Morphological and Quantitative Parametric MRI Follow-up of Cartilage Changes Before and After Intra-articular Injection Therapy in Patients With Mild to Moderate Knee Osteoarthritis: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Intra-articular injections are routinely used for conservative treatment of knee osteoarthritis (OA). The detailed comparative therapeutic effects of these injections on cartilage tissue are still unclear. OBJECTIVE: The aim of this study was to detect and compare knee cartilage changes after intra-articular injection of glucocorticoid, hyaluronic acid, or platelet-rich plasma (PRP) to placebo using quantitative (T2 and T2* mapping) and morphological magnetic resonance imaging parameters in patients with mild or moderate osteoarthritis. MATERIALS AND METHODS: In a double-blinded, placebo-controlled, single-center trial, knees with mild or moderate osteoarthritis (Kellgren-Lawrence grade 1-3) were randomly assigned to an intra-articular injection with 1 of these substances: glucocorticoid, hyaluronic acid, PRP, or placebo. Cartilage degeneration on baseline and follow-up magnetic resonance imaging scans (after 3 and 12 months) was assessed by 2 readers using quantitative T2 and T2* times (milliseconds) and morphological parameters (modified Outerbridge grading, subchondral bone marrow edema, subchondral cysts, osteophytes). RESULTS: One hundred twenty knees (30 knees per treatment group) were analyzed with a median patient age of 60 years (interquartile range, 54.0-68.0 years). Interreader reliability was good for T2 (ICC, 0.76; IQR, 0.68-0.83) and T2* (ICC, 0.83; IQR, 0.76-0.88) measurements. Morphological parameters showed no significant changes between all groups after 3 and 12 months. T2 mapping after 12 months showed the following significant ( P = 0.001-0.03) changes between groups in 6 of 14 compartments: values after PRP injection decreased compared with glucocorticoid in 4 compartments (complete medial femoral condyle and central part of lateral condyle) and compared with placebo in 2 compartments (anterior and central part of medial tibial plateau); values after glucocorticoid injection decreased compared with placebo in 1 compartment (central part of medial tibial plateau). No significant changes were seen for T2 and T2* times after 3 months and T2* times after 12 months. No correlation was found between T2/T2* times and Kellgren-Lawrence grade, age, body mass index, or pain (Spearman ρ, -0.23 to 0.18). CONCLUSIONS: Platelet-rich plasma injection has a positive long-term effect on cartilage quality in the medial femoral compartment compared to glucocorticoid, resulting in significantly improved T2 values after 12 months. For morphological cartilage parameters, injections with glucocorticoid, PRP, or hyaluronic acid showed no better effect in the short or long term compared with placebo.

[Definition of hip dysplasia in 2023 : Signs of macro and micro instability]. / Definition der Hüftdysplasie im Jahr 2023 : Zeichen der Makro- und Mikroinstabilität.

BACKGROUND: Hip dysplasia is a complex static-dynamic pathology leading to chronic joint instability and osteoarthritis. Because our understanding of the underlying pathomorphologies of hip dysplasia, both on the macro and micro levels, has evolved, an updated definition is needed. QUESTION: What is the definition of hip dysplasia in 2023? METHODS: By summarizing and reviewing relevant literature, we provide an up-to-date definition of hip dysplasia with a guide to appropriately making the diagnosis. RESULTS: In addition to the pathognomonic parameters, supportive and descriptive indicators, as well as secondary changes are used to fully characterize instability inherent in hip dysplasia. The primary diagnostic tool is always the plain anteroposterior pelvis radiograph, which can be supplemented by additional investigations (MRI of the hip with intraarticular contrast agent; CT) if necessary. CONCLUSION: The complexity, subtlety, and diversity of the pathomorphology of residual hip dysplasia requires careful, multilevel diagnosis and treatment planning in specialized centers.

Atypical patterns of spinal segment degeneration in patients with abdominal aortic aneurysms.

