Optimization of CT pulmonary angiography for pulmonary embolism using task-based image quality assessment and diagnostic reference levels: A multicentric study.

PURPOSE: To establish size-specific diagnostic reference levels (DRLs) for pulmonary embolism (PE) based on patient CT examinations performed on 74 CT devices. To assess task-based image quality (IQ) for each device and to investigate the variability of dose and IQ across different CTs. To propose a dose/IQ optimization. METHODS: 1051 CT pulmonary angiography dose data were collected. DRLs were calculated as the 75th percentile of CT dose index (CTDI) for two patient categories based on the thoracic perimeters. IQ was assessed with two thoracic phantom sizes using local acquisition parameters and three other dose levels. The area under the ROC curve (AUC) of a 2 mm low perfused vessel was assessed with a non-prewhitening with eye-filter model observer. The optimal IQ-dose point was mathematically assessed from the relationship between IQ and dose. RESULTS: The DRLs of CTDIvol were 6.4 mGy and 10 mGy for the two patient categories. 75th percentiles of phantom CTDIvol were 6.3 mGy and 10 mGy for the two phantom sizes with inter-quartile AUC values of 0.047 and 0.066, respectively. After the optimization, 75th percentiles of phantom CTDIvol decreased to 5.9 mGy and 7.55 mGy and the interquartile AUC values were reduced to 0.025 and 0.057 for the two phantom sizes. CONCLUSION: DRLs for PE were proposed as a function of patient thoracic perimeters. This study highlights the variability in terms of dose and IQ. An optimization process can be started individually and lead to a harmonization of practice throughout multiple CT sites.

Photon-Counting Detector CT for Liver Lesion Detection-Optimal Virtual Monoenergetic Energy for Different Simulated Patient Sizes and Radiation Doses.

OBJECTIVES: The aim of this study was to evaluate the optimal energy level of virtual monoenergetic images (VMIs) from photon-counting detector computed tomography (CT) for the detection of liver lesions as a function of phantom size and radiation dose. MATERIALS AND METHODS: An anthropomorphic abdominal phantom with liver parenchyma and lesions was imaged on a dual-source photon-counting detector CT at 120 kVp. Five hypoattenuating lesions with a lesion-to-background contrast difference of -30 HU and -45 HU and 3 hyperattenuating lesions with +30 HU and +90 HU were used. The lesion diameter was 5-10 mm. Rings of fat-equivalent material were added to emulate medium- or large-sized patients. The medium size was imaged at a volume CT dose index of 5, 2.5, and 1.25 mGy and the large size at 5 and 2.5 mGy, respectively. Each setup was imaged 10 times. For each setup, VMIs from 40 to 80 keV at 5 keV increments were reconstructed with quantum iterative reconstruction at a strength level of 4 (QIR-4). Lesion detectability was measured as area under the receiver operating curve (AUC) using a channelized Hotelling model observer with 10 dense differences of Gaussian channels. RESULTS: Overall, highest detectability was found at 65 and 70 keV for both hypoattenuating and hyperattenuating lesions in the medium and large phantom independent of radiation dose (AUC range, 0.91-1.0 for the medium and 0.94-0.99 for the large phantom, respectively). The lowest detectability was found at 40 keV irrespective of the radiation dose and phantom size (AUC range, 0.78-0.99). A more pronounced reduction in detectability was apparent at 40-50 keV as compared with 65-75 keV when radiation dose was decreased. At equal radiation dose, detection as a function of VMI energy differed stronger for the large size as compared with the medium-sized phantom (12% vs 6%). CONCLUSIONS: Detectability of hypoattenuating and hyperattenuating liver lesions differed between VMI energies for different phantom sizes and radiation doses. Virtual monoenergetic images at 65 and 70 keV yielded highest detectability independent of phantom size and radiation dose.

Solid-state NMR enhanced by dynamic nuclear polarization as a novel tool for ribosome structural biology.

