Jean-Paul Vallée

Clinical Magnetic Resonance Imaging of Pancreatic Islet Grafts After Iron Nanoparticle Labeling

There is a crucial need for noninvasive assessment tools after cell transplantation. This study investigates whether a magnetic resonance imaging (MRI) strategy could be clinically applied to islet transplantation. The purest fractions of seven human islet preparations were labeled with superparamagnetic iron oxide particles (SPIO, 280 μg/mL) and transplanted into four patients with type 1 diabetes. MRI studies (T2*) were performed prior to and at various time points after transplantation. Viability and in vitro and in vivo functions of labeled islets were similar to those of control islets. All patients could stop insulin after transplantation. The first patient had diffuse hypointense images on her baseline liver MRI, typical for spontaneous high iron content, and transplant‐related modifications could not be observed. The other three patients had normal intensity on pretransplant images, and iron‐loaded islets could be identified after transplantation as hypointense spots within the liver. In one of them, i.v. iron therapy prevented subsequent visualization of the spots because of diffuse hypointense liver background. Altogether, this study demonstrates the feasibility and safety of MRI‐based islet graft monitoring in clinical practice. Iron overload (spontaneous or induced) represents the major obstacle to the technique.

Quantification of myocardial perfusion with FAST sequence and Gd bolus in patients with normal cardiac function

The present study reports on a new calibration of the magnetic resonance imaging (MRI) signal intensity of a fast gradient‐echo sequence used for in vivo myocardial perfusion quantification in patients. The signal from a FAST sequence preceded by a arrhythmia‐insensitive magnetization preparation was calibrated in vitro using tubes filled with various gadolinium (Gd) solutions. Single short‐axis views of the heart were obtained in patients (n = 10) with normal cardiac function. Myocardial and blood signal intensity were converted to concentration of Gd according to the in vitro calibration curve and fitted by a one‐compartment model. K1 [first‐order transfer constant from the blood to the myocardium for the gadolinium‐diethylene‐triamine‐pentaacetic acid (Gd‐DTPA)] and Vd (distribution volume of Gd‐DTPA in myocardium) obtained from the fit of the MRI‐derived perfusion curves were 0.72 ± 0.22 (mL/min/g) and 15.3 ± 5.22%. These results were in agreement with previous observations on animals and demonstrated that a reliable measurement of myocardial perfusion can be obtained by MRI in patients with an in vitro calibration procedure.J. Magn. Reson. Imaging 1999;9:197–203.

Automated registration of dynamic MR images for the quantification of myocardial perfusion

Cardiac dynamic magnetic resonance imaging (MRI) after contrast media injection suffers from motion induced by free breathing during acquisition. This work presents an automated approach for motion correction of the heart. The registration is based on the multipass/multiresolution iterative minimizing of intrinsic differences between each image and a reference image coupled to a two‐dimensional/3 parameters rigid body correction. The efficiency of this correction method was evaluated with anatomical landmarks, various cost functions, and for a compartment model fit of the data with 2 parameters: K1, the blood to myocardium transfer coefficient; and Vd, the distribution volume of the contrast media. The variability of K1 and Vd, derived from the fit of the registered images (using the manual correction as a gold standard), was significantly reduced by comparison with the variability obtained from the uncorrected images (P < 0.04). This motion correction method also clearly improves the analysis of dynamic cardiac MRI after contrast media injection in comparison to manual correction. J. Magn. Reson. Imaging 2001;13:648–655.

CC chemokine CCL5 plays a central role impacting infarct size and post-infarction heart failure in mice

AIMS The chemokine CCL5 plays a critical role as neutrophil and macrophage activator do in atherosclerosis and myocardial infarction. Thus, we investigated whether the treatment with a neutralizing monoclonal antibody (mAb) to mouse CCL5 would provide therapeutic benefit when provoking a coronary-associated ischaemic event. METHODS AND RESULTS C57Bl/6 mice were submitted to left coronary artery permanent ligature. Then, various parameters were monitored for up to 21 days. At5 min and 3 days after coronary occlusion, mice received one intravenous injection of the rat anti-mouse CCL5 mAb or isotype IgG control. Infarct size was assessed histologically and by measuring serum cardiac troponin I levels. Kinetics of CCL5 tissue expression, leucocyte infiltration, matrix metalloproteinase (MMP) levels, and collagen deposition were histologically assessed. Serum chemokine levels were measured by enzyme-linked immunosorbent assay. Cardiac function and dimensions were assessed by magnetic resonance imaging (MRI). Chronic ischaemia increased both circulating and intracardiac levels of CCL5. At 24 h, treatment with the anti-CCL5 mAb resulted in a smaller infarct size and reduced circulating levels of chemokines. This effect was associated with reduction of neutrophil and macrophage infiltration within the infarcted myocardium. After 3 days of chronic ischaemia, anti-CCL5 mAb treatment reduced cardiac MMP-9. At 7 days, collagen content was significantly lower. At 21 days, neutralizing CCL5 improved mouse survival, cardiac myocyte size, and cardiac function. CONCLUSION Treatment with anti-CCL5 mAb significantly reduced both infarct size and post-infarction heart failure in a mouse model of chronic cardiac ischaemia. Cardioprotective effects were associated with the reduction of leucocyte recruitment within infarcted hearts.

Application technique: placement of a prostate-rectum spacer in men undergoing prostate radiation therapy.

Study Type – Therapy (case series)

Inflow effect correction in fast gradient-echo perfusion imaging.

