Tricuspid valve flow measurement using a deep learning framework for automated valve-tracking 2D phase contrast.

PURPOSE: Tricuspid valve flow velocities are challenging to measure with cardiovascular MR, as the rapidly moving valvular plane prohibits direct flow evaluation, but they are vitally important to diastolic function evaluation. We developed an automated valve-tracking 2D method for measuring flow through the dynamic tricuspid valve. METHODS: Nine healthy subjects and 2 patients were imaged. The approach uses a previously trained deep learning network, TVnet, to automatically track the tricuspid valve plane from long-axis cine images. Subsequently, the tracking information is used to acquire 2D phase contrast (PC) with a dynamic (moving) acquisition plane that tracks the valve. Direct diastolic net flows evaluated from the dynamic PC sequence were compared with flows from 2D-PC scans acquired in a static slice localized at the end-systolic valve position, and also ventricular stroke volumes (SVs) using both planimetry and 2D PC of the great vessels. RESULTS: The mean tricuspid valve systolic excursion was 17.8 ± 2.5 mm. The 2D valve-tracking PC net diastolic flow showed excellent correlation with SV by right-ventricle planimetry (bias ± 1.96 SD = -0.2 ± 10.4 mL, intraclass correlation coefficient [ICC] = 0.92) and aortic PC (-1.0 ± 13.8 mL, ICC = 0.87). In comparison, static tricuspid valve 2D PC also showed a strong correlation but had greater bias (p = 0.01) versus the right-ventricle SV (10.6 ± 16.1 mL, ICC = 0.61). In most (8 of 9) healthy subjects, trace regurgitation was measured at begin-systole. In one patient, valve-tracking PC displayed a high-velocity jet (380 cm/s) with maximal velocity agreeing with echocardiography. CONCLUSION: Automated valve-tracking 2D PC is a feasible route toward evaluation of tricuspid regurgitant velocities, potentially solving a major clinical challenge.

Constrained alternating minimization for parameter mapping (CAMP).

OBJECTIVE: To improve image quality in highly accelerated parameter mapping by incorporating a linear constraint that relates consecutive images. APPROACH: In multi-echo T1 or T2 mapping, scan time is often shortened by acquiring undersampled but complementary measures of k-space at each TE or TI. However, residual undersampling artifacts from the individual images can then degrade the quality of the final parameter maps. In this work, a new reconstruction method, dubbed Constrained Alternating Minimization for Parameter mapping (CAMP), is introduced. This method simultaneously extracts T2 or T1* maps in addition to an image for each TE or TI from accelerated datasets, leveraging the constraints of the decay to improve the reconstructed image quality. The model enforces exponential decay through a linear constraint, resulting in a biconvex objective function that lends itself to alternating minimization. The method was tested in four in vivo volunteer experiments and validated in phantom studies and healthy subjects, using T2 and T1 mapping, with accelerations of up to 12. MAIN RESULTS: CAMP is demonstrated for accelerated radial and Cartesian acquisitions in T2 and T1 mapping. The method is even applied to generate an entire T2 weighted image series from a single TSE dataset, despite the blockwise k-space sampling at each echo time. Experimental undersampled phantom and in vivo results processed with CAMP exhibit reduced artifacts without introducing bias. SIGNIFICANCE: For a wide array of applications, CAMP linearizes the model cost function without sacrificing model accuracy so that the well-conditioned and highly efficient reconstruction algorithm improves the image quality of accelerated parameter maps.

Clinical physiology: the crucial role of MRI in evaluation of peripheral artery disease.

