Self-gated free-running 5D whole-heart MRI using blind source separation for automated cardiac motion extraction.

PURPOSE: To compare two blind source separation (BSS) techniques to principal component analysis and the electrocardiogram for the identification of cardiac triggers in self-gated free-running 5D whole-heart MRI. To ascertain the precision and robustness of the techniques, they were compared in three different noise and contrast regimes. METHODS: The repeated superior-inferior (SI) projections of a 3D radial trajectory were used to extract the physiological signals in three cardiac MRI cohorts: (1) 9 healthy volunteers without contrast agent injection at 1.5T, (2) 30 ferumoxytol-injected congenital heart disease patients at 1.5T, and (3) 12 gadobutrol-injected patients with suspected coronary artery disease at 3T. Self-gated cardiac triggers were extracted with the three algorithms (principal component analysis [PCA], second-order blind identification [SOBI], and independent component analysis [ICA]) and the difference with the electrocardiogram triggers was calculated. PCA and SOBI triggers were retained for image reconstruction. The image sharpness was ascertained on whole-heart 5D images obtained with PCA and SOBI and compared among the three cohorts. RESULTS: SOBI resulted in smaller trigger differences in Cohorts 1 and 3 compared to PCA (p < 0.01) and in all cohorts compared to ICA (p < 0.04). In Cohorts 1 and 3, the sharpness increased significantly in the reconstructed images when using SOBI instead of PCA (p < 0.03), but not in Cohort 2 (p = 0.4). CONCLUSION: We have shown that SOBI results in more precisely extracted self-gated triggers than PCA and ICA. The validation across three diverse cohorts demonstrates the robustness of the method against acquisition variability.

High on sparsity: Interbin compensation of cardiac motion for improved assessment of left-ventricular function using 5D whole-heart MRI.

PURPOSE: Cardiac magnetic resonance is the gold standard for evaluating left-ventricular ejection fraction (LVEF). Standard protocols, however, can be inefficient, facing challenges due to significant operator and patient involvement. Although the free-running framework (FRF) addresses these challenges, the potential of the extensive data it collects remains underutilized. Therefore, we propose to leverage the large amount of data collected by incorporating interbin cardiac motion compensation into FRF (FRF-MC) to improve both image quality and LVEF measurement accuracy, while reducing the sensitivity to user-defined regularization parameters. METHODS: FRF-MC consists of several steps: data acquisition, self-gating signal extraction, deformation field estimations, and motion-resolved reconstruction with interbin cardiac motion compensation. FRF-MC was compared with the original 5D-FRF method using LVEF and several image-quality metrics. The cardiac regularization weight ( λ c $$ {\lambda}_c $$ ) was optimized for both methods by maximizing image quality without compromising LVEF measurement accuracy. Evaluations were performed in numerical simulations and in 9 healthy participants. In vivo images were assessed by blinded expert reviewers and compared with reference standard 2D-cine images. RESULTS: Both in silico and in vivo results revealed that FRF-MC outperformed FRF in terms of image quality and LVEF accuracy. FRF-MC reduced temporal blurring, preserving detailed anatomy even at higher cardiac regularization weights, and led to more accurate LVEF measurements. Optimized λ c $$ {\lambda}_c $$ produced accurate LVEF for both methods compared with the 2D-cine reference (FRF-MC: 0.59% [-7.2%, 6.0%], p = 0.47; FRF: 0.86% [-8.5%, 6.7%], p = 0.36), but FRF-MC resulted in superior image quality (FRF-MC: 2.89 ± 0.58, FRF: 2.11 ± 0.47; p < 10-3). CONCLUSION: Incorporating interbin cardiac motion compensation significantly improved image quality, supported higher cardiac regularization weights without compromising LVEF measurement accuracy, and reduced sensitivity to user-defined regularization parameters.

Combined free-running four-dimensional anatomical and flow magnetic resonance imaging with native contrast using Synchronization of Neighboring Acquisitions by Physiological Signals.

