Quantitation Errors Research Articles

A mathematical model for velocity-selective arterial spin labeling.

To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.

Correcting gradient chain induced fat quantification errors in radial multi-echo Dixon imaging using a gradient modulation transfer function

Purpose: Multi-echo Stack-of-stars (SoS) radial k-space trajectories with golden angle ordering are becoming popular for free-breathing abdominal Dixon imaging and proton density fat fraction (PDFF) mapping. Gradient chain imperfections including eddy currents and system delays are known to affect the image quality of radial imaging and to confound the estimation of PDFF mapping. This work proposes a retrospective trajectory correction method based on a simple gradient modulation transfer function (GMTF) measurement to predict and correct gradient chain induced k-space trajectory errors.Methods: The GMTF was measured using the standard hardware of a 3 Tesla scanner on a phantom using the thin slice method and was applied to a 3D radial SoS Dixon imaging sequence. The impact of the GMTF-based correction on image reconstruction and PDFF quantification was investigated using numerical simulations and validated on experimental phantom data as well as on in vivo leg and liver data of healthy volunteers.Results: Correcting the k-space trajectories with the measured GMTF during image reconstruction reduced PDFF quantification errors for phantom and in vivo acquisitions. A Bland-Altman comparison of the measured PDFF phantom and reference data confirmed that the GMTF correction narrowed down the limits of agreement (LoA) from 1.3% ± 8.1% (uncorrected) to 1.9% ± 5.4% (GMTF-corrected) over the full PDFF range (0%–100%) and from −0.26% ± 2.8% (uncorrected) to 0.12% ± 1.5% (GMTF-corrected) within the 0%–50% PDFF range. Liver PDFF estimation was improved by reducing the standard deviation of the mean liver PDFF and the bias of the mean liver PDFF for all subjects.Conclusion: The proposed GMTF-based k-space trajectory correction is a fast alternative method for avoiding PDFF quantitation errors caused by gradient-system induced k-space trajectory errors in 3D radial multi-echo gradient-echo acquisitions.

Improving quantitation accuracy in isobaric-labeling mass spectrometry experiments with spectral library searching and feature-based peptide-spectrum match filter

Isobaric labeling relative quantitation is one of the dominating proteomic quantitation technologies. Traditional quantitation pipelines for isobaric-labeled mass spectrometry data are based on sequence database searching. In this study, we present a novel quantitation pipeline that integrates sequence database searching, spectral library searching, and a feature-based peptide-spectrum-match (PSM) filter using various spectral features for filtering. The combined database and spectral library searching results in larger quantitation coverage, and the filter removes PSMs with larger quantitation errors, retaining those with higher quantitation accuracy. Quantitation results show that the proposed pipeline can improve the overall quantitation accuracy at the PSM and protein levels. To our knowledge, this is the first study that utilizes spectral library searching to improve isobaric labeling-based quantitation. For users to conveniently perform the proposed pipeline, we have implemented the feature-based filter being executable on both Windows and Linux platforms; its executable files, user manual, and sample data sets are freely available at https://ms.iis.sinica.edu.tw/comics/Software_FPF.html. Furthermore, with the developed filter, the proposed pipeline is fully compatible with the Trans-Proteomic Pipeline.

Estimation of confidence intervals for quantitation of coeluted peaks in liquid chromatography–Photodiode array detection through a combination of multivariate curve resolution-alternating least-square and Bayesian inference techniques

There is a dramatic increase in drug candidates that exhibit complex structures and do not comply with Lipinski's rule of five. One of the most critical and complex technical challenges in the quality control of such drug candidates is the control of analogous substances contained in active pharmaceutical ingredients and related formulations. Although the development of ultrahigh-performance liquid chromatography and high-performance columns has improved efficiency per unit time, the difficulty of peak separation to quantify impurities with similar structures and physicochemical properties continues to rise, and so does the probability of failure to achieve the necessary separation. Coeluting peaks observed in the case of high-performance liquid chromatography (HPLC) with photodiode array detection can be separated using the multivariate curve resolution-alternating least-square (MCR-ALS) method exploiting differences in analyte UV spectra. However, relatively large quantitation errors have been observed for coeluting analogous substances, and the reliability of the corresponding quantitative data requires improvement. Herein, Bayesian inference is applied to separation by the MCR-ALS method to develop an algorithm assigning a confidence interval to the quantitative data of each analogous substance. The usefulness and limitations of this approach are tested using two analogs of telmisartan as models. For this test, a simulated two-component HPLC-UV dataset with an intensity ratio (relative to the main peak) of 0.1–1.0 and a resolution of 0.5–1.0 is used. The developed algorithm allows the prediction confidence interval, including the true value, to be assigned to the peak area in almost all cases, even when the intensity ratio, resolution, and signal-to-noise ratio are changed. Finally, the developed algorithm is also evaluated on a real HPLC-UV dataset to confirm that reasonable prediction confidence intervals including true values are assigned to peak areas. In addition to allowing the separation and quantitation of substances such as impurities challenging to separate by HPLC in a scientifically valid manner, which is impossible for conventional HPLC-UV detection, our method can assign confidence intervals to quantitative data. Therefore, the adopted approach is expected to resolve the issues associated with assessing impurities in the quality control of pharmaceuticals.

Novel Isotope-Labeled Derivatization Strategy for the Simultaneous Analysis of Fatty Acids and Fatty Alcohols and Its Application in Idiopathic Inflammatory Myopathies and Pancreatic Cancer.

Fatty acids (FAs) and fatty alcohols (FOHs) are essential compounds for maintaining life. Due to the inherent poor ionization efficiency, low abundance, and complex matrix effect, such metabolites are challenging to precisely quantify and explore deeply. In this study, a pair of novel isotope derivatization reagents known as d0/d5-1-(2-oxo-2-(piperazin-1-yl) ethyl) pyridine-1-ium (d0/d5-OPEPI) were designed and synthesized, and an in-depth screening strategy for FAs and FOHs was established based on d0/d5-OPEPI coupled with liquid chromatography-tandem high-resolution mass spectrometry (LC-HRMS/MS). Using this approach, a total of 332 metabolites were identified and annotated (some of the FAs and FOHs were reconfirmed by standards). Our results demonstrated that OPEPI labeling could significantly enhance the MS response of FAs and FOHs via the introduction of permanently charged tags. The detection sensitivities of FAs were increased by 200-2345-fold compared with the nonderivatization method. At the same time, for FOHs, due to the absence of ionizable functional groups, sensitive detection was achieved utilizing OPEPI derivatization. One-to-one internal standards were provided by using d5-OPEPI labeling to minimize the errors in quantitation. Moreover, the method validation results showed that the method was stable and reliable. Finally, the established method was successfully applied to the study of the FA and FOH profiles of two heterogeneous severe clinical disease tissues. This study would improve our understanding of the pathological and metabolic mechanisms of FAs and FOHs for inflammatory myopathies and pancreatic cancer and also prove the generality and accuracy of the developed analytical method for complex samples.

In vivo absolute quantification of carnosine in the vastus lateralis muscle with 1H MRS using a surface coil and water as internal reference.

To standardize a method for 1H MRS intramuscular absolute quantification of carnosine in the thigh, using a surface coil and water as internal reference. Carnosine spectra were acquired in phantoms (5, 10, and 15mM) as well as in the right gastrocnemius medialis (GM) and right vastus lateralis (VLM) muscles of young team sports athletes, using volume (VC) and surface (SC) coils on a 3T scanner, with the same receiver gain. Water spectra were used as internal reference for the absolute quantification of carnosine. Phantom's experiments showed a maximum error of 7%, highlighting the validity of the measurements in the study setup. The carnosine concentrations (mmol/kg ww, mean ± SD) measured in the GM were 6.8 ± 2.2 with the VC (CcarVC) and 10.2 ± 3.0 with the SC (CcarSC) (P = 0.013; n = 9). Therefore, a correction was applied to these measurements (CcarVC = 0.6582*CcarSC), to make coils performance comparable (6.8 ± 2.2 for VC and 6.7 ± 2.0 for SC, P = 0.97). After that, only the SC was used to quantify carnosine in the VLM, where a concentration of 5.4 ± 1.5 (n = 30) was found, with significant differences between men (6.2 ± 1.3; n = 15) and women (4.6 ± 1.2; n = 15). The error in quantitation was 5.3-5.5% with both coils. The method using the SC and water as internal reference can be used to quantify carnosine in voluminous muscles and regions of the body in humans, where the VC is not suitable, such as the VLM.

