Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic animals,
but the mechanisms remain unknown. Equally elusive is the interplay between the
cardiomyocyte alterations induced by hyperglycemia and the accompanying
inflammation. Here we show that exposure of primary cardiomyocytes to high
glucose and pro-inflammatory stimuli leads to MAO-dependent increase in reactive
oxygen species that causes permeability transition pore opening and
mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum
(ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the
role of these flavoenzymes in the ER/mitochondria cross-talk. In
vivo, streptozotocin administration to mice induced oxidative
changes and ER stress in the heart, events that were abolished by pargyline.
Moreover, MAO inhibition prevented both mast cell degranulation and altered
collagen deposition, thereby normalizing diastolic function. Taken together,
these results elucidate the mechanisms underlying MAO-induced damage in diabetic
cardiomyopathy and provide novel evidence for the role of MAOs in inflammation
and inter-organelle communication. MAO inhibitors may be considered as a
therapeutic option for diabetic complications as well as for other disorders in
which mast cell degranulation is a dominant phenomenon.
Purpose
To investigate a computationally efficient method for optimizing the Cramér‐Rao Lower Bound (CRLB) of quantitative sequences without using approximations or an analytical expression of the signal.
Methods
Automatic differentiation was applied to Bloch simulations and used to optimize several quantitative sequences without the need for approximations or an analytical expression. The results were validated with in vivo measurements and comparisons to prior art. Multi‐echo spin echo and DESPOT1 were used as benchmarks to verify the CRLB implementation. The CRLB of the Magnetic Resonance Fingerprinting (MRF) sequence, which has a complicated analytical formulation, was also optimized using automatic differentiation.
Results
The sequence parameters obtained for multi‐echo spin echo and DESPOT1 matched results obtained using conventional methods. In vivo, MRF scans demonstrate that the CRLB optimization obtained with automatic differentiation can improve performance in presence of white noise. For MRF, the CRLB optimization converges in 1.1 CPU hours for NitalicTR = 400 and has O(NTR) asymptotic runtime scaling for the calculation of the CRLB objective and gradient.
Conclusions
Automatic differentiation can be used to optimize the CRLB of quantitative sequences without using approximations or analytical expressions. For MRF, the runtime is computationally efficient and can be used to investigate confounding factors as well as MRF sequences with a greater number of repetitions.
Novel methods for quantitative, transient-state multiparametric imaging are increasingly being demonstrated for assessment of disease and treatment efficacy. Here, we build on these by assessing the most common Non-Cartesian readout trajectories (2D/3D radials and spirals), demonstrating efficient anti-aliasing with a
k-
space view-sharing technique, and proposing novel methods for parameter inference with neural networks that incorporate the estimation of proton density. Our results show good agreement with gold standard and phantom references for all readout trajectories at 1.5 T and 3 T. Parameters inferred with the neural network were within 6.58% difference from the parameters inferred with a high-resolution dictionary. Concordance correlation coefficients were above 0.92 and the normalized root mean squared error ranged between 4.2 and 12.7% with respect to gold-standard phantom references for T1 and T2. In vivo acquisitions demonstrate sub-millimetric isotropic resolution in under five minutes with reconstruction and inference times < 7 min. Our 3D quantitative transient-state imaging approach could enable high-resolution multiparametric tissue quantification within clinically acceptable acquisition and reconstruction times.
Purpose
To obtain a fast and robust fat‐water separation with simultaneous estimation of water T
1
, fat T
1
, and fat fraction maps.
Methods
We modified an MR fingerprinting (MRF) framework to use a single dictionary combination of a water and fat dictionary. A variable TE acquisition pattern with maximum TE = 4.8 ms was used to increase the fat–water separability. Radiofrequency (RF) spoiling was used to reduce the size of the dictionary by reducing T
2
sensitivity. The technique was compared both in vitro and in vivo to an MRF method that incorporated 3‐point Dixon (DIXON MRF), as well as Cartesian IDEAL with different acquisition parameters.
Results
The proposed dictionary‐based fat–water separation technique (DBFW MRF) successfully provided fat fraction, water, and fat T
1
, B
0
, and B
1+
maps both in vitro and in vivo. The fat fraction and water T
1
values obtained with DBFW MRF show excellent agreement with DIXON MRF as well as with the reference values obtained using a Cartesian IDEAL with a long TR (concordance correlation coefficient: 0.97/0.99 for fat fraction–water T
1
). Whereas fat fraction values with Cartesian IDEAL were degraded in the presence of T
1
saturation, MRF methods successfully estimated and accounted for T
1
in the fat fraction estimates.
Conclusion
The DBFW MRF technique can successfully provide T
1
and fat fraction quantification in under 20 s per slice, intrinsically correcting T
1
biases typical of fast Dixon techniques. These features could improve the diagnostic quality and use of images in presence of fat.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.