BACKGROUND: Four-dimensional (4D) flow magnetic resonance imaging (MRI) often relies on the injection of gadolinium- or iron-oxide-based contrast agents to improve vessel delineation. In this work, a novel technique is developed to acquire and reconstruct 4D flow data with excellent dynamic visualization of blood vessels but without the need for contrast injection. Synchronization of Neighboring Acquisitions by Physiological Signals (SyNAPS) uses pilot tone (PT) navigation to retrospectively synchronize the reconstruction of two free-running three-dimensional radial acquisitions, to create co-registered anatomy and flow images. METHODS: Thirteen volunteers and two Marfan syndrome patients were scanned without contrast agent using one free-running fast interrupted steady-state (FISS) sequence and one free-running phase-contrast MRI (PC-MRI) sequence. PT signals spanning the two sequences were recorded for retrospective respiratory motion correction and cardiac binning. The magnitude and phase images reconstructed, respectively, from FISS and PC-MRI, were synchronized to create SyNAPS 4D flow datasets. Conventional two-dimensional (2D) flow data were acquired for reference in ascending (AAo) and descending aorta (DAo). The blood-to-myocardium contrast ratio, dynamic vessel area, net volume, and peak flow were used to compare SyNAPS 4D flow with Native 4D flow (without FISS information) and 2D flow. A score of 0-4 was given to each dataset by two blinded experts regarding the feasibility of performing vessel delineation. RESULTS: Blood-to-myocardium contrast ratio for SyNAPS 4D flow magnitude images (1.5 ± 0.3) was significantly higher than for Native 4D flow (0.7 ± 0.1, p < 0.01) and was comparable to 2D flow (2.3 ± 0.9, p = 0.02). Image quality scores of SyNAPS 4D flow from the experts (M.P.: 1.9 ± 0.3, E.T.: 2.5 ± 0.5) were overall significantly higher than the scores from Native 4D flow (M.P.: 1.6 ± 0.6, p = 0.03, E.T.: 0.8 ± 0.4, p < 0.01) but still significantly lower than the scores from the reference 2D flow datasets (M.P.: 2.8 ± 0.4, p < 0.01, E.T.: 3.5 ± 0.7, p < 0.01). The Pearson correlation coefficient between the dynamic vessel area measured on SyNAPS 4D flow and that from 2D flow was 0.69 ± 0.24 for the AAo and 0.83 ± 0.10 for the DAo, whereas the Pearson correlation between Native 4D flow and 2D flow measurements was 0.12 ± 0.48 for the AAo and 0.08 ± 0.39 for the DAo. Linear correlations between SyNAPS 4D flow and 2D flow measurements of net volume (r2 = 0.83) and peak flow (r2 = 0.87) were larger than the correlations between Native 4D flow and 2D flow measurements of net volume (r2 = 0.79) and peak flow (r2 = 0.76). CONCLUSION: The feasibility and utility of SyNAPS were demonstrated for joint whole-heart anatomical and flow MRI without requiring electrocardiography gating, respiratory navigators, or contrast agents. Using SyNAPS, a high-contrast anatomical imaging sequence can be used to improve 4D flow measurements that often suffer from poor delineation of vessel boundaries in the absence of contrast agents.

Intra-bin correction and inter-bin compensation of respiratory motion in free-running five-dimensional whole-heart magnetic resonance imaging.

BACKGROUND: Free-running cardiac and respiratory motion-resolved whole-heart five-dimensional (5D) cardiovascular magnetic resonance (CMR) can reduce scan planning and provide a means of evaluating respiratory-driven changes in clinical parameters of interest. However, respiratory-resolved imaging can be limited by user-defined parameters which create trade-offs between residual artifact and motion blur. In this work, we develop and validate strategies for both correction of intra-bin and compensation of inter-bin respiratory motion to improve the quality of 5D CMR. METHODS: Each component of the reconstruction framework was systematically validated and compared to the previously established 5D approach using simulated free-running data (N = 50) and a cohort of 32 patients with congenital heart disease. The impact of intra-bin respiratory motion correction was evaluated in terms of image sharpness while inter-bin respiratory motion compensation was evaluated in terms of reconstruction error, compression of respiratory motion, and image sharpness. The full reconstruction framework (intra-acquisition correction and inter-acquisition compensation of respiratory motion [IIMC] 5D) was evaluated in terms of image sharpness and scoring of image quality by expert reviewers. RESULTS: Intra-bin motion correction provides significantly (p < 0.001) sharper images for both simulated and patient data. Inter-bin motion compensation results in significant (p < 0.001) lower reconstruction error, lower motion compression, and higher sharpness in both simulated (10/11) and patient (9/11) data. The combined framework resulted in significantly (p < 0.001) sharper IIMC 5D reconstructions (End-expiration (End-Exp): 0.45 ± 0.09, End-inspiration (End-Ins): 0.46 ± 0.10) relative to the previously established 5D implementation (End-Exp: 0.43 ± 0.08, End-Ins: 0.39 ± 0.09). Similarly, image scoring by three expert reviewers was significantly (p < 0.001) higher using IIMC 5D (End-Exp: 3.39 ± 0.44, End-Ins: 3.32 ± 0.45) relative to 5D images (End-Exp: 3.02 ± 0.54, End-Ins: 2.45 ± 0.52). CONCLUSION: The proposed IIMC reconstruction significantly improves the quality of 5D whole-heart MRI. This may be exploited for higher resolution or abbreviated scanning. Further investigation of the diagnostic impact of this framework and comparison to gold standards is needed to understand its full clinical utility, including exploration of respiratory-driven changes in physiological measurements of interest.

Trajectory correction enables free-running chemical shift encoded imaging for accurate cardiac proton-density fat fraction quantification at 3T.

BACKGROUND: Metabolic diseases can negatively alter epicardial fat accumulation and composition, which can be probed using quantitative cardiac chemical shift encoded (CSE) cardiovascular magnetic resonance (CMR) by mapping proton-density fat fraction (PDFF). To obtain motion-resolved high-resolution PDFF maps, we proposed a free-running cardiac CSE-CMR framework at 3T. To employ faster bipolar readout gradients, a correction for gradient imperfections was added using the gradient impulse response function (GIRF) and evaluated on intermediate images and PDFF quantification. METHODS: Ten minutes free-running cardiac 3D radial CSE-CMR acquisitions were compared in vitro and in vivo at 3T. Monopolar and bipolar readout gradient schemes provided 8 echoes (TE1/ΔTE = 1.16/1.96 ms) and 13 echoes (TE1/ΔTE = 1.12/1.07 ms), respectively. Bipolar-gradient free-running cardiac fat and water images and PDFF maps were reconstructed with or without GIRF correction. PDFF values were evaluated in silico, in vitro on a fat/water phantom, and in vivo in 10 healthy volunteers and 3 diabetic patients. RESULTS: In monopolar mode, fat-water swaps were demonstrated in silico and confirmed in vitro. Using bipolar readout gradients, PDFF quantification was reliable and accurate with GIRF correction with a mean bias of 0.03% in silico and 0.36% in vitro while it suffered from artifacts without correction, leading to a PDFF bias of 4.9% in vitro and swaps in vivo. Using bipolar readout gradients, in vivo PDFF of epicardial adipose tissue was significantly lower compared to subcutaneous fat (80.4 ± 7.1% vs 92.5 ± 4.3%, P < 0.0001). CONCLUSIONS: Aiming for an accurate PDFF quantification, high-resolution free-running cardiac CSE-MRI imaging proved to benefit from bipolar echoes with k-space trajectory correction at 3T. This free-breathing acquisition framework enables to investigate epicardial adipose tissue PDFF in metabolic diseases.

Ingrained city rhythms: flexible activity timing but more persistent circadian pace in urban birds.

Urbanization dramatically increases the amount of light at night, which may disrupt avian circadian organization. We measured activity patterns of great tits breeding in the city and forest, and subsequently measured two clock properties of these birds under controlled conditions: tau (endogenous circadian clock speed) and after-effects (history dependency of the clock relative to previous conditions). City and forest birds showed a high repeatability of activity onset (0.60 and 0.41, respectively), with no difference between habitats after controlling for date effects. Activity duration and offset showed more variance, without a difference between birds from the two habitats. Tau did not differ between city and forest birds, however, city birds showed stronger after-effects, taking more days to revert to their endogenous circadian period. Finally, onset of activity was correlated with clocks speed in both habitats. Our results suggest that potential differences in activity timing of city birds is not caused by different clock speeds, but by a direct response to light. Persistence in after-effects suggests a reduced sensitivity of the clock to light at night. Urbanization may select for clock properties that increase the inertia of the endogenous circadian system to improve accuracy of activity rhythms when exposed to noisier lighting cues.

Focused navigation for respiratory-motion-corrected free-running radial 4D flow MRI.

PURPOSE: To validate a respiratory motion correction method called focused navigation (fNAV) for free-running radial whole-heart 4D flow MRI. METHODS: Using fNAV, respiratory signals derived from radial readouts are converted into three orthogonal displacements, which are then used to correct respiratory motion in 4D flow datasets. Hundred 4D flow acquisitions were simulated with non-rigid respiratory motion and used for validation. The difference between generated and fNAV displacement coefficients was calculated. Vessel area and flow measurements from 4D flow reconstructions with (fNAV) and without (uncorrected) motion correction were compared to the motion-free ground-truth. In 25 patients, the same measurements were compared between fNAV 4D flow, 2D flow, navigator-gated Cartesian 4D flow, and uncorrected 4D flow datasets. RESULTS: For simulated data, the average difference between generated and fNAV displacement coefficients was 0.04 ± $$ \pm $$ 0.32 mm and 0.31 ± $$ \pm $$ 0.35 mm in the x and y directions, respectively. In the z direction, this difference was region-dependent (0.02 ± $$ \pm $$ 0.51 mm up to 5.85 ± $$ \pm $$ 3.41 mm). For all measurements (vessel area, net volume, and peak flow), the average difference from ground truth was higher for uncorrected 4D flow datasets (0.32 ± $$ \pm $$ 0.11 cm2 , 11.1 ± $$ \pm $$ 3.5 mL, and 22.3 ± $$ \pm $$ 6.0 mL/s) than for fNAV 4D flow datasets (0.10 ± $$ \pm $$ 0.03 cm2 , 2.6 ± $$ \pm $$ 0.7 mL, and 5.1 ± 0 $$ \pm 0 $$ .9 mL/s, p < 0.05). In vivo, average vessel area measurements were 4.92 ± $$ \pm $$ 2.95 cm2 , 5.06 ± $$ \pm $$ 2.64 cm2 , 4.87 ± $$ \pm $$ 2.57 cm2 , 4.87 ± $$ \pm $$ 2.69 cm2 , for 2D flow and fNAV, navigator-gated and uncorrected 4D flow datasets, respectively. In the ascending aorta, all 4D flow datasets except for the fNAV reconstruction had significantly different vessel area measurements from 2D flow. Overall, 2D flow datasets demonstrated the strongest correlation to fNAV 4D flow for both net volume (r2  = 0.92) and peak flow (r2  = 0.94), followed by navigator-gated 4D flow (r2  = 0.83 and r2  = 0.86, respectively), and uncorrected 4D flow (r2  = 0.69 and r2  = 0.86, respectively). CONCLUSION: fNAV corrected respiratory motion in vitro and in vivo, resulting in fNAV 4D flow measurements that are comparable to those derived from 2D flow and navigator-gated Cartesian 4D flow datasets, with improvements over those from uncorrected 4D flow.

Free-running 3D whole-heart T1 and T2 mapping and cine MRI using low-rank reconstruction with non-rigid cardiac motion correction.

PURPOSE: To introduce non-rigid cardiac motion correction into a novel free-running framework for the simultaneous acquisition of 3D whole-heart myocardial T 1 $$ {T}_1 $$ and T 2 $$ {T}_2 $$ maps and cine images, enabling a ∼ $$ \sim $$ 3-min scan. METHODS: Data were acquired using a free-running 3D golden-angle radial readout interleaved with inversion recovery and T 2 $$ {T}_2 $$ -preparation pulses. After correction for translational respiratory motion, non-rigid cardiac-motion-corrected reconstruction with dictionary-based low-rank compression and patch-based regularization enabled 3D whole-heart T 1 $$ {T}_1 $$ and T 2 $$ {T}_2 $$ mapping at any given cardiac phase as well as whole-heart cardiac cine imaging. The framework was validated and compared with established methods in 11 healthy subjects. RESULTS: Good quality 3D T 1 $$ {T}_1 $$ and T 2 $$ {T}_2 $$ maps and cine images were reconstructed for all subjects. Septal T 1 $$ {T}_1 $$ values using the proposed approach ( 1200 ± 50 $$ 1200\pm 50 $$ ms) were higher than those from a 2D MOLLI sequence ( 1063 ± 33 $$ 1063\pm 33 $$ ms), which is known to underestimate T 1 $$ {T}_1 $$ , while T 2 $$ {T}_2 $$ values from the proposed approach ( 51 ± 4 $$ 51\pm 4 $$ ms) were in good agreement with those from a 2D GraSE sequence ( 51 ± 2 $$ 51\pm 2 $$ ms). CONCLUSION: The proposed technique provides 3D T 1 $$ {T}_1 $$ and T 2 $$ {T}_2 $$ maps and cine images with isotropic spatial resolution in a single ∼ $$ \sim $$ 3.3-min scan.

An Investigation of All Fiber Free-Running Dual-Comb Spectroscopy.

A dual-comb spectroscopy (DCS) system uses two phase-locked optical frequency combs with a slight difference in the repetition frequency. The spectrum can be sampled in the optical frequency (OF) domain and reproduces the characteristics in the radio frequency (RF) domain through asynchronous optical sampling. Therefore, the DCS system shows great advantages in achieving precision spectral measurement. During application, the question of how to reserve the mutual coherence between the two combs is the key issue affecting the application of the DCS system. This paper focuses on a software algorithm used to realize the mutual coherence of the two combs. Therefore, a pair of free-running large anomalous dispersion fiber combs, with a center wavelength of approximately 1064 nm, was used. After the signal process, the absorption spectra of multiple species were simultaneously obtained (simulated using the reflective spectra of narrow-bandwidth fiber Bragg gratings, abbreviated as FBG). The signal-to-noise ratio (SNR) could reach 13.97 dB (25) during the 100 ms sampling time. In this study, the feasibility of the system was first verified through the simulation system; then, a principal demonstration experiment was successfully executed. The whole system was connected by the optical fiber without additional phase-locking equipment, showing promise as a potential solution for the low-cost and practical application of DCS systems.