Peripheral artery disease (PAD) is a common vascular disease that primarily affects the lower limbs and is defined by the constriction or blockage of peripheral arteries and may involve microvascular dysfunction and tissue injury. Patients with diabetes have more prominent disease of microcirculation and develop peripheral neuropathy, autonomic dysfunction, and medial vascular calcification. Early and accurate diagnosis of PAD and disease characterization are essential for personalized management and therapy planning. Magnetic resonance imaging (MRI) provides excellent soft tissue contrast and multiplanar imaging capabilities and is useful as a noninvasive imaging tool in the comprehensive physiological assessment of PAD. This review provides an overview of the current state of the art of MRI in the evaluation and characterization of PAD, including an analysis of the many applicable MR imaging techniques, describing the advantages and disadvantages of each approach. We also present recent developments, future clinical applications, and future MRI directions in assessing PAD. The development of new MR imaging technologies and applications in preclinical models with translation to clinical research holds considerable potential for improving the understanding of the pathophysiology of PAD and clinical applications for improving diagnostic precision, risk stratification, and treatment outcomes in patients with PAD.

The future of CMR: All-in-one vs. real-time CMR (Part 2).

Cardiac Magnetic Resonance (CMR) protocols can be lengthy and complex, which has driven the research community to develop new technologies to make these protocols more efficient and patient-friendly. Two different approaches to improving CMR have been proposed, specifically "all-in-one" CMR, where several contrasts and/or motion states are acquired simultaneously, and "real-time" CMR, in which the examination is accelerated to avoid the need for breathholding and/or cardiac gating. The goal of this two-part manuscript is to describe these two different types of emerging rapid CMR protocols. To this end, the vision of all-in-one and real-time imaging are described, along with techniques which have been devised and tested along the pathway of clinical implementation. The pros and cons of the different methods are presented, and the remaining open needs of each are detailed. Part 1 tackles the "All-in-One" approaches, and Part 2 focuses on the "Real-Time" approaches along with an overall summary of these emerging methods.

K-t PCA accelerated in-plane balanced steady-state free precession phase-contrast (PC-SSFP) for all-in-one diastolic function evaluation.

PURPOSE: Diastolic function evaluation requires estimates of early and late diastolic mitral filling velocities (E and A) and of mitral annulus tissue velocity (e'). We aimed to develop an MRI method for simultaneous all-in-one diastolic function evaluation in a single scan by generating a 2D phase-contrast (PC) sequence with balanced steady-state free precession (bSSFP) contrast (PC-SSFP). E and A could then be measured with PC, and e' estimated by valve tracking on the magnitude images, using an established deep learning framework. METHODS: Our PC-SSFP used in-plane flow-encoding, with zeroth and first moment nulling over each TR. For further acceleration, different k-t principal component analysis (PCA) methods were investigated with both retrospective and prospective undersampling. PC-SSFP was compared to separate balanced SSFP cine and PC-gradient echo acquisitions in phantoms and in 10 healthy subjects. RESULTS: Phantom experiments showed that PC-SSFP measured accurate velocities compared to PC-gradient echo (r = 0.98 for a range of pixel-wise velocities -80 cm/s to 80 cm/s). In subjects, PC-SSFP generated high SNR and myocardium-blood contrast, and excellent agreement for E (limits of agreement [LOA] 0.8 ± 2.4 cm/s, r = 0.98), A (LOA 2.5 ± 4.1 cm/s, r = 0.97), and e' (LOA 0.3 ± 2.6 cm/s, r = 1.00), versus the standard methods. The best k-t PCA approach processed the complex difference data and substituted in raw k-space data. With prospective k-t PCA acceleration, higher frame rates were achieved (50 vs. 25 frames per second without k-t PCA), yielding a 13% higher e'. CONCLUSION: The proposed PC-SSFP method achieved all-in-one diastolic function evaluation.

Atrial fibrosis by cardiac MRI is a correlate for atrial stiffness in patients with atrial fibrillation.

A relationship between left atrial strain and pressure has been demonstrated in many studies, but not in an atrial fibrillation (AF) cohort. In this work, we hypothesized that elevated left atrial (LA) tissue fibrosis might mediate and confound the LA strain vs. pressure relationship, resulting instead in a relationship between LA fibrosis and stiffness index (mean LA pressure/LA reservoir strain). Sixty-seven patients with AF underwent a standard cardiac MR exam including long-axis cine views (2 and 4-ch) and a free-breathing high resolution three-dimensional late gadolinium enhancement (LGE) of the atrium (N = 41), within 30 days prior to AF ablation, at which procedure invasive mean left atrial pressure (LAP) was measured. LV and LA Volumes, EF, and comprehensive analysis of LA strains (strain and strain rates and strain timings during the atrial reservoir, conduit and active, i.e. active atrial contraction, phases) were measured and LA fibrosis content (LGE (ml)) was assessed from 3D LGE volumes. LA LGE was well correlated to atrial stiffness index overall (R = 0.59, p < 0.001), and among patient subgroups. Pressure was only correlated to maximal LA volume (R = 0.32) and the time to peak reservoir strain rate (R = 0.32) (both p < 0.01), among all functional measurements. LA reservoir strain was strongly correlated with LAEF (R = 0.95, p < 0.001) and LA minimum volume (r = 0.82, p < 0.001). In our AF cohort, pressure is correlated to maximum LA volume and time to peak reservoir strain. LA pressure/ LA reservoir strain, a metric of stiffness, correlates with LA fibrosis (LA LGE), reflecting Hook's Law.

High-sensitivity deuterium metabolic MRI differentiates acute pancreatitis from pancreatic cancers in murine models.

Deuterium metabolic imaging (DMI) is a promising tool for investigating a tumor's biology, and eventually contribute in cancer diagnosis and prognosis. In DMI, [6,6'-2H2]-glucose is taken up and metabolized by different tissues, resulting in the formation of HDO but also in an enhanced formation of [3,3'-2H2]-lactate at the tumor site as a result of the Warburg effect. Recent studies have shown DMI's suitability to highlight pancreatic cancer in murine models by [3,3'-2H2]-lactate formation; an important question is whether DMI can also differentiate between these tumors and pancreatitis. This differentiation is critical, as these two diseases are hard to distinguish today radiologically, but have very different prognoses requiring distinctive treatments. Recent studies have shown the limitations that hyperpolarized MRI faces when trying to distinguish these pancreatic diseases by monitoring the [1-13C1]-pyruvate→[1-13C1]-lactate conversion. In this work, we explore DMI's capability to achieve such differentiation. Initial tests used a multi-echo (ME) SSFP sequence, to identify any metabolic differences between tumor and acute pancreatitis models that had been previously elicited very similar [1-13C1]-pyruvate→[1-13C1]-lactate conversion rates. Although ME-SSFP provides approximately 5 times greater signal-to-noise ratio (SNR) than the standard chemical shift imaging (CSI) experiment used in DMI, no lactate signal was observed in the pancreatitis model. To enhance lactate sensitivity further, we developed a new, weighted-average, CSI-SSFP approach for DMI. Weighted-average CSI-SSFP improved DMI's SNR by another factor of 4 over ME-SSFP-a sensitivity enhancement that sufficed to evidence natural abundance 2H fat in abdominal images, something that had escaped the previous approaches even at ultrahigh (15.2 T) MRI fields. Despite these efforts to enhance DMI's sensitivity, no lactate signal could be detected in acute pancreatitis models (n = 10; [3,3'-2H2]-lactate limit of detection < 100 µM; 15.2 T). This leads to the conclusion that pancreatic tumors and acute pancreatitis may be clearly distinguished by DMI, based on their different abilities to generate deuterated lactate.

Deuterium imaging of the Warburg effect at sub-millimolar concentrations by joint processing of the kinetic and spectral dimensions.

Deuterium metabolic imaging (DMI) is a promising molecular MRI approach, which follows the administration of deuterated substrates and their metabolization. [6,6'-2 H2 ]-glucose for instance is preferentially converted in tumors to [3,3'-2 H2 ]-lactate as a result of the Warburg effect, providing a distinct resonance whose mapping using time-resolved spectroscopic imaging can diagnose cancer. The MR detection of low-concentration metabolites such as lactate, however, is challenging. It has been recently shown that multi-echo balanced steady-state free precession (ME-bSSFP) increases the signal-to-noise ratio (SNR) of these experiments approximately threefold over regular chemical shift imaging; the present study examines how DMI's sensitivity can be increased further by advanced processing methods. Some of these, such as compressed sensing multiplicative denoising and block-matching/3D filtering, can be applied to any spectroscopic/imaging methods. Sensitivity-enhancing approaches were also specifically tailored to ME-bSSFP DMI, by relying on priors related to the resonances' positions and to features of the metabolic kinetics. Two new methods are thus proposed that use these constraints for enhancing the sensitivity of both the spectral images and the metabolic kinetics. The ability of these methods to improve DMI is evidenced in pancreatic cancer studies carried at 15.2 T, where suitable implementations of the proposals imparted eightfold or more SNR improvement over the original ME-bSSFP data, at no informational cost. Comparisons with other propositions in the literature are briefly discussed.

Atrial Fibrosis by cardiac MRI is a correlate for atrial stiffness in patients with atrial fibrillation.

Aims: A relationship between left atrial strain and pressure has been demonstrated in many studies, but not in an atrial fibrillation (AF) cohort. In this work, we hypothesized that elevated left atrial (LA) tissue fibrosis might mediate and confound the LA strain vs. pressure relationship, resulting instead in a relationship between LA fibrosis and stiffness index (mean pressure/LA reservoir strain). Methods and Results: Sixty-seven patients with AF underwent a standard cardiac MR exam including long-axis cine views (2 and 4-ch) and a free-breathing high resolution three-dimensional late gadolinium enhancement (LGE) of the atrium (N=41), within 30 days prior to AF ablation, at which procedure invasive mean left atrial pressure (LAP) was measured. LV and LA Volumes, EF, and comprehensive analysis of LA strains (strain and strain rates and strain timings during the atrial reservoir, conduit and active phases) were measured and LA fibrosis content (LGE (ml)) was assessed from 3D LGE volumes. LA LGE was well correlated to atrial stiffness index (LA mean pressure/LA reservoir strain) overall (R=0.59, p<0.001), and among patient subgroups. Pressure was only correlated to maximal LA volume (R=0.32) and the time to peak reservoir strain rate (R=0.32), among all functional measurements. LA reservoir strain was strongly correlated with LAEF (R=0.95, p<0.001) and LA minimum volume (r=0.82, p<0.001). Conclusion: In our AF cohort, pressure is correlated to maximum LA volume and time to peak reservoir strain. LA LGE is a strong marker of stiffness.

Impaired left-ventricular global longitudinal strain by feature-tracking cardiac MRI predicts mortality in systemic sclerosis.

Impaired left-ventricular (LV) and right-ventricular (RV) cardiac magnetic resonance (CMR) strain has been documented in systemic sclerosis (SSc). However, it is unknown whether the CMR strain is predictive of adverse outcomes in SSc. Therefore, we set out to investigate the prognostic value of CMR strain in SSc. Patients with SSc who underwent CMR for clinical indications between 11/2010 and 07/2020 were retrospectively studied. LV and RV strain was evaluated by feature tracking. The association between strain, late gadolinium enhancement (LGE), and survival was evaluated with time to event and Cox-regression analyses. During the study period, 42 patients with SSc (age: 57 ± 14 years, 83% female, 57% limited cutaneous SSc, SSc duration: 7 ± 8 years) underwent CMR. During the median follow-up of 3.6 years, 11 patients died (26%). Compared to surviving patients, patients who died had significantly worse LV GLS (- 8.2 ± 6.2% versus - 12.1 ± 2.9%, p = 0.03), but no difference in LV global radial, circumferential, or RV strain values. Patients within the quartile of most impaired LV GLS (≥ - 12.8%, n = 10) had worse survival when compared to patients with preserved LV GLS (< - 12.8%, n = 32, log-rank p = 0.02), which persisted after controlling for LV cardiac output, LV cardiac index, reduced LV ejection fraction, or presence of LGE. In addition, patients who had both impaired LV GLS and LGE (n = 5) had worse survival than patients with LGE or impaired GLS alone (n = 14) and compared to those without any of these features (n = 17, p = 0.003). In our retrospective cohort of patients with SSc undergoing CMR for clinical indications, LV GLS and LGE were found to be predictive of overall survival.

