Simultaneous creatine and phosphocreatine mapping of skeletal muscle by CEST MRI at 3T.

PURPOSE: To confirm that CrCEST in muscle exhibits a slow-exchanging process, and to obtain high-resolution amide, creatine (Cr), and phosphocreatine (PCr) maps of skeletal muscle using a POlynomial and Lorentzian Line-shape Fitting (PLOF) CEST at 3T. METHODS: We used dynamic changes in PCr/CrCEST of mouse hindlimb before and after euthanasia to assign the Cr and PCr CEST peaks in the Z-spectrum at 3T and to obtain the optimum saturation parameters. Segmented 3D EPI was employed to obtain multi-slice amide, PCr, and Cr CEST maps of human skeletal muscle. Subsequently, the PCrCEST maps were calibrated using the PCr concentrations determined by 31 P MRS. RESULTS: A comparison of the Z-spectra in mouse hindlimb before and after euthanasia indicated that CrCEST is a slow-exchanging process in muscle (<150.7 s-1 ). This allowed us to simultaneously extract PCr/CrCEST signals at 3T using the PLOF method. We determined optimal B1 values ranging from 0.3 to 0.6 µT for CrCEST in muscle and 0.3-1.2 µT for PCrCEST. For the study on human calf muscle, we determined an optimum saturation time of 2 s for both PCr/CrCEST (B1 = 0.6 µT). The PCr/CrCEST using 3D EPI were found to be comparable to those obtained using turbo spin echo (TSE). (3D EPI/TSE PCr: (2.6 ± 0.3) %/(2.3 ± 0.1) %; Cr: (1.3 ± 0.1) %/(1.4 ± 0.07) %). CONCLUSIONS: Our study showed that in vivo CrCEST is a slow-exchanging process. Hence, amide, Cr, and PCr CEST in the skeletal muscle can be mapped simultaneously at 3T by PLOF CEST.

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

Deep-Learning-Based Segmentation of the Shoulder from MRI with Inference Accuracy Prediction.

Three-dimensional (3D)-image-based anatomical analysis of rotator cuff tear patients has been proposed as a way to improve repair prognosis analysis to reduce the incidence of postoperative retear. However, for application in clinics, an efficient and robust method for the segmentation of anatomy from MRI is required. We present the use of a deep learning network for automatic segmentation of the humerus, scapula, and rotator cuff muscles with integrated automatic result verification. Trained on N = 111 and tested on N = 60 diagnostic T1-weighted MRI of 76 rotator cuff tear patients acquired from 19 centers, a nnU-Net segmented the anatomy with an average Dice coefficient of 0.91 ± 0.06. For the automatic identification of inaccurate segmentations during the inference procedure, the nnU-Net framework was adapted to allow for the estimation of label-specific network uncertainty directly from its subnetworks. The average Dice coefficient of segmentation results from the subnetworks identified labels requiring segmentation correction with an average sensitivity of 1.0 and a specificity of 0.94. The presented automatic methods facilitate the use of 3D diagnosis in clinical routine by eliminating the need for time-consuming manual segmentation and slice-by-slice segmentation verification.

Massive rotator cuff tears with short tendon length can be successfully repaired using synthetic patch augmentation.

BACKGROUND: Choosing the optimal treatment for massive rotator cuff tears (MRCTs) still poses a surgical problem. In MRCTs with good muscle quality, but short tendon length, nonaugmented repairs lead to high failure rates of up to 90%. The aim of the study was to evaluate midterm clinical and radiologic outcomes of massive rotator cuff tears with good muscle quality, but short tendon length, which were repaired with synthetic patch augmentation. METHODS: A retrospective study of patients who underwent arthroscopic or open rotator cuff repairs with patch augmentation between 2016 and 2019 was performed. We included patients older than 18 years, who presented with an MRCT confirmed by an magnetic resonance imaging (MRI) arthrogram showing good muscle quality (Goutallier ≤ II) and short tendon length (length <15 mm). Constant-Murley score (CS), Subjective Shoulder Value (SSV), and range of motion (ROM) were compared pre- and postoperatively. We excluded patients older than 75 years or with presence of rotator cuff arthropathy Hamada stage ≥2a. Patients were followed up for 2 years minimum. Clinical failures were defined by reoperation, forward flexion <120° or a relative CS < 70. Structural integrity of the repair was assessed using an MRI scan. Comparison between different variables and outcomes was performed using Wilcoxon-Mann-Whitney and χ2 tests. RESULTS: Fifteen patients (mean age 57 years, 13 [86.7%] male, 9 [60%] right shoulders) were reevaluated with a mean follow-up of 43.8 months (27-55 months). There was a significant improvement in the absolute CS (from 33 to 81 points, P = .03), the relative CS (from 41% to 88%, P = .04), the SSV (from 31% to 93%, P = .007), and forward flexion (from 111° to 163°, P = .004) but not in external rotation (from 37° to 38°, P = .5). There were 3 clinical failures (1 atraumatic, 2 traumatic) with reoperations (2 reverse total shoulder arthroplasties and 1 refixation). Structurally, there were 3 Sugaya grade 4 and 5 Sugaya grade 5 reruptures resulting in a retear rate of 53%. The presence of a complete or partial rerupture was not associated with inferior outcomes compared with intact cuff repairs. There were no correlations between the grade of retraction, muscle quality, or rotator cuff tear configuration and rerupture or functional outcomes. CONCLUSION: Patch augmented cuff repair leads to a significant improvement of functional and structural outcomes. Partial reruptures were not associated with inferior functional outcomes. Prospective randomized trials are needed to confirm the results found in our study.

