Forensic age estimation in males by MRI based on the medial epiphysis of the clavicle.

Increasing cross-border migration has brought forensic age assessment into focus in recent decades. Forensic age estimation is based on the three pillars: physical and medical constitution, bone age, and tooth age. Part of the bone age examination includes the assessment of the medial end of the clavicles when the hand bones are already fully developed and a minority must be excluded. Recent research has brought MRI to the forefront as a radiation-free alternative for age assessment. However, there exits only a few studies with large sample size regarding the clavicles and with controversies about staging, motion artifacts, and exclusion based on anatomic norm variants. In the current prospective study, 338 central European male individuals between 13 and 24 years of age underwent MRI examination of the sternoclavicular region. Development was assessed by three blinded raters according to the staging system described by Schmeling et al. and Kellinghaus et al. and related to age by descriptive statistics and transition analyses with a cumulative probit model. In addition, reliability calculations were performed. No statistically significant developmental difference was found between the left and right clavicles. Inter-rater agreement was only moderate, but intra-rater agreement, on the other hand, was good. Stage 3c had a minimum age of 19.36 years and appears to be a good indicator of proof of majority. The minimum age of stage 4 was lower compared with other studies, 20.18 years, and therefore seems not to be an indicator of age of 21 years. In conclusion, we confirmed the value of clavicular MRI in the age estimation process. The transition analysis model is a good approach to circumvent the problems of age mimicry and samples that are not fully equilibrated. Given the moderate agreement between raters, a consensus reading is recommended.

Bone age estimation with the Greulich-Pyle atlas using 3T MR images of hand and wrist.

The age estimation of the hand bones by means of X-ray examination is a pillar of the forensic age estimation. Since the associated radiation exposure is controversial, the search for ionizing radiation-free alternatives such as MRI is part of forensic research. The aim of the current study was to use the Greulich-Pyle (GP) atlas on MR images of the hand and wrist to provide reference values for assessing the age of the hand bones. 3T hand MR images of 238 male participants between the ages of 13 and 21 were acquired using 3D gradient echo sequences (VIBE, DESS). Two readers rated the images using the X-ray-based GP atlas method. A descriptive analysis and a transitional analysis were used for the statistical processing of the data. The agreement between and within the raters was assessed. In addition, a comparison was made with the chronological age and with X-ray studies. The descriptive analysis and the transition analysis showed similar results. Both evaluations showed good agreement with X-ray studies. The comparison with the chronological age showed a difference of 0.37 and 0.54 years for the two readers. The age estimate based on the cross-validated transition analysis showed a mean error of -0.28 years. Inter- and intra-rater agreement were good. In summary, it can be concluded that age estimation of hand bones with MR images is routinely applicable with the GP atlas as an alternative without ionizing radiation. However, in order to reduce the estimation error, a multi-factorial assessment based on examinations of several body regions is still recommended.

Dental and Skeletal Imaging in Forensic Age Estimation: Disparities in Current Approaches and the Continuing Search for Optimization.

Medical imaging for forensic age estimation in living adolescents and young adults continues to be controversial and a subject of discussion. Because age estimation based on medical imaging is well studied, it is the current gold standard. However, large disparities exist between the centers conducting age estimation, both between and within countries. This review provides an overview of the most common approaches applied in Europe, with case examples illustrating the differences in imaging modalities, in staging of development, and in statistical processing of the age data. Additionally, the review looks toward the future because several European research groups have intensified studies on age estimation, exploring four strategies for optimization: (1) increasing sample sizes of the reference populations, (2) combining single-site information into multifactorial information, (3) avoiding ionizing radiation, and (4) conducting a fully automated analysis.

The four-minute approach revisited: accelerating MRI-based multi-factorial age estimation.

OBJECTIVES: This feasibility study aimed to investigate the reliability of multi-factorial age estimation based on MR data of the hand, wisdom teeth and the clavicles with reduced acquisition time. METHODS: The raw MR data of 34 volunteers-acquired on a 3T system and using acquisition times (TA) of 3:46 min (hand), 5:29 min (clavicles) and 10:46 min (teeth)-were retrospectively undersampled applying the commercially available CAIPIRINHA technique. Automatic and radiological age estimation methods were applied to the original image data as well as undersampled data to investigate the reliability of age estimates with decreasing acquisition time. Reliability was investigated determining standard deviation (SSD) and mean (MSD) of signed differences, intra-class correlation (ICC) and by performing Bland-Altman analysis. RESULTS: Automatic age estimation generally showed very high reliability (SSD < 0.90 years) even for very short acquisition times (SSD ≈ 0.20 years for a total TA of 4 min). Radiological age estimation provided highly reliable results for images of the hand (ICC ≥ 0.96) and the teeth (ICC ≥ 0.79) for short acquisition times (TA = 16 s for the hand, TA = 2:21 min for the teeth), imaging data of the clavicles allowed for moderate acceleration (TA = 1:25 min, ICC ≥ 0.71). CONCLUSIONS: The results demonstrate that reliable multi-factorial age estimation based on MRI of the hand, wisdom teeth and the clavicles can be performed using images acquired with a total acquisition time of 4 min.

T2 and T2∗ mapping in ex situ porcine myocardium: myocardial intravariability, temporal stability and the effects of complete coronary occlusion.

Diagnosis of ischaemia-related sudden cardiac death in the absence of microscopic and macroscopic ischaemic lesions remains a challenge for medical examiners. Medical imaging techniques increasingly provide support in post-mortem examinations by detecting and documenting internal findings prior to autopsy. Previous studies have characterised MR relaxation times to investigate post-mortem signs of myocardial infarction in forensic cohorts. In this prospective study based on an ex situ porcine heart model, we report fundamental findings related to intramyocardial variability and temporal stability of T2 as well as the effects of permanent coronary occlusion on T2 and T2∗ relaxation in post-mortem myocardium. The ex situ porcine hearts included in this study (n= 19) were examined in two groups (Ss, n= 11 and Si, n= 8). All magnetic resonance imaging (MRI) examinations were performed ex situ, at room temperature and at 3 T. In the Ss group, T2 mapping was performed on slaughterhouse porcine hearts at different post-mortem intervals (PMI) between 7 and 26 h. Regarding the intramyocardial variability, no statistically significant differences in T2 were observed between myocardial segments (p= 0.167). Assessment of temporal stability indicated a weak negative correlation (r=- 0.21) between myocardial T2 and PMI. In the Si group, animals underwent ethanol-induced complete occlusion of the left anterior descending artery. T2 and T2∗ mapping were performed within 3 h of death. Differences between the expected ischaemic and remote regions were statistically significant for T2 (p= 0.007), however not for T2∗ (p= 0.062). Our results provide important information for future assessment of the diagnostic potential of quantitative MRI in the post-mortem detection of early acute myocardial infarction.

Dental age estimation: The chronology of mineralization and eruption of male third molars with 3T MRI.

Forensic age estimation has recently become an important topic due to a steady increase of cross border migration. Dental age assessment is one pillar of the forensic age estimation in living persons. Currently it is done by evaluating an orthopantomogram, which is generated using ionizing radiation. Nevertheless, the use of X-ray without medical indication is ethically questionable. Therefore, the aim of the study was to provide reference values for dental MRI to have an alternative radiation-free method for the assessment of dental age. In this cross-sectional study, 316 adolescent, male individuals were investigated. Two dentists evaluated the stage of mineralization and eruption of the third molars of the upper and lower jaws, according to the staging systems established by Demirjian and Olze. Following data analysis and the creation of reference tables, the likelihood ratios to be over specific age limits were calculated. In the mineralization evaluation mainly stages D-H were seen (range A-H); regarding eruption, all four stages (A-D) appeared. A significant difference between the teeth was only found for eruption stage A. However, the evaluation of participants who had all four third molars, showed partly different stages for the individual teeth as well for mineralization as for the eruption. Therefore, it seems to be important to include all available teeth in the age estimation. The likelihood ratios showed about 99% probability to be 18 years or older for stage H (mineralization), but only about 93% for stage D (eruption). In summary, it can be concluded that dental MRI holds promise as an alternative to conventional orthopantomogram based age assessment.

Reducing acquisition time for MRI-based forensic age estimation.

Radiology-based estimation of a living person's unknown age has recently attracted increasing attention due to large numbers of undocumented immigrants entering Europe. To avoid the application of X-ray-based imaging techniques, magnetic resonance imaging (MRI) has been suggested as an alternative imaging modality. Unfortunately, MRI requires prolonged acquisition times, which potentially represents an additional stressor for young refugees. To eliminate this shortcoming, we investigated the degree of reduction in acquisition time that still led to reliable age estimates. Two radiologists randomly assessed original images and two sets of retrospectively undersampled data of 15 volunteers (N = 45 data sets) applying an established radiological age estimation method to images of the hand and wrist. Additionally, a neural network-based age estimation method analyzed four sets of further undersampled images from the 15 volunteers (N = 105 data sets). Furthermore, we compared retrospectively undersampled and acquired undersampled data for three volunteers. To assess reliability with increasing degree of undersampling, intra-rater and inter-rater agreement were analyzed computing signed differences and intra-class correlation. While our findings have to be confirmed by a larger prospective study, the results from both radiological and automatic age estimation showed that reliable age estimation was still possible for acquisition times of 15 seconds.

