A pharmacokinetic model for hyperpolarized 13C-pyruvate MRI when using metabolite-specific bSSFP sequences.

PURPOSE: Metabolite-specific balanced SSFP (MS-bSSFP) sequences are increasingly used in hyperpolarized [1-13C]Pyruvate (HP 13C) MRI studies as they improve SNR by refocusing the magnetization each TR. Currently, pharmacokinetic models used to fit conversion rate constants, kPL and kPB, and rate constant maps do not account for differences in the signal evolution of MS-bSSFP acquisitions. METHODS: In this work, a flexible MS-bSSFP model was built that can be used to fit conversion rate constants for these experiments. The model was validated in vivo using paired animal (healthy rat kidneys n = 8, transgenic adenocarcinoma of the mouse prostate n = 3) and human renal cell carcinoma (n = 3) datasets. Gradient echo (GRE) acquisitions were used with a previous GRE model to compare to the results of the proposed GRE-bSSFP model. RESULTS: Within simulations, the proposed GRE-bSSFP model fits the simulated data well, whereas a GRE model shows bias because of model mismatch. For the in vivo datasets, the estimated conversion rate constants using the proposed GRE-bSSFP model are consistent with a previous GRE model. Jointly fitting the lactate T2 with kPL resulted in less precise kPL estimates. CONCLUSION: The proposed GRE-bSSFP model provides a method to estimate conversion rate constants, kPL and kPB, for MS-bSSFP HP 13C experiments. This model may also be modified and used for other applications, for example, estimating rate constants with other hyperpolarized reagents or multi-echo bSSFP.

Drp1-dependent mitochondrial fragmentation mediates photoreceptor abnormalities in type 1 diabetic retina.

Recent studies have highlighted that retinal neurodegeneration precedes microvascular changes in diabetic retinopathy (DR), but the specific mechanisms remain unclear. Given the pivotal role of dysfunctional mitochondria and oxidative stress in early DR, our objective was to observe mitochondria-related alterations in the neural retina of type one diabetic mellitus mice with no evidence of DR (T1DM-NDR). We aimed to identify the key mitochondrial-related proteins contributing to mitochondrial injury. Our study revealed that T1DM-NDR mice exhibited outer retina thinning, including the ellipsoid zone, inner segment, and outer segment. Additionally, there was an impaired amplitude of the b-wave in electroretinogram (ERG) and a disorganized arrangement of the photoreceptor layer. In both the retina of DM mice and high glucose (HG)-treated 661w cells, mitochondria appeared swollen and fragmented, with disrupted cristae, disorganized or shortened branches in the mitochondrial network, and decreased mitochondrial membrane potential. Among the mitochondrial-related proteins, dynamin-related protein 1 (Drp1) was upregulated, and the ratio of phosphorylated Drp1 protein at serine 616 (S616) and serine 637 (S637) sites significantly increased in the retina of DM mice. The administration of Mdivi-1 ameliorated high-glucose-induced dysfunctional mitochondria, thereby protecting T1DM-NDR mice retina from morphological and functional injuries. Our findings suggest that hyperglycemia promotes Drp1-mediated mitochondrial dysfunction, which may be a significant factor in the development of DR. The inhibition of high-glucose-induced mitochondrial fission emerges as a potential and innovative intervention strategy for preventing DR.

Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate CMR evaluated in an oral glucose challenge.

BACKGROUND: The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy. METHODS: We developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load). RESULTS: We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant. CONCLUSIONS: We demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.

Heart rhythm complexity analysis in patients with inferior ST-elevation myocardial infarction.

Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1-5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1-5) had the best predictive value. MSE slope 1-5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1-5 was a good predictor of postinfarct LV systolic impairment.

H/F Substitution Achieved Enantiomeric Organic Inorganic Hybrid Perovskites and Trigonal Structure [DMFP]3(CdBr3)(CdBr4).

