The uncovered biases and errors in clinical determination of bone age by using deep learning models.

OBJECTIVES: To evaluate AI biases and errors in estimating bone age (BA) by comparing AI and radiologists' clinical determinations of BA. METHODS: We established three deep learning models from a Chinese private dataset (CHNm), an American public dataset (USAm), and a joint dataset combining the above two datasets (JOIm). The test data CHNt (n = 1246) were labeled by ten senior pediatric radiologists. The effects of data site differences, interpretation bias, and interobserver variability on BA assessment were evaluated. The differences between the AI models' and radiologists' clinical determinations of BA (normal, advanced, and delayed BA groups by using the Brush data) were evaluated by the chi-square test and Kappa values. The heatmaps of CHNm-CHNt were generated by using Grad-CAM. RESULTS: We obtained an MAD value of 0.42 years on CHNm-CHNt; this result indicated an appropriate accuracy for the whole group but did not indicate an accurate estimation of individual BA because with a kappa value of 0.714, the agreement between AI and human clinical determinations of BA was significantly different. The features of the heatmaps were not fully consistent with the human vision on the X-ray films. Variable performance in BA estimation by different AI models and the disagreement between AI and radiologists' clinical determinations of BA may be caused by data biases, including patients' sex and age, institutions, and radiologists. CONCLUSIONS: The deep learning models outperform external validation in predicting BA on both internal and joint datasets. However, the biases and errors in the models' clinical determinations of child development should be carefully considered. KEY POINTS: • With a kappa value of 0.714, clinical determinations of bone age by using AI did not accord well with clinical determinations by radiologists. • Several biases, including patients' sex and age, institutions, and radiologists, may cause variable performance by AI bone age models and disagreement between AI and radiologists' clinical determinations of bone age. • AI heatmaps of bone age were not fully consistent with human vision on X-ray films.

Applicability of Magnetic Resonance Imaging for Bone Age Estimation in the Context of Medical Issues. / Einsatz der MRT zur Knochenalterbestimmung im Rahmen medizinischer Fragestellungen.

OBJECTIVE: The determination of bone age is a method for analyzing biological age and structural maturity. Bone age estimation is predominantly used in the context of medical issues, for example in endocrine diseases or growth disturbance. As a rule, conventional X-ray images of the left wrist and hand are used for this purpose. The aim of the present study is to investigate the extent to which MRI can be used as a radiation-free alternative for bone age assessment. METHODS: In 50 patients, 19 females and 31 males, in addition to conventional left wrist and hand radiographs, MRI was performed with T1-VIBE (n = 50) and T1-TSE (n = 34). The average age was 11.87 years (5.08 to 17.50 years). Bone age assessment was performed by two experienced investigators blinded for chronological age according to the most widely used standard of Greulich and Pyle. This method relies on a subjective comparison of hand radiographs with gender-specific reference images from Caucasian children and adolescents. In addition to interobserver and intraobserver variability, the correlation between conventional radiographs and MRI was determined using the Pearson correlation coefficient. RESULTS: Between the bone age determined from the MRI data and the results of the conventional X-ray images, a very good correlation was found for both T1-VIBE with r = 0.986 and T1-TSE with r = 0.982. Gender differences did not arise. The match for the interobserver variability was very good: r = 0.985 (CR), 0.966 (T1-VIBE) and 0.971 (T1-TSE) as well as the match for the intraobserver variability for investigator A (CR = 0.994, T1-VIBE = 0.995, T1-TSE = 0.998) and for investigator B (CR = 0.994, T1-VIBE = 0.993, T1-TSE = 0.994). CONCLUSION: The present study shows that MRI of the left wrist and hand can be used as a possible radiation-free alternative to conventional X-ray imaging for bone age estimation in the context of medical issues. KEY POINTS: · MRI and X-ray show a very good correlation for bone age determination in medical issues.. · With short examination times, T1 VIBE shows slight advantages over T1 TSE.. · Both investigators show high intra- and interobserver variability.. CITATION FORMAT: · Diete V, Wabitsch M, Denzer C et al. Applicability of Magnetic Resonance Imaging for Bone Age Estimation in the Context of Medical Issues. Fortschr Röntgenstr 2021; 193: 692 - 700.

