On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

PURPOSE: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation. METHODS: Water phantom acquisitions were carried out on 39 scanners. DWI acquisitions (b-value = 0-200-400-600-800-1000 s/mm2) with different acquisition plans (axial, coronal, sagittal) and phase encoding directions (anterior/posterior and right/left, for the axial acquisition plan), for 3 orthogonal diffusion weighting gradient directions, were performed. For each acquisition setup, ADC values were measured in-center and off-center (6 different positions), resulting in an entire dataset of 84 × 39 = 3276 ADC values. Spatial uniformity of ADC maps was assessed by means of the percentage difference between off-center and in-center ADC values (Δ). RESULTS: No significant dependence of in-center ADC values on acquisition plan/phase encoding direction was found. Ward unsupervised clustering analysis showed 3 distinct clusters of scanners and an association between Δ-values and manufacturer/model, whereas no association between Δ-values and maximum gradient strength, slew rate or static magnetic field strength was revealed. Several acquisition setups showed significant differences among groups, indicating the introduction of different biases in ADC estimation. CONCLUSIONS: Unsupervised clustering analysis of DWI data, obtained from several scanners using an extensive acquisition protocol, allows to reveal an association between measured ADC values and manufacturer/model of scanner, as well as to identify suboptimal DWI acquisition setups for accurate ADC estimation.

Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo-radiotherapy.

BACKGROUND: We investigated whether the pattern of intensity-modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD). METHODS: A frequency-matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models. RESULTS: The incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both). CONCLUSION: Along with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patient's surface may help predict the development of severe RD.

Surgeon eye lens dose monitoring in catheterization lab: A multi-center survey: Invited for ECMP 2018 Focus Issue.

PURPOSE: To perform a multi-centre survey on the eye lens equivalent dose absorbed by primary interventionalist during catheterization procedures, using a personal dosimeter placed close to the eye lens. METHODS: 15 different cardiologists working in 3 different centers, for a total of 5 operating rooms were enrolled. All of them were provided with a single thermoluminescent dosimeter positioned on the inner side of the temples of eyeglasses. The dose monitoring, performed on a two-months basis, started in 2016 and is still running. All dose measurements were performed by a ISO 17025 standard accredited dosimetry service thus providing certified uncertainties as well. Correlation of eye lens and wrist dose with KAP was also investigated. RESULTS: A total number of 101 eye lens measurements were performed. Annual eye lens dose estimation was obtained for all 15 surgeons (mean, mode, range, standard deviation: 10.8, 8, 4.9-27.3, 5.6  mSv, respectively). Uncertainties on annual eye lens dose estimations ranged between 10% and 20%. No significant correlation was found between eye lens dose and KAP. CONCLUSIONS: Cardiologists involved in catheterization procedures may receive annual eye lens doses close to the ICRP 118 dose limit and thus individual monitoring with a dedicated dosimeter should be carried out. Uncertainty assessment play a relevant role in eye lens equivalent dose estimation to ensure not to exceed dose limit.

A straightforward multiparametric quality control protocol for proton magnetic resonance spectroscopy: Validation and comparison of various 1.5 T and 3 T clinical scanner systems.

PURPOSE: The aim of this study was to propose and validate across various clinical scanner systems a straightforward multiparametric quality assurance procedure for proton magnetic resonance spectroscopy (MRS). METHODS: Eighteen clinical 1.5 T and 3 T scanner systems for MRS, from 16 centres and 3 different manufacturers, were enrolled in the study. A standard spherical water phantom was employed by all centres. The acquisition protocol included 3 sets of single (isotropic) voxel (size 20 mm) PRESS acquisitions with unsuppressed water signal and acquisition voxel position at isocenter as well as off-center, repeated 4/5 times within approximately 2 months. Water peak linewidth (LW) and area under the water peak (AP) were estimated. RESULTS: LW values [mean (standard deviation)] were 1.4 (1.0) Hz and 0.8 (0.3) Hz for 3 T and 1.5 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficient of variation of LW and AP for different spatial positions of acquisition voxel were 43% (20%) and 11% (11%), respectively. The mean (standard deviation) phantom T2values were 1145 (50) ms and 1010 (95) ms for 1.5 T and 3 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficients of variation for repeated measurements of LW, AP and T2 were 25% (20%), 10% (14%) and 5% (2%), respectively. CONCLUSIONS: We proposed a straightforward multiparametric and not time consuming quality control protocol for MRS, which can be included in routine and periodic quality assurance procedures. The protocol has been validated and proven to be feasible in a multicentre comparison study of a fairly large number of clinical 1.5 T and 3 T scanner systems.

Dependence of apparent diffusion coefficient measurement on diffusion gradient direction and spatial position - A quality assurance intercomparison study of forty-four scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose an MRI quality assurance procedure that can be used for routine controls and multi-centre comparison of different MR-scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: 44 MR-scanners with different field strengths (1 T, 1.5 T and 3 T) were included in the study. DWI acquisitions (b-value range 0-1000 s/mm2), with three different orthogonal diffusion gradient directions, were performed for each MR-scanner. All DWI acquisitions were performed by using a standard spherical plastic doped water phantom. Phantom solution ADC value and its dependence with temperature was measured using a DOSY sequence on a 600 MHz NMR spectrometer. Apparent diffusion coefficient (ADC) along each diffusion gradient direction and mean ADC were estimated, both at magnet isocentre and in six different position 50 mm away from isocentre, along positive and negative AP, RL and HF directions. RESULTS: A good agreement was found between the nominal and measured mean ADC at isocentre: more than 90% of mean ADC measurements were within 5% from the nominal value, and the highest deviation was 11.3%. Away from isocentre, the effect of the diffusion gradient direction on ADC estimation was larger than 5% in 47% of included scanners and a spatial non uniformity larger than 5% was reported in 13% of centres. CONCLUSION: ADC accuracy and spatial uniformity can vary appreciably depending on MR scanner model, sequence implementation (i.e. gradient diffusion direction) and hardware characteristics. The DWI quality assurance protocol proposed in this study can be employed in order to assess the accuracy and spatial uniformity of estimated ADC values, in single- as well as multi-centre studies.