PURPOSE: Abdominal aortic aneurysms (AAAs) affect the vascular perfusion of the lumbar spine. The treatment of AAAs with endovascular aortic aneurysm repair (EVAR) completely occludes the direct vascular supply to the lumbar spine. We hypothesized that patients with AAA who undergo EVAR show a different pattern of spinal degeneration than individuals without AAA. METHODS: In this retrospective institutional review board-approved study, 100 randomly selected patients with AAA who underwent EVAR with computed tomography (CT) scans between 2005 and 2017 were compared with age- and gender-matched controls without AAA. In addition, long-term follow-up CT images (> 6 months before EVAR, at the time of EVAR, and > 12 months after EVAR) of the patients were analysed to compare the progression of degeneration from before to after EVAR. Degeneration scores, lumbar levels with the most severe degeneration, and lumbar levels with progressive degeneration were analysed in all CT images. Fisher's exact test, Wilcoxon signed-rank test, and Mann-Whitney U test were performed for statistical analyses. RESULTS: Compared with the control group (n = 94), the most severe degeneration was more commonly detected in the mid-lumbar area in the patient group (n = 100, p = 0.016), with significantly more endplate erosions being detected in the lumbar spine (p = 0.015). However, EVAR did not result in significant additional acceleration of the degenerative process in the long-term follow-up analysis (n = 51). CONCLUSION: AAA is associated with atypical, more cranially located spinal degradation, particularly in the mid-lumbar segments; however, EVAR does not seem to additionally accelerate the degenerative process. This observation underlines the importance of disc and endplate vascularization in the pathomechanism of spinal degeneration. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

The Vulcan salute sign: a non-sensitive but specific sign for Morton's neuroma on radiographs.

OBJECTIVES: To assess the value of the divergence of toes on conventional radiographs of the foot for diagnosing Morton's neuroma. METHODS: This retrospective case-control study was approved by the local ethics committee. In 100 patients with MRI-proven Morton's neuroma 2/3 or 3/4 (study group) and 100 patients without (control group), conventional weight-bearing dorso-plantar view radiographs were evaluated for the subjective presence of interphalangeal divergence, called the Vulcan salute sign or V-sign, by two blinded, independent musculoskeletal radiologists. Interphalangeal angles (2/3 and 3/4) and intermetatarsal angle I/V were measured. The t test and chi-squared test were used to compare the groups. Diagnostic performance was calculated. Interobserver reliability was assessed using κ statistics and intraclass correlation coefficient (ICC). RESULTS: The difference between the groups was significant (P < 0.05) regarding the presence of the V-sign, which was found in 30 of 100 patients with Morton neuroma and in 3 of 100 control patients, with a sensitivity of 30% and a specificity of 97%. The differences between interphalangeal angles were significant (P < 0.05) between the groups. The interphalangeal angle 2/3 mean values were 7.9° (± 4.8) for the study group vs 5.4° (± 2.6) for the controls; the 3/4 angle values were 6.5° (± 3.8) and 3.4° (± 2.5), respectively. There was no significant difference between the groups in the intermetatarsal angle I/V. Interobserver agreement was substantial for the V-sign, with a κ value of 0.78. The ICC was excellent concerning angle measurements, with all values ≥ 0.94. CONCLUSION: The Vulcan salute sign on conventional radiographs is specific for Morton's neuroma.

Ultra-high resolution 3D MRI for chondrocalcinosis detection in the knee-a prospective diagnostic accuracy study comparing 7-tesla and 3-tesla MRI with CT.