Post-mortem MR angiography: quantitative investigation and intravascular retention of perfusates in ex situ porcine hearts.

As the implementation of minimally invasive imaging techniques in both forensic and pathological practice increases, research in this area focuses on addressing recognised diagnostic weaknesses of current approaches. Assessment of sudden cardiac death (SCD) can be considered one such area in which post-mortem imaging still shows diagnostic weaknesses. We hypothesise that magnetic resonance imaging (MRI) with an angiographic adjunct may improve the visualisation and interpretation of cardiac pathologies in a post-mortem setting. To systematically investigate this hypothesis, selected perfusates (paraffin oil, Gadovist®;-doped physiological solution and polyethylene glycol (PEG)) were injected into the left anterior descending (LAD) artery of ex situ porcine hearts to assess the visualisation of perfusates in MRI as well as their intravascular retention over 12 h. Morphological images were acquired and quantitative T1 maps were generated from inversion recovery data. Visualisation of vascular structure and image quality were assessed using signal-to-noise and contrast-to-noise ratios. Intravascular retention was assessed both visually and statistically using a volume of interest (VOI) approach to analyse significant changes in signal intensity in and around the filled LAD artery, as well as changes in the longitudinal relaxation time (T1) in adjacent myocardium. In addition to presenting possible mechanisms explaining perfusate extravasation given the increased permeability of post-mortem vessels, the potential diagnostic consequences of this phenomenon and the importance of contrast stability and extended intravascular retention are discussed. In light of our findings and these considerations, paraffin oil emerged as the preferred perfusate for use in post-mortem MR angiography.

Reproducibility of relaxometry of human lumbar vertebrae at 3 Tesla using 1 H MR spectroscopy.

BACKGROUND: MR spectroscopy is widely used for fat fraction quantification of human lumbar vertebrae. However, the measurements need to be corrected for relaxation effects. PURPOSE: The aim of this study was to determine the reproducibility of relaxometry in human lumbar vertebrae required for the correction of fat fraction measurements using magnetic resonance spectroscopy at 3 Tesla. Such information provides error estimates and guidance regarding reliability for future studies. STUDY TYPE: Prospective. SUBJECTS: Forty-six healthy volunteers (22 female [f], 24 male [m]) participated in this study. FIELD STRENGTH: All subjects underwent three consecutive multi-TE /multi-TR MR spectroscopy measurements at 3 Tesla. ASSESSMENT: A total of 2580 spectra of lumbar vertebrae L2 and L3 of 43 subjects (21f, 22m) were quantified using jMRUI software. Data were exported and mono-exponential fits were applied to the signals of water and fat compartments to derive relaxation times and calculate the fat fraction corrected for relaxation effects. Finally, relaxation times and fat fraction results of repeated measurements were analyzed for reproducibility. STATISTICAL TESTS: Reproducibility was evaluated by calculating the coefficient of variation (CV). Influences of volunteer age and sex were tested by analysis of covariance. RESULTS: The CV for all calculated parameters ranged between 1.22% (T2 of the fat compartment) and 3.02% (T1 of the fat compartment). Relaxation times and fat fraction were statistically different for female and male volunteers (P < 0.01) and relaxation times of the water compartment showed significant (P < 0.01) correlation with the fat fraction. DATA CONCLUSION: Based on repeated acquisitions using the measurement parameters applied in this study, magnetic resonance spectroscopy allowed a reproducible calculation of the fat fraction corrected for relaxation effects. T1 of the water compartment showed high reproducibility and correlation with the fat fraction. It, therefore, might be considered as a parameter linked to the composition of the water compartment and patient health. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.

Forensic age estimation by morphometric analysis of the manubrium from 3D MR images.

