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.

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.

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.

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.

The future of cardiovascular magnetic resonance: All-in-one vs. real-time (Part 1).

Cardiovascular 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. To this end, the vision of each is 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 will tackle the "all-in-one" approaches, and Part 2 the "real-time" approaches along with an overall summary of these emerging methods.

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.

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.

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.

The Cost of Operating Sexual Health Clinics During the Ending the (HIV) Epidemic Initiative in New York City.

BACKGROUND: As part of New York State's Ending the Epidemic (EtE) initiative, sexual health clinics (SHCs) in New York City invested in clinic enhancements and expanded their HIV-related services to increase access to HIV prevention interventions and treatment. The objective of this study was to estimate and describe the change in SHC operating costs related to clinic enhancements and expanded patient services implemented as part of the EtE initiative. METHODS: A comprehensive microcosting approach was used to collect retrospective cost information from SHCs, broken down by category and programmatic activity. Cost information was collected from 8 clinics across New York City during two 6-month time periods before (2015) and during (2018-2019) EtE. RESULTS: Eight SHCs reported comprehensive cost data. Costs increased by $800,000 on average per clinic during the 6-month EtE period. The cost per visit at an SHC increased by $120 on average to $381 (ranging from $302 to $464) during the EtE period. Personnel costs accounted for 69.9% of EtE costs, and HIV-related medications accounted for 8.9% of costs. Employment of social workers and patient navigators increased costs by approximately $150,000 on average per clinic. Postexposure prophylaxis was the costliest medication with average expenditures of $103,800 per clinic. CONCLUSIONS: This study demonstrates the key drivers of cost increases when offering enhanced HIV services in SHCs. Documenting the changes in resources necessary to implement these services and their costs can inform other health departments on the viability of offering enhanced HIV services within their own clinics.

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.

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.

FDG PET imaging of vascular inflammation in post-traumatic stress disorder: A pilot case-control study.

The prevalence of cardiovascular diseases (CVD) is increased in subjects with post-traumatic stress disorder (PTSD). Vascular inflammation mediates CVD and may be assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging. In this pilot study, we investigated whether subjects with PTSD have enhanced vascular and systemic inflammation compared to healthy controls, as assessed by FDG PET imaging. METHODS: A prospective group of 16 subjects (9 PTSD and 7 controls, age 34 ± 7) without prior history of CVD underwent FDG PET/CT imaging. The presence of PTSD symptoms at the time of the study was confirmed using PTSD checklist for DSM-5 (PCL5) questionnaire. Blood samples were collected to determine blood glucose, lipid and inflammatory biomarkers (tumor necrosis factor α, interleukin-1ß, and interleukin-6) levels. FDG signal in the ascending aorta, amygdala, spleen and bone marrow was quantified. RESULTS: The two groups matched closely with regards to cardiovascular risk factors. The inflammatory biomarkers were all within the normal range. There was no significant difference in FDG signal in the aorta (target to background ratio: 2.40 ± 0.29 and 2.34 ± 0.29 for control and PTSD subjects, difference: - 0.06, 95% confidence interval of difference: - 0.38 to 0.26), spleen, bone marrow, or amygdala between control and PTSD subjects. There was no significant correlation between aortic and amygdala FDG signal. However, a significant positive correlation existed between amygdala, splenic, and bone marrow FDG signal. CONCLUSION: This pilot, small study did not reveal any difference in vascular or systemic inflammation as assessed by FDG PET imaging between PTSD and healthy control subjects. Because of the small number of subjects, a modest increase in vascular inflammation, which requires larger scale studies to establish, cannot be excluded. The correlation between FDG signal in amygdala, spleen and bone marrow may reflect a link between amygdala activity and systemic inflammation.

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.

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.

Extracellular pH mapping of liver cancer on a clinical 3T MRI scanner.

PURPOSE: To demonstrate feasibility of developing a noninvasive extracellular pH (pHe ) mapping method on a clinical MRI scanner for molecular imaging of liver cancer. METHODS: In vivo pHe mapping has been demonstrated on preclinical scanners (e.g., 9.4T, 11.7T) with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), where the pHe readout by 3D chemical shift imaging (CSI) depends on hyperfine shifts emanating from paramagnetic macrocyclic chelates like TmDOTP5- which upon extravasation from blood resides in the extracellular space. We implemented BIRDS-based pHe mapping on a clinical 3T Siemens scanner, where typically diamagnetic 1 H signals are detected using millisecond-long radiofrequency (RF) pulses, and 1 H shifts span over ±10 ppm with long transverse (T2 , 102 ms) and longitudinal (T1 , 103 ms) relaxation times. We modified this 3D-CSI method for ultra-fast acquisition with microsecond-long RF pulses, because even at 3T the paramagnetic 1 H shifts of TmDOTP5- have millisecond-long T2 and T1 and ultra-wide chemical shifts (±200 ppm) as previously observed in ultra-high magnetic fields. RESULTS: We validated BIRDS-based pH in vitro with a pH electrode. We measured pHe in a rabbit model for liver cancer using VX2 tumors, which are highly vascularized and hyperglycolytic. Compared to intratumoral pHe (6.8 ± 0.1; P < 10-9 ) and tumor's edge pHe (6.9 ± 0.1; P < 10-7 ), liver parenchyma pHe was significantly higher (7.2 ± 0.1). Tumor localization was confirmed with histopathological markers of necrosis (hematoxylin and eosin), glucose uptake (glucose transporter 1), and tissue acidosis (lysosome-associated membrane protein 2). CONCLUSION: This work demonstrates feasibility and potential clinical translatability of high-resolution pHe mapping to monitor tumor aggressiveness and therapeutic outcome, all to improve personalized cancer treatment planning.