The role of platelet-rich plasma in shoulder pathologies: a critical review of the literature.

Platelet-rich plasma (PRP) is a revolutionary treatment that harnesses the regenerative power of the body's own platelets to promote healing and tissue regeneration. While PRP therapy has emerged as a promising option for augmenting biologic healing in the shoulder, the complexity of shoulder disorders makes it difficult to draw definitive conclusions about the efficacy of PRP across different conditions and stages of disease. Our comprehensive review of twenty-four studies highlights the current state of PRP therapy in shoulder pathologies, revealing a wide variety of number of patients, control groups and results. Despite these challenges, the regenerative potential of PRP therapy is moderate in some conditions, with numerous studies demonstrating the positive effects. In conclusion, the authors of this study recommend the use of PRP therapy for adhesive capsulitis and rotator cuff repair of medium to large tears. However, they do not recommend the use of PRP for subacromial impingement or rotator cuff tears. It is up to the clinician's discretion to decide whether PRP therapy is appropriate for individual cases. However, there is still insufficient evidence to support the inclusion of PRP therapy in treatment protocols for other shoulder disorders. Therefore, further research is needed to fully explore the potential of PRP therapy in the treatment of various shoulder conditions.

Effect of PARP-1 Inhibition on Rotator Cuff Healing: A Feasibility Study Using Veliparib in a Rat Model of Acute Rotator Cuff Repair.

BACKGROUND: PARP-1 (poly[ADP-ribose]) was shown to influence the inflammatory response after rotator cuff tear, leading to fibrosis, muscular atrophy, and fatty infiltration in mouse rotator cuff degeneration. So far, it is not known how PARP-1 influences enthesis healing after rotator cuff tear repair. HYPOTHESIS/PURPOSE: This study aimed to examine the feasibility of oral PARP-1 inhibition and investigate its influence on rat supraspinatus enthesis and muscle healing after rotator cuff repair. The hypothesis was that oral PARP-1 inhibition would improve enthesis healing after acute rotator cuff repair in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: In 24 Sprague-Dawley rats, the supraspinatus tendon was sharply detached and immediately repaired with a single transosseous suture. The rats were randomly allocated into 2 groups, with the rats in the inhibitor group receiving veliparib with a target dose of 12.5 mg/kg/d via drinking water during the postoperative recovery period. The animals were sacrificed 8 weeks after surgery. For the analysis, macroscopic, biomechanical, and histologic methods were used. RESULTS: Oral veliparib was safe for the rats, with no adverse effects observed. In total, the inhibitor group had a significantly better histologic grading of the enthesis with less scar tissue formation. The macroscopic cross-sectional area of the supraspinatus muscles was 10.5% higher (P = .034) in the inhibitor group, which was in agreement with an 8.7% higher microscopic muscle fiber diameter on histologic sections (P < .0001). There were no statistically significant differences in the biomechanical properties between the groups. CONCLUSION: This study is the first to investigate the influence of PARP-1 inhibition on healing enthesis. On the basis of these findings, we conclude that oral veliparib, which was previously shown to inhibit PARP-1 effectively, is safe to apply and has beneficial effects on morphologic enthesis healing and muscle fiber size. CLINICAL RELEVANCE: Modulating the inflammatory response through PARP-1 inhibition during the postoperative healing period is a promising approach to improve enthesis healing and reduce rotator cuff retearing. With substances already approved by the Food and Drug Administration, PARP-1 inhibition bears high potential for future translation into clinical application.

