New starch-based radiotracer for lung perfusion scintigraphy.

PURPOSE: In order to avoid the microbiological risks linked to human serum albumin macroaggregates (MAA) used for lung perfusion scintigraphy, we developed a new starch-based Tc-99m potential radiopharmaceutical. METHODS: Microparticles were prepared from oxidised starch coupled to natural polyamine for Tc-99m complexation. Suspensions were formulated as ready-to-use kits for easy one-step labelling procedures. RESULTS: Particle-size analysis, electron microscopy, and confocal microscopy were performed for microparticle characterisation, and gave a typical size distribution ranging from 7 to 63 microm, with a homogenous population of spherical or oval-shaped microparticles. Radiochemical purity exceeded 95%, and was stable for at least 8 h. When challenged with histidine and human plasma, labelling was also stable. Dynamic scintigraphic acquisitions and biodistribution studies conducted on healthy Wistar rats showed a tracer accumulation with more than 80% of the ID in the lungs after 15 min. CONCLUSIONS: With clinically significant characteristics such as a lung half-life of 3 h, a lung-to-vascular ratio of 900, and a lung-to-liver ratio of 90, starch-based microparticles exhibit all the qualities for an effective new lung perfusion agent.

Imaging E-selectin expression following traumatic brain injury in the rat using a targeted USPIO contrast agent.

INTRODUCTION: The aim of this work was to map E-selectin expression in a traumatic brain injury model using a newly-designed MR contrast agent. Iron cores, responsible for susceptibility effects and therefore used as T2* contrast agents, need to be coated in order to be stabilized and need to be targeted to be useful. METHODS: We have designed a molecule coating composed, at one end, of bisphosphonate to ensure anchorage of the coating on the iron core and, at the other end, of Fukuda's defined heptapeptide known to target selectin binding sites. CONCLUSION: The synthesized nanoparticles were able to non-invasively target the traumatic brain lesion, inducing a specific T2* decrease of about 25% up to at least 70 min post-injection of the targeted contrast agent.

Uncommon breast tumor attenuation artifact on radionuclide ventriculography.

A 39-year-old woman with locally advanced left breast cancer (T4 N0 M0) underwent equilibrium radionuclide ventriculography for baseline assessment of left ventricular function before neoadjuvant chemotherapy. The left ventricular ejection fraction was 76% at 75 beats per minute, without localized wall motion abnormality. In the best septal left anterior oblique projection, a large photopenic "halo" surrounded the cardiac chambers, mimicking a pericardial effusion. In fact, this aspect resulted from an attenuation artifact by a large left breast tumor, as demonstrated by FDG-PET/CT imaging.

Perfusional deficit and the dynamics of cerebral edemas in experimental traumatic brain injury using perfusion and diffusion-weighted magnetic resonance imaging.

The aim of this work was to characterize edema dynamics, cerebral blood volume, and flow alterations in an experimental model of brain trauma using quantitative diffusion and perfusion magnetic resonance imaging (MRI). Associated with an influx of water in the intracellular space 1-5 h post-trauma as demonstrated by the 40% reduction in apparent diffusion coefficient, a 70-80% reduction in cerebral blood flow was measured within the lesioned region. Transient hypoperfusion (40-50%) was also observed in the non-traumatized contralateral hemisphere, although there was no evidence of edema formation. After the initial cytotoxic edema, a clear evolution toward extracellular water accumulation was observed, demonstrated by an increase in apparent diffusion coefficient.

Assessment of biventricular remodeling by magnetic resonance imaging after successful primary stenting for acute myocardial infarction.

Inferior acute myocardial infarction (AMI) is associated with a better outcome compared with anterior AMI, even in the presence of comparable infarct size. Whether left ventricular remodeling, a major predictor of poor outcome, and right ventricular (RV) remodeling depend on the site of an AMI remains unknown. Biventricular volumes were assessed by magnetic resonance imaging 7 +/- 2 days and 3.4 +/- 0.3 months after successful primary stenting in 51 consecutive patients with inferior or anterior AMI. This study documents RV involvement and biventricular reverse remodeling in patients with inferior AMI in the absence of RV infarction, as opposed to those with anterior AMI who show progressive biventricular remodeling.

