Methodological approaches to planar and volumetric scintigraphic imaging of small volume targets with high spatial resolution and sensitivity

Single-photon emission computed tomography (SPECT) is a non-invasive imaging technique, which provides information reporting the functional states of tissues. SPECT imaging has been used as a diagnostic tool in several human disorders and can be used in animal models of diseases for physiopathological, genomic and drug discovery studies. However, most of the experimental models used in research involve rodents, which are at least one order of magnitude smaller in linear dimensions than man. Consequently, images of targets obtained with conventional gamma-cameras and collimators have poor spatial resolution and statistical quality. We review the methodological approaches developed in recent years in order to obtain images of small targets with good spatial resolution and sensitivity. Multipinhole, coded mask- and slit-based collimators are presented as alternative approaches to improve image quality. In combination with appropriate decoding algorithms, these collimators permit a significant reduction of the time needed to register the projections used to make 3-D representations of the volumetric distribution of target’s radiotracers. Simultaneously, they can be used to minimize artifacts and blurring arising when single pinhole collimators are used. Representation images are presented, which illustrate the use of these collimators. We also comment on the use of coded masks to attain tomographic resolution with a single projection, as discussed by some investigators since their introduction to obtain near-field images. We conclude this review by showing that the use of appropriate hardware and software tools adapted to conventional gamma-cameras can be of great help in obtaining relevant functional information in experiments using small animals.

Reliability of intraoperative high-resolution 2D ultrasound as an alternative to high-field strength MR imaging for tumor resection control: a prospective comparative study

OBJECT: Ultrasound may be a reliable but simpler alternative to intraoperative MR imaging (iMR imaging) for tumor resection control. However, its reliability in the detection of tumor remnants has not been definitely proven. The aim of the study was to compare high-field iMR imaging (1.5 T) and high-resolution 2D ultrasound in terms of tumor resection control. METHODS: A prospective comparative study of 26 consecutive patients was performed. The following parameters were compared: the existence of tumor remnants after presumed radical removal and the quality of the images. Tumor remnants were categorized as: detectable with both imaging modalities or visible only with 1 modality. RESULTS: Tumor remnants were detected in 21 cases (80.8%) with iMR imaging. All large remnants were demonstrated with both modalities, and their image quality was good. Two-dimensional ultrasound was not as effective in detecting remnants<1 cm. Two remnants detected with iMR imaging were missed by ultrasound. In 2 cases suspicious signals visible only on ultrasound images were misinterpreted as remnants but turned out to be a blood clot and peritumoral parenchyma. The average time for acquisition of an ultrasound image was 2 minutes, whereas that for an iMR image was approximately 10 minutes. Neither modality resulted in any procedure-related complications or morbidity. CONCLUSIONS: Intraoperative MR imaging is more precise in detecting small tumor remnants than 2D ultrasound. Nevertheless, the latter may be used as a less expensive and less time-consuming alternative that provides almost real-time feedback information. Its accuracy is highest in case of more confined, deeply located remnants. In cases of more superficially located remnants, its role is more limited.

High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment

Rapid imaging by antitumor antibodies has been limited by the prolonged targeting kinetics and clearance of labeled whole antibodies. Genetically engineered fragments with rapid access and high retention in tumor tissue combined with rapid blood clearance are suitable for labeling with short-lived radionuclides, including positron-emitting isotopes for positron-emission tomography (PET). An engineered fragment was developed from the high-affinity anticarcinoembryonic antigen (CEA) monoclonal antibody T84.66. This single-chain variable fragment (Fv)-CH3, or minibody, was produced as a bivalent 80 kDa dimer. The macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N′,N′′, N′′′-tetraacetic acid (DOTA) was conjugated to the anti-CEA minibody for labeling with copper-64, a positron-emitting radionuclide (t1/2 = 12.7 h). In vivo distribution was evaluated in athymic mice bearing paired LS174T human colon carcinoma (CEA positive) and C6 rat glioma (CEA negative) xenografts. Five hours after injection with 64Cu-DOTA-minibody, microPET imaging showed high uptake in CEA-positive tumor (17.9% injected dose per gram ± 3.79) compared with control tumor (6.0% injected dose per gram ± 1.0). In addition, significant uptake was seen in liver, with low uptake in other tissues. Average target/background ratios relative to neighboring tissue were 3–4:1. Engineered antibody fragments labeled with positron-emitting isotopes such as copper-64 provide a new class of agents for PET imaging of tumors.

