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The balance of cell proliferation and size is key for the control of organ development and repair. Moreover, this balance has to be coordinated within tissues and between tissues to achieve robustness in the organ’s pattern and size. The tetrapod limb has been used to study these topics during development and repair, and several conserved pathways have emerged. Among them, mechanistic target of rapamycin (mTOR) signaling, despite being active in several cell types and developmental stages, is one of the least understood in limb development, perhaps because of its multiple potential roles and interactions with other pathways. In the body of this review, we have collated and integrated what is known about the role of mTOR signaling in three aspects of tetrapod limb development: 1) limb outgrowth; 2) chondrocyte differentiation after mesenchymal condensation and 3) endochondral ossification-driven longitudinal bone growth. We conclude that, given its ability to interact with the most common signaling pathways, its presence in multiple cell types, and its ability to influence cell proliferation, size and differentiation, the mTOR pathway is a critical integrator of external stimuli and internal status, coordinating developmental transitions as complex as those taking place during limb development. This suggests that the study of the signaling pathways and transcription factors involved in limb patterning, morphogenesis and growth could benefit from probing the interaction of these pathways with mTOR components.

Acral clinical and radiographic characteristics of a further patient with Coffin‐Siris syndrome (CSS), which is caused by mutations in the ARID1B gene, encoding a subunit of the BAF‐complex, are here described. Metacarpophalangeal profile pattern analysis (MCPPPA) of the present proband and other two known ARID1B mutated individuals has been performed for the first time, demonstrating hands brachydactyly. In this novel study, the utility of an accurate appendicular radiographic examination and MCPPPA in this congenital condition is highlighted. The MCPPPA could be considered in the clinical practice, to better study the hand skeletal morphology in patients with a syndrome characterized by limb defects, including CSS. [ABSTRACT FROM AUTHOR]

Background: Iterative reconstruction is well established for CT. Plain radiography also takes advantage of iterative algorithms to reduce scatter radiation and improve image quality. First applications have been described for bedside chest X-ray. A recent experimental approach also provided proof of principle for skeletal imaging.Purpose: To examine clinical applicability of iterative scatter correction for skeletal imaging in the trauma setting.Material and Methods: In this retrospective single-center study, 209 grid-less radiographs were routinely acquired in the trauma room for 12 months, with imaging of the chest (n = 31), knee (n = 111), pelvis (n = 14), shoulder (n = 24), and other regions close to the trunk (n = 29). Radiographs were postprocessed with iterative scatter correction, doubling the number of images. The radiographs were then independently evaluated by three radiologists and three surgeons. A five-step rating scale and visual grading characteristics analysis were used. The area under the VGC curve (AUCVGC) quantified differences in image quality.Results: Images with iterative scatter correction were generally rated significantly better (AUCVGC = 0.59, P < 0.01). This included both radiologists (AUCVGC = 0.61, P < 0.01) and surgeons (AUCVGC = 0.56, P < 0.01). The image-improving effect was significant for all body regions; in detail: chest (AUCVGC = 0.64, P < 0.01), knee (AUCVGC = 0.61, P < 0.01), pelvis (AUCVGC = 0.60, P = 0.01), shoulder (AUCVGC = 0.59, P = 0.02), and others close to the trunk (AUCVGC = 0.59, P < 0.01).Conclusion: Iterative scatter correction improves the image quality of grid-less skeletal radiography in the clinical setting for a wide range of body regions. Therefore, iterative scatter correction may be the future method of choice for free exposure imaging when an anti-scatter grid is omitted due to high risk of tube-detector misalignment. [ABSTRACT FROM AUTHOR]

Background: Although magnetic resonance imaging (MRI) is a valuable method in staging musculoskeletal tumors, it may not give enough information on the association between the tumor and the main vascular structures adjacent to the tumor. In this respect, computed tomographic angiography (CTA) may be a useful alternative imaging technique. Purpose: To evaluate the effectiveness of CTA in determining vascular invasion in patients with musculoskeletal tumors and suspected vascular invasion by MRI, and to correlate the CTA findings with the surgical findings. Material and Methods: Twenty patients who had musculoskeletal tumors and lacked a fat plane between the tumor and adjacent vessels by MRI were included in this study. All patients were evaluated with CTA, and the CTA findings were reviewed by two radiologists to determine the presence of vascular invasion. Statistical analysis was carried out by using surgical findings as the gold standard. Results: There were nine women and 11 men (mean age 31 years) with either bone ( n=9) or soft-tissue ( n=11) tumors. Twelve patients without invasion according to the CTA examination were also surgically negative (true-negative cases). Of the eight patients with invasion shown by CTA, only three had adhesions and were considered surgically negative (false-positive cases). Five had invasions proven by surgery and were considered surgically positive (true-positive cases). Compared to the surgical findings, CTA had 100% sensitivity, 80% specificity, 62.5% positive predictive value, 100% negative predictive value, and 80% accuracy. Conclusion: CTA is a more accurate imaging technique than MRI in evaluating vascular invasion of musculoskeletal tumors, and provides valuable preoperative data. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis screening with dual-energy absorptiometry (DXA) is not recommended due to low diagnostic utility and costs. Radiographic absorptiometry (RA) determines bone mineral density (BMD) of the phalangeal bones of the hand and is a potential osteoporosis pre-screening tool. Purpose: To determine the ability of RA to identify patients with osteoporosis in a male population. Material and Methods: As part of the Odense Androgen Study, we measured BMD of the intermediate phalanges of the second to fourth finger, lumbar spine (L2-L4), and total hip in 218 men aged 60-74 years (mean 68.8 years), randomly invited from the population, using RA (MetriScan) and DXA (Hologic 4500-A). Osteopenia and osteoporosis were defined as a T-score of less than -1.0 and -2.5, respectively, in the hip and/or lumbar spine. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were computed. Results: BMDRA of the phalanges correlated significantly with BMDDXA of the hip (R=0.47, P<0.001) and lumbar spine (R=0.46, P<0.001). A total of 105 men (48.2%) were osteopenic and 15 (6.9%) osteoporotic. The AUC (SE) value for detecting osteoporosis was 0.75 (0.06). The sensitivity and specificity of RA in identifying osteoporosis were 0.93 and 0.50, respectively. Conclusion: BMDRA correlated weakly with BMDDXA of the lumbar spine and total hip, and RA has a moderate ability to identify osteoporotic individuals. Nevertheless, RA may be used as a pre-screening tool in men, since the diagnosis may be ruled out in half the population at little cost. [ABSTRACT FROM AUTHOR]

Background: The literature is limited concerning the epidemiological issues of fracture in the fifth metacarpal bone. Purpose: To explore the incidence and types of this fracture, and how the fracture is related to age, gender, trauma mechanism, and at what day of the week the causing trauma occurred. Material and Methods: All hand fractures registered at the Department of Radiology, Buskerud Hospital, Norway, in the period between 2004 and 2006 were reviewed. Results: Of 1475 hand fractures, 271 (18.4%) were located in the fifth metacarpal bone. In 130 of these cases (121 male, nine female), the trauma had occurred through aggression, such as a fistfight or from punching a hard object. The majority of fractures were located in the neck of the metacarpal bone (boxer's fracture). The median age of this group was 22 (7-51) years. Concerning the time of trauma, there was a significant peak during weekends (95 patients). One hundred forty-one of the fifth metacarpal fractures were caused by accidental trauma (99 males, 42 females). In this group, the fractures were located approximately equally in the subcapital, diaphyseal, and basal part of the metacarpal. The median age was 34 (2-90) years. The accidental traumas occurred about as often during the weekdays as during the weekend. Conclusion: Of all hand fractures, fractures of the fifth metacarpal bone are the most common. There are as many aggression-related fractures as accidental fractures in the fifth metacarpal bone. When the fracture is caused by aggression, the typical patient is a young male sustaining fracture during the weekend. [ABSTRACT FROM AUTHOR]

