Short TRs Research Articles

Evaluation of the safety and efficacy of high-dose rate brachytherapy for radiorecurrent prostate cancer: asystematic review and meta-analysis.

High-dose-rate brachytherapy (HDR-BT) plays an important role in the treatment of locally recurrent prostate cancer after definitive treatment. The objective of this study is to summarize the efficacy and toxicity of HDR-BT in these patients. We performed asystematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. Asemi-automated tool (WebPlotDigitizer) and anew Shiny application combined with Rsoftware (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves. Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. Atotal of 761 patients from 13studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0months). The estimated 2‑, 3‑, and 5‑year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70years vs. 71-75years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported. HDR-BT has ahigh safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.

A complete pipeline enables haplotyping and phasing macrohaplotype in long sequencing reads for polyploidy samples and a multi-source DNA mixture.

Macrohaplotype combines multiple types of phased DNA variants, increasing forensic discrimination power. High-quality long-sequencing reads, for example, PacBio HiFi reads, provide data to detect macrohaplotypes in multiploidy and DNA mixtures. However, the bioinformatics tools for detecting macrohaplotypes are lacking. In this study, we developed a bioinformatics software, MacroHapCaller, in which targeted loci (i.e., short TRs [STRs], single nucleotide polymorphisms, and insertion and deletions) are genotyped and combined with novel algorithms to call macrohaplotypes from long reads. MacroHapCaller uses physical phasing (i.e., read-backed phasing) to identify macrohaplotypes, and thus it can detect multi-allelic macrohaplotypes for a given sample. MacroHapCaller was validated with data generated from our designed targeted PacBio HiFi sequencing pipeline, which sequenced ∼8-kb amplicon regions harboring 20 core forensic STR loci in human benchmark samples HG002 and HG003. MacroHapCaller also was validated in whole-genome long-read sequencing data. Robust and accurate genotyping and phased macrohaplotypes were obtained with MacroHapCaller compared with the known ground truth. MacroHapCaller achieved a higher or consistent genotyping accuracy and faster speed than existing tools HipSTR and DeepVar. MacroHapCaller enables efficient macrohaplotype analysis from high-throughput sequencing data and supports applications using discriminating macrohaplotypes.

The role of DSC MR perfusion in predicting IDH mutation and 1p19q codeletion status in gliomas: meta-analysis and technical considerations

PurposeIsocitrate dehydrogenase (IDH) mutation and 1p19q codeletion status are important for managing glioma patients. However, current practice dictates invasive tissue sampling for histomolecular classification. We investigated the current value of dynamic susceptibility contrast (DSC) MR perfusion imaging as a tool for the non-invasive identification of these biomarkers.MethodsA systematic search of PubMed, Medline, and Embase up to 2023 was performed, and meta-analyses were conducted. We removed studies employing machine learning models or using multiparametric imaging. We used random-effects standardized mean difference (SMD) and bivariate sensitivity-specificity meta-analyses, calculated the area under the hierarchical summary receiver operating characteristic curve (AUC) and performed meta-regressions using technical acquisition parameters (e.g., time to echo [TE], repetition time [TR]) as moderators to explore sources of heterogeneity. For all estimates, 95% confidence intervals (CIs) are provided.ResultsSixteen eligible manuscripts comprising 1819 patients were included in the quantitative analyses. IDH mutant (IDHm) gliomas had lower rCBV values compared to their wild-type (IDHwt) counterparts. The highest SMD was observed for rCBVmean, rCBVmax, and rCBV 75th percentile (SMD≈ − 0.8, 95% CI ≈ [− 1.2, − 0.5]). In meta-regression, shorter TEs, shorter TRs, and smaller slice thicknesses were linked to higher absolute SMDs. When discriminating IDHm from IDHwt, the highest pooled specificity was observed for rCBVmean (82% [72, 89]), and the highest pooled sensitivity (i.e., 92% [86, 93]) and AUC (i.e., 0.91) for rCBV 10th percentile. In the bivariate meta-regression, shorter TEs and smaller slice gaps were linked to higher pooled sensitivities. In IDHm, 1p19q codeletion was associated with higher rCBVmean (SMD = 0.9 [0.2, 1.5]) and rCBV 90th percentile (SMD = 0.9 [0.1, 1.7]) values.ConclusionsIdentification of vascular signatures predictive of IDH and 1p19q status is a novel promising application of DSC perfusion. Standardization of acquisition protocols and post-processing of DSC perfusion maps are warranted before widespread use in clinical practice.