OBJECTIVES: To test the diagnostic accuracy of a 3D dual-echo steady-state (DESS) sequence at 7-T MRI regarding the detection of chondral calcific deposits of the knee in comparison to 3-T MRI, using CT as cross-sectional imaging reference standard. METHODS: CT and 7-T MRI (DESS) of knee joints in 42 patients with radiographically known chondrocalcinosis (13 of 42 bilateral) were prospectively acquired for all included patients (n = 55 knee joints). Additionally, 3-T MRI (DESS) was performed for 20 of these 55 knee joints. Two fellowship-trained musculoskeletal radiologists scored eight cartilage regions of each knee joint separately regarding presence of cartilage calcification, diagnostic confidence level, and sharpness of calcific deposits. In an explorative subanalysis, micro-CT of the menisci was evaluated after knee arthroplasty in one patient. Diagnostic performance metrics and nonparametric tests were used to compare between modalities. p values < 0.05 were considered to represent statistical significance. RESULTS: Sensitivity for chondrocalcinosis detection was significantly higher for 7-T MRI (100%) compared to 3-T MRI (reader 1: 95.9%, p = 0.03; reader 2: 93.2%, p = 0.002). The diagnostic confidence was significantly higher for both readers at 7 T compared to both 3-T MRI (p < 0.001) and to CT (p = 0.03). The delineation of chondral calcifications was significantly sharper for 7-T compared to both 3-T MRI and CT (p < 0.001, both readers). Micro-CT in one patient suggested that 7-T MRI may potentially outperform standard CT in diagnosing chondral calcifications. CONCLUSION: 3D-DESS imaging at 7-T MRI offers a significantly higher sensitivity in detection of chondral calcific deposits compared to 3-T MRI. KEY POINTS: • 3D dual-echo steady-state (DESS) MRI at 7 T has a higher sensitivity in detection of chondral calcific deposits compared to 3-T MRI (p ≤ 0.03). • 3D DESS MRI at 7 T yields no false-negative cases regarding presence of chondral calcific deposits. • 3D DESS MRI at 7 T offers better delineation and higher diagnostic confidence in detection of chondral calcific deposits compared to 3-T MRI (p < 0.001).

Pelvic bone CT: can tin-filtered ultra-low-dose CT and virtual radiographs be used as alternative for standard CT and digital radiographs?

OBJECTIVES: To compare ultra-low-dose CT (ULD-CT) of the osseous pelvis with tin filtration to standard clinical CT (CT), and to assess the quality of computed virtual pelvic radiographs (VRs). METHODS: CT protocols were optimized in a phantom and three pelvic cadavers. Thirty prospectively included patients received both standard CT (automated tube voltage selection and current modulation) and tin-filtered ULD-CT of the pelvis (Sn140kV/50mAs). VRs of ULD-CT data were computed using an adapted cone beam-based projection algorithm and were compared to digital radiographs (DRs) of the pelvis. CT and DR dose parameters and quantitative and qualitative measures (1 = worst, 4 = best) were compared. CT and ULD-CT were assessed for osseous pathologies. RESULTS: Dose reduction of ULD-CT was 84% compared to CT, with a median effective dose of 0.38 mSv (quartile 1-3: 0.37-0.4 mSv) versus 2.31 mSv (1.82-3.58 mSv; p < .001), respectively. Mean dose of DR was 0.37 mSv (± 0.14 mSv). The median signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of bone were significantly higher for CT (64.3 and 21.5, respectively) compared to ULD-CT (50.4 and 18.8; p ≤ .01), while ULD-CT was significantly more dose efficient (figure of merit (FOM) 927.6) than CT (FOM 167.6; p < .001). Both CT and ULD-CT were of good image quality with excellent depiction of anatomy, with a median score of 4 (4-4) for both methods (p = .1). Agreement was perfect between both methods regarding the prevalence of assessed osseous pathologies (p > .99). VRs were successfully calculated and were equivalent to DRs. CONCLUSION: Tin-filtered ULD-CT of the pelvis at a dose equivalent to standard radiographs is adequate for assessing bone anatomy and osseous pathologies and had a markedly superior dose efficiency than standard CT. KEY POINTS: • Ultra-low-dose pelvic CT with tin filtration (0.38 mSv) can be performed at a dose of digital radiographs (0.37 mSv), with a dose reduction of 84% compared to standard CT (2.31 mSv). • Tin-filtered ultra-low-dose CT had lower SNR and CNR and higher image noise than standard CT, but showed clear depiction of anatomy and accurate detection of osseous pathologies. • Virtual pelvic radiographs were successfully calculated from ultra-low-dose CT data and were equivalent to digital radiographs.

High-resolution in vivo MR imaging of intraspinal cervical nerve rootlets at 3 and 7 Tesla.