Forensic age estimation research based on skeletal structures focuses on patterns of growth and development using different bones. In this work, our aim was to study growth-related evolution of the manubrium in living adolescents and young adults using magnetic resonance imaging (MRI), which is an image acquisition modality that does not involve ionizing radiation. In a first step, individual manubrium and subject features were correlated with age, which confirmed a statistically significant change of manubrium volume (Mvol:p<0.01, R2¯=0.50) and surface area (Msur:p<0.01, R2¯=0.53) for the studied age range. Additionally, shapes of the manubria were for the first time investigated using principal component analysis. The decomposition of the data in principal components allowed to analyse the contribution of each component to total shape variation. With 13 principal components, ∼96% of shape variation could be described (Mshp:p<0.01, R2¯=0.60). Multiple linear regression analysis modelled the relationship between the statistically best correlated variables and age. Models including manubrium shape, volume or surface area divided by the height of the subject (Y∼MshpMsur/Sh:p<0.01, R2¯=0.71; Y∼MshpMvol/Sh:p<0.01, R2¯=0.72) presented a standard error of estimate of two years. In order to estimate the accuracy of these two manubrium-based age estimation models, cross validation experiments predicting age on held-out test sets were performed. Median absolute difference of predicted and known chronological age was 1.18 years for the best performing model (Y∼MshpMsur/Sh:p<0.01, Rp2=0.67). In conclusion, despite limitations in determining legal majority age, manubrium morphometry analysis presented statistically significant results for skeletal age estimation, which indicates that this bone structure may be considered as a new candidate in multi-factorial MRI-based age estimation.

Temperature dependence of viscosity, relaxation times (T1, T2) and simulated contrast for potential perfusates in post-mortem MR angiography (PMMRA).

Developments in post-mortem imaging increasingly focus on addressing recognised diagnostic weaknesses, especially with regard to suspected natural deaths. Post-mortem MR angiography (PMMRA) may offer additional diagnostic information to help address such weaknesses, specifically in the context of sudden cardiac death. Complete filling of the coronary arteries and acceptable contrast with surrounding tissue are essential for a successful approach to PMMRA. In this work, the suitability of different liquids for inclusion in a targeted PMMRA protocol was evaluated. Factors influencing cooling of paraffinum liquidum + Angiofil® (6 %) in cadavers during routine multiphase post-mortem CT angiography were investigated. The temperature dependence of dynamic viscosity (8-20 °C), longitudinal (T1) and transverse (T2) relaxation (1-23 °C) of the proposed liquids was quadratically modelled. The relaxation behaviour of these liquids and MR scan parameters were further investigated by simulation of a radiofrequency (RF)-spoiled gradient echo (GRE) sequence to estimate potentially achievable contrast between liquids and post-mortem tissue at different temperatures across a forensically relevant temperature range. Analysis of the established models and simulations indicated that based on dynamic viscosity (27-33 mPa · s), short T1 relaxation times (155-207 ms) and a minimal temperature dependence over the investigated range of these parameters, paraffin oil and a solution of paraffin oil + Angiofil® (6 %) would be most suitable for post-mortem reperfusion and examination in MRI.

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.

Quantitative MR imaging in fracture dating--Initial results.

For exact age determinations of bone fractures in a forensic context (e.g. in cases of child abuse) improved knowledge of the time course of the healing process and use of non-invasive modern imaging technology is of high importance. To date, fracture dating is based on radiographic methods by determining the callus status and thereby relying on an expert's experience. As a novel approach, this study aims to investigate the applicability of magnetic resonance imaging (MRI) for bone fracture dating by systematically investigating time-resolved changes in quantitative MR characteristics after a fracture event. Prior to investigating fracture healing in children, adults were examined for this study in order to test the methodology for this application. Altogether, 31 MR examinations in 17 subjects (♀: 11 ♂: 6; median age 34 ± 15 y, scanned 1-5 times over a period of up to 200 days after the fracture event) were performed on a clinical 3T MR scanner (TimTrio, Siemens AG, Germany). All subjects were treated conservatively for a fracture in either a long bone or in the collar bone. Both, qualitative and quantitative MR measurements were performed in all subjects. MR sequences for a quantitative measurement of relaxation times T1 and T2 in the fracture gap and musculature were applied. Maps of quantitative MR parameters T1, T2, and magnetisation transfer ratio (MTR) were calculated and evaluated by investigating changes over time in the fractured area by defined ROIs. Additionally, muscle areas were examined as reference regions to validate this approach. Quantitative evaluation of 23 MR data sets (12 test subjects, ♀: 7 ♂: 5) showed an initial peak in T1 values in the fractured area (T1=1895 ± 607 ms), which decreased over time to a value of 1094 ± 182 ms (200 days after the fracture event). T2 values also peaked for early-stage fractures (T2=115 ± 80 ms) and decreased to 73 ± 33 ms within 21 days after the fracture event. After that time point, no significant changes could be detected for T2. MTR remained constant at 35.5 ± 8.0% over time. The study shows that the quantitative assessment of T1 and T2 behaviour over time in the fractured region enable the generation of a novel model allowing for an objective age determination of a fracture.

