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.

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 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.

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.

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.

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.

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.

Unsupervised learning for magnetization transfer contrast MR fingerprinting: Application to CEST and nuclear Overhauser enhancement imaging.

PURPOSE: To develop a fast, quantitative 3D magnetization transfer contrast (MTC) framework based on an unsupervised learning scheme, which will provide baseline reference signals for CEST and nuclear Overhauser enhancement imaging. METHODS: Pseudo-randomized RF saturation parameters and relaxation delay times were applied in an MR fingerprinting framework to generate transient-state signal evolutions for different MTC parameters. Prospectively compressed sensing-accelerated (four-fold) MR fingerprinting images were acquired from 6 healthy volunteers at 3 T. A convolutional neural network framework in an unsupervised fashion was designed to solve an inverse problem of a two-pool MTC Bloch equation, and was compared with a conventional Bloch equation-based fitting approach. The MTC images synthesized by the convolutional neural network architecture were used for amide proton transfer and nuclear Overhauser enhancement imaging as a reference baseline image. RESULTS: The fully unsupervised learning scheme incorporated with the two-pool exchange model learned a set of unique features that can describe the MTC-MR fingerprinting input, and allowed only small amounts of unlabeled data for training. The MTC parameter values estimated by the unsupervised learning method were in excellent agreement with values estimated by the conventional Bloch fitting approach, but dramatically reduced computation time by ~1000-fold. CONCLUSION: Given the considerable time efficiency compared to conventional Bloch fitting, unsupervised learning-based MTC-MR fingerprinting could be a powerful tool for quantitative MTC and CEST/nuclear Overhauser enhancement imaging.

Three-dimensional assessment of brain arterial compliance: Technical development, comparison with aortic pulse wave velocity, and age effect.

PURPOSE: The ability to measure cerebral vascular compliance (VC) is important in the evaluation of vascular diseases. Additionally, quantification of arterial wall pulsation in the brain may be useful for understanding the driving force of the recently discovered glymphatic system. Our goal is to develop an MRI technique to measure VC and arterial wall pulsation in major intracranial vessels. METHODS: A total of 17 healthy subjects were studied on a 3T MRI system. The technique, called VaCom-PCASL, uses pseudo-continuous arterial spin labeling (PCASL) to obtain pure blood vessel signal, uses a 3D radial acquisition, and applies a golden-angle radial sparse parallel (GRASP) algorithm for image reconstruction. The k-space data were retrospectively sorted into different cardiac phases. The GRASP algorithm allows the reconstruction of 5D (three spatial dimensions, one control/label dimension, and one cardiac-phase dimension) data simultaneously. The proposed technique was optimized in terms of reconstruction parameters and labeling duration. Intracranial VC was compared with aortic pulse wave velocity measured with phase-contrast MRI. Age differences in VC were studied. RESULTS: The VaCom-PCASL technique using 10 cardiac phases and GRASP sparsity constraints of λlabel/control = 0.05 and λcardiac = 0.05 provided the highest contrast-to-noise ratio. A labeling duration of 800 ms was found to yield signals comparable to those of longer duration (P > .2), whereas 400 ms yielded significant overestimation (P < .005). A significant correlation was observed between intracranial VC and aortic pulse wave velocity (r = -0.73, P = .038, N = 8). Vascular compliance in the older group was lower than that in the younger group. CONCLUSION: The VaCom-PCASL-MRI technique represents a promising approach for noninvasive assessment of arterial stiffness and pulsatility.

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.

Across-vendor standardization of semi-LASER for single-voxel MRS at 3T.

The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B1 limit of 15 µT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B0 shimming and voxel-based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 µT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts.

The glenohumeral ligaments: Superior, middle, and inferior: Anatomy, biomechanics, injury, and diagnosis.

