Diagnostic Image Quality of a Low-Field (0.55T) Knee MRI Protocol Using Deep Learning Image Reconstruction Compared with a Standard (1.5T) Knee MRI Protocol.

OBJECTIVES: Low-field MRI at 0.55 Tesla (T) with deep learning image reconstruction has recently become commercially available. The objective of this study was to evaluate the image quality and diagnostic reliability of knee MRI performed at 0.55T compared with 1.5T. METHODS: A total of 20 volunteers (9 female, 11 male; mean age = 42 years) underwent knee MRI on a 0.55T system (MAGNETOM Free.Max, Siemens Healthcare, Erlangen, Germany; 12-channel Contour M Coil) and a 1.5T scanner (MAGNETOM Sola, Siemens Healthcare, Erlangen, Germany; 18-channel transmit/receive knee coil). Standard two-dimensional (2D) turbo spin echo (TSE), fat-suppressed (fs) proton density-weighted (PDw), T1w TSE, and T2w TSE sequences were acquired in approximately 15 min. In total, 2 radiologists blinded to the field strength subjectively assessed all MRI sequences (overall image quality, image noise, and diagnostic quality) using a 5-point Likert scale (1-5; 5 = best). Additionally, both radiologists evaluated the possible pathologies of menisci, ligaments, and cartilage. Contrast ratios (CRs) of different tissues (bone, cartilage, and menisci) were determined on coronal PDw fs TSE images. The statistical analysis included Cohen's kappa and the Wilcoxon rank sum test. RESULTS: The overall image quality of the 0.55T T2w, T1w, and PDw fs TSE sequences was diagnostic and rated similar for T1w (p > 0.05), but lower for PDw fs TSE and T2w TSE compared with 1.5T (p < 0.05). The diagnostic accordance of meniscal and cartilage pathologies at 0.55T was similar to 1.5T. The CRs of the tissues were not significantly different between 1.5T and 0.55T (p > 0.05). The inter-observer agreement of the subjective image quality was generally fair between both readers and almost perfect for the pathologies. CONCLUSIONS: Deep learning-reconstructed TSE imaging at 0.55T yielded diagnostic image quality for knee MRI compared with standard 1.5T MRI. The diagnostic performance of meniscal and cartilage pathologies was equal for 0.55T and 1.5T without a significant loss of diagnostic information.

Clinical Low Dose Photon Counting CT for the Detection of Urolithiasis: Evaluation of Image Quality and Radiation Dose.

The purpose of this study was the evaluation of image quality and radiation dose parameters of the novel photon counting CT (PCCT, Naeotom Alpha, Siemens Healthineers) using low-dose scan protocols for the detection of urolithiasis. Standard CT scans were used as a reference (S40, Somatom Sensation 40, Siemens Healthineers). Sixty-three patients, who underwent CT scans between August and December 2021, were retrospectively enrolled. Thirty-one patients were examined with the PCCT and 32 patients were examined with the S40. Radiation dose parameters, as well as quantitative and qualitative image parameters, were analyzed. The presence of urolithiasis, image quality, and diagnostic certainty were rated on a 5-point-scale by 3 blinded readers. Both patient groups (PCCT and S40) did not differ significantly in terms of body mass index. Radiation dose was significantly lower for examinations with the PCCT compared to the S40 (2.4 ± 1.0 mSv vs. 3.4 ± 1.0 mSv; p < 0.001). The SNR was significantly better on images acquired with the PCCT (13.3 ± 3.3 vs. 8.2 ± 1.9; p < 0.001). The image quality of the PCCT was rated significantly better (4.3 ± 0.7 vs. 2.8 ± 0.6; p < 0.001). The detection rate of kidney or ureter calculi was excellent with both CT scanners (PCCT 97.8% and S40 99%, p = 0.611). In high contrast imaging, such as the depiction of stones of the kidney and the ureter, PCCT allows a significant reduction of radiation dose, while maintaining excellent diagnostic confidence and image quality. Given this image quality with our current protocol, further adjustments towards ultra-low-dose CT scans appear feasible.

Photon Counting CT Angiography of the Head and Neck: Image Quality Assessment of Polyenergetic and Virtual Monoenergetic Reconstructions.