Multiphoton high-resolution 3D imaging of Langerhans cells and keratinocytes in the mouse skin model adopted for epidermal powdered immunization

Langerhans cells (LCs) can be targeted with DNA-coated gold micro-projectiles ("Gene Gun") to induce potent cellular and humoral immune responses. It is likely that the relative volumetric distribution of LCs and keratinocytes within the epidermis impacts on the efficacy of Gene Gun immunization protocols. This study quantified the three-dimensional (3D) distribution of LCs and keratinocytes in the mouse skin model with a near-infrared multiphoton laser-scanning microscope (NIR-MPLSM). Stratum corneum (SC) and viable epidermal thickness measured with MPLSM was found in close agreement with conventional histology. LCs were located in the vertical plane at a mean depth of 14.9 mum, less than 3 mum above the dermo-epidermal boundary and with a normal histogram distribution. This likely corresponds to the fact that LCs reside in the suprabasal layer (stratum germinativum). The nuclear volume of keratinocytes was found to be approximately 1.4 times larger than that of resident LCs (88.6 mum3). Importantly, the ratio of LCs to keratinocytes in mouse ear skin (1:15) is more than three times higher than that reported for human breast skin (1:53). Accordingly, cross-presentation may be more significant in clinical Gene Gun applications than in pre-clinical mouse studies. These interspecies differences should be considered in pre-clinical trials using mouse models.

A binary engine fuelling HD 87643's complex circumstellar environment Determined using AMBER/VLTI imaging

Context. The star HD 87643, exhibiting the ""B[e] phenomenon"", has one of the most extreme infrared excesses for this object class. It harbours a large amount of both hot and cold dust, and is surrounded by an extended reflection nebula. Aims. One of our major goals was to investigate the presence of a companion in HD87643. In addition, the presence of close dusty material was tested through a combination of multi-wavelength high spatial resolution observations. Methods. We observed HD 87643 with high spatial resolution techniques, using the near-IR AMBER/VLTI interferometer with baselines ranging from 60 m to 130 m and the mid-IR MIDI/VLTI interferometer with baselines ranging from 25 m to 65 m. These observations are complemented by NACO/VLT adaptive-optics-corrected images in the K and L-bands, and ESO-2.2m optical Wide-Field Imager large-scale images in the B, V and R-bands. Results. We report the direct detection of a companion to HD 87643 by means of image synthesis using the AMBER/VLTI instrument. The presence of the companion is confirmed by the MIDI and NACO data, although with a lower confidence. The companion is separated by similar to 34 mas with a roughly north-south orientation. The period must be large (several tens of years) and hence the orbital parameters are not determined yet. Binarity with high eccentricity might be the key to interpreting the extreme characteristics of this system, namely a dusty circumstellar envelope around the primary, a compact dust nebulosity around the binary system and a complex extended nebula suggesting past violent ejections.

The close circumstellar environment of Betelgeuse II. Diffraction-limited spectro-imaging from 7.76 to 19.50 mu m with VLT/VISIR

Context. Mass-loss occurring in red supergiants (RSGs) is a major contributor to the enrichment of the interstellar medium in dust and molecules. The physical mechanism of this mass loss is however relatively poorly known. Betelgeuse is the nearest RSG, and as such a prime object for high angular resolution observations of its surface (by interferometry) and close circumstellar environment. Aims. The goal of our program is to understand how the material expelled from Betelgeuse is transported from its surface to the interstellar medium, and how it evolves chemically in this process. Methods. We obtained diffraction-limited images of Betelgeuse and a calibrator (Aldebaran) in six filters in the N band (7.76 to 12.81 mu m) and two filters in the Q band (17.65 and 19.50 mu m), using the VLT/VISIR instrument. Results. Our images show a bright, extended and complex circumstellar envelope at all wavelengths. It is particularly prominent longwards of approximate to 9-10 mu m, pointing at the presence of O-rich dust, such as silicates or alumina. A partial circular shell is observed between 0.5 and 1.0 '' from the star, and could correspond to the inner radius of the dust envelope. Several knots and filamentary structures are identified in the nebula. One of the knots, located at a distance of 0.9 '' west of the star, is particularly bright and compact. Conclusions. The circumstellar envelope around Betelgeuse extends at least up to several tens of stellar radii. Its relatively high degree of clumpiness indicates an inhomogeneous spatial distribution of the material lost by the star. Its extension corresponds to an important intermediate scale, where most of the dust is probably formed, between the hot and compact gaseous envelope observed previously in the near infrared and the interstellar medium.