The three glenohumeral ligaments (superior, middle, and inferior) are discrete thickenings of the glenohumeral joint capsule and are critical to shoulder stability and function. Injuries to this area are a cause of significant musculoskeletal morbidity. A literature search was performed by a review of PubMed, Google Scholar, and OVID for all relevant articles published up until 2020. This study highlights the anatomy, biomechanical function, and injury patterns of the glenohumeral ligaments, which may be relevant to clinical presentation and diagnosis. A detailed understanding of the normal anatomy and biomechanics is a necessary prerequisite to understanding the injury patterns and clinical presentations of disorders involving the glenohumeral ligaments of the shoulder.

Measuring Myocardial Energetics with Cardiovascular Magnetic Resonance Spectroscopy.

The heart has the highest energy demands per gram of any organ in the body and energy metabolism fuels normal contractile function. Metabolic inflexibility and impairment of myocardial energetics occur with several common cardiac diseases, including ischemia and heart failure. This review explores several decades of innovation in cardiac magnetic resonance spectroscopy modalities and their use to noninvasively identify and quantify metabolic derangements in the normal, failing, and diseased heart. The implications of this noninvasive modality for predicting significant clinical outcomes and guiding future investigation and therapies to improve patient care are discussed.

A deep learning approach for magnetization transfer contrast MR fingerprinting and chemical exchange saturation transfer imaging.

Semisolid magnetization transfer contrast (MTC) and chemical exchange saturation transfer (CEST) MRI based on MT phenomenon have shown potential to evaluate brain development, neurological, psychiatric, and neurodegenerative diseases. However, a qualitative MT ratio (MTR) metric commonly used in conventional MTC imaging is limited in the assessment of quantitative semisolid macromolecular proton exchange rates and concentrations. In addition, CEST signals measured by MTR asymmetry analysis are unavoidably contaminated by upfield nuclear Overhauser enhancement (NOE) signals of mobile and semisolid macromolecules. To address these issues, we developed an MTC-MR fingerprinting (MTC-MRF) technique to quantify tissue parameters, which further allows an estimation of accurate MTC signals at a certain CEST frequency offset. A pseudorandomized RF saturation scheme was used to generate unique MTC signal evolutions for different tissues and a supervised deep neural network was designed to extract tissue properties from measured MTC-MRF signals. Through detailed Bloch equation-based digital phantom and in vivo studies, we demonstrated that the MTC-MRF can quantify MTC characteristics with high accuracy and computational efficiency, compared to a conventional Bloch equation fitting approach, and provide baseline reference signals for CEST and NOE imaging. For validation, MTC-MRF images were synthesized using the tissue parameters estimated from the deep-learning method and compared with experimentally acquired MTC-MRF images as the reference standard. The proposed MTC-MRF framework can provide quantitative 3D MTC, CEST, and NOE imaging of the human brain within a clinically acceptable scan time.

Growth Factor Delivery to a Cartilage-Cartilage Interface Using Platelet-Rich Concentrates on a Hyaluronic Acid Scaffold.

PURPOSE: To determine whether (1) human leukocyte-platelet-rich plasma (L-PRP) or (2) leukocyte-platelet-rich fibrin (L-PRF) delivered on a hyaluronic acid (HA) scaffold at a bovine chondral defect, a simulated cartilage tear interface, in vitro would improve tissue formation based on biomechanical, histologic, and biochemical measures. METHODS: L-PRF and L-PRP were prepared from 3 healthy volunteer donors and delivered in conjunction with HA scaffolds to defects created in full-thickness bovine cartilage plugs harvested from bovine femoral condyle and trochlea. Specimens were cultured in vitro for up to 42 days. Treatment groups included an HA scaffold alone and scaffolds containing L-PRF or L-PRP. Cartilage repair was assessed using biomechanical testing, histology, DNA quantification, and measurement of sulfated glycosaminoglycan and collagen content at 28 and 42 days. RESULTS: L-PRF elicited the greatest degree of defect filling and improvement in other histologic measures. L-PRF-treated specimens also had the greatest cellularity when compared with L-PRP and control at day 28 (560.4 µg vs 191.4 µg vs 124.2 µg, P = .15); at day 48, there remained a difference, although not significant, between L-PRF versus L-PRP (761.1 µg vs 589.3 µg, P = .219) . L-PRF had greater collagen deposition when compared with L-PRP at day 42 (40.1 µg vs 16.3 µg, P < .0001). L-PRF had significantly greater maximum interfacial strength compared with the control at day 42 (10.92 N vs 0.66 N, P = .015) but had no significant difference compared with L-PRP (10.92 N vs 6.58 N, P = .536). L-PRP facilitated a greater amount of sulfated glycosaminoglycan production at day 42 when compared with L-PRF (15.9 µg vs 4.3 µg, P = .009). CONCLUSIONS: Delivery of leukocyte-rich platelet concentrates in conjunction with a HA scaffold may allow for improvements in cartilage healing through different pathways. L-PRF was not superior to L-PRP in its biomechanical strength, suggesting that both treatments may be effective in improving biomechanical strength of healing cartilage through different pathways. CLINICAL RELEVANCE: The delivery of platelet-rich concentrates in conjunction HA scaffolds may augment healing cartilaginous injuries.

