The choice of statistical methods for comparisons of dosimetric data in radiotherapy.

PURPOSE: Novel irradiation techniques are continuously introduced in radiotherapy to optimize the accuracy, the security and the clinical outcome of treatments. These changes could raise the question of discontinuity in dosimetric presentation and the subsequent need for practice adjustments in case of significant modifications. This study proposes a comprehensive approach to compare different techniques and tests whether their respective dose calculation algorithms give rise to statistically significant differences in the treatment doses for the patient. METHODS: Statistical investigation principles are presented in the framework of a clinical example based on 62 fields of radiotherapy for lung cancer. The delivered doses in monitor units were calculated using three different dose calculation methods: the reference method accounts the dose without tissues density corrections using Pencil Beam Convolution (PBC) algorithm, whereas new methods calculate the dose with tissues density correction for 1D and 3D using Modified Batho (MB) method and Equivalent Tissue air ratio (ETAR) method, respectively. The normality of the data and the homogeneity of variance between groups were tested using Shapiro-Wilks and Levene test, respectively, then non-parametric statistical tests were performed. Specifically, the dose means estimated by the different calculation methods were compared using Friedman's test and Wilcoxon signed-rank test. In addition, the correlation between the doses calculated by the three methods was assessed using Spearman's rank and Kendall's rank tests. RESULTS: The Friedman's test showed a significant effect on the calculation method for the delivered dose of lung cancer patients (p <0.001). The density correction methods yielded to lower doses as compared to PBC by on average (-5 ± 4.4 SD) for MB and (-4.7 ± 5 SD) for ETAR. Post-hoc Wilcoxon signed-rank test of paired comparisons indicated that the delivered dose was significantly reduced using density-corrected methods as compared to the reference method. Spearman's and Kendall's rank tests indicated a positive correlation between the doses calculated with the different methods. CONCLUSION: This paper illustrates and justifies the use of statistical tests and graphical representations for dosimetric comparisons in radiotherapy. The statistical analysis shows the significance of dose differences resulting from two or more techniques in radiotherapy.

A phantom and animal study of temperature changes during fMRI with intracerebral depth electrodes.

BACKGROUND: MRI is routinely used in patients undergoing intracerebral electroencephalography (icEEG) in order to precisely locate the position of intracerebral electrodes. In contrast, fMRI has been considered unsafe due to suspected greater risk of radiofrequency-induced (RF) tissue heating at the vicinity of intracerebral electrodes. We determined the possible temperature change at the tip of such electrodes during fMRI sessions in phantom and animals. METHODS: A human-shaped torso phantom and MRI-compatible intracerebral electrodes approved for icEEG in humans were used to mimic a patient with four intracerebral electrodes (one parasagittal and three coronal). Six rabbits were implanted with one or two coronal electrodes. MRI-induced temperature changes at the tip of electrodes were measured using a fibre-optic thermometer. All experiments were performed on Siemens Sonata 1.5T scanner. RESULTS: For coronally implanted electrodes with wires pulled posteriorly to the magnetic bore, temperature increase recorded during EPI sequences reached a maximum of 0.6°C and 0.9°C in phantom and animals, respectively. These maximal figures were decreased to 0.2°C and 0.5°C, when electrode wires were connected to cables and amplifier. When electrode wires were pulled anteriorly to the magnetic bore, temperature increased up to 1.3°C in both phantom and animals. Greater temperature increases were recorded for the single electrode implanted parasagitally in the phantom. CONCLUSION: Variation of the temperature depends on the electrode and wire position relative to the transmit body coil and orientation of the constant magnetic field (B0). EPI sequence with intracerebral electrodes appears as safe as standard T1 and T2 sequence for implanted electrodes placed perpendicular to the z-axis of the magnetic bore, using a 1.5T MRI system, with the free-end wires moving posteriorly, in phantom and animals.

Milk protein intake, the metabolic-endocrine response, and growth in infancy: data from a randomized clinical trial.

