outputs, and ethical governance. We highlight evaluated training models such as the Pathology Informatics Essentials for Residents curriculum, Stanford Artificial Intelligence in Machine and Imaging workshops, and College of American Pathologists bootcamps and propose integration strategies adaptable across resource settings. By pairing rigorous validation with targeted education, AI can elevate rather than eclipse the diagnostic role of the leukemia specialist, enabling more timely, reproducible, and personalized patient care.

Humans

A study of capillary morphology in the digits of patients with acquired clubbing.

We sought to determine the capillary morphology in patients with clubbing to compare it with that in subjects without clubbing. Subjects were placed in the clubbed or nonclubbed groups on the basis of caliper measurements of their index fingers. In each subject, photomicrographs of eight fingers were done focusing on the dorsal skin just proximal to the base of the nail. Each photomicrograph was randomly graded with respect to the presence and extent of plexus formation, the presence of arborized loops, and the presence of splayed loops. Comparison of the plexus score, presence of arborized loops, and presence of splayed loops were significantly different between the clubbed and nonclubbed groups (p less than 0.001 in all three analyses). Only a plexus score of 2 or greater demonstrated a useful degree of sensitivity and specificity (89 and 90%, respectively). We concluded that a significant difference in the morphologic features of the capillaries existed between nonclubbed subjects and those with acquired clubbing.

Adult

Regeneration of digits and forelimbs in the Kenyan reed frog Hyperolius viridiflavus ferniquei.

Newly metamorphosed individuals of the Kenyan reed frog, Hyperolius viridiflavus ferniquei, are able completely to regenerate amputated digits, including the morphologically complex digital pad. The sequence of morphological events is very similar to that seen in the typical epimorphic regeneration of amphibian extremities. Amputated forearms typically produce hypomorphic spike regenerates. Despite the lack of underlying hand and digital structures, an apical "digital" pad commonly differentiates.

Animals

Palmar, plantar, and digital flexion creases: morphologic and clinical considerations.

The above overview illustrates the areas of interest in flexion creases in human biology studies in general and in studies of medical disorders in particular. Clearly, flexion creases have a significance of their own rather than only as appendices of the dermatoglyphic analysis and should, therefore, be approached appropriately. In some instances, they may be of more interest than the dermatoglyphics. Our understanding of the creases and their value is, however, as yet incomplete and the gaps in our insight limit the possible interpretations and practical applications of the knowledge gained from studies of various aspects of the flexion creases. Creases provide important clues of the early fetal development and thus may be of practical value in clinical medicine. So far, most of these studies have been carried out in relation to specific disorders, often without a clear reasoning why flexion creases should be altered in the given disorder. The examples of aberrant flexion creases discussed above illustrate the general lack of specificity of crease anomalies in association with a particular syndrome or disorder that does not include malformations or malfunctions of the limbs. Instead, the anomalous flexion creases reflect the altered shape and function of hand and foot, which, in turn, are determined during early fetal development and affected by factors interfering with normal embryogenesis. A more promising approach to studying flexion creases in medical disorders, therefore, is to explore the developmental correlations between the creases and the structure and function of hands and feet. This does not mean that information gained from the case reports of individuals with various congenital defects is of no value. On the contrary, it should be collected systematically to determine the variety of crease aberrations and their frequencies in a given disorder, which would help elucidate the presence and timing of the developmental factors involved in the origin of the defect. The usefulness and limitations of the flexion creases are to a large degree parallel to those of dermatoglyphics. Altered flexion creases are indicative of intrauterine disturbances occurring early in pregnancy. As such, they may be of a predictive value in otherwise apparently normal infants in whom cryptic damage may be manifested later. They may serve to alert the physician to perform careful or more detailed examinations or to reexamine already obtained (and possibly inaccurate) test results. A better understanding of the crease embryology, both normal and abnormal, is a prerequisite for progress in studies of flexion creases.(ABSTRACT TRUNCATED AT 400 WORDS)

Congenital Abnormalities

Computerized detection of pulmonary nodules in digital chest images: use of morphological filters in reducing false-positive detections.