Balanced Steady-State Free Precession Cine MR Imaging in the Presence of Cardiac Devices: Value of Interleaved Radial Linear Combination Acquisition With Partial Dephasing.

BACKGROUND: Balanced steady-state free precession (bSSFP) is important in cardiac MRI but suffers from off-resonance artifacts. The interpretation-limiting artifacts in patients with cardiac implants remain an unsolved issue. PURPOSE: To develop an interleaved radial linear combination bSSFP (lcSSFP) method with partial dephasing (PD) for improved cardiac cine imaging when implanted cardiovascular devices are present. STUDY TYPE: Prospective. PHANTOM AND SUBJECTS: Flow phantom adjacent to a pacemaker and 10 healthy volunteers (mean age ± standard deviation: 31.9 ± 2.9 years, 4 females) with a cardioverter-defibrillator (ICD) positioned extracorporeally at the left chest in the prepectoral region. FIELD STRENGTH/SEQUENCE: A 3-T, 1) Cartesian bSSFP, 2) Cartesian gradient echo (GRE), 3) Cartesian lcSSFP, and 4) radial lcSSFP cine sequences. ASSESSMENT: Flow artifacts mitigation using PD was validated with phantom experiments. Undersampled radial lcSSFP with interleaving across phase-cyclings and cardiac phases (RLC-SSFP), combined with PD, was then employed for achieving improved quality of cine images from left ventricular short-axis view. The image quality in the presence of cardiac devices was qualitatively assessed by three independent raters (1 = worst, 5 = best), regarding five criteria (banding artifacts, streak artifacts, flow artifacts, cavity visibility, and overall image quality). STATISTICAL TESTS: Wilcoxon rank-sum test for the five criteria between Cartesian bSSFP cine and RLC-SSFP with PD. Fleiss kappa test for inter-reader agreement. A P value < 0.05 was considered statistically significant. RESULTS: Based on simulations and phantom experiments, 60 projections per phase cycling and 1/6 PD were chosen. The in vivo experiments demonstrated significantly reduced banding artifacts (4.8 ± 0.4 vs. 2.7 ± 0.7), fewer streak artifacts (3.7 ± 0.6 vs. 2.6 ± 0.7) and flow artifacts (4.4 ± 0.4 vs. 3.7 ± 0.6), therefore improved cavity visibility (4.1 ± 0.4 vs. 2.9 ± 0.9) and overall quality (4.0 ± 0.4 vs. 2.7 ± 0.7). DATA CONCLUSION: RLC-SSFP method with PD may improve cine image quality in subjects with cardiac devices. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.

MVnet: automated time-resolved tracking of the mitral valve plane in CMR long-axis cine images with residual neural networks: a multi-center, multi-vendor study.