BACKGROUND: Protein intake in early infancy has been suggested to be an important risk factor for later obesity, but information on potential mechanisms is very limited. OBJECTIVE: This study examined the influence of protein intake in infancy on serum amino acids, insulin, and the insulin-like growth factor I (IGF-I) axis and its possible relation to growth in the first 2 y of life. DESIGN: In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow-milk-based infant and follow-on formulas with lower protein (LP; 1.77 and 2.2 g protein/100 kcal) or higher protein (HP; 2.9 and 4.4 g protein/100 kcal) contents for the first year. Biochemical variables were measured at age 6 mo in 339 infants receiving LP formula and 333 infants receiving HP formula and in 237 breastfed infants. RESULTS: Essential amino acids, especially branched-chain amino acids, IGF-I, and urinary C-peptide:creatinine ratio, were significantly (P < 0.001) higher in the HP group than in the LP group, whereas IGF-binding protein (IGF-BP) 2 was lower and IGF-BP3 did not differ significantly. The median IGF-I total serum concentration was 48.4 ng/mL (25th, 75th percentile: 27.2, 81.8 ng/mL) in the HP group and 34.7 ng/mL (17.7, 57.5 ng/mL) in the LP group; the urine C-peptide:creatinine ratios were 140.6 ng/mg (80.0, 203.8 ng/mg) and 107.3 ng/mg (65.2, 194.7 ng/mg), respectively. Most essential amino acids, IGF-I, C-peptide, and urea increased significantly in both the LP and HP groups compared with the breastfed group. Total IGF-I was significantly associated with growth until 6 mo but not thereafter. CONCLUSIONS: HP intake stimulates the IGF-I axis and insulin release in infancy. IGF-I enhances growth during the first 6 mo of life. This trial was registered at clinicaltrials.gov as NCT00338689.

Effects of galacto-oligosaccharide ingestion on the mucosa-associated mucins and sucrase activity in the small intestine of mice.

BACKGROUND: Galacto-oligosaccharides (GOS) are non-digestible oligosaccharides with short galactosyl chain units produced by lactose fermentation which are considered as prebiotics. Only few studies have investigated the effects of GOS medium-term ingestion on the small intestinal epithelium characteristics. AIM OF THE STUDY: In this study, we evaluated the consequences of GOS ingestion on small intestinal mucosal morphology, on brush-border membrane enzyme activities and on mucin content in BALB/c mice. METHODS: Mice received the experimental diets for 4 weeks and then the small intestine was collected to measure sucrase, lactase and alkaline phosphatase activities, to study the villus heights in the jejunum mucosa and to determine mucosal mucin content as well as MUC-2 and MUC-4 mRNAs expression by qRT-PCR. RESULTS: Our results showed that GOS has no detectable effect on the intestine villus height but increased the total protein content by twofold. Sucrase activity was significantly increased in the intestinal mucosa recovered from animals fed the GOS diet without any detectable modification of lactase and phosphatase activities. Interestingly, GOS was also able to increase sucrase activity in cultured Caco-2 cells raising the view that they likely act directly on these cells. Furthermore, GOS was found to markedly increase O-linked glycoproteins associated with the intestinal mucosa without modifying MUC-2, MUC-4 mRNAs expression. Lastly, TNF-alpha mRNA expression was also not modified after GOS ingestion. CONCLUSIONS: These results suggest that, in BALB/c mice, 4-week GOS ingestion is able to increase the small intestinal mucosa-associated mucin content and enterocyte-associated sucrase activity without modifying villus height.

Estimation of optical properties of turbid media: experimental comparison of spatially and temporally resolved reflectance methods.

We compare two methods for the optical characterization of turbid media. The estimates of the absorption and reduced scattering coefficients (mu(a) and mu(')(s)) by a spatially resolved method and a time-resolved method are performed on tissue-like phantoms. Aqueous suspension of microspheres and Intralipid are used as scattering media with the addition of ink as an absorber. mu(')(s) is first measured on weakly absorbing media. The robustness of these measurements is then tested with respect to a variation of mu(a). The spatially resolved method gave more accurate estimates for mu(')(s) whereas the time-resolved method gave better results for mu(a) estimates.

Analysis of simulated and experimental backscattered images of turbid media in linearly polarized light: estimation of the anisotropy factor.