A novel microfluidic RNA chip for direct, single-nucleotide specific, rapid and partially-degraded RNA detection

Direct RNA detection is critical for providing the RNA insights into gene expression profiling, noncoding RNAs, RNA-associated diseases and pathogens, without reverse transcription. However, classical RNA analysis usually requires RT-PCR, which can cause bias amplification and quantitation errors. To address this challenge, herein we report a microfluidic RNA chip (the microchip prototype) for direct RNA detection, which is primarily based on RNA extension and labeling with DNA polymerase. This detection strategy is of high specificity (discriminating against single-nucleotide differences), rapidity, accuracy, nuclease resistance, and reusability. Further, we have successfully detected disease-associated RNAs in clinical samples, demonstrating its great potentials in biomedical research and clinical diagnosis.

A modified quick, easy, cheap, effective, rugged, and safe method with hydrophobic natural deep eutectic solvent as extractant and analyte protectant for analyzing pyrethroid residues in tomatoes.

In this work, a novel quick, easy, cheap, effective, rugged, and safe technique with hydrophobic natural deep eutectic solvent as both extractant and analyte protectant was developed and combined with gas chromatography-tandem mass spectrometry to analyze pyrethroid residues in tomatoes. Eight hydrophobic natural deep eutectic solvents were first evaluated as analyte protectants and those with decanoic acid or lactic acid as hydrogen bond donor were demonstrated to be effective in compensating for the matrix effects of pyrethroids in the gas chromatography system. Hence, they were added to solvent standards for correcting the quantitation errors instead of matrix-matched calibration standards. Then the abilities of these acid-based deep eutectic solvents to extract pyrethriods from tomatoes were evaluated. Results showed the recoveries of all pyrethroids reached to over 80% with only 5mL menthol:decanoic acid (1:1) used, and good phase separation was easily achieved without the addition of inorganic salt in the extraction step, indicating hydrophobic natural deep eutectic solvent could be a green substitute for acetonitrile in the quick, easy, cheap, effective, rugged, and safe extraction. Compared with the conventional method, the proposed protocol improved the recoveries, reduced the matrix effects, and simplified the extraction step, demonstrating to be an effective, fast, and green method.

Effects of apodization smoothing and denoising on spectral fitting

PurposeVisual review of individual spectra in magnetic resonance spectroscopic imaging (MRSI) data benefits from the application of spectral smoothing; however, if this processing step is applied prior to spectral analysis this can impact the accuracy of the quantitation. This study aims to analyze the effect of spectral denoising and apodization smoothing on the quantitation of whole-brain MRSI data obtained at short TE. MethodsShort-TE MRSI data obtained at 3 T were analyzed with no spectral smoothing, following (i) Gaussian apodization with values of 1, 2, 4, 6, and 8 Hz, and (ii) denoising using principal component analysis (dnPCA) with 3 different values for the number of retained principal components. The mean lobar white matter estimates for four metabolites, signal-to-noise ratio (SNR), spectral linewidth, and confidence intervals were compared to data reconstructed using no smoothing. Additionally, a voxel-wise comparison for N-acetylaspartate quantitation with different smoothing schemes was performed. ResultsSignificant pairwise differences were seen for all Gaussian smoothing methods as compared to no smoothing (p<0.001) in linewidth and metabolite estimates, whereas dnPCA methods showing no statistically significant differences in these measures. Confidence intervals decreased, and SNR increased with increasing levels of apodization smoothing or dnPCA denoising. ConclusionMild Gaussian apodization (≤2 Hz at 3 T) can be applied with minimal (1%) errors in quantitation; however, smoothing values greater than that can significantly affect metabolite quantification. In contrast, mild to moderate dnPCA based denoising provides quantitative results that are consistent with the analysis of unsmoothed data and this method is recommended for spectral denoising.