The impact of Nuclear Magnetic Resonance (NMR) on studies of large macromolecular complexes hinges on improvements in sensitivity and resolution. Dynamic nuclear polarization (DNP) in the solid state can offer improved sensitivity, provided sample preparation is optimized to preserve spectral resolution. For a few nanomoles of intact ribosomes and an 800 kDa ribosomal complex we demonstrate that the combination of DNP and magic-angle spinning NMR (MAS-NMR) allows one to overcome current sensitivity limitations so that homo- and heteronuclear (13)C and (15)N NMR correlation spectra can be recorded. Ribosome particles, directly pelleted and frozen into an NMR rotor, yield DNP signal enhancements on the order of ~25-fold and spectra that exhibit narrow linewidths, suitable for obtaining site-specific information. We anticipate that the same approach is applicable to other high molecular weight complexes.

Analysis of sensitivity enhancement by dynamic nuclear polarization in solid-state NMR: a case study of functionalized mesoporous materials.

We systematically studied the enhancement factor (per scan) and the sensitivity enhancement (per unit time) in (13)C and (29)Si cross-polarization magic angle spinning (CP-MAS) NMR boosted by dynamic nuclear polarization (DNP) of functionalized mesoporous silica nanoparticles (MSNs). Specifically, we separated contributions due to: (i) microwave irradiation, (ii) quenching by paramagnetic effects, (iii) the presence of frozen solvent, (iv) the temperature, as well as changes in (v) relaxation and (vi) cross-polarization behaviour. No line-broadening effects were observed for MSNs when lowering the temperature from 300 to 100 K. Notwithstanding a significant signal reduction due to quenching by TOTAPOL radicals, DNP-CP-MAS at 100 K provided global sensitivity enhancements of 23 and 45 for (13)C and (29)Si, respectively, relative to standard CP-MAS measurements at room temperature. The effects of DNP were also ascertained by comparing with state-of-the-art two-dimensional heteronuclear (1)H{(13)C} and (29)Si{(1)H} correlation spectra, using, respectively, indirect detection or Carr-Purcell-Meiboom-Gill (CPMG) refocusing to boost signal acquisition. This study highlights opportunities for further improvements through the development of high-field DNP, better polarizing agents, and improved capabilities for low-temperature MAS.

Dynamic Nuclear Polarization and other magnetic ideas at EPFL.

Although nuclear magnetic resonance (NMR) can provide a wealth of information, it often suffers from a lack of sensitivity. Dynamic Nuclear Polarization (DNP) provides a way to increase the polarization and hence the signal intensities in NMR spectra by transferring the favourable electron spin polarization of paramagnetic centres to the surrounding nuclear spins through appropriate microwave irradiation. In our group at EPFL, two complementary DNP techniques are under investigation: the combination of DNP with magic angle spinning at temperatures near 100 K ('MAS-DNP'), and the combination of DNP at 1.2 K with rapid heating followed by the transfer of the sample to a high-resolution magnet ('dissolution DNP'). Recent applications of MAS-DNP to surfaces, as well as new developments of magnetization transfer of (1)H to (13)C at 1.2 K prior to dissolution will illustrate the work performed in our group. A second part of the paper will give an overview of some 'non-enhanced' activities of our laboratory in liquid- and solid-state NMR.

Fast characterization of functionalized silica materials by silicon-29 surface-enhanced NMR spectroscopy using dynamic nuclear polarization.

We demonstrate fast characterization of the distribution of surface bonding modes and interactions in a series of functionalized materials via surface-enhanced nuclear magnetic resonance spectroscopy using dynamic nuclear polarization (DNP). Surface-enhanced silicon-29 DNP NMR spectra were obtained by using incipient wetness impregnation of the sample with a solution containing a polarizing radical (TOTAPOL). We identify and compare the bonding topology of functional groups in materials obtained via a sol-gel process and in materials prepared by post-grafting reactions. Furthermore, the remarkable gain in time provided by surface-enhanced silicon-29 DNP NMR spectroscopy (typically on the order of a factor 400) allows the facile acquisition of two-dimensional correlation spectra.

A spinning thermometer to monitor microwave heating and glass transitions in dynamic nuclear polarization.