Quantifying amide proton exchange rate and concentration in chemical exchange saturation transfer imaging of the human brain.

Current chemical exchange saturation transfer (CEST) neuroimaging protocols typically acquire CEST-weighted images, and, as such, do not essentially provide quantitative proton-specific exchange rates (or brain pH) and concentrations. We developed a dictionary-free MR fingerprinting (MRF) technique to allow CEST parameter quantification with a reduced data set. This was accomplished by subgrouping proton exchange models (SPEM), taking amide proton transfer (APT) as an example, into two-pool (water and semisolid macromolecules) and three-pool (water, semisolid macromolecules, and amide protons) models. A variable radiofrequency saturation scheme was used to generate unique signal evolutions for different tissues, reflecting their CEST parameters. The proposed MRF-SPEM method was validated using Bloch-McConnell equation-based digital phantoms with known ground-truth, which showed that MRF-SPEM can achieve a high degree of accuracy and precision for absolute CEST parameter quantification and CEST phantoms. For in-vivo studies at 3 T, using the same model as in the simulations, synthetic Z-spectra were generated using rates and concentrations estimated from the MRF-SPEM reconstruction and compared with experimentally measured Z-spectra as the standard for optimization. The MRF-SPEM technique can provide rapid and quantitative human brain CEST mapping.

Multi-vendor standardized sequence for edited magnetic resonance spectroscopy.

Spectral editing allows direct measurement of low-concentration metabolites, such as GABA, glutathione (GSH) and lactate (Lac), relevant for understanding brain (patho)physiology. The most widely used spectral editing technique is MEGA-PRESS, which has been diversely implemented across research sites and vendors, resulting in variations in the final resolved edited signal. In this paper, we describe an effort to develop a new universal MEGA-PRESS sequence with HERMES functionality for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and timings. New RF pulses were generated for the universal sequence. Phantom experiments were conducted on Philips, Siemens, GE and Canon 3 T MRI scanners using 32-channel head coils. In vivo experiments were performed on the same six subjects on Philips and Siemens scanners, and on two additional subjects, one on GE and one on Canon scanners. On each platform, edited MRS experiments were conducted with the vendor-native and universal MEGA-PRESS sequences for GABA (TE = 68 ms) and Lac editing (TE = 140 ms). Additionally, HERMES for GABA and GSH was performed using the universal sequence at TE = 80 ms. The universal sequence improves inter-vendor similarity of GABA-edited and Lac-edited MEGA-PRESS spectra. The universal HERMES sequence yields both GABA- and GSH-edited spectra with negligible levels of crosstalk on all four platforms, and with strong agreement among vendors for both edited spectra. In vivo GABA+/Cr, Lac/Cr and GSH/Cr ratios showed relatively low variation between scanners using the universal sequence. In conclusion, phantom and in vivo experiments demonstrate successful implementation of the universal sequence across all four major vendors, allowing editing of several metabolites across a range of TEs.