Prostate lesions characterization using diffusion-weighted spatiotemporal encoded MRI: Feasibility and initial assessment.

To assess the feasibility and reliability of a DWI protocol based on spatiotemporally encoding (SPEN), to target prostate lesions along guidelines normally used in EPI-based DWI clinical practice. Prostate Imaging-Reporting and Data System recommendations underlying clinical prostate scans were used to develop a SPEN-based DWI protocol, which included a novel, local, low-rank regularization algorithm. These DWI acquisitions were run at 3 T under similar nominal spatial resolutions and diffusion-weighting b-values as used in EPI-based clinical studies. Prostates of 11 patients suspected of clinically significant prostate cancer lesions were therefore scanned using the two methods, with the same number of slices, same slice thickness, and same interslice gaps. Of the 11 patients scanned, SPEN and EPI provided comparable information in 7 of the cases, whereas EPI was deemed superior in a case for which SPEN images had to be acquired with a shorter effective TR owing to scan-time constraints. SPEN provided reduced susceptibility to field-derived distortions in 3 of the cases. SPEN's ability to provide prostate lesion contrast was most clearly evidenced for DW images acquired with b ≥ 900 s/mm2 . SPEN also succeeded in decreasing occasional image distortions in regions close to the rectum, affected by field inhomogeneities. EPI advantages arose when using short effective TRs, a regime in which SPEN-based DWI was handicapped by its use of nonselective spin inversions, leading to the onset of an additional T1 weighting.

Arterial spin labeling using spatio-temporal encoding readout for robust perfusion imaging ininhomogenous magnetic fields.

To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. A 2D self-refocused T2 *-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp *Tchirp ) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q˜ 75 encodes with the same off-resonance robustness as EPI. The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately ˜85 and ˜108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p< 0.05) for TR=4000 ms compared to TR=2100 ms, while SE-EPI did not. tSNR remained relatively stable when the time between SPEN-excitation and start of the next labeling-module was more than ˜1000 ms. Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q> 75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning.

Intravascular BOLD signal characterization of balanced SSFP experiments in human blood at high to ultrahigh fields

To investigate the intravascular contribution to the overall balanced SSFP (bSSFP) BOLD effect in human blood at high to ultrahigh field strengths (3 T, 9.4 T, and 14.1 T). Venous blood prepared at two different oxygenation levels (deoxygenated: Y ≈ 71%, oxygenated: Y ≈ 94%) was measured with phase-cycled bSSFP for varying TRs/flip angles at 3 T, 9.4 T, and 14.1 T. The oxygen sensitivity was analyzed by intrinsic MIRACLE (motion-insensitive rapid configuration relaxometry)-R2 estimation and passband signal differences. The intravascular BOLD-related signal change was extracted from the measured data for microvasculature and macrovasculature, and compared with the extravascular contribution obtained by Monte Carlo simulations. The MIRACLE-R2 values showed a characteristic increase with longer TRs in deoxygenated blood, corroborating that SE-R2 data cannot be used to assess the intravascular bSSFP BOLD effect. Passband bSSFP signal differences measured at optimal flip angles of 30° at 3 T and 20° at 9.4 T/14.1 T revealed considerable relative intravascular contributions of 95%/70% at 3 T, 74%/43% at 9.4 T, 66%/46% at 14.1 T for TR = 5 ms, and 90%/65% at 3 T, 36%/27% at 9.4 T, 13%/15% at 14.1 T for TR = 10 ms in macrovascular/microvascular regimes. The results indicate that intravascular effects have to be considered to better understand the origin of bSSFP BOLD contrast in functional MRI experiments, especially at short TRs. The MIRACLE-R2 method demonstrated the ability to quantify the apparent decrease in R2 due to rapid RF refocusing.