BACKGROUND: The purpose of the present study was the evaluation of the image quality of polyenergetic and monoenergetic reconstructions (PERs and MERs) of CT angiographies (CTAs) of the head and neck acquired with the novel photon counting CT (PCCT) method in clinical routine. METHODS: Thirty-seven patients were enrolled in this retrospective study. Quantitative image parameters of the extracranial, intracranial and cerebral arteries were evaluated for the PER and MER (40-120 keV). Additionally, two radiologists rated the perceived image quality. RESULTS: The mean CTDIvol used in the PCCT was 8.31 ± 1.19 mGy. The highest signal within the vessels was detected in the 40 keV MER, whereas the lowest noise was detected in the 115 keV MER. The most favorable contrast-to-noise-ratio (CNR) and signal-to-noise-ratio (SNR) were detected in the PER and low keV MER. In the qualitative image analysis, the PER was superior to the MER in all rated criteria. For MER, 60-65 keV was rated as best image quality. CONCLUSION: Overall, PCCT offers excellent image quality for CTAs of the head and neck. At the current state, the PER of the PCCT seems to be the most favorable reconstruction for diagnostic reporting.

Designing Shape Morphing Behavior through Local Programming of Mechanical Metamaterials.

Shape morphing implicates that a specific condition leads to a morphing reaction. The material thus transforms from one shape to another in a predefined manner. In this paper, not only the target shape but rather the evolution of the material's shape as a function of the applied strain is programmed. To rationalize the design process, concepts from informatics (processing functions, for example, Poisson's ratio (PR) as function of strain: ν = f(ε) and if-then-else conditions) will be introduced. Three types of shape morphing behavior will be presented: (1) achieving a target shape by linearly increasing the amplitude of the shape, (2) filling up a target shape in linear steps, and (3) shifting a bulge through the material to a target position. In the first case, the shape is controlled by a geometric gradient within the material. The filling kind of behavior was implemented by logical operations. Moreover, programming moving hillocks (3) requires to implement a sinusoidal function εy  = sin (εx ) and an if-then-else statement into the unit cells combined with a global stiffness gradient. The three cases will be used to show how the combination of mechanical mechanisms as well as the related parameter distribution enable a programmable shape morphing behavior in an inverse design process.

Open Dislocation Injury of the Metacarpophalangeal Joints III-V: Case Report.

A 79-year-old man sustained left open metacarpophalangeal joints III-V dislocation injury in the dorsal direction associated with avulsions of the volar fibrocartilaginous plates. Surgical revision became necessary. Three months after the injury, the patient was very satisfied with his intermedium outcome; however, complete restoration of hand function was not observed at this time. To our knowledge, this is the first case presentation in the literature that describes such an injury involving the metacarpophalangeal joints III-V.

Explant analysis of a Maestro™ wrist prosthesis and calculation of its lubrication regime.

Explant analysis can provide key insights to understanding failures of artificial joints and thus how they might be improved for the ultimate benefit of patients. There are no previous reports of explant analysis of an artificial wrist joint. In this study, an explanted metal-on-polymer Maestro wrist was analysed both in macro and nanoscales to estimate its biotribological performance. The articulation was formed between a cobalt chromium carpal head and an ultrahigh molecular weight polyethylene bearing. The surface roughness values of its articulating surfaces and the backside of the articulation were measured. On average, the articulating surface roughness values were calculated as 0.06 ± 0.02 µm and 1.29 ± 0.63 µm for the cobalt chromium carpal head and ultrahigh molecular weight polyethylene bearing, respectively. Both surfaces had negative skewness, indicating a preponderance of valleys. On the articulating surface of the carpal head, light scratches were observed, and no impingement was observed throughout the component. The polymeric surface had a polished appearance. It had unidirectional scratches at the centre of the articulation, pits of different sizes on its articulating surface, and matt white subsurface regions. The backside of the UHMWPE bearing and the convex surface of the radial body that it was sitting on, were found to have average surface roughness values of 4.23 ± 0.69 µm and 5.57 ± 1.05 µm, respectively. The difference in the means was not significant (p > 0.05). Taking the articulating surface roughness values, the lubrication regime that the explanted Maestro wrist operated under in vivo was estimated for varying physiological conditions, i.e. varying loads, entraining velocities and lubricant viscosities. In every case considered, the explant was found to operate under boundary lubrication.

Newly formed and remodeled human bone exhibits differences in the mineralization process.