As previously demonstrated by Thurber and Tycko, the peak position of (79)Br in potassium bromide (KBr) allows one to determine the temperature of a spinning sample. We propose to adapt the original design by using a compact KBr tablet placed at the bottom of the magic angle spinning rotor, separated from the sample under investigation by a thin disk made of polytetrafluoroethylene (or 'Teflon'®). This design allows spinning the sample up to at least 16 kHz. The KBr tablet can remain in the rotor when changing the sample under investigation. Calibration in the range of 98 < T < 320 K has been carried out in a static rotor by inserting a platinum thermometer. The accuracy is better than ± 0.9 K, even in the presence of microwave irradiation. Irradiation with 5 W microwaves at 263 GHz leads to a small temperature increase of 3.6 ± 1.4 K in either static or spinning samples. The dynamic nuclear polarization enhancement decreases with increasing temperature, in particular when a frozen glassy sample undergoes a glass transition.

Extending timescales and narrowing linewidths in NMR.

Among the different fields of research in nuclear magnetic resonance (NMR) which are currently investigated in the Laboratory of Biomolecular Magnetic Resonance (LRMB), two subjects that are closely related to each other are presented in this article. On the one hand, we show how to populate long-lived states (LLS) that have long lifetimes T(LLS) which allow one to go beyond the usual limits imposed by the longitudinal relaxation time T1. This makes it possible to extend NMR experiments to longer time-scales. As an application, we demonstrate the extension of the timescale of diffusion measurements by NMR spectroscopy. On the other hand, we review our work on long-lived coherences (LLC), a particular type of coherence between two spin states that oscillates with the frequency of the scalar coupling constant J(IS) and decays with a time constant T(LLC). Again, this time constant T(LLC) can be much longer than the transverse relaxation time T2. By extending the coherence lifetimes, we can narrow the linewidths to an unprecedented extent. J-couplings and residual dipolar couplings (RDCs) in weakly-oriented phases can be measured with the highest precision.

Surface enhanced NMR spectroscopy by dynamic nuclear polarization.

It is shown that surface NMR spectra can be greatly enhanced using dynamic nuclear polarization. Polarization is transferred from the protons of the solvent to the rare nuclei (here carbon-13 at natural isotopic abundance) at the surface, yielding at least a 50-fold signal enhancement for surface species covalently incorporated into a silica framework.

The Munich Ankle Questionnaire (MAQ): a self-assessment tool for a comprehensive evaluation of ankle disorders.

BACKGROUND: There are many approved patient-related outcome measurement tools regarding ankle pathologies. However, there is none incorporating the range of motion (ROM) as an objective parameter. Most instruments focus on subjective parameters such as pain and impairment at work or daily living. Furthermore, the majority is only applicable to a specific pathology. Therefore, the objective of our study was to develop and validate the Munich Ankle Questionnaire (MAQ) as a universal self-assessment score including subjective and objective items. METHODS: The established McGuire Score, Bray Score, Ankle Hindfoot Score (AOFAS) and Olerud and Molander Score were analyzed for relevant items and subscales. Items of interest were then condensed and allocated to the respective subscales of the MAQ. The final MAQ consists of 6 items addressing general and demographic data and 12 items addressing three domains: pain (3 items), work and daily living (5 items), movement and ROM (4 items). The evaluation of validity, reliability and responsiveness of the MAQ was performed in a prospective clinical study including traumatic as well as degenerative ankle pathologies. RESULTS: In total, 148 patients (79 female, 69 male, median age 45 years) were included in the validation study. With intra-class correlation coefficients of at least 0.77, test-retest reliability was proven. Construct validity with a correlation coefficient of 0.82 and responsiveness with a correlation coefficient ranging from 0.42 to 0.47 were confirmed. CONCLUSION: The MAQ is a reliable and valid self-assessment measurement tool for the follow-up examination regarding subjective and objective parameters of traumatic and degenerative ankle pathologies. The MAQ has no limitation to specific disorders and allows a broad application.

Performance evaluation of a collapsed cone dose calculation algorithm for HDR Ir-192 of APBI treatments.

