Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.

Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas.

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 µm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment.

Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.

Muscle fatty infiltration in rotator cuff tears: descriptive analysis of 1688 cases.

INTRODUCTION: Fatty infiltration (FI) is an important prognosis factor in the anatomical and functional outcomes of rotator cuff repairs. The objective of this study was to analyze the natural history of muscle FI and better evaluate its onset and aggravation time frame. MATERIAL AND METHODS: A total of 1688 medical charts of patients operated on for rotator cuff tear and with a preoperative CT arthrogram (82%) or an MRI (18%) were reviewed. Surgery was performed between 1988 and 2005. The FI of each muscle was assessed as minimal (in Goutallier's stages 0 and 1), intermediate (in stage 2), and severe (in stages 3 and 4). Regarding supraspinatus, we retained the mean FI observed in the sagittal, coronal, and axial planes; for the infraspinatus and the subscapularis, we retained the observed mean on two views at the upper and lower levels of the glenoid in the axial plane. RESULTS: We found a statistically significant correlation (p<0.0005) between FI, the type of tendon lesion, and patient age for the supraspinatus, the infraspinatus, and the subscapularis. Statistically, the FI significantly increased (p<0.0005) with time elapsed for the supraspinatus and the infraspinatus but not significantly for the subscapularis. The mean time to tendon rupture observed for intermediate FI was three years for the supraspinatus and 2.5 years for the infraspinatus and the subscapularis when their tendons ruptured. The mean time observed to severe FI was five, four, and three years for the supraspinatus, the infraspinatus, and the subscapularis, respectively. DISCUSSION AND CONCLUSION: The more extensive the lesion, the longer the time following rupture, and the older the patient is, the more severe the FI is. The objective of surgery is to intervene before intermediate FI sets in, which means irreversible functional loss. LEVEL OF EVIDENCE: Level IV. Diagnostic Retrospective Study.

Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials.

Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

Monitoring of Dermanyssus gallinae in free-range poultry farms.

Various methods for monitoring Dermanyssus gallinae infestations within free-range egg production units were compared. The study was carried out in five egg-producing free-range poultry buildings infested with D. gallinae. Each farm was divided into six zones (each zone including nest boxes, perches and duckboard) for placing two types of traps (corrugated cardboard and thick card traps) or examining dried droppings for presence of mites. Traps were removed 24 h later, placed into bags and mites were counted at the laboratory using binocular magnification. Droppings were also inspected by eye and mite numbers were estimated. All the methods used allowed us to detect mites although their efficacy differed. The number of mites collected was independent of the type of trap used. Examination of the droppings did not differentiate between buildings with differing mite populations. Placing traps in the nest boxes is a less reliable indicator than placing them on the perches. It appears that the most coherent method for evaluating the D. gallinae population within a free-range flock is to place thick card traps throughout the building, on perches favoured by birds.

Brain stem diffusion-weighted imaging lesion score: a potential marker of outcome in acute basilar artery occlusion.

BACKGROUND AND PURPOSE: The benefit of recanalization in basilar artery occlusion (BAO) has been established. The baseline extent of brain stem damage may also influence the outcome. We investigated whether a baseline diffusion-weighted imaging (DWI) score may provide additional prognostic value in BAO. MATERIALS AND METHODS: We analyzed baseline clinical and DWI parameters in consecutive patients treated with endovascular procedures for acute BAO. Brain stem DWI lesions were assessed by using a semiquantitative score based on arterial territory segmentation. Outcome at 3 months was dichotomized according to the modified Rankin Scale (mRS) as favorable (mRS, 0-2) or unfavorable (mRS, 3-6). Spearman rank correlation tests assessed the correlation between DWI and clinical variables. Univariate and multivariate logistic regression analyses were used to identify clinical and MR imaging predictors of outcome. RESULTS: Twenty-nine patients were included. The brain stem DWI score (median, 3; range, 0-14) was correlated with the baseline National Institutes of Health Stroke Scale (NIHSS) score and the presence and length of coma (r = 0.67, 0.49, and 0.53, respectively; P < .01). Recanalization was achieved in 76%. A higher baseline NIHSS score (P = .02) and brain stem DWI score (P = .03), a lower Glasgow Coma Scale score (P = .04), and the presence of coma (P = .05) were associated with poor outcome in univariate analysis. Multivariate analysis showed that the brain stem DWI score was the only independent baseline predictor for clinical outcome (P = .026). CONCLUSIONS: Baseline brain stem DWI lesion score is an independent marker of outcome in BAO.