Currently, radiologists can fail to detect lung nodules in up to 30% of actually positive cases. If a computerized scheme could alert the radiologist to locations of suspected nodules, then potentially the number of missed nodules could be reduced. We are developing such a computerized scheme that involves a difference-image approach and various feature-extraction techniques. In this paper, we describe our use of digital morphological processing in the reduction of computer-identified false-positive detections. A feature-extraction technique, which includes the sequential application of nonlinear filters of erosion and dilation, is employed to reduce the camouflaging effect of ribs and vessels on nodule detection. This additional feature-extraction technique reduced the true-positive rate of the computerized scheme by 13% and the false-positive rate by 50%. In a comparison of the scheme with and without the additional feature-extraction technique, inclusion of the additional technique increased the detection sensitivity by about half at the level of three to four false-positive detections per chest image.

False Positive Reactions

Three-dimensional digitization: method for evaluating morphological differences between teeth.

A new comparative method has been developed for evaluating morphological differences between a pair of teeth. This method consists of five steps: 1) digitization of the surface morphology of the teeth, 2) standardization to enable comparison of the teeth on a common axis, 3) reversal of data on one tooth to enable comparison with the opposite tooth, 4) qualitative evaluation by computer graphic superimposition and 5) quantitative evaluation by the set operation. To illustrate its effectiveness, this method was applied to a pair of extracted premolars. Application to the dental crown on a clinical plaster cast was also discussed.

Bicuspid

Embryological development and prevalence of digital flexion creases.

The embryological development and morphology of digital flexion creases were studied in 178 human embryos and fetuses 6-20 weeks of gestational age. The results suggest the existence of two types of digital flexion creases, that differ from each other in their development. The regular creases, with the exception of the distal crease of the proximal interphalangeal creases, and the oblique and extra creases of the irregular creases, develop concurrently with the appearance of the digital pads by about 11 weeks of gestation. The remaining creases, i.e., the distal crease of the proximal interphalangeal creases and the accessory crease develop later unrelated to the pads but, apparently, secondary to the flexion movements of the hand. Our observations further suggest that, because of their high frequencies, the oblique creases on the ulnar side of digits I and II and on the radial side of digit V and the extra creases on the proximal phalanx of digits I, III, and IV should be considered as "regular" creases. Previously unreported pads were also found on the middle phalanges at about 11 weeks of gestation. Unlike the single, large pads with high elevation, typically found on the distal phalanges, those on the middle phalanges are multiple, small, and only slightly elevated. This observation provides further support to the concept of the relationship between the fetal digital pads and the development of the epidermal ridge patterns.

Fetus

Morphological analysis of abnormal digital chondrogenesis in the brachypod (bpH) mouse limb in organ culture.

Brachypod (bpH/bpH), an autosomal mutation in mice, is characterized by a shortening of the long bones and paws, and a delay or absence of ossification in some of the distal limb elements. The present study represents a detailed description of the brachypod phenotype in day 12 hindlimb buds maintained for 6 days in a submerged, serum-free organ culture system. Using this in vitro system, the proximal-to-distal effect on the severity of cartilage reduction was intensified in the brachypod explants with an intermediate expression in the heterozygotes. Immunofluorescent staining of the brachypod cartilage revealed a deficiency in and an abnormal distribution of the proteoglycans. Although there was no recognizable difference in the immunofluorescent staining for type II collagen between the mutant and wild-type, electron micrographs showed the presence of thick fibrils in the matrix. Other atypical structures in the brachypod cartilage included pleomorphic nuclei, reduced intracellular glycogen granules and profuse intercellular contacts. It is proposed that with the use of this in vitro system which supports the autonomous development of the individual limb elements, experiments concerning the pathogenesis of skeletal mutations such as brachypod should be more feasible.

Animals

Characterization of the morphological properties of welding fume particles by transmission electron microscopy and digital image analysis.

The morphological characteristics of welding fume particles have been determined using transmission electron microscopy (TEM) and automatic image analysis (AIA). Two personal samples and one background sample were collected using a new, easy to handle sampling method, during tungsten inert gas (TIG) and manual metal arc (MMA) welding on Inconel in the same shop. The collection method gave samples which were suitable for TEM and AIA. Electron micrographs were taken in a transmission electron microscope and further analyzed using an image analysis unit. Aggregates composed of many individual particles were analyzed both for the parameters of the aggregate and for the parameters of the individual particles by using an algorithm based on a grain boundary reconstruction technique. The morphological parameters allowed the welding fume's particulate matter to be divided into three types - here called small, medium, and large - with a somewhat unclear distinction between medium and large. Medium and large particles occur either as individual particles or as clusters of approximately spherical particles with average diameters of 0.07 and 0.15 microm, respectively. Small particles occur almost exclusively as long chains or lace-like structures of aggregates of particles, often in the range of 5-10 microm. The aggregates have an average projected area of 2.6 x 10-3 microm2 and are composed of several hundred individual particles.

Air Pollutants

[The value of venous digital angiography in the postoperative follow-up of thromboendarterectomy and aorto-iliac-femoral prosthetic replacement].

Personal experience of 21 patients controlled by venous digital angiography following thrombendarterectomy and aorto-iliac-femoral prosthetic substitution is reported. The technique can be usefully employed because it is not too invasive and gives excellent results, peripheral venous injection usually being sufficient to document vasal recanalisation and prosthetic morphology. Venous digital angiography is therefore the examination of choice in the follow-up of patients submitted to aortofemoral revascularisation operations, a field in which traditional angiography has been little utilised owing to the problems of arterial approach.

Angiography, Digital Subtraction

Determination of three-dimensional morphometry of adherent cells by surface profilometry.

A three-dimensional, non-contacting surface profiler was used to analyse cells that had been previously prepared for scanning electron microscopy. The height of ten attached and spread cells was measured in both two- and three-dimensions (2-D and 3-D). The 2-D scan is a typical, linear profilometer output, while a 3-D image is produced with a 3-D detector. The 3-D contour plots of each cell were then compared with scanning electron microscopy micrographs by digitizing four morphological parameters: perimeter, surface area, long axis and short axis of each cell. A paired Student's t test showed that the two imaging techniques are not equivalent. Non-equivalence was attributed to a difference in the method of calibration. However, when combined with scanning electron microscopy, the profiler allowed complete three-dimensional quantitative analysis of cellular morphology.

Animals

Teratogenicity of 5-azacytidine in the Sprague-Dawley rat.

5-Azacytidine (5-aza), a chemical that is incorporated into DNA and RNA with consequent alterations in the expression of mammalian genes, was administered to pregnant Sprague-Dawley rats on single days during gestation. Doses of 0.5, 1, and 2 mg/kg were given by intraperitoneal injection on d 9, 10, 11, or 12. Dams were killed on d 20 of gestation and fetuses were examined for both external and skeletal defects. 5-Azacytidine affected development on all days tested. The compound was embryolethal, caused reductions in fetal weight, and had profound effects on morphological development. Digit and limb anomalies, exencephaly, micrognathia, gastroschisis, and various rib defects were observed and related to the day of exposure.

Abnormalities, Drug-Induced

Circulatory counter-regulations induced by continuous administration of nitroglycerin.

In a placebo-controlled, double-blind, cross-over study in seven healthy volunteers, continuous transdermal administration of nitroglycerin over 48 h by means of Nitroderm TTS 10 evoked counter-regulations that interfered with the nitrate effects. These counter-regulations comprised an increase in sympathico-adrenal activity, manifested in elevated plasma levels of adrenaline and noradrenaline, and an internal hemodilution, readily perceptible from the decrease in the hematocrit readings. As a result, several of the circulatory effects of nitroglycerin were no longer in evidence, or much weaker on the second day of the study. The effects concerned were the reduction of systolic and diastolic blood pressure, the increase in heart rate, the prolongation of PEPc, and shortening of LVETc, and the change in digital-pulse morphology (increase in the a/b quotient). On the other hand, the increase in venous distensibility and the decrease in hematocrit were unaltered throughout the observation period. The attenuation of the action of nitroglycerin noticeable 24 h after application of the patches is, therefore, not indicative of any loss of effect of the substance per se, but due to the circulatory counter-regulations, which were largely confined to the arterial side of the circulation and scarcely affected the venous system. One or two hours after removal of the patches, counter-regulations had practically ceased.