Valvular imaging in the era of feature-tracking: A slice-following cardiac MR sequence to measure mitral flow.

BACKGROUND: In mitral valve dysfunction, noninvasive measurement of transmitral blood flow is an important clinical examination. Flow imaging of the mitral valve, however, is challenging, since it moves in and out of the image plane during the cardiac cycle. PURPOSE: To more accurately measure mitral flow, a slice-following MRI phase contrast sequence is proposed. This study aimed to implement such a sequence, validate its slice-following functionality in a phantom and healthy subjects, and test its feasibility in patients with mitral valve dysfunction. STUDY TYPE: Prospective. PHANTOM AND SUBJECTS: The slice-following functionality was validated in a cone-shaped phantom by measuring the depicted slice radius. Sixteen healthy subjects and 10 mitral valve dysfunction patients were enrolled at two sites. FIELD STRENGTH/SEQUENCE: 1.5T and 3T gradient echo cine phase contrast. ASSESSMENT: A single breath-hold retrospectively gated sequence using offline feature-tracking of the mitral valve was developed. Valve displacements were measured and imported to the scanner, allowing the slice position to change dynamically based on the cardiac phase. Mitral valve imaging was performed with slice-following and static imaging planes. Validation was performed by comparing mitral stroke volume with planimetric and aortic stroke volume. STATISTICAL TESTS: Measurements were compared using linear regression, Pearson's R, parametric paired t-tests, Bland-Altman analysis, and intraclass correlation coefficient (ICC). RESULTS: Phantom experiments confirmed accurate slice displacements. Slice-following was feasible in all subjects, yielding physiologically accurate mitral flow patterns. In healthy subjects, mitral and aortic stroke volumes agreed, with ICC = 0.72 and 0.90 for static and slice-following planes; with bias ±1 SDs 23.2 ± 13.2 mls and 8.4 ± 10.8 mls, respectively. Agreement with planimetry was stronger, with ICC = 0.84 and 0.96; bias ±1 SDs 13.7 ± 13.7 mls and -2.0 ± 8.8 mls for static and slice-following planes, respectively. DATA CONCLUSION: Slice-following outperformed the conventional sequence and improved the accuracy of transmitral flow, which is important for assessment of diastolic function and mitral regurgitation. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1412-1421.

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.

SUPER: A blockwise curve-fitting method for accelerating MR parametric mapping with fast reconstruction.

PURPOSE: To investigate Shift Undersampling improves Parametric mapping Efficiency and Resolution (SUPER), a novel blockwise curve-fitting method for accelerating parametric mapping with very fast reconstruction. METHODS: SUPER uses interleaved k-space undersampling, which enables a blockwise decomposition of the otherwise large-scale cost function to improve the reconstruction efficiency. SUPER can be readily combined with SENSE to achieve at least 4-fold acceleration. D-factor, a parametric-mapping counterpart of g-factor, was proposed and formulated to compare spatially heterogeneous noise amplification because of different acceleration methods. As a proof-of-concept, SUPER/SUPER-SENSE was validated using T1 mapping, by comparing them to alternative model-based methods, including MARTINI and GRAPPATINI, via simulations, phantom imaging, and in vivo brain imaging (N = 5), over criteria of normalized root-mean-squares error (NRMSE), average d-factor, and computational time per voxel (TPV). A novel SUPER-SENSE MOLLI cardiac T1 -mapping sequence with improved resolution (1.4 mm × 1.4 mm) was compared to standard MOLLI (1.9 mm × 2.5 mm) in 8 healthy subjects. RESULTS: In brain imaging, 2-fold SUPER achieved lower NRMSE (0.04 ± 0.02 vs. 0.11 ± 0.02, P < 0.01), lower average d-factor (1.01 ± 0.002 vs. 1.12 ± 0.004, P < 0.001), and lower TPV (4.6 ms ± 0.2 ms vs. 79 ms ± 3 ms, P < 0.001) than 2-fold MARTINI. Similarly, 4-fold SUPER-SENSE achieved lower NRMSE (0.07 ± 0.01 vs. 0.13 ± 0.03, P = 0.02), lower average d-factor (1.15 ± 0.01 vs. 1.20 ± 0.01, P < 0.001), and lower TPV (4.0 ms ± 0.1 ms vs. 72 ms ± 3 ms, P < 0.001) than 4-fold GRAPPATINI. In cardiac T1 mapping, SUPER-SENSE MOLLI yielded similar myocardial T1 (1151 ms ± 63 ms vs. 1159 ms ± 32 ms, P = 0.6), slightly lower blood T1 (1643 ms ± 86 ms vs. 1680 ms ± 79 ms, P = 0.004), but improved spatial resolution compared with standard MOLLI in the same imaging time. CONCLUSION: SUPER and SUPER-SENSE provide fast model-based reconstruction methods for accelerating parametric mapping and improving its clinical appeal.