During human skeletal growth, bone is formed via different processes. Two of them are: new bone formation by depositing bone at the periosteal (outer) surface and bone remodeling corresponding to a local renewal of tissue. Since in remodeling formation is preceded by resorption, we hypothesize that modeling and remodeling could require radically different transport paths for ionic precursors of mineralization. While remodeling may recycle locally resorbed mineral, modeling implies the transport over large distances to the site of bone apposition. Therefore, we searched for potential differences of size, arrangement and chemical composition of mineral particles just below surfaces of modeling and remodeling sites in femur midshaft cross-sections from healthy children. These bone sites were mapped using scanning synchrotron X-ray scattering, Raman microspectroscopy, energy dispersive X-ray analysis and quantitative backscattered electron microscopy. The results show clear differences in mineral particle size and composition between the sites, which cannot be explained by a change in the rate of mineral apposition or accumulation. At periosteal modeling sites, mineral crystals are distinctly larger, display higher crystallinity and exhibit a lower calcium to phosphorus ratio and elevated Na and Mg content. The latter may originate from Mg used for phase stabilization of mineral precursors and therefore indicate different time periods for mineral transport. We conclude that the mineralization process is distinctively different between modeling and remodeling sites due to varying requirements for the transport distance and, therefore, the stability of non-crystalline ionic precursors, resulting in distinct compositions of the deposited mineral phase. STATEMENT OF SIGNIFICANCE: In growing children new bone is formed either due to apposition of bone tissue e.g. at the outer ridge of long bones to allow growth in thickness (bone modeling), or in cavities inside the mineralized matrix when replacing tissue (bone remodeling). We demonstrate that mineral crystal shape and composition are not the same between these two sites, which is indicative of differences in mineralization precursors. We suggest that this may be due to a longer mineral transport distance to sites of new bone formation as compared to remodeling where mineral can be locally recycled.

A Devasting Course of an Iliopsoas Muscle Abscess Subsequently Leading to Septic Shock, Septic Hip Arthritis, and Extended Gluteal Soft Tissue Necroses in an Elderly Immunocompromised Patient with Multiple Carcinomas: A Case Report and Brief Review of Literature.

BACKGROUND: A devasting course of Iliopsoas Muscle (IPM) abscess remains a challenging therapeutic problem. METHODS: A 69-year-old polymorbid male had a history of multiple carcinomas and presented with advanced stage of septic shock due to a right IPM abscess which communicated with the right hip joint and subsequently led to septic hip arthritis accompanied with post-infectious right gluteal deep soft tissue necroses. Management of surgical treatment included abscess revision, coverage with the use of Long Head Biceps Femoris Muscle (LHBFM) 180° turnover flap, and creating a Girdlestone resection-arthroplasty. RESULTS: After a duration of patient's hospitalization of six months that included the necessity of artificial respiration over two months accompanied with in summary 18 required surgical procedures, the patient could be recovered successfully regarding his polymorbidity and his low-demand claims in activities of daily living with his Girdlestone resection-arthroplasty. CONCLUSION: Recovery of immunocompromised patients with those life-threatening situations can only be achieved by an interdisciplinary management. The LHBFM 180° turnover flap can be useful for filling off post-infectious deep soft tissue cavities communicating with the hip joint. The definitive Girdlestone resection-arthroplasty for treatment of septic hip arthritis is the method of choice for mobilization of elderly polymorbid patients with low demand claims in their activities of daily living.

Correlations between nanostructure and micromechanical properties of healing bone.