BACKGROUND: Mitral annular plane systolic excursion (MAPSE) and left ventricular (LV) early diastolic velocity (e') are key metrics of systolic and diastolic function, but not often measured by cardiovascular magnetic resonance (CMR). Its derivation is possible with manual, precise annotation of the mitral valve (MV) insertion points along the cardiac cycle in both two and four-chamber long-axis cines, but this process is highly time-consuming, laborious, and prone to errors. A fully automated, consistent, fast, and accurate method for MV plane tracking is lacking. In this study, we propose MVnet, a deep learning approach for MV point localization and tracking capable of deriving such clinical metrics comparable to human expert-level performance, and validated it in a multi-vendor, multi-center clinical population. METHODS: The proposed pipeline first performs a coarse MV point annotation in a given cine accurately enough to apply an automated linear transformation task, which standardizes the size, cropping, resolution, and heart orientation, and second, tracks the MV points with high accuracy. The model was trained and evaluated on 38,854 cine images from 703 patients with diverse cardiovascular conditions, scanned on equipment from 3 main vendors, 16 centers, and 7 countries, and manually annotated by 10 observers. Agreement was assessed by the intra-class correlation coefficient (ICC) for both clinical metrics and by the distance error in the MV plane displacement. For inter-observer variability analysis, an additional pair of observers performed manual annotations in a randomly chosen set of 50 patients. RESULTS: MVnet achieved a fast segmentation (<1 s/cine) with excellent ICCs of 0.94 (MAPSE) and 0.93 (LV e') and a MV plane tracking error of -0.10 ± 0.97 mm. In a similar manner, the inter-observer variability analysis yielded ICCs of 0.95 and 0.89 and a tracking error of -0.15 ± 1.18 mm, respectively. CONCLUSION: A dual-stage deep learning approach for automated annotation of MV points for systolic and diastolic evaluation in CMR long-axis cine images was developed. The method is able to carefully track these points with high accuracy and in a timely manner. This will improve the feasibility of CMR methods which rely on valve tracking and increase their utility in a clinical setting.

Left atrial evaluation by cardiovascular magnetic resonance: sensitive and unique biomarkers.

Left atrial (LA) imaging is still not routinely used for diagnosis and risk stratification, although recent studies have emphasized its importance as an imaging biomarker. Cardiovascular magnetic resonance is able to evaluate LA structure and function, metrics that serve as early indicators of disease, and provide prognostic information, e.g. regarding diastolic dysfunction, and atrial fibrillation (AF). MR angiography defines atrial anatomy, useful for planning ablation procedures, and also for characterizing atrial shapes and sizes that might predict cardiovascular events, e.g. stroke. Long-axis cine images can be evaluated to define minimum, maximum, and pre-atrial contraction LA volumes, and ejection fractions (EFs). More modern feature tracking of these cine images provides longitudinal LA strain through the cardiac cycle, and strain rates. Strain may be a more sensitive marker than EF and can predict post-operative AF, AF recurrence after ablation, outcomes in hypertrophic cardiomyopathy, stratification of diastolic dysfunction, and strain correlates with atrial fibrosis. Using high-resolution late gadolinium enhancement (LGE), the extent of fibrosis in the LA can be estimated and post-ablation scar can be evaluated. The LA LGE method is widely available, its reproducibility is good, and validations with voltage-mapping exist, although further scan-rescan studies are needed, and consensus regarding atrial segmentation is lacking. Using LGE, scar patterns after ablation in AF subjects can be reproducibly defined. Evaluation of 'pre-existent' atrial fibrosis may have roles in predicting AF recurrence after ablation, predicting new-onset AF and diastolic dysfunction in patients without AF. LA imaging biomarkers are ready to enter into diagnostic clinical practice.

Improving deuterium metabolic imaging (DMI) signal-to-noise ratio by spectroscopic multi-echo bSSFP: A pancreatic cancer investigation.