Motion correction in magnetic resonance spectroscopy.

In vivo proton magnetic resonance spectroscopy and spectroscopic imaging (MRS/MRSI) are valuable tools to study normal and abnormal human brain physiology. However, they are sensitive to motion, due to strong crusher gradients, long acquisition times, reliance on high magnetic field homogeneity, and particular acquisition methods such as spectral editing. The effects of motion include incorrect spatial localization, phase fluctuations, incoherent averaging, line broadening, and ultimately quantitation errors. Several retrospective methods have been proposed to correct motion-related artifacts. Recent advances in hardware also allow prospective (real-time) correction of the effects of motion, including adjusting voxel location, center frequency, and magnetic field homogeneity. This article reviews prospective and retrospective methods available in the literature and their implications for clinical MRS/MRSI. In combination, these methods can attenuate or eliminate most motion-related artifacts and facilitate the acquisition of high-quality data in the clinical research setting.

Dexamethasone Degradation in Aqueous Medium and Implications for Correction of In Vitro Release from Sustained Release Delivery Systems.

The in vitro drug release in an aqueous medium is a critical performance metric for a sustained release drug product. During long-term release studies, drugs may degrade in the release medium, and such degradation can lead to errors in drug release quantitation. Using dexamethasone as a model drug and LC-MS/MS methods employing dexamethasone-d4 as an internal standard, this study identified that dexamethasone can degrade into 13 major degradation products in phosphate buffered saline (PBS) as a function of time, temperature (25, 37, and 45°C), and light exposure. A putative scheme for dexamethasone degradation pathways in PBS has been proposed. In proof-of-concept studies, the analytical method was used to quantitate dexamethasone and its degradation products during in vitro release studies with sustained release dexamethasone-poly(D,L-lactide-co-glycolide) (PLGA) implants incubated in phosphate buffer saline (PBS). Further, mathematical approaches were developed to estimate drug release from implants after accounting for drug degradation in PBS. The LC-MS/MS analytical method and the mathematical approaches developed could be used for assessing the stability and/or release of dexamethasone during manufacturing, storage, and use of various dosage forms.

Improvements for absolute quantitation using electrochemical mass spectrometry

We recently reported a new quantitation method using mass spectrometry (MS) in combination with electrochemistry (EC, J. Am. Soc. Mass Spectrom., 2019, 30, 685). The strength of this method is that no reference standard or isotope-labeled compound is required for absolute quantitation. The method relies on electrochemical oxidation of an electrochemically active target compound to determine the amount of the oxidized compound using Faraday's Law. On the other hand, the oxidation reaction yield can be determined based on the MS signal change following electrolysis. Therefore, the absolute amount of the analyte can be calculated. Our experiment is carried out using a coupled liquid chromatography/electrochemistry/mass spectrometry (LC/EC/MS) apparatus. In this study, the method is further optimized. First, quantifying the compounds in a mixture is possible after the chromatographic separation. Gradient elution is used for separation and each compound can be quantified using the electrochemical mass spectrometry method. Second, for compounds that are already purified, LC column is not necessary and can be removed (i.e., flow-through analysis), thus shortening the analysis time for each injected sample from 10 min to 2 min. With using an LC auto-sampler, multiple samples can be injected sequentially. All the quantitation errors shown in this study are within 5%, indicating a good accuracy of our method.

M-BLANK: a program for the fitting of X-ray fluorescence spectra.

The X-ray fluorescence data from X-ray microprobe and nanoprobe measurements must be fitted to obtain reliable elemental maps. The most common approach in many fitting programs is to initially remove a per-pixel baseline. Using X-ray fluorescence data of yeast and glial cells, it is shown that per-pixel baselines can result in significant, systematic errors in quantitation and that significantly improved data can be obtained by calculating an average blank spectrum and subtracting this from each pixel.

The Resolution Matrix in Tomographic Multiplexing: Optimization of Inter-Parameter Cross-Talk, Relative Quantitation, and Localization.