Zero drift suppression for PdNi nano-film hydrogen sensor by vacuum annealing

Zero drift is one of the important factors affecting the accuracy of hydrogen sensor. To restrain the zero drift, the PdNi nano-film hydrogen sensors were vacuum annealed and effects of different vacuum annealing temperatures on the micro-structure, morphology and hydrogen sensing performances were explored in detail. The results show that with the annealing temperature increasing, the grains grow and the lattice constantly decreases. And the morphology of the surface grains changes from cone to sphere when the annealing temperature is more than 250 °C. Moreover, we provide a concept of EZD (effect of zero drift) to quantitative analysis of the effect of zero drift on hydrogen sensing performance. Repeatability tests reveal that annealing can inhibit EZD when the annealing temperature is more than 150 °C, which is attributed to defects of PdNi nano-film reducing and stability improving. However, increasing annealing temperature leads to the deterioration of sensing performances such as response (Rs), response time (trs) and recover time (trc), especially when the annealing temperature is more than 250 °C. Only annealing at 250 °C can decrease EZD availably and make the PdNi nano-film hydrogen sensor maintain a high Rs and short trs and trc. In addition, the sensor annealed at 250 °C is appropriate for detecting hydrogen with low concentration and the detection limit is low to 2 ppm.

Multi-shot Echo Planar Imaging for accelerated Cartesian MR Fingerprinting: An alternative to conventional spiral MR Fingerprinting

PurposeTo develop an accelerated Cartesian MRF implementation using a multi-shot EPI sequence for rapid simultaneous quantification of T1 and T2 parameters. MethodsThe proposed Cartesian MRF method involved the acquisition of highly subsampled MR images using a 16-shot EPI readout. A linearly varying flip angle train was used for rapid, simultaneous T1 and T2 quantification. The results were compared to a conventional spiral MRF implementation. The acquisition time per slice was 8s and this method was validated on two different phantoms and three healthy volunteer brains in vivo. ResultsJoint T1 and T2 estimations using the 16-shot EPI readout are in good agreement with the spiral implementation using the same acquisition parameters (<4% deviation for T1 and <6% deviation for T2). The T1 and T2 values also agree with the conventional values previously reported in the literature. The visual qualities of fine brain structures in the multi-parametric maps generated by multi-shot EPI-MRF and Spiral-MRF implementations were comparable. ConclusionThe multi-shot EPI-MRF method generated accurate quantitative multi-parametric maps similar to conventional Spiral-MRF. This multi-shot approach achieved considerable k-space subsampling and comparatively short TRs in a similar manner to spirals and therefore provides an alternative for performing MRF using an accelerated Cartesian readout; thereby increasing the potential usability of MRF.

Optimal repetition time reduction for single subject event-related functional magnetic resonance imaging.

PurposeShort TRs are increasingly used for fMRI as fast sequences such as simultaneous multislice excitation become available. These have been associated with apparent sensitivity improvements, although greater temporal autocorrelation at shorter TRs can inflate sensitivity measurements leading to uncertainty regarding the optimal approach.MethodsIn volunteers (n = 10), the optimal TR was assessed at the single subject level for event‐related designs (visual stimulation) with 4 frequencies of presentation at 4 TR values (412‐2550 ms). T‐values in the visual cortex localized in each individual were obtained and receiver operating characteristics (ROC) analysis was performed by counting voxels within and outside expected task active regions at different thresholds. This analysis was repeated using 4 different autoregressive (AR) models; SPM AR(1) and SPM AR(fast) which globally estimate autocorrelation, and fMRIstat AR(1) and AR(5) that use a local estimate.ResultsThe use of modest multiband factors of 2 or 3 with a reduction in TR to 1000 ± 200 ms had greater sensitivity and specificity as shown by higher T‐values in visual cortex and ROC analysis. At these TRs, the ROC analysis demonstrated that a local AR model fit improved performance while high order AR models were unnecessary.ConclusionsModest TR reductions (to 1000 ± 200 ms) optimally improved event‐related fMRI performance independent of design frequency. Autoregressive models with a local as opposed to global fit performed better, while low order autoregressive models were sufficient at the optimal TR.

Cerebrovascular blood oxygenation level dependent pulsatility at baseline and following acute exercise among healthy adolescents

Arterial stiffness is linked to cerebral small vessel damage and neurodegeneration, but barriers to accessing deep cerebrovascular anatomy limit our ability to assess the brain. This study describes an adaptation of a cardiac-related scrubbing method as a means of generating blood oxygenation level-dependent pulsatility maps based on the cardiac cycle. We examine BOLD pulsatility at rest, based on the non-parametric deviation from null metric, as well as changes following acute physiological stress from 20 min of moderate-intensity cycling in 45 healthy adolescents. We evaluate the influence of repetition time (TR) and echo time (TE) using simulated and multi-echo empirical data, respectively. There were tissue-specific and voxel-wise BOLD pulsatility decreases 20 min following exercise cessation. BOLD pulsatility detection was comparable over a range of TR and TE values when scan volumes were kept constant; however, short TRs (≤500 ms) and TEs (∼14 ms) acquisitions would yield the most efficient detection. Results suggest cardiac-related BOLD pulsatility may represent a robust and easily adopted method of mapping cerebrovascular pulsatility with voxel-wise resolution.