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.

ESPRESO: An algorithm to estimate the slice profile of a single magnetic resonance image.

To reduce scan time, magnetic resonance (MR) images are often acquired using 2D multi-slice protocols with thick slices that may also have gaps between them. The resulting image volumes have lower resolution in the through-plane direction than in the in-plane direction, and the through-plane resolution is in part characterized by the protocol's slice profile which acts as a through-plane point spread function (PSF). Although super-resolution (SR) has been shown to improve the visualization and down-stream processing of 2D multi-slice MR acquisitions, previous algorithms are usually unaware of the true slice profile, which may lead to sub-optimal SR performance. In this work, we present an algorithm to estimate the slice profile of a 2D multi-slice acquisition given only its own image volume without any external training data. We assume that an anatomical image is isotropic in the sense that, after accounting for a correctly estimated slice profile, the image patches along different orientations have the same probability distribution. Our proposed algorithm uses a modified generative adversarial network (GAN) where the generator network estimates the slice profile to reduce the resolution of the in-plane direction, and the discriminator network determines whether a direction is generated or real low resolution. The proposed algorithm, ESPRESO, which stands for "estimating the slice profile for resolution enhancement of a single image only", was tested with a state-of-the-art internally supervised SR algorithm. Specifically, ESPRESO is used to create training data for this SR algorithm, and results show improvements when ESPRESO is used over commonly-used PSFs.

Effect of Sex on Coronary Endothelial Dysfunction in People Living With HIV.

Background Impaired coronary endothelial function (CEF) predicts cardiovascular events and occurs in people living with HIV (PLWH). Women compared with men living with HIV have worse cardiovascular outcomes, but prior CEF studies included few women. The authors aimed to compare CEF in women with HIV versus without HIV, investigate sex differences in CEF and PCSK9 (proprotein convertase subtilisin/kexin type 9) (a proinflammatory biomarker), and evaluate whether increased serum levels of PCSK9 are associated with CEF in PLWH. Methods and Results Magnetic resonance imaging was performed to measure CEF (as percent change in coronary cross-sectional area and coronary blood flow during isometric handgrip exercise, an endothelial-dependent stressor) and serum PCSK9 levels were measured in 106 PLWH and 76 people without HIV. CEF was significantly reduced in women with versus without HIV (cross-sectional area change -0.5%±9.7 versus 9.5%±3.2, respectively). After adjustment for age, body mass index, and menopausal status, women with HIV still had reduced CEF (percentage of cross-sectional area: ß -8.3 [-13 to -3.6], P=0.001) compared with women without HIV. PCSK9 was elevated in women living with HIV versus without (306 ng/mL [200-412 ng/mL] versus 180 ng/mL [154-223 ng/mL], P<0.001), and no sex differences in either CEF or PCSK9 were detected in PLWH. Elevated PCSK9 was associated with impaired CEF in PLWH; however, no significant sex differences in the association were detected. Conclusions Among PLWH, coronary endothelial dysfunction is present in women and comparable to men. PCSK9 is higher in women with versus without HIV and a significant inverse relationship between PCSK9 and CEF was shown. Future studies should determine whether PLWH would benefit from interventions to improve endothelial function.

Myocardial ATP depletion detected noninvasively predicts sudden cardiac death risk in patients with heart failure.

BACKGROUNDSudden cardiac death (SCD) remains a worldwide public health problem in need of better noninvasive predictive tools. Current guidelines for primary preventive SCD therapies, such as implantable cardioverter defibrillators (ICDs), are based on left ventricular ejection fraction (LVEF), but these guidelines are imprecise: fewer than 5% of ICDs deliver lifesaving therapy per year. Impaired cardiac metabolism and ATP depletion cause arrhythmias in experimental models, but to our knowledge a link between arrhythmias and cardiac energetic abnormalities in people has not been explored, nor has the potential for metabolically predicting clinical SCD risk.METHODSWe prospectively measured myocardial energy metabolism noninvasively with phosphorus magnetic resonance spectroscopy in patients with no history of significant arrhythmias prior to scheduled ICD implantation for primary prevention in the setting of reduced LVEF (≤35%).RESULTSBy 2 different analyses, low myocardial ATP significantly predicted the composite of subsequent appropriate ICD firings for life-threatening arrhythmias and cardiac death over approximately 10 years. Life-threatening arrhythmia risk was approximately 3-fold higher in patients with low ATP and independent of established risk factors, including LVEF. In patients with normal ATP, rates of appropriate ICD firings were several-fold lower than reported rates of ICD complications and inappropriate firings.CONCLUSIONTo the best of our knowledge, these are the first data linking in vivo myocardial ATP depletion and subsequent significant arrhythmic events in people, suggesting an energetic component to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of metabolic strategies that limit ATP loss to treat or prevent life-threatening cardiac arrhythmias and herald noninvasive metabolic imaging as a complementary SCD risk stratification tool.TRIAL REGISTRATIONClinicalTrials.gov NCT00181233.FUNDINGThis work was supported by the DW Reynolds Foundation, the NIH (grants HL61912, HL056882, HL103812, HL132181, HL140034), and Russell H. Morgan and Clarence Doodeman endowments at Johns Hopkins.

Ultrafast B1 mapping with RF-prepared 3D FLASH acquisition: Correcting the bias due to T1 -induced k-space filtering effect.

PURPOSE: The traditional radiofrequency (RF)-prepared B1 mapping technique consists of one scan with an RF preparation module for flip angle-encoding and a second scan without this module for normalizing. To reduce the T1 -induced k-space filtering effect, this method is limited to 2D FLASH acquisition with a two-parameter method. A novel 3D RF-prepared three-parameter method for ultrafast B1 -mapping is proposed to correct the T1 -induced quantification bias. THEORY: The point spread function analysis of FLASH shows that the prepared longitudinal magnetization before the FLASH acquisition and the image signal obeys a linear (not proportional) relationship. The intercept of the linear function causes the quantification bias and can be captured by a third saturated scan. METHODS: Using the 2D double-angle method (DAM) as the reference, a 3D RF-prepared three-parameter protocol with 9 s duration was compared with the two-parameter method, as well as the saturated DAM (SDAM) method, the dual refocusing echo acquisition mode (DREAM) method, and the actual flip-angle imaging (AFI) method, for B1 mapping of brain, breast, and abdomen with different orientations and shim settings at 3T. RESULTS: The 3D RF-prepared three-parameter method with complex-subtraction delivered consistently lower RMS error, error mean, error standard deviation, and higher concordance correlation coefficients values than the two-parameter method, the three-parameter method with magnitude-subtraction, the multi-slice DREAM and the 3D AFI, and were close to the results of 2D or multi-slice SDAM. CONCLUSION: The proposed ultrafast 3D RF-prepared three-parameter method with complex-subtraction was demonstrated with high accuracy for B1 mapping of brain, breast, and abdomen.

Use of small animal PET-CT imaging for in vivo assessment of tendon-to-bone healing: A pilot study.

BACKGROUND: The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (µPET) using 18F-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo µPET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model. METHODS: Unilateral autograft ACL reconstruction was performed in six rats. µPET/CT-scans using 18F-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with µCT and histological analysis. RESULTS: SUVs in both bone tunnels showed an increased 18F-Fluoride uptake at 7 days when compared to 14, 21, and 28 days. SUVs showed a gradient on the tibial side, with most bone turnover in the IAA and least in the EAA. At 7, 14, 21, and 28 days, there were significantly higher SUV values in the IAA compared to the EAA (p = .01, < .01, < .01, < .01). SUVs positively correlated with new bone volumetric density obtained with µCT (r = 0.449, p = .013). Volumetric density of newly formed bone detected on µCT correlated with osteoblast numbers observed along the tunnels in histological sections (r = 0.452, p < .016). CONCLUSIONS: Serial in-vivo µPET/CT-scanning has the potential to provide insight into bone turnover and therefore osteoblastic activity during the healing process. As a result, it allows us to directly measure the effect of interventional strategies in tendon-bone healing.

Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.

BACKGROUND: Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF. METHODS: First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance 31P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression of either Ckmyofib (myofibrillar CK) or Ckmito (mitochondrial CK) on HF-related maladaptive hypertrophy in mice. RESULTS: In people, pathologic left ventricular hypertrophy and dilatation correlate closely with reduced myocardial ATP levels and rates of ATP synthesis through CK. In mice, transverse aortic constriction-induced left ventricular hypertrophy and dilatation are attenuated by overexpression of CKmito, but not by overexpression of CKmyofib. CKmito overexpression also attenuates hypertrophy after chronic isoproterenol stimulation. CKmito lowers mitochondrial reactive oxygen species, tissue reactive oxygen species levels, and upregulates antioxidants and their promoters. When the CK capacity of CKmito-overexpressing mice is limited by creatine substrate depletion, the protection against pathologic remodeling is lost, suggesting the ADP regenerating capacity of the CKmito reaction rather than CK protein per se is critical in limiting adverse HF remodeling. CONCLUSIONS: In the failing human heart, pathologic hypertrophy and adverse remodeling are closely related to deficits in ATP levels and in the CK energy reserve reaction. CKmito, sitting at the intersection of cardiac energetics and redox balance, plays a crucial role in attenuating pathologic remodeling in HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00181259.

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.

Magnetic resonance spectroscopic imaging of downfield proton resonances in the human brain at 3 T.

PURPOSE: To develop an MRSI technique capable of mapping downfield proton resonances in the human brain. METHODS: A spectral-spatial excitation and frequency-selective refocusing scheme, in combination with 2D phase encoding, was developed for mapping of downfield resonances without any perturbation of the water magnetization. An alternative scheme using spectral-spatial refocusing was also investigated for simultaneous detection of both downfield and upfield resonances. The method was tested in 5 healthy human volunteers. RESULTS: Downfield metabolite maps with a nominal spatial resolution of 1.5 cm3 were recorded at 3 T in a scan time of 12 minutes. Cramer-Rao lower bounds for nine different downfield peaks were 20% or less over a single supraventricular slice. Downfield spectral profiles were similar to those in the literature recorded previously using single-voxel localization methods. The same approach was also used for upfield MRSI, and simultaneous upfield and downfield acquisitions. CONCLUSION: The developed MRSI pulse sequence was shown to be an efficient way of rapidly mapping downfield resonances in the human brain at 3 T, maximizing sensitivity through the relaxation enhancement effect. Because the MRSI approach is efficient in terms of data collection and can be readily implemented at short TE, somewhat higher spatial resolution can be achieved than has been reported in previous single-voxel downfield MRS studies. With this approach, nine downfield resonances could be mapped in a single slice for the first time using MRSI at 3 T.

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.

Accelerating whole-heart 3D T2 mapping: Impact of undersampling strategies and reconstruction techniques.

PURPOSE: We aim to determine an advantageous approach for the acceleration of high spatial resolution 3D cardiac T2 relaxometry data by comparing the performance of different undersampling patterns and reconstruction methods over a range of acceleration rates. METHODS: Multi-volume 3D high-resolution cardiac images were acquired fully and undersampled retrospectively using 1) optimal CAIPIRINHA and 2) a variable density random (VDR) sampling. Data were reconstructed using 1) multi-volume sensitivity encoding (SENSE), 2) joint-sparsity SENSE and 3) model-based SENSE. Four metrics were calculated on 3 naïve swine and 8 normal human subjects over a whole left-ventricular region of interest: root-mean-square error (RMSE) of image signal intensity, RMSE of T2, the bias of mean T2, and standard deviation (SD) of T2. Fully sampled data and volume-by-volume SENSE with standard equally spaced undersampling were used as references. The Jaccard index calculated from one swine with acute myocardial infarction (MI) was used to demonstrate preservation of segmentation of edematous tissues with elevated T2. RESULTS: In naïve swine and normal human subjects, all methods had similar performance when the net reduction factor (Rnet) <2.5. VDR sampling with model-based SENSE showed the lowest RMSEs (10.5%-14.2%) and SDs (+1.7-2.4 ms) of T2 when Rnet>2.5, while VDR sampling with the joint-sparsity SENSE had the lowest bias of mean T2 (0.0-1.1ms) when Rnet>3. The RMSEs of parametric T2 values (9.2%-24.6%) were larger than for image signal intensities (5.2%-18.4%). In the swine with MI, VDR sampling with either joint-sparsity or model-based SENSE showed consistently higher Jaccard index for all Rnet (0.71-0.50) than volume-by-volume SENSE (0.68-0.30). CONCLUSIONS: Retrospective exploration of undersampling and reconstruction in 3D whole-heart T2 parametric mapping revealed that maps were more sensitive to undersampling than images, presenting a more stringent limiting factor on Rnet. The combination of VDR sampling patterns with model-based or joint-sparsity SENSE reconstructions were more robust for Rnet>3.

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.