Organic-inorganic hybrid perovskites (OIHPs) have been emerging as a hot research topic due to their potential applications in energy storage, semiconductors, and electronic devices. Herein, we systematically investigated the synthesis and phase transition behaviors of the enantiomeric OIHPs, (R) and (S)-N,N-dimethyl-3-fluoropyrrolidinium cadmium bromide ([DMFP][CdBr3]), and the hybrid trigonal structure [DMFP]3 (CdBr3)(CdBr4). The enantiomers have a mirror-symmetric structure and enhanced solid-state phase transition points of 417 and 443 K, in contrast to the nonfluorinated parent compound, N,N-dimethyl-pyrrolidinium cadmium bromide ([DMP][CdBr3], 385 K). Moreover, racemic H/F substitution on the pyrrolidinium cations leads to the formation of a trigonal compound, showing above-room-temperature structural phase transition and dominant ferroelasticity. This work discovers chiral enantiomeric OIHPs through H/F substitution, demonstrating a useful chemical synthesis strategy for exploring novel phase transition materials.

Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate MRI evaluated in an oral glucose challenge.

Background: The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy. Methods: We developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load). Results: We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6×6×21 mm3 (13C-pyruvate) and 12×12×21 mm3 (13C-lactate, 13C-bicarbonate) . 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant. Conclusions: We demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.

A metabolite specific 3D stack-of-spirals bSSFP sequence for improved bicarbonate imaging in hyperpolarized [1-13C]Pyruvate MRI.

13C-bicarbonate is a crucial measure of pyruvate oxidation and TCA cycle flux, but is challenging to measure due to its relatively low concentration and thus will greatly benefit from improved signal-to-noise ratio (SNR). To address this, we developed and investigated the feasibility of a 3D stack-of-spirals metabolite-specific balanced steady-state free precession (MS-bSSFP) sequence for improving the SNR and spatial resolution of dynamic 13C-bicarbonate imaging in hyperpolarized [1-13C]pyruvate studies. The bicarbonate MS-bSSFP sequence was evaluated by simulations, phantoms studies, preclinical studies on five rats, brain studies on two healthy volunteers and renal study on one renal cell carcinoma patient. The simulations and phantom results showed that the bicarbonate-specific pulse had minimal perturbation of other metabolites (<1%). In the animal studies, the MS-bSSFP sequence provided an approximately 2.6-3 × improvement in 13C-bicarbonate SNR compared to a metabolite-specific gradient echo (MS-GRE) sequence without altering the bicarbonate or pyruvate kinetics, and the shorter spiral readout in the MS-bSSFP approach reduced blurring. Using the SNR ratio between MS-bSSFP and MS-GRE, the T2 values of bicarbonate and lactate in the rat kidneys were estimated as 0.5 s and 1.1 s, respectively. The in-vivo feasibility of bicarbonate MS-bSSFP sequence was demonstrated in two human brain studies and one renal study. These studies demonstrate the potential of the sequence for in-vivo applications, laying the foundation for future studies to observe this relatively low concentration metabolite with high-quality images and improve measurements of pyruvate oxidation.

Ferroelectric Phase Transition Driven by Switchable Covalent Bonds.

The mechanism on ferroelectric phase transitions is mainly attributed to the displacive and/or order-disorder transition of internal components since the discovery of the ferroelectricity in 1920, rather than the breaking and recombination of chemical bonds. Here, we demonstrate how to utilize the chemical bond rearrangement in a diarylethene-based crystal to realize the light-driven mm2F1-type ferroelectric phase transition. Such a photoinduced phase transition is entirely driven by switchable covalent bonds with breaking and reformation, enabling the reversible light-controllable ferroelectric polarization switching, dielectric and nonlinear optical bistability. Moreover, light as quantized energy can achieve contactless, nondestructive, and remote-control operations. This work proposes a new mechanism of ferroelectric phase transition, and highlights the significance of photochromic molecules in designing new ferroelectrics for photocontrol data storage and sensing.

High-T c Single-Component Organosilicon Ferroelectric Crystal Obtained by H/F Substitution.

Organic single-component ferroelectrics are highly desirable for their low molecular mass, light weight, low processing temperature, and excellent film-forming properties. Organosilicon materials with a strong film-forming ability, weather resistance, nontoxicity, odorlessness, and physiological inertia are very suitable for device applications related to the human body. However, the discovery of high-T c organic single-component ferroelectrics has been very scarce, and the organosilicon ones even less so. Here, we used a chemical design strategy of H/F substitution to successfully synthesize a single-component organosilicon ferroelectric tetrakis(4-fluorophenylethynyl)silane (TFPES). Systematic characterizations and theory calculations revealed that, compared with the parent nonferroelectric tetrakis(phenylethynyl)silane, fluorination caused slight modifications of the lattice environment and intermolecular interactions, inducing a 4/mmmFmm2-type ferroelectric phase transition at a high T c of 475 K in TFPES. To our knowledge, this T c should be the highest among the reported organic single-component ferroelectrics, providing a wide operating temperature range for ferroelectrics. Moreover, fluorination also brought about a significant improvement in the piezoelectric performance. Combined with excellent film properties, the discovery of TFPES provides an efficient path for designing ferroelectrics suitable for biomedical and flexible electronic devices.

