Jean-Michel Serfaty

Intratendinous Injection of Platelet-Rich Plasma under US Guidance to Treat Tendinopathy: A Long-Term Pilot Study

PURPOSE To assess the potential therapeutic effect of intratendinous injection of platelet-rich plasma (PRP) under ultrasound (US) guidance to treat tendon tears and tendinosis in a pilot study with long-term follow-up. MATERIALS AND METHODS The study included 408 consecutive patients referred for treatment by PRP injection of tendinopathy in the upper (medial and lateral epicondylar tendons) and the lower (patellar, Achilles, hamstring and adductor longus, and peroneal tendons) limb who received a single intratendinous injection of PRP under US guidance. Clinical and US data were retrospectively collected for each anatomic compartment for upper and lower limbs before treatment (baseline) and 6 weeks after treatment. Late clinical data without US were collected until 32 months after the procedure (mean, 20.2 months). The McNemar test and regression model were used to compare clinical and US data. RESULTS QuickDASH score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and residual US size of lesions were significantly lower after intratendinous injection of PRP under US guidance at 6 weeks and during long-term follow-up compared with baseline (P < .001 in upper and lower limb) independent of age, gender, and type of tendinopathy (P > .29). No clinical complication was reported during follow-up. CONCLUSIONS Intratendinous injection of PRP under US guidance appears to allow rapid tendon healing and is well tolerated.

Quantification of Multicontrast Vascular MR Images with NLSnake, an Active Contour Model: In Vitro Validation and In Vivo Evaluation

Vessel‐wall measurements from multicontrast MRI provide information on plaque structure and evolution. This requires the extraction of numerous contours. In this work a contour‐extraction method is proposed that uses an active contour model (NLSnake) adapted for a wide range of MR vascular images. This new method employs length normalization for the purpose of deformation computation and offers the advantages of simplified parameter tuning, fast convergence, and minimal user interaction. The model can be initialized far from the boundaries of the region to be segmented, even by only one pixel. The accuracy and reproducibility of NLSnake endoluminal contours were assessed on vascular phantom MR angiography (MRA) and high‐resolution in vitro MR images of rabbit aorta. An in vivo evaluation was performed on rabbit and clinical data for both internal and external vessel‐wall contours. In phantoms with 95% stenoses, NLSnake measured 94.3% ± 3.8%, and the accuracy was even better for milder stenoses. In the images of rabbit aorta, variability between NLSnake and experts was less than interobserver variability, while the maximum intravariability of NLSnake was equal to 1.25%. In conclusion, the NLSnake technique successfully quantified the vessel lumen in multicontrast MR images using constant parameters. Magn Reson Med 51:370–379, 2004.

Leukocyte mimetic polysaccharide microparticles tracked in vivo on activated endothelium and in abdominal aortic aneurysm

We have developed injectable microparticles functionalized with fucoidan, in which sulfated groups mimic the anchor sites of P-selectin glycoprotein ligand-1 (PSGL-1), one of the principal receptors supporting leukocyte adhesion. These targeted microparticles were combined with a fluorescent dye and a T2(∗) magnetic resonance imaging (MRI) contrast agent, and then tracked in vivo with small animal imaging methods. Microparticles of 2.5μm were obtained by a water-in-oil emulsification combined with a cross-linking process of polysaccharide dextran, fluorescein isothiocyanate dextran, pullulan and fucoidan mixed with ultrasmall superparamagnetic particles of iron oxide. Fluorescent intravital microscopy observation revealed dynamic adsorption and a leukocyte-like behaviour of fucoidan-functionalized microparticles on a calcium ionophore induced an activated endothelial layer of a mouse mesentery vessel. We observed 20times more adherent microparticles on the activated endothelium area after the injection of functionalized microparticles compared to non-functionalized microparticles (197±11 vs. 10±2). This imaging tool was then applied to rats presenting an elastase perfusion model of abdominal aortic aneurysm (AAA) and 7.4T in vivo MRI was performed. Visual analysis of T2(∗)-weighted MR images showed a significant contrast enhancement on the inner wall of the aneurysm from 30min to 2h after the injection. Histological analysis of AAA cryosections revealed microparticles localized inside the aneurysm wall, in the same areas in which immunostaining shows P-selectin expression. The developed leukocyte mimetic imaging tool could therefore be relevant for molecular imaging of vascular diseases and for monitoring biologically active areas prone to rupture in AAA.