OBJECTIVES: No routine imaging technology allows reliable visualization of nerve rootlets inside the spinal canal with positive contrast. The stronger MR signal at 7 T, with optimized protocols, may offer a solution. The purpose was to evaluate the potential of 3D Dual-Echo Steady-State (DESS) MR imaging of the cervical spine at 3 and 7 T in assessing the micro-anatomy of the nerve rootlets. MATERIALS/METHODS: This prospective study was approved by the local ethics committee. Twenty-one patients, clinically referred to cervical-spine MRI, underwent additional MR exams at 3 T and 7 T, each of which consisted of a single 3D-DESS series with equal acquisition times. Artifacts, visualization quality, and number of identified rootlets (C2 to C8) were rated by two musculoskeletal radiologists. Results were compared by Wilcoxon tests. Interobserver reliability was assessed using weighted κ statistics and intraclass correlation coefficient (ICC). RESULTS: Intraspinal rootlets could successfully be visualized at both field strengths. Rating differences for artifacts and quality of rootlet depiction were not significant for the two field strengths. The mean number of identified rootlets was larger for 7-T than for 3-T MR for every assessed nerve; however, this difference was not statistically significant using the Bonferroni correction (p values ranging from 0.002 to 0.53). Interobserver agreement was substantial to almost perfect (weighted κ values of 0.69 and 0.82). The ICC for the number of identified rootlets was 0.80. CONCLUSION: Non-invasive 3D-DESS MR-imaging at 3 and 7 T has the potential to provide precise assessments of the micro-anatomy of intraspinal cervical nerve roots. KEY POINTS: • Cervical rootlets can be successfully visualized with positive contrast using 3D-DESS MR-imaging. • 3D-DESS MR-imaging at 3 and 7 T provides precise assessments of the micro-anatomy of cervical nerves. • The mean number of identified cervical rootlets using 3D-DESS was larger for 7 T than for 3 T MR; however, this difference was not statistically significant.

Distal Femoral Cortical Irregularity at Knee MRI: Increased Prevalence in Youth Competitive Alpine Skiers.

Background Tumor-like cortical irregularities at the posterior distal femur are common incidental findings in adolescents, but the origin of these irregularities is debated. Purpose To compare the prevalence of distal femoral cortical irregularities (DFCIs) at different tendon attachment sites in youth competitive alpine skiers with that in young adults. Materials and Methods In this secondary analysis of a prospective trial, unenhanced 3-T knee MRI scans obtained in youth competitive alpine skiers were compared with images in control participants of the same age from 2014 to 2019 (Cantonal Ethics Committee Zurich registry number: KEK-ZH-2017-01395) for presence of DFCIs at the femoral attachment of the medial head of the gastrocnemius muscle (MHG) and/or lateral head of the gastrocnemius muscle (LHG) and adductor magnus tendon by two radiologists. DFCI size and tendon attachment position were measured. Tendon attachment position and associated MRI findings (meniscus, cartilage, bone marrow edema, joint effusion, ligaments, tendons) were examined for an association with DFCI. Pearson χ2, Student t test, logistic regression, and κ statistics were applied. Results Unilateral knee MRI scans obtained in 105 skiers (mean age, 14.8 years ± 0.6 [standard deviation]; 66 boys) and in 105 control participants (mean age, 14.6 years ± 0.5; 59 boys) were evaluated. DFCIs were found in 61 of 105 skiers (58%; 95% confidence interval [CI]: 48.5%, 67.2%) compared with 28 of 105 control participants (27%; 95% CI: 18.9%, 35.7%) (P < .001). Two skiers had more than one DFCI. Distribution of DFCIs for skiers and control participants was 60 of 63 (95.2%) and 26 of 28 (92.8%) at the MHG, three of 63 (4.8%) and one of 28 (3.6%) at the LHG, and zero of 63 (0%) and one of 28 (3.6%) at the adductor magnus attachment site, respectively. Interreader agreement was almost perfect (κ = 0.87; 95% CI: 0.80, 0.93). The mean size of MHG-related DFCIs in skiers (3.7 mm) was not different compared to the size of those in control participants (3.4 mm) (P = .32), nor was a difference found for the MHG tendon attachment position in knees with DFCI (63.9 mm vs 63.0 mm, P = .83) or without DFCI (63.6 mm vs 62.8 mm, P = .86). Regarding associated MRI findings, increased signal intensity of the MHG tendon showed a significant association with MHG-related DFCI in both groups (P = .01 for both). Conclusion A distal femoral cortical irregularity at the attachment sites of tendons was a frequent incidental finding on knee MRI scans, with an increased prevalence in youth competitive alpine skiers. © RSNA, 2020 Online supplemental material is available for this article.