PURPOSE: Deuterium metabolic imaging (DMI) maps the uptake of deuterated precursors and their conversion into lactate and other markers of tumor metabolism. Even after leveraging 2 H's short T1 s, DMI's signal-to-noise ratio (SNR) is limited. We hypothesize that a multi-echo balanced steady-state free precession (ME-bSSFP) approach would increase SNR compared to chemical shift imaging (CSI), while achieving spectral isolation of the metabolic precursors and products. METHODS: Suitably tuned 2 H ME-bSSFP (five echo times [TEs], ΔTE = 2.2 ms, repetition time [TR]/flip-angle = 12 ms/60°) was implemented at 15.2T and compared to CSI (TR/flip-angle = 95 ms/90°) regarding SNR and spectral isolation, in simulations, in deuterated phantoms and for the in vivo diagnosis of a mouse tumor model of pancreatic adenocarcinoma (N = 10). RESULTS: Simulations predicted an SNR increase vs. CSI of 3-5, and that the peaks of 2 H-water, 2 H6,6' -glucose, and 2 H3,3' -lactate can be well isolated by ME-bSSFP; phantoms confirmed this. In vivo, at equal spatial resolution (1.25 × 1.25 mm2 ) and scan time (10 min), 2 H6,6' -glucose's and 2 H3,3' -lactate's SNR were indeed higher for bSSFP than for CSI, three-fold for glucose (57 ± 30 vs. 19 ± 11, P < .001), doubled for water (13 ± 5 vs. 7 ± 3, P = .005). The time courses and overall localization of all metabolites agreed well, comparing CSI against ME-bSSFP. However, a clearer localization of glucose in kidneys and bladder, the detection of glucose-avid rims in certain tumors, and a heterogeneous pattern of intra-tumor lactate production could only be observed using ME-bSSFP's higher resolution. CONCLUSIONS: ME-bSSFP provides greater SNR per unit time than CSI, providing for higher spatial resolution mapping of glucose uptake and lactate production in tumors.

Automated left atrial time-resolved segmentation in MRI long-axis cine images using active contours.

BACKGROUND: Segmentation of the left atrium (LA) is required to evaluate atrial size and function, which are important imaging biomarkers for a wide range of cardiovascular conditions, such as atrial fibrillation, stroke, and diastolic dysfunction. LA segmentations are currently being performed manually, which is time-consuming and observer-dependent. METHODS: This study presents an automated image processing algorithm for time-resolved LA segmentation in cardiac magnetic resonance imaging (MRI) long-axis cine images of the 2-chamber (2ch) and 4-chamber (4ch) views using active contours. The proposed algorithm combines mitral valve tracking, automated threshold calculation, edge detection on a radially resampled image, edge tracking based on Dijkstra's algorithm, and post-processing involving smoothing and interpolation. The algorithm was evaluated in 37 patients diagnosed mainly with paroxysmal atrial fibrillation. Segmentation accuracy was assessed using the Dice similarity coefficient (DSC) and Hausdorff distance (HD), with manual segmentations in all time frames as the reference standard. For inter-observer variability analysis, a second observer performed manual segmentations at end-diastole and end-systole on all subjects. RESULTS: The proposed automated method achieved high performance in segmenting the LA in long-axis cine sequences, with a DSC of 0.96 for 2ch and 0.95 for 4ch, and an HD of 5.5 mm for 2ch and 6.4 mm for 4ch. The manual inter-observer variability analysis had an average DSC of 0.95 and an average HD of 4.9 mm. CONCLUSION: The proposed automated method achieved performance on par with human experts analyzing MRI images for evaluation of atrial size and function. Video Abstract.

Left ventricular myocardial strain and tissue characterization by cardiac magnetic resonance imaging in immune checkpoint inhibitor associated cardiotoxicity.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. METHODS: We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. RESULTS: Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of -9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at -12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = -0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = -0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. CONCLUSION: In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.

Idarubicin-Loaded ONCOZENE Drug-Eluting Bead Chemoembolization in a Rabbit Liver Tumor Model: Investigating Safety, Therapeutic Efficacy, and Effects on Tumor Microenvironment.

