54475777
Morphometric study of the primary ossification center of the fibular shaft in the human fetus
PurposesPrecise morphometric data on the development of ossification centers in human fetuses may be useful in the early detection of skeletal dysplasias associated with delayed ossification center development and mineralization. The present study was performed to quantitatively examine the primary ossification center of the fibular shaft with respect to its linear, planar and volumetric parameters.Materials and methodsUsing methods of CT, digital-image analysis (Osirix 3.9 MD) and statistics (Student’s t-test, Shapiro–Wilk, Fisher’s test, Tukey’s test, Kruskal–Wallis test, regression analysis), the size of the primary ossification center of the fibular shaft in 47 spontaneously aborted human fetuses (25 ♂ and 22 ♀) aged 17–30 weeks was studied. In each fetus, the assessment of linear dimensions (length, transverse diameters for: proximal end, middle part and distal end), projection surface area and volume of the fibular shaft ossification center was carried out.ResultsWith no sex and laterality differences, the best fit growth dynamics for the primary ossification center of the fibular shaft was modelled by the following functions: y = − 13.241 + 1.567 × age ± 1.556 (R2 = 0.94) for its length, y = − 0.091 + 0.063 × age ± 0.073 (R2 = 0.92) for its proximal transverse diameter, y = − 1.201 + 0.717 × ln(age) ± 0.054 (R2 = 0.83) for its middle transverse diameter, y = − 2.956 + 1.532 × ln(age) ± 0.090 (R2 = 0.89) for its distal transverse diameter, y = − 69.038 + 4.699 × age ± 4.055 (R2 = 0.95) for its projection surface area, and y = − 126.374 + 9.462 × age ± 8.845 (R2 = 0.94) for its volume.ConclusionsThe ossification center in the fibular shaft follows linear functions with respect to its length, proximal transverse diameter, projection surface area and volume, and natural logarithmic functions with respect to its middle and distal transverse diameters. The obtained morphometric data of the fibular shaft ossification center is considered normative for their respective prenatal weeks and may be of relevance in both the estimation of fetal age and the ultrasound diagnostics of congenital defects.
15181132
Length Measurement Of Fetal Long Bone And Fetal Anomaly Detection
Fetal long bone estimation is a pivotal estimation for abnormal fetus development and fetus weight. Moreover, estimation of limb length becomes an important indicator for osteochondrodysplasia and chromosomal abnormalities. Especially, femur length is the most commonly estimated limb length that must be measured to monitor fetal malformation. In fetal length measurement, femur length measurement is the only long bone that is commonly estimated in fetus. Femur length not only helps estimating accurate gestational age, but also becomes an invaluable hint of abnormality in fetal skeletal system. Despite difficulty of accurate diagnosis, detection rate of fatal skeletal abnormality with ultrasonography is as high as 94-96%. Although prenatal ultrasonography plays the most important role in detecting skeletal abnormality, the authors believe that genetics test at molecular level should be employed at needs to confirm chromosomal mutation and help improving accuracy of prenatal diagnosis.
43677727
Charts of fetal size: limb bones
Objective To construct new size charts for all fetal limb bones.
12733344
Ultrasound measurement of fetal limb bones.
A study was made of 41 patients with known menstrual dates in whom the duration of gestation, as determined by physical examination and ultrasound scan, corresponded with those dates. Examination of the fetal limb lengths was done every 1 to 3 weeks, starting at 8 weeks' gestation. A Kretz Combison 100 ultrasound sector scanner with a 2.5 MHz transducer (velocity = 1,540 meters per second) was used. A freeze frame was used when the full bone length was visualized, and then electronic calipers were employed to measure its full length. Serial measurements of the humerus and femur and the radius-ulna and tibia-fibula complexes were made. The values were expressed as means +/- 2 standard deviations for each week of gestation. The growth of the fetal limb bones was linear from 12 through 22 weeks' gestation, but the various bones appeared to grow at different rates. The femur was the first to be well defined and the easiest to measure with reproducibility. All of the limb bone lengths correlate with gestational age and may serve as indicators of skeletal dysplasia. A patient who was delivered of an infant affected with diastrophic dwarfism syndrome was diagnosed at 16 weeks' gestation to have a fetus affected with this problem. Two other patients whose pregnancies were at risk for skeletal dysplasias were correctly diagnosed to be normal.
36458973
High‐resolution sonographic assessment of the fetal extremities.
