A Geant4 simulation for three-dimensional proton imaging of microscopic samples.

Proton imaging can be carried out on microscopic samples by focusing the beam to a diameter ranging from a few micrometers down to a few tens of nanometers, depending on the required beam intensity and spatial resolution. Three-dimensional (3D) imaging by tomography is obtained from proton transmission (STIM: Scanning Transmission Ion Microscopy) and/or X-ray emission (PIXE: Particle Induced X-ray Emission). In these experiments, the samples are dehydrated for under vacuum analysis. In situ quantification of nanoparticles has been carried out at CENBG in the frame of nanotoxicology studies, on cells and small organisms used as biological models, especially on Caenorhabditis elegans (C. elegans) nematodes. Tomography experiments reveal the distribution of mass density and chemical content (in g.cm-3) within the analyzed volume. These density values are obtained using an inversion algorithm. To investigate the effect of this data reduction process, we defined different numerical phantoms, including a (dehydrated) C. elegans phantom whose geometry and density were derived from experimental data. A Monte Carlo simulation based on the Geant4 toolkit was developed. Using different simulation and reconstruction conditions, we compared the resulting tomographic images to the initial numerical reference phantom. A study of the relative error between the reconstructed and the reference images lead to the result that 20 protons per shot can be considered as an optimal number for 3D STIM imaging. Preliminary results for PIXE tomography are also presented, showing the interest of such numerical phantoms to produce reference data for future studies on X-ray signal attenuation in thick samples.

Three-dimensional imaging of past skeletal TB: From lesion to process.

3D imaging has become an essential tool in the field of biological anthropology, notably for human evolution purposes. High resolution virtual 3D reconstructions of original specimens contribute to their preservation and broaden the ability for research, teaching and exchanges. Paleopathology can get substantial benefit from these methods, among others for reconstructing infectious pathological processes on ancient bones. Tuberculosis is frequently diagnosed on ancient human remains; however, some osseous expressions are difficult to interpret using classical methods. We illustrate here the interest of 3D methods for reconstructing processes involved in pathological bone changes due to Mycobacterium tuberculosis infection. Four paleopathological specimens attributed to this infection, dating from different time periods and concerning diverse parts of the skeleton have been analyzed using a specific 3D digital chain we have previously developed. These 3D analyses allow to virtually reconstruct the initial location and aspect of the infectious process, its extension as well as its possible diffusion to the surrounding soft tissues. This possible virtual follow-up of the disease leads to the concept of processual paleopathology that we would like to introduce in the field. The 3D methodology can help to improve our knowledge of natural history and evolution of ancient human infections such as tuberculosis.

Anthropological facial approximation in three dimensions (AFA3D): computer-assisted estimation of the facial morphology using geometric morphometrics.

This study presents Anthropological Facial Approximation in Three Dimensions (AFA3D), a new computerized method for estimating face shape based on computed tomography (CT) scans of 500 French individuals. Facial soft tissue depths are estimated based on age, sex, corpulence, and craniometrics, and projected using reference planes to obtain the global facial appearance. Position and shape of the eyes, nose, mouth, and ears are inferred from cranial landmarks through geometric morphometrics. The 100 estimated cutaneous landmarks are then used to warp a generic face to the target facial approximation. A validation by re-sampling on a subsample demonstrated an average accuracy of c. 4 mm for the overall face. The resulting approximation is an objective probable facial shape, but is also synthetic (i.e., without texture), and therefore needs to be enhanced artistically prior to its use in forensic cases. AFA3D, integrated in the TIVMI software, is available freely for further testing.

Impairment of GABAB receptor dimer by endogenous 14-3-3ζ in chronic pain conditions.

In the central nervous system, the inhibitory GABAB receptor is the archetype of heterodimeric G protein-coupled receptors (GPCRs). However, the regulation of GABAB dimerization, and more generally of GPCR oligomerization, remains largely unknown. We propose a novel mechanism for inhibition of GPCR activity through de-dimerization in pathological conditions. We show here that 14-3-3ζ, a GABAB1-binding protein, dissociates the GABAB heterodimer, resulting in the impairment of GABAB signalling in spinal neurons. In the dorsal spinal cord of neuropathic rats, 14-3-3ζ is overexpressed and weakens GABAB inhibition. Using anti-14-3-3ζ siRNA or competing peptides disrupts 14-3-3ζ/GABAB1 interaction and restores functional GABAB heterodimers in the dorsal horn. Importantly, both strategies greatly enhance the anti-nociceptive effect of intrathecal Baclofen in neuropathic rats. Taken together, our data provide the first example of endogenous regulation of a GPCR oligomeric state and demonstrate its functional impact on the pathophysiological process of neuropathic pain sensitization.

Three-dimensional computer-assisted craniometrics: a comparison of the uncertainty in measurement induced by surface reconstruction performed by two computer programs.