Comparison of apparent diffusion coefficient in spondylarthritis axial active inflammatory lesions and type 1 Modic changes.

OBJECTIVE The goal of this study was to evaluate whether the values of ADC in spondylarthritis axial active inflammatory lesions are different from ADC values in type 1 Modic changes. SUBJECTS AND METHODS 95 patients with recent lumbar pain, including 46 patients with diagnosed or suspected spondylarthritis and 49 patients with purely degenerative history, underwent spine MRI. T1w, STIR, and diffusion-weighted images (DWI) were obtained. Two musculoskeletal radiologists interpreted the images. Axial active inflammatory lesions from the SpA group and type 1 Modic changes from the degenerative group were identified on T1w and STIR sequences. ADC values from these lesions and from healthy subchondral bone were compared. RESULTS All axial active inflammatory lesions (n=27) and type 1 Modic changes (n=22) identified in T1w and STIR images were visible on DWI. ADC values were significantly higher (p<0.05) for axial active inflammatory lesions (median=0.788×10(-3)mm(2)/s, IQR 25-75 [0.7×10(-3)mm(2)/s; 0.9×10(-3)mm(2)/s]) than for type 1 Modic changes (median=0.585×10(-3)mm(2)/s, IQR 25-75 [0.55×10(-3)mm(2)/s; 0.60×10(-3)mm(2)/s]) and normal subchondral bone (median=0.443×10(-3)mm(2)/s, IQR 25-75 [0.40×10(-3)mm(2)/s; 0.50×10(-3)mm(2)/s]). Intra-class correlation coefficients for intra- and inter-reader ADC values comparison were excellent (0.89 and 0.98 respectively). CONCLUSION DWI is a sensitive and fast sequence that offer the possibility of quantifying diffusion coefficients of the lesions, which could help to discriminate between spondylarthritis axial active inflammatory and type 1 Modic changes.

Evaluation of mitral stenosis in 2008.

Percutaneous mitral valve commissurotomy (PMC) is the treatment of choice for patients with mitral stenosis (MS) and favorable anatomy. Evaluation of MS should answer two questions: is MS severe? And is the valve suitable for PMC? Evaluation of MS severity relies on accurate echocardiographic assessment of the mitral valve area (MVA). Several methods can be used, often in combination. The planimetry is the reference method but must be precisely performed at the tips of the leaflets in a well-oriented plane and thus requires experienced operators. New imaging technologies, such as 3D-echocardiography, MRI or computed tomography may reduce planimetrys operator dependence. The pressure half-time method (PHT) has the merit of simplicity but should be used cautiously in elderly patients or those in atrial fibrillation. It is invalid immediately after PMC but can still be used as a semi-quantitative method: a PHT less than 130 msec is associated with a good valve opening with an excellent specificity and positive predictive value whereas a PHT 130 msec does not allow any conclusion. The continuity equation, easy to perform, may be invalidated by the commonly associated aortic or mitral regurgitation or in case of atrial fibrillation. The PISA method, is reputed technically challenging and requires a direct measurement of angle between the mitral leaflets, although the use of a fixed value of 100 degrees provides an accurate MVA estimation. The main indication of transesophageal echocardiography is the exclusion of left atrial thrombus, which is a contra-indication to PMC as well as a 2/4 or greater mitral regurgitation grade. Two-dimensional-echocardiography allows detailed evaluation of valve morphology, including leaflet thickness and mobility, degree and localization of calcifications, extent of the subvalvular involvement. Unfavorable valve anatomy is associated with a lower rate of PMC success and lower event-free survival. However, given the low predictive value of all anatomic scores, the decision to perform or not the procedure should be based on a global approach taking into account not only the valve anatomy but also individual patients characteristics such as age, rhythm, NYHA class, MVA and the predicted operative mortality based on associated comorbidities.

Efficacy of second intra-tendinous platelet-rich-plasma injection in case of incomplete response of the first injection: Three-year follow up experience

PURPOSE Tendinopathy is a frequent and ubiquitous disease developing early disorganized collagen fibers with neo-angiogenesis on histology. Peritendinous injection of corticosteroid is the commonly accepted strategy despite the absence of inflammation in tendinopathy. Platelet-rich plasma (PRP) might be a useful strategy to rapidly accelerate healing of the tendinopathy but there is a lack ok knowledge about the amount of PRP to be injected and the opportunity of a second injection in case of partial pain relief. The aim of our study was to assess the potential therapeutic effect of early second PRP intra-tendinous to treat persistent painful tendon tear and tendinosis in a long-term follow-up by ultrasonography (US) and clinical data in case of incomplete efficiency of first PRP treatment injection. MATERIALS AND METHODS Twenty-four consecutive patients referred for US treatment of tendon tear or tendinosis (T+) were included retrospectively. All had previously received a single intra-tendinous injection of PRP under US guidance (PRPT+) and benefited of a second PRP injection (PRPT2+) under US guidance in order to treat persistent painful. US and clinical data were collected for each anatomic compartment for upper and lower limbs before treatment (D0), 6 weeks (W6) after first treatment, 6 weeks (W12) after second treatment and until 32-month follow-up. We used Mac Nemar test and regression model to compare US and clinical data. RESULTS The residual US size of lesions was not significantly lower at W12 after PRPT2+ as compared to W6 (P=0.86 in upper and P=NS in lower member) independently of age (P=0.22), gender (P=0.97) and kind of tendinopathy (P=NS). Quick dash test values and WOMAC values were not significantly lower in PRPT+ at W12 (average: 21.5 months) as compared to W6 (P>0.66) and long-term follow-up (P>0.75) independently of age (P=0.39), gender (P=0.63) and kind of tendinopathy (P=NS). Nevertheless, comparison between D0 and long-term follow-up (LTF) functionnal score was statistically significant (p<0.001 in upper and lower member). CONCLUSION Our study suggests that second early intra-tendinous PRP injection under US guidance does not permit rapid decrease of tendinopathy area in US, nor does it quickly improve clinical pain and functional data in case of incomplete efficiency of first PRP injection. However, in long-term follow-up, patients improved their ability to mobilize pathologic tendons.

Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

PURPOSE Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. MATERIALS AND METHOD Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1(®) (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T-) after injecting AA in 40 (AAT-). RESULTS All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p<0.004), and less disorganized collagen fibers and neovessels on histology (p<0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p>0.05). Comparison between AAT- and T- showed no AA toxicity on tendon (p = 0.18). CONCLUSION Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendons healing, with no local toxicity.

In Vitro, Nonrigid Model of Aortic Arch Aneurysm

PURPOSE To develop and validate a controlled patient-derived process for producing an in vitro, nonrigid model of aortic arch aneurysm. MATERIALS AND METHODS A three-dimensional magnetic resonance (MR) angiogram derived from a patient with an aortic arch aneurysm was segmented by using a homemade software package, meshed and converted to Standard Tessellation Language (STL) file format. The authors transferred this format to a stereolithography machine to produce a replica of the entire aorta, including the arch aneurysm and supraaortic arteries, by pouring silicone rubber. RESULTS A sturdy, life-size, soft, transparent plastic cast, accurately reproducing both the internal and external anatomy of the aortic aneurysm, was produced in less than 1 week. Comparison between the STL file format of MR angiographic images of both the patients aorta and model enabled validation of the reliability of the manufacturing process. CONCLUSIONS The combination of easy segmentation and conversion to the STL file format with stereolithography techniques enabled a realistic, life-size, silicone vascular phantom to be created from a live patient imaging dataset.

In vivo targeted molecular imaging for activated platelets by mri using USPIO-fucoidan in rat abdominal aortic aneuryms model

Background P-selectin, expressed on the activated platelets and endothelial cells, is one of the key adhesion molecules that regulate leukocyte trafficking in atherosclerosis. The natural and canonical ligand of selectins is a specific tetrasaccharide structure known as 6-sulfo sialyl Lewis X (SLeX). Fucoidans refer to a type of polysaccharide that contains L-fucose and sulfate ester groups, mainly derived from brown seaweed, and binds strongly to P-selectin. We assessed the hypothesis that a new MRI contrast agent made of fucoidan conjugated with ultra small paramagnetic iron oxide (USPIO) can demonstrate the presence of activated platelets in thrombus of an expanding aneurysm.

Efficacy of subcutaneous injection of platelet-rich plasma in alopecia: A clinical and histological pilot study on a rat model with a six-month long-term follow-up experience

To assess the potential of platelet‐rich plasma (PRP) subcutaneous injection of to treat alopecia and to evaluate local toxicity.