Treatment Response Evaluation by Computed Tomography Pulmonary Vasculature Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension.

OBJECTIVE: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. MATERIALS AND METHODS: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). RESULTS: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). CONCLUSION: Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Axial-Chiral BINOL Multiferroic Crystals with Coexistence of Ferroelectricity and Ferroelasticity.

Chirality exists everywhere from natural amino acids to particle physics. The introduction of point chirality has recently been shown to be an efficient strategy for the construction of molecular ferroelectrics. In contrast to point chirality, however, axial chirality is rarely used to design ferroelectrics so far. Here, based on optically active 1,1'-bi-2-naphthol (BINOL), which has been applied extensively as a versatile chiral reagent in asymmetric catalysis, chiral recognition, and optics, we successfully design a pair of axial-chiral BINOL multiferroics, (R)-BINOL-DIPASi and (S)-BINOL-DIPASi. They experience a 2F1-type full ferroelectric/ferroelastic phase transition at a high temperature of 362 and 363 K, respectively. Piezoelectric force microscopy and polarization-voltage hysteresis loops demonstrate their ferroelectric domains and domain switching, and polarized light microscopy visualizes the evolution of stripe-shaped ferroelastic domains. The axial-chiral BINOL building block promotes the generation of the polar structure and ferroelectricity, and the organosilicon component increases the rotational energy barrier and thus the phase transition temperature. This work presents the first axial-chiral high-temperature multiferroic crystals, offering an efficient path for designing molecular multiferroics through the introduction of axial chirality.

Chemical design of homochiral heterocyclic organic ferroelectric crystals.

Single component organic ferroelectrics of spirooxazacamphorsultam derivatives, 1-SSR and 1-RRS, exhibit well-defined ferroelectricity (Ps = 2.2 µC cm-2) and piezoelectricity (d33 = 10 pC N-1) below their melting point. More importantly, they possess a low acoustic impedance value of 2.7 × 106 kg s-1 m-2, which is well-matched with body tissues.

Development of specialized magnetic resonance acquisition techniques for human hyperpolarized [13 C,15 N2 ]urea + [1-13 C]pyruvate simultaneous perfusion and metabolic imaging.

PURPOSE: This study aimed to develop and demonstrate the in vivo feasibility of a 3D stack-of-spiral balanced steady-state free precession(3D-bSSFP) urea sequence, interleaved with a metabolite-specific gradient echo (GRE) sequence for pyruvate and metabolic products, for improving the SNR and spatial resolution of the first hyperpolarized 13 C-MRI human study with injection of co-hyperpolarized [1-13 C]pyruvate and [13 C,15 N2 ]urea. METHODS: A metabolite-specific bSSFP urea imaging sequence was designed using a urea-specific excitation pulse, optimized TR, and 3D stack-of-spiral readouts. Simulations and phantom studies were performed to validate the spectral response of the sequence. The image quality of urea data acquired by the 3D-bSSFP sequence and the 2D-GRE sequence was evaluated with 2 identical injections of co-hyperpolarized [1-13 C]pyruvate and [13 C,15 N2 ]urea formula in a rat. Subsequently, the feasibility of the acquisition strategy was validated in a prostate cancer patient. RESULTS: Simulations and phantom studies demonstrated that 3D-bSSFP sequence achieved urea-only excitation, while minimally perturbing other metabolites (<1%). An animal study demonstrated that compared to GRE, bSSFP sequence provided an ∼2.5-fold improvement in SNR without perturbing urea or pyruvate kinetics, and bSSFP approach with a shorter spiral readout reduced blurring artifacts caused by J-coupling of [13 C,15 N2 ]urea. The human study demonstrated the in vivo feasibility and data quality of the acquisition strategy. CONCLUSION: The 3D-bSSFP urea sequence with a stack-of-spiral acquisition demonstrated significantly increased SNR and image quality for [13 C,15 N2 ]urea in co-hyperpolarized [1-13 C]pyruvate and [13 C,15 N2 ]urea imaging studies. This work lays the foundation for future human studies to achieve high-quality and high-SNR metabolism and perfusion images.