Background: Although magnetic resonance imaging (MRI) is now considered the gold standard in second-line imaging of patients with suspected scaphoid fracture and negative radiographs, bone scintigraphy can be used in patients with pacemakers, metallic implants, or other contraindications to MRI. Bone scintigraphy is highly sensitive for the detection of fractures, but exact localization of scintigraphic lesions may be difficult and can negatively affect diagnostic accuracy. Purpose: To investigate the influence of image fusion of planar bone scintigraphy and radiographs on image interpretation in patients with suspected scaphoid fracture. Material and Methods: In 24 consecutive patients with suspected scaphoid fracture, a standard planar bone scintigraphy of both hands was supplemented with fusion imaging of the injured wrist. Standard and fusion images were evaluated independently by three experienced nuclear medicine physicians. In addition to the diagnosis, the degree of diagnostic confidence was scored in each case. Results: The addition of fusion images changed the interpretation of each of the three observers in seven, four, and two cases, respectively, reducing the number of positive interpretations of two of the observers from 11 and nine cases to six and seven cases, respectively. The degree of diagnostic confidence increased significantly in two observers, and interobserver agreement increased in all three pairs of observers from 0.83, 0.57, and 0.73 to 0.89, 0.8, and 0.9, respectively. Conclusion: Image fusion of planar bone scintigrams and radiographs has a significant influence on image interpretation and increases both diagnostic confidence and interobserver agreement. [ABSTRACT FROM AUTHOR]

Bone marrow edema (BME) has been a topic of increasing interest in the literature in recent years. BME is associated with numerous pathologies and is becoming recognized not only as a considerable pain generator, but also as an entity which is, in some cases, significantly linked to the worsening of patient prognosis. To date, no thorough imaging review of BME has been published. An electronic literature search was conducted through PubMed with a time parameter of January 1975 through December 2007. The primary search parameter was “bone marrow edema.” Over 800 papers were listed as written in English and involving humans. Other refining parameters included “AND syndrome,” “AND transient,” “AND arthritis,” “AND infection,” “AND tumor,” “AND neoplasm,” “AND iatrogenic,” “AND radiation therapy,” and “AND inflammation.” More current articles were favored over dated articles on the same topic. A total of 106 journal articles were collected concerning BME and multiple pathologic processes. The data contained therein was compiled and organized into a comprehensive format. BME can be caused by, and found concurrent with, a broad spectrum of pathologies which exhibit a variety of imaging findings. BME is also associated with the deterioration of certain pathologies. This presentation is a comprehensive discussion of different pathological conditions inducing or associated with BME. Differential diagnosis through appropriate imaging is vital to case management and could contribute to the prevention or decreased progression of certain pathologies. Continued investigation into the imaging of BME and its associated diseases, as well as the effect of BME on prognosis, is warranted. [ABSTRACT FROM AUTHOR]

Background: Growth plate or physeal cartilage trauma may result in delayed or immediate failure of growth due to bone bridge formation at the insult site. With computed tomography (CT) and magnetic resonance imaging (MRI), the role of imaging has expanded from diagnosis to treatment planning and therapy guidance. Purpose: To describe a technique for MR-guided growth plate bone bridge resection and to evaluate feasibility of the procedure. Material and Methods: Three consecutive patients with growth plate bone bridges were treated surgically under MR guidance. All bridges were detected with prior MRI and radiographs. All patients were referred to procedure due to growth plate bridge associated growth anomaly and pertaining clinical symptoms. The effect of the treatment was evaluated after 48 months with a clinical follow-up. Results: All bridges were successfully detected, marked, and removed under MRI guidance. All patients had relief from their symptoms. Two patients had lasting results from the operation with no further operative treatment needed or scheduled at 48 months from primary treatment. There was one clinical failure, with the patient requiring repeated osteotomies. Conclusion: We have successfully implemented a novel therapy for growth plate bridge resection. [ABSTRACT FROM AUTHOR]