The purposes of this study were to assess the extent of the inflow effect on signal intensity (SI) for fast gradient‐recalled‐echo (GRE) sequences used to observe first‐pass perfusion, and to develop and validate a correction method for this effect. A phantom experiment with a flow apparatus was performed to determine SI as a function of Gd‐DTPA concentration for various velocities. Subsequently a flow‐sensitive calibration method was developed, and validated on bolus injections into an open‐circuit flow apparatus and in vivo. It is shown that calibration methods based on static phantoms are not appropriate for accurate signal‐to‐concentration conversion in images affected by high flow. The flow‐corrected calibration method presented here can be used to improve the accuracy and robustness of the arterial input function (AIF) determination for tissue perfusion quantification using MRI and contrast media. Magn Reson Med 50:885–891, 2003.

Noninvasive measurement of absolute renal perfusion by contrast medium-enhanced magnetic resonance imaging

Objective:The aim of this study was to validate the quantification of absolute renal perfusion (RP) determined by dynamic magnetic resonance imaging (MRI) and contrast media using an experimental model in the rabbit and a transit-timed ultrasound flow probe around the left renal artery as comparison. Material and Methods:An MR-compatible ultrasonic time-of-flight flow-probe was placed around the left renal artery in 9 new Zealand white rabbits. Absolute RP in basal state, after mechanical renal artery stenosis, intravenous dopamine, angiotensin II, or colloid infusion was measured using dynamic MRI and intravenous injection of gadoteridol. The results were correlated to the renal artery flow measured inside the magnet with the transit-timed flow-probe. For the signal intensity concentration conversion, we applied different calibrations according to various velocities measured in the aorta by a phase contrast sequence to correct for inflow effect. MRI-derived RP (in mL/min) was calculated by the maximum upslope method, where RP/volume was defined as the ratio of the cortex contrast enhancement slope over the maximum of the arterial input function determined in the aorta. Results:Reproducible arterial and renal transit curve with excellent contrast to noise ratio were obtained. The MRI derived perfusion was systematically underestimated by comparison to the ultrasonic transit-timed flow-probe but was linearly correlated with these measures (r = 0.80, P < 0.001). Conclusions:Using a flow-sensitive calibration, an accurate arterial input function can be measured from the blood MR signal and used in a realistic model to assess the RP. There was a good correlation between the MR-derived RP and the renal artery blood flow measured by the flow-meter. This experimental study validates absolute RP quantification by MRI and contrast media injection and justifies further clinical studies.

Approaches for the optimization of MR protocols in clinical hybrid PET/MRI studies

Magnetic resonance imaging (MRI) is the examination method of choice for the diagnosis of a variety of diseases. MRI allows us to obtain not only anatomical information but also identification of physiological and functional parameters such as networks in the brain and tumor cellularity, which plays an increasing role in oncologic imaging, as well as blood flow and tissue perfusion. However, in many cases such as in epilepsy, degenerative neurological diseases and oncological processes, additional metabolic and molecular information obtained by PET can provide essential complementary information for better diagnosis. The combined information obtained from MRI and PET acquired in a single imaging session allows a more accurate localization of pathological findings and better assessment of the underlying physiopathology, thus providing a more powerful diagnostic tool. Two hundred and twenty-one patients were scanned from April 2011 to January 2012 on a Philips Ingenuity TF PET/MRI system. The purpose of this review article is to provide an overview of the techniques used for the optimization of different protocols performed in our hospital by specialists in the following fields: neuroradiology, head and neck, breast, and prostate imaging. This paper also discusses the different problems encountered, such as the length of studies, motion artifacts, and accuracy of image fusion including physical and technical aspects, and the proposed solutions.

Current status of cardiac MRI in small animals

Cardiac magnetic resonance imaging (MRI) on small animals is possible but remains challenging and not well standardized. This publication aims to provide an overview of the current techniques, applications and challenges of cardiac MRI in small animals for researchers interested in moving into this field. Solutions have been developed to obtain a reliable cardiac trigger in both the rat and the mouse. Techniques to measure ventricular function and mass have been well validated and are used by several research groups. More advanced techniques like perfusion imaging, delayed enhancement or tag imaging are emerging. Regarding cardiac applications, not only coronary ischemic disease but several other pathologies or conditions including cardiopathies in transgenic animals have already benefited from these new developments. Therefore, cardiac MRI has a bright future for research in small animals.

Magnetic resonance imaging with hepatospecific contrast agents in cirrhotic rat livers

Objective:During biliary cirrhosis in rats, organic anion-transporting peptides (Oatps) and ATP-dependent multidrug resistance-associated protein 2 (Mrp2) that are likely to transport the contrast agent Gd-BOPTA through hepatocytes are down-regulated. However, the consequences of such down-regulation on the signal intensity (SI) enhancement are unknown. Consequently, the aim of our study was to measure the hepatic SI enhancement during Gd-BOPTA perfusion as well as the Oatp and Mrp2 expression in normal and cirrhotic livers. Materials and Methods:The hepatic SI enhancement during Gd-BOPTA perfusion was measured in livers isolated from normal rats and rats that had a bile duct ligation (BDL) 15, 30, and 60 days before the perfusion. Hepatic injury and transporter expression were measured in control and cirrhotic rats. Results:BDL induced a severe hepatic injury that increased over time with a down-regulation of the transporter expression. The extracellular space (assessed by Gd-DTPA perfusion) increased with the severity of the disease. Gd-BOPTA-induced SI enhancement remained similar in BDL-15 and BDL-30 rats than in control rats but significantly decreased in severe cirrhosis (BDL-60 rats). In comparison, the Mn-DPDP-induced SI enhancement decreases proportionally to the severity of the disease. Conclusion:During biliary cirrhosis, Gd-BOPTA-induced SI enhancement could not be related to the hepatic expression of transporters.