We use a resolution matrix-based Bayesian framework to compare inversion methods for tomographic fluorescence lifetime multiplexing in a diffuse medium, such as biological tissue. We consider three inversion methods; an asymptotic time domain (ATD) approach, based on a multiexponential analysis of time domain data, a direct time domain (DTD) approach, which is a minimum error solution, and a cross-talk constrained time domain (CCTD) inversion, which is a solution to an optimization problem that minimizes both error and cross-talk. We compare these methods using Monte Carlo simulations and time domain fluorescence measurements with tissue-mimicking phantoms. The ATD approach provides high accuracy of relative quantitation and spatial localization of two fluorophores embedded in a 18-mm thick turbid medium, with concentration ratios of up to 1:4.25. DTD leads to significant errors in relative quantitation and localization. CCTD provides improved quantitation accuracy over DTD, and better spatial resolution compared to ATD. We present a rigorous theoretical basis for these results and provide a complete derivation of the CCTD estimator. The Bayesian analysis also leads to a formula for rapid computation of the DTD inverse operator for large-scale tomography measurements. The ATD and CCTD inversion methods provide significant advantages over DTD for accurately estimating multiple overlapping fluorophores. Time domain fluorescence tomography, using zero cross-talk estimators, can serve as a powerful tool for quantifying multiple fluorescently labeled biological processes. The Bayesian framework presented here can be applied to general multiparameter inverse problems for the quantitative estimation of multiple overlapping parameters.

Unbiased Measurement of Phosphate and Phosphorus Speciation in Surface Waters.

Trace-level phosphate analysis and phosphorus speciation in surface water remained challenging due to adsorption and phosphate uptake by microorganisms. In this study a two-dimensional ion chromatography separation coupled to electrospray ionization high-resolution mass spectrometry (2D-IC-ESI-MS) allowed isotope dilution quantitation of phosphate with simultaneous analysis of 11 phosphate-containing metabolites and two inorganic condensed phosphates. Samples were collected from Lake St. Clair, Lake Ontario, and Georgian Bay (ON, Canada). Comparative experiments showed lower phosphate results for samples not immediately spiked and for external calibration quantitation. Field spiking with 18O-labeled phosphate combined with isotope dilution quantitation allows measurement of the phosphate levels existent at the collection time instead of the phosphate concentrations remaining in the samples at the analysis time. This is a significant advantage against the traditional colorimetric and ion chromatographic (IC) analysis methods, which are unable to compensate for the adsorption loss occurring in standards and samples, especially when phosphate is present at levels below 20 μg L-1 as P (61 μg L-1 as PO43-). Two phosphate-containing metabolites, adenosine 5'-monophosphate (AMP) and d-glucose 6-phosphate (Glucose-P), were detected in a subset of samples collected from Lake St. Clair, with no statistically significant correlation between them and the simultaneously measured phosphate. Directly bioavailable P (phosphate), indirectly bioavailable P (phosphatase-hydrolyzed P) and nonbioavailable P (nonhydrolizable P) fractions were quantified by measuring phosphate, phosphate after phosphatase addition and total phosphorus. The proposed 2D-IC-ESI-MS method developed for a QExactive MS instrument with field spiking of the internal standard provides accurate phosphate results and eliminates quantitation errors caused by phosphate adsorption. This setup allows simultaneous collection of targeted and nontargeted analysis data and thus the detection of trace polar organic phosphorus metabolites as well.

Joint activity and attenuation estimation for PET with TOF data and single events