Dynamic-flip-angle ECG-gating with nuisance signal regression improves resting-state BOLD functional connectivity mapping by reducing cardiogenic noise.

PURPOSE: To investigate an ECG-gated dynamic-flip-angle BOLD sequence with improved robustness against cardiogenic noise in resting-state fMRI. METHODS: ECG-gating minimizes the cardiogenic noise but introduces T1 -dependent signal variation, which is minimized by combination of a dynamic-flip-angle technique and retrospective nuisance signal regression (NSR) using signals of white matter, CSF, and global average. The technique was studied with simulations in a wide range of T1 and B1 fields and phantom imaging with pre-programmed TR variations. Resting-state fMRI of 20 healthy subjects was acquired with non-gated BOLD (NG), ECG-gated constant-flip-angle BOLD (GCFA), ECG-gated BOLD with retrospective T1 -correction (GRC), and ECG-gated dynamic-flip-angle BOLD (GDFA), all processed by the same NSR method. GDFA was compared to alternative methods over temporal SNR (tSNR), seed-based connectivity, and whole-brain voxelwise connectivity based on intrinsic connectivity distribution (ICD). A previous large-cohort data set (N = 100) was used as a connectivity gold standard. RESULTS: Simulations and phantom imaging show substantial reduction of the T1 -dependent signal variation with GDFA alone, and further reduction with NSR. The resting-state study shows improved tSNR in the basal brain, comparing GDFA to NG, after both processed with NSR. Furthermore, GDFA significantly improved subcortical-subcortical and cortical-subcortical connectivity for several representative seeds and significantly improved ICD in the brainstem, thalamus, striatum, and prefrontal cortex, compared to the other 3 approaches. CONCLUSION: GDFA with NSR improves mapping of the resting-state functional connectivity of the basal-brain regions by reducing cardiogenic noise.

REPAIRit: Improving Myocardial Nulling and Ghosting Artifacts of 3D Navigator-Gated Late Gadolinium Enhancement Imaging During Arrhythmia.

BACKGROUND: Cardiac 3D navigator-gated late gadolinium enhancement (LGE) imaging is important for assessment of left atrial fibrosis, but the image quality is often degraded due to arrhythmia. PURPOSE: To investigate a novel 3D LGE sequence with improved myocardial nulling and reduced ghosting artifacts during arrhythmia. STUDY TYPE: Prospective. POPULATION: Arrhythmia patients (n = 14). SEQUENCE: The proposed technique, REPAIRit (Regrowth Equalization Pulse for Arrhythmias in Inversion Recovery with automatic inversion time calculation), inserts a saturation pulse with a dynamic flip angle into the 3D LGE sequence to minimize arrhythmia-induced signal fluctuations. Using ShMOLLI (shortened modified Look-Locker imaging) to estimate myocardial T1 , REPAIRit automatically calculates the optimal inversion time (TI) based on Bloch equations. ASSESSMENT: REPAIRit LGE and the standard LGE were compared with simulations, phantom imaging, and patient studies. Patient images were assessed quantitatively, based on ghost-to-noise ratio (GNR), blood signal-to-noise ratio (SNRb), myocardial signal-to-noise ratio (SNRm), and blood-to-myocardium contrast-to-noise ratio (CNR), and qualitatively on a 4-point scale. Patients were subgrouped based on the presence of arrhythmia to assess the image quality difference. STATISTICAL TESTS: The two LGE sequences were compared by Student's t-test and Wilcoxon signed-rank test. The two patient-subgroups were compared using Welch's t-test and Wilcoxon rank-sum test. RESULTS: In 14 analyzed patients, REPAIRit LGE significantly lowered GNR (1.25 ± 0.41 vs. 1.42 ± 0.42, P = 0.04), reduced SNRm (1.90 ± 0.60 vs. 3.16 ± 1.66, P = 0.01), improved ghosting artifact scores (2.5 ± 0.6 vs. 2.2 ± 0.9, P = 0.03), myocardial nulling scores (2.7 ± 0.5 vs. 2.3 ± 0.7, P = 0.02), and atrial quality scores (2.8 ± 0.3 vs. 2.4 ± 0.8, P = 0.03) compared with the standard LGE. Comparing patients with arrhythmia (n = 6) to those without (n = 8) during the scan, the former had lower left ventricular (LV) myocardial T1 s (430 ± 26 msec vs. 469 ± 39 msec, P = 0.06) but similar blood T1 s (318 ± 55 msec vs. 316 ± 27 msec, P = 0.96), and significantly lower blood SNR (5.2 ± 1.8 vs. 9.2 ± 3.0, P = 0.01) and significantly worse image quality (P = 0.01 for REPAIRit and P = 0.03 for standard). DATA CONCLUSION: REPAIRit improves myocardial nulling and reduces ghosting artifacts of 3D LGE under arrhythmia. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:688-699.