H/F Substitution on the Spacer Cations Leads to 1D-to-2D Increment of the Pyrrolidinium-Containing Lead Iodide Hybrid Perovskites.

Hybrid organic-inorganic perovskites (HOIPs) have emerged as multifunctional materials with remarkable optical and electronic properties. In particular, 2D-layered lead iodide-based HOIPs possess great practical application potential in the photoelectric field. In this work, we report H/F substitution-induced 1D-to-2D increment of lead iodide HOIPs. The enantiomeric HOIPs, S- and R-FPPbI3 (FP = 3-fluoropyrrolidinium), were achieved by monofluoride substitution on the spacer cations of the parent HOIP, PyPbI3 (Py = pyrrolidinium), showing mirror image structural relationship and reversible solid-state phase transition. A 2D-layered HOIP, (DFP)2PbI4 (DFP = 3,3-difluoropyrrolidinium), was achieved with a low band gap of 2.09 eV through difluoride substitution, thanks to the expansion of the Pb-I network from 1D to 2D. This work highlights the exploration of 1D chiral and 2D-layered HOIP materials with reversible phase transitions through H/F substitution strategies.

H/F Substitution induced switchable coordination bonds in a cyano-bridged hybrid double perovskite ferroelastic.

A three-dimensional cyano-bridged double perovskite ferroelastic [(CH3)3NCH2F]2[KFe(CN)6] was constructed by introducing unprecedented switchable C-F-K coordination bonds. H/F substitution not only preserves the basic structure of the parent [(CH3)4N]2[KFe(CN)6] but also affords an m3̄mF2/m-type ferroelastic phase transition.

Clinical translation of hyperpolarized 13 C pyruvate and urea MRI for simultaneous metabolic and perfusion imaging.

PURPOSE: The combined hyperpolarized (HP) 13 C pyruvate and urea MRI has provided a simultaneous assessment of glycolytic metabolism and tissue perfusion for improved cancer diagnosis and therapeutic evaluation in preclinical studies. This work aims to translate this dual-probe HP imaging technique to clinical research. METHODS: A co-polarization system was developed where [1-13 C]pyruvic acid (PA) and [13 C, 15 N2 ]urea in water solution were homogeneously mixed and polarized on a 5T SPINlab system. Physical and chemical characterizations and toxicology studies of the combined probe were performed. Simultaneous metabolic and perfusion imaging was performed on a 3T clinical MR scanner by alternatively applying a multi-slice 2D spiral sequence for [1-13 C]pyruvate and its downstream metabolites and a 3D balanced steady-state free precession (bSSFP) sequence for [13 C, 15 N2 ]urea. RESULTS: The combined PA/urea probe has a glass-formation ability similar to neat PA and can generate nearly 40% liquid-state 13 C polarization for both pyruvate and urea in 3-4 h. A standard operating procedure for routine on-site production was developed and validated to produce 40 mL injection product of approximately 150 mM pyruvate and 35 mM urea. The toxicology study demonstrated the safety profile of the combined probe. Dynamic metabolite-specific imaging of [1-13 C]pyruvate, [1-13 C]lactate, [1-13 C]alanine, and [13 C, 15 N2 ]urea was achieved with adequate spatial (2.6 mm × 2.6 mm) and temporal resolution (4.2 s), and urea images showed reduced off-resonance artifacts due to the JCN coupling. CONCLUSION: The reported technical development and translational studies will lead to the first-in-human dual-agent HP MRI study and mark the clinical translation of the first HP 13 C MRI probe after pyruvate.

Association between Levels of Urine Di-(2-ethylhexyl)phthalate Metabolites and Heart Rate Variability in Young Adults.