The radiotherapy clinical trials projects at the ESRF: technical aspects.

The radiotherapy clinical trials projects, both aiming at treating aggressive brain tumors, require several major modifications and new constructions at the ESRF ID17 Biomedical beamline. The application of the Stereotactic Synchrotron Radiation Therapy (SSRT) technique mainly necessitates an upgrade of the existing patient positioning system, which was formerly used for the angiography program. It will allow for accurate positioning, translation and rotation of the patient during the treatment. For the Microbeam Radiation Therapy (MRT) clinical trials project, a new white beam hutch will be constructed to accommodate a dedicated patient positioning system. Consequently, the existing control hutches and the related installations will also be completely refurbished. Furthermore, the foreseen installation of a second X-ray source, which will allow doubling the currently available photon flux at high energies, requires a redesign of most optical components to handle the increased power and power densities. Starting from the current ID17 Biomedical beamline layout, the paper will present an update of the different modification/construction projects, including the general organization and planning.

[Comparison of IPSS and ICS male SF in the initial assessment of urinary disorders]. / Comparaison de l'IPSS et de l'ICS male SF dans le bilan initial des troubles urinaires.

UNLABELLED: The IPSS is considered to be the standard questionnaire for evaluation of lower urinary tract voiding disorders in men with benign prostatic hyperplasia (BPH). However, the absence of questions concerning urinary incontinence can be considered to be a weakness of this tool in view of the symptom profile of these patients. The ICS male SF, which comprises a supplementary domain of urinary incontinence, was compared to the IPSS in the context of the initial assessment of men with BPH. METHODS: One hundred and fifty-eight patients with voiding disorders associated with BPH completed the two questionnaires on two occasions at an interval of two weeks. RESULTS: The prevalence of urinary incontinence symptoms was very low (3.7%) and these symptoms were not independent of the symptoms of the urinary frequency domain. CONCLUSION: Despite the addition of a urinary incontinence domain, the ICS male SF does not provide any decisive advantage compared to the IPSS for the initial assessment of urinary disorders related to BPH.

[Psychophysiological factors in high intellectual potential: comparative study in children aged from 8 to 11 years old]. / Les facteurs psychophysiologiques de la précocité intellectuelle: résultats d'une enquête comparative chez l'enfant entre 8 et 11 ans.

UNLABELLED: Factors of intellectual talent as well as physiological and psychological characteristics are little known. However, giftedness is now a social problem and the knowledge of precocity hallmarks should permit the diagnosis in order to undertake the adequate educational orientation of these children. From questionnaires given anonymously to parents, this work showed comparative results between a population of gifted children and a control one. OBJECTIVES: The aim of this study was to present precocity hallmarks in the gifted population, following factorial analysis of socio-economic and familial parameters, as well as medical and psycho-physiological variables linked with the children's post-natal life. POPULATION: Four hundred and twelve children aged eight to 11 years, from Lyon, have been used in the survey: 217 children (control group) were included after a random selection in schools, and 195 children (gifted group, IQ >130, Wechsler test) were enrolled after clinician's diagnoses in four medical departments. RESULTS: Regression analysis allowed to draw relation between several factors and giftedness: abnormal pregnancy (CR =3.205, P =0.009), perinatal stress (CR =2.166, P =0.003), and presence of migraine (CR =3.169, P =0.001). Parents living together (married or not) (CR =2.100, P =0.080) with a good and superior level of learning (CR =5.464, P =0.0002) were also linked with giftedness. CONCLUSION: Our results indicate that precocity hallmarks are multifactorial. These data confirm some socio-economic and medical physiological features correlated with giftedness, and suggest that psychological factors may bear on the etiology of intellectual talent. We focus on the hypothesis than early stress may play a role on central nervous system maturation in these children.

Effect of tidal volume on distribution of ventilation assessed by synchrotron radiation CT in rabbit.

