Choukri Mekkaoui

Endovascular treatment of idiopathic intracranial hypertension: clinical and radiologic outcome of 10 consecutive patients.

Objective: To explore the relation between venous disease and idiopathic intracranial hypertension. Background: Optic nerve sheath fenestration and ventricular shunting are the classic methods when medical treatment has failed. Idiopathic intracranial hypertension is caused by venous sinus obstruction in an unknown percentage of cases. Recently, endoluminal venous sinus stenting was proposed as an alternative treatment. Methods: Ten consecutive patients with refractory idiopathic intracranial hypertension underwent examination with direct retrograde cerebral venography and manometry to characterize the morphologic features and venous pressures in their cerebral venous sinus. All patients demonstrated morphologic obstruction of the venous lateral sinuses. The CSF pressure was measured in all patients. The CSF pressure on lumbar puncture ranged from 27 to 45 mm Hg with normal composition. All patients had headache, and visual acuity loss was noted in eight patients. Funduscopic examination demonstrated papilledema for all patients. All patients had stenting of the venous sinuses. Intrasinus pressures were recorded before and after the procedure and correlated with clinical outcome. Results: Intrasinus pressures were invariably reduced by stenting. For headache, six patients were rendered asymptomatic, two were improved, and two were unchanged after venous sinus stenting for a mean (± SD) follow-up of 17 ± 10.1 months (range 6 to 36 months). Papilledema disappeared in all patients. In all cases, CSF pressure was normalized at 3-month follow-up. In all patients, direct retrograde cerebral venography or multidetector row CT angiography was performed at 6-month follow-up and demonstrated the absence of stent thrombosis. Conclusion: The importance of venous sinus disease in the etiology of idiopathic intracranial hypertension is probably underestimated. Patients with idiopathic intracranial hypertension in whom a venous sinus stenosis is demonstrated by a noninvasive radiologic workup should be evaluated with direct retrograde cerebral venography and manometry. In patients with a lesion of the venous sinuses who experienced medical treatment failure, endovascular stent placement seems to be an interesting alternative to classic surgical approaches.

Hemodynamics and Wall Mechanics of a Compliance Matching Stent: In Vitro and In Vivo Analysis

PURPOSE Evidence is emerging that the abrupt compliance mismatch that exists at the junction between the stent ends and the host arterial wall disturbs both the vascular hemodynamics and the natural wall stress distribution. These stent-induced alterations are greatly reduced by smoothing the compliance mismatch between the stent and host vessel. A stent that provides this smooth transition in compliance, the compliance matching stent (CMS), has been developed. This study attempts to evaluate the hemodynamics and wall mechanical consequences of the CMS both in vitro and in vivo. MATERIALS AND METHODS Finite element analysis was used to assess the solid mechanical behavior (compliance and stress) of the CMS in a stent/artery hybrid structure. A similar analysis was performed with a Palmaz stent. In vivo hemodynamics and wall mechanical changes induced by the CMS were investigated in a swine model from direct measurements of flow, pressure, diameter, and histology in the stented segment of superficial femoral arteries after 7 days. RESULTS Finite element analysis showed that the abrupt compliance mismatch was substantially smoothed between the vessel portions with and without the stent with CMS segments. Circumferential stress was also markedly reduced with the CMS compared to other stent. The in vivo results showed that the CMS was efficient in compliance matching and did not dampen flow or pressure waves downstream the stent. Concurrent histology showed limited thrombus and inflammatory cell accumulation around the stent struts. CONCLUSION These results indicate that the stent/artery hybrid structure can be compliance matched with proper stent design and that this structure limits solid mechanical stress and hemodynamic disturbances. It remains to be seen whether compliance-matched vascular stents reduce in-stent restenosis.

In vivo diffusion tensor MRI of the human heart: reproducibility of breath-hold and navigator-based approaches.

The aim of this study was to implement a quantitative in vivo cardiac diffusion tensor imaging (DTI) technique that was robust, reproducible, and feasible to perform in patients with cardiovascular disease. A stimulated‐echo single‐shot echo‐planar imaging (EPI) sequence with zonal excitation and parallel imaging was implemented, together with a novel modification of the prospective navigator (NAV) technique combined with a biofeedback mechanism. Ten volunteers were scanned on two different days, each time with both multiple breath‐hold (MBH) and NAV multislice protocols. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) fiber maps were created. Comparison of initial and repeat scans showed good reproducibility for both MBH and NAV techniques for FA (P > 0.22), MD (P > 0.15), and HA (P > 0.28). Comparison of MBH and NAV FA (FAMBHday1 = 0.60 ± 0.04, FANAVday1 = 0.60 ± 0.03, P = 0.57) and MD (MDMBHday1 = 0.8 ± 0.2 × 10−3 mm2/s, MDNAVday1 = 0.9 ± 0.2 × 10−3 mm2/s, P = 0.07) values showed no significant differences, while HA values (HAMBHday1Endo = 22 ± 10°, HAMBHday1Mid‐Endo = 20 ± 6°, HAMBHday1Mid‐Epi = −1 ± 6°, HAMBHday1Epi = −17 ± 6°, HANAVday1Endo = 7 ± 7°, HANAVday1Mid‐Endo = 13 ± 8°, HANAVday1Mid‐Epi = −2 ± 7°, HANAVday1Epi = −14 ± 6°) were significantly different. The scan duration was 20% longer with the NAV approach. Currently, the MBH approach is the more robust in normal volunteers. While the NAV technique still requires resolution of some bulk motion sensitivity issues, these preliminary experiments show its potential for in vivo clinical cardiac diffusion tensor imaging and for delivering high‐resolution in vivo 3D DTI tractography of the heart. Magn Reson Med 70:454–465, 2013.

Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure.

Objective:Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. Design:Prospective, controlled, randomized animal study. Setting:University research laboratory. Subjects:Fourteen anesthetized piglets. Interventions:Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 &mgr;g/kg was administered in 10 mins followed by 0.2 &mgr;g/kg/min or same volumes of isotonic saline. Measurements and Main Results:Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 ± 0.17 to 5.58 ± 0.37 mm Hg/mL, decreased Ees from 1.75 ± 0.12 to 1.29 ± 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 ± 0.20 to 0.24 ± 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. Conclusions:A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.

Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation.

BackgroundThe study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts.MethodsDiffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy.ResultsIn normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p<0.05). This was confirmed histologically by the reduction of HA in the subepicardium from −52.03° ± 2.94° in normal hearts to −37.48° ± 4.05° in the remote zone of the remodeled hearts (p < 0.05).ConclusionsA significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

Dose reduction with iterative reconstruction: Optimization of CT protocols in clinical practice

OBJECTIVES To create an adaptable and global approach for optimizing MDCT protocols by evaluating the influence of acquisition parameters and Iterative Reconstruction (IR) on dose reduction and image quality. MATERIALS AND METHODS MDCT acquisitions were performed on quality image phantom by varying kVp, mAs, and pitch for the same collimation. The raw data were reconstructed by FBP and Sinogram Affirmed Iterative Reconstruction (SAFIRE) with different reconstruction kernel and thickness. A total of 4032 combinations of parameters were obtained. Indices of quality image (image noise, NCT, CNR, SNR, NPS and MTF) were analyzed. We developed a software in order to facilitate the optimization between dose reduction and image quality. Its outcomes were verified on an adult anthropomorphic phantom. RESULTS Dose reduction resulted in the increase of image noise and the decrease of SNR and CNR. The use of IR improved these indices for the same dose without affecting NCT and MTF. The image validation was performed by the anthropomorphic phantom. The software proposed combinations of parameters to reduce doses while keeping indices of the image quality adequate. We observed a CTDIvol reduction between -44% and -83% as compared to the French diagnostic reference levels (DRL) for different anatomical localization. CONCLUSION The software developed in this study may help radiologists in selecting adequate combinations of parameters that allows to obtain an appropriate image with dose reduction.

Dual-Phase Cardiac Diffusion Tensor Imaging with Strain Correction

Purpose In this work we present a dual-phase diffusion tensor imaging (DTI) technique that incorporates a correction scheme for the cardiac material strain, based on 3D myocardial tagging. Methods In vivo dual-phase cardiac DTI with a stimulated echo approach and 3D tagging was performed in 10 healthy volunteers. The time course of material strain was estimated from the tagging data and used to correct for strain effects in the diffusion weighted acquisition. Mean diffusivity, fractional anisotropy, helix, transverse and sheet angles were calculated and compared between systole and diastole, with and without strain correction. Data acquired at the systolic sweet spot, where the effects of strain are eliminated, served as a reference. Results The impact of strain correction on helix angle was small. However, large differences were observed in the transverse and sheet angle values, with and without strain correction. The standard deviation of systolic transverse angles was significantly reduced from 35.9±3.9° to 27.8°±3.5° (p<0.001) upon strain-correction indicating more coherent fiber tracks after correction. Myocyte aggregate structure was aligned more longitudinally in systole compared to diastole as reflected by an increased transmural range of helix angles (71.8°±3.9° systole vs. 55.6°±5.6°, p<0.001 diastole). While diastolic sheet angle histograms had dominant counts at high sheet angle values, systolic histograms showed lower sheet angle values indicating a reorientation of myocyte sheets during contraction. Conclusion An approach for dual-phase cardiac DTI with correction for material strain has been successfully implemented. This technique allows assessing dynamic changes in myofiber architecture between systole and diastole, and emphasizes the need for strain correction when sheet architecture in the heart is imaged with a stimulated echo approach.