Recent advances in ultrasound technology, especially phased‐array sonography, now permit striking visualization of fetal morphology. Although several reports document the sonographic appearance of the fetal appendicular skeleton, no reports describe the nonosseous structures of the fetal limbs. Prior to the middle of the second trimester of pregnancy, adequate size and intrinsic subject contrast enable distinction among numerous limb structures. The sonographic features of the fetal limbs are described, with emphasis upon the visible nonosseous structures. All images were obtained between August 1983 and January 1984 using a 128‐channel phased‐array real‐time scanner (Acuson) with a 3.5‐MHz transducer.
39257429
Ultrasonographic and radiologic visualization of the developing embryonic skeleton
We investigated the development of the skeleton in the embryonic and early fetal period both with ultrasonography and radiology. Eight normal embryos/fetuses were studied weekly with real‐time transvaginal sonography between 8 and 16 weeks of gestation to establish the ultrasonographic characteristics of normal ossification. Additionally, ossification was studied in radiographs obtained from five embryos/fetuses between 9 and 14 weeks of gestation.
567811
Fetal biometry of skeletal dysplasias: a multicentric study.
Twenty‐three diagnostic centers worldwide contributed 127 cases of 17 skeletal dysplasias. Discriminant analysis showed that the femur length was the best biometric parameter to distinguish among the five most common disorders in this series (thanatophoric dysplasia, osteogenesis imperfecta type II, achondrogenesis, achondroplasia and hypochondroplasia). Fifty‐four percent of fetuses with femur length below 30% of the mean for gestational age had achondrogenesis. Seventy‐eight percent of measurements between 40 and 60% of the mean for gestational age represented either thanatophoric dysplasia or osteogenesis imperfecta type II. Fetuses who had over 80% of the mean for gestational age had predominantly hypochondroplasia, achondroplasia, and osteogenesis imperfecta type III.
4034429
Quantitative anatomy of the primary ossification center of the femoral shaft in human fetuses
PurposeEarly clinical distinction of congenital defects in the femur is extremely important, as it determines the prognosis of the development of the lower limb. This study was performed to quantitatively examine the primary center of ossification in the femoral shaft with respect to its linear, planar, and volumetric parameters.Materials and methodsUsing methods of CT, digital-image analysis, and statistics, the size of the primary ossification center of the femoral shaft in 47 spontaneously aborted human fetuses aged 17–30 weeks was studied.ResultsWith no sex and laterality differences, the best fit growth dynamics for femoral shaft ossification center was modelled by the following functions: y = 5.717 + 0.040 × (age)2 ± 2.905 (R2 = 0.86) for its length, y = −3.579 + 0.368 × age ± 0.529 (R2 = 0.88) for its proximal transverse diameter, y = −1.105 + 0.187 × age ± 0.309 (R2 = 0.84) for its middle transverse diameter, y = −2.321 + 0.323 × age ± 0.558 (R2 = 0.83) for its distal transverse diameter, y = −50.306 + 0.308 × (age)2 ± 18.289 (R2 = 0.90) for its projection surface area, and y = −91.458 + 0.390 × (age)3 ± 92.146 (R2 = 0.88) for its volume.ConclusionsThe size of the femoral shaft ossification center displays neither sex nor laterality differences. The ossification center in the femoral shaft follows quadratic functions with respect to its length and projection surface area, linear functions with respect to its proximal, middle, and distal transverse diameters, and a cubic function with respect to its volume. The obtained morphometric data of the femoral shaft ossification center are considered normative for respective prenatal weeks and may be of relevance in both the estimation of fetal ages and the ultrasound diagnostics of congenital defects.
24608614
The fetal skeleton; ultrasonographic evaluation of the normal growth.
A longitudinal study of normal fetal growth is presented as a basis for prenatal diagnosis of skeletal dysplasias. The lengths of fetal limb bones, abdominal circumference, thoracic circumference, head circumference, foot length and orbital diameters were measured in 63 normal fetuses between 12 and 40 weeks of gestation. From these data, ratios were calculated which may have relevance for the prenatal diagnosis of skeletal dysplasias. In addition, rates were calculated for fetal limb growth. From these parameters (absolute measurements, ratios and growth rates), the 10th, 50th and 90th centiles were determined as reference values.
30270769
Prenatal diagnosis of femur–fibula–ulna complex by ultrasound examination at 20 weeks of gestation
We describe the prenatal sonographic diagnosis of femur–fibula–ulna complex at 20 weeks of gestation. On targeted ultrasound examination, a severe malformation of the lower limbs was observed. Further sonographic exploration demonstrated bilateral asymmetrical femoral hypoplasia, hypoplasia of both tibiae, bilateral aplasia of the fibulae and oligosyndactyly of the right hand with absence of the 4th and 5th rays. The prenatal sonographic features and differential diagnosis are discussed. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.