MRI of complex regional pain syndrome in the foot.

PURPOSE: To evaluate the diagnostic potential of MRI in patients with suspected CRPS (complex regional pain syndrome). METHOD: A retrospective health-record search was conducted for patients with suspected CRPS (foot). Fifty patients with initially suspected CRPS were included (37 females (51 ± 13 years) and 13 males (44 ± 15 years)). All patients underwent MRI. Two radiologists assessed skin, bone, and soft tissue parameters on MRI. The final diagnosis was CRPS (Gold standard: Budapest criteria) or non-CRPS. MRI parameters were compared between CRPS patients and non-CRPS patients. RESULTS: CRPS was diagnosed in 22/50(44 %) patients. Skin thickness (1.9 ± 0.5 mm vs. 1.7 ± 0.3 mm, p = 0.399), enhancement, and subcutaneous edema showed no differences between CRPS and non-CRPS patients. Bone marrow edema presence and pattern were not different between groups. Up to 50 % of CRPS patients showed no bone marrow edema. Subcortical enhancement and periosteal enhancement were not different between groups. For reader 1, muscle edema score was higher in the non-CRPS group compared to the CRPS group (0.1 ± 0.2 vs. 0.6 ± 1.0, p = 0.008), but not different for reader 2 (0.1 ± 0.5 vs. 0.2 ± 0.8, p = 0.819). Perfusion pattern was more extensive in non-CRPS patients for reader 1 (p = 0.048), but not for reader 2 (p = 0.157). Joint effusions showed no difference between groups. CONCLUSIONS: MRI cannot distinguish between CRPS and non-CRPS patients. The role of MR imaging in patients with suspected CRPS is to exclude alternative diagnoses that would better explain patients' symptoms.

Diagnosis of Periprosthetic Hip Joint Infection Using MRI with Metal Artifact Reduction at 1.5 T.

Background MRI with metal artifact reduction has gained importance in assessment of pain with total hip arthroplasty (THA). However, its role in diagnosis of periprosthetic joint infection (PJI) has not been well defined. Purpose To evaluate findings of PJI after THA and to determine the diagnostic performance of 1.5-T MRI with metal artifact reduction. Materials and Methods Dedicated compressed sensing-based slice encoding for metal artifact correction 1.5-T MRI examinations (from January 2015 to April 2018) in patients with THA PJI (infection group) and noninfected THA (control group) were retrospectively evaluated by two musculoskeletal radiologists. Fisher exact test was used to compare the groups. Sensitivity, specificity, and accuracy were evaluated for each finding. Interobserver reliability was assessed with κ statistics. Results Forty patients (mean age, 69 years ± 11 [standard deviation]; 26 men) in the infection group and 100 patients (mean age, 67 years ± 11; 42 men) in the control group were evaluated. Periosteal reaction, capsule edema, and intramuscular edema differed between the two groups (P < .001 for each finding). Periosteal reaction was found in 31 of 40 patients with infection and 10 of 100 participants in the control group (sensitivity, 78%; specificity, 90%; accuracy, 86%); capsule edema was found in 33 of 40 (infection group) and five of 100 (control group) (sensitivity, 83%; specificity, 95%; accuracy, 91%); and intramuscular edema was found in 38 of 40 (infection group) and 14 of 100 (control group) (sensitivity, 95%; specificity, 86%; accuracy, 89%). Interobserver agreement was almost perfect, with κ values between 0.88 and 0.92. No difference between the two groups was found regarding the presence of osteolysis (infection group, 23 of 40; control group, 60 of 100), bone marrow edema (39 of 40 vs 87 of 100), effusion (20 of 40 vs 26 of 100), abductor tendon lesion (22 of 40 vs 62 of 100), or bursitis (14 of 40 vs 34 of 100) (P > .05 for each finding). Conclusion The presence of periosteal reaction, capsule edema, and intramuscular edema after total hip arthroplasty at 1.5-T MRI with metal artifact reduction had a high accuracy in evaluation of periprosthetic joint infection. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zanetti in this issue.

