Diffusion-weighted MRI in the evaluation of renal lesions:preliminary results

The purpose of this study was to evaluate the capability and the reliability of diffusion-weighted MRI in the evaluation of normal kidney and different renal lesions. 39 patients (10 normal volunteers and 29 patients with known renal lesions) underwent MRI of the kidneys by using a 1.5 T superconducting magnet. Axial fat suppressed turbo spin echo (TSE) T2 and coronal fast field echo (FFE) T1 or TSE T1 weighted images were acquired for each patient. Diffusion-weighted (DW) images were obtained in the axial plane during breath-hold (17 s) with a spin-echo echo planar imaging (SE EPI) single shot sequence (repetition time (TR)52883 ms, echo time (TE)561 ms, flip angle590°), with b value of 500 s mm22. 16 slices were produced with slice thickness of 7 mm and interslice gap of 1 mm. An apparent diffusion coefficient (ADC) map was obtained at each slice position. The ADC was measured in an approximately 1 cm region of interest (ROI) within the normal renal parenchyma, the detected renal lesions and the collecting system if dilated. ADC values in normal renal parenchyma ranged from 1.7261023 mm2 s21 to 2.6561023 mm2 s21, while ADC values in simple cysts (n513) were higher (2.8761023 mm2 s21 to 4.0061023 mm2 s21). In hydronephrotic kidneys (n56) the ADC values of renal pelvis ranged from 3.3961023 mm2 s21 to 4.0061023 mm2 s21. In cases of pyonephrosis (n53) ADC values of the renal pelvis were found to be lower than those of renal pelvis of hydronephrotic kidneys (0.7761023 mm2 s21 to 1.0761023 mm2 s21). Solid benign and malignant renal tumours (n57) showed ADC values ranging between 1.2861023 mm2 s21 and 1.8361023 mm2 s21. In conclusion diffusion-weighted MR imaging of the kidney seems to be a reliable way to differentiate normal renal parenchyma and different renal diseases. Clinical experience with this method is still preliminary and further studies are required

An in vivo study of quantum dots tissue accumulation

Nanotechnology represents a new frontier for the science progress and there are great expectations in relation to diagnostic and therapeutic envelopes [1]. Living organisms are built of cells that are typically 10 \u3bcm across. However, the cell parts are much smaller and are in the sub-micron size domain, for example a red blood cell is approximately 7,000 nm wide. Even smaller are the proteins with a typical size of just 5 nm, which is comparable with the dimensions of smallest manmade nanoparticles. This simple size comparison gives an idea of using nanoparticles as very small probes that would allow us to spy at the cellular machinery without introducing too much interference. Understanding of biological processes on the nanoscale level is a strong driving force behind development of nanotechnologyOur current knowledge of the toxicology of nanoparticles in vivo is poor [2] but suggests that nanoparticles may able to have adverse effects at their portal of entry , for example, the lungs, but that some nanoparticles may also escape the normal defences and translocate from their portal of entry to have diverse effects in other target organs [3].There is no cut-off below witch particles suddenly become harmful, in the lung at least. This is because harmful particles have their effects as a consequence of two factors that act together to determine their potential to cause harm: their large surface area, and the reactivity or intrinsic toxicity of the surface. It is self evident that the smaller particles are, the more surface area they have per unit mass; therefore any intrinsic toxicity of the particles surface will be emphasised. Some of the most complex nanoparticles are likely to be produced for therapeutic purposes, furthermore nanoparticles binding to protein may result in a series of consequences not expected to occur when proteins bind to large particles. Very small particles may be not detected by the normal phagocytic defences, allowing them to gain access to the blood or nervous system [4]. Very small particles are smaller than some molecules and could act like haptens to modify protein structures, either altering their function or rendering them antigenic, raising the potential for autoimmune effects.Tracers that we have used are nanoparticles with optical properties, fluorescent semiconductors, that absorb photons of light and re-emit photons at a different wavelength They are known as quantum dots (QDs), nanocrystals that are nanometres-scale (10-20nm, roughly protein-sized) atom clusters, containing from a few hundred to a few thousand atoms of a semiconductor material (cadmium mixed with selenium), which has been coated with an additional semiconductor shell (zinc sulfide) to improve the optical properties of the material. These nanoparticles fluoresce in a different way than do traditional fluorophores, they exhibit some important differences as compared to organic fluorescent dyes and naturally fluorescent proteins: they have an extinction coefficient 10-50 times bigger than them. These nanoparticles projected around their optical properties: stable , bright and photo-stable fluorescence, observed and measured for hours, and that persists also into isolated tissues. Nanoparticles like QDs, could be targeted and not targeted and provided several unique features and capabilities[5, 6]: the size-effect does the QDs cancer biomarkers and there is the possibility to functionalize their surface area with a several numbers of functional groups that can be linked with multiple diagnostic (e.g. radio-isotopic or magnetic) and therapeutic agents. The aim of the study is to monitor nanoparticles behaviour into blood system: kinetic, T1/2, bio distribution, and tissues accumulation. We would extrapolate from optics parameters physiological ones, in specific districts so as liver and lungs that are the most probably targets of toxicity

Nanoelectrode ensembles as recognition platform for electrochemical immunosensors

In this study we demonstrate the possibility to prepare highly sensitive nanostructured electrochemical immunosensors by immobilizing biorecognition elements on nanoelectrode ensembles (NEEs) prepared in track-etch polycarbonate membranes. The gold nanodisk electrodes act as electrochemical transducers while the surrounding polycarbonate binds the antibody-based biorecognition layer. The interaction between target protein and antibody is detected by suitable secondary antibodies labelled with a redox enzyme. A redox mediator, added to the sample solution, shuttles electrons from the nanoelectrodes to the biorecognition layer, so generating an electrocatalytic signal. This allows one to fully exploit the highly improved signal-to-background current ratio, typical of NEEs. In particular, the receptor protein HER2was studied as the target analyte. HER2 detection allows the identification of breast cancer that can be treated with the monoclonal antibody trastuzumab. NEEs were functionalized with trastuzumab which interacts specifically with HER2. The biorecognition process was completed by adding a primary antibody and a secondary antibody labelled with horseradish peroxidase. Hydrogen peroxide was added to modulate the label electroactivity; methylene blue was the redox mediator generating voltammetric signals. NEEs functionalized with trastuzumab were tested to detect small amounts of HER2 in diluted cell lysates and tumour lysates

Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: Results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme