A Kinesin-14 Motor Activates Neocentromeres to Promote Meiotic Drive in Maize.

Maize abnormal chromosome 10 (Ab10) encodes a classic example of true meiotic drive that converts heterochromatic regions called knobs into motile neocentromeres that are preferentially transmitted to egg cells. Here, we identify a cluster of eight genes on Ab10, called the Kinesin driver (Kindr) complex, that are required for both neocentromere motility and preferential transmission. Two meiotic drive mutants that lack neocentromere activity proved to be kindr epimutants with increased DNA methylation across the entire gene cluster. RNAi of Kindr induced a third epimutant and corresponding loss of meiotic drive. Kinesin gliding assays and immunolocalization revealed that KINDR is a functional minus-end-directed kinesin that localizes specifically to knobs containing 180 bp repeats. Sequence comparisons suggest that Kindr diverged from a Kinesin-14A ancestor ∼12 mya and has driven the accumulation of > 500 Mb of knob repeats and affected the segregation of thousands of genes linked to knobs on all 10 chromosomes.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

BACKGROUND: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. PURPOSE: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. STUDY TYPE: Prospective, single-center, two arm, interventional vs. nonintervention observational study. POPULATION: Forty-four patients (male N = 30; median age 68 [59-75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing "watchful waiting" (WW). FIELD STRENGTH/SEQUENCE: 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). ASSESSMENT: Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). STATISTICAL TESTS: Included Student t-test/Mann-Whitney test/Fisher's exact test, Bland-Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. RESULTS: While Bland-Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement -36 mL to 65 mL), than between 4DF-MR and TTE (bias -8; limits of agreement -106 mL to 90 mL) and PMRI and TTE (bias -23; limits of agreement -105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). DATA CONCLUSION: This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Evaluation of a Statewide Online, At-Home Sexually Transmitted Infection and Human Immunodeficiency Virus Screening Program.

BACKGROUND: Innovative approaches such as online, at-home programs may address important barriers to sexually transmitted infection (STI) and human immunodeficiency virus (HIV) screening in the United States. This study evaluated the first year of an online, at-home program offering HIV and triple-site (urogenital, rectal, and pharyngeal) gonorrhea (GC) and chlamydia (CT) testing in Colorado. METHODS: Test Yourself Colorado (TYC) is an online, at-home program that provides free mailed HIV tests and/or GC/CT tests to Colorado adults. Program use and outcomes between 1 June 2021 and 31 May 2022 were analyzed. RESULTS: A total of 1790 unique clients utilized TYC. Of 1709 clients who ordered HIV tests, 508 (29.7%) were men who have sex with men (MSM), and 41.3% (210/508) of these clients reported having never been tested for HIV before or were not tested in the prior year. Hispanic clients had lower STI test return rates (37.1%; 134/361) compared with non-Hispanic clients (45.9%; 518/1128) (P = .003). Positive STI tests were identified in 9.6% (68/708) of clients. Positive STI tests were more common in MSM clients (15.7%; 34/216) compared with all other sexual orientations (6.9%; 34/492) (P < .001). STI treatment was confirmed in 80.9% (55/68) of clients. CONCLUSIONS: The TYC online, home testing portal is a scalable tool that reaches clients at risk of STIs and HIV and navigates those with positive STI tests to treatment. HIV/STI home testing programs need to further assess and address utilization and outcomes for disparities by race and ethnicity to assure programs equitably benefit all at-risk communities.

Evaluation of the Impact and Outcomes of a Rapid Transition to Telehealth PrEP Delivery at a Sexual Health Clinic During the COVID-19 Pandemic.

BACKGROUND: Increasing human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) use is a critical part of ending the HIV epidemic. In response to the COVID-19 pandemic, many PrEP services transitioned to a telehealth model (telePrEP). This report evaluates the effect of COVID-19 and the addition of telePrEP on delivery of PrEP services at the Denver Sexual Health Clinic (DSHC), a regional sexual health clinic in Denver, CO. METHODS: Before COVID-19, DSHC PrEP services were offered exclusively in-clinic. In response to the pandemic, after March 15, 2020, most PrEP initiation and follow-up visits were converted to telePrEP. A retrospective analysis of DSHC PrEP visits compared pre-COVID-19 (September 1, 2019 to March 15, 2020) to post-COVID-19 (March 16, 2020 to September 30, 2020) visit volume, demographics, and outcomes. RESULTS: The DSHC completed 689 PrEP visits pre-COVID-19 and maintained 96.8% (n = 667) of this volume post-COVID-19. There were no differences in client demographics between pre-COVID-19 (n = 341) and post-COVID-19 PrEP start visits (n = 283) or between post-COVID-19 in-clinic (n = 140) vs telePrEP start visits (n = 143). There were no differences in 3- to 4-month retention rates pre-COVID-19 (n = 17/43) and post-COVID-19 (n = 21/43) ( P = 0.52) or between in-clinic (n = 12/21) and telePrEP clients (n = 9/22) in the post-COVID-19 window ( P = 0.37). Also, there were no significant differences in lab completion rates between in-clinic (n = 140/140) and telePrEP clients (n = 138/143) ( P = 0.06) and prescription fill rates between in-clinic (n = 115/136) and telePrEP clients (n = 116/135) in the post-COVID-19 window ( P = 0.86). CONCLUSIONS: Implementation of TelePrEP enabled the DSHC to sustain PrEP services during the COVID-19 pandemic without significant differences in demographics, engagement, or retention in PrEP services.

Cardiac reverse remodeling in primary mitral regurgitation: mitral valve replacement vs. mitral valve repair.

BACKGROUND: When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. METHODS: 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). RESULTS: 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; - 29 ± 21 ml/m2 vs - 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (- 23 ± 30 ml/m2 and - 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p < 0.001) baseline multivariate predictor of lower residual MR. CONCLUSION: In primary MR, MVR with chordal preservation may offer comparable cardiac reverse remodeling and functional benefits at 6-months when compared to MVr. Larger, multicenter CMR studies are required, which if the findings are confirmed could impact future surgical practice.

Rationale and clinical applications of 4D flow cardiovascular magnetic resonance in assessment of valvular heart disease: a comprehensive review.

BACKGROUND: Accurate evaluation of valvular pathology is crucial in the timing of surgical intervention. Whilst transthoracic echocardiography is widely available and routinely used in the assessment of valvular heart disease, it is bound by several limitations. Although cardiovascular magnetic resonance (CMR) imaging can overcome many of the challenges encountered by echocardiography, it also has a number of limitations. MAIN TEXT: 4D Flow CMR is a novel technique, which allows time-resolved, 3-dimensional imaging. It enables visualisation and direct quantification of flow and peak velocities of all valves simultaneously in one simple acquisition, without any geometric assumptions. It also has the unique ability to measure advanced haemodynamic parameters such as turbulent kinetic energy, viscous energy loss rate and wall shear stress, which may add further diagnostic and prognostic information. Although 4D Flow CMR acquisition can take 5-10 min, emerging acceleration techniques can significantly reduce scan times, making 4D Flow CMR applicable in contemporary clinical practice. CONCLUSION: 4D Flow CMR is an emerging CMR technique, which has the potential to become the new reference-standard method for the evaluation of valvular lesions. In this review, we describe the clinical applications, advantages and disadvantages of 4D Flow CMR in the assessment of valvular heart disease.

T1 mapping performance and measurement repeatability: results from the multi-national T1 mapping standardization phantom program (T1MES).

BACKGROUND: The T1 Mapping and Extracellular volume (ECV) Standardization (T1MES) program explored T1 mapping quality assurance using a purpose-developed phantom with Food and Drug Administration (FDA) and Conformité Européenne (CE) regulatory clearance. We report T1 measurement repeatability across centers describing sequence, magnet, and vendor performance. METHODS: Phantoms batch-manufactured in August 2015 underwent 2 years of structural imaging, B0 and B1, and "reference" slow T1 testing. Temperature dependency was evaluated by the United States National Institute of Standards and Technology and by the German Physikalisch-Technische Bundesanstalt. Center-specific T1 mapping repeatability (maximum one scan per week to minimum one per quarter year) was assessed over mean 358 (maximum 1161) days on 34 1.5 T and 22 3 T magnets using multiple T1 mapping sequences. Image and temperature data were analyzed semi-automatically. Repeatability of serial T1 was evaluated in terms of coefficient of variation (CoV), and linear mixed models were constructed to study the interplay of some of the known sources of T1 variation. RESULTS: Over 2 years, phantom gel integrity remained intact (no rips/tears), B0 and B1 homogenous, and "reference" T1 stable compared to baseline (% change at 1.5 T, 1.95 ± 1.39%; 3 T, 2.22 ± 1.44%). Per degrees Celsius, 1.5 T, T1 (MOLLI 5s(3s)3s) increased by 11.4 ms in long native blood tubes and decreased by 1.2 ms in short post-contrast myocardium tubes. Agreement of estimated T1 times with "reference" T1 was similar across Siemens and Philips CMR systems at both field strengths (adjusted R2 ranges for both field strengths, 0.99-1.00). Over 1 year, many 1.5 T and 3 T sequences/magnets were repeatable with mean CoVs < 1 and 2% respectively. Repeatability was narrower for 1.5 T over 3 T. Within T1MES repeatability for native T1 was narrow for several sequences, for example, at 1.5 T, Siemens MOLLI 5s(3s)3s prototype number 448B (mean CoV = 0.27%) and Philips modified Look-Locker inversion recovery (MOLLI) 3s(3s)5s (CoV 0.54%), and at 3 T, Philips MOLLI 3b(3s)5b (CoV 0.33%) and Siemens shortened MOLLI (ShMOLLI) prototype 780C (CoV 0.69%). After adjusting for temperature and field strength, it was found that the T1 mapping sequence and scanner software version (both P < 0.001 at 1.5 T and 3 T), and to a lesser extent the scanner model (P = 0.011, 1.5 T only), had the greatest influence on T1 across multiple centers. CONCLUSION: The T1MES CE/FDA approved phantom is a robust quality assurance device. In a multi-center setting, T1 mapping had performance differences between field strengths, sequences, scanner software versions, and manufacturers. However, several specific combinations of field strength, sequence, and scanner are highly repeatable, and thus, have potential to provide standardized assessment of T1 times for clinical use, although temperature correction is required for native T1 tubes at least.

Visualizing the autonomic and somatic innervation of the female pelvis with 3D MR neurography: a feasibility study.

BACKGROUND: Treatment of female pelvic malignancies often causes pelvic nerve damage. Magnetic resonance (MR) neurography mapping the female pelvic innervation could aid in treatment planning. PURPOSE: To depict female autonomic and somatic pelvic innervation using a modified 3D NerveVIEW sequence. MATERIAL AND METHODS: Prospective study in 20 female volunteers (n = 6 normal, n = 14 cervical pathology) who underwent a modified 3D short TI inversion recovery (STIR) turbo spin-echo (TSE) scan with a motion-sensitive driven equilibrium (MSDE) preparation radiofrequency pulse and flow compensation. Modifications included offset independent trapezoid (OIT) pulses for inversion and MSDE refocusing. Maximum intensity projections (MIP) were evaluated by two observers (Observer 1, Observer 2); image quality was scored as 2 = high, 1 = medium, or 0 = low with the sciatic nerve serving as a reference. Conspicuity of autonomic superior (SHP) and bilateral inferior hypogastric plexuses (IHP), hypogastric nerves, and somatic pelvic nerves (sciatic, pudendal) was scored as 2 = well-defined, 1 = poorly defined, or 0 = not seen, and inter-observer agreement was determined. RESULTS: Images were of medium to high quality according to both observers agreeing in 15/20 (75%) of individuals. SHP and bilateral hypogastric nerves were seen in 30/60 (50%) of cases by both observers. Bilateral IHP was seen in 85% (34/40) by Observer 1 and in 75% (30/40) by Observer 2. Sciatic nerves were well identified in all cases, while pudendal nerves were seen bilaterally by Observer 1 in 65% (26/40) and by Observer 2 in 72.5% (29/40). Agreement between observers for scoring nerve conspicuity was in the range of 60%-100%. CONCLUSION: Modified 3D NerveVIEW renders high-quality images of the female autonomic and pudendal nerves.

Reference range determination for imaging biomarkers: Myocardial T1.

BACKGROUND: Imaging biomarkers, such as the T1 relaxation time of the myocardium using MRI, can be valuable in cardiac medicine if they are properly validated. Consensus statements recommend that for myocardial T1 , each investigator should establish a reference range. PURPOSE: To describe a statistically valid method for determining and reporting the reference range in each center, which simultaneously minimizes the twin risks of undersampling, leading to a uselessly uncertain range, and oversampling, which exposes volunteers to unnecessary scanning and wastes resources. STUDY TYPE: Cohort. POPULATION: In all, 278 normal human subjects without cardiac disease from two cardiac MR centers. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T; Modified Look-Locker Inversion recovery sequence. ASSESSMENT: The T1 relaxation time was estimated from multiple samples of tissue magnetization after inversion. A valid method for calculating a reference range was used. STATISTICAL TESTS: Shapiro-Wilk test for normality; Tukey robust approach for identification of outliers; reference range calculation with confidence intervals. RESULTS: Reference ranges for measurement of myocardial T1 were calculated, with confidence intervals, enabling comparison with clinically important differences. At 3 T: 1129 to 1301 msec at site 1 (n = 21) and 1160 to 1309 msec at site 2 (n = 59), and at 1.5 T at site 2: 933 to 1020 msec (male, n = 130) and 965 to 1054 msec (female, n = 68). The 3 T reference range from site 1 was successfully benchmarked against the 3 T reference range at site 2. DATA CONCLUSION: Myocardial T1 reference ranges can be properly characterized, enabling clinical comparison to a valid reference range with known confidence intervals, using methodology similar to that described in this report. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:771-778.

Clinical evaluation of two dark blood methods of late gadolinium quantification of ischemic scar.

BACKGROUND: Late gadolinium enhancement (LGE) imaging was validated for diagnosis and quantification of myocardial infarction (MI). Despite good contrast between scar and normal myocardium, contrast between blood pool and myocardial scar can be limited. Dark blood LGE sequences attempt to overcome this issue. PURPOSE: To evaluate T1 rho (T1 ρ)-prepared dark blood sequence and compare to blood nulled (BN) phase sensitive inversion recovery (PSIR) and standard myocardium nulled (MN) PSIR for detection and quantification of scar. STUDY TYPE: Prospective. POPULATION: Thirty patients with prior MI. FIELD STRENGTH/SEQUENCE: Patients underwent identical 1.5 T MRI protocols. Following routine LGE imaging, a slice with scar, remote myocardium, and blood pool was selected. PSIR LGE was repeated with inversion time set to MN, to BN, and T1 ρ FIDDLE (flow-independent dark-blood delayed enhancement) in random order. ASSESSMENT: Three observers. Qualitative assessment of confidence scores in scar detection and degree of transmurality. Quantitative assessment of myocardial scar mass (grams), and contrast-to-noise ratio (CNR) measurements between scar, blood pool, and myocardium. STATISTICAL TESTS: Repeated-measures analysis of variance (ANOVA) with Bonferroni correction, coefficient of variation, and the Cohen κ statistic. RESULTS: CNRscar-blood was significantly increased for both BN (27.1 ± 10.4) and T1 ρ (30.2 ± 15.1) compared with MN (15.3 ± 8.4 P < 0.001 for both sequences). There was no significant difference in CNRscar-myo between BN (55.9 ± 17.3) and MN (51.1 ± 17.8 P = 0.512); both had significantly higher CNRscar-myo compared with the T1 ρ (42.6 ± 16.9 P = 0.007 and P = 0.014, respectively). No significant difference in scar size between LGE methods: MN (2.28 ± 1.58 g) BN (2.16 ± 1.57 g) and T1 ρ (2.29 ± 2.5 g). Confidence scores were significantly higher for BN (3.87 ± 0.346) compared with MN (3.1 ± 0.76 P < 0.001) and T1 ρ (3.20 ± 0.71 P < 0.001). DATA CONCLUSION: PSIR with inversion time (TI) set for blood nulling and the T1 ρ LGE sequence demonstrated significantly higher scar to blood CNR compared with routine MN. PSIR with TI set for blood nulling demonstrated significantly higher reader confidence scores compared with routine MN and T1 ρ LGE, suggesting routine adoption of a BN PSIR approach might be appropriate for LGE imaging. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:146-152.

Feasibility study of a single breath-hold, 3D mDIXON pulse sequence for late gadolinium enhancement imaging of ischemic scar.

BACKGROUND: Late gadolinium enhancement (LGE) imaging is well validated for the diagnosis and quantification of myocardial infarction (MI). 2D LGE imaging involves multiple breath-holds for acquisition of short-axis slices to cover the left ventricle (LV). 3D LGE methods cover the LV in a single breath-hold; however, breath-hold duration is typically long with images susceptible to motion artifacts. PURPOSE/HYPOTHESIS: To assess a single breath-hold 3D mDIXON LGE pulse sequence for image quality and quantitation of MI. STUDY TYPE: Prospective. POPULATION: Ninety- two patients with prior MI. FIELD STRENGTH/SEQUENCE: 1.5T cardiac MRI protocol using both conventional 2D phase sensitive inversion recovery and 3D mDIXON LGE imaging 10 minutes following contrast administration in random order to avoid bias. ASSESSMENT: Data were analyzed qualitatively for image quality (three observers). Quantitative assessment of myocardial scar mass (full-width half-maximum), scar transmurality, and contrast-to-noise ratio measurements were performed. Time for 2D and 3D LGE imaging was recorded. STATISTICAL TESTS: Paired Student's t-test, Wilcoxon rank test, Cohen κ statistic, Pearson correlation, linear regression, and Bland-Altman analysis. RESULTS: Image quality scores were comparable between 3D and 2D LGE (1.4 ± 0.6 vs. 1.3 ± 0.5; P = 0.162). 3D LGE was associated with greater scar tissue mass (3D: 18.9 ± 17.5 g vs. 2D: 17.8 ± 16.2 g P = 0.03), although this difference was less pronounced when scar tissue was expressed as %LV mass (3D: 13.4 ± 9.9% vs. 2D: 12.7 ± 9.5% P = 0.07). For 3D vs. 2D scar mass there was a strong and significant positive correlation; Bland-Altman analysis showed mean mass bias of 1.1 g (95% confidence interval [CI]: -5.7 to 7.9). Segmental level agreement of scar transmurality between 3D and 2D LGE at the clinical viability threshold of 50% transmurality was excellent (κ = 0.870). 3D image acquisition (15.6 ± 1.4 sec) was just 5% of time required for 2D images (311.6 ± 43.2 sec) P < 0.0001. DATA CONCLUSION: Single breath-hold 3D mDIXON LGE imaging allows quantitative assessment of MI mass and transmurality, with comparable image quality, in vastly shorter overall acquisition time compared with standard 2D LGE imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1437-1445.

Anaphase asymmetry and dynamic repositioning of the division plane during maize meiosis.

The success of an organism is contingent upon its ability to transmit genetic material through meiotic cell division. In plant meiosis I, the process begins in a large spherical cell without physical cues to guide the process. Yet, two microtubule-based structures, the spindle and phragmoplast, divide the chromosomes and the cell with extraordinary accuracy. Using a live-cell system and fluorescently labeled spindles and chromosomes, we found that the process self- corrects as meiosis proceeds. Metaphase spindles frequently initiate division off-center, and in these cases anaphase progression is asymmetric with the two masses of chromosomes traveling unequal distances on the spindle. The asymmetry is compensatory, such that the chromosomes on the side of the spindle that is farthest from the cell cortex travel a longer distance at a faster rate. The phragmoplast forms at an equidistant point between the telophase nuclei rather than at the original spindle mid-zone. This asymmetry in chromosome movement implies a structural difference between the two halves of a bipolar spindle and could allow meiotic cells to dynamically adapt to errors in metaphase and accurately divide the cell volume.

Comparison of fast acquisition strategies in whole-heart four-dimensional flow cardiac MR: Two-center, 1.5 Tesla, phantom and in vivo validation study.

PURPOSE: To validate three widely-used acceleration methods in four-dimensional (4D) flow cardiac MR; segmented 4D-spoiled-gradient-echo (4D-SPGR), 4D-echo-planar-imaging (4D-EPI), and 4D-k-t Broad-use Linear Acquisition Speed-up Technique (4D-k-t BLAST). MATERIALS AND METHODS: Acceleration methods were investigated in static/pulsatile phantoms and 25 volunteers on 1.5 Tesla MR systems. In phantoms, flow was quantified by 2D phase-contrast (PC), the three 4D flow methods and the time-beaker flow measurements. The later was used as the reference method. Peak velocity and flow assessment was done by means of all sequences. For peak velocity assessment 2D PC was used as the reference method. For flow assessment, consistency between mitral inflow and aortic outflow was investigated for all pulse-sequences. Visual grading of image quality/artifacts was performed on a four-point-scale (0 = no artifacts; 3 = nonevaluable). RESULTS: For the pulsatile phantom experiments, the mean error for 2D PC = 1.0 ± 1.1%, 4D-SPGR = 4.9 ± 1.3%, 4D-EPI = 7.6 ± 1.3% and 4D-k-t BLAST = 4.4 ± 1.9%. In vivo, acquisition time was shortest for 4D-EPI (4D-EPI = 8 ± 2 min versus 4D-SPGR = 9 ± 3 min, P < 0.05 and 4D-k-t BLAST = 9 ± 3 min, P = 0.29). 4D-EPI and 4D-k-t BLAST had minimal artifacts, while for 4D-SPGR, 40% of aortic valve/mitral valve (AV/MV) assessments scored 3 (nonevaluable). Peak velocity assessment using 4D-EPI demonstrated best correlation to 2D PC (AV:r = 0.78, P < 0.001; MV:r = 0.71, P < 0.001). Coefficient of variability (CV) for net forward flow (NFF) volume was least for 4D-EPI (7%) (2D PC:11%, 4D-SPGR: 29%, 4D-k-t BLAST: 30%, respectively). CONCLUSION: In phantom, all 4D flow techniques demonstrated mean error of less than 8%. 4D-EPI demonstrated the least susceptibility to artifacts, good image quality, modest agreement with the current reference standard for peak intra-cardiac velocities and the highest consistency of intra-cardiac flow quantifications. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:272-281.

Towards accurate and precise T 1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions.

Mapping of the longitudinal relaxation time (T 1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T 1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson-Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T 1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T 1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T 1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field.

Dark-blood late gadolinium enhancement without additional magnetization preparation.

BACKGROUND: This study evaluates a novel dark-blood late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) method, without using additional magnetization preparation, and compares it to conventional bright-blood LGE, for the detection of ischaemic myocardial scar. LGE is able to clearly depict myocardial infarction and macroscopic scarring from viable myocardium. However, due to the bright signal of adjacent left ventricular blood, the apparent volume of scar tissue can be significantly reduced, or even completely obscured. In addition, blood pool signal can mimic scar tissue and lead to false positive observations. Simply nulling the blood magnetization by choosing shorter inversion times, leads to a negative viable myocardium signal that appears equally as bright as scar due to the magnitude image reconstruction. However, by combining blood magnetization nulling with the extended grayscale range of phase-sensitive inversion-recovery (PSIR), a darker blood signal can be achieved whilst a dark myocardium and bright scar signal is preserved. METHODS: LGE was performed in nine male patients (63 ± 11y) using a PSIR pulse sequence, with both conventional viable myocardium nulling and left ventricular blood nulling, in a randomized order. Regions of interest were drawn in the left ventricular blood, viable myocardium, and scar tissue, to assess contrast-to-noise ratios. Maximum scar transmurality, scar size, circumferential scar angle, and a confidence score for scar detection and maximum transmurality were also assessed. Bloch simulations were performed to simulate the magnetization levels of the left ventricular blood, viable myocardium, and scar tissue. RESULTS: Average scar-to-blood contrast was significantly (p < 0.001) increased by 99% when nulling left ventricular blood instead of viable myocardium, while scar-to-myocardium contrast was maintained. Nulling left ventricular blood also led to significantly (p = 0.038) higher expert confidence in scar detection and maximum transmurality. No significant changes were found in scar transmurality (p = 0.317), normalized scar size (p = 0.054), and circumferential scar angle (p = 0.117). CONCLUSIONS: Nulling left ventricular blood magnetization for PSIR LGE leads to improved scar-to-blood contrast and increased expert confidence in scar detection and scar transmurality. As no additional magnetization preparation is used, clinical application on current MR systems is readily available without the need for extensive optimizations, software modifications, and/or additional training.

Accelerating MR Imaging Liver Steatosis Measurement Using Combined Compressed Sensing and Parallel Imaging: A Quantitative Evaluation.

PURPOSE: To determine the limits of agreement of hepatic fat fraction and R2* relaxation rate quantified with accelerated magnetic resonance (MR) imaging reconstructed with combined compressed sensing and parallel imaging compared with conventional fully sampled acquisitions. MATERIALS AND METHODS: Eleven subjects with type 2 diabetes and a healthy control subject were recruited with the approval of the Newcastle and North Tyneside 2 ethics committee and written consent. Undersampled data at ratios of 2.6×, 2.9×, 3.8×, and 4.8× were prospectively acquired in addition to fully sampled data by using five gradient echoes per repetition time at 3.0 T. Fat fraction maps were calculated by using combined compressed sensing and parallel imaging (CS-PI) reconstruction and Bland-Altman analysis performed to assess bias and 95% limits of agreement. Inter- and intrarater analysis was performed for quantitative fat fraction and R2* relaxation rate, and image quality was assessed with a four-point scale by two independent observers. RESULTS: The fat fractions from the accelerated acquisitions had 95% limits of agreement of 1.2%, 1.2%, 1.1%, and 1.5%, respectively, with no bias. When compared with the intra- and interrater 95% limits of agreement (0.7% and 0.8%), acceleration of up to 3.8× did not greatly degrade the fat fraction measurements. No or minimal artifact was detected at 2.6× and 2.9× accelerations, moderate artifact was detected at 3.8× acceleration, and substantial artifact was detected at 4.8× acceleration. CONCLUSION: Prospective undersampling and CS-PI reconstruction of liver fat fractions can be used to accelerate liver fat fraction measurements. The fat fractions and image quality produced were acceptable up to a factor of 3.8×, thereby shortening the required breath-hold duration from 17.7 seconds to 4.7 seconds.

Sensitivity of quantitative myocardial dynamic contrast-enhanced MRI to saturation pulse efficiency, noise and t1 measurement error: Comparison of nonlinearity correction methods.

PURPOSE: To compare methods designed to minimize or correct signal nonlinearity in quantitative myocardial dynamic contrast-enhanced (DCE) MRI. METHODS: DCE-MRI studies were simulated and data acquired in eight volunteers. Signal nonlinearity was corrected using either a dual-bolus approach or model-based correction using proton-density weighted imaging (conventional or dual-sequence acquisition) or T1 data (native or bookend). Scanning of healthy and infarcted myocardium at 3 T was simulated, including noise, saturation imperfection and T1 measurement error. Data were analyzed using model-based deconvolution with a one-compartment (mono-exponential) model. RESULTS: Substantial variation between methods was demonstrated in volunteers. In simulations the dual-bolus method proved stable for realistic levels of saturation efficiency but demonstrated bias due to residual nonlinearity. Model-based methods performed ideally in the absence of confounding error sources and were generally robust to noise or saturation imperfection, except for native T1 based correction which was highly sensitive to the latter. All methods demonstrated large variation in accuracy above an over-saturation level where baseline signal was nulled. For the dual-sequence approach this caused substantial bias at the saturation efficiencies observed in volunteers. CONCLUSION: The choice of nonlinearity correction method in myocardial DCE-MRI impacts on accuracy and precision of estimated parameters, particularly in the presence of nonideal saturation.

Improving highly accelerated fat fraction measurements for clinical trials in muscular dystrophy: origin and quantitative effect of R2* changes.

Purpose To investigate the effect of R2* modeling in conventional and accelerated measurements of skeletal muscle fat fraction in control subjects and patients with muscular dystrophy. Materials and Methods Eight patients with Becker muscular dystrophy and eight matched control subjects were recruited with approval from the Newcastle and North Tyneside 2 Research Ethics Committee and with written consent. Chemical-shift images with six widely spaced echo times (in 3.5-msec increments) were acquired to correlate R2* and muscle fat fraction. The effect of incorporating or neglecting R2* modeling on fat fraction magnitude and variance was evaluated in a typical three-echo protocol (with 0.78-msec increments). Accelerated acquisitions with this protocol with 3.65×, 4.94×, and 6.42× undersampling were reconstructed by using combined compressed sensing and parallel imaging and fat fraction maps produced with R2* modeling. Results Muscle R2* at 3.0 T (33-125 sec(-1)) depended on the morphology of fat replacement, the highest values occurring with the greatest interdigitation of fat. The inclusion of R2* modeling removed bias, which was greatest at low fat fraction, but did not increase variance. The 95% limits of agreement of the accelerated acquisitions were tight and not degraded by R2* modeling (1.65%, 1.95%, and 2.22% for 3.65×, 4.94×, and 6.42× acceleration, respectively). Conclusion Incorporating R2* modeling prevents systematic errors in muscle fat fraction by up to 3.5% without loss of precision and should be incorporated into all muscular dystrophy studies. Fat fraction measurements can be accelerated fivefold by using combined compressed sensing and parallel imaging, modeling for R2* without loss of fidelity.

Robust myocardial T2 and T2 * mapping at 3T using image-based shimming.

PURPOSE: Intramyocardial hemorrhage and area at risk are both prognostic markers in acute myocardial infarction (AMI). Myocardial T2 and T2 * mapping have been used to detect such tissue changes at 1.5T but these techniques are challenging at 3.0T due to additional susceptibility variation. We studied T2 and T2 * myocardial mapping techniques at 3.0T on a system employing B1 shimming and compared two different methods of B0 shimming. MATERIALS AND METHODS: Fifteen volunteers and six AMI patients were scanned on a 3T system. Volume and image-based (IB) B0 shimming techniques were implemented. Single breath-hold, multiecho gradient, and spin echo sequences were employed from which T2 * and T2 maps were calculated. RESULTS: In volunteers, there was no significant difference in mean values obtained with volume or IB shimming for T2 mapping (39.1 ± 6.0 msec vs. 39.4 ± 6.1 msec; P > 0.05) or for T2 * mapping (24.2 ± 6.7 msec vs. 24.1 ± 5.2 msec; P > 0.05). There were no significant regional differences in mean T2 values between septal, anterior, and posterior segments with either shimming technique (all P > 0.05); but there were significant regional differences in mean T2 * values using volume shimming (27.8 ± 5.2 msec vs. 28.4 ± 5.8 msec vs. 15.9 ± 8.3 msec; P < 0.05)-but not with IB shimming (25.7 ± 5.4 msec vs. 25.3 ± 5.9 msec vs. 18.7 ± 4.6 msec; P > 0.05). CONCLUSION: At 3.0T, cardiac T2 mapping is robust. Although T2 * mapping is prone to more regional heterogeneity this can be reduced by using IB instead of conventional volume B0 shimming.