19203875
FFU complex: an analysis of 491 cases
A study of 491 patients with femur-fibula-ulna (FFU) complex is presented. The term FFU complex has been proposed for cases in which the femur, fibula and/or ulna show defects, which tend to be associated. These cases are usually sporadic. Some rare anomalies of the arms which are present are particularly frequent in FFU complex. These are amelia, peromelia of humerus, humeroradial synostosis and defect of ulna. In our study, 491 patients were investigated for involvement of limb malformations. Our results, showing nearly equal proportions of the most common malformations in four analysed groups (with one, two, three and four limbs affected) supports the hypothesis that even if one arm or one leg only is affected, the cases may still be classifiable as FFU complex. There is a striking asymmetry in presence and in degree. All malformations are more often unilateral than bilateral. Upper limbs are affected more often than lower limbs. The right side and the male sex are preferentially affected. The limb malformations present in the FFU complex are different from those seen in most other types of limb defects, so there is virtually no overlap between FFU and other limb malformations. Some arguments in favour of early somatic mutation as a cause are discussed.
21915793
On the assessment of the growth patterns in human fetal limbs: longitudinal measurements and allometric analysis.
The total length (TL) and length of the ossified part (OL) of some long bones of the upper (humerus, ulna, radius) and lower limb (femur, tibia, fibula) were evaluated in 58 aborted human fetuses (crown-rump length, CRL, between 38 and 116 mm, developmental age from 8 to 14 weeks). The specimens, without any detectable malformation, were cleared and double-stained with alcian blue and alizarin red S to obtain a differential detection of the ossified part within the comprehensive outline between the cartilaginous epiphyses. The correlation between the values of TL and OL and those of CRL emphasized that the systematic OL measurement in limb long bones correlated better than TL with development age, since OL increased faster than TL. TL and OL also correlated with the CRL by bivariate allometry (ln y = ln a + b ln x) and the data obtained showed that they grew with positive allometry. The comparison between the cumulative values of the bones examined in each limb showed that both TL and OL grew relatively faster in the lower limb than the upper; the greatest growth rate was found for OL in the lower limb. These results many provide a tool for a comprehensive assessment of long bone growth patterns and may be useful in determining fetal growth even in incomplete specimens, in which one or some long bones can still be measured.
6730204
Analysis of the presence of osteocalcin, S-100 protein, and proliferating cell nuclear antigen in cells of various types of osteosarcomas.
Osteosarcomas are characterized by different histologic subtypes that are composed of heterogeneous tumor cells. Although the histological origin of the malignant cells is unknown, it has been speculated that osteoblasts lead to the malignant cells. In the current study, the osteosarcoma cells in 27 lesions were assessed by means of immunohistochemical staining for osteocalcin (OC), S-100 protein (S-100) and proliferating cell nuclear antigen (PCNA). PCNA labeling indices were the highest in osteoblastic and stromal areas, and significantly lower in chondroblastic areas (p < 0.01). Cells that were positive for both PCNA and OC were abundant in osteoblastic and stromal areas, while cells that were positive for both PCNA and S-100 were rarely observed. These results were almost similar for conventional, parosteal and periosteal osteosarcomas. In contrast, OC reactivity was poor in fibroblastic osteosarcoma, in osteosarcoma with giant cells, and in telangiectatic osteosarcoma. Pulmonary metastatic osteosarcoma lesions weakly expressed OC (p < 0.01), but showed high values for the PCNA labeling indices. In conclusion, immunohistochemical staining for OC, S-100, and PCNA are useful to analyze the proliferating cells in osteosarcomas. The main proliferating cells in most osteosarcomas are mature osteoblast-like cells. OC-negative tumor cells predominate in some of osteosarcoma subtypes, and these tumors therefore probably represent a distinct osteosarcoma variant. OC expression in pulmonary metastatic lesions may be suppressed.