Sagittal suture maturation: Morphological reorganization, relation to aging, and reliability as an age-at-death indicator.

OBJECTIVES: The sagittal suture (SS) is assumed to be an initial site for the commencement of cranial suture closure as well as the most frequent spot of isolated craniosynostosis. The present study aimed to inspect the reorganization of the SS at the microlevel to assess the relation between its closure and aging and to establish whether it could be used as a reliable indicator in age-at-death prediction. MATERIALS AND METHODS: The SS was investigated in 68 dry contemporary adult male skulls of known age-at-death. An additional series of 20 skulls was used for verification. The skulls were scanned using a micro-computed tomography system. The SS closure degree was assessed along the three bone layers on cross-sectional tomograms by using a scoring scale. RESULTS: In the entirely open SS, the bone edges consist of compact bone and are widely separated. With SS maturation, the bone edges come into contact, and the remodeling process leads to a decrease in the sutural area and bone homogenization across all three layers. SS closure is an irregular process roughly related to aging, beginning in the early 20s, reaching its peak at about 30 years of age and abating in the late 40s. DISCUSSION: Although related to aging, SS closure is not a simple function of it. Rather, the underlying factors inducing and managing this process are multifaceted and complex. Although the etiology of SS maturation remains unclear, it is reasonable to use SS closure cautiously and only as a supportive method for age prediction.

Age estimation accuracies from black South African os coxae.

The accurate estimation of age is considered important from an ethical, legal and archaeological perspective. Among the numerous methods based on macroscopic skeletal studies for age estimation, the Brooks and Suchey (1990) method for aging from the pubic symphysis and the Buckberry and Chamberlain (2002) method for aging from the auricular surface are considered more reliable. However, both these methods have been derived from American populations. Therefore, the following study aimed to assess the accuracy of the estimation of age-at-death from morphological age related changes seen on the pubic symphysis and the auricular surface in a black South African population. A total of 197 individuals of known age of both sexes using both left and right ossa coxae were investigated. Age was estimated using descriptions stipulated by Brooks and Suchey (1990) and Buckberry and Chamberlain (2002). Correlation coefficients, inaccuracies and bias were calculated for both skeletal elements for both sexes and sides. Inaccuracies and bias were lower in the pubic symphysis than in the auricular surface thus making the pubic symphysis a more reliable age estimator. Similarly, males indicated lower inaccuracies and bias than did females. Overall, the pubic symphysis outperformed the auricular surface, even though the method described by Buckberry and Chamberlain (2002) is considered more reliable. It is advised that these two methods be improved to produce better accuracies, particularly when applying the methods to a black South African population.

Early Maturity as the New Normal: A Century-long Study of Bone Age.