High-density electric source imaging (esi) in focal epilepsy: a prospective study of 150 operated patients

Purpose: EEG is mandatory in the diagnosis of the epilepsy syndrome. However, its potential as imaging tool is still under estimated. In the present study, we aim to determine the prerequisites of maximal benefit of electric source imaging (ESI) to localize the irritative zone in patients with focal epilepsy. Methods: One hundred fifty patients suffering from focal epilepsy and with minimum 1 year postoperative follow-up were studied prospectively and blinded to the underlying diagnosis. We evaluated the influence of two important factors on sensitivity and specificity of ESI: the number of electrodes (low resolution, LR-ESI: <30 versus high resolution, HR-ESI: 128-256 electrodes), and the use of individual MRI (i-MRI) versus template MRI (t-MRI) as the head model. Findings: ESI had a sensitivity of 85% and a specificity of 87% when HR-ESI with i-MRI was used. Using LR-ESI, sensitivity decreased to 68%, or even 57% when only t-MRI was available. The sensitivity of HR-ESI/i-MRI compared favorably with those of MRI (76%), PET (69%) and ictal/interictal SPECT (64%). Interpretation: This study on a large patient group shows excellent sensitivity and specificity of ESI if 128 EEG channels or more are used for ESI and if the results are coregistered to the patient's individual MRI. Localization precision is as high as or even higher than established brain imagery techniques. HR-ESI appears to be a valuable additional imaging tool, given that larger electrode arrays are easily and rapidly applied with modern EEG equipment and that structural MRI is nearly always available for these patients.

Brain network analysis of patients with Temporal Lobe Epilepsy

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

The yield of high-density electric source imaging in focal epilepsy

Background: EEG is the cornerstone of epilepsy diagnostics and mandatory to determine the underlying epilepsy syndrome (e.g. focal vs idiopathic generalized). However, its potential as imaging tool is still underrecognized. In the present study, we aim to determine the prerequisites of maximal benefit of electric source imaging (ESI) to localize the irritative zone in patients with focal epilepsy. Methods: 150 patients suffering from focal epilepsy and with minimum 1 year post-operative follow-up were studied prospectively by reviewers blinded to the underlying diagnosis and outcome. We evaluated the influence of two important factors on sensitivity and specificity of ESI: the number of electrodes (low resolution, LR-ESI: \30 vs. high resolution, HR-ESI: 128-256 electrodes), and the use of individual MRI (i-MRI) vs. template MRI (t-MRI) as head model.Results: ESI had a sensitivity of 85% and a specificity of 87% when HR-ESI with i-MRI was used. Using LR-ESI, sensitivity decreased to 68%, or even 57% when only t-MRI was available. The sensitivity of HR-ESI/i-MRI compared favorably with those of MRI (76%), PET (69%) and ictal/interictal SPECT (64%).Interpretation: This study on a large patient group shows excellent sensitivity and specificity of ESI if 128 EEG channels or more are used for ESI and if the results are co-registered to the patient's individual MRI. Localization precision is as high as or even higher than established brain imaging techniques, providing excellent costeffectiveness in epilepsy evaluation. HR-ESI appears to be a valuable additional imaging tool, given that larger electrode arrays are easily and rapidly applied with modern EEG equipment and that structural MRI is nearly always available for these patients.

Residual Stress Measurement on a MEMS Structure With High-Spatial Resolution

A new approach to the local measurement of residual stress in microstructures is described in this paper. The presented technique takes advantage of the combined milling-imaging features of a focused ion beam (FIB) equipment to scale down the widely known hole drilling method. This method consists of drilling a small hole in a solid with inherent residual stresses and measuring the strains/displacements caused by the local stress release, that takes place around the hole. In the presented case, the displacements caused by the milling are determined by applying digital image correlation (DIC) techniques to high resolution micrographs taken before and after the milling process. The residual stress value is then obtained by fitting the measured displacements to the analytical solution of the displacement fields. The feasibility of this approach has been demonstrated on a micromachined silicon nitride membrane showing that this method has high potential for applications in the field of mechanical characterization of micro/nanoelectromechanical systems.

New Developments and Applications of the MP2RAGE Sequence - Focusing the Contrast and High Spatial Resolution R1 Mapping.

MR structural T1-weighted imaging using high field systems (>3T) is severely hampered by the existing large transmit field inhomogeneities. New sequences have been developed to better cope with such nuisances. In this work we show the potential of a recently proposed sequence, the MP2RAGE, to obtain improved grey white matter contrast with respect to conventional T1-w protocols, allowing for a better visualization of thalamic nuclei and different white matter bundles in the brain stem. Furthermore, the possibility to obtain high spatial resolution (0.65 mm isotropic) R1 maps fully independent of the transmit field inhomogeneities in clinical acceptable time is demonstrated. In this high resolution R1 maps it was possible to clearly observe varying properties of cortical grey matter throughout the cortex and observe different hippocampus fields with variations of intensity that correlate with known myelin concentration variations.