Administration, Topical

The fate of tendon grafts used to reconstruct the digital annular pulleys.

An experimental morphological study on the reconstruction of the digital annular pulleys has been carried out in dogs. The segment corresponding to zones 1 and 2 of the flexor apparatus of the 2nd and 5th digits of the left forepaw was chosen for the experiment. The whole flexor apparatus was resected and a single digital pulley (A 2) was reconstructed, using segments of the animals own deep flexor tendon. A length of silicone rubber tube was used as tendon spacer. The new pulleys showed marked degeneration of the collagen fibres and thinning which increased with time and may be the cause of decrease in strength. A layer of mesothelial cells with secretory properties developed at the interface between the tendon graft and the spacer.

Animals

Comparison of intravascular ultrasound, external ultrasound and digital angiography for evaluation of peripheral artery dimensions and morphology.

Validation of catheter-based intravascular ultrasound imaging has been based on comparisons with histology and digital angiography, each of which may have limitations in the assessment of arterial size and morphology. External, high-frequency ultrasound can accurately determine vessel dimensions and morphology and because, like ultravascular ultrasound, it also provides cross-sectional arterial ultrasound images, it may be a more appropriate technique for the in vivo comparison of arterial dimensions and morphology determined by intravascular ultrasound. Thus, intravascular ultrasound, external 2-dimensional ultrasound, Doppler color-flow imaging and digital angiography were compared for assessment of arterial dimensions and wall morphology at 29 femoral artery sites in 15 patients. Intravascular ultrasound and the other 3 imaging modalities correlated well in determination of lumen diameter (2-dimensional, r = 0.98, standard error of the estimate [SEE] = 0.14; Doppler color flow, r = 0.91, SEE = 1.11; angiography, r = 0.95, SEE = 0.91) and cross-sectional area (2-dimensional, r = 0.97, SEE = 0.04; Doppler color flow, r = 0.92, SEE = 0.14; angiography, r = 0.96, SEE = 0.08). However, lumen size measured by Doppler color flow was consistently smaller than that measured by the other 3 imaging modalities. Intravascular ultrasound detected arterial plaque at 15 sites, 5 of which were hypoechoic (soft) and 10 hyperechoic with distal shadowing (hard). Plaque was identified at 12 of 15 sites by Z-dimensional imaging (p = 0.30 vs intravascular ultrasound), but at only 6 of 15 sites by angiography (p = 0.003 vs intravascular ultrasound), only 1 of which was thought to be calcified plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Clinical and morphological studies in a case of congenital glaucoma combined with an ocular-dental-digital dysplasia (author's transl)].

Clinical and morphological studies were undertaken to characterize a case of congenital glaucoma combined with an ocular-dental-digital dysplasia in a two year old patient. Light and electromicroscopic investigations of a surgically removed trabecular specimen were carried out. A trabeculotomy had been performed at this exact site 10 months prior to removal. The existence of a canal of Schlemm was demonstrated. The regular trabecular meshwork and trabecular region was replaced by fairly dense scar tissue, containing rudimentary intertrabecular spaces. Proliferating corneal endothelial cells covered the wound area up to the uveal part of the trabecular region. The morphological findings correlated well with the clinical observation of continued raised intraocular pressure despite trabeculotomy. It is concluded that, contrary to the situation in adult onset glaucoma, the strong proliferative tendency of juvenile tissue has a marked influence on the postoperative efficacy of the trabeculotomy.

Child, Preschool