Non-electrocardiogram-gated, free-breathing, off-resonance reduced, high-resolution, whole-heart myocardial T2 * mapping at 3 T within 5 min.

PURPOSE: Widely used conventional 2D T2 * approaches that are based on breath-held, electrocardiogram (ECG)-gated, multi-gradient-echo sequences are prone to motion artifacts in the presence of incomplete breath holding or arrhythmias, which is common in cardiac patients. To address these limitations, a 3D, non-ECG-gated, free-breathing T2 * technique that enables rapid whole-heart coverage was developed and validated. METHODS: A continuous random Gaussian 3D k-space sampling was implemented using a low-rank tensor framework for motion-resolved 3D T2 * imaging. This approach was tested in healthy human volunteers and in swine before and after intravenous administration of ferumoxytol. RESULTS: Spatial-resolution matched T2 * images were acquired with 2-3-fold reduction in scan time using the proposed T2 * mapping approach relative to conventional T2 * mapping. Compared with the conventional approach, T2 * images acquired with the proposed method demonstrated reduced off-resonance and flow artifacts, leading to higher image quality and lower coefficient of variation in T2 *-weighted images of the myocardium of swine and humans. Mean myocardial T2 * values determined using the proposed and conventional approaches were highly correlated and showed minimal bias. CONCLUSION: The proposed non-ECG-gated, free-breathing, 3D T2 * imaging approach can be performed within 5 min or less. It can overcome critical image artifacts from undesirable cardiac and respiratory motion and bulk off-resonance shifts at the heart-lung interface. The proposed approach is expected to facilitate faster and improved cardiac T2 * mapping in those with limited breath-holding capacity or arrhythmias.

On the loss of image contrast in double-inversion-recovery prepared T2* MRI of Intramyocardial hemorrhage.

PURPOSE: Studies have shown that double-inversion-recovery (DIR) prepared dark-blood T2*-weighted images result in lower SNR, CNR and diagnostic accuracy for intramyocardial hemorrhage (IMH) detection compared to non-DIR-prepared (bright-blood) T2*-weighted images; however, the mechanism contributing to this observation has not been investigated and explained in detail. This work tests the hypothesis that the loss of SNR on dark-blood cardiac T2*-weighted images of IMH stems from spin-relaxation during the long RF pulses in double inversion preparation, as a result, compromising image contrast for intramyocardial hemorrhage detection. METHODS: Phantom and in-vivo animal studies were performed to test the hypothesis of the study. An agar phantom was imaged with multi-gradient-echo T2* imaging protocols with and without double-inversion-recovery (DIR) preparation. Image acquisitions were placed at different delay times (TD) after DIR preparation. SNR, T2* and Coefficient of Variation (COV) were measured and compared between DIR-prepared and non-DIR-prepared images. Canines with hemorrhagic myocardial infarctions were scanned at 3.0 T with DIR-prepared (dark-blood) and non-DIR-prepared (bright-blood) T2* imaging protocols. DIR-prepared T2* images were acquired with short, medium, and long delay times (TD). SNR, CNR, intramyocardial hemorrhage (IMH) extent, T2* and COV were measured and compared between DIR-prepared T2* images with short, medium, and long delay times (TD) to non-DIR-prepared bright-blood T2* images. RESULTS: Phantom studies confirmed the hypothesis that the SNR loss on DIR-prepared T2* images originated from signal loss during DIR preparation. SNR followed T1 recovery curve with increased delay times (TD) indicating that SNR can be recovered with longer time delay between DIR and image acquisition. Myocardial T2* values were not affected by DIR preparation but COV of T2* was elevated. Animal studies supported the hypothesis and showed that DIR-prepared T2* images with insufficient delay time (TD) had impaired sensitivity for IMH detection due to lower SNR and CNR, and higher COV. CONCLUSION: We conclude that lower SNR and CNR on DIR-prepared T2* images originate from signal loss during DIR preparation and insufficient recovery between DIR preparation and image acquisition. Although, the impaired sensitivity can be recovered by extending delay time (TD), it will extend the scan time. Bright-blood T2* imaging protocols should remain the optimal choice for assessment of intramyocardial hemorrhage. DIR-prepared dark-blood T2* imaging protocols should be performed with extra attention on image signal-to-noise ratio when used for intramyocardial hemorrhage detection.

Intramyocardial hemorrhage drives fatty degeneration of infarcted myocardium.

Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.

Quantification of myocardial hemorrhage using T2* cardiovascular magnetic resonance at 1.5T with ex-vivo validation.

BACKGROUND: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information. METHODS: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. RESULTS: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*. CONCLUSION: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.

Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance.

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

Visual-perceptual mismatch in robotic surgery.

BACKGROUND: The principal objective of the experiment was to analyze the effects of the clutch operation of robotic surgical systems on the performance of the operator. The relative coordinate system introduced by the clutch operation can introduce a visual-perceptual mismatch which can potentially have negative impact on a surgeon's performance. We also assess the impact of the introduction of additional tactile sensory information on reducing the impact of visual-perceptual mismatch on the performance of the operator. METHODS: We asked 45 novice subjects to complete peg transfers using the da Vinci IS 1200 system with grasper-mounted, normal force sensors. The task involves picking up a peg with one of the robotic arms, passing it to the other arm, and then placing it on the opposite side of the view. Subjects were divided into three groups: aligned group (no mismatch), the misaligned group (10 cm z axis mismatch), and the haptics-misaligned group (haptic feedback and z axis mismatch). Each subject performed the task five times, during which the grip force, time of completion, and number of faults were recorded. RESULTS: Compared to the subjects that performed the tasks using a properly aligned controller/arm configuration, subjects with a single-axis misalignment showed significantly more peg drops (p = 0.011) and longer time to completion (p < 0.001). Additionally, it was observed that addition of tactile feedback helps reduce the negative effects of visual-perceptual mismatch in some cases. Grip force data recorded from grasper-mounted sensors showed no difference between the different groups. CONCLUSIONS: The visual-perceptual mismatch created by the misalignment of the robotic controls relative to the robotic arms has a negative impact on the operator of a robotic surgical system. Introduction of other sensory information and haptic feedback systems can help in potentially reducing this effect.

Enhancement of osteogenesis and biodegradation control by brushite coating on Mg-Nd-Zn-Zr alloy for mandibular bone repair.

To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Gieson's picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.