Vascular study of decellularized porcine long bones: Characterization of a tissue engineering model.

INTRODUCTION: Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability. MATERIAL AND METHODS: 32 porcine long bones (humeri and femurs) were used to assess the quality of their vascular network prior and after undergoing a perfusion-decellularization protocol. 12 paired bones were used to assess the vascular matrix prior (N = 6) and after our protocol (N = 6) by immunohistochemistry. Collagen IV, Von Willebrand factor and CD31 were targeted then quantified. The medullary macroscopic vascular network was evaluated with 12 bones: 6 were decellularized and the other 6 were, as control, not treated. All 12 underwent a contrast-agent injection through the nutrient artery prior an angio CT-scan acquisition. The images were processed and the length of medullary vessels filled with contrast agent were measured on angiographic cT images obtained in control and decellularized bones by 4 independent observers to evaluate the vascular network preservation. The microscopic cortical vascular network was evaluated on 8 bones: 4 control and 4 decellularized. After injection of gelatinous fluorochrome mixture (calcein green), non-decalcified fluoroscopic microscopy was performed in order to assess the perfusion quality of cortical vascular lacunae. RESULTS: The continuity of the microscopic vascular network was assessed with Collagen IV immunohistochemistry (p-value = 0.805) while the decellularization quality was observed through CD31 and Von Willebrand factor immunohistochemistry (p-values <0.001). The macroscopic vascular network was severely impaired after perfusion-decellularization; nutrient arteries were still patent but the amount of medullary vascular channels measured was significantly higher in the control group compared to the decellularized group (p-value <0.001). On average, the observers show good agreement on these results, except in the decellularized group where more inter-observer discrepancies were observed. The microscopic vascular network was observed with green fluoroscopic signal in almost every canals and lacunae of the bone cortices, in three different bone locations (proximal metaphysis, diaphysis and distal metaphysis). CONCLUSION: Despite the aggressiveness of the decellularization protocol on medullary vessels, total porcine long bones decellularized by perfusion retain an acellular cortical microvascular network. By injection through the intact nutrient arteries, this latter vascular network can still be used as a total bone infusion access for bone tissue engineering in order to enhance massive bone allografts prior implantation.

Diffuse vertebral marrow changes at MRI: Multiple myeloma or normal?

Five MRI patterns of marrow involvement (diffuse, focal, combined diffuse and focal, variegated, and normal) are observed in patients with a marrow proliferative disorder including MM. The wide range of marrow involvement patterns in monoclonal plasma cell proliferative disorders mirrors that of their natural histories that can vary from indolent to rapidly lethal. MRI of the axial bone marrow contributes to stage these disorders, but it should not be obtained for disease detection and characterization because of its limited specificity and sensitivity. At MRI, diffuse benign hematopoietic marrow hyperplasia and marrow heterogeneities in elderly patients mimic the diffuse and variegated patterns observed in MM patients. Careful analysis of fat- and fluid-sensitive MR images and quantitative marrow assessment by using MRI and FDG-PET can contribute in differentiating these changes from those associated with neoplastic marrow infiltration, with some residual overlapping findings.

Diagnostic performance of sacroiliac joint MRI and added value of spine MRI to detect active spondyloarthritis.

PURPOSE: To investigate the diagnostic performance of sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and the incremental value of spine MRI to "predict" clinical disease activity in patients with axial spondyloarthritis (axSpA). MATERIALS AND METHODS: This cross-sectional study included adult patients with known axSpA according to the SpondyloArthritis International Society (ASAS) classification criteria, radiological arm. MRI disease activity was scored semi-quantitatively for SIJ and total spine MRI in each patient. Two cut-off levels (≥ 1.3 and ≥ 2.1) for ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP) were considered for clinical disease activity categorization. MRI scores were first evaluated individually. Then, SIJ score was combined with the score from a spine segment (lumbar, cervical, thoracic or total spine) to build a bi-parametric model using a classification tree. Receiver operating characteristic (ROC) curves were constructed to evaluate the classification performance according to disease activity category of these models. RESULTS: Forty-four patients (30 men, 14 women; mean age, 37 years±10 [SD] [range: 17-64 years]) with a mean disease duration of 5 years±8 (SD) (range: 0-35 years) were included. Thirty-six patients (36/44; 82%) had ASDAS-CRP≥1.3 and 27 patients (27/44; 61%) had ASDAS-CRP≥2.1. The most frequently involved spinal segment was mid-thoracic (T7-T8). The SIJ MRI score was an informative model to identify active axSpA (AUC≥0.7, regardless of the cut-off level on ASDAS-CRP). Performance of bi-parametric models based on "SIJ+thoracic spine" (for detecting patients with ASDAS-CRP≥1.3) or "SIJ+total spine" (for detecting patients with ASDAS-CRP≥2.1) outperformed that of the individual SIJ score (P<0.05). CONCLUSION: The combination of MRI of the SIJ and spine allows to accurately discriminate between active and inactive axSpA, outperforming SIJ MRI alone.

Comparison of bone lesion distribution between prostate cancer and multiple myeloma with whole-body MRI.