Advantage of deep inspiration breath hold in left-sided breast cancer patients treated with 3D conformal radiotherapy.

PURPOSE: To compare 3D-conformal radiotherapy (3D-CRT) treatment plans based on free-breathing (FB) and deep inspiration breath hold (DIBH) and investigated whether DIBH technique enables a decrease of cardiac left anterior descending coronary artery (LADCA) and lungs dose with respect to the FB. METHODS: Twenty-three left-sided breast cancer patients referred for breast radiotherapy were included. The planning target volume (PTV) encompassed the breast and organs at risk including heart, LADCA, lungs, and contralateral breast, which were contoured in FB and DIBH CT scans. Dose to PTV was 50 Gy in 25 fractions. Two treatment plans were generated for each patient: FB-3D-CRT and DIBH-3D-CRT. Dosimetry parameters were obtained from dose volume histograms. Data were compared using the paired-sample Wilcoxon signed rank test. RESULTS: For heart, LADCA, and left lung, a significant dose reduction was found using DIBH technique. By using DIBH, an average reduction of 25% was observed in LADCA for the volume receiving 20 Gy and of 48% considering the mean heart dose. CONCLUSIONS: The DIBH technique results in a significant decrease of dose to the heart, LADCA, and left lung compared to FB.

Quality assurance multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose a magnetic resonance imaging (MRI) quality assurance procedure that can be used for multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Twenty-six centers (35 MR scanners with field strengths: 1T, 1.5T, and 3T) were enrolled in the study. Two different DWI acquisition series (b-value ranges 0-1000 and 0-3000 s/mm(2) , respectively) were performed for each MR scanner. All DWI acquisitions were performed by using a cylindrical doped water phantom. Mean apparent diffusion coefficient (ADC) values as well as ADC values along each of the three main orthogonal directions of the diffusion gradients (x, y, and z) were calculated. Short-term repeatability of ADC measurement was evaluated for 26 MR scanners. RESULTS: A good agreement was found between the nominal and measured mean ADC over all the centers. More than 80% of mean ADC measurements were within 5% from the nominal value, and the highest deviation and overall standard deviation were 9.3% and 3.5%, respectively. Short-term repeatability of ADC measurement was found <2.5% for all MR scanners. CONCLUSION: A specific and widely accepted protocol for quality controls in DWI is still lacking. The DWI quality assurance protocol proposed in this study can be applied in order to assess the reliability of DWI-derived indices before tackling single- as well as multicenter studies.

pH Dependence of the photocycle kinetics of the E46Q mutant of photoactive yellow protein: protonation equilibrium between I1 and I2 intermediates, chromophore deprotonation by hydroxyl uptake, and protonation relaxation of the dark state.

The kinetics of the photocycle of PYP and its mutants E46Q and E46A were investigated as a function of pH. E46 is the putative donor of the chromophore which becomes protonated in the I(2) intermediate. For E46Q we find that I(2) is in a pH-dependent equilibrium with its precursor I(1)' with a pK(a) of 8.15 and n = 1. From this result and from experiments with pH indicator dyes, we conclude that in the I(1)' to I(2) transition one proton is taken up from the external medium. The pK(a) of 8.15 is that of the surface-exposed chromophore in the equilibrium between I(1)' and I(2) and is close to that of the phenolate group of p-hydroxycinnamic acid. The pH-dependent I(1)'/I(2) equilibrium with associated H(+) uptake is reminiscent of the M(I)/M(II) equilibrium in the formation of the signaling state of rhodopsin. Well above this pK(a) no I(2) is formed and I(1)' returns in a pH-independent manner to the initial state P. The decay rate for the return to P via I(2) is between pH 4 and pH 8, exactly proportional to the hydroxide concentration (first order), and the deprotonation of the chromophore in this transition occurs by hydroxide uptake. Well above the pK(a) of 8.15 the apparent rate constant for the return to P is constant due to the branching from I(1)'. Complementary measurements with the pH indicator dye cresol red at pH 8.3 show that the remaining PYP molecules that still cycle via I(2) take up one proton in the formation of I(2). Together, these observations provide compelling evidence that during the photocycle the chromophore in E46Q is protonated and deprotonated from the external medium. For the yellow form of the mutant E46A the apparent rate constant for the return to P is also linear in [OH(-)] below about pH 8.3 and constant above about pH 9.5, with a pK(a) value of 8.8 for I(1)', suggesting a similar mechanism of chromophore protonation/deprotonation as in E46Q. For wild type qualitatively similar observations were made: the amplitude of I(2) decreased at alkaline pH, I(1)' and I(2) were in equilibrium, and I(1)' decayed together with the return to P. Chromophore hydrolysis prevented, however, an accurate determination of the pK(a) of I(1)'. We estimate that its value is above 11. The ground state P is in the dark in a pH-dependent equilibrium with a low-pH bleached form P(bl) with protonated chromophore. The pK(a) values for these equilibria are 4.8 and 7.9 for E46Q and E46A, respectively. When the pH is close to these pK(a)'s, the kinetics of the photocycle contains additional components in the millisecond time range. Using pH-jump stopped-flow experiments, we show that these contributions are due to the relaxation of the P/P(bl) equilibrium which is perturbed by the rapid decrease in the P concentration caused by the flash excitation of P. The condition for the occurrence of this effect is that the relaxation time of the P/P(bl) equilibrium is faster than the photocycle time.