Use of FDG-PET/CT for peritoneal carcinomatosis before hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis (PC) is associated with a very poor prognosis. Complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy has been shown to improve survival rates of PC. However, this treatment is beneficial for patients if the complete cytoreductive surgery is macroscopically completed before implementing hyperthermic intraperitoneal chemotherapy. Even so, a strict selection of patients is of fundamental importance because of the invasive nature of the intervention. The aim of this study was to assess the performance of FDG-PET/CT examinations for the diagnosis and evaluation of the extent of PC. METHODS: A retrospective analysis was conducted on 28 consecutive patients with suspected PC, scheduled for a complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, and who underwent an FDG-PET/CT examination. We compared the results of PET examinations with histological and intraoperative findings. The extent of PC was assessed precisely using a simplified 'peritoneal cancer index', within the three modalities (PET, surgery and histology). RESULTS: Of 28 patients, 23 had histological PC. The sensitivity and specificity of the PET examination for the diagnosis of PC were, respectively, 82 and 100%. Even if the extent of PC was underestimated by PET, there was a good correlation when compared with histology and intraoperative results. CONCLUSION: PET presented a good performance level in the diagnosis and evaluation of the extent of PC. PET/CT examinations could be useful to avoid unnecessary surgery.

Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: in vitro characterization and migration potential in rat brain.

Mesenchymal stem cells (MSC) may transdifferentiate into neural cells in vitro under the influence of matrix molecules and growth factors present in neurogenic niches. However, further experiments on the behavior of such stem cells remain to be done in vivo. In this study, rat MSC (rMSC) have been grafted in a neurogenic environment of the rat brain, the subventricular zone (SVZ), in order to detect and follow their migration using superparamagnetic iron oxide (SPIO) nanoparticles. We sought to characterize the potential effect of iron loading on the behavior of rMSC as well as to address the potential of rMSC to migrate when exposed to the adequate brain microenvironment. 1-hydroxyethylidene-1.1-bisphosphonic acid (HEDP)-coated SPIO nanoparticles efficiently labeled rMSC without significant adverse effects on cell viability and on the in vitro differentiation potential. In opposition to iron-labeled rat neural stem cells (rNSC), used as a positive control, iron-labeled rMSC did not respond to the SVZ microenvironment in vivo and did not migrate, unless a mechanical lesion of the olfactory bulb was performed. This confirmed the known potential of iron-labeled rMSC to migrate toward lesions and, as far as we know, this is the first study describing such a long distance migration from the SVZ toward the olfactory bulb through the rostral migratory stream (RMS).

Three-dimensional MRI assessment of regional wall stress after acute myocardial infarction predicts postdischarge cardiac events.

PURPOSE: To determine the prognostic significance of systolic wall stress (SWS) after reperfused acute myocardial infarction (AMI) using MRI. MATERIALS AND METHODS: A total of 105 patients underwent MRI 7.8 +/- 4.2 days after AMI reperfusion. SWS was calculated by using a three-dimensional (3D) MRI approach to left ventricular (LV) wall thickness and to the radius of curvature. Between hospital discharge and the end of follow-up, an average of 4.1 +/- 1.7 years after AMI, 19 patients experienced a major cardiac event, including cardiac death, nonfatal reinfarction or heart failure (18.3%). RESULTS: The results were mainly driven by heart failure outcome. In univariate analysis the following factors were predictive of postdischarge major adverse cardiac events: 1) at the time of AMI: higher heart rate, previous calcium antagonist treatment, in-hospital congestive heart failure, proximal left anterior descending artery (LAD) occlusion, a lower ejection fraction, higher maximal ST segment elevation before reperfusion, and ST segment reduction lower than 50% after reperfusion; 2) MRI parameters: higher LV end-systolic volume, lower ejection fraction, higher global SWS, higher SWS in the infarcted area (SWS MI) and higher SWS in the remote myocardium (SWS remote). In the final multivariate model, only SWS MI (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.01-2.60; P = 0.046) and SWS remote (OR: 2.17; 95% CI: 1.02-4.65; P = 0.046) were independent predictors. CONCLUSION: Regional SWS assessed by means of MRI a few days after AMI appears to be strong predictor of postdischarge cardiac events, identifying a subset of at risk patients who could qualify for more aggressive management.