Pilot tone navigation for respiratory and cardiac motion-resolved free-running 5D flow MRI.

PURPOSE: In this work, we integrated the pilot tone (PT) navigation system into a reconstruction framework for respiratory and cardiac motion-resolved 5D flow. We tested the hypotheses that PT would provide equivalent respiratory curves, cardiac triggers, and corresponding flow measurements to a previously established self-gating (SG) technique while being independent from changes to the acquisition parameters. METHODS: Fifteen volunteers and 9 patients were scanned with a free-running 5D flow sequence, with PT integrated. Respiratory curves and cardiac triggers from PT and SG were compared across all subjects. Flow measurements from 5D flow reconstructions using both PT and SG were compared to each other and to a reference electrocardiogram-gated and respiratory triggered 4D flow acquisition. Radial trajectories with variable readouts per interleave were also tested in 1 subject to compare cardiac trigger quality between PT and SG. RESULTS: The correlation between PT and SG respiratory curves were 0.95 ± 0.06 for volunteers and 0.95 ± 0.04 for patients. Heartbeat duration measurements in volunteers and patients showed a bias to electrocardiogram measurements of, respectively, 0.16 ± 64.94 ms and 0.01 ± 39.29 ms for PT versus electrocardiogram and of 0.24 ± 63.68 ms and 0.09 ± 32.79 ms for SG versus electrocardiogram. No significant differences were reported for the flow measurements between 5D flow PT and from 5D flow SG. A decrease in the cardiac triggering quality of SG was observed for increasing readouts per interleave, whereas PT quality remained constant. CONCLUSION: PT has been successfully integrated in 5D flow MRI and has shown equivalent results to the previously described 5D flow SG technique, while being completely acquisition-independent.

A fixed single meal in the subjective day prevents free-running of the human sleep-wake cycle but not of the circadian pacemaker under temporal isolation.

Effects of a fixed single meal per day were examined on the circadian pacemaker and sleep-wake cycle in subjects under temporal isolation. When the time of single meal was allowed to take at any time of day (ad-lib meal), the sleep-wake cycle as well as the circadian rhythms in plasma melatonin, cortisol, and core body temperature were significantly phase-delayed in 8 days. On the other hand, when the time of meal was fixed at 1800 h in local time (RF meal), the phase-shift of sleep-wake cycle was not significant while those of the circadian rhythms were significant. The differential effects of a fixed single meal schedule were confirmed in most individual subjects. There was no evidence for the prefeeding increase in plasma cortisol and leptin levels under the fixed single meal schedule. The plasma ghrelin level was apparently high before meal in both ad-lib and RF meal groups, which was, however, likely sculptured by a nonspecific prandial drop and gradual increase after meal intake. Single meal augmented the prandial increase of plasma insulin levels by four to five times. These findings indicate that a single meal at a fixed time of the day during the subjective day failed to prevent the human circadian pacemaker but prevented the sleep-wake cycle from free running for at least 8 days under temporal isolation, suggesting that mealtime was a potent nonphotic time cue for the human sleep-wake cycle.

Paclitaxel chemotherapy disrupts behavioral and molecular circadian clocks in mice.

Cancer patients experience circadian rhythm disruptions in activity cycles and cortisol release that correlate with poor quality of life and decreased long-term survival rates. However, the extent to which chemotherapy contributes to altered circadian rhythms is poorly understood. In the present study, we examined the extent to which paclitaxel, a common chemotherapy drug, altered entrained and free-running circadian rhythms in wheel running behavior, circulating corticosterone, and circadian clock gene expression in the brain and adrenal glands of tumor-free mice. Paclitaxel injections delayed voluntary wheel running activity onset in a light-dark cycle (LD) and lengthened the free-running period of locomotion in constant darkness (DD), indicating an effect on inherent suprachiasmatic nucleus (SCN) pacemaker activity. Paclitaxel attenuated clock gene rhythms in multiple brain regions in LD and DD. Furthermore, paclitaxel disrupted circulating corticosterone rhythms in DD by elevating its levels across a 24-hour cycle, which correlated with blunted amplitudes of Arntl, Nr1d1, Per1, and Star rhythms in the adrenal glands. Paclitaxel also shortened SCN slice rhythms, increased the amplitude of adrenal gland oscillations in PER2::luciferase cultures, and increased the concentration of pro-inflammatory cytokines and chemokines released from the SCN. These findings indicate that paclitaxel disrupts clock genes and behavior driven by the SCN, other brain regions, and adrenal glands, which were associated with chemotherapy-induced inflammation. Together, this preclinical work demonstrates that chemotherapy disrupts both central and peripheral circadian rhythms and supports the possibility that targeted circadian realignment therapies may be a novel and non-invasive way to improve patient outcomes after chemotherapy.