MRI with state-of-the-art metal artifact reduction after total hip arthroplasty: periprosthetic findings in asymptomatic and symptomatic patients.

OBJECTIVES: To assess the spectrum of periprosthetic MRI findings after primary total hip arthroplasty (THA). METHODS: This multi-center cohort study analyzed 31 asymptomatic patients (65.7 ± 12.7 years) and 27 symptomatic patients (62.3 ± 11.9 years) between 6 months and 2 years after THA. 1.5-T MRI was performed using Compressed Sensing SEMAC and high-bandwidth sequences. Femoral stem and acetabular cup were assessed for bone marrow edema, osteolysis, and periosteal reaction in Gruen zones and DeLee and Charnley zones. Student t test and Fisher's exact test were performed. RESULTS: The asymptomatic and symptomatic groups showed different patterns of imaging findings. Bone marrow edema was seen in 19/31 (61.3%) asymptomatic and 22/27 (81.5%) symptomatic patients, most commonly in Gruen zones 1, 7, and 8 (p ≥ 0.18). Osteolysis occurred in 14/31 (45.2%) asymptomatic and 14/27 (51.9%) symptomatic patients and was significantly more common in Gruen zone 7 in the symptomatic group (8/27 (29.6%)) compared to the asymptomatic group (2/31 (6.5%)) (p = 0.03). Periosteal reaction was present in 4/31 asymptomatic (12.9%) and 9/27 symptomatic patients (33.3%) and more common in Gruen zones 5 and 6 in the symptomatic group (p = 0.04 and 0.02, respectively). In the acetabulum, bone marrow edema pattern was encountered in 3/27 (11.1%) symptomatic patients but not in asymptomatic patients (p ≥ 0.21). Patient management was altered in 8/27 (29.6%) patients based on MRI findings. CONCLUSIONS: Periprosthetic bone marrow edema is common after THA both in asymptomatic and symptomatic patients. Osteolysis and periosteal reaction are more frequent in symptomatic patients. MRI findings led to altered patient management in 29.6% of patients. KEY POINTS: • Bone marrow edema pattern was frequent in both asymptomatic and symptomatic patients after THA, particularly around the proximal femoral stem in Gruen zones 1, 7, and 8. • Osteolysis was significantly more frequent in symptomatic patients in Gruen zone 7. • Periosteal reaction occurred more frequently in symptomatic patients in Gruen zones 5 and 6.

Revisiting Radiographic L5-S1 Parallelism Using MRI T1 Mapping.

PURPOSE: Thirty years ago, we reported that parallel aspect of the L5-S1 disc on a lateral view of the spine might be considered to be an initial stage of disk degeneration. The current study represents an attempt to increase the validity of parallel sign on conventional radiograph using MR real T1 mapping. METHODS: Forty-four young asymptomatic volunteers (mean age 21.6 ± 2.3) underwent lumbar spine MRI, twice the same day, morning and afternoon. Dedicated sequences using the inversion-recovery technique were used to calculate the T1 relaxation time. A region of interest (ROI) representing the nucleus pulposus was defined in each disk. The volunteers were stratified according to the presence or absence of a parallel morphology of L5-S1. Correlation between endplates angles, sacral slopes and T1 values were then evaluated. RESULTS: L5-S1 space looks parallel for angles <10° (mean value 6.9° ± 1.4°). Sacral slope was lower in parallel disks (31.7 ± 4.9° vs. 40.1 ± 5.6°), showing a significant difference of 8.4° (p < 0.05). The T1 relaxation values show a significant difference between the two groups (p < 0.05) with a difference of 96 ms for the morning (1090.9 ± 33.3 ms for the parallel group and 1186.9 ± 41.2 ms for the non-parallel) and 121.9 ms for the afternoon (respectively 1004.7 ± 22.2 ms and 1126.6 ± 12.9 ms). CONCLUSION: The difference between the two groups suggests that parallel morphology of the L5-S1 disk is associated with lower water content.