BACKGROUND: Epiphyseal fusion (EF) marks the completion of longitudinal bone growth, a critical milestone monitored during treatment of skeletal growth and/or developmental disorders. Recently, a trend toward accelerated skeletal maturation in children has been documented. Because current methods for assessing skeletal maturation include children in their reference populations born as early as the 1930s, the timing of EF events in contemporary patients may differ substantially from those standards. QUESTIONS/PURPOSES: (1) Do children today initiate the process of EF in the hand and wrist earlier than past generations on which maturity standards are based? (2) Do children today complete EF in the hand and wrist earlier than past generations on which maturity standards are based? METHODS: A total of 1292 children (665 males, 627 females) participating in the Fels Longitudinal Study, born between 1915 and 2006, were included in this retrospective, observational study. Each participant had between one and 39 serial left hand-wrist radiographs during childhood obtained specifically for research purposes. Main outcomes were the chronological age at the first sign of EF initiation (EF-I) and the first chronological age when EF was complete (EF-C) in the radius and ulna, and metacarpals and phalanges of the first, third, and fifth rays according to criteria of the Fels method. EF is a reliable metric with an average κ agreement statistic of 0.91. Penalized B-splines were used to model the changes in EF-I and EF-C ages and to identify changes across continuous birth years with major comparisons between children born in 1935 and 1995. RESULTS: Approximately half of the epiphyses of the hand and wrist examined exhibited earlier EF-I and/or earlier EF-C in children born in 1995 compared with those born in 1935. The age at each milestone (EF-I and EF-C) decreased by as much as 6.7 and 6.8 months in males and 9.8 and 9.7 months in females, respectively. This change occurred gradually over the past century. The more proximal traits (EF of the distal radius, distal ulna, and metacarpals) were more likely to experience a shift in timing, whereas timing of EF in the phalanges remained relatively stable across birth years. CONCLUSIONS: A trend has occurred over the past century in the timing of EF, in both initiation and completion of the process, for many of the bones of the hand and wrist. Earlier EF reflects modern population advances in both skeletal and sexual maturation. Shifts in the timing of EF have the potential to influence treatment strategies for skeletal growth and/or developmental disorders such as scoliosis or leg length inequality, moving treatment windows to earlier ages. Earlier EF-I and EF-C identified in this study signals a need to reevaluate the timing of maturational milestones and current standards for skeletal assessment. LEVEL OF EVIDENCE: Level II, prognostic study.

Testing inter-observer reliability of the Transition Analysis aging method on the William M. Bass forensic skeletal collection.

OBJECTIVES: Skeletal age estimation is an integral part of the biological profile. Recent work shows how multiple-trait approaches better capture senescence as it occurs at different rates among individuals. Furthermore, a Bayesian statistical framework of analysis provides more useful age estimates. The component-scoring method of Transition Analysis (TA) may resolve many of the functional and statistical limitations of traditional phase-aging methods and is applicable to both paleodemography and forensic casework. The present study contributes to TA-research by validating TA for multiple, differently experienced observers using a collection of modern forensic skeletal cases. MATERIALS AND METHODS: Five researchers independently applied TA to a random sample of 58 documented individuals from the William M. Bass Forensic Skeletal Collection, for whom knowledge of chronological age was withheld. Resulting scores were input into the ADBOU software and maximum likelihood estimates (MLEs) and 95% confidence intervals (CIs) were produced using the forensic prior. Krippendorff's alpha was used to evaluate interrater reliability and agreement. Inaccuracy and bias were measured to gauge the magnitude and direction of difference between estimated ages and chronological ages among the five observers. RESULTS: The majority of traits had moderate to excellent agreement among observers (≥0.6). The superior surface morphology had the least congruence (0.4), while the ventral symphyseal margin had the most (0.9) among scores. Inaccuracy was the lowest for individuals younger than 30 and the greatest for individuals over 60. Consistent over-estimation of individuals younger than 30 and under-estimation of individuals over 40 years old occurred. Individuals in their 30s showed a mixed pattern of under- and over-estimation among observers. DISCUSSION: These results support the use of the TA method by researchers of varying experience levels. Further, they validate its use on forensic cases, given the low error overall.

Validation of a standard forensic anthropology examination protocol by measurement of applicability and reliability on exhumed and archive samples of known biological attribution.

Forensic anthropology makes an important contribution to human identification and assessment of the causes and mechanisms of death and body disposal in criminal and civil investigations, including those related to atrocity, disaster and trafficking victim identification. The methods used are comparative, relying on assignment of questioned material to categories observed in standard reference material of known attribution. Reference collections typically originate in Europe and North America, and are not necessarily representative of contemporary global populations. Methods based on them must be validated when applied to novel populations. This study describes the validation of a standardized forensic anthropology examination protocol by application to two contemporary Brazilian skeletal samples of known attribution. One sample (n=90) was collected from exhumations following 7-35 years of burial and the second (n=30) was collected following successful investigations following routine case work. The study presents measurement of (1) the applicability of each of the methods: used and (2) the reliability with which the biographic parameters were assigned in each case. The results are discussed with reference to published assessments of methodological reliability regarding sex, age and-in particular-ancestry estimation.