40595780
S100A4: A Novel Negative Regulator of Mineralization and Osteoblast Differentiation
S100A4 is an intracellular calcium‐binding protein expressed by osteoblastic cells. However, its roles in bone physiology are unknown. Because before matrix mineralization, its expression is markedly diminished, we hypothesized that S100A4 negatively regulates the mineralization process. In this study, we investigated the effects of the inhibition of S100A4 synthesis on osteoblast differentiation and in vitro mineralized nodule formation. Inhibition of S100A4 synthesis was achieved by an antisense approach in the mouse osteoblastic cell line MC3T3‐E1. Cell clones that synthesized low levels of S100A4 (AS clones) produced markedly increased number of mineralized nodules at much earlier stages in comparison with controls as demonstrated by Alizarin red S and von Kossa staining. The expression of type I collagen (COLI) and osteopontin (OPN) increased in AS clones compared with controls. Bone sialoprotein (BSP) and osteocalcin (OCN), molecules associated with mineralization and markers for mature osteoblastic phenotype, were expressed in AS clones before their detection in controls. Because S100A4 was not localized in the nucleus of MC3T3‐E1 cells and AS clones, it is unlikely that S100A4 directly regulates the expression of these genes. Moreover, the expression of Cbfa1/Osf‐2 and Osx, transcription factors necessary for the expression of osteoblast‐associated genes, remained unchanged in AS clones, indicating that S100A4 may be downstream to these transcription factors. These findings indicate that S100A4 is a novel negative regulator of matrix mineralization likely by modulating the process of osteoblast differentiation.
4980966
Quantitative anatomy of the ilium’s primary ossification center in the human fetus
PurposeAn understanding of the development of the ilium’s primary ossification center may be useful in both determining the fetal stage and maturity, and for detecting congenital disorders. This study was performed to quantitatively examine the ilium’s primary ossification center with respect to its linear, planar and volumetric parameters.Materials and methodsUsing methods of CT, digital-image analysis and statistics, the size of the ilium’s primary ossification center in 42 spontaneously aborted human fetuses of crown–rump length (CRL) ranged from 130 to 265 mm (aged 18–30 weeks) was studied.ResultsWith no sex and laterality differences, the best fit growth dynamics for the ilium’s primary ossification center was modelled by the following functions: y = − 63.138 + 33.413 × ln(CRL) ± 1.609 for its vertical diameter, y = − 59.220 + 31.353 × ln(CRL) ± 1.736 for its transverse diameter, y = − 105.681 + 1.137 × CRL ± 16.035 for its projection surface area, and y = 478.588 + 4.035 × CRL ± 14.332 for its volume. The shape of the ilium’s primary ossification center did not change over the study period, because its transverse -to- vertical diameter ratio was stable at the level of 0.94 ± 0.07.ConclusionsThe size of the ilium’s primary ossification center displays neither sex nor laterality differences. The ilium’s primary ossification center grows logarithmically with respect to its vertical and transverse diameters, and linearly with respect to its projection surface area and volume. The shape of the ilium’s primary ossification center does not change throughout the examined period. The obtained quantitative data of the ilium’s primary ossification center is considered normative for respective prenatal weeks and may contribute to the prenatal ultrasound diagnostics of congenital defects.
22680439
Low-dose fetal CT in the prenatal evaluation of skeletal dysplasias and other severe skeletal abnormalities.
OBJECTIVE
Prenatal diagnosis of skeletal dysplasia is often difficult and based on findings with ultrasound, a technique with 40-60% sensitivity. The purpose of this study was to evaluate a preliminary experience in assessing severe prenatal osseous abnormalities with low-dose fetal CT. The hypothesis was that use of CT may improve the prenatal diagnosis of skeletal dysplasia beyond the available capabilities of ultrasound.


MATERIALS AND METHODS
Retrospective search of a radiology database (July 2008-February 2011) yielded the records of unenhanced CT examinations of patients referred because of abnormal fetal bones. The original ultrasound and CT reports as interpreted at image acquisition were independently analyzed by two radiologists blinded to the final diagnosis and to the findings of the opposing imaging modality. Blinded review of the images was also performed. Correlation was made with the postmortem and postnatal findings.


RESULTS
According to the reports of the studies, 5 of 21 cases were interpreted correctly with CT and incorrectly with ultrasound. In 17 cases, CT revealed additional osseous findings not in the ultrasound report. There were no cases in which ultrasound findings were correct and CT findings were incorrect. Blinded review of the images revealed that CT outperformed ultrasound (p < 0.001). There were a total of four CT errors among 218 total measures recorded and a total of 19 ultrasound errors among 218 total measures.


CONCLUSION
Although low-dose fetal CT should never be used as the initial diagnostic modality in cases of suspected skeletal dysplasia, it is a powerful imaging adjunct that depicts the fetal bones in exquisite detail. Use of CT of fetuses at risk of skeletal dysplasia may provide clinicians with more accurate information for counseling of families regarding neonatal morbidity and mortality.