PURPOSE: To assess the distribution of bone lesions in patients with prostate cancer (PCa) and those with multiple myeloma (MM) using whole-body magnetic resonance imaging (MRI); and to assess the added value of four anatomical regions located outside the thoraco-lumbo-pelvic area to detect the presence of bone lesions in a patient-based perspective. MATERIALS AND METHODS: Fifty patients (50 men; mean age, 67±10 [SD] years; range, 59-87 years) with PCa and forty-seven patients (27 women, 20 men; mean age, 62.5±9 [SD] years; range, 47-90 years) with MM were included. Three radiologists assessed bone involvement in seven anatomical areas reading all MRI sequences. RESULTS: In patients with PCa, there was a cranio-caudal increasing prevalence of metastases (22% [11/50] in the humeri and cervical spine to 60% [30/50] in the pelvis). When the thoraco-lumbo-pelvic region was not involved, the prevalence of involvement of the cervical spine, proximal humeri, ribs, or proximal femurs was 0% in patients with PCa and≥4% (except for the cervical spine, 0%) in those with MM. CONCLUSION: In patients with PCa, there is a cranio-caudal positive increment in the prevalences of metastases and covering the thoraco-lumbo-pelvic area is sufficient to determine the metastatic status of a patient with PCa. In patients with MM, there is added value of screening all regions, except the cervical spine, to detect additional lesions.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group.

Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique.

MRI for response assessment in metastatic bone disease.

BACKGROUND: Beyond lesion detection and characterisation, and disease staging, the quantification of the tumour load and assessment of response to treatment are daily expectations in oncology. METHODS: Bone lesions have been considered "non-measurable" for years as opposed to lesions involving soft tissues and "solid" organs like the lungs or liver, for which response evaluation criteria are used in every day practice. This is due to the lack of sensitivity, specificity and measurement capabilities of imaging techniques available for bone assessment, i.e. skeletal scintigraphy (SS), radiographs and computed tomography (CT). RESULTS: This paper reviews the possibilities and limitations of these techniques and highlights the possibilities of positron emission tomography (PET), but mainly concentrates on magnetic resonance imaging (MRI). CONCLUSION: Practical morphological and quantitative approaches are proposed to evaluate the treatment response of bone marrow lesions using "anatomical" MRI. Recent developments of MRI, i.e. dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI), are also covered. KEY POINTS: • MRI offers improved evaluation of skeletal metastases and their response to treatment. • This new indication for MRI has wide potential impact on radiological practice. • MRI helps meet the expectations of the oncological community. • We emphasise the practical aspects, with didactic cases and illustrations.

Whole-body MRI (WB-MRI) versus axial skeleton MRI (AS-MRI) to detect and measure bone metastases in prostate cancer (PCa).

OBJECTIVE: To compare whole-body MRI (WB-MRI) and axial skeleton MRI (AS-MRI) in detecting and measuring bone metastases in patients with prostate cancer (PCa). METHODS: WB-MRI and AS-MRI examinations were performed in 60 patients with PCa at high risk of metastases. Two radiologists separately categorised the AS-MRI and WB-MRI as negative or positive for metastases, and measured focal metastases using the "Response evaluation criteria in solid tumours" (RECIST) criteria transposed to bone. One radiologist reviewed all examinations 2 months later. Inter- and intraobserver agreements in establishing the presence/absence of metastases were calculated. Bland-Altman plots were used to assess measurement agreement between AS-MRI and WB-MRI. RESULTS: Strong to perfect inter- and intraobserver agreements were found between AS-MRI and WB-MRI in defining the presence/absence of bone metastases. There were no patients with isolated "peripheral" metastases at WB-MRI, missed at AS-MRI. There was no difference in lesion count between the two radiologists. AS-MRI and WB-MRI provided statistically equivalent RECIST values for one radiologist and slightly lower values at AS-MRI for the other. CONCLUSIONS: In our series of PCa patients, AS-MRI and WB-MRI were equivalent in determining the presence/absence of bone metastases and provided similar evaluation of the metastatic burden.

Fracture-associated and idiopathic subchondral vertebral lesions: a magnetic resonance study in autopsy specimens with histologic correlation.

OBJECTIVE: The aim of this study was to describe and compare the magnetic resonance (MR) and histological appearance of subchondral vertebral lesions that are idiopathic or that develop with vertebral fractures. MATERIALS AND METHODS: T1- and T2-weighted spin-echo images and radiographs were obtained in 81 cadaveric spine specimens. All subchondral vertebral lesions that were considered to be idiopathic or associated with vertebral end plate fractures were selected. Lesions due to growth disturbance were excluded. Radiographs and MR images were analyzed in consensus by two radiologists, and sampled specimens were analyzed by a pathologist. RESULTS: Eleven idiopathic and ten fracture-associated vertebral lesions were available. On T1-weighted images, all lesion signal intensity was low and homogeneous. On T2-weighted images, all idiopathic lesions showed a heterogeneous signal with a central low or intermediate signal component and a peripheral high or intermediate component. All but one fracture-related lesions showed a homogeneous intermediate to high signal intensity. Histological analysis of idiopathic lesions showed a central acellular fibrous connective tissue in all cases surrounded by loose connective tissue in nine cases. Herniated disk material and cartilage metaplasia were found in one lesion only. Fracture-associated lesions contained herniated disk material, necrotic tissue, and loose connective tissue with a peripheral component of loose fibrovascular connective tissue in four cases only. CONCLUSION: MR and histological appearance of idiopathic and fracture-associated subchondral vertebral lesions differ, suggesting that they might have a different origin.