Digital investigation of anthropological material through computed tomography (CT) offers several new opportunities in morphometrics. However, an object measured with computer-assisted methods does not necessarily exactly match the original one. The scanning and surface reconstruction of the object induce some alterations, and data acquisition is prone to measurement uncertainty. The purpose of this research is to evaluate the intra- and inter-observers variations in medical CT scan measurements of a known-size phantom and two dry crania. Two software packages, AMIRA and Treatment and Increased Vision for Medical Imaging (TIVMI), which use different techniques of surface reconstructions, were compared. The mean difference between the measurements was lower for TIVMI, using an objective algorithm based on the half-maximum height (HMH) protocol in three dimensions (3D). AMIRA can induce up to a 4% error in known measurements and 5% uncertainty in dry skull measurements. This study emphasises the risk of object shape alteration in each step of its digitisation.

On two equations about brain volume, cranial capacity and age.

AIM: We decided to study the relationship between brain volume and cranial capacity and the relationship between brain volume and age on a series of CT from healthy adults. METHODS: Fifty-eight healthy volunteers (27 women, 31 men, age range 18-95 years) were examined using our imaging protocols. The volunteers had no present or past neuropsychiatric illness and no abuse of alcohol or illicit drugs. RESULTS: Mean intracranial volume was 1,384.6 cm(3) (standard deviation = 135.27, range 1,106-1,656) and mean brain volume was 1,201.0 cm(3) (standard deviation = 142.52, range 791-1,500). Linear regression between brain volume and cranial capacity yielded this formula: brain volume = 182.3 + 0.7 × cranial capacity. Multivariate analysis yielded a relationship between cranial capacity, brain volume and age as follows: brain volume = 396.5-3.5 × age + 0.7 × cranial capacity. CONCLUSION: This study could be supplemented by the collection of data such as, the size of the individuals in order to study the relationship between size of the brain and stature because this relation remains unclear.

Measurement of glomerular filtration rate with magnetic resonance imaging: principles, limitations, and expectations.

Glomerular filtration rate (GFR) is the most useful quantitative index of renal function and is used clinically as the gold standard of renal dysfunction. Follow-up of patients with impaired renal function requires reliable measurements of GFR. Thus, serial GFR values estimated from magnetic resonance imaging (MRI) would be worthwhile if easy to obtain, accurate, and reproducible. Nuclear medicine-based techniques remain at present the reference method for quantification of GFR, but MRI should be able to compete in the near future. Several methods are available for measurement of GFR using MRI and freely filtered Gd-chelates: (1) measurement of the clearance of the agent using blood samplings; (2) measurement of the plasma clearance of the agent using signal intensity changes within abdominal organs; (3) measurement of the extraction fraction of the agent; and (4) monitoring of tracer intrarenal kinetics. A high heterogeneity of protocols (e.g., in acquisition mode, dose of contrast, postprocessing techniques) is noted in the literature, reflecting the number of technical challenges that will have to be solved before to reach a consensus, and the reported accuracy and reproducibility are insufficient for justifying their use in clinical practice now.

Airway wall thickness in cigarette smokers: quantitative thin-section CT assessment.

PURPOSE: To design and validate a dedicated software tool to measure airway dimensions on thin-section computed tomographic (CT) images and to use the tool to prospectively compare airway wall thickness in nonsmokers with normal lung function with that in smokers with and without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: All subjects gave written informed consent. The study was approved by local ethics committee. With Laplacian of Gaussian algorithm, software was tested in phantom and excised sheep lung fixed in inflation and validated with Bland-Altman analysis. Study prospectively included nine nonsmokers (six women, three men; mean age, 53 years +/- 5.6 [standard error of the mean]) with normal lung function (group 1), seven smokers (three women, four men; mean age, 56 years +/- 5.6) with normal lung function (group 2), and eight smokers (zero women, eight men; mean age, 65 years +/- 4.0) with COPD. Calculations were determined with spirometrically gated CT: For each selected bronchus, the wall area (WA), internal area (IA), airway caliber (sum of IA and WA), and WA/IA ratio were calculated. For each patient, summation of WA to summation of IA (SigmaWA/SigmaIA) ratio, which reflected normalized airway wall thickness, was calculated. Groups were compared by using analysis of variance with generalized linear model and unpaired t test. Pearson correlation coefficient was used to assess correlation between software measurements and pulmonary function test results. RESULTS: Comparison of measurements in phantom and excised sheep lung with algorithm measurements revealed that the latter were reliable and repeatable. In clinical study, SigmaWA/SigmaIA ratio was significantly different among three groups (P < .001). Normalized airway wall thickness and IA were significantly related to lung function test data, including forced expiratory volume in 1 second (r = -0.54, P = .006), specific airway conductance (r = -0.45, P = .03), and forced expiratory flow between 25% and 75% of vital capacity (r = -0.65, P < .001). CONCLUSION: This software provides accurate and reproducible measurements of IA and WA of bronchi on thin-section CT images and demonstrates that in vivo normalized airway wall thickness was larger in smokers with COPD than it was in smokers or nonsmokers without COPD.