Large-scale 3D non-Cartesian coronary MRI reconstruction using distributed memory-efficient physics-guided deep learning with limited training data.

OBJECT: To enable high-quality physics-guided deep learning (PG-DL) reconstruction of large-scale 3D non-Cartesian coronary MRI by overcoming challenges of hardware limitations and limited training data availability. MATERIALS AND METHODS: While PG-DL has emerged as a powerful image reconstruction method, its application to large-scale 3D non-Cartesian MRI is hindered by hardware limitations and limited availability of training data. We combine several recent advances in deep learning and MRI reconstruction to tackle the former challenge, and we further propose a 2.5D reconstruction using 2D convolutional neural networks, which treat 3D volumes as batches of 2D images to train the network with a limited amount of training data. Both 3D and 2.5D variants of the PG-DL networks were compared to conventional methods for high-resolution 3D kooshball coronary MRI. RESULTS: Proposed PG-DL reconstructions of 3D non-Cartesian coronary MRI with 3D and 2.5D processing outperformed all conventional methods both quantitatively and qualitatively in terms of image assessment by an experienced cardiologist. The 2.5D variant further improved vessel sharpness compared to 3D processing, and scored higher in terms of qualitative image quality. DISCUSSION: PG-DL reconstruction of large-scale 3D non-Cartesian MRI without compromising image size or network complexity is achieved, and the proposed 2.5D processing enables high-quality reconstruction with limited training data.

Submillimeter T1 atlas for subject-specific abnormality detection at 7T.

PURPOSE: Studies at 3T have shown that T1 relaxometry enables characterization of brain tissues at the single-subject level by comparing individual physical properties to a normative atlas. In this work, an atlas of normative T1 values at 7T is introduced with 0.6 mm isotropic resolution and its clinical potential is explored in comparison to 3T. METHODS: T1 maps were acquired in two separate healthy cohorts scanned at 3T and 7T. Using transfer learning, a template-based brain segmentation algorithm was adapted to ultra-high field imaging data. After segmenting brain tissues, volumes were normalized into a common space, and an atlas of normative T1 values was established by modeling the T1 inter-subject variability. A method for single-subject comparisons restricted to white matter and subcortical structures was developed by computing Z-scores. The comparison was applied to eight patients scanned at both field strengths for proof of concept. RESULTS: The proposed method for morphometry delivered segmentation masks without statistically significant differences from those derived with the original pipeline at 3T and achieved accurate segmentation at 7T. The established normative atlas allowed characterizing tissue alterations in single-subject comparisons at 7T, and showed greater anatomical details compared with 3T results. CONCLUSION: A high-resolution quantitative atlas with an adapted pipeline was introduced and validated. Several case studies on different clinical conditions showed the feasibility, potential and limitations of high-resolution single-subject comparisons based on quantitative MRI atlases. This method in conjunction with 7T higher resolution broadens the range of potential applications of quantitative MRI in clinical practice.

Phase contrast coronary blood velocity mapping with both high temporal and spatial resolution using triggered Golden Angle rotated Spiral k-t Sparse Parallel imaging (GASSP) with shifted binning.

PURPOSE: High temporal and spatial resolutions are required for coronary blood flow measures. Current spiral breath-hold phase contrast (PC) MRI at 3T focus on either high spatial or high temporal resolution. We propose a golden angle (GA) rotated Spiral k-t Sparse Parallel imaging (GASSP) sequence for both high spatial (0.8 mm) and high temporal (<21 ms) resolutions. METHODS: GASSP PC data are acquired in left anterior descending and right coronary arteries of eight healthy subjects. Binning of GA rotated spiral data into cardiac frames may lead to large k-space gaps. To reduce those gaps, the binning window is shifted and a triggered GA scheme that resets the rotation angle every heartbeat is proposed. The gap reductions are evaluated in simulations and all subjects. Peak systolic velocity (PSV), peak diastolic velocity (PDV), coronary blood flow rate, and vessel area are validated against two reference scans, and repeatability/reproducibility are determined. RESULTS: Shifted binning reduced the mean k-space gaps of the triggered GA scheme by 14°-22° in simulations and about 20° in vivo. The k-space gap across three cardiac frames was reduced with the triggered GA scheme compared to the standard GA scheme (35.3°± 3.6° vs. 43°± 13.7°, t-test P = .04). PSV, PDV, flow rate, and area had high intra-scan repeatability (0.92 ≤ intraclass correlation coefficient [ICC] ≤ 0.99), and inter-scan (0.78 ≤ ICC ≤ 0.91) and intra-observer (0.91 ≤ ICC ≤ 0.98) reproducibility. CONCLUSION: GASSP enables single breath-hold coronary PC MRI with high temporal and spatial resolutions. Shifted binning and a triggered GA scheme reduce k-space gaps. Quantitative coronary flow metrics are highly reproducible, especially within the same scanning session.

Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.

Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.

Precision and accuracy of cross-sectional area measurements used to measure coronary endothelial function with spiral MRI.

PURPOSE: Coronary endothelial function (CEF) reflects vascular health and conventional invasive CEF measures predict cardiovascular events. MRI can now noninvasively measure CEF by quantifying coronary artery cross-sectional area changes in response to isometric handgrip exercise, an endothelial-dependent stressor. Area changes (10 to 20% in healthy; 2 to -12% in impaired vessels) are only a few imaging voxels because of MRI's limited spatial resolution. Here, with numerical simulations and phantom studies, we test whether Fourier interpolation enables sub-pixel area measurement precision and determine the smallest detectable area change using spiral MRI. METHODS: In vivo coronary SNR with the currently used CEF protocol at 3T was measured in 7 subjects for subsequent in vitro work. Area measurements of circular vessels were simulated by varying partial volume, vessel diameter, voxel size, SNR, and Fourier interpolation factor. A phantom with precision-drilled holes (diameters 3-3.42 mm) was imaged 10 times with the current CEF protocol (voxel size, Δx = 0.89 mm) and a high-resolution protocol (Δx = 0.6 mm) to determine precision, accuracy, and the smallest detectable area changes. RESULTS: In vivo coronary SNR ranged from 30-76. Eight-fold Fourier interpolation improved area measurement precision by a factor 6.5 and 4.9 in the simulations and phantom scans, respectively. The current CEF protocol can detect mean area changes of 4-5% for SNR above 30, and 3-3.5% for SNR above 40 with a higher-resolution protocol. CONCLUSION: Current CEF spiral MRI with in vivo SNR allows detection of a 4-5% area change and Fourier interpolation improves precision several-fold to sub-voxel dimensions.

Self-gated golden angle spiral cine MRI for coronary endothelial function assessment.

PURPOSE: Depressed coronary endothelial function (CEF) is a marker for atherosclerotic disease, an independent predictor of cardiovascular events, and can be quantified non-invasively with ECG-triggered spiral cine MRI combined with isometric handgrip exercise (IHE). However, MRI-CEF measures can be hindered by faulty ECG-triggering, leading to prolonged breath-holds and degraded image quality. Here, a self-gated golden angle spiral method (SG-GA) is proposed to eliminate the need for ECG during cine MRI. METHODS: SG-GA was tested against retrospectively ECG-gated golden angle spiral MRI (ECG-GA) and gold-standard ECG-triggered spiral cine MRI (ECG-STD) in 10 healthy volunteers. CEF data were obtained from cross-sectional images of the proximal right and left coronary arteries in a 3T scanner. Self-gating heart rates were compared to those from simultaneous ECG-gating. Coronary vessel sharpness and cross-sectional area (CSA) change with IHE were compared among the 3 methods. RESULTS: Self-gating precision, accuracy, and correlation-coefficient were 7.7 ± 0.5 ms, 9.1 ± 0.7 ms, and 0.93 ± 0.01, respectively (mean ± standard error). Vessel sharpness by SG-GA was equal or higher than ECG-STD (rest: 63.0 ± 1.7% vs. 61.3 ± 1.3%; exercise: 62.6 ± 1.3% vs. 56.7 ± 1.6%, P < 0.05). CSA changes were in agreement among the 3 methods (ECG-STD = 8.7 ± 4.0%, ECG-GA = 9.6 ± 3.1%, SG-GA = 9.1 ± 3.5%, P = not significant). CONCLUSION: CEF measures can be obtained with the proposed self-gated high-quality cine MRI method even when ECG is faulty or not available. Magn Reson Med 80:560-570, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Improved respiratory self-navigation for 3D radial acquisitions through the use of a pencil-beam 2D-T2 -prep for free-breathing, whole-heart coronary MRA.

PURPOSE: In respiratory self-navigation (SN), signal from static structures, such as the chest wall, may complicate motion detection or introduce post-correction artefacts. Suppressing signal from superfluous tissues may therefore improve image quality. We thus test the hypothesis that SN whole-heart coronary magnetic resonance angiography (MRA) will benefit from an outer-volume suppressing 2D-T2 -Prep and present both phantom and in vivo results. METHODS: A 2D-T2 -Prep and a conventional T2 -Prep were used prior to a free-breathing 3D-radial SN sequence. Both techniques were compared by imaging a home-built moving cardiac phantom and by performing coronary MRA in nine healthy volunteers. Reconstructions were performed using both a reference-based and a reference-independent approach to motion tracking, along with several coil combinations. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared, along with vessel sharpness (VS). RESULTS: In phantoms, using the 2D-T2 -Prep increased SNR by 16% to 53% and mean VS by 8%; improved motion tracking precision was also achieved. In volunteers, SNR increased by an average of 29% to 33% in the blood pool and by 15% to 25% in the myocardium, depending on the choice of reconstruction coils and algorithm, and VS increased by 34%. CONCLUSION: A 2D-T2 -Prep significantly improves image quality in both phantoms and volunteers when performing SN coronary MRA. Magn Reson Med 79:1293-1303, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Isotropic three-dimensional T2 mapping of knee cartilage: Development and validation.

PURPOSE: 1) To implement a higher-resolution isotropic 3D T2 mapping technique that uses sequential T2 -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. MATERIALS AND METHODS: The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T2 estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T2 values were compared with those from a clinical standard 2D multislice multiecho (MSME) T2 mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). RESULTS: The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R2 ≥ 0.99). Repeated measurements of cartilage T2 values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T2 values (P < 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T2 mapping in healthy volunteers, and significantly higher in OA (P = 0.01). CONCLUSION: This study successfully demonstrated that high-resolution isotropic 3D T2 mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T2 quantification in any plane of interest. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371.

Four-dimensional respiratory motion-resolved whole heart coronary MR angiography.

PURPOSE: Free-breathing whole-heart coronary MR angiography (MRA) commonly uses navigators to gate respiratory motion, resulting in lengthy and unpredictable acquisition times. Conversely, self-navigation has 100% scan efficiency, but requires motion correction over a broad range of respiratory displacements, which may introduce image artifacts. We propose replacing navigators and self-navigation with a respiratory motion-resolved reconstruction approach. METHODS: Using a respiratory signal extracted directly from the imaging data, individual signal-readouts are binned according to their respiratory states. The resultant series of undersampled images are reconstructed using an extradimensional golden-angle radial sparse parallel imaging (XD-GRASP) algorithm, which exploits sparsity along the respiratory dimension. Whole-heart coronary MRA was performed in 11 volunteers and four patients with the proposed methodology. Image quality was compared with that obtained with one-dimensional respiratory self-navigation. RESULTS: Respiratory-resolved reconstruction effectively suppressed respiratory motion artifacts. The quality score for XD-GRASP reconstructions was greater than or equal to self-navigation in 80/88 coronary segments, reaching diagnostic quality in 61/88 segments versus 41/88. Coronary sharpness and length were always superior for the respiratory-resolved datasets, reaching statistical significance (P < 0.05) in most cases. CONCLUSION: XD-GRASP represents an attractive alternative for handling respiratory motion in free-breathing whole heart MRI and provides an effective alternative to self-navigation. Magn Reson Med 77:1473-1484, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Respiratory optimized data selection for more resilient self-navigated whole-heart coronary MR angiography.