44885744
Factors influencing development of secondary ossification centres in the fetus and newborn
Whole body radiographs of 379 consecutive perinatal necropsies were used to determine the presence and diameters of secondary ossification centres in the os calcis, talus, distal femur, proximal tibia, cuboid bone, and proximal humerus. An estimate of the normal development for gestational age was obtained from 164 selected cases. The variation in number and size of bone centres was too wide for accurate estimation of maturity in the individual case, but ossification could be classified as relatively normal, advanced, or retarded, and comparisons made between groups of cases. Retardation of ossification was found mainly in association with males and small-for-dates babies, but also in some congenital malformations such as the trisomy syndromes and some multiple births: retardation was suggested in association with toxaemia of pregnancy, increasing maternal age, and increasing parity. Advanced ossification was mainly related to female babies but was also found in relation to other malformations, especially anencephalus, and was suggested in association with Negro infants.
10566137
Prenatal diagnosis of congenital absence of the fibula.
Congenital absence of the fibula is the most common of the mesomelic paraxial hemimelias, frequently associated with anteromedial bowing and shortening of the tibia and mild equinovalgus of the foot. 1.2 Although the majority of these cases occur as sporadic, isolated events, agenesis of the fibula also may be part of more complex dysostoses, sporadic syndromes, aneuploidy, and several other genetic conditions, or it mal be the result of disruption or teratogenic insults. This etiologic polymorphism has been taken as evidence that this anomaly represents a developmental field defect involving defects of the pubic portion of the pelvis, proximal end of the femur, patella, fibula, and a variable number of lateral tarsal bones and toes in the most severe form to isolated, unilateral fibular hypoplasia in the mildest form.:! In this report we describe a case of congenital absence of the fibula diagnosed prenatally by ultrasonography.
28570811
Contribution of three‐dimensional computed tomography in the assessment of fetal skeletal dysplasia
To compare the diagnostic accuracy of two‐dimensional (2D) ultrasound and three‐dimensional (3D) computed tomography (CT) for the diagnosis of fetal skeletal anomalies.
22035963
Normal anatomy of the fetus at MR imaging.
Owing to recent advances in magnetic resonance (MR) imaging, the role of obstetric MR imaging has increased in cases in which the results of ultrasonography are equivocal. Fast MR imaging sequences, such as T2-weighted fast spin-echo (SE), half-Fourier single-shot fast SE, 0.5-signal-acquired single-shot fast SE, and echo-planar imaging, have virtually eliminated the need for fetal premedication, with a concomitant improvement in image resolution and diminished blurring. Artifacts related to maternal respiratory motion and fetal motion no longer limit the anatomic detail that can be demonstrated with MR imaging. With such advances in obstetric MR imaging, knowledge of normal fetal anatomy at MR imaging is essential to detect disease in utero. MR imaging can demonstrate fetal anatomy in detail, especially the brain, thorax, abdomen, pelvis, and vasculature. Major developmental structures of the fetus, particularly the cranial nervous system, naso- and oropharynx, lungs, and major abdominal viscera, can be adequately evaluated with targeted fast MR imaging as early as the beginning of the second trimester. However, MR imaging of the heart remains limited. Fetal MR imaging during the first trimester remains controversial secondary to biosafety issues and is limited due to diminutive fetal size.
3752821
Modeling the biomechanics of fetal movements
Fetal movements in the uterus are a natural part of development and are known to play an important role in normal musculoskeletal development. However, very little is known about the biomechanical stimuli that arise during movements in utero, despite these stimuli being crucial to normal bone and joint formation. Therefore, the objective of this study was to create a series of computational steps by which the forces generated during a kick in utero could be predicted from clinically observed fetal movements using novel cine-MRI data of three fetuses, aged 20–22 weeks. A custom tracking software was designed to characterize the movements of joints in utero, and average uterus deflection of $$6.95 \pm 0.41$$6.95±0.41 mm due to kicking was calculated. These observed displacements provided boundary conditions for a finite element model of the uterine environment, predicting an average reaction force of $$0.52 \pm 0.15$$0.52±0.15 N generated by a kick against the uterine wall. Finally, these data were applied as inputs for a musculoskeletal model of a fetal kick, resulting in predicted maximum forces in the muscles surrounding the hip joint of approximately 8 N, while higher maximum forces of approximately 21 N were predicted for the muscles surrounding the knee joint. This study provides a novel insight into the closed mechanical environment of the uterus, with an innovative method allowing elucidation of the biomechanical interaction of the developing fetus with its surroundings.