Free-running cardiac and respiratory motion-resolved 5D whole-heart coronary cardiovascular magnetic resonance angiography in pediatric cardiac patients using ferumoxytol.

BACKGROUND: Coronary cardiovascular magnetic resonance angiography (CCMRA) of congenital heart disease (CHD) in pediatric patients requires accurate planning, adequate sequence parameter adjustments, lengthy scanning sessions, and significant involvement from highly trained personnel. Anesthesia and intubation are commonplace to minimize movements and control respiration in younger subjects. To address the above concerns and provide a single-click imaging solution, we applied our free-running framework for fully self-gated (SG) free-breathing 5D whole-heart CCMRA to CHD patients after ferumoxytol injection. We tested the hypothesis that spatial and motion resolution suffice to visualize coronary artery ostia in a cohort of CHD subjects, both for intubated and free-breathing acquisitions. METHODS: In 18 pediatric CHD patients, non-electrocardiogram (ECG) triggered 5D free-running gradient echo CCMRA with whole-heart 1 mm3 isotropic spatial resolution was performed in seven minutes on a 1.5T CMR scanner. Eleven patients were anesthetized and intubated, while seven were breathing freely without anesthesia. All patients were slowly injected with ferumoxytol (4 mg/kg) over 15 minutes. Cardiac and respiratory motion-resolved 5D images were reconstructed with a fully SG approach. To evaluate the performance of motion resolution, visibility of coronary artery origins was assessed. Intubated and free-breathing patient sub-groups were compared for image quality using coronary artery length and conspicuity as well as lung-liver interface sharpness. RESULTS: Data collection using the free-running framework was successful in all patients in less than 8 min; scan planning was very simple without the need for parameter adjustments, while no ECG lead placement and triggering was required. From the resulting SG 5D motion-resolved reconstructed images, coronary artery origins could be retrospectively extracted in 90% of the cases. These general findings applied to both intubated and free-breathing pediatric patients (no difference in terms of lung-liver interface sharpness), while image quality and coronary conspicuity between both cohorts was very similar. CONCLUSIONS: A simple-to-use push-button framework for 5D whole-heart CCMRA was successfully employed in pediatric CHD patients with ferumoxytol injection. This approach, working without any external gating and for a wide range of heart rates and body sizes provided excellent definition of cardiac anatomy for both intubated and free-breathing patients.

Constant Light, Pdp1, and Tim Exert Influence on Free-Running Period of Locomotor Rhythms in the Cricket Gryllus bimaculatus.

Most insects show circadian rhythms of which the free-running period changes in a light-dependent manner and is generally longer under constant light (LL) than under constant dark conditions in nocturnal animals. However, the mechanism underlying this LL-dependent period change remains unclear. Here, using the cricket Gryllus bimaculatus, we examined the effects of long-term LL exposure on the free-running period of locomotor rhythms. Initially, the free-running period was considerably longer than 24 h but it gradually became shorter during long-term exposure to LL. The initial lengthening and ensuing gradual shortening under long-term LL exposure were observed even after unilateral removal of the optic lobe. Thus, these changes in the free-running period could be attributable to a single optic lobe clock. RNA interference (RNAi)-mediated silencing of the clock genes Par domain protein 1 (Pdp1) and timeless (tim) revealed that the treatments eliminated the initial period lengthening by LL without reducing circadian photoreceptor gene expression. However, they did not affect the period shortening during long-term LL exposure. The slopes of the regression line for the period change during long-term LL for Pdp1RNAi-treated and timRNAi-treated crickets were not different from that of the dsDsRed2-treated control. These results suggest that the initial period lengthening after transfer to LL requires tim and Pdp1, while the ensuing period shortening during long-term LL exposure is caused by a mechanism independent of tim and Pdp1.

Polygalae Radix shortens the circadian period through activation of the CaMKII pathway.

CONTEXT: The mammalian circadian clock system regulates physiological function. Crude drugs, containing Polygalae Radix, and Kampo, combining multiple crude drugs, have been used to treat various diseases, but few studies have focussed on the circadian clock. OBJECTIVE: We examine effective crude drugs, which cover at least one or two of Kampo, for the shortening effects on period length of clock gene expression rhythm, and reveal the mechanism of shortening effects. MATERIALS AND METHODS: We prepared 40 crude drugs. In the in vitro experiments, we used mouse embryonic fibroblasts from PERIOD2::LUCIFERASE knock-in mice (background; C57BL/6J mice) to evaluate the effect of crude drugs on the period length of core clock gene, Per2, expression rhythm by chronic treatment (six days) with distilled water or crude drugs (100 µg/mL). In the in vivo experiments, we evaluated the free-running period length of C57BL/6J mice fed AIN-93M or AIN-93M supplemented with 1% crude drug (6 weeks) that shortened the period length of the PERIOD2::LUCIFERASE expression rhythm in the in vitro experiments. RESULTS: We found that Polygalae Radix (ED50: 24.01 µg/mL) had the most shortened PERIOD2::LUCIFERASE rhythm period length in 40 crude drugs and that the CaMKII pathway was involved in this effect. Moreover, long-term feeding with AIN-93M+Polygalae Radix slightly shortened the free-running period of the mouse locomotor activity rhythm. DISCUSSION AND CONCLUSIONS: Our results indicate that Polygalae Radix may be regarded as a new therapy for circadian rhythm disorder and that the CaMKII pathway may be regarded as a target pathway for circadian rhythm disorders.