PURPOSE: Most dose calculations for HDR brachytherapy treatments are based on the AAPM-TG43 formalism. Because patient's anatomy, heterogeneities, and applicator shielding are not considered, the dose calculation based on this formalism is inaccurate in some cases. Alternatively, collapsed cone (CC) methods as well as Monte Carlo (MC) algorithms belong to the model-based dose calculation algorithms, which are expected to improve the accuracy of calculated dose distributions. In this work, the performance of a CC algorithm, ACE in Oncentra Brachy 4.5 (ACE 4.5), has been investigated by comparing the calculated dose distributions to the AAPM-TG43 and MC calculations for 10 HDR brachytherapy accelerated partial breast irradiation treatments (APBI). Comparisons were also performed with a corrected version of ACE 4.5 (ACE 4.5/corr). METHODS: The brachytherapy source microSelectron mHDR-v2 (Elekta Brachytherapy) has been implemented in a MC environment and validated by comparing MC dose distributions simulated in a water phantom of 80 cm in diameter with dose distributions calculated with the AAPM-TG43 algorithm. Dose distributions calculated with ACE 4.5, ACE 4.5/corr, AAPM-TG43 formalism, and MC for 10 APBI patients plans have then been computed and compared using HU scaled densities. In addition, individual dose components have been computed using ACE 4.5, ACE 4.5/corr, and MC, and compared individually. RESULTS: Local differences between MC and AAPM-TG43 calculated dose distributions in a large water phantom are < 1%. When using HUs scaled densities for the breast cancer patients, both accuracy levels of ACE 4.5 overestimate the MC calculated dose distributions for all analyzed dosimetric parameters. In the planning target volume (PTV), ACE 4.5 (ACE 4.5/corr) overestimates on average V100%,PTV by 3% ± 1% (1% ± 1%) and D50,PTV by 3% ± 1% (1% ± 1%) and in the organs at risk D1cc, skin by 4% ± 2% (1% ± 1%), D0.5cc, ribs by 4% ± 2% (0% ± 1%), and D1cc, heart by 8% ± 2% (3% ± 1%) compared to MC. Comparisons of the individual dose components reveals an agreement for the primary component of < 2% local differences for both ACE 4.5 and ACE 4.5/corr. Local differences of about 40% (20%) for the first and residual scatter components where observed when using ACE 4.5 (ACE 4.5/corr). Using uniform densities for one case shows a better agreement between ACE 4.5 and MC for all dosimetric parameters considered in this work. CONCLUSIONS: In general, on the 10 APBI patients the ACE 4.5/corr algorithm results in similar dose distributions as the commonly used AAPM-TG43 within the PTV. However, the accuracy of the ACE 4.5/corr calculated dose distribution is closer to MC than to AAPM-TG43. The differences between commercial version ACE 4.5 and MC dose distributions are mainly located in the first and residual scatter components. In ACE 4.5/corr, the changes done in the algorithm for the scatter components substantially reduce these differences.

Uniform broadband excitation of crystallites in rotating solids using interleaved sequences of delays alternating with nutation.

In solids that are spinning about the magic angle, trains of short pulses in the manner of Delays Alternating with Nutations for Tailored Excitation (DANTE) allow one to improve the efficiency of the excitation of magnetization compared to rectangular pulses. By interleaving N pulse trains with N>1, one obtains 'DANTE-N' sequences comprising N pulses per rotor period that extend over K rotor periods. Optimized interleaved DANTE schemes with N>1 are shorter than basic DANTE-1 sequences with N=1. Therefore, they are less affected by coherent or incoherent decays, thus leading to higher signal intensities than can be obtained with basic DANTE-1 or with rectangular pulses. Furthermore, the shorter length of DANTE-N with N>1 increases the width of the spikelets in the excitation profile, allowing one to cover the range of isotropic chemical shifts and second-order quadrupolar effects typical for side-chain and backbone amide (14)N sites in peptides at B(0)=18.8 T. In DANTE-N, spinning sidebands only appear at multiples of the spinning frequency ν(rot), as if the samples were rotating at Nν(rot). We show applications to direct detection of nitrogen-14 nuclei with spin I=1 subject to large quadrupole interactions, using fast magic angle spinning (typically ν(rot)≥60 kHz), backed up by simulations that provide insight into the properties of basic and interleaved DANTE sequences. When used for indirect detection, we show by numerical simulations that even basic DANTE-1 sequences can lead to a four-fold boost of efficiency compared to standard rectangular pulses.