PURPOSE: To investigate toxicity, efficacy, and microenvironmental effects of idarubicin-loaded 40-µm and 100-µm drug-eluting embolic (DEE) transarterial chemoembolization in a rabbit liver tumor model. MATERIALS AND METHODS: Twelve male New Zealand White rabbits with orthotopically implanted VX2 liver tumors were assigned to DEE chemoembolization with 40-µm (n = 5) or 100-µm (n = 4) ONCOZENE microspheres or no treatment (control; n = 3). At 24-72 hours postprocedurally, multiparametric magnetic resonance (MR) imaging including dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), and biosensor imaging of redundant deviation in shifts (BIRDS) was performed to assess extracellular pH (pHe), followed by immediate euthanasia. Laboratory parameters and histopathologic ex vivo analysis included fluorescence confocal microscopy and immunohistochemistry. RESULTS: DCE MR imaging demonstrated a similar degree of devascularization of embolized tumors for both microsphere sizes (mean arterial enhancement, 8% ± 12 vs 36% ± 51 in controls; P = .07). Similarly, DWI showed postprocedural increases in diffusion across the entire lesion (apparent diffusion coefficient, 1.89 × 10-3 mm2/s ± 0.18 vs 2.34 × 10-3 mm2/s ± 0.18 in liver; P = .002). BIRDS demonstrated profound tumor acidosis at baseline (mean pHe, 6.79 ± 0.08 in tumor vs 7.13 ± 0.08 in liver; P = .02) and after chemoembolization (6.8 ± 0.06 in tumor vs 7.1 ± 0.04 in liver; P = .007). Laboratory and ex vivo analyses showed central tumor core penetration and greater increase in liver enzymes for 40-µm vs 100-µm microspheres. Inhibition of cell proliferation, intratumoral hypoxia, and limited idarubicin elution were equally observed with both sphere sizes. CONCLUSIONS: Noninvasive multiparametric MR imaging visualized chemoembolic effects in tumor and tumor microenvironment following DEE chemoembolization. Devascularization, increased hypoxia, coagulative necrosis, tumor acidosis, and limited idarubicin elution suggest ischemia as the predominant therapeutic mechanism. Substantial size-dependent differences indicate greater toxicity with the smaller microsphere diameter.

Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders.

OBJECTIVES: The authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population. BACKGROUND: LA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown. METHODS: Cardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. RESULTS: Patients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm2 increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm2 increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. CONCLUSIONS: Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450).

Interleaved, undersampled radial multiple-acquisition steady-state free precession for improved left atrial cine imaging.

PURPOSE: Balanced steady-state free precession (bSSFP) left atrial (LA) cine suffers from off-resonance artifacts, particularly in the pulmonary veins (PVs). Linear combination or multiple-acquisition SSFP (MA-SSFP) effectively removes banding but greatly increases scan time. We hypothesized that MA-SSFP with interleaved radial undersampling, where each phase-cycling is acquired with an interleaved set of radial projections, would improve image quality of LA cine with a small increase of scan time and streak artefacts. METHODS: Undersampled radial MA-SSFP with and without interleaving was compared with fully sampled radial bSSFP by means of simulations, phantoms, and in vivo imaging. Ten healthy subjects were imaged on a 3T scanner, with bSSFP and MA-SSFP cine of the left atrium, and B0-mapping. Images were assessed (1 = worst, 5 = best) by 2 independent readers, with respect to 5 qualitative criteria and apparent signal-to-noise ratio. RESULTS: In healthy subjects, off-resonance differed from the right inferior PVs to the LA cavity by 163 Hz ± 73 Hz at 3T. Compared with fully sampled radial bSSFP, interleaved radial MA-SSFP significantly improved image quality with respect to off-resonance artifacts (3.8 ± 0.6 versus 2.3 ± 1.0; P = 0.005), PV conspicuity (2.8 ± 1.0 versus 4.3 ± 0.5; P = 0.005), and the number of visualized PVs (1.7 ± 0.4 versus 0.9 ± 0.7; P = 0.008), although with greater streak artifacts (3.4 ± 0.4 versus 4.9 ± 0.2; P = 0.004) and lower measured apparent signal-to-noise ratio (24 ± 9 versus 69 ± 36; P = 0.002). Flow artifacts were similar. Interleaved radial MA-SSFP reduced streaking artifacts and increased apparent signal-to-noise ratio versus noninterleaved radial. CONCLUSIONS: Interleaved radial MA-SSFP cine reduces banding artifacts with an acceptable increase of scan time and streak artifacts. The proposed technique improves the LA and PV visualization in bSSFP cine imaging.