Artifact reduction in free-breathing, free-running myocardial perfusion imaging with interleaved non-selective RF excitations.

PURPOSE: To reduce inflow and motion artifacts in free-breathing, free-running, steady-state spoiled gradient echo T1 -weighted (SPGR) myocardial perfusion imaging. METHOD: Unsaturated spins from inflowing blood or out-of-plane motion cause flashing artifacts in free-running SPGR myocardial perfusion. During free-running SPGR, 1 non-selective RF excitation was added after every 3 slice-selective RF excitations to suppress inflow artifacts by forcing magnetization in neighboring regions to steady-state. Bloch simulations and phantom experiments were performed to evaluate the impact of the flip angle and non-selective RF frequency on inflowing spins and tissue contrast. Free-running perfusion with (n = 11) interleaved non-selective RF or without (n = 11) were studied in 22 subjects (age = 60.2 ± 14.3 years, 11 male). Perfusion images were graded on a 5-point Likert scale for conspicuity of wall enhancement, inflow/motion artifact, and streaking artifact and compared using Wilcoxon sum-rank testing. RESULT: Numeric simulation showed that 1 non-selective RF excitation applied after every 3 slice-selective RF excitations produced superior out-of-plane signal suppression compared to 1 non-selective RF excitation applied after every 6 or 9 slice-selective RF excitations. In vitro experiments showed that a 30° flip angle produced near-optimal myocardial contrast. In vivo experiments demonstrated that the addition of interleaved non-selective RF significantly (P < .01) improved conspicuity of wall enhancement (mean score = 4.4 vs. 3.2) and reduced inflow/motion (mean score = 4.5 vs. 2.5) and streaking (mean score = 3.9 vs. 2.4) artifacts. CONCLUSION: Non-selective RF excitations interleaved between slice-selective excitations can reduce image artifacts in free-breathing, ungated perfusion images. Further studies are warranted to assess the diagnostic accuracy of the proposed solution for evaluating myocardial ischemia.

Similarity-driven multi-dimensional binning algorithm (SIMBA) for free-running motion-suppressed whole-heart MRA.

PURPOSE: Whole-heart MRA techniques typically target predetermined motion states, address cardiac and respiratory dynamics independently, and require either complex planning or computationally demanding reconstructions. In contrast, we developed a fast data-driven reconstruction algorithm with minimal physiological assumptions and compatibility with ungated free-running sequences. THEORY AND METHODS: We propose a similarity-driven multi-dimensional binning algorithm (SIMBA) that clusters continuously acquired k-space data to find a motion-consistent subset for whole-heart MRA reconstruction. Free-running 3D radial data sets from 12 non-contrast-enhanced scans of healthy volunteers and six ferumoxytol-enhanced scans of pediatric cardiac patients were reconstructed with non-motion-suppressed regridding of all the acquired data ("All Data"), with SIMBA, and with a previously published free-running framework (FRF) that uses cardiac and respiratory self-gating and compressed sensing. Images were compared for blood-myocardium sharpness and contrast ratio, visibility of coronary artery ostia, and right coronary artery sharpness. RESULTS: Both the 20-second SIMBA reconstruction and FRF provided significantly higher blood-myocardium sharpness than All Data in both patients and volunteers (P < .05). The SIMBA reconstruction provided significantly sharper blood-myocardium interfaces than FRF in volunteers (P < .001) and higher blood-myocardium contrast ratio than All Data and FRF, both in volunteers and patients (P < .05). Significantly more ostia could be visualized with both SIMBA (31 of 36) and FRF (34 of 36) than with All Data (4 of 36) (P < .001). Inferior right coronary artery sharpness using SIMBA versus FRF was observed (volunteers: SIMBA 36.1 ± 8.1%, FRF 40.4 ± 8.9%; patients: SIMBA 35.9 ± 7.7%, FRF 40.3 ± 6.1%, P = not significant). CONCLUSION: The SIMBA technique enabled a fast, data-driven reconstruction of free-running whole-heart MRA with image quality superior to All Data and similar to the more time-consuming FRF reconstruction.