Dental age estimation of living persons: Comparison of MRI with OPG.

The need for forensic age estimations in living adolescents is high mainly due to migration, particularly from countries where birth dates are not reliably documented. To date, the gold standard of dental age estimation is the evaluation of the mineralization and eruption stages of the third molars using an orthopantomogram (OPG). However, the use of ionizing radiation without medical indication is ethically controversial and not permitted in many countries. Thus, the aim of this study was to investigate if dental MRI can be used for the assessment of dental age with equally good results as when using an OPG. 27 healthy volunteers (19 ♀, 8 ♂, age range 13.6-23.1 years, median 18.9 years) underwent an MRI scan of the jaw after a clinically indicated OPG. Mineralization and eruption stages of the molars were independently analyzed on OPGs and MRI by two blinded dentists according to the staging system established by Demirjian and Olze, respectively. The results of OPG and MRI were compared and inter-rater agreement was determined. The developmental stages of the 262 evaluated molars could be clearly differentiated in MRI. For both, mineralization and eruption, there was a good correlation between MRI and OPG. Overall MRI tended to yield slightly lower stages than the OPG. Inter-rater agreement was moderate for mineralization and good regarding eruption. Although a validation of these results using modality-specific reference values is needed, dental MRI seems to be suitable for a use in dental age estimation.

Contrast of artificial subcutaneous hematomas in MRI over time.

In clinical forensic medicine, hematomas and other externally visible injuries build the basis for the reconstruction of events. However, dating of subcutaneous hematomas based on their external aspect is difficult. Magnetic resonance imaging (MRI) has proven its use in dating intracranial hemorrhage. Thus, the aim was to investigate if MRI can also be used for dating subcutaneous hematomas and to analyze an eventual influence of the hematoma shape. In 20 healthy volunteers (11 females, 9 males, aged 26.9 ± 3.8 years), 4 ml of autologous blood were injected subcutaneously in the thigh. The hematoma was scanned immediately after the injection, after 3 and 24 h and 3, 7, and 14 days using three sequences with different contrast. Data was analyzed by measuring signal intensities of the hematoma, the muscle, and the subcutaneous tissue over time, and the Michelson contrast coefficients between the tissues were calculated. In the analysis, hematoma shape was considered. Signal intensity of blood in the proton density-weighted sequence reached its maximum 3 h after the injection with a subsequent decrease, whereas the signal intensities of muscle and fatty tissue remained constant. The time course of the Michelson coefficient of blood versus muscle decreased exponentially with a change from hyperintensity to hypointensity at 116.9 h, depending on hematoma shape. In the other sequences, either variability was large or contrast coefficients stayed constant over time. The observed change of contrast of blood versus muscle permits a quick estimate of a hematoma's age. The consideration of the hematoma shape is expected to further enhance dating using MRI.

Age determination of soft tissue hematomas.

In clinical forensic medicine, the estimation of the age of injuries such as externally visible subcutaneous hematomas is important for the reconstruction of violent events, particularly to include or exclude potential suspects. Since the estimation of the time of origin based on external inspection is unreliable, the aim of this study was to use contrast in MRI to develop an easy-to-use model for hematoma age estimation. In a longitudinal study, artificially created subcutaneous hematomas were repetitively imaged using MRI over a period of two weeks. The hemorrhages were created by injecting autologous blood into the subcutaneous tissue of the thigh in 20 healthy volunteers. For MRI, standard commercially available sequences, namely proton-density-weighted, T2 -weighted and inversion recovery sequences, were used. The hematomas' MRI data were analyzed regarding their contrast behavior using the most suitable sequences to derive a model allowing an objective estimation of the age of soft tissue hematomas. The Michelson contrast between hematoma and muscle in the proton-density-weighted sequence showed an exponentially decreasing behavior with a dynamic range of 0.6 and a maximum standard deviation of 0.1. The contrast of the inversion recovery sequences showed increasing characteristics and was hypointense for TI = 200ms and hyperintense for TI =1000ms. These sequences were used to create a contrast model. The cross-validation of the model finally yielded limits of agreement for hematoma age determination (corresponding to ±1.96 SD) of ±38.7h during the first three days and ±54 h for the entire investigation period. The developed model provides lookup tables which allow for the estimation of a hematoma's age given a single contrast measurement applicable by a radiologist or a forensic physician. This is a first step towards an accurate and objective dating method for subcutaneous hematomas, which will be particularly useful in child abuse.