OBJECTIVES: Our objective was to test a data-exclusion strategy for respiratory motion suppression by retrospectively eliminating data acquired at extreme respiratory positions for improved coronary vessel sharpness (VS) of 1-D self-navigated 3-D radial whole-heart coronary angiography acquisitions. MATERIALS AND METHODS: 3-D radial self-navigated acquisitions were performed on a 1.5T scanner in volunteers during free-breathing (n = 8), in coached volunteers (n = 13) who were asked to breathe in a controlled manner to mimic cardiovascular patients presenting with Cheyne-Stokes breathing, and in free-breathing patients (n = 20). Data collected during large respiratory excursions were gradually excluded retrospectively from the reconstruction yielding 14 data sets per subject on average. The impact on VS, blood and myocardium signal-to-noise and contrast-to-noise was measured. From these results, two retrospective gating strategies were defined for the k-line elimination procedure and tested in all groups. RESULTS: Maximum right coronary artery VS improvement was +7.4 and +2.7% in coached volunteers and patients (P < 0.0001 for both), respectively, and 1.6% for the free-breathing volunteers (P = 0.13). The first gating strategy was defined as a fixed undersampling factor of 5 compared to a fully sampled 3-D radial acquisition, yielding significant VS improvement in coached volunteers and patients while myocardial signal-to-noise decreased in these. The second strategy was defined as a fixed gating window of 5.7 mm, leading to similar improvements. CONCLUSION: The presented strategies improve image quality of self-navigated acquisitions by retrospectively excluding data collected during end-inspiration.

An iterative approach to respiratory self-navigated whole-heart coronary MRA significantly improves image quality in a preliminary patient study.

PURPOSE: In respiratory self-navigated coronary MRA, the selection of a reference position may have a direct effect on image quality. While end-expiration is commonly used as reference, it may be ill defined in cases of irregular breathing. Here, an iterative self-navigation approach that operates without a reference position was implemented and tested in healthy volunteers and patients. METHODS: Data were acquired in 15 healthy volunteers and in 23 patients. Images obtained with end-expiratory self-navigation were compared with those obtained with the iterative approach that incorporates cross-correlation to iteratively minimize a global measure of respiratory displacement. Vessel sharpness, length, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated while differences in breathing patterns between the two sub-groups were assessed, too. RESULTS: Vessel sharpness and length were similar for both methods in healthy volunteers. In patients, a significant improvement in vessel sharpness and length was obtained using the iterative approach. SNR and CNR remained constant. While end-expiration was the most frequent respiratory phase in healthy volunteers (57.6 ± 16.2%), intermediate respiratory phases (43.4 ± 30.1%) were predominantly found in patients. CONCLUSION: An iterative approach to respiratory motion correction in self-navigation may lead to significant improvements in coronary MRA image quality in patients with a less consistent end-expiratory respiratory phase.

Is there an optimal respiratory reference position for self-navigated whole-heart coronary MR angiography?

PURPOSE: To test the direct influence of the reference respiratory position on image quality for self-navigated whole-heart coronary MRI. METHODS: Self-navigated whole-heart coronary MRI was performed in 11 healthy adult subjects. Respiratory motion was compensated for by using three different respiratory reference positions of the heart: end-inspiratory, end-expiratory, and the mean of the entire respiratory excursion. All datasets were reconstructed without motion compensation for comparison. Image quality was assessed in all reconstructions using signal-to-noise ratio (SNR) and contrst-to-noise ratio (CNR) measurements, as well as percentage vessel sharpness and visible length of the coronary arteries. RESULTS: While SNR and CNR remained close to constant in all reconstructions, a clear and significant improvement in vessel sharpness was identified in all motion corrected datasets with respect to their uncorrected counterpart (e.g., percentage sharpness of the proximal right coronary artery (RCA): 61.6 ± 8.2% for end-inspiration, 64.1 ± 10.7% for end-expiration, and 63.3 ± 7.0% for the mean respiratory position versus 55.0 ± 10.4 for the uncorrected datasets; P < 0.05). Among all motion corrected reconstructions, the use of an end-expiratory reference position most consistently provided the highest image quality. In particular, some of the improvements in vessel sharpness and length measured for end-expiration were statistically significant with respect to the reconstructions performed at end-inspiration (e.g., percentage sharpness of the proximal left anterior descending coronary: 58.2 ± 7.4% versus 55.8 ± 8.4%; P < 0.05; and visible length of the RCA: 125.7 ± 25.9 mm versus 114.4 ± 27.4 mm; P < 0.05). CONCLUSION: The use of end-expiration as a reference position for respiratory motion correction in free-breathing self-navigated whole heart coronary MRA significantly improves image quality. J