A respiration-gated synchrotron radiation computed tomography (SRCT) technique, which allows visualization and direct quantification of inhaled stable xenon gas, was used to study the effect of tidal volume (Vt) on regional lung ventilation. High-resolution maps (pixel size 0.35 x 0.35 mm) of local washin time constants (tau) and regional specific ventilation were obtained in five anesthetized, paralyzed, and mechanically ventilated rabbits in upright body position at the fourth, sixth, and eighth dorsal vertebral levels with a Vt from 4.9 +/- 0.3 to 7.9 +/- 0.4 ml/kg (means +/- SE). Increasing Vt without an increase in minute ventilation resulted in a proportional increase of mean specific ventilation up to 65% in all studied lung levels and reduced the scattering of washin tau values. The tau values had log-normal distributions. The results indicate that an increase in Vt decreases nonuniformity of intraregional ventilatory gas exchange. The findings suggest that (SRCT) provides a new quantitative tool with high spatial discrimination ability for assessment of changes in peripheral pulmonary gas distribution during mechanical ventilation.

Lack of cell death enhancement after irradiation with monochromatic synchrotron X rays at the K-shell edge of platinum incorporated in living SQ20B human cells as cis-diamminedichloroplatinum (II).

In this paper we describe the results of experiments using synchrotron radiation to trigger the Auger effect in living human cancer cells treated with a widely used chemotherapy drug: cis-diamminedichloroplatinum (II) (cisplatin). The experiments were carried out at the ID17 beamline of the European Synchrotron Radiation Facility, which produces a high-fluence monochromatic beam that is adjustable from 20 to 80 keV. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). Cell survival curves were comparable with those obtained for the same cells under conventional irradiation conditions. At a low dose of cisplatin (0.1 microM, 48 h), no difference was seen in survival when the cells were irradiated above and below the K-shell edge of platinum. Higher cisplatin concentrations were investigated to enhance the cellular platinum content. The results with 1 microM cisplatin for 12 h showed no difference when the cells were irradiated with beams above or below the platinum K-shell edge with the exception of the higher cell death resulting from drug toxicity. The intracellular content of platinum was significant, as measured macroscopically by inductively coupled plasma mass spectrometry. Its subcellular localization and particularly its presence in the cell nucleus were verified by microscopic synchrotron X-ray fluorescence. This was the first known attempt at K-shell edge photon activation of stable platinum in living cells with a platinum complex used for chemotherapy. Its evident toxicity in these cells leads us to put forth the hypothesis that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation above the K-shell edge. However, K-shell edge photon activation of stable elements provides a powerful technique for the understanding of the biological effects of Auger processes. Further avenues of development are discussed.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent.

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.

Venous allografts preserved at 4 degrees C for infrainguinal bypass: long-term results from 170 procedures.

From April 21, 1982 to December 31, 1997, we performed 170 infrainguinal bypass procedures using isolated (n = 35) or composite (n = 135) venous allografts preserved at 4 degrees C as a substitute for saphenous autografts in 146 patients. The mean age of the patient population was 74 years. The indication was critical lower limb ischemia in 71% of cases. Seventy-five percent of procedures were below the knee and 26% were infrapopliteal. Mean length and diameter were 19.5 +/- 0.5 cm and 4.8 +/- 0.5 mm, respectively. After December 8, 1993, a reinforcement net was placed over the graft to prevent expansion in 71% of cases. Primary and secondary 5-year patency, calculated according to the Kaplan-Meier method, were 33 +/- 6% and 43 +/- 6%, respectively. Factors correlated with secondary patency were studied using the log-rank test. Previous ipsilateral infrainguinal revascularization was associated with a 40% decrease in secondary patency at 2 years (71% vs. 31%). Patency at 5 years was correlated with the level of anastomosis (47% for low popliteal anastomosis vs. 30% for infrapopliteal anastomosis). The likelihood of stenosis or dilatation of the allograft was 8% and 29.5%, respectively, at 5 years. The 5-year limb salvage and survival rates were 84% and 57%, respectively. The encouraging results of this series suggest that venous allografts provide a useful alternative for infrainguinal bypass when autologous grafts or other more reliable conduits are unavailable.

First human transvenous coronary angiography at the European Synchrotron Radiation Facility.