Phase-sensitive B1 mapping: Effects of relaxation and RF spoiling.

To develop a phase-based B1 mapping technique accounting for the effects of imperfect RF spoiling and magnetization relaxation. The technique is based on a multi-gradient-echo sequence with 2 successive orthogonal radiofrequency (RF) excitation pulses followed by the train of gradient echoes measurements. We have derived a theoretical expression relating the MR signal phase produced by the 2 successive RF pulses to the B1 field and B0 -related frequency shift. The expression takes into account effects of imperfections of RF spoiling and T1 and T2* relaxations. Our computer simulations and experiments revealed that imperfections of RF spoiling cause significant errors in B1 mapping if not accounted for. By accounting for these effects along with effects of magnetization relaxation and frequency shift, we demonstrated the high accuracy of our approach. The technique has been tested on spherical phantoms and a healthy volunteer. In this paper, we have proposed, implemented, and demonstrated the accuracy of a new phase-based technique for fast and robust B1 mapping based on the measured MR signal phase, frequency, and relaxation. Because imperfect RF spoiling effects are accounted for, this technique can be applied with short TRs and therefore substantially reduces the scan time. Magn Reson Med 80:101-111, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Dual-Pathway sequences for MR thermometry: When and where to use them.

Dual-pathway sequences have been proposed to help improve the temperature-to-noise ratio (TNR) in MR thermometry. The present work establishes how much of an improvement these so-called "PSIF-FISP" sequences may bring in various organs and tissues. Simulations and TNR calculations were validated against analytical equations, phantom, abdomen, and brain scans. Relative TNRs for PSIF-FISP, as compared to a dual-FISP reference standard, were calculated for flip angle (FA) = 1 to 85 º and repetition time (TR) = 6 to 60 ms, for gray matter, white matter, cervix, endometrium, myometrium, prostate, kidney medulla and cortex, bone marrow, pancreas, spleen, muscle, and liver tissues. PSIF-FISP was TNR superior in the kidney, pelvis, spleen, or gray matter at most tested TR and FA settings, and benefits increased at shorter TRs. PSIF-FISP was TNR superior in other tissues, e.g., liver, muscle, pancreas, for only short TR settings (20 ms or less). The TNR benefits of PSIF-FISP increased slightly with FA, and strongly with decreasing TR. Up to two- to three-fold reductions in TR with 20% TNR gains were achievable. In any given tissue, TNR performance is expected to further improve with heating, due to changes in relaxation rates. Dual-pathway PSIF-FISP can improve TNR and acquisition speed over standard gradient-recalled echo sequences, but optimal acquisition parameters are tissue dependent. Magn Reson Med 77:1193-1200, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Effect of temporal resolution and serial autocorrelations in event‐related functional MRI

To assess the impact of colored noise on statistics in event-related functional MRI (fMRI) (visual stimulation using checkerboards) acquired by simultaneous multislice imaging enabling repetition times (TRs) between 2.64 to 0.26 s. T-values within the visual cortex obtained with analysis tools that assume a first-order autoregressive plus white noise process (AR(1)+w) with a fixed AR coefficient versus higher-order AR models with spatially varying AR coefficients were compared. In addition, dependency of T-values on correction of physiological noise (respiration, heart rate) was evaluated. Optimal statistical power was obtained for a TR of 0.33 s, but T-values as obtained by AR(1)+w models were strongly dependent on the predefined AR coefficients in fMRI with short TRs which required higher-order AR models to achieve stable statistics. Direct estimation of AR coefficients revealed the highest values within the default mode network while physiological noise had little influence on statistics in cortical structures. Colored noise in event-related fMRI obtained at short TRs originates mainly from neural sources and calls for more sophisticated correction of serial autocorrelations which cannot be achieved with standard methods relying on AR(1)+w models with globally fixed AR coefficients. Magn Reson Med 76:1805-1813, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Reducing slab boundary artifacts in three-dimensional multislab diffusion MRI using nonlinear inversion for slab profile encoding (NPEN).