All hierarchical levels in bone are known to contribute to its mechanical behavior. The basic building block is the mineralized collagen fibril which is assembled into larger structures with varying fibrillar organization. The collagen organization increases from unordered woven bone in the callus which is gradually replaced by higher ordered lamellar bone during bone development and healing and finally results in cortical lamellar bone with highest degree of organization. The structural and mechanical description of these organizational motifs is not yet complete. We investigated a femoral osteotomy mouse model and analyzed newly formed callus tissue and mature lamellar bone in the cortex. This model exhibits three bone types with different fibrillar organization: (i) woven, (ii) moderate lamellar and (iii) lamellar. Using high resolution synchrotron small angle X-ray scattering in combination with back-scattered electron imaging we characterized the ultrastructure of the different regions in terms of degree of mineralization, averaged mineral particle thickness and mineral particle orientation. We further used microindentation to correlate hardness, induced crack lengths and crack patterns with the bone ultrastructure. The newly formed callus tissue contains highly mineralized woven bone islands, featuring thick but poorly ordered mineral particles. Such islands are surrounded by layers of lamellar bone with a low mineralization level and thin but well aligned particles. Callus tissue shows lower hardness values and longer cracks than the cortex. Callus woven bone exhibits shorter cracks than callus lamellar bone. However, the poorly mineralized callus lamellar bone shows crack propagation mechanisms similar to cortical bone due to its very similar lamellar organization and high degree of mineral particle orientation. In conclusion we demonstrate that woven and increasingly higher oriented lamellar bone do not only differ in collagen fibril organization, but also that the amount, orientation and different shape of mineral particles are also likely to contribute to the reduced mechanical competence of woven as compared to lamellar bone. This may explain why many organisms replace less organized bone types with higher organized ones.

Irreparable Radial Nerve Palsy Due to Delayed Diagnostic Management of a Giant Lipoma at the Proximal Forearm Resulting in a Triple Tendon Transfer Procedure: Case report and Brief Review of Literature.

BACKGROUND: Non-traumatic radial nerve palsy (RNP) caused by local tumors is a rare and uncommon entity. METHODS: A 62-year-old female presented with a left non-traumatic RNP, initially starting with weakness only. It was caused by a benign giant lipoma at the proximal forearm that was misdiagnosed over a period of 2 years. The slowly growth of the tumor led to an irreparable overstretching-related partial nerve disruption. For functional recovery of the patient, a triple tendon transfer procedure had to be performed. RESULTS: Four months after surgery, the patient was completely able to perform her activities of daily living again. At the 10-months follow-up, strength of wrist extension, thumb's extension and abduction, and long fingers II-V extension had all improved to grade 4 in Medical Research Council scale (0-5). In order to restore motion, the patient reported that she would undergo the same triple tendon transfer procedure a second time where necessary. Due to the initially misdiagnosed tumor, there was an overall delayed duration of time for functional recovery of the patient. CONCLUSION: The triple tendon transfer procedure offers a useful and reliable method to restore functionality for patients sustaining irreparable RNP. However, it must be noted critically with our patient that this procedure probably would have been avoided. Initially, there was weakness only by entrapment of the radial nerve. RNP caused by local tumors are uncommon but known from the literature, and so it should be considered generally in differential diagnosis of non-traumatic RNP.

A Complicated Course of a Coronal Shear Fracture Type IV of the Distal Part of Humerus Resulting in Resurfacing Radiocapitellar Joint Replacement.

BACKGROUND: Coronal shear fracture type IV of the distal part of humerus is a very rare injury with articular complexity potentially leading to posttraumatic osteoarthritis. One option for surgical treatment of advanced unicompartmental radiocapitellar osteoarthritis is resurfacing radiocapitellar joint replacement. METHOD: A 62-year- old female sustained a coronal shear fracture type IV of the distal part of left humerus that was primarily treated with open reduction and internal fixation using headless compression screws. Three years postoperatively, there was a migration of one screw into radiocapitellar joint that led to circular deep cartilage defect of radial head. Four years after ORIF, a distinctive radiocapitellar osteoarthritis has evolved leading to a resurfacing radiocapitellar joint replacement using the Lateral Resurfacing ElbowTM (LRE) system. RESULT: At the 2-year follow-up after that procedure, there was an excellent subjective and functional outcome. Radiographically, no loosening or subsidence of implant without any signs of overstuffing could be found. The patient reported that she would have the same procedure again. CONCLUSION: The goal of unicompartmental radiocapitellar replacement is to obtain stability in elbow joint by avoiding cubitus valgus with subsequent instability of the distal radioulnar joint, and it does not alter the unaffected ulnohumeral joint. Additionally, the feature of the LRETM system is that the radial head is not excised, and so will receive the anatomical length of the overall radius articulating with the capitellum by preserving the annular ligament. In the literature only three publications could be found in which short-term results with the use of the LRETM system have been described. Hence, further studies are needed to validate this concept.

Does Total Wrist Arthroplasty for Treatment of Posttraumatic Wrist Joint Osteoarthritis in Young Patients Always Lead to Restriction of High-demand Activities of Daily Living? Case Report and Brief Review of Recent Literature.