Phthalate exposure is associated with cardiovascular risk. Among the various phthalates, di-(2-ethylhexyl) phthalate (DEHP) is a deleterious plasticizer in our daily lives. This study investigated the association between DEHP exposure and the alteration of heart rate variability (HRV). During 2017-2019, we recruited 974 young adults to investigate the effects of living environments and dietary habits on cardiometabolic disorders in Taiwan. We quantitatively analyzed urinary metabolites of DHEP. A continuous electrocardiogram was recorded to obtain a 5-min ECG. Time-domain and frequency-domain HRV analyses were performed. Multiple linear regression showed that urinary oxidized DEHP metabolites MEHHP and MEOHP were associated with decreased HRV after controlling for associated cardiovascular risk factors. A higher MEHHP level was associated with a lower triangular interpolation of NN interval histogram (TINN), very low frequency (VLF), and low frequency/high frequency (LF/HF) ratio. A higher MEOHP level was associated with a decreased LF/HF ratio. In addition, trend analysis showed that higher MEHHP and MEOHP quantiles were significantly associated with a decreased LF/HF ratio. DEHP is a potentially harmful and invisible chemical. The urinary DEHP metabolites MEHHP and MEOHP are associated with decreased HRV, indicating an adverse effect on autonomic balance in young adults in Taiwan.

The Value of Heart Rhythm Complexity in Identifying High-Risk Pulmonary Hypertension Patients.

Pulmonary hypertension (PH) is a fatal disease-even with state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE), were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5, and area 6-20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.

Metabolic imaging with hyperpolarized 13 C pyruvate magnetic resonance imaging in patients with renal tumors-Initial experience.

BACKGROUND: Optimal treatment selection for localized renal tumors is challenging because of their variable biologic behavior and limitations in the preoperative assessment of tumor aggressiveness. The authors investigated the emerging hyperpolarized (HP) 13 C magnetic resonance imaging (MRI) technique to noninvasively assess tumor lactate production, which is strongly associated with tumor aggressiveness. METHODS: Eleven patients with renal tumors underwent HP 13 C pyruvate MRI before surgical resection. Tumor 13 C pyruvate and 13 C lactate images were acquired dynamically. Five patients underwent 2 scans on the same day to assess the intrapatient reproducibility of HP 13 C pyruvate MRI. Tumor metabolic data were compared with histopathology findings. RESULTS: Eight patients had tumors with a sufficient metabolite signal-to-noise ratio for analysis; an insufficient tumor signal-to-noise ratio was noted in 2 patients, likely caused by poor tumor perfusion and, in 1 patient, because of technical errors. Of the 8 patients, 3 had high-grade clear cell renal cell carcinoma (ccRCC), 3 had low-grade ccRCC, and 2 had chromophobe RCC. There was a trend toward a higher lactate-to-pyruvate ratio in high-grade ccRCCs compared with low-grade ccRCCs. Both chromophobe RCCs had relatively high lactate-to-pyruvate ratios. Good reproducibility was noted across the 5 patients who underwent 2 HP 13 C pyruvate MRI scans on the same day. CONCLUSIONS: The current results demonstrate the feasibility of HP 13 C pyruvate MRI for investigating the metabolic phenotype of localized renal tumors. The initial data indicate good reproducibility of metabolite measurements. In addition, the metabolic data indicate a trend toward differentiating low-grade and high-grade ccRCCs, the most common subtype of renal cancer. LAY SUMMARY: Renal tumors are frequently discovered incidentally because of the increased use of medical imaging, but it is challenging to identify which aggressive tumors should be treated. A new metabolic imaging technique was applied to noninvasively predict renal tumor aggressiveness. The imaging results were compared with tumor samples taken during surgery and showed a trend toward differentiating between low-grade and high-grade clear cell renal cell carcinomas, which are the most common type of renal cancers.

Di-chromatic interpolation of magnetic resonance metabolic images.

OBJECTIVE: Magnetic resonance imaging with hyperpolarized contrast agents can provide unprecedented in vivo measurements of metabolism, but yields images that are lower resolution than that achieved with proton anatomical imaging. In order to spatially localize the metabolic activity, the metabolic image must be interpolated to the size of the proton image. The most common methods for choosing the unknown values rely exclusively on values of the original uninterpolated image. METHODS: In this work, we present an alternative method that uses the higher-resolution proton image to provide additional spatial structure. The interpolated image is the result of a convex optimization algorithm which is solved with the fast iterative shrinkage threshold algorithm (FISTA). RESULTS: Results are shown with images of hyperpolarized pyruvate, lactate, and bicarbonate using data of the heart and brain from healthy human volunteers, a healthy porcine heart, and a human with prostate cancer.