Assessment of Reliability of Greulich and Pyle (GP) Method for Determination of Age of Children at Debre Markos Referral Hospital, East Gojjam Zone.

BACKGROUND: Greulich and Pyle standards are the most widely used age estimation standards all over the world. The applicability of the Greulich and Pyle standards to populations which differ from their reference population is often questioned. This study aimed to assess the reliability of Greulich and Pyle (GP) method for determination of age of children at Debre Markos Referral Hospital, East Gojjam Zone, Ethiopia. SUBJECTS AND METHODS: Hospital based cross sectional study design was applied to children who came to Debre Markos Referral Hospital from May to October 2015 and fulfilled the inclusion criteria of the study. The data was analyzed using SPSS version 20 and medcalc version 15 softwares. Significance was set at α = 0.05. RESULTS: A total of 108 radiographs were analyzed. Chronological age in most of the children was under estimated. The mean under-estimation was 11.8 months in the female sample and 8.7 months in the male sample. Greulich and Pyle method became inapplicable for the sample at 16 years for females and 16.5 years for males and later. Delay in skeletal maturation was observed in both sexes, but the females in the sample matured earlier than the males. CONCLUSION: The findings of this study suggest against the applicability of GP atlas which were not directly applicable to an East Gojjam Zone population. Large scale studies should be planned and nationwide guideline, and atlas which can easily be used throughout the country should be developed.

Ossification of the Medial Clavicular Epiphysis on Chest Radiographs: Utility and Diagnostic Accuracy in Identifying Korean Adolescents and Young Adults under the Age of Majority.

The aim of our study was to evaluate the utility and diagnostic accuracy of the ossification grade of medial clavicular epiphysis on chest radiographs for identifying Korean adolescents and young adults under the age of majority. Overall, 1,151 patients (age, 16-30) without any systemic disease and who underwent chest radiography were included for ossification grading. Two radiologists independently classified the ossification of the medial clavicular epiphysis from chest radiographs into five grades. The age distribution and inter-observer agreement on the ossification grade were assessed. The diagnostic accuracy of the averaged ossification grades for determining whether the patient is under the age of majority was analyzed by using receiver operating characteristic (ROC) curves. Two separate inexperienced radiologists assessed the ossification grade in a subgroup of the patients after reviewing the detailed descriptions and image atlases developed for ossification grading. The median value of the ossification grades increased with increasing age (from 16 to 30 years), and the trend was best fitted by a quadratic function (R-square, 0.978). The inter-observer agreements on the ossification grade were 0.420 (right) and 0.404 (left). The area under the ROC curve (AUC) was 0.922 (95% CI, 0.902-0.942). The averaged ossification scores of 2.62 and 4.37 provided 95% specificity for a person < 19 years of age and a person ≥ 19 years of age, respectively. A preliminary assessment by inexperienced radiologists resulted in an AUC of 0.860 (95% CI, 0.740-0.981). The age of majority in Korean adolescents and young adults can be estimated using chest radiographs.

Applicability of Greulich-Pyle and Tanner-Whitehouse grading methods to MRI when assessing hand bone age in forensic age estimation: A pilot study.