Free-running 4D whole-heart self-navigated golden angle MRI: Initial results.

PURPOSE: To test the hypothesis that both coronary anatomy and ventricular function can be assessed simultaneously using a single four-dimensional (4D) acquisition. METHODS: A free-running 4D whole-heart self-navigated acquisition incorporating a golden angle radial trajectory was implemented and tested in vivo in nine healthy adult human subjects. Coronary magnetic resonance angiography (MRA) datasets with retrospective selection of acquisition window width and position were extracted and quantitatively compared with baseline self-navigated electrocardiography (ECG) -triggered coronary MRA. From the 4D datasets, the left-ventricular end-systolic, end-diastolic volumes (ESV & EDV) and ejection fraction (EF) were computed and compared with values obtained from conventional 2D cine images. RESULTS: The 4D datasets enabled dynamic assessment of the whole heart with isotropic spatial resolution of 1.15 mm(3). Coronary artery image quality was very similar to that of the ECG-triggered baseline scan despite some SNR penalty. A good agreement between 4D and 2D cine imaging was found for EDV, ESV, and EF. CONCLUSION: The hypothesis that both coronary anatomy and ventricular function can be assessed simultaneously in vivo has been tested positive. Retrospective and flexible acquisition window selection allows to best visualize each coronary segment at its individual time point of quiescence.

Respiratory self-navigated postcontrast whole-heart coronary MR angiography: initial experience in patients.

PURPOSE: To assess the diagnostic performance of respiratory self-navigation for whole-heart coronary magnetic resonance (MR) angiography in a patient cohort referred for diagnostic cardiac MR imaging. MATERIALS AND METHODS: Written informed consent was obtained from all participants for this institutional review board-approved study. Self-navigated coronary MR angiography was performed after administration of a contrast agent in 78 patients (mean age, 48.5 years ± 20.7 [standard deviation]; 53 male patients) referred for cardiac MR imaging because of coronary artery disease (n = 40), cardiomyopathy (n = 14), congenital anomaly (n = 17), or "other" (n = 7). Examination duration was recorded, and the image quality for each coronary segment was assessed with consensus reading. Vessel sharpness, length, and diameter were measured. Quantitative values in proximal, middle, and distal segments were compared by using analysis of variance and t tests. A double-blinded comparison with the results of x-ray angiography was performed when such results were available. RESULTS: When patients with different indications for cardiac MR imaging were examined with self-navigated postcontrast coronary MR angiography, whole-heart data sets with 1.15-mm isotropic spatial resolution were acquired in an average of 7.38 minutes ± 1.85. The main and proximal coronary segments could be visualized in 92.3% of cases, while the middle and distal segments could be visualized in 84.0% and 55.8% of cases, respectively. Subjective scores and vessel sharpness were significantly higher in the proximal segments than in the middle and distal segments (P < .05). Anomalies of the coronary arteries could be confirmed or excluded in all cases. Per-vessel sensitivity and specificity for stenosis detection were 64.7% and 85.0%, respectively, in the 31 patients for whom reference standard x-ray coronary angiography results were available. CONCLUSION: The self-navigated coronary MR angiography sequence shows promise for coronary imaging. However, technical improvements are needed to improve image quality, especially in the more distal coronary segments.

The Relationship Between Impaired Coronary Endothelial Function and Systemic Markers of Inflammation in People Living With HIV.