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.

Accuracy of tibial cuts with patient-specific instrumentation is not influenced by the surgeon's level of experience.

PURPOSE: It was hypothesized that surgeon's experience as well as bone density play a significant role in achieving accurate cuts with patient-specific instrumentation (PSI). The aim of this study was to compare the accuracy of the tibial cuts in different bone densities made by a highly experienced orthopedic surgeon on one hand and a less experienced orthopedic surgeon on the other. METHODS: Tibial models from three different sawbone densities were developed for this study. Each surgeon performed 21 cuts. A coordinate measuring machine was used to analyse the cuts. The K-Cohen test was performed to evaluate the results. The analyzed parameters were guide positioning and deviation from the guide cut to the tibial cut, including varus/valgus angle, the tibial slope, cut height, planarity (mm2), and rugosity (mm). RESULTS: There was a significant difference in the positioning of the tibial cut guide between the two surgeons for the tibial slope (p < 0.05), while no difference was observed for the varus/valgus angle (n.s.) and the cut height (n.s.). No significant difference in the tibial cut was observed between the surgeons for the tibial slope angle (n.s.), varus/valgus angle (n.s.), planarity (n.s.), and rugosity (n.s.). In the different bone types, no significant difference was observed for the tibial slope (n.s.) and varus/valgus angle (n.s.), while planarity and rugosity showed significant differences (p < 0.05). Our study showed no significant difference in the tibial cuts for the tibial slope, varus/valgus angle, planarity, and rugosity between the two surgeons. CONCLUSIONS: In the present study, it could be demonstrated that accuracy of the cuts is ensured by PSI not depending on the surgeon's experience and the bone mineral density. This speaks to its clinical significance: PSI might be suited for less experienced surgeons to reduce outliers in total knee arthroplasty (TKA).

Biomechanical comparison of two biplanar and one monoplanar reconstruction techniques of the acromioclavicular joint.

INTRODUCTION: The purpose of this proof-of-concept study was to investigate the biomechanical performance of two surgical techniques, namely (1) the double Tight-Rope fixation with an additional acromioclavicular FiberTape fixation (DTRC) and (2) the fixation of the clavicle to the acromion and coracoid in a bipodal manner (Bipod) using a Poly-Tape and FiberTape. Both techniques intend to address vertical and horizontal instability after acromioclavicular dislocation. They were compared with the commonly used (3) double Tight-Rope (DTR) technique, which only stabilizes the clavicle to the coracoid. MATERIALS AND METHODS: The acromioclavicular joint (ACJ) of 18 composite Sawbone shoulder specimens (6 per reconstruction group) were tested for posterosuperior elongation (70N cyclical load, 1500 cycles), load-to-failure and stiffness. RESULTS: After 1500 cycles, the DTRC, Bipod and DTR group showed an elongation of 0.45 mm (SD 0.14 mm), 1.19 mm (SD 0.54 mm), and 0.46 mm (SD 0.15 mm), respectively. Although the elongation of the Bipod group was increased when compared to the other two groups (Bipod versus DTRC p = 0.008; Bipod versus DTR p = 0.006), the difference was less than 0.7 mm. The DTRC showed a higher load-to-failure of 656.1N (SD 58.1 N) compared to the Bipod [531.1 N (SD 108.2N) (p = 0.039)] and DTR group [522.8 N (SD 32.8 N) (p = 0.033)]. CONCLUSION: The DTRC and the DTR group resulted in similar low elongation, while the elongation in the Bipod technique was slightly higher. Even though this difference of 0.7 mm shows statistical significance, it most likely has no clinical relevance. When testing in posterosuperior direction, which is the clinically relevant load vector, an additional fixation of the clavicle to the acromion did not reduce elongation in this study. It is, furthermore, questionable if the benefit of an increased load-to-failure in combination with no improvement in elongation and stiffness as seen in the DTRC group outweighs the possible risks and increased costs coming with the DTRC refixation.