PurposeTo propose a method to reduce the slab boundary artifacts in three‐dimensional multislab diffusion MRI.MethodsBloch simulation is used to investigate the effects of multiple factors on slab boundary artifacts, including characterization of residual errors on diffusion quantification. A nonlinear inversion method is proposed to simultaneously estimate the slab profile and the underlying (corrected) image.ResultsCorrection results of numerical phantom and in vivo data demonstrate that the method can effectively remove slab boundary artifacts for diffusion data. Notably, the nonlinear inversion is also successful at short TR, a regimen where previously proposed methods (slab profile encoding and weighted average) retain residual artifacts in both diffusion‐weighted images and diffusion metrics (mean diffusion coefficient and fractional anisotropy).ConclusionThe nonlinear inversion for removing slab boundary artifacts provides improvements over existing methods, particularly at the short TRs required to maximize SNR efficiency. Magn Reson Med 76:1183–1195, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

ZTE imaging with long-T2 suppression.

Three-dimensional radial zero echo time (ZTE) imaging enables efficient direct MRI of tissues with rapid transverse relaxation. Yet, the feature of capturing signals with a wide range of T2 and T2 * values is accompanied by a lack of contrast between the corresponding tissues. In particular, the targeted short-T2 tissues may not be easily identified, and various approaches have been proposed to generate T2 contrast by reducing the long-T2 signal of water and/or fat. The aim of this work was to provide efficient long-T2 suppression for selective direct MRI of short-T2 tissues using the ZTE technique. For magnetization preparation, suppression pulses for water and fat were designed to provide both good T2 selectivity and off-resonance performance. To obtain high efficiency at short TRs, the pulses were applied in a segmented sequence scheme with minimized timing overhead, thus leading to a quasi-steady state of magnetization. The sequence timing was adjusted for optimal tissue contrast in musculoskeletal applications by means of simulations and experiments, incorporating both T2 and T1 of the involved tissues. The developed technique was employed for imaging of a lamb joint sample at 4.7 T. ZTE images were obtained with effective suppression of signals from tissues with long-T2 water, such as muscle or articular spaces, and fat. Hence, primarily short-T2 tissues were visible, such as bone and tendon. The MR image intensity of bone showed strong similarity with bone density imaged with micro-computed tomography.

Tracking cerebral blood flow in BOLD fMRI using recursively generated regressors.

BOLD functional MRI (fMRI) data are dominated by low frequency signals, many of them of unclear origin. We have recently shown that some portions of the low frequency oscillations found in BOLD fMRI are systemic signals closely related to the blood circulation (Tong et al. [2013]: NeuroImage 76:202-215). They are commonly treated as physiological noise in fMRI studies. In this study, we propose and test a novel data-driven analytical method that uses these systemic low frequency oscillations in the BOLD signal as a tracer to follow cerebral blood flow dynamically. Our findings demonstrate that: (1) systemic oscillations pervade the BOLD signal; (2) the temporal traces evolve as the blood propagates though the brain; and, (3) they can be effectively extracted via a recursive procedure and used to derive the cerebral circulation map. Moreover, this method is independent from functional analyses, and thus allows simultaneous and independent assessment of information about cerebral blood flow to be conducted in parallel with the functional studies. In this study, the method was applied to data from the resting state scans, acquired using a multiband EPI sequence (fMRI scan with much shorter TRs), of seven healthy participants. Dynamic maps with consistent features resembling cerebral blood circulation were derived, confirming the robustness and repeatability of the method.

Distinct Mutational Behaviors Differentiate Short Tandem Repeats from Microsatellites in the Human Genome

A tandem repeat’s (TR) propensity to mutate increases with repeat number, and can become very pronounced beyond a critical boundary, transforming it into a microsatellite (MS). However, a clear understanding of the mutational behavior of different TR classes and motifs and related mechanisms is lacking, as is a consensus on the existence of a boundary separating short TRs (STRs) from MSs. This hinders our understanding of MSs’ mutational properties and their effective use as genetic markers. Using indel calls for 179 individuals from 1000 Genomes Pilot-1 Project, we determined polymorphism incidence for four major TR classes, and formalized its varying relationship with repeat number using segmented regression. We observed a biphasic regime with a transition from a faster to a slower exponential growth at 9, 5, 4, and 4 repeats for mono-, di-, tri-, and tetranucleotide TRs, respectively. We used an in vitro mutagenesis assay to evaluate the contribution of strand slippage errors to mutability. STRs and MSs differ in their absolute polymorphism levels, but more importantly in their rates of mutability growth. Although strand slippage is a major factor driving mononucleotide polymorphism incidence, dinucleotide polymorphism incidence is greater than that expected due to strand slippage alone, indicating that additional cellular factors might be driving dinucleotide mutability in the human genome. Leveraging on hundreds of human genomes, we present the first comprehensive, genome-wide analysis of TR mutational behavior, encompassing several motif sizes and compositions.