Determination of skeletal development is a key pillar in forensic age estimation of living persons. Radiological assessment of hand bone age is widely used until the age of about 17-18 years, applying visual grading techniques to hand radiographs. This study investigated whether Greulich-Pyle (GP) and Tanner-Whitehouse (TW2) grading can be equally used for magnetic resonance imaging (MRI) data, which would offer the huge benefit of avoiding ionizing radiation. In 18 subjects aged between 7 and 17 years a radiograph and an MRI scan of the hand were performed. Epiphyseal ossification of hand bones was rated by two blinded radiologists with both GP and TW2. Correlation between hand MRIs and radiographs was analyzed by linear regression and inter-observer agreement was assessed. Correlation between age estimates from MRI and radiographs was high for both GP (r(2)=0.98) and TW2 (r(2)=0.93). MRI showed a tendency to estimate age slightly lower for 14-18 year-olds, which would be favorable regarding majority age determination in case this result could be reproduced using a currently not existing reference estimation method based on MRI data. Inter-observer agreement was similar for GP in radiographs and MRI, while for TW2, agreement in MRI was lower than in radiographs. In spite of limitations regarding sample size and recruited subjects, our results indicate that the use of GP and TW2 on MRI data offers the possibility of hand bone age estimation without the need for ionizing radiation.

Forensic Age Estimation.

BACKGROUND: Forensic age estimation is requested by courts and other government authorities so that immigrants whose real age is unknown should not suffer unfair disadvantages because of their supposed age, and so that all legal procedures to which an individual's age is relevant can be properly followed. 157 age estimations were requested in Berlin in 2014, more than twice as many as in 2004. METHODS: This review is based on pertinent articles retrieved by a selective search in the PubMed and MEDPILOT databases, supplemented by relevant recommendations and by the findings of the authors' own research. RESULTS: The essential components of age estimation are the history, physical examination, X-rays of the hands, panorama films of the jaws, and, if indicated, a thin-slice CT of the medial clavicular epiphyses, provided that there is a legal basis for X-ray examinations without a medical indication. Multiple methods are always used in combination, for optimal accuracy. Depending on the legal issues at hand, the examiner may be asked to estimate the individual's minimum age and/or his or her most probable age. The minimum-age concept can be used in determinations whether an individual has reached the age of legal majority. It is designed to ensure that practically all persons classified as adults have, in fact, attained legal majority, even though some other persons will be incorrectly classified as minors. CONCLUSION: Forensic age estimation lets courts and other government authorities determine the official age of persons whose actual age is unknown-in most cases, unaccompanied refugees who may be minors. The goal is to carry out age-dependent legal procedures appropriately in accordance with the rule of law. The minimum-age concept is designed to prevent the erroneous classification of minors as legal adults.

The reliability of clinical decisions based on the cervical vertebrae maturation staging method.

OBJECTIVES: Of the various techniques used to determine the optimum timing for growth modification treatments, the cervical vertebrae maturation method has great advantages, including validity and no need for extra X-ray exposure. Recently, the reproducibility of this method has been questioned. The aim of this study was to investigate the cause of poor reproducibility of this method and to assess the reproducibility of the clinical decisions made based on it. MATERIALS/METHODS: Seventy lateral cephalograms of Iranian patients aged 9‒15 years were observed twice by five experienced orthodontists. In addition to determining the developmental stage, each single parameter involved in this method was assessed in terms of inter- and intra-observer reproducibility. In order to evaluate the reproducibility of clinical decisions based on this method, cervical vertebrae maturation staging (CVMS) I and II were considered as phase 1 and CVMS IV and V were considered as phase 3. RESULTS: By considering the clinical approach of the CVMS method, inter-observer reproducibility of this method increased from 0.48 to 0.61 (moderate to substantial) and intra-observer reproducibility enhanced from 0.72 to 0.74. LIMITATIONS: 1. Complete visualization of the first four cervical vertebrae was an inclusion criterion, which also limits the clinical application of CVMS method. 2. These results can be generalized when determining growth modification treatments solely for Class II patients. CONCLUSIONS: Difficulty in determining the morphology of C3 and C4 leads to poor reproducibility of the CVMS method. Despite this, it has acceptable reproducibility in determining the timing of functional treatment for Class II patients.