Model based and iconic multimodal registration to merge gated cardiac PET, CT and MR sequences.

In this paper, we present a multimodal registration method applied to gated positron emission tomography (PET), X-ray Computed Tomography (CT) and Magnetic Resonance (MR) cardiac images. CT images acquired on the same device as the PET ones are used as link to merge anatomical MR images and functional PET images. The registration process is divided in two steps: a 3D structure registration and a grey-levels registration. This approach enables global to local transformations. The structure registration uses a 3D biventricular heart model initialized on CT and MR data to define a rigid transform. This global registration is then refined with a grey-levels step based on mutual information and free form deformations. To improve endocardium registration, we propose a composite PET-CT image to find the optimal transformation on MR image. We also take into account the temporal problematic of heart motion by initializing the searched transformation, at a current frame, with the composition of a monomodal transformation (representing the heart motion between the previous and current frames) and a multimodal one (representing the spatial transformation between the two images at the previous frame).

Single-scan quantitative T2* methods with susceptibility artifact reduction.

Two imaging methods, MSSAVE (Multiple echo SubSlice AVEraging imaging), based on sub-slice averaging and MGESEPI (Multiple echo Gradient-Echo Slice-Excitation Profile Imaging), based on over-sampling in the slice direction, are proposed for single-scan quantitative T(2)* evaluation with susceptibility artifact compensation. Their potentials in terms of sensitivity, minimum performance time, susceptibility artifact reduction and T(2)* quantitation quality, were compared with existing single-scan methods such as classical FLASH two- or three-dimensional or z-shimmed methods both in vitro and in vivo in normal rat brain. MGESEPI offered good quality T(2)* maps nearly free of artifacts but required a long acquisition time. MSSAVE was faster, but at the expense of reduced artifact compensation and the achievable T(2)* quantitation quality.

Dynamics of cerebral edema and the apparent diffusion coefficient of water changes in patients with severe traumatic brain injury. A prospective MRI study.

The distinction between intracellular (ICE) and extracellular edema (ECE) has a crucial prognostic and therapeutic importance in patients with severe traumatic brain injury (STBI). Indeed, ICE usually leads to cellular death, and maintenance of a cerebral perfusion pressure (CPP) above 70 mmHg is still under debate since this practice may increase ECE. The purpose of this study was to describe the ECE and ICE kinetics associated with STBI using quantitative diffusion MRI. Twelve patients were prospectively studied. The initial ADC in ICE measured on day 1.3+/-0.7 is significantly reduced compared to normal-appearing parenchyma (0.51+/-0.12 * 10(-3) mm2/s vs. 0.76+/-0.03 * 10(-3) mm2/s, n=12, P<0.0001) and reaches normality on MRI 3 performed on day 14.2+/-3.3. In patients presenting an extension of ICE on MRI 2 performed on day 6.7+/-1.4 (ADC(MRI2)=0.40+/-0.11 * 10(-3) mm2/s), ADC values in the extension area at the first MRI were slightly, but not significantly reduced compared to normal parenchyma (0.69+/-0.05 * 10(-3) mm2/s, P=0.29). Normalization occurred equally by day 14. ADC in ECE (1.34+/-0.22 * 10(-3) mm2/s) was elevated and stable with time under CPP therapy. Therefore, ECE is not worsened by CCP therapy, and ICE appears more relevant than ECE in STBI.

Assessment of myocardial viability in rats: Evaluation of a new method using superparamagnetic iron oxide nanoparticles and Gd-DOTA at high magnetic field.