Therapeutic Benefits and Adverse Effects of Combined Proangiogenic Gene Therapy in Mouse Critical Leg Ischemia.

BACKGROUND: Critical leg ischemia (CLI) represents the ultimate stage of peripheral arterial disease. Despite current surgery advances, patients with CLI have limited therapeutic options. Therapeutic angiogenesis thus appears as a powerful approach, aiming to stimulate vessel formation by angiogenic molecules administration. In this context, combined gene therapy has been proved to be the most efficient. The present study aims to compare, in a preclinical mouse model, the therapeutic benefit of a combination of 2 angiogenic factors fibroblast growth factor 2 (FGF2) and Cyr61 using plasmid and viral vectors, able to generate short- or long-term transgene expression in the leg, respectively. METHODS: Two therapeutic genes, FGF2 and Cyr61, were introduced into internal ribosome entry site-based expression vectors (FGFiCyr) allowing co-expression of the 2 transgenes. The proangiogenic plasmid pC-FGFiCyr was assessed by intramuscular administration followed by electrotransfer into ischemic legs. To generate long-term transgene expression, the FGFiCyr bicistronic cassette was introduced into an adenoassociated virus-derived vector (rAAV). The rAAV treatment was performed either before or immediately after surgery. Therapeutic effects were analyzed by laser Doppler imaging, clinical score, and angiography. RESULTS: The plasmid pC-FGFiCyr improved revascularization, reperfusion, and clinical score. Surprisingly, when AAV-FGFiCyr was injected 21 or 28 days before surgery, the proangiogenic rAAV was drastically deleterious on all measured parameters. In contrast, when administrated shortly after surgery, AAV-FGFiCyr generated therapeutic benefits, with a significantly better clinical score than after treatment with the plasmid. CONCLUSIONS: Therapeutic effects of the angiogenic combination FGF2-Cyr61 is observed with short-term transgene expression, but the treatment is significantly more efficient when a long-term expression viral vector is used. However, the rAAV-FGFiCyr generated therapeutic benefit only when injected in an ischemic leg, whereas the same dose of rAAV exhibited deleterious effects when administrated to healthy animals. These data may contribute to the understanding of the moderate success of proangiogenic treatments in CLI gene therapy clinical assays.

Preservation of the Internal Iliac Arteries with Branched Iliac Stent Grafts (Zenith Bifurcated Iliac Side): 5 Years of Experience.

BACKGROUND: The extension of the aneurysmal disease to the iliac bifurcations is one of the limits of the endovascular treatment of aortoiliac aneurysms. The Zenith Bifurcated Iliac Side (ZBIS(®)) stent graft (Cook Medical) is a branched stent graft making it possible to preserve the internal iliac arteries (IIAs) using a totally endovascular procedure. METHODS: The purpose of this monocentric retrospective study was to analyze the results of the ZBIS stent graft among patients presenting aortoiliac aneurysms extending to the iliac bifurcation treated between January 1st, 2010 and January 1st, 2015 in the department of vascular surgery of the University Hospital of Toulouse. RESULTS: A total of 26 ZBIS stent grafts were implanted in 25 patients. The perioperative mortality was null, and the technical success rate was 96% (24 of 25). The median duration of follow-up was 29 months (1-60). Mortality rate at 30 days was null. The rate of early complications was 4% (1 of 25), with only one early reintervention for acute ischemia. Patency rate at 30 days was 96.1% (25 of 26) with 1 type 1a endoleak observed with 1 aortobi-iliac stent graft. The midterm patency rate without endoleak was 94.7% (18 of 19), with 2 patients presenting a persistent buttock claudication due to the embolization of the IIA. CONCLUSIONS: The ZBIS stent graft makes it possible to exclude aortoiliac aneurysms by endovascular route, whereas preserving the IIA with satisfactory results in the short and medium term. The careful study of the preoperative quality of the IIAs and the respect of the "Instructions for Use" made it possible to obtain a very satisfactory patency rate.