BACKGROUND: Posttraumatic ulnar carpal translocation is a very rare condition that is caused either by fracture-dislocation injury or by purely ligamentous injury of the wrist. Its prognosis is poor and development of posttraumatic pancarpal wrist joint osteoarthritis is inevitable, and options for treatment are total wrist fusion or total wrist arthroplasty. METHODS: A 24-year-old male sustained a fracture-related injury in his left wrist that was accompanied with a second ligamentous distorsion-related injury 1 year later in the same wrist. Seven years after first injury, a posttraumatic pancarpal wrist joint osteoarthritis has developed that was caused by posttraumatic ulnar carpal translocation. The patient was treated by total wrist arthroplasty with use of the MaestroTM Wrist Reconstructive System. RESULTS: With our patient, it is unclear whether posttraumatic ulnar carpal translocation occurred either as result of the first fracture-related injury or as result of the second ligamentous distorsion-related injury or as result of both injuries. The 31-year-old patient could be reemployed completely in his original occupation as a mechanic for big agriculture machines and load his wrist with more than 10 pounds. In order to preserve motion, the patient reported that he would undergo the same total wrist arthroplasty a second time were it necessary. CONCLUSION: We report on a young male receiving total wrist arthroplasty and resulting in good restoration of his high-demand claims in activities of daily living, respectively. However, it cannot be concluded that total wrist arthroplasty is to be preferred generally over total wrist fusion in young patients. Essential prerequisite for this motion-preserving procedure is the compliance of patients.

Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone.

Osteogenesis imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures, and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65-kDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon, and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10fl/fl mice (Mus musculus; C57BL/6) using the osteoblast-specific Col1a1 2.3-kb Cre recombinase. Using µCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy (MS) of bone collagen demonstrated a decrease in mature, hydroxylysine-aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral-to-matrix ratio and in crystal size as shown by Raman spectroscopy and small-angle X-ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild-type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton. © 2017 American Society for Bone and Mineral Research.

An Unusual and Complicated Course of a Giant Cell Tumor of the Capitate Bone.

A 51-year-old female patient presented with a carpal giant cell tumor (GCT) of the right capitate bone. The lesion was initially misdiagnosed as having an osteomyelitis. First, the diagnosis of a benign GCT was confirmed by histological examination. Second, an intralesional curettage and packing of the cavity with cancellous iliac crest bone grafts combined with a fusion of the third carpometacarpal (CMC III) joint were carried out. Third, due to a secondary midcarpal osteoarthritis and a secondary scaphoid nonunion, the CMC III joint fusion plate was removed and the midcarpal joint completely excised. Fourth, in the absence of recurrence of GCT, a four-corner fusion (4CF) with a corticocancellous iliac crest bone graft and complete excision of the scaphoid bone had to be performed. Fifth, a total wrist arthroplasty (TWA) was performed due to hardware failure of 4CF with migration of a headless compression screw into radiocarpal joint which led to erosion of articular surface of the distal radius. At the 3-year follow-up that includes a 1-year follow-up after TWA, there was no recurrence of GCT, and the TWA was not failed. The patient reported that she would have the motion-preserving TWA again.

Underwater 3D Surface Measurement Using Fringe Projection Based Scanning Devices.

In this work we show the principle of optical 3D surface measurements based on the fringe projection technique for underwater applications. The challenges of underwater use of this technique are shown and discussed in comparison with the classical application. We describe an extended camera model which takes refraction effects into account as well as a proposal of an effective, low-effort calibration procedure for underwater optical stereo scanners. This calibration technique combines a classical air calibration based on the pinhole model with ray-based modeling and requires only a few underwater recordings of an object of known length and a planar surface. We demonstrate a new underwater 3D scanning device based on the fringe projection technique. It has a weight of about 10 kg and the maximal water depth for application of the scanner is 40 m. It covers an underwater measurement volume of 250 mm × 200 mm × 120 mm. The surface of the measurement objects is captured with a lateral resolution of 150 µm in a third of a second. Calibration evaluation results are presented and examples of first underwater measurements are given.

Can Total Wrist Arthroplasty Be an Option for Treatment of Highly Comminuted Distal Radius Fracture in Selected Patients? Preliminary Experience with Two Cases.