BACKGROUND: People with HIV (PWH) are at an increased risk of cardiovascular disease, partially believed to be related to chronically elevated systemic inflammation. Abnormal systemic endothelial function (SEF) and coronary endothelial function (CEF) develop early in atherogenesis and predict adverse events. It is unknown whether abnormal CEF is related to systemic inflammation in PWH. METHODS: In this substudy of a prior randomized controlled trial in PWH without prior clinical coronary artery disease suppressed on antiretroviral therapy with CEF as a primary end point (N = 82), we investigated the associations between baseline serum markers of inflammation and adhesion and baseline CEF, assessed by noninvasive MRI measures of percentage changes in coronary blood flow and cross-sectional area during isometric handgrip exercise, and SEF using brachial ultrasound for flow-mediated dilation. We also evaluated whether baseline marker levels were associated with CEF after 8 weeks in the placebo group (N = 40). RESULTS: CEF measures were abnormal at baseline, based on trial entry criteria. A higher value of CEF was directly associated with levels of interleukin 10, whereas CEF at baseline was inversely associated with E-selectin. Worse CEF at 8 weeks was directly associated with baseline tumor necrosis factor alpha, intercellular adhesion molecule 1, C-reactive protein, interferon gamma and sICAM-3. SEF at baseline or 8 weeks was not associated with any baseline markers. CONCLUSION: Coronary but not systemic endothelial dysfunction was significantly associated with select markers of inflammation and adhesion in PWH. Furthermore, CEF but not SEF at 8 weeks was associated with baseline levels of inflammation. Our findings suggest that abnormal CEF and systemic markers of inflammation are linked in PWH.

Motion compensation strategies in magnetic resonance imaging.

Image quality in magnetic resonance imaging (MRI) is considerably affected by motion. Therefore, motion is one of the most common sources of artifacts in contemporary cardiovascular MRI. Such artifacts in turn may easily lead to misinterpretations in the images and a subsequent loss in diagnostic quality. Hence, there is considerable research interest in strategies that help to overcome these limitations at minimal cost in time, spatial resolution, temporal resolution, and signal-to-noise ratio. This review summarizes and discusses the three principal sources of motion: the beating heart, the breathing lungs, and bulk patient movement. This is followed by a comprehensive overview of commonly used compensation strategies for these different types of motion. Finally, a summary and an outlook are provided.

Coronary Endothelial Dysfunction in People Living With HIV Is Related to Body Fat Distribution.

BACKGROUND: People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH. SETTING: Prospective cohort study. METHODS: PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified using MRI. Linear regression was used to determine associations between CEF and independent variables. RESULTS: Among 84 PLWH (52 ± 11 years; 33% women), mean cross-sectional area change was 0.74 ± 11.7%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R = -0.31, P = 0.014), hip circumference (R = -0.27, P = 0.037), and subcutaneous fat area (R = -0.25, P = 0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction. CONCLUSION: Waist and hip circumference and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.

Randomized Trial of Anti-inflammatory Medications and Coronary Endothelial Dysfunction in Patients With Stable Coronary Disease.

Aims: Inflammation plays a critical role in the pathogenesis of coronary artery disease (CAD), however the impact of anti-inflammatory therapies to reduce those processes which promote atherosclerosis in CAD patients is unknown. We aimed to test the hypothesis that anti-inflammatory approaches improve impaired coronary endothelial function (CEF), a driver of coronary atherosclerosis, in stable CAD patients. Methods and Results: We performed a single-center, randomized, placebo-controlled, double-blinded trial to assess whether low dose methotrexate (MTX), low dose colchicine (LDC), and/or their combination (MTX+LDC), improves CEF using non-invasive MRI measures in patients with stable CAD (N = 94). The primary endpoint was the MRI-detected change in coronary cross-sectional area from rest to isometric handgrip exercise (IHE), a predominantly nitric oxide-dependent endothelial dependent stressor. Coronary and systemic endothelial endpoints, and serum inflammatory markers, were collected at baseline, 8 and 24 weeks. Anti-inflammatory study drugs were well-tolerated. There were no significant differences in any of the CEF parameters among the four groups (MTX, LDC, MTX+LDC, placebo) at 8 or 24 weeks. Serum markers of inflammation and systemic endothelial function measures were also not significantly different among the groups. Conclusion: This is the first study to examine the effects of the anti-inflammatory approaches using MTX, LDC, and/or the combination in stable CAD patients on CEF, a marker of vascular health and the primary endpoint of the study. Although these anti-inflammatory approaches were relatively well-tolerated, they did not improve coronary endothelial function in patients with stable CAD. Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT02366091.