Effects of image contrast on functional MRI image registration

Lack of tissue contrast and existing inhomogeneous bias fields from multi-channel coils have the potential to degrade the output of registration algorithms; and consequently degrade group analysis and any attempt to accurately localize brain function. Non-invasive ways to improve tissue contrast in fMRI images include the use of low flip angles (FAs) well below the Ernst angle and longer repetition times (TR). Techniques to correct intensity inhomogeneity are also available in most mainstream fMRI data analysis packages; but are not used as part of the pre-processing pipeline in many studies. In this work, we use a combination of real data and simulations to show that simple-to-implement acquisition/pre-processing techniques can significantly improve the outcome of both functional-to-functional and anatomical-to-functional image registrations. We also emphasize the need of tissue contrast on EPI images to be able to appropriately evaluate the quality of the alignment. In particular, we show that the use of low FAs (e.g., θ≤40°), when physiological noise considerations permit such an approach, significantly improves accuracy, consistency and stability of registration for data acquired at relatively short TRs (TR≤2s). Moreover, we also show that the application of bias correction techniques significantly improves alignment both for array-coil data (known to contain high intensity inhomogeneity) as well as birdcage-coil data. Finally, improvements in alignment derived from the use of the first infinite-TR volumes (ITVs) as targets for registration are also demonstrated. For the purpose of quantitatively evaluating the different scenarios, two novel metrics were developed: Mean Voxel Distance (MVD) to evaluate registration consistency, and Deviation of Mean Voxel Distance (dMVD) to evaluate registration stability across successive alignment attempts.

１．５ Ｔと３ Ｔにおけるスピンエコー法のクロストークの影響に関する検討

The purpose of this study is to evaluate the crosstalk effect on spin-echo (SE) images at 1.5 and 3 T MRI. We examined the influence of crosstalk by comparing the full width at half-maximum (FWHM) and slice profile of images of a wedge-shaped phantom for various slice gaps. We also assessed crosstalk effect in the brain by comparing image contrast among healthy volunteers (n=8). Among the subjects, the shapes of the slice profiles at 1.5 T were similar to those at 3 T for long repetition times (TRs); however, at shorter TRs, differences in slice profiles were observed among the subjects and were more apparent at 3 than at 1.5 T. The relative contrast between white matter and gray matter on T(1)-weighted images was lower at 3 than at 1.5 T. The crosstalk effect was strongest when the TR of the excitation pulse was short. The influence of the adjacent excitation pulse is important in the process of T(1) relaxation because T(1) values are greater at 3 T. In conclusion, the influence of crosstalk on SE T(1)-weighted images is greater at 3 than at 1.5 T.

A Serial Dilution Study of Gadolinium-Based MR Imaging Contrast Agents

With the approval of gadobenate dimeglumine, higher relaxivity MR contrast agents were introduced into the clinical environment, and multiple in vivo studies compared the efficacy and safety with the previously approved agents. An in vitro study was conducted to demonstrate differences between the various agents to confirm published values and for imaging-sequence optimization. A contrast phantom was made with serial dilutions of commercially available formulations of 5 US Food and Drug Administration-approved gadolinium-based MR imaging contrast agents in human serum substitute. Dilution factors ranging from 1:8 to 1:4096 were included in the phantom. Spin-echo sequences were performed at 1.5T and 3T with varying TRs and TEs. At physiologic concentrations and by using short TRs and TEs, gadobenate demonstrated the highest signal intensities, confirming greater R1 relaxivity. At higher concentrations and with longer TR and TE values, the greatest signal intensity loss was appreciated for gadobenate, confirming greater R2 relaxivity. Using rigorous in vitro methodology and serial dilution techniques, this study confirms the reported higher R1 and R2 relaxivities of gadobenate relative to the other agents at 1.5T and 3T.