Maximum likelihood reconstruction of activity and attenuation (MLAA) for PET data with time-of-flight (TOF) information can determine the activity distribution up to a scale, and the attenuation map Radon transform up to a related constant. Prior knowledge is widely used for the determination of the constant. However, prior knowledge could be inaccurate due to patient variation and may result in quantitation errors. Our goal is to develop a method that can determine the scale and the related constant in the TOF-MLAA algorithm to obtain quantitatively accurate activity and attenuation maps.Our idea is to utilize the single events which have depth dependent attenuation factors, contrary to coincidence events. We show that in a 2D case, with the combination of TOF information and single events, a unique solution of attenuation and activity can be achieved. A three-step iterative image reconstruction algorithm is developed. In each iteration, the activity distribution is first updated using the MLEM approach with TOF PET data; the attenuation map is then updated using MLTR with non-TOF data; finally, both activity distribution and attenuation map are updated using a scale estimated from single events. Noisy and noise-free projection data are generated for 2D XCAT phantoms through analytical simulation. Both scatter information and randoms information are assumed to be known. The proposed method and the conventional TOF-MLAA algorithm are used to reconstruct the simulated data. Conventional MLEM method with known attenuation map is implemented for comparison as well. Normalized root mean square error (NRMSE) and optimal constant are defined for the quantitative analysis of reconstructed images. Our proposed image reconstruction method achieves ~1% NRMSE for the activity map and ~5% NRMSE for the attenuation map with a correct scale after 150 iterations for noise-free data. Results of noisy simulations are consistent with noise-free data.In summary, we have proposed to use the single events for constant determination in TOF-MLAA algorithm to obtain a unique solution of attenuation map and activity distribution without prior information. Future work will be dedicated to the extension of our method to the 3D situation.

Technical Note: Adapting a GE SIGNA PET/MR scanner for radiotherapy.

Simultaneous collection of PET and MR data for radiotherapy purposes are useful for, for example, target definition and dose escalations. However, a prerequisite for using PET/MR in the radiotherapy workflow is the ability to image the patient in treatment position. The aim of this work was to adapt a GE SIGNA PET/MR scanner to image patients for radiotherapy treatment planning and evaluate the impact on signal-to-noise (SNR) of the MR images, and the accuracy of the PET attenuation correction. A flat tabletop and a coil holder were developed to image patients in the treatment position, avoid patient contour deformation, and facilitate attenuation correction of flex coils. Attenuation corrections for the developed hardware and an anterior array flex coil were also measured and implemented to the PET/MR system to minimize PET quantitation errors. The reduction of SNR in the MR images due to the added distance between the coils and the patient was evaluated using a large homogenous saline-doped water phantom, and the activity quantitation errors in PET imaging were evaluated with and without the developed attenuation corrections. We showed that the activity quantitation errors in PET imaging were within ±5% when correcting for attenuation of the flat tabletop, coil holder, and flex coil. The SNR of the MRI images were reduced to 74% using the tabletop, and 66% using the tabletop and coil holders. We present a tabletop and coil holder for an anterior array coil to be used with a GE SIGNA PET/MR scanner, for scanning patients in the radiotherapy work flow. Implementing attenuation correction of the added hardware from the radiotherapy setup leads to acceptable PET image quantitation. The drop in SNR in MR images may require adjustment of the imaging protocols.

Quantitation Error in 1H MRS Caused by B1 Inhomogeneity and Chemical Shift Displacement.

Purpose:The quantitation accuracy in proton magnetic resonance spectroscopy (1H MRS) improves at higher B0 field. However, a larger chemical shift displacement (CSD) and stronger B1 inhomogeneity exist. In this work, we evaluate the quantitation accuracy for the spectra of metabolite mixtures in phantom experiments at 4.7T. We demonstrate a position-dependent error in quantitation and propose a correction method by measuring water signals.Materials and Methods:All experiments were conducted on a whole-body 4.7T MR system with a quadrature volume coil for transmission and reception. We arranged three bottles filled with metabolite solutions of N-acetyl aspartate (NAA) and creatine (Cr) in a vertical row inside a cylindrical phantom filled with water. Peak areas of three singlets of NAA and Cr were measured on three 1H spectra at three volume of interests (VOIs) inside three bottles. We also measured a series of water spectra with a shifted carrier frequency and measured a reception sensitivity map.Results:The ratios of NAA and Cr at 3.92 ppm to Cr at 3.01 ppm differed amongst the three VOIs in peak area, which leads to a position-dependent error. The nature of slope depicting the relationship between peak areas and the shifted values of frequency was like that between the reception sensitivities and displacement at every VOI.Conclusion:CSD and inhomogeneity of reception sensitivity cause amplitude modulation along the direction of chemical shift on the spectra, resulting in a quantitation error. This error may be more significant at higher B0 field where CSD and B1 inhomogeneity are more severe. This error may also occur in reception using a surface coil having inhomogeneous B1. Since this type of error is around a few percent, the data should be analyzed with greater attention while discussing small differences in the studies of 1H MRS.

Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy system: Sequence verification and preliminary clinical experience.

Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers from limited resolution, severe distortion, and possibly inaccurate ADC at low field strength. The purpose of this work was to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI-guided radiotherapy system. A diffusion-prepared turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging sequence on a 0.35 T MRI-guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantitate and compare the geometric accuracy of the two diffusion sequences for three orthogonal orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on a diffusion phantom under both 0 °C and room temperature to cover a diffusivity range between 0.40 × 10-3 and 2.10 × 10-3 mm2 /s. Ten room temperature measurements repeated on five different days were conducted to assess the ADC reproducibility of DP-TSE. Two glioblastoma (GBM) and six sarcoma patients were included to examine the in vivo feasibility. The target registration error (TRE) was calculated to quantitate the geometric accuracy where structural CT or MR images were co-registered to the diffusion images as references. ADC maps from DP-TSE and DW-ssEPI were calculated and compared. A tube phantom was placed next to patients not treated on ViewRay, and ADCs of this reference tube were also compared. The proposed DP-TSE passed the spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm radius) under the three orthogonal orientations. The detected errors were 0.474 ± 0.355 mm, 0.475 ± 0.287 mm, and 0.546 ± 0.336 mm in the axial, coronal, and sagittal plane. DW-ssEPI, however, failed the tests due to severe distortion and low signal intensity. Noise correction must be performed for the DW-ssEPI to avoid ADC quantitation errors, whereas it is optional for DP-TSE. At 0 °C, the two sequences provided accurate quantitation with < 3% variation with the reference. In the room temperature study, discrepancies between ADCs from DP-TSE and the reference were within 4%, but could be as high as 8% for DW-ssEPI after the noise correction. Excellent ADC reproducibility with a coefficient of variation < 5% was observed among the 10 measurements of DP-TSE, indicating desirable robustness for ADC-based tumor response assessment. In vivo TRE in DP-TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW-ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP-TSE were within the ranges found in literature. ADC differences between the two techniques were within 8% among the six sarcoma patients. For the reference tube that had a relatively low diffusivity, the two diffusion sequences provided matched measurements. A diffusion technique with excellent geometric fidelity, accurate, and reproducible ADC measurement was demonstrated for longitudinal tumor response assessment using a low-field MRI-guided radiotherapy system.

Errors in alkylated polycyclic aromatic hydrocarbon and sulfur heterocycle concentrations caused by currently employed standardized methods

Alkylated polycyclic aromatic hydrocarbon (PAH) and polycyclic aromatic sulfur heterocycle (PASH) standardized methods often rely on gas chromatography/mass spectrometry operated in the selected ion monitoring mode (GC/MS-SIM). The objective of this study is to develop a method that produces accurate data while minimizing sample preparation and achieving low levels of detection. Most standardized methods are based on acquiring a given homologue's molecular ion (1-ion). Some methods include a second, confirming ion (2-ion) in the hopes of excluding non-target ion signals from the total homologue peak area. Although all methods use homologue-specific retention windows, these windows differ greatly among the methods. In this paper we evaluate, for the first time, errors in quantitation caused by using different windows as well as common ion effects when target and/or matrix compounds coelute. Two NIST-certified Standard Reference Materials (SRMs), crude oil SRM 1582 and marine sediment SRM 1941b, were analyzed by five standardized methods and by the new method we developed, which relies on spectral deconvolution of three to five ions per PAH/PASH and as many fragmentation patterns as needed to correctly identify the C1 to C4 homologues (MFPPH). All of the standardized methods overestimated the concentrations of the majority of alkylated homologues whereas MFPPH obtained values much closer to NIST-certified concentrations. Rather than straight-line integration of all peaks in the retention window or recognizing peak patterns, the MFPPH data analysis software integrates only those peaks that meet the compound identity criteria.