Dynamic nuclear polarization of quadrupolar nuclei using cross polarization from protons: surface-enhanced aluminium-27 NMR.

The surface of γ-alumina nanoparticles can be characterized by dynamic nuclear polarization (DNP) surface-enhanced NMR of (27)Al. DNP is combined with cross-polarization and MQ-MAS to determine local symmetries of (27)Al sites at the surface.

Broadband excitation and indirect detection of nitrogen-14 in rotating solids using Delays Alternating with Nutation (DANTE).

A train of short rotor-synchronized pulses in the manner of Delays Alternating with Nutations for Tailored Excitation (DANTE) applied to nitrogen-14 nuclei (I=1) in samples spinning at the magic angle at high frequencies (typically νrot=62.5 kHz so that τrot=16 µs) allows one to achieve uniform excitation of a great number of spinning sidebands that arise from large first-order quadrupole interactions, as occur for aromatic nitrogen-14 nuclei in histidine. With routine rf amplitudes ω1(14N)/(2π)=60 kHz and very short pulses of a typical duration 0.5<τp<2 µs, efficient excitation can be achieved with 13 rotor-synchronized pulses in 13 τrot=208 µs. Alternatively, with 'overtone' DANTE sequences using 2, 4, or 8 pulses per rotor period one can achieve efficient broadband excitation in fewer rotor periods, typically 2-4 τrot. These principles can be combined with the indirect detection of 14N nuclei via spy nuclei with S=½ such as 1H or 13C in the manner of Dipolar Heteronuclear Multiple-Quantum Correlation (D-HMQC).

Solid-state nitrogen-14 nuclear magnetic resonance enhanced by dynamic nuclear polarization using a gyrotron.

By combining indirect detection of 14N with dynamic nuclear polarization (DNP) using a gyrotron, the signal-to-noise ratio can be dramatically improved and the recovery delay between subsequent experiments can be shortened. Spectra of glassy samples of the amino acid proline doped with the stable bi-radical TOTAPOL rotating at 15.625 kHz at 110K were obtained in a 400 MHz solid-state NMR spectrometer equipped with a gyrotron for microwave irradiation at 263 GHz. DNP enhancement factors on the order of epsilon approximately 40 were achieved. The recovery delays can be reduced from 60 s without radicals at 300 K to 6 s with radicals at 110 K. In the absence of radicals at room temperature, the proton relaxation in proline is inefficient due to the absence of rotating methyl groups and other heat sinks, thus making long recovery delays mandatory. DNP allows one to reduce the acquisition times of 13C-detected 14N spectra from several days to a few hours.

Line-narrowing in proton-detected nitrogen-14 NMR.

In solids spinning at the magic angle, the indirect detection of single-quantum (SQ) and double-quantum (DQ) (14)N spectra (I=1) via spy nuclei S=1/2 such as protons can be achieved in the manner of heteronuclear single- or multiple-quantum correlation (HSQC or HMQC) spectroscopy. The HMQC method relies on the excitation of two-spin coherences of the type T(11)(I)T(11)(S) and T(21)(I)T(11)(S) at the beginning of the evolution interval t(1). The spectra obtained by Fourier transformation from t(1) to omega(1) may be broadened by the homogenous decay of the transverse terms of the spy nuclei S. This broadening is mostly due to homonuclear dipolar S-S' interactions between the proton spy nuclei. In this work we have investigated the possibility of inserting rotor-synchronized symmetry-based C or R sequences and decoupling schemes such as Phase-Modulated Lee-Goldburg (PMLG) sequences in the evolution period. These schemes reduce the homonuclear proton-proton interactions and lead to an enhancement of the resolution of both SQ and DQ proton-detected (14)N HMQC spectra. In addition, we have investigated the combination of HSQC with symmetry-based sequences and PMLG and shown that the highest resolution in the (14)N dimension is achieved by using HSQC in combination with symmetry-based sequences of the R-type. We show improvements in resolution in samples of l-alanine and the tripeptide ala-ala-gly (AAG). In particular, for l-alanine the width of the (14)N SQ peak is reduced from 2 to 1.2 kHz, in agreement with simulations. We report accurate measurements of quadrupolar coupling constants and asymmetry parameters for amide (14)N in AAG peptide bonds.