Optical characterization of biological tissues is of real interest to improve medical diagnosis, in particular in the detection of precancerous tissues. We propose a new, noninvasive method allowing the estimation of the anisotropy factor. This method is based on the image analysis of the Q element of the Stokes vector backscattered from the turbid medium. These Q-element images show specific patterns depending on g. Therefore the use of Fourier descriptors (FDs) on simulated data to discriminate the specific geometrical features of the Q element enabled us to determine a linear relation between the anisotropy factor and six FDs. This method was applied on experimental data obtained with calibrated solutions. The anisotropy factor was estimated with a maximum relative error of 13%.

Backscattered stokes vectors of turbid media: anisotropy factor and reduced scattering coefficient estimation.

Optical characterization of biological tissues is of real interest to improve medical diagnosis and in particular in the detection of precancerous tissues. The reduced scattering coefficient micro's and the absorption coefficient microa are the most commonly retrieved coefficients. Some methods also allow to obtain the anisotropy factor g, but only few of them are non-invasive. We propose a new non-invasive method allowing the estimation of the anisotropy factor and the reduced scattering coefficient. This method is based on the image analysis of the Q-element of Stokes vector backscattered from the turbid medium. These Q-element images show specific patterns depending on g, and micro's is determined by the size of the patterns. Therefore the use of Fourier Descriptors (FD) on simulated and experimental data, to discriminate the specific geometrical features of the Q-element, enabled us to determine the anisotropy factor and the scattering coefficient.

High-resolution MR imaging appearance of colonic tissue in rabbits using an endoluminal coil.

PURPOSE: This study assessed the value of high-resolution magnetic resonance imaging (MRI) of the distal colon by means of a dedicated endoluminal magnetic resonance receiver coil on a 1.5-T clinical scanner. MATERIALS AND METHODS: To this end, single-loop, receive-only radio-frequency coils, housed in 18 F sheaths, were built. A 1.5-T clinical imager was used. A 18 French diameter internal MRI receiver coil was inserted into the distal colon in 15 New Zealand rabbits to obtain high-resolution magnetic resonance images by using T1-weighted Flash sequences with and without Fat Saturation (FS), T2-weighted True-Fisp, turbo spin-echo, and T1-weighted Flash FS after contrast media injection. Images were compared to histological sections. RESULTS: An adequate image quality was obtained in all specimens without significant artefacts. Based on histological reports, a five-layer structure of the wall was considered normal. On different MR sequences, only two layers were identified on the images of all rabbits specimens. The nearest layer to the mucosal surface was usually seen as a hyper intense layer and likely corresponds to the mucosa. The highest difference of signal value between internal and external layers was performed on 2D Fat saturation T1 weighted gradient echo. Comparison of mean signal value between the internal and external layers was statistically different in for each sequence used in our protocol (P < 0.05). CONCLUSION: Dedicated endoluminal RF coil provides good spatial resolution at the region of interest. On this prospective study of in vivo rabbit, evaluation of colon walls allowed to provide detailed information.

RF-induced temperature elevation along metallic wires in clinical magnetic resonance imaging: influence of diameter and length.

With the development of interventional MRI, heating of biological tissues along the metallic wires in the MRI scanner has become an important issue. To assess thermal response to RF exposure during MRI, we studied the temperature elevation near nonmagnetic metallic wires. All tests were performed on a 1.5 T clinical scanner. Four experiments were conducted to investigate the effects of the wire diameter, the excitation flip angle, the temperature distribution along the wire, and the wire length. Electromagnetic simulations of the experimental setup were made with the use of commercial method of moments (MoM) software and numerical simulations of Hallen's equations. Comparisons between measured and calculated values of the electric field are presented. This study demonstrates that 1) temperature decreases with the diameter of the wire,2) temperature increases quadratically with the excitation flip angle, 3) heating occurs not only at the tip but also along the wire, and 4) the heating peaks are not obtained for the classical resonant length multiple of lambda/4 (where lambda is the RF field wavelength). In addition, significant and rapid heating increases were observed in the close vicinity of the wire.