The aim of this study was to detect salvageable peri-infarction myocardium by MRI in rats after infarction, using with a double contrast agent (CA) protocol at 7 Tesla. Intravascular superparamagnetic iron oxide (SPIO) nanoparticles and an extracellular paramagnetic CA (Gd-DOTA) were used to characterize the peri-infarction zone, which may recover function after reperfusion occurs. Infarcted areas measured from T1-weighted (T1-w) images post Gd-DOTA administration were overestimated compared to histological TTC staining (52% +/- 3% of LV surface area vs. 40% +/- 3%, P=0.03) or to T2-w images post SPIO administration (41% +/- 4%, P=0.04), whereas areas measured from T2-w images post SPIO administration were not significantly different from those measured histologically (P=0.7). Viable and nonviable myocardium portions of ischemically injured myocardium were enhanced after diffusive Gd-DOTA injection. The subsequent injection of vascular SPIO nanoparticles enables the discrimination of viable peri-infarction regions by specifically altering the signal of the still-vascularized myocardium.

Routine breath-hold gradient echo MRI-derived right ventricular mass, volumes and function: accuracy, reproducibility and coherence study.

Right ventricular (RV) dysfunction is a predictor of poor outcome in patients with heart disease. Conventional imaging modalities fail to assess RV volumes accurately. We sought to assess the accuracy and reproducibility of routine breath-hold gradient echo magnetic resonance imaging (MRI)-derived RV mass, volumes and function. We assessed: (1) The accuracy of in vivo MRI-derived RV mass in comparison to the RV weight in 9 minipigs. (2) Intra- and inter-observer reproducibility of RV mass, end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fraction (EF) in 15 normal volunteers and 10 patients with heart disease. (3) Inter-study reproducibility of the former parameters in 25 coronary artery disease patients. (4) The correlation between right and left ventricular stroke volumes in the total population. Strong statistically significant correlations were found between: (1) MRI-derived RV mass and RV weight (r = 0.98, bias = 2.5 g), (2) Intra-observer measurements of RV mass (r = 0.96, bias = 0.5 g), EDV (r = 0.99, bias = -1.5 ml), ESV (r = 0.98, bias = 0.1 ml) and EF (r = 0.92, bias = -1.4%), (3) Inter-observer measurements of RV mass (r = 0.95, bias = 1.1 g), EDV (r = 0.98, bias = -1.1 ml), ESV (r = 0.98, bias = 1.2 ml) and EF (r = 0.87, bias = -1.9%), (4) Inter-study measurements of RV mass (r = 0.91, bias = -0.1 g), EDV (r = 0.96, bias = 3.8 ml), ESV (r = 0.98, bias = 0.3 ml) and EF (r = 0.90, bias = 0.9%), (5) MRI-derived right and left ventricular stroke volumes (r = 0.87). The assessment of the RV mass, volumes and function by routine breath-hold gradient echo MRI is accurate and highly reproducible. The correlation between left and RV MRI-derived stroke volumes indicates excellent coherence of simultaneous bi-ventricular volume measurements.

3-D MRI assessment of regional left ventricular systolic wall stress in patients with reperfused MI.

The goal of this study was to assess the regional variations of end-systolic wall stress in patients with reperfused Q wave acute myocardial infarction (AMI), with the use of a three-dimensional (3-D) approach. Fifteen normal volunteers and fifty patients with reperfused AMI underwent cardiac MRI that used a short-axis fast-gradient-echo sequence. The end-systolic wall stress was calculated with the use of the Grossman formula with the radius and the wall thickness defined with a 3-D approach using the tridimensional curvature. The mean wall stress was significantly increased at each level of the short-axis plane only in patients with anterior AMI. When calculated at a regional level in patients with anterior AMI, wall stress significantly increased in anterior sector as well as normal sector. In patients with inferior AMI, wall stress significantly increased only in inferior and lateral sectors. In conclusion, the quantification of regional wall stress by cardiac MRI is better with the 3D approach than other methods for precise evaluation in patients with AMI. Despite early reperfusion, the wall stress remained high in patients with anterior AMI.