A randomized, placebo-controlled, double-blinded clinical trial of colchicine to improve vascular health in people living with HIV.

OBJECTIVES: People living with HIV (PWH) experience an increased burden of coronary artery disease (CAD) believed to be related, in part, to an interplay of chronically increased inflammation and traditional risk factors. Recent trials suggest cardiovascular benefits of the anti-inflammatory, colchicine, in HIV-seronegative CAD patients. However, the impact of colchicine on impaired vascular health, as measured by coronary endothelial function (CEF), an independent contributor to CAD, has not been studied in PWH. We tested the hypothesis that colchicine improves vascular health in PWH. DESIGN: This was a randomized, placebo-controlled, double-blinded trial in 81 PWH to test whether low-dose colchicine (0.6 mg daily) improves CEF over 8-24 weeks. METHODS: Coronary and systemic endothelial function and serum inflammatory markers were measured at baseline, and at 8 and 24 weeks. The primary endpoint was CEF, measured as the change in coronary blood flow from rest to that during an isometric handgrip exercise, an endothelial-dependent stressor, measured with non-invasive MRI at 8 weeks. RESULTS: Colchicine was well tolerated and not associated with increased adverse events. However, there were no significant improvements in coronary or systemic endothelial function or reductions in serum inflammatory markers at 8 or 24 weeks with colchicine as compared to placebo. CONCLUSIONS: In PWH with no history of CAD, low-dose colchicine was well tolerated but did not improve impaired coronary endothelial function, a predictor of cardiovascular events. These findings suggest that this anti-inflammatory approach using colchicine in PWH does not improve vascular health, the central, early driver of coronary atherosclerosis.

Noninvasive detection of impaired pulmonary artery endothelial function in people living with HIV.

OBJECTIVE: People living with HIV (PLWH) have an increased risk of pulmonary vascular disease and pulmonary hypertension. Endothelial cell dysfunction is thought to contribute, but human studies have been limited by the invasive nature of conventional measures of pulmonary artery endothelial function (PAEF). We report here a noninvasive MRI approach to measure nitric oxide mediated PAEF by quantifying changes in pulmonary artery area and blood flow during isometric handgrip exercise (IHE), an endothelial nitric oxide dependent stressor. We used this to test the hypothesis that PLWH have impaired PAEF, even before development of pulmonary hypertension. DESIGN: A prospective cohort study. METHODS: We enrolled 25 HIV-positive viral-suppressed individuals on stable antiretroviral therapy without known or suspected pulmonary hypertension and 19 matched seronegative control individuals (HIV-negative). Pulmonary artery area and blood flow changes in response to IHE were measured with noncontrast MRI. Data previously collected during nitric oxide-synthase inhibition were analysed to determine the role of nitric oxide in the pulmonary artery response to IHE. RESULTS: Seronegative individuals exhibited the anticipated PA vasodilatory response to IHE, but this was completely absent in HIV-positive individuals who exhibited an impaired area change (-1.1 ±â€Š1.2 vs. +7.7 ±â€Š2.2%, HIV-positive vs. HIV-negative, mean ±â€ŠSEM, respectively, P = 0.002) and blood flow response (0.2 ±â€Š2.3 vs. 13.5 ±â€Š4.8%, P = 0.005). The pulmonary artery vasodilatory effect of IHE in healthy individuals was fully blocked by nitric oxide-synthase, demonstrating this pulmonary artery response is predominantly nitric oxide mediated. CONCLUSION: Using noninvasive MRI methods to quantify PAEF, we observed significantly impaired PAEF in PLWH compared with matched HIV-negative controls. Noninvasive PAEF testing may be useful in evaluating early HIV-related pulmonary vascular disease.