MR appearance of cartilage defects of the knee: preliminary results of a spiral CT arthrography-guided analysis.

The aim of this study was to determine signal intensity patterns of cartilage defects at MR imaging. The MR imaging (3-mm-thick fat-suppressed intermediate-weighted fast spin-echo images) was obtained in 31 knees (21 male and 10 female patients; mean age 45.5 years) blindly selected from a series of 252 consecutive knees investigated by dual-detector spiral CT arthrography. Two radiologists determined in consensus the MR signal intensity of the cartilage areas where cartilage defects had been demonstrated on the corresponding reformatted CT arthrographic images. There were 83 cartilage defects at spiral CT arthrography. In 52 (63%) lesion areas, the MR signal intensity was higher than that of adjacent normal cartilage with signal intensity equivalent to (n=31) or lower than (n=21) that of articular fluid. The MR signal intensity was equivalent to that of adjacent normal cartilage in 17 (20%) lesion areas and lower than that of adjacent cartilage in 8 (10%) lesion areas. In 6 (7%) lesion areas, mixed low and high signal intensity was observed. The MR signal intensity of cartilage defects demonstrated on spiral CT arthrographic images varies from low to high on fat-suppressed intermediate-weighted fast spin-echo MR images obtained with our equipment and MR parameters.

Frequency and topography of lesions of the femoro-tibial cartilage at spiral CT arthrography of the knee: a study in patients with normal knee radiographs and without history of trauma.

OBJECTIVE: To determine the frequency and topography of cartilage lesions involving the femoro-tibial joints in patients with normal knee radiographs and without a remembered history of trauma. DESIGN AND PATIENTS: A radiologist retrospectively reviewed the dual-detector spiral CT knee arthrograms performed in 209 consecutive patients (mean age 37.6 years) with normal knee radiographs. Images were analyzed for the presence, grade (Noyes classification system) and location of cartilage lesions, the location being designated by dividing each articular surface into a grid of 16 parts. RESULTS: Fifty-three percent of knees had cartilage lesions of grade 2A or higher that involved articular surfaces to a variable extent: lateral tibial plateau (31%), medial femoral condyle (27%), medial tibial plateau (14%) and lateral femoral condyle (5%). Areas of the posterior half of the lateral tibial plateau and of the inner half of the medial femoral condyle were statistically more frequently involved than their counterparts (P<0.0001). The bare area of the medial tibial plateau, but not that of the lateral tibial plateau, was more frequently involved than the corresponding meniscus-covered area (P<0.0001). CONCLUSION: Cartilage lesions of grade 2A or higher, detected at spiral CT arthrography in 53% of the knees, predominantly involved the posterior half of the lateral tibial plateau, the inner half of the medial femoral condyle and the bare area of the medial tibial plateau.

Spiral CT arthrography of the knee: technique and value in the assessment of internal derangement of the knee.

Computed tomography imaging has achieved excellent multiplanar capability and submillimeter spatial resolution due to the development of the spiral acquisition mode and multidetector row technology. Multidetector spiral CT arthrography (CTA) yields valuable information for the assessment of internal derangement of the joints. This article focuses on the value of spiral CTA of the knee in the assessment of the meniscus, anterior cruciate ligament, and hyaline cartilage lesions. Advantages and disadvantages of spiral CTA with respect to MR imaging are presented.

Concurrent spinal cord and vertebral bone marrow radionecrosis 8 years after therapeutic irradiation.

Concurrent radionecrosis within the spinal cord and the bone marrow at the same thoracic level was observed 8 years after localized therapeutic irradiation in a patient who had undergone repeated cycles of radiotherapy, glucocorticoid treatment, and chemotherapy for a non-Hodgkin's lymphoma. Mechanisms combining radiotoxic potentialization by glucocorticoids/alkylating agents and delayed radiation-induced vasculitis involving the common arterial pathways to the spinal cord and to the vertebrae were speculated to have acted in a synergistic way.

Spiral CT arthrography of the postoperative knee.

Computed tomography (CT) has gained multiplanar capability and submillimeter spatial resolution due to the development of spiral acquisition mode and multidetector row technology. Multidetector spiral CT arthrography of the knee is a valuable imaging modality for the assessment of lesions of the meniscus, anterior cruciate ligament (ACL), and articular cartilage. This article presents the value of spiral CT arthrography in the assessment of the postoperative knee with emphasis on the postoperative meniscus, articular cartilage, and ACL graft. This technique may be proposed as an alternative to magnetic resonance arthrography.