Fully self-gated free-running 3D Cartesian cardiac CINE with isotropic whole-heart coverage in less than 2 min.

PURPOSE: To develop a novel fast water-selective free-breathing 3D Cartesian cardiac CINE scan with full self-navigation and isotropic whole-heart (WH) coverage. METHODS: A free-breathing 3D Cartesian cardiac CINE scan with a water-selective balanced steady-state free precession and a continuous (non-ECG-gated) variable-density Cartesian sampling with spiral profile ordering, out-inward sampling and acquisition-adaptive alternating tiny golden and golden angle increment between spiral arms is proposed. Data is retrospectively binned based on respiratory and cardiac self-navigation signals. A translational respiratory-motion-corrected and cardiac-motion-resolved image is reconstructed with a multi-bin patch-based low-rank reconstruction (MB-PROST) within about 15 min. A respiratory-motion-resolved approach is also investigated. The proposed 3D Cartesian cardiac CINE is acquired in sagittal orientation in 1 min 50 s for 1.9 mm3 isotropic WH coverage. Left ventricular (LV) function parameters and image quality derived from a blinded reading of the proposed 3D CINE framework are compared against conventional multi-slice 2D CINE imaging in 10 healthy subjects and 10 patients with suspected cardiovascular disease. RESULTS: The proposed framework provides free-breathing 3D cardiac CINE images with 1.9 mm3 spatial and about 45 ms temporal resolution in a short acquisition time (<2 min). LV function parameters derived from 3D CINE were in good agreement with 2D CINE (10 healthy subjects and 10 patients). Bias and confidence intervals were obtained for end-systolic volume, end-diastolic volume and ejection fraction of 0.1 ± 3.5 mL, -0.6 ± 8.2 mL and -0.1 ± 2.2%, respectively. CONCLUSION: The proposed framework enables isotropic 3D Cartesian cardiac CINE under free breathing for fast assessment of cardiac anatomy and function.

A Two-Step Model of Human Entrainment: A Quantitative Study of Circadian Period and Phase of Entrainment.

One of the essential characteristics of an authentic circadian clock is that the free-running period sustains an approximately 24-hour cycle. When organisms are exposed to an external stimulus, the endogenous oscillators synchronize to the cycling environment signal in a process known as entrainment. These environmental cues perform an important role in resetting the phase and period of the circadian clock. A "generalized assumption" states that when an organism has a short period, it will experience a phase advance, while an organism with a long period experiences a phase delay. Despite widespread use, this positive relationship relating period to the phase of entrainment does not describe all known experimental data. We developed a two-step entrainment model to explain a broader range of results as well as provide more quantitative analysis. We prove existence and stability of periodic orbits and given analytical solutions of the range of entrainment, fit the phase trajectory over the entire entrainment process to data from a published study for 12 subjects in extended day cycles, i.e., longer than 24 h. Our simulations closely replicated the phase data and predicted correctly the phase of entrainment. We investigate the factors related to the rate of entrainment (ROE) and present the three-dimensional parameter spaces, illustrating the various behaviors of the phase of entrainment and ROE. Our findings can be applied to diagnostics and treatments for patients with sleep disorders caused by shift work or jet lag.

3D magnetization transfer (MT) for the visualization of cardiac free-running Purkinje fibers: an ex vivo proof of concept.

OBJECTIVES: We investigate the possibility to exploit high-field MRI to acquire 3D images of Purkinje network which plays a crucial role in cardiac function. Since Purkinje fibers (PF) have a distinct cellular structure and are surrounded by connective tissue, we investigated conventional contrast mechanisms along with the magnetization transfer (MT) imaging technique to improve image contrast between ventricular structures of differing macromolecular content. METHODS: Three fixed porcine ventricular samples were used with free-running PFs on the endocardium. T1, T2*, T2, and M0 were evaluated on 2D slices for each sample at 9.4 T. MT parameters were optimized using hard pulses with different amplitudes, offset frequencies and durations. The cardiac structure was assessed through 2D and 3D T1w images with isotropic resolutions of 150 µm. Histology, immunofluorescence, and qPCR were performed to analyze collagen contents of cardiac tissue and PF. RESULTS: An MT preparation module of 350 ms duration inserted into the sequence with a B1 = 10 µT and frequency offset = 3000 Hz showed the best contrast, approximately 0.4 between PFs and myocardium. Magnetization transfer ratio (MTR) appeared higher in the cardiac tissue (MTR = 44.7 ± 3.5%) than in the PFs (MTR = 25.2 ± 6.3%). DISCUSSION: MT significantly improves contrast between PFs and ventricular myocardium and appears promising for imaging the 3D architecture of the Purkinje network.