We present two case reports of successful primary shortening of the forearm and total wrist arthroplasty (TWA) using the new angle-stable Maestro Wrist Reconstructive System (WRS) for treatment of highly comminuted distal radius fracture in selected autonomous patients. In a 56-year-old male patient with adequate bone stock, insertion of the noncemented Maestro WRS was combined with ulnar shortening osteotomy. In an 84-year-old female patient with poor osteoporotic bone stock, insertion of the radial cemented Maestro WRS was combined with ulnar head resection. Both patients could resume their work without additional surgery after TWA. At the 1-year follow-up, there were no changes in position of either implant without signs of loosening, no impingement, and no instability of the distal radioulnar joint or the distal ulna stump. All clinical parameters (DASH score, pain through VAS, and grip strength) were satisfactory. Both patients reported that they would have the same procedure again. Further experience is needed to validate this concept.

Multi-scale thermal stability of a hard thermoplastic protein-based material.

Although thermoplastic materials are mostly derived from petro-chemicals, it would be highly desirable, from a sustainability perspective, to produce them instead from renewable biopolymers. Unfortunately, biopolymers exhibiting thermoplastic behaviour and which preserve their mechanical properties post processing are essentially non-existent. The robust sucker ring teeth (SRT) from squid and cuttlefish are one notable exception of thermoplastic biopolymers. Here we describe thermoplastic processing of squid SRT via hot extrusion of fibres, demonstrating the potential suitability of these materials for large-scale thermal forming. Using high-resolution in situ X-ray diffraction and vibrational spectroscopy, we elucidate the molecular and nanoscale features responsible for this behaviour and show that SRT consist of semi-crystalline polymers, whereby heat-resistant, nanocrystalline ß-sheets embedded within an amorphous matrix are organized into a hexagonally packed nanofibrillar lattice. This study provides key insights for the molecular design of biomimetic protein- and peptide-based thermoplastic structural biopolymers with potential biomedical and 3D printing applications.

Surgical Treatment Options in Thumb Carpometacarpal Osteoarthritis: A Recent Literature Overview Searching for Practice Pattern with Special Focus on Total Joint Replacement.

Thumb carpometacarpal joint osteoarthritis is the most common site of non-rheumatic degenerative lesion in the hand, and there are special features in rheumatic patients. None of various surgical treatment options can be declared as "gold standard" recently. The surgical treatment depends on patient's age, patient's claims in work and leisure, local bone stock, possible allergies, local comorbities, and local deformities.

Unique micro- and nano-scale mineralization pattern of human osteogenesis imperfecta type VI bone.

Osteogenesis imperfecta (OI) is a heterogeneous group of inheritable connective tissue disorders characterized by mutation in genes involved in collagen synthesis and leading to increased bone fragility, low bone mass, impaired bone material properties and abnormally high bone matrix mineralization. Recessive OI type VI is caused by mutation in SERPINF1 leading to a loss-of-function of pigment epithelium-derived factor (PEDF) a collagen-binding protein with potent antiangiogenic activity. Affected patients develop a severe OI phenotype with a striking histological characteristic, rare in other OI types, of an excess of osteoid tissue and prolonged mineralization lag time. To get insights into matrix mineralization, we evaluated biopsies from 9 affected children by quantitative and by high-resolution backscattered electron imaging and assessed bone mineralization density distribution. Thickness, shape and arrangement of mineral particles were measured in a subset of 4 patients by synchrotron small angle X-ray scattering. Typical calcium content in the bone matrix was found to be increased compared to controls, even exceeding values found previously in OI patients with collagen-gene mutations. A main characteristic however, is the coexistence of this highly mineralized bone matrix with seams showing abnormally low mineral content. Atypical collagen fibril organization was found in the perilacunar region of young osteocytes, suggesting a disturbance in the early steps of mineralization. These observations are consistent with the presence of a heterogeneous population of mineral particles with unusual size, shape and arrangement, especially in the region with lower mineral content. The majority of the particles in the highly mineralized bone areas were less disorganized, but smaller and more densely packed than in controls and in previously measured OI patients. These data suggest that the lack of PEDF impairs a proper osteoblast-osteocyte transition and consequently affects the early steps of mineralization, downstream collagen assembly making OI type VI different from "classical" OI with mutations in collagen-type I encoding genes, despite the typical hypermineralization of the bone matrix.