The first operation of the European Synchrotron Radiation Facility (ESRF) medical beamline is reported in this paper. The goal of the angiography project is to develop a reduced risk imaging technique, which can be used to follow up patients after coronary intervention. After the intravenous injection of a contrast agent (iodine) two images are produced with monochromatic beams, bracketing the iodine K-edge. The logarithmic subtraction of the two measurements results in an iodine enhanced image, which can be precisely quantified. A research protocol has been designed to evaluate the performances of this method in comparison with the conventional technique. Patients included in the protocol have previously undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both at the ESRF and at the hospital with the conventional technique, within the next few days. This paper reports the results obtained with the first patients. To date, eight patients have been imaged and excellent image quality was obtained.

Research at the European Synchrotron Radiation Facility medical beamline.

The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy is progressing. This paper will present a very brief overview of the beamline and the imaging and therapy programs.

In vivo K-edge imaging with synchrotron radiation.

We present in this paper two imaging techniques using contrast agents assessed with in vivo experiments. Both methods are based on the same physical principle, and were implemented at the European Synchrotron Radiation Facility medical beamline. The first one is intravenous coronary angiography using synchrotron radiation X-rays. This imaging technique has been planned for human studies in the near future. We describe the first experiments that were carried out with pigs at the ESRF. The second imaging mode is computed tomography using synchrotron radiation on rats bearing brain tumors. Owing to synchrotron radiation physical properties, these new imaging methods provide additional information compared to conventional techniques. After infusion of the contrast agent, it is possible to derive from the images the concentration of the contrast agent in the tumor area for the computed tomography and in any visible vessel for the angiography method.

Using thoracic helical CT to assess iodine concentration in a small volume of nonionic contrast medium during vascular opacification: a prospective study.

OBJECTIVE: The goal of the study was to assess whether, using thoracic helical CT, diagnostic mediastinal and hilar vascular enhancement can be obtained with a small amount of nonionic contrast material (80 ml) injected at a relatively slow rate (2 ml/sec). SUBJECTS AND METHODS: One hundred twenty patients (60 in their fourth decade of life and 60 in their seventh decade of life) referred for contrast-enhanced thoracic CT for malignancies or infections prospectively entered the study. They were randomly assigned to be given one of three iodine concentrations of a nonionic contrast material: 250 mg/ml (1250), 300 mg/ml (1300), and 350 mg/ml (1350). Two radiologists independently graded perivenous artifacts and arterial enhancement of mediastinal and hilar vessels on a 4-point scale: 1, poor; 2, fair; 3, good; and 4, excellent. Measurements of arterial attenuation values (quantitative assessment) were obtained on the aorta and pulmonary artery. RESULTS: Mean scores were equal to or greater than 3 for all vessels only using 1350. The higher the iodine concentration was, the higher the mean score, but there was a statistically significant difference only between scores obtained with 1350 and those obtained with 1300 or 1250. Mean scores were higher for the patients in their seventh decade of life than those in their fourth decade; however, there was no statistically significant difference between scores of the two decade groups. We found a highly significant statistical relationship between scores and arterial attenuation values. CONCLUSION: During contrast-enhanced helical CT examinations for general thoracic evaluations, good opacification of central vascular structures is obtained with a low volume of high iodine concentration nonionic contrast medium.

Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial.

PURPOSE: The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown. The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery. PATIENTS AND METHODS: Patients with rectal carcinoma accessible to rectal digital examination, staged T2 to T3, NX, M0, were randomized before radiotherapy (39 Gy in 13 fractions) into two groups: in the short interval (SI) group, surgery had to be performed within 2 weeks after completion of radiation therapy, compared with 6 to 8 weeks in the long interval (LI) group. Between 1991 and 1995, 201 patients were enrolled onto the study. RESULTS: A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response (53. 1% in the SI group v 71.7% in the LI group, P =.007) and pathologic downstaging (10.3% in the SI group v 26% in the LI group, P =.005). At a median follow-up of 33 months, there were no differences in morbidity, local relapse, and short-term survival between the two groups. Sphincter-preserving surgery was performed in 76% of cases in the LI group versus 68% in the SI group (P = 0.27). CONCLUSION: A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results. When sphincter preservation is questionable, a long interval may increase the chance of a successful sphincter-saving surgery.