Background: Discrepancy between neonatal hip morphology and stability has been reported in the literature. Comparative ultrasound studies on this issue are limited. Purpose: To compare neonatal hip instability, as assessed by dynamic ultrasound and clinical examination, with acetabular morphology, as assessed by Graf's method. Material and Methods: 536 newborn infants with clinical signs of hip instability, ambiguous findings at clinical hip examination, or positive risk factors for DDH were investigated with two ultrasound methods, the Graf method and anterior dynamic ultrasound, at an average age of 12 days. The hips were allocated to three groups according to the Graf result: A, normal (type Ia and b); B, borderline or immature (type IIa); and C, pathologic (type IIc and worse). Graf examination was compared with two diagnostic tests for instability, namely clinical examination by senior pediatric orthopedists and anterior dynamic ultrasound. Results: According to Graf's method, 77% of the hips were normal, 20% borderline/immature, and 3% pathologic. On clinical hip examination, 82% were stable, 14% unstable, and 4% dislocatable. The dynamic ultrasound outcome was 88% stable hips, 10% unstable, and 2% dislocatable. Of the hips considered unstable or dislocatable on dynamic ultrasound, 21% had normal (type I) and 66% immature acetabular morphology according to the Graf method. Of the hips that were stable on dynamic ultrasound, only one (0.1%) was dysplastic according to the Graf method. Graf's examination showed the smallest number of normal hips, but also the fewest pathologic hips, with many indeterminate results that needed follow-up. Conclusion: Acetabular morphology correlated better to stability as assessed by dynamic ultrasound than to the clinical examination results, with fair to moderate agreement. Graf's examination resulted in a large number of indeterminate results that needed follow-up, but when used as the sole criterion for deciding treatment did not lead to a higher treatment rate than when the decision was based on clinical hip examination. [ABSTRACT FROM AUTHOR]

Background: Ultrasound is increasingly being used to complement the clinical examination in assessing neonatal hip instability. The clinical examination, although highly sensitive in detecting hip instability, can lead to considerable overtreatment. Purpose: To compare anterior dynamic ultrasound and clinical examination in the assessment of neonatal hip instability and regarding treatment rates. Material and Methods: 536 newborn infants (out of a population of 18,031) were selected, on the basis of a combination of risk factors, clinical signs of hip instability or ambiguous clinical findings, to undergo an anterior dynamic ultrasound examination of the hip, by a method developed by our group. This examination, performed by one out of seven experienced examiners, was compared with the standard clinical hip examination conducted by one of four pediatric orthopedic surgeons. The clinical examination was carried out both prior to and within a few hours after the ultrasound examination. Results: The clinical examination diagnosed 81.7% of the hips as normal, 14.5% as unstable, and 3.8% as dislocatable or dislocated. With the dynamic ultrasound method, the corresponding figures were 87.8%, 10.4%, and 1.8%, respectively. Use of the criteria of the clinical examination resulted in treatment of 147 infants. Using the dynamic ultrasound examination as a criterion meant that 87 infants would receive treatment. The calculated treatment rate was 0.85% when based on the clinical stress test and 0.49% when based on the dynamic ultrasound. Conclusion: The dynamic ultrasound results reduced the treatment rate by over 40% when used as a basis for the decision regarding treatment. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance (MR) imaging has proved to be an excellent tool in diagnosing injuries of the cruciate ligaments and menisci. However, multiple planes and sometimes optimal oblique or double-oblique scan planes are needed due to the variability in the positioning of important structures, which means there is a lower throughput and longer scanning time. Purpose: To compare the performance of a 1-mm-thickness fast spin-echo (FSE) proton-density-weighted (PDW) MR imaging technique with multiplanar reconstruction (MPR) in diagnosing tears of the menisci and cruciate ligaments with that of conventional MR imaging. Material and Methods: Twenty-five consecutive patients underwent preoperative conventional and 1-mm-thickness FSE PDW MR imaging with subsequent knee arthroscopic surgery. Two musculoskeletal radiologists evaluated the status of the cruciate ligaments and menisci using two sets of MR images (method A: conventional images including seven sequences, taking 26 min; method B: 1-mm-thickness FSE PDW images with MPR, taking 7 min 20 s). The diagnostic efficacies of both methods for tears of the cruciate ligament and menisci were calculated and compared. Results: Arthroscopic surgery revealed 10 anterior cruciate ligament (ACL) tears, one posterior cruciate ligament (PCL) tear, and 26 meniscal tears. The diagnostic values of both methods were 100% for a cruciate ligament tear. The diagnostic values (sensitivity, specificity, accuracy, positive predictive value, and negative predictive value) for meniscal tears were 90%, 100%, 96%, 100%, and 94% for method A, and 95%, 100%, 98%, 100%, and 97% for method B, respectively. There were no significant differences in the diagnostic values between methods A and B. Conclusion: 1-mm-slice-thickness FSE PDW imaging with MPR showed comparable performance in diagnosing tears of the cruciate ligaments and menisci to conventional sequences but the scan time was much shorter. Therefore, this technique (method B) might improve the throughput of a 3T MR imaging system. [ABSTRACT FROM AUTHOR]