Microstructural Impact of Ischemia and Bone Marrow–Derived Cell Therapy Revealed With Diffusion Tensor Magnetic Resonance Imaging Tractography of the Heart In Vivo

Background— The arrangement of myofibers in the heart is highly complex and must be replicated by injected cells to produce functional myocardium. A novel approach to characterize the microstructural response of the myocardium to ischemia and cell therapy, with the use of serial diffusion tensor magnetic resonance imaging tractography of the heart in vivo, is presented. Methods and Results— Validation of the approach was performed in normal (n=6) and infarcted mice (n=6) as well as healthy human volunteers. Mice (n=12) were then injected with bone marrow mononuclear cells 3 weeks after coronary ligation. In half of the mice the donor and recipient strains were identical, and in half the strains were different. A positive response to cell injection was defined by a decrease in mean diffusivity, an increase in fractional anisotropy, and the appearance of new myofiber tracts with the correct orientation. A positive response to bone marrow mononuclear cell injection was seen in 1 mouse. The response of the majority of mice to bone marrow mononuclear cell injection was neutral (9/12) or negative (2/12). The in vivo tractography findings were confirmed with histology. Conclusions— Diffusion tensor magnetic resonance imaging tractography was able to directly resolve the ability of injected cells to generate new myofiber tracts and provided a fundamental readout of their regenerative capacity. A highly novel and translatable approach to assess the efficacy of cell therapy in the heart is thus presented.

Optimization of nonviral transfection: variables influencing liposome-mediated gene transfer in proliferating vs. quiescent cells in culture and in vivo using a porcine restenosis model.

Abstract. Cationic liposomes/DNA complexes are widely used vectors for delivering genes in clinical and experimental trials. Relatively low transfer efficiencies in vivo compared with viral gene transfer may be improved using local application. In addition, markedly increased transfer efficiency may be achieved in vitro and in vivo via optimization of known variables influencing liposomal transfection. Lipofection under different conditions was performed in various cell lines and primary porcine smooth muscle cells. Optimized conditions found in vitro were verified in vivo using a porcine restenosis model. Toxicity was monitored analyzing cell metabolism. Transfer efficiency and safety were determined using morphometry, histology, galactosidase assays, PCR, and RT-PCR. The most important variables enabling maximum transfer efficiency were firstly the appropriate selection of cationic lipids for the cell type to be transfected, secondly the DNA/liposome ratio chosen, which depended on the cell type and cationic lipids used, and thirdly the state of proliferation of the targeted cells. Transfection in vivo demonstrated two- to fivefold higher transfer efficiencies when transfer conditions were extrapolated from optimization experiments in stationary cells compared with the use of conditions established in proliferating cells. Application of the therapeutic gene for cecropin using optimized transfer conditions resulted in a significantly reduced neointima formation compared with the transfection using a control gene for ß-galactosidase. Thus, in this vascular model, initial optimization of lipofection in stationary cells in culture followed by local delivery in vivo and with selection of a suitable therapeutic gene led to markedly improved transfer efficiencies, gene expression, and biological effect. Stationary cell cultures simulate more realistically the in vivo situation and may therefore represent a better model for future in vivo experiments. In addition, the advantages of liposomes are easy handling, low toxicity, and the lack of carcinogenicity or immunogenic reactions.

Molecular MRI of acute necrosis with a novel DNA-binding gadolinium chelate: kinetics of cell death and clearance in infarcted myocardium.

Background— Current techniques to image cell death in the myocardium are largely nonspecific. We report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo. Methods and Results— In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points after MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction but peaked 9 to 18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R1) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours after MI (R1=1.24±0.08 and 0.92±0.03 s−1, respectively, P <0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection ( P <0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy. Conclusions— Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury.Background— Current techniques to image cell death in the myocardium are largely nonspecific. We report the use of a novel DNA-binding gadolinium chelate (Gd-TO) to specifically detect the exposed DNA in acutely necrotic (ruptured) cells in vivo. Methods and Results— In vivo MRI was performed in 20 mice with myocardial infarction (MI). The mice were injected with Gd-TO or Gd-DTPA at varying time points after MI. MRI was performed 2 hours after probe injection, to avoid nonspecific signal from the late gadolinium enhancement effect. Cell rupture (Gd-TO uptake) was present within 2 hours of infarction but peaked 9 to 18 hours after the onset of injury. A significant increase in the longitudinal relaxation rate (R1) in the infarct was seen in mice injected with Gd-TO within 48 hours of MI, but not in those injected more than 72 hours after MI (R1=1.24±0.08 and 0.92±0.03 s−1, respectively, P<0.001). Gd-DTPA, unlike Gd-TO, washed completely out of acute infarcts within 2 hours of injection (P<0.001). The binding of Gd-TO to exposed DNA in acute infarcts was confirmed with fluorescence microscopy. Conclusions— Gd-TO specifically binds to acutely necrotic cells and can be used to image the mechanism and chronicity of cell death in injured myocardium. Cell rupture in acute MI begins early but peaks many hours after the onset of injury. The ruptured cells are efficiently cleared